Conditions: Uveal Melanoma Ocular Melanoma Choroidal Melanoma
Keywords: Uveal melanoma Eye cancer Ocular melanoma Choroidal melanoma
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 57
Healthy volunteers: no

Brief summary:
The primary objective is to assess the safety, immunogenicity and efficacy of one of three dose levels and repeat dose regimens of Light-activated AU-011 and one or two laser applications for the treatment of subjects with primary choroidal melanoma.

Detailed description:
This is a phase 1B/2 open-label, ascending single and repeat dose clinical trial designed to evaluate the safety and efficacy of Light-activated AU-011 for the treatment of subjects with small primary choroidal melanoma.

Throughout the study, subjects will be monitored through medical and ophthalmic assessments. Subjects will be followed for a total of 2 years.

Arms:
arm 1: Low dose Light-activated AU-011 followed by a single laser light application arm 2: Medium dose Light-activated AU-011 followed by a single laser light application arm 3: High dose Light-activated AU-011 followed by a single laser light application arm 4: 2 repeat medium doses of Light-activated AU-011 each followed by a single laser light application arm 5: 3 repeat medium doses of Light-activated AU-011 followed by a single laser light application arm 6: High dose Light-activated AU-011 followed by two laser light applications arm 7: 3 repeat high doses of Light-activated AU-011 each followed by a single laser light application arm 8: 3 repeat high doses of Light-activated AU-011 each followed by two laser light applications arm 9: Expansion of 3 repeat high doses of Light-activated AU-011 each followed by two laser light applications (up to 12 additional subjects) arm 10: Observation until documented growth of tumor and then treatment with 2 cycles each of 3 repeat high doses of Light-activated AU-011 each followed by two laser light applications arm 11: 2 cycles each of 3 repeat high doses of Light-activated AU-011 each followed by two laser light applications arm 12: 2 cycles each of 3 repeat high doses of Light-activated AU-011 each followed by two laser light applications in subjects with evidence of documented tumor growth prior to study entry

Interventions: intervention 1: Light-activated AU-011 intervention 2: Laser Activation
Intervention descriptions: intervention 1: Study treatment intervention 2: Study treatment

Protocol document:
Prot_000.pdf: 
Clinical Protocol, Rev-15 
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LIGHT-ACTIVATED AU-011 
PROTOCOL AU-011-101 
NCT03052127 
A PHASE 1B/2 OPEN-LABEL, ASCENDING SINGLE 
AND REPEAT DOSE CLINICAL TRIAL DESIGNED TO 
EVALUATE THE SAFETY AND EFFICACY OF LIGHT- 
ACTIVATED AU-011 FOR THE TREATMENT OF 
SUBJECTS WITH SMALL 
PRIMARY CHOROIDAL MELANOMA 
Rev-15  21 February 2020 
 
Aura Biosciences, Inc. 
85 Bolton Street 
Cambridge, MA 02140 
 
 
 
The information in this document is confidential and will not be disclosed to others without 
written authorization from Aura Biosciences, Inc., except to the extent necessary to obtain 
informed consent from persons involved in the clinical study or their legal guardians, or for 
discussions with local regulatory authorities, institutional review boards (IRB), or persons 
participating in the conduct of the trial. 


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INVESTIGATOR’S AGREEMENT 
 
Study title: A Phase 1b/2 open-label, ascending single and repeat dose clinical trial designed to 
evaluate the safety and efficacy of Light-activated AU-011 for the treatment of subjects with 
small primary choroidal melanoma. 
 
My signature confirms that I have carefully read, and that I understand this protocol. I agree to 
follow the study procedures as outlined in this protocol in compliance with current Good Clinical 
Practice and all other regulatory requirements. 
 
This protocol contains confidential information with respect to products and clinical trials. I 
agree to hold this information in confidence and not to disclose it to any third parties unless and 
until this information becomes a matter of public knowledge, or until a formal agreement for that 
purpose has been entered into by the parties. 
 
 
 
 
 
Printed Name of Investigator 
 
 
 
Signature of Investigator 
 
 
 
Date 


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AURA BIOSCIENCES SIGNATURE PAGE 
 
Title 
A Phase 1b/2 open-label, ascending single and repeat dose clinical trial 
designed to evaluate the safety and efficacy of Light-activated AU-011 for 
the treatment of subjects with small primary choroidal melanoma. 
 
Version/Date Rev-15 21 February 2020 
 
 
 
Protocol Approvers: 
 
 
Signature: 
Date: 
 
 
 
 
Signature: 
Date: 
 
 
 
 
Signature: 
Date: 


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1. 
SYNOPSIS 
 
Name of Sponsor/Company: Aura Biosciences, Inc. 
Name of Investigational Product: Light-activated AU-011 
Name of Active Ingredient: AU-011 
Title of Study: A Phase 1b/2 open-label, ascending single and repeat dose clinical trial designed to 
evaluate the safety and efficacy of light-activated AU-011 for the treatment of subjects with small 
primary choroidal melanoma. 
Number of Subjects (planned): Approximately 60 adult subjects 
Number of Study Sites: Up to 15 clinical sites 
Phase of Development: Phase 1b/2 
Objectives: 
The primary objective of this study is to evaluate the safety of IVT administration of one of 3 dose 
levels, repeat dose regimens and one or two laser applications of Light-activated AU-011 given in one 
or two treatment cycles in the treatment of subjects with small primary choroidal melanoma. 
Secondary objectives include evaluating: 
• 
Efficacy of AU-011 with one or two cycles of treatment with the maximum safe and feasible dose 
• 
Efficacy and safety of AU-011 in subjects with documented growth 
• 
The immunogenicity of AU-011 
• 
A-scan amplitudes of the internal reflectivity of the lesion at sites with diagnostic probes 
• 
Optical coherence tomography angiography (OCTA) image changes at sites with OCTA imaging 
systems for Cohorts 6 through 9 
Study Design: 
This is an open-label, ascending single and repeat dose and cycle, multicenter study designed to 
evaluate the safety and efficacy of Light-activated AU-011 at three dose levels and repeat dose 
regimens and cycles of Light-activated AU-011 and one or two laser applications in subjects with 
small primary choroidal melanoma (CM). The dose escalation design is shown in the figure below. 


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Dose Escalation Schematic
Single and Multiple Dose Cohorts
Expansion Cohort (#9)
1 to 8 (20μg X1 to 80μg 3XQ.Wk)
80μg 3XQ.Wk x 2 lasers
Observation Cohort (#10)*- Risk Factors
2 Cycles of AU-011 (#11)*– Risk Factors 
No Documented Growth
With or Without Documented Growth
2 Cycles of AU-011 (#12)– Documented 
Growth
*Alternating enrollment; enrollment in Cohorts 10 and 11 closed following approval of protocol revision 11 
(Rev-11) at each site and subjects will be enrolled in Cohort 12.
Single Ascending Dose (SAD) Cohorts
Three subjects will receive a single intravitreal (IVT) injection of Light-activated AU-011 low dose 
(20 µg in
µL). The injection is followed 6 to 8 hours later by exposure to 689 nm laser light. No 
more than one subject may be treated per day, and the treated subject must complete the 24-hour post- 
treatment visit with no safety issues before the next subject in a given cohort may be treated.
If all 3 subjects in the low dose group complete treatment without any dose limiting toxicity (DLT), 
escalation to the medium dose level group will be initiated. If a DLT is observed in 1 subject in the 
low dose group, this group will be expanded to 6 subjects. Dose escalation will not be allowed if 2 or 
more subjects in the low dose group experience a treatment-related DLT. Instead, if 2 or more 
subjects in the low dose group experience a treatment-related DLT, dose reduction to 10 µg in 
µL 
may be considered for enrolling an additional 3 subjects.
One week after the last subject in the low dose group completes treatment, the study medical monitor 
and an independent ocular oncologist will review safety data for all subjects in the low dose group. 
After review and confirmation that the data support proceeding to treatment with the medium dose 
group, three subjects will receive a single intravitreal injection of Light-activated AU-011 medium 
dose (40 µg in
µL). The injection is followed 6 to 8 hours later by exposure to 689 nm laser light.
If all 3 subjects in the medium dose group complete treatment without any dose limiting toxicity 
(DLT), escalation to the high dose level group will be initiated. If a DLT is observed in 1 subject in 
the medium dose group, this group will be expanded to 6 subjects. If 2 or more subjects in the 
medium dose group experience a DLT after their treatment, this will confirm that the lower dose level 
is the maximum feasible dose (due to formulation limits).


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One week after the last subject in the medium dose group completes treatment, the study medical 
monitor and an independent ocular oncologist will review safety data for all subjects in the medium 
dose group. After review and confirmation that the data support proceeding to treatment with the high 
dose group, 3 subjects will receive a single dose of Light-activated AU-011 high dose (80 µg 
administered as 2 injections of 
µg in 
µL not more than 2 hours apart). The second injection is 
followed 6 to 8 hours later by exposure to 689 nm laser light. If a DLT is observed in 1 subject in the 
high dose group, this group will be expanded to 6 subjects. If 2 or more subjects in the high dose 
group experience a DLT after their treatment, this will confirm that the medium dose level is the 
maximum feasible dose and the dose chosen for the repeat dose phase of the study will drop to one 
dose below the maximum feasible dose of 40 µg and the lower dose of 20 µg will be given as repeat 
doses. 
Multiple Ascending Dose (MAD) Cohorts 
One day after the last subject in the high dose group completes treatment, the study medical monitor 
and independent ocular oncologist will review safety data for all subjects and identify the maximum 
feasible dose for evaluation in the repeat dose phase of the study. After review and confirmation that 
the data support proceeding to a repeat dose regimen, 3 subjects will receive an intravitreal injection 
of 40 µg in 
µL of Light-activated AU-011 as 2 repeat doses one week apart. Each injection is 
followed 6 to 8 hours later by exposure to 689 nm laser light. 
If all 3 subjects in this 2 repeat 40 µg dose group complete treatment without any dose limiting 
toxicity (DLT) after 2 injections, then this regimen of Light-activated AU-011 may be investigated 
further in subsequent studies. If a DLT is observed in 1 subject in this 2 repeat 40 µg dose group, this 
group will be expanded to 6 subjects. If 2 or more subjects in this 2 repeat 40 µg dose group 
experience a DLT after their treatment, this will confirm that a lower dose repeat regimen should be 
investigated. 
One day after the last subject in the 2 repeat 40 µg dose group completes treatment, the study medical 
monitor and independent ocular oncologist will review safety data for all subjects and identify 
whether it is safe to evaluate 3 repeat 40 µg doses in the next cohort of the study. 
After review and confirmation that the data support proceeding to a 3 repeat 40 µg dose regimen, 3 
subjects will receive an intravitreal injection of 40 µg in 
µL of Light-activated AU-011 as 3 
repeat doses 1 week apart. Each injection is followed 6 to 8 hours later by exposure to 689 nm laser 
light. 
If all 3 subjects in this 3 repeat 40 µg dose group complete treatment without any dose limiting 
toxicity (DLT) after 3 injections, escalation to the next dose cohort will be initiated. If a DLT is 
observed in 1 subject in this 3 repeat 40 µg dose group, this group will be expanded to 6 subjects. If 2 
or more subjects in this 3 repeat 40 µg dose group experience a DLT after their treatment, this will 
confirm that a fewer number of repeat administrations, or a lower dose at each administration should 
be investigated. 
One day after the last subject in the 3 repeat 40 µg dose group completes treatment, the study medical 
monitor and independent ocular oncologist will review safety data for all subjects and identify the 
maximum feasible dose for continued evaluation in the repeat dose phase of the study. After review 
and confirmation that the data support proceeding, an 80 µg single dose repeat laser regimen will be 
initiated. Three subjects will receive intravitreal administration of 80 µg of Light-activated AU-011 
administered as 2 injections of 40 µg in 
µL (not more than 2 hours apart) followed by two 689 


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nm laser applications 30 minutes (± 10 minutes) apart, with the first of the 2 laser applications 
occurring 6 to 8 hours after the second injection. 
If all 3 subjects in this 80 µg single dose followed by 2 laser applications dose group complete 
treatment without any dose limiting toxicity (DLT), then the study may progress to the next cohort. If 
a DLT is observed in 1 subject in this 2 repeat laser applications following 80 µg single dose group, 
this group will be expanded to 6 subjects. If 2 or more subjects in this 2 repeat laser applications 
following 80 µg single dose group experience a DLT after their treatment, this will confirm that a 
lower dose followed by repeat laser regimen, or a repeat dose followed by single laser application 
should be investigated further. 
One day after the last subject in the 2 repeat laser applications following 80 µg single dose group 
completes treatment, the study medical monitor and independent ocular oncologist will review safety 
data for all subjects and identify whether it is safe to evaluate repeat laser applications after each of 3 
repeat doses of 80 µg in the study. 
After review and confirmation that the data support proceeding to the 3 repeat 80 µg dose regimen 
followed by a single laser application, 3 subjects will receive an intravitreal administration of 80 µg 
of Light-activated AU-011 administered as 2 injections of 
µg in 
µL (not more than 2 hours 
apart) as 3 repeat doses one week apart. Each administration is followed 6 to 8 hours (after the second 
injection) later by exposure to 689 nm laser light. 
One day after the last subject in the 3 repeat 80 µg dose group followed by a single laser application 
completes treatment, and 4 weeks after the last subject in the 80 µg single dose followed by 2 laser 
applications dose group complete treatment, the study medical monitor and independent ocular 
oncologist will review safety data for all subjects and identify whether it is safe to evaluate 3 repeat 
doses of 80 µg, each followed by 2 repeat laser applications, in the next cohort of the study. 
After review and confirmation that the data support proceeding to repeat laser applications after each 
of 3 repeat 80 µg doses, 3 subjects will receive an intravitreal administration of 80 µg of Light- 
activated AU-011 administered as 2 injections of 
µg in 
µL (not more than 2 hours apart) as 3 
repeat doses one week apart. Each administration is followed 6 to 8 hours (after the second injection) 
later by 2 exposures to 689 nm laser light 30 minutes (± 10 minutes) apart. 
If all 3 subjects in this group, who receive 3 repeat 80 µg doses, each followed by 2 repeat laser 
applications, complete treatment and have been followed for 4 weeks without any dose limiting 
toxicity (DLT) after 3 weekly administrations, then this dose and regimen will be considered the 
maximum feasible dose and investigated in the expanded cohort. If a DLT is observed in 1 subject in 
this 3 repeat 80 µg dose with 2 repeat laser applications group, this group will be expanded to 6 
subjects. If 2 or more subjects in this 3 repeat 80 µg dose with 2 repeat laser applications group 
experience a DLT after their treatment, this will confirm that a fewer number 
of repeat administrations of either Light-activated AU-011 or laser, or both, or a lower dose of Light- 
activated AU-011 at each administration should be investigated further. 
Four weeks after the final treatment of the final subject in this cohort, a review of the safety data 
(including EDI-OCT) by the study medical monitor and independent ocular oncologist will occur. If 
safety is confirmed, the 3 repeat 80 µg dose with 2 repeat laser applications will be considered the 
maximum feasible and tolerated dose and this regimen will be expanded by up to 12 additional 
subjects in Cohort 9. 


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Efficacy will be assessed at all study visits from Week 12 onwards. 
Repeat Cycle and Observation Cohorts 
Once the last subject in the expansion cohort has been enrolled and safety of the maximum safe and 
feasible dose is confirmed, approximately 6 additional subjects, who fulfil the criteria for the clinical 
diagnosis of CM, but without documented growth, will be enrolled into an observation cohort (Cohort 
10). These subjects will be assessed every 3 months (ie, 90 day (+/- 7 days) intervals from the 
Screening Visit) until tumor growth of the CM lesion is established (as defined in Section 8.3.4.) and 
at which time will then receive treatment with AU-011, as 3 repeat 80 µg doses, each followed by 2 
repeat laser applications and move to the same visit schedule as subjects entering the trial and 
receiving treatment with AU-011 immediately. These subjects will receive Cycle 2 of AU-011 
administered as 3 repeat 80 µg doses, each followed by 2 repeat laser applications no earlier than the 
Week 12 Visit and after resolution of any inflammation resulting from the first cycle or when the 
inflammation is minimal and decreasing based on investigator judgement. Cycle 2 should be 
administered as soon as reasonably possible after inflammation has resolved or is minimal and 
decreasing based on investigator judgement. If the fovea is near the tumor edge, an adjustment to the 
laser procedure should be performed on each treatment day of both cycles as outlined in section 8.2.2 
and the Injection and Laser Procedure Manual. 
In addition, approximately 6 additional subjects, who meet the criteria for a clinical diagnosis of CM, 
with or without documented growth, will enter Cohort 11 and receive two cycles of AU-011 treatment 
(each cycle will be comprised of 3 repeat 80 µg doses, each followed by 2 repeat laser applications). 
Cycle 2 of AU-011 will be administered as 3 repeat 80 µg doses, each followed by 2 repeat laser 
applications no earlier than the Week 12 Visit and after resolution of any inflammation resulting from 
the first cycle or when the inflammation is minimal and decreasing based on investigator judgement. 
Cycle 2 should be administered as soon as reasonably possible after inflammation has resolved or is 
minimal and decreasing based on investigator judgement. If the fovea is near the tumor edge, an 
adjustment to the laser procedure should be performed on each treatment day of both cycles as 
outlined in section 8.2.2 and the Injection and Laser Procedure Manual. 
The intention is to alternate the enrollment of Cohorts 10 and 11. If during the enrollment of these 
subjects, a subject has just been enrolled into Cohort 11 and a subject with documented growth 
presents, then that subject may instead be enrolled into Cohort 11 rather than Cohort 10 for which 
they would not be eligible due to the presence of documented growth and instead will be assigned to 
receive the first of 2 cycles of AU-011. 
If 2 subjects experience a DLT during treatment with Cycle 2, as defined in Section 8.4.1., then no 
further subjects will receive Cycle 2 of AU-011 until discussed with the independent ocular 
oncologist and medical monitor and continuation of enrollment is confirmed. 
Subjects with Documented Growth 
Enrollment in Cohorts 10 and 11 was closed following approval of protocol revision 11 (Rev-11) at 
each site. An additional cohort, Cohort 12, of subjects with minimum defined levels of documented 
growth will be initiated to allow assessment of safety and efficacy of 2 cycles of AU-011 treatment in 
this key subgroup of subjects with CM. Since Cohort 12 has the same dose as Cohort 11 no additional 
safety review will be required prior to initiating this cohort. 


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Up to 15 subjects, who meet the criteria for a clinical diagnosis of CM with documented growth as 
defined in Inclusion Criteria 5C, will enter Cohort 12 and receive two cycles of AU-011 treatment 
(each cycle will be comprised of 3 repeat 80 µg doses, each followed by 2 repeat laser applications). 
Cycle 2 of AU-011 will be administered as 3 repeat 80 µg doses, each followed by 2 repeat laser 
applications no earlier than the Week 12 Visit and after resolution of any inflammation resulting from 
the first cycle or when the inflammation is minimal and decreasing based on investigator judgement. 
Cycle 2 should be administered as soon as reasonably possible after inflammation has resolved or is 
minimal and decreasing based on investigator judgement. If the fovea is near the tumor edge, an 
adjustment to the laser procedure should be performed on each treatment day of both cycles as 
outlined in section 8.2.2 and the Injection and Laser Procedure Manual. 
If 2 subjects experience a DLT during treatment with Cycle 2, as defined in Section 8.4.1., then no 
further subjects will receive Cycle 2 of AU-011 until discussed with the independent ocular 
oncologist and medical monitor and continuation of enrollment is confirmed. 
Study Methods: 
Subjects will be screened for enrollment into the study after providing written informed consent 
between Day -28 and Day 1. Screening procedures include medical history, ophthalmic assessments, 
vital signs, and safety laboratory analyses. To be eligible for enrollment, subjects will have a small 
CM of ≥ 2.0 and ≤ 3.0 mm in thickness, and largest basal diameter ≤ 13.0 mm, OR tumor thickness of 
≥ 1.2 and ≤ 3.0 mm with documented growth and largest basal diameter ≤ 13.0 mm. To be eligible for 
enrollment in Cohort 12, subjects will have clinically diagnosed primary CM with tumor thickness of 
≥ 0.5 mm and ≤ 3.0 mm on B-scan ultrasound, a largest basal diameter of ≤ 13.0 mm on fundus 
photos with an estimated tumor volume ≤50 mm3 associated with documented tumor growth, defined 
as ≥ 0.4 mm based on intersite measurements (clinical site and referring center) or ≥ 0.3 mm based 
on within site measurements on tumor thickness within 2 years of screening. 
Qualified subjects will be enrolled into one of twelve cohorts and treated as described above. Each 
subject in the first 3 cohorts and in cohort 6 will receive a single IVT treatment with Light-activated 
AU-011, subjects in Cohort 4 will receive 2 repeat doses, and subjects in Cohorts 5, 7, 8, 9, 10, 11 
and 12 will receive 3 repeat doses. After administration of Light-activated AU-011, the CM is 
exposed to 689 nm laser light. Subjects in Cohorts 6, 8, 9, 10, 11 and 12 will receive 2 laser 
applications 30 minutes (± 10 minutes) apart at 6 to 8 hours after each intravitreal administration 
(after the second injection for these 80 µg cohorts), while the remaining cohorts will receive a single 
laser application at 6 to 8 hours after each intravitreal administration (after the second injection in the 
80 µg cohorts). In addition, Cohorts 10, 11 and 12 will receive Cycle 2 of AU-011 at the same dose 
and regimen no earlier than the Week 12 Visit and after resolution of any inflammation resulting from 
the first cycle or when the inflammation is minimal and decreasing based on investigator judgement. 
Cycle 2 should be administered as soon as reasonably possible after inflammation has resolved or is 
minimal and decreasing based on investigator judgement. If the fovea is near the tumor edge, an 
adjustment to the laser procedure should be performed on each treatment day of both cycles as 
outlined in section 8.2.2 and the Injection and Laser Procedure Manual. 
If subjects are discharged during daylight hours, appropriate sun protection, e.g., sunglasses and a hat, 
will be required. 
Study subjects will be required to return for ocular assessments 24 hours (± 4 hours) following 
intravitreal administration of study drug and on Day 8, Day 15, Day 29, Week 6, Week 8, Week 12, 


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Week 26, Week 39, Week 52, Week 78, and Week 104. In addition, subjects in both the 2 and 3 
repeat Light-activated AU-011 administration cohorts will have an additional safety visit on Day 9. 
Subjects in the 3 repeat Light-activated AU-011 administration cohorts will have an additional safety 
visit at Day 16. Subjects in the observation cohort (Cohort 10) will be seen every 3 months (ie, 90 day 
(+/- 7 days) intervals from the Screening Visit) until tumor growth is established and then seen at the 
schedule described in Section 10 and Appendix 1 until the time of receiving Cycle 2, when they will 
then follow the schedule described in Appendix 4. Subjects in the observation cohort in whom tumor 
growth is not observed during the 2 year study period will exit the study at Week 104. Subjects in the 
repeat cycle of AU-011 cohorts (Cohorts 11 and 12) will also follow the schedule described in 
Section 10 and Appendix 1 until the time they receive the second cycle of AU-011, when they will 
then follow the schedule described in Appendix 4. 
If the second cycle of AU-011 occurs after Visit 15 (Week 78), subjects will be followed for 26 
weeks post-treatment and then may be rolled into the long-term follow-up study pending subject 
consent. Details regarding the follow-up visit schedule after the second cycle of AU-011 can be found 
in Appendix 4. 
All subjects’ study participation will be for a minimum of 2 years and all subjects in this study may 
then be rolled into the long-term follow-up study pending consent. 
Ocular assessments include: 
• 
Best Corrected Visual Acuity (BCVA) 
• 
Slit lamp biomicroscopy 
• 
Intraocular pressure (IOP) 
• 
Fundoscopy 
• 
Color fundus photography (fundus photos) 
• 
Fluorescein angiography (FA) 
• 
B-scan ultrasound (B-scan) 
• 
A-scan ultrasound (A-scan) as a separate sub-study at sites with diagnostic probes 
• 
Enhanced depth imaging optical coherence tomography (EDI-OCT) 
• 
Optical coherence tomography angiography (OCTA) as a separate sub-study at sites with 
OCTA imaging systems for Cohorts 6 through 9 
• 
Visual field 
• 
Tumor size will be evaluated during the study. 
• 
Hematology, serum chemistry and anti-drug antibodies (ADA) 
• 
Concomitant medications and adverse events (AEs) will be reviewed through 30 days 
following the study treatment. After 30 days, for Cohorts 1 to 9, only AEs or SAEs 
determined by the Investigator to be related to study product and/or study procedures are to 
be reported. For Cohort 10, 11 and 12 subjects concomitant medications and all adverse 
events will be reviewed through their last study visit. 


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• 
If peri-tumoral whitening/pigmentary changes are seen during the study, additional 
assessments as outlined in Section 10.3.10 should be conducted. 
Section 10 provides further details on the conduct of the study, study visits, and assessments. Ocular 
imaging, including B-scan ultrasound (B-scan), A-scan ultrasound (A-scan), fundus photos, FA, EDI- 
OCT, and OCTA will be read by a centralized Independent Reading Center (IRC) 
Eligibility Criteria: 
Inclusion Criteria 
Subjects must: 
1. Be at least 18 years of age of either gender or any race. 
2. Have been informed about the nature and requirements of the study, voluntarily agreed to 
participate in the study, and documented this by signing the Informed Consent Form (ICF) 
before participating in any study-related activities. 
3. Be willing and able to follow all instructions and attend all study visits. 
4. Per the expert opinion of the Investigator, have clinically diagnosed primary CM with no 
known metastatic disease. 
5. Have clinically diagnosed primary CM: 
A. with tumor thickness of ≥ 1.2 mm and ≤ 3.0 mm on B-scan ultrasound and with a largest 
basal diameter of ≤ 13.0 mm on fundus photos associated with tumor growth, 
OR 
B. with tumor thickness of ≥ 2.0 mm and ≤ 3.0 mm on B-scan ultrasound and with a largest 
basal diameter of ≤ 13.0 mm on fundus photos associated with the presence of subretinal 
fluid by OCT AND at least one of the following: 
a. Overlying orange pigment (lipofuscin) on fundus photos 
b. Vision loss 
c. Flashes or floaters 
OR 
C. Criteria for Cohort 12: with tumor thickness of ≥ 0.5 mm and ≤ 3.0 mm on B-scan 
ultrasound, a largest basal diameter of ≤ 13.0 mm on fundus photos with an estimated 
tumor volume ≤50 mm3 associated with tumor growth within 2 years of screening 
(defined as ≥ 0.4 mm increase based on intersite measurements or ≥ 0.3 mm based on 
within site measurements on tumor thickness) 
NOTE: Whenever available at the investigative site or referring site, historical images (B- 
scans and/or color fundus photos) for all subjects should be provided to the Independent 
Reading Center at the time of entry to the study. The investigative site should make all 
reasonable efforts to obtain this information from referring sites. 
6. In the opinion of the treating physician, the subject could be managed by interventional 
therapy, or by cautious observation. 
7. Be treatment-naïve for their primary CM. 


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8. Have a tumor for which the entire extent must be able to be imaged on required fundus 
photography in a single frame and treated by the laser. 
9. If female and capable of becoming pregnant, agree to have pregnancy testing performed at 
screening (must be negative) and if required at Visit 2 (must be negative); must not be 
lactating; and must agree to use a medically acceptable form of birth control before 
administration of the investigational product and for three months after administration of the 
investigational product. Women considered capable of becoming pregnant include all females 
who have experienced menarche and have not experienced menopause (as defined by 
amenorrhea for greater than 12 consecutive months) or have not undergone successful 
surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy). 
10. For women of childbearing potential and for males with sexual partners of childbearing 
potential: Acceptable forms of birth control are spermicide with barrier, oral contraceptive, 
injectable or implantable method of contraception, transdermal contraceptive, intrauterine 
device, or surgical sterilization of partner. For non-sexually active females and males, 
abstinence will be considered an acceptable form of birth control. 
11. Be otherwise in good general health, with no significant or uncontrolled medical conditions, 
as determined by the Investigator. 
12. Be able and willing to avoid all prohibited medications for the appropriate washout period. 
Exclusion Criteria 
Subjects must not: 
1. Have known contraindications or sensitivities to IRDye®700DX phthalocyanine-based dye, or 
laser in the study eye. 
2. Have any ocular condition in the study eye that, in the Investigator’s opinion, could affect the 
subject's safety or trial parameters. 
3. Have a CM that invades or encompasses the optic nerve that precludes treatment, as 
determined by the investigator and/or shows extraocular extension. 
4. Have metastatic disease confirmed by abdominal and chest imaging within three months prior 
to screening. 
5. Have undergone vitrectomy at any time or have undergone any ocular surgical intervention in 
the study eye within three months before Visit 1, or are planning/will require ocular surgery 
in the study eye prior to the study drug administration. If the subject is likely to require 
cataract surgery in the study eye at any time prior to the Week 104 visit, he/she should not be 
enrolled. 
6. Have a history of rhegmatogenous retinal detachment, diabetic retinopathy, or other active 
retinal disease in the study eye unrelated to the CM. 
7. Have any active ocular disease in the study eye (other than CM) that may progress during the 
study and result in a change in vision or loss in vision (e.g., clinically significant corneal 
dystrophies, keratoconus, glaucoma or clinically significant retinal or macular disease). 
8. Have an active ocular infection (bacterial, viral or fungal). 


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9. Use or require use of heparin or low molecular weight heparins within one week of treatment. 
10. Use or require use of immunosuppressive or antineoplastic medications within five half-lives 
of Visit 1. Steroids, including inhalation steroids, are permitted. 
11. Have previously received human papillomavirus (HPV) vaccination. 
12. Any active malignancies other than CM, or squamous or basal cell skin cancer. If there is 
evidence of clinical remission for at least one year, the subject’s eligibility may be discussed 
with the medical monitor. 
13. Have any significant illness (e.g., an uncontrolled autoimmune disease, severe cardiovascular 
disease [confirmed by a cardiologist], active infection, etc.) that the Investigator determines 
could interfere with study participation or safety, or put the subject at any unnecessary risk. 
14. Have planned or will require systemic surgery during the active study treatment period. 
15. Have used an investigational drug or medical device within 30 days or 5 half-lives of Visit 1 
or be concurrently enrolled in another investigational product trial. 
Additional Therapy with AU-011 
Subjects may receive additional therapy with AU-011 at the maximum tolerated and feasible dose 
which is 3 repeat doses of 80 µg each followed by two laser applications (treatment regimen) as 
outlined in Section 8.3.3 of the protocol. Also, as outlined in Section 8.2.2 and the Injection and Laser 
Procedure Manual, if the fovea is near the tumor edge, an adjustment to the laser procedure should be 
performed on each treatment day. 
Investigational product, dosage and mode of administration: 
The investigational treatment is Light-activated AU-011, a combination product consisting of a drug 
(AU-011) and a laser (Aura Photoactivation System) that delivers 689 nm light to activate the drug 
once it is bound to the tumor cells. AU-011 drug substance is a modified human papillomavirus- 
derived, empty viral like particle (VLP) conjugated to approximately 200 molecules of a 
phthalocyanine-based photosensitizer IRDye®700DX (the “Dye”). 
AU-011 is administered by intravitreal injection. Laser light (689 nm) is applied to the CM from 
6 hours to 8 hours after administration. 
Statistical Methods: 
Since this is an open-label, exploratory study, no formal hypothesis testing will be performed. 
Efficacy will be assessed at the Week 12, 26, 39, 52, 78 and 104 visits for any potential tumor 
response and changes in ETDRS best corrected visual acuity (BCVA). This will include change from 
baseline at each visit in tumor thickness by ultrasound and largest basal diameter by digital fundus 
photography. The proportion of subjects who meet the definition of stable disease (do not meet the 
definition of disease progression) will also be reported for each visit using change in tumor thickness 
and changes in largest basal diameter. Change from baseline in ETDRS BCVA letter score at Week 
12 and at each subsequent visit and the proportion of subjects who lose or gain 5, 10 or 15 letters will 
also be evaluated. 


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Exploratory analyses will be performed for change in internal reflectivity of tumors by A-scan 
ultrasound at each visit and macular changes (foveal avascular zone and capillary density) by OCTA 
at each visit. 
Background and demographic characteristics will be presented. Continuous variables will be 
summarized by descriptive statistics (sample size, mean, standard deviation, median, minimum and 
maximum). Discrete variables will be summarized by frequencies and percentages. 
Efficacy and safety will be analyzed at various intervals after the first 2 cohorts have completed 12 
months of follow-up and then at further intervals as subsequent cohorts reach similar milestones. 
Specific details of the timing of such analyses will be included in the Statistical Analysis Plan. 


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2. 
TABLE OF CONTENTS 
1. 
SYNOPSIS .................................................................................................................... 4 
2. 
TABLE OF CONTENTS ............................................................................................ 15 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ............................. 19 
4. 
INTRODUCTION ...................................................................................................... 21 
4.1. 
Uveal Melanoma ......................................................................................................... 21 
4.2. 
Existing Therapies for Choroidal Melanoma .............................................................. 22 
4.3. 
Viruses as Anti-Cancer Agents ................................................................................... 23 
4.4. 
Light Activated AU-011 for the Treatment of Choroidal Melanoma ......................... 23 
4.5. 
Nonclinical Studies of AU-011 ................................................................................... 24 
4.5.1. 
Pharmacodynamic Studies .......................................................................................... 25 
4.5.2. 
Pharmacokinetics ........................................................................................................ 25 
4.5.3. 
Toxicology .................................................................................................................. 25 
4.6. 
Rationale for the Phase 1b/2 Clinical Trial of Light-Activated AU-011 in 
Choroidal Melanoma................................................................................................... 25 
5. 
TRIAL OBJECTIVES AND PURPOSE .................................................................... 27 
5.1. 
Primary Objective ....................................................................................................... 27 
5.2. 
Secondary and Exploratory Objectives ....................................................................... 27 
6. 
INVESTIGATIONAL PLAN ..................................................................................... 28 
6.1. 
Overall Study Design .................................................................................................. 28 
6.2. 
Criteria for Study Termination .................................................................................... 34 
7. 
SELECTION AND WITHDRAWAL OF SUBJECTS .............................................. 35 
7.1. 
Subject Inclusion Criteria ............................................................................................ 35 
7.2. 
Subject Exclusion Criteria .......................................................................................... 36 
7.3. 
Withdrawal of Subjects ............................................................................................... 37 
7.3.1. 
Subject Discontinuation .............................................................................................. 37 
7.3.2. 
Loss to Follow-up ....................................................................................................... 37 
7.3.3. 
Early Subject Termination or Subject Withdrawal ..................................................... 38 
7.3.4. 
Follow-up of Subjects with Adverse Events ............................................................... 38 
8. 
TREATMENT OF SUBJECTS .................................................................................. 39 
8.1. 
Description of Study Drug .......................................................................................... 39 
8.2. 
AU-011 Treatment ...................................................................................................... 39 
8.2.1. 
Administration of AU-011 .......................................................................................... 39 


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8.2.2. 
Laser Activation of AU-011 .......................................................................................40 
8.3. 
Concomitant Medications ...........................................................................................40 
8.3.1. 
Concomitant Steroid Treatment ..................................................................................41 
8.3.2. 
Prohibited Concomitant Medications ..........................................................................42 
8.3.3. 
Additional Therapy .....................................................................................................42 
8.3.4. 
AU-011 Treatment Criteria for Observation Cohort ...................................................43 
8.4. 
Dose Escalation Design and Toxicity .........................................................................43 
8.4.1. 
DLT Definition ...........................................................................................................43 
8.4.2. 
Dose Escalation / Termination ....................................................................................43 
9. 
STUDY DRUG ...........................................................................................................44 
9.1. 
Study Drug ..................................................................................................................44 
9.2. 
Study Drug Packaging, Labeling, and Storage ...........................................................44 
9.3. 
Study Drug Preparation ...............................................................................................44 
9.4. 
Study Drug Accountability .........................................................................................44 
9.5. 
Laser System ...............................................................................................................44 
10. 
CONDUCT OF STUDY AND STUDY ASSESSMENTS ........................................45 
10.1. 
Conduct of Study ........................................................................................................45 
10.1.1. 
Screening and Informed Consent ................................................................................45 
10.1.2. 
Screening (Visit 1 [Day -28 to Day 1]) .......................................................................45 
10.1.3. 
Single Light-activated AU-011 Administration (or Initial for Repeat) Study 
Treatment (Visit 2 [Day 1]) ........................................................................................46 
10.1.4. 
Visit 3 (Day 2, 24 hours [± 4 hours] Post-Injection Follow-up) .................................47 
10.1.5. 
Visit 4 (Day 8 to Day 9) ..............................................................................................48 
10.1.6. 
Visit 5 (Day 9 to Day 10, 24 hours [± 4 hours] Post-Injection Follow-up for 
2 and 3 Repeat Light-activated AU-011 Administration Cohorts ..............................49 
10.1.7. 
Visit 6 (Day 15 to Day 16) ..........................................................................................49 
10.1.8. 
Visit 7 (Day 16 to Day 17, 24 hours [± 4 hours] Post-Injection Follow-up for 
3 Repeat Light-activated AU-011 Administration Cohorts only) ...............................50 
10.1.9. 
Follow-up Visit 8 (Day 29 ± 1 day) ............................................................................51 
10.1.10. 
Follow-up Visit 9 (Week 6 ± 3 days) ..........................................................................51 
10.1.11. 
Follow-up Visit 10 (Week 8 ± 3 days) ........................................................................52 
10.1.12. 
Follow-up Visit 11 (Week 12 ± 3 days) ......................................................................52 
10.1.13. 
Follow-up Visit 12 (Week 26 ± 7 days) ......................................................................53 


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10.1.14. 
Follow-up Visit 13 (Week 39 ± 7 days) ...................................................................... 53 
10.1.15. 
Follow-up Visit 14 (Week 52 ± 7 days) ...................................................................... 54 
10.1.16. 
Follow-up Visit 15 (Week 78 ± 7 days) ...................................................................... 54 
10.1.17. 
Follow-up Visit 16 (Week 104 ± 7 days), End of Study or Early Termination .......... 55 
10.2. 
Safety Assessments ..................................................................................................... 55 
10.2.1. 
History and Vital Signs ............................................................................................... 55 
10.2.2. 
Laboratory Assessments.............................................................................................. 56 
10.2.2.1. 
Hematology and Differential Panel ............................................................................. 56 
10.2.2.2. 
Comprehensive Metabolic Panel (CMP) and Electrolyte Panel ................................. 56 
10.2.2.3. 
Pregnancy Test and Contraception Requirements ...................................................... 56 
10.2.2.4. 
Anti-Drug Antibodies (ADA) ..................................................................................... 57 
10.2.3. 
Safety Monitoring ....................................................................................................... 57 
10.2.3.1. 
Definitions of Adverse Events .................................................................................... 57 
10.2.3.2. 
Serious Adverse Events .............................................................................................. 58 
10.2.3.3. 
Adverse Event Recording and Reporting .................................................................... 59 
10.2.3.4. 
Classification of Adverse Events by Intensity/Severity .............................................. 60 
10.2.3.5. 
Serious Adverse Event Reporting ............................................................................... 61 
10.3. 
Ophthalmic Assessments ............................................................................................ 62 
10.3.1. 
Best Corrected Visual Acuity (BCVA) ....................................................................... 62 
10.3.2. 
Intraocular Pressure (IOP)........................................................................................... 62 
10.3.3. 
Slit Lamp Biomicroscopy and Fundoscopy ................................................................ 62 
10.3.4. 
Fluorescein Angiography (FA) and Color Fundus Photography (Fundus 
Photos) ........................................................................................................................ 63 
10.3.5. 
Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT) .................... 63 
10.3.6. 
Optical Coherence Tomography Angiography (OCTA) ............................................ 63 
10.3.7. 
B-scan Ultrasound ....................................................................................................... 64 
10.3.8. 
A-scan Ultrasound ....................................................................................................... 64 
10.3.9. 
Visual Field Examination ............................................................................................ 64 
10.3.10. 
Additional Assessments .............................................................................................. 65 
10.4. 
General Methodology.................................................................................................. 65 
10.5. 
Efficacy ....................................................................................................................... 66 
11. 
SOURCE DATA/DOCUMENTS ............................................................................... 67 
11.1. 
Study Monitoring ........................................................................................................ 67 


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11.2. 
Audits and Inspections ................................................................................................67 
11.3. 
Institutional Review Board (IRB) ...............................................................................67 
12. 
QUALITY CONTROL AND QUALITY ASSURANCE ..........................................68 
13. 
ETHICS.......................................................................................................................69 
13.1. 
IRB Review .................................................................................................................69 
13.2. 
Ethical Conduct of the Study ......................................................................................69 
13.3. 
Written Informed Consent ..........................................................................................69 
13.4. 
Subject Confidentiality ................................................................................................70 
14. 
DATA HANDLING AND RECORDKEEPING ........................................................71 
14.1. 
Data Collection ...........................................................................................................71 
14.2. 
Study Documentation and Retention of Records ........................................................71 
14.3. 
Amendments to the Protocol .......................................................................................71 
15. 
DISCLOSURE AND PUBLICATION POLICY .......................................................73 
16. 
LIST OF REFERENCES ............................................................................................74 
17. 
APPENDICES ............................................................................................................77 
APPENDIX 1. SCHEDULE OF ASSESSMENTS .....................................................................78 
APPENDIX 2. SPONSOR’S COMMITMENTS ........................................................................80 
APPENDIX 3. COMMON TECHNICAL CRITERIA FOR ADVERSE EVENTS 
(CTCAE) .....................................................................................................................81 
APPENDIX 4. AU-011 ADDITIONAL THERAPY AND SECOND CYCLE 
(COHORTS 10, 11 & 12) VISIT SCHEDULE ..........................................................82 
 
LIST OF TABLES 
 
Table 1 
Abbreviations and Specialist Terms ............................................................................19 
 
LIST OF FIGURES 
Figure 1 
Structure of AU-011 ....................................................................................................24 
Figure 2 
Dose Escalation Schematic .........................................................................................28 


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3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
The following abbreviations and specialist terms are used in this study protocol. 
 
Table 1 
Abbreviations and Specialist Terms 
 
Abbreviation or Specialist Term 
Explanation 
ADA 
Anti-drug antibodies 
ADL 
Activities of Daily Living 
AE 
Adverse event 
ALT 
Alanine transaminase 
AST 
Aspartate transaminase 
A-scan 
A-scan ultrasonography 
AU-011 
A modified human papillomavirus-derived, empty viral like 
particle (VLP) conjugated to approximately 200 molecules of 
photosensitizer IRDye® 700DX 
BCVA 
Best corrected visual acuity 
BP 
Blood pressure 
B-scan 
B-scan ultrasonography 
CBC 
Complete blood count 
CM 
Choroidal melanoma 
CMP 
Comprehensive metabolic panel 
CRO 
Contract research organizations 
dL 
Deciliter 
DLT 
Dose limiting toxicity 
eCRF 
Electronic case report form 
EDI-OCT 
Enhanced Depth Imaging Optical Coherence Tomography 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
FA 
Fluorescein angiography 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
HPV 
Human papillomavirus 
HSPG 
Heparan sulfate proteoglycan 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IND 
Investigational New Drug application 


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Abbreviation or Specialist Term 
Explanation 
IOP 
Intraocular pressure 
IRB 
Institutional Review Board 
IRC 
Independent Reading Center 
J 
Joules 
LBD 
Largest basal diameter 
Min 
Minute 
mg 
Milligram 
mL 
Milliliter 
μg 
Microgram 
μL 
Microliter 
N 
Number (refers to subjects) 
nm 
Nanometer 
OCTA 
Optical coherence tomography angiography 
PHI 
Protected health information 
PI 
Principal Investigator 
PK 
Pharmacokinetic 
PV 
Papillomavirus 
SAE 
Serious adverse event 
SGOT 
Serum glucose-oxaloacetic transaminase 
SGPT 
Serum glucose-pyruvic transaminase 
SOP 
Standard operating procedure 
TEAE 
Treatment emergent adverse event 
UM 
Uveal melanoma 
US 
United States of America 
VLP 
Viral like particle 


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4. 
INTRODUCTION 
4.1. 
Uveal Melanoma 
The most common primary malignancy of the eye is uveal melanoma (UM)., or more precisely, 
choroidal melanoma (CM) (Bell 2004). The neoplasm is most commonly manifested in the 
choroid (90% of cases) followed by the ciliary body (7%), or iris (2%). It is more common in 
Caucasian adults of northern European descent, who have blue or green eyes and fair skin with a 
tendency to sunburn, though a definitive link between sun exposures and UM has not been 
proven (Shields 2014). There are some who believe that blue-eyed persons with extensive sun 
exposure have higher risk for melanoma (Schmidt-Pokrzywniak 2009). Nevi on the skin have 
been shown to have an association with increased risk for development of CM (Shah 2005; 
Singh 2012; Weis 2009). The condition rarely appears in pediatric populations (Shields 2012). 
Intraocular tumors present with general visual symptoms, but some patients are asymptomatic 
with tumors detected as an incidental finding on routine ophthalmologic examination. Visual 
symptoms include persistent photopsia, floaters, visual field loss, or visual acuity loss (Shields 
2014). Diagnosis is based on fundoscopic examination by an experienced clinician using 
noninvasive testing techniques such as ultrasound, fluorescein angiography (FA) and ocular 
coherence tomography (OCT). This trial will utilize enhanced depth imaging optical coherence 
tomography (EDI-OCT) which is more sensitive in assessing disease findings in choroidal 
melanoma than standard spectral domain optical coherence tomography (SD-OCT). CM is 
believed to result from transformation of benign choroidal nevi or develop as a de novo 
malignancy. Though early detection can be challenging, there are clinical features that suggest a 
lesion is “at-risk” for transforming into melanoma and these include lesion thickness over 2 mm, 
presence of orange pigment, ≤ 3 mm distance from the optic nerve, subretinal fluid 
accumulation, hollowness on ultrasound, and absence of halo (Shields 2014). Poor prognosis 
depends on several clinical factors including large tumor size, involvement with the ciliary body, 
increased age, and extraocular extension. 
Because CM is less prevalent than other cancers, is often asymptomatic in early phases, and is 
slow-growing, detection and prompt diagnosis have complicated treatment studies. In the 
absence of new therapies and efficacy trials, historical treatment focused on local control of 
tumor growth, most often through radiation treatments (both plaque brachytherapy and proton 
beam radiotherapy) or a surgery called enucleation (complete removal of the affected globe). 
Even with radical treatment such as enucleation; however, metastatic growth – most often and 
always fatally to the liver – has been widely reported (Collaborative Ocular Melanoma Study 
Group [COMS] 2004; Bishop 2014).The Collaborative Ocular Melanoma Study (COMS 1998), 
which recruited 3,217 patients with primary ciliary body or choroidal melanoma in the US from 
1987 to 1998, was commissioned to address the paucity of data regarding prospective evaluation 
of CM treatment, and it has subsequently produced a large body of data regarding CM. This 3- 
arm study included two multicenter randomized clinical trials. One arm compared the 
effectiveness of brachytherapy (also known as plaque brachytherapy, plaque radiotherapy or 
simply, plaque) to enucleation for treatment of medium-size (>2.5 mm to <10.00 mm) choroidal 
melanomas. The second arm compared the effectiveness of enucleation with and without 
preoperative external-beam radiotherapy for large choroidal melanomas (>10.00 mm). The third 
arm was an observational study of small (<2.5 mm) choroidal melanomas. 


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Cumulative rates of metastases at 5 and 10 years after treatment have been reported at 25% and 
34%, respectively (COMS 2005). The most frequently reported sites of metastases include the 
liver (90%), lungs (24%), and bone (16%) (COMS 2001a; COMS 2004). Patients with 
metastases that do not involve the liver have longer survival (19–28 months) (Eskelin 2000). 
The median survival for a patient with hepatic metastasis is 6 months (estimated survival of 15– 
20% at 1 year; 10% at 2 years), irrespective of treatment (Bedikian 2006; COMS 2005). 
Asymptomatic patients at the time of diagnosis of metastases have a slightly longer survival in 
relation to symptomatic patients (Kim 2010). 
COMS provides excellent historical control data for melanoma treatments, and has refined 
standard CM treatment protocols. For example, COMS showed no difference in 5- or 10- year 
mortality for large- and medium-sized UMs whether treated with plaque brachytherapy or 
enucleation (COMS 2001b); nor was there improved survival with preoperative radiation for 
large choroidal melanomas. Consequently, plaque has remained the standard of care treatment, 
while enucleation is reserved for patients with the most symptomatic and recurrent CM. The data 
also steer the direction of optimal treatment to secondary outcomes, such as preservation of 
visual acuity, instead of solely focusing on mortality and tumor growth. 
It is hypothesized that since Light-activated AU-011 treatment is both potent and highly targeted 
to the tumor that healthy ocular tissues will be preserved. 
 
4.2. 
Existing Therapies for Choroidal Melanoma 
CM is commonly treated according to size (or thickness) of the neoplasm (small ≤ 2.4 mm, 
medium = 2.5-10 mm, and large > 10 mm according to thickness as measured by ultrasound), 
documented growth rate, and location (COMS 2004b; Shields 2014). Currently, the most 
widely used first line treatment options are radiation therapy and enucleation. Management of 
small suspicious nevi that are at high risk of evolving into CM and small neoplasms is not 
standardized. Depending on a number of clinical judgment factors, including patient choice and 
rate of tumor growth, the patient may be treated immediately or followed further before being 
treated. 
There are two main types of radiation therapy: plaque brachytherapy (using iodine-125, 
ruthenium-106, or palladium-103) and external beam radiation therapy applied as proton beam 
radiotherapy (Laver 2010). Both of these radiation-based therapies require surgical procedures. 
In plaque brachytherapy, surgery is required to place the plaque, and in proton beam 
radiotherapy, surgery is required to enable localization of the tumor. In addition, radiation 
therapy lacks tumor tissue specificity. As such, it is usually accompanied by irreversible 
radiation damage to the retina and other ocular structures and results in up to a 6 line or more 
vision loss at 24 months (COMS 2001c; Bianciotto 2010). In 4% of cases, enucleation is 
performed after radiation therapy due to blindness, painful eyes or uncontrolled tumor growth 
(COMS 2001c). 
Alternatives to radiation therapy that are not standard of care but have been explored include 
transpupillary thermotherapy and photodynamic therapy. These therapies are not targeted and 
may offer limited benefit or may be appropriate for only a subset of patients (e.g., amelanotic 
tumors), and are not without risks, such as retinal bleeding or vision loss shortly after treatment 


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(Shields 2002; Pereira 2013). Larger scale tumors cannot be treated by radiation therapies and 
require enucleation. 
4.3. 
Viruses as Anti-Cancer Agents 
The use of viruses as anti-cancer agents has been considered for many years. Initially, the use of 
viruses in cancer therapy has been towards cancer cell lysis, as many viruses undergo a lytic 
phase in their life cycle. For instance, the Herpes Simplex Virus-1 is an oncolytic virus that has 
been developed for anti-cancer therapy as talimogene laherparepvec (T-VEC; Imlygic®) 
(Andtbacka 2013), and the FDA has approved T-VEC for the local treatment of unresectable 
cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial 
surgery, based on results from the Phase III OPTiM study (Andtbacka 2013, Broderick 2015). It 
utilizes the property of tumor lysis as a result of viral replication within the tumor as its 
mechanism of action. Other similar therapies based on other oncolytic virus types (Reovirus, 
Vaccinia virus) are also in clinical trials (Alemany 2013; Vacchelli 2013). However, the 
limitation of oncolytic virus based anti-cancer therapy is that of tumor targeting, and as such, T- 
VEC must be administered by direct intra-lesional injection. Additionally, the tumor cytotoxicity 
is dependent upon the active replication of the viral agent within the tumor, which may limit its 
efficacy and increase the risk of toxicity after multiple administrations. 
A novel approach to anti-cancer therapy is the use of viral like particles or pseudo-viruses as 
drug delivery vehicles for targeted therapy. The use of these novel viral-derived structures 
presents advantages over using full replicating viruses. VLPs and pseudo-viruses are comprised 
of the outer protein capsid of a virus without any of its genetic material and can be used to 
deliver drugs efficiently to tumors without relying on viral replication and as such, overcomes 
the limitations of oncolytic technologies. 
In particular, the papillomavirus (PV) has a simple two protein outer shell structure that self- 
assembles into 55 nM VLPs without incorporating the viral genome. Papillomaviruses have a 
unique tropism towards cancer cells that is mediated by the binding of the viral capsid to specific 
modifications of heparan sulfate proteoglycans (HSPGs) on the surface of the cancer cell 
(Handisurya 2012). 
In a number of nonclinical studies, it has been found that PV can bind cancer cells with high 
selectivity both in vitro and in vivo through a mechanism of action that involves the initial 
binding to HSPGs on the tumor cell membrane as well as the basement membrane (Handisurya 
2012). HSPGs interact with many proteins, playing a role in cell signaling via growth factors 
and chemokines modulating cell growth, motility, adhesion and differentiation. Up-regulation of 
HSPGs can be found on tumors, which can lead to unregulated autocrine signaling loops 
promoting tumorigenesis and angiogenesis (Blackhall 2001; Perrimon 2000; Schlessinger 2000; 
Yu 2002). 
4.4. 
Light Activated AU-011 for the Treatment of Choroidal Melanoma 
Though several treatment options exist for CM, no treatment both reliably controls tumor growth 
and preserves vision. Since Light-activated AU-011 therapy is extremely potent and highly 
targeted to the tumor itself, this therapy has great potential to preserve healthy ocular tissues. 


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The investigational treatment is Light-activated AU-011, a combination product consisting of a 
drug (AU-011) and a laser (Aura Photoactivation System) that delivers 689 nm light to activate 
the drug once it is bound to the tumor cells. AU-011 drug substance is a modified human 
papillomavirus-derived, empty viral like particle conjugated to approximately 200 molecules of 
a phthalocyanine-based photosensitizer IRDye® 700DX (the “Dye”). 
Figure 1 
Structure of AU-011 
 
The VLP is composed of two modified viral capsid proteins that self-assemble into an empty 
proteinaceous sphere of approximately 55 nM in diameter. Each VLP comprises 72 capsomeres, 
which are made of ~5 molecules of viral capsid protein L1 and ~1 molecule of capsid protein L2. 
The native amino acid sequence of the L1 protein FG loop which harbors the major epitopes for 
immune recognition has been altered to minimize an immunogenic response (Fleury 2014). 
The Dye molecule is a phthalocyanine that is derivatized with hydrophilic chains for aqueous 
application on one end and with a labile succinimido group on the other. The labile succinimido 
moiety covalently cross-links to proteins via the primary amine of lysyl residues. An aliphatic 
chain acts as a spacer to relieve steric hindrance between the protein and the phthalocyanine core 
for subsequent activation with light at 689 nm. Upon light activation at 689 nm, the 
phthalocyanine core acts as a photosensitizer. When targeted to the CM via the AU-011 VLP 
component, the photosensitizer activity of the Dye results in the selective cell necrosis of the CM 
tumor cells while sparing healthy cells (Mitsunaga 2012, Kines 2018). A second laser 
application will also be investigated in this study to ensure that maximum tumor cell necrosis 
occurs with each administration of Light-activated AU-011. This will ensure selection of the 
maximum feasible dose in terms of drug dose, number of treatments and number of laser 
applications. 
4.5. 
Nonclinical Studies of AU-011 
The nonclinical program for AU-011 consists of pharmacology (pharmacodynamic), 
pharmacokinetic, and toxicology studies. The results of these studies support the clinical 
development of Light-activated AU-011 for the treatment of primary CM. Refer to the IB for 
additional information. 


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4.5.1. 
Pharmacodynamic Studies 
In vitro and in vivo pharmacology or pharmacodynamic studies with AU-011 were undertaken to 
demonstrate the following attributes of AU-011: 
• AU-011 binding to ocular melanoma cells and the dependence of this binding on the 
interaction of AU-011 with HSPGs on the tumor cell surface. 
• AU-011 killing of uveal tumor cells as a function of AU-011 concentration or dose 
and the amount of light delivered. 
• Additionally, efficacy in orthotopic xenograft, animal models of UM after systemic 
and IVT administration of AU-011. 
Additional information on the AU-011 pharmacodynamic studies conducted to date is provided 
in the IB. 
 
4.5.2. 
Pharmacokinetics 
After IVT administration in a rabbit orthotopic xenograft model of UM, AU-011 was able to 
penetrate the tumor and was evenly distributed throughout the tumor. Studies in a rabbit 
orthotopic xenograft model demonstrated that detectable and quantifiable AU-011 concentrations 
were seen in tumor tissue at 30 minutes and 8 hours and less so at 16 and 24 hours. 
In separate studies in naïve rabbits, AU-011 was readily detectable in the vitreous and 
retina/choroid samples at 24 hours after IVT injection, and at 96 hours, AU-011 vitreous and 
retina/choroid concentrations were no longer detectable. No detectable concentrations of AU-011 
were found in the lens, and results showed that the systemic concentrations of AU-011 were near 
or below the limit of detection. 
4.5.3. 
Toxicology 
AU-011 was administered as a single dose via IVT injection at doses of 5, 20, or 40 µg/eye 
followed by laser photoactivation to dogs; after dosing, animals were observed for 7 days (Study 
Day 8, terminal sacrifice) or 35 days (Study Day 29, recovery sacrifice) to assess the 
reversibility, persistence, or delayed occurrence of effects (AU-TOX-020). No AU-011-related 
organ weight, macroscopic, or microscopic findings occurred at any of the doses and the No- 
Observable-Adverse-Effect Level (NOAEL) was considered to be 40 µg/eye of AU-011 
delivered as a single IVT dose with a corresponding laser treatment of 50 J/cm2. 
Additional information on the AU-011 toxicology studies conducted to date is provided in the 
Investigator’s Brochure (IB). 
 
4.6. 
Rationale for the Phase 1b/2 Clinical Trial of Light-Activated AU- 
011 in Choroidal Melanoma 
Light-activated AU-011 is being developed for the treatment of primary CM. This treatment is 
designed as a targeted tumor killing agent that has the potential to preserve healthy ocular tissues 
while controlling the tumor. This mechanism of action addresses a significant unmet medical 
need in patients with CM where vision loss is a common side effect of current therapies. If AU- 
011 treatment controls tumor growth successfully without the concomitant loss of vision 
associated with radiotherapy or complete loss of vision following enucleation, earlier treatment 


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of CM may become the standard of care for these patients. Because AU-011 specifically targets 
tumor cells, the response of tumors after treatment may be different than that following plaque 
radiotherapy, which is less selective and will cause death, not only to the melanoma tumor cells, 
but also the benign choroidal nevus cells, the vascular cells and even the sclera within the 
treatment area. The number of malignant tumor cells versus benign nevus cells in small 
melanomas is currently unknown. Some clinical trials (Singh 2005) presume that all melanomas 
arise from transdifferentiated nevi whereas others presume a portion of these lesions will occur 
spontaneously or ‘de novo.’ Despite the possibility of a different tumor response with a targeted 
therapy like AU-011 versus radioactivity, all tumors being treated with AU-011 should meet the 
definition of stable disease as a result of the selective necrosis of the tumor cell component of the 
lesion. 
The first expansion cohort (Cohort 9) is designed to establish the preliminary efficacy of AU-011 
delivered at the highest dose that is safe and well tolerated from the escalation phase of the trial. 
Cohort 10 is designed to provide estimates of growth rates in observation subjects and Cohort 11 
is designed to demonstrate the safety and tolerability of administering two 3-week treatment 
cycles of AU-011. Cohort 12 is designed to evaluate the efficacy and safety of AU-011 in 
subjects with documented growth who are similar to the planned Phase 3 population. 


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5. 
TRIAL OBJECTIVES AND PURPOSE 
5.1. 
Primary Objective 
The objective of this study is to evaluate the safety of IVT administration of one of 3 dose levels, 
repeat dose regimens and one or two laser applications of Light-activated AU-011 given in one 
or two treatment cycles in the treatment of subjects with small primary choroidal melanoma. 
5.2. 
Secondary and Exploratory Objectives 
Secondary objectives include evaluating: 
• Efficacy of AU-011 with one or two treatment cycles with the maximum safe and 
feasible dose 
• Efficacy and safety of AU-011 in subjects with documented growth 
• The immunogenicity of AU-011 
• A-scan amplitudes of the internal reflectivity of the lesion at study sites with diagnostic 
probes 
• Optical coherence tomography angiography (OCTA) image changes at study sites with 
OCTA imaging systems for Cohorts 6 through 9 


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6.
INVESTIGATIONAL PLAN
6.1.
Overall Study Design
Study Design:
This is an open-label, ascending single and repeat dose and cycle, multicenter study, designed to 
evaluate the safety, immunogenicity and efficacy of Light-activated AU-011 at 3 dose levels and 
single and 2 repeat dose regimens and cycles of Light-activated AU-011 and up to two laser 
applications in approximately 60 subjects with primary CM. The dose escalation design is shown 
in the figure below. Safety assessments will take place at all study visits and the efficacy 
assessments will commence at the Week 12 visit.
Figure 2 
Dose Escalation Schematic
*Alternating enrollment; enrollment in Cohorts 10 and 11 closed following approval of protocol revision 11 (Rev- 
11) at each site and subjects will be enrolled in Cohort 12.
Single Ascending Dose (SAD) Cohorts
Three subjects will receive a single IVT injection of Light-activated AU-011 low dose (20 µg in 
50 µL). The injection is followed 6 to 8 hours later by exposure to 689 nm laser light. No more 
than one subject may be treated per day, and the treated subject must complete his/her 24-hour 
post-treatment visit with no safety issues before the next subject in a given cohort may be 
treated.
If all 3 subjects in the low dose group complete treatment without any dose limiting toxicity 
(DLT), escalation to the medium dose level (40 µg in 
µL) group will be initiated. If a DLT
is observed in 1 subject in the low dose group, this group will be expanded to 6 subjects. Dose 
escalation will not be allowed if 2 or more subjects in the low dose group experience a treatment- 
related DLT. Instead, if 2 or more subjects in the low dose group experience a treatment-related 
DLT, dose reduction to 10 µg in 
µL may be considered for enrolling an additional 3 subjects. 
Single and Multiple Dose Cohorts
1 to 8 (20μg X1 to 80μg 3XQ.Wk)
Expansion Cohort (#9)
80μg 3XQ.Wk x 2 lasers
2 Cycles of AU-011 (#12) – Documented
Growth
2 Cycles of AU-011 (#11)*– Risk Factors 
With or Without Documented Growth
Observation Cohort (#10)* - Risk Factors 
No Documented Growth


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One week after the last subject in the low dose group completes treatment, the study medical 
monitor and independent ocular oncologist will review safety data for all subjects in the low dose 
group. After review and confirmation that the data support proceeding to treatment with the 
medium dose group, three subjects will receive a single IVT injection of Light-activated AU-011 
medium dose (40 µg in 
µL). The injection is followed 6 to 8 hours later by exposure to 689 
nm laser light. If all 3 subjects in the medium dose group complete treatment without any dose 
limiting toxicity (DLT), escalation to the high dose level group will be initiated. If a DLT is 
observed in 1 subject in the medium dose group, this group will be expanded to 6 subjects. If 2 
or more subjects in the medium dose group experience a DLT after their treatment, this will 
confirm that the low dose level is the maximum feasible dose (due to formulation limits). 
One week after the last subject in the medium dose group completes treatment, the study medical 
monitor and an independent ocular oncologist will review safety data for all subjects in the 
medium dose group. After review and confirmation that the data support proceeding to treatment 
with the high dose group, three subjects will receive a single dose of Light-activated AU-011 
high dose (80 µg administered as 2 injections of 40 µg in 
µL not more than two hours apart). 
The second injection is followed 6 to 8 hours later by exposure to 689 nm laser light. If a DLT is 
observed in 1 subject in the high dose group, this group will be expanded to 6 subjects. If 2 or 
more subjects in the high dose group experience a DLT after their treatment, this will confirm 
that the medium dose level is the maximum feasible dose and the dose chosen for the repeat dose 
phase of the study will drop to one dose below the maximum feasible dose of 40 µg and the 
lower dose of 20 µg will be given as repeat doses. 
Multiple Ascending Dose (MAD) Cohorts 
One day after the last subject in the high dose group completes treatment, the study medical 
monitor and independent ocular oncologist will review safety data for all subjects and 
recommend proceeding to the repeat dose phase of the study. 
After review and confirmation that the data support proceeding to repeat dose regimens, 3 
subjects will receive an intravitreal injection of 40 µg in 
µL of Light-activated AU-011 as 2 
repeat doses 1 week apart. Each injection is followed 6 to 8 hours later by exposure to 689 nm 
laser light. 
If all 3 subjects in this 2 repeat 40 µg dose group complete treatment without any dose limiting 
toxicity (DLT) after 2 injections, then this regimen may be investigated further in subsequent 
studies. If a DLT is observed in 1 subject in this 2 repeat 40 µg dose group, this group will be 
expanded to 6 subjects. If 2 or more subjects in this 2 repeat 40 µg dose group experience a DLT 
after their treatment, this will confirm that a lower repeat dose regimen should be investigated. 
One day after the last subject in the 2 repeat 40 µg dose group completes treatment, the study 
medical monitor and independent ocular oncologist will review safety data for all subjects and 
identify whether it is safe to evaluate 3 repeat 40 µg doses in the next cohort of the study. 
After review and confirmation that the data support proceeding to 3 repeat 40 µg dose regimen, 3 
subjects will receive an intravitreal injection of 40 µg in 
µL of Light-activated AU-011 as 3 
repeat doses 1 week apart. Each injection is followed 6 to 8 hours later by exposure to 689 nm 
laser light. 


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If all 3 subjects in this 3 repeat 40 µg dose group complete treatment without any dose limiting 
toxicity (DLT) after 3 injections, escalation to the next dose cohort will be initiated. If 2 or more 
subjects in this 3 repeat 40 µg dose group experience a DLT after their treatment, this will 
confirm that a fewer number of repeat administrations, or a lower dose at each 
administration should be investigated. 
One day after the last subject in the 3 repeat 40 µg dose group completes treatment, the study 
medical monitor and independent ocular oncologist will review safety data for all subjects and 
identify the maximum feasible dose for continued evaluation in the repeat dose phase of the 
study. After review and confirmation that the data support proceeding, an 80 µg single dose 
repeat laser regimen will be initiated. Three subjects will receive intravitreal administration of 80 
µg of Light-activated AU-011 administered as 2 injections of 40 µg in 
µL (not more than 2 
hours apart) followed by two 689 nm laser applications 30 minutes (± 10 minutes) apart, with the 
first of the 2 laser applications occurring 6 to 8 hours after the second injection. 
If all 3 subjects in this 80 µg single dose followed by 2 laser applications dose group complete 
treatment without any dose limiting toxicity (DLT), then the study may progress to the next 
cohort. If a DLT is observed in 1 subject in this 2 repeat laser applications following 80 µg single 
dose group, this group will be expanded to 6 subjects. If 2 or more subjects in this 2 repeat laser 
applications following 80 µg single dose group experience a DLT after their treatment, this will 
confirm that a lower dose followed by repeat laser regimen, or a repeat dose followed by single 
laser application, should be investigated further. 
One day after the last subject in the 2 repeat laser applications following 80 µg single dose group 
completes treatment, the study medical monitor and independent ocular oncologist will review 
safety data for all subjects and identify whether it is safe to evaluate repeat laser applications 
after each of 3 repeat doses of 80 µg in the study. 
After review and confirmation that the data support proceeding to the 3 repeat 80 µg dose 
regimen followed by a single laser application, 3 subjects will receive an intravitreal 
administration of 80 µg of Light-activated AU-011 administered as 2 injections of 40 µg in 
µL (not more than 2 hours apart) as 3 repeat doses one week apart. Each administration is 
followed 6 to 8 hours (after the second injection) later by exposure to 689 nm laser light. 
One day after the last subject in the 3 repeat 80 µg dose group, followed by a single laser 
application, completes treatment and 4 weeks after the last subject in the 80 µg single dose 
followed by 2 laser applications dose group complete treatment, the study medical monitor and 
independent ocular oncologist will review safety data for all subjects and identify whether it is 
safe to evaluate 3 repeat doses of 80 µg, each followed by 2 repeat laser applications, in the next 
cohort of the study. 
After review and confirmation that the data support proceeding to repeat laser applications after 
each of 3 repeat 80 µg doses, 3 subjects will receive an intravitreal administration of 80 µg of 
Light-activated AU-011 administered as 2 injections of 40 µg in 
µL (not more than 2 hours 
apart) as 3 repeat doses one week apart. Each administration is followed 6 to 8 hours (after the 
second injection) later by 2 exposures to 689 nm laser light 30 minutes (± 10 minutes) apart. 
If all 3 subjects in this group, who receive 3 repeat 80 µg doses, each followed by 2 repeat laser 
applications, complete treatment and have been followed for 4 weeks without any dose limiting 
toxicity (DLT) after 3 weekly administrations, then this dose and regimen will be considered the 


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maximum feasible dose and investigated in the expanded cohort. If a DLT is observed in 1 
subject in this 3 repeat 80 µg dose with 2 repeat laser applications group, this group will be 
expanded to 6 subjects. If 2 or more subjects in this 3 repeat 80 µg dose with 2 repeat laser 
applications group experience a DLT after their treatment, this will confirm that a fewer number 
of repeat administrations of either Light-activated AU-011 or laser, or both, or a lower dose of 
Light-activated AU-011 at each administration should be investigated further. 
Four weeks after the final treatment of the final subject in this cohort, a review of the safety data 
(including EDI-OCT) by the study medical monitor and independent ocular oncologist will 
occur. If safety is confirmed, the 3 repeat 80 µg dose with 2 repeat laser applications will be 
considered the maximum feasible and tolerated dose and this regimen will be expanded by up to 
12 additional subjects in Cohort 9. 
Repeat Cycle and Observation Cohorts 
Once the last subject in the expansion cohort has been enrolled and safety of the maximum safe 
and feasible dose is confirmed, approximately 6 additional subjects, who fulfil the criteria for the 
clinical diagnosis of CM, but without documented growth, will be enrolled into an observation 
cohort (Cohort 10). These subjects will be assessed every 3 months (ie, 90 day (+/- 7 days) 
intervals from the Screening Visit) until tumor growth of the CM lesion is established (as defined 
in Section 8.3.4.) and at which time will then receive treatment with AU-011, as 3 repeat 80 µg 
doses, each followed by 2 repeat laser applications and move to the same visit schedule as 
subjects entering the trial and receiving treatment with AU-011 immediately. These subjects will 
receive Cycle 2 of AU-011 administered as 3 repeat 80 µg doses, each followed by 2 repeat laser 
applications no earlier than the Week 12 Visit and after resolution of any inflammation resulting 
from the first cycle or when the inflammation is minimal and decreasing based on investigator 
judgement. Cycle 2 should be administered as soon as reasonably possible after inflammation 
has resolved or is minimal and decreasing based on investigator judgement. If the fovea is near 
the tumor edge, an adjustment to the laser procedure should be performed on each treatment day 
of both cycles as outlined in section 8.2.2 and the Injection and Laser Procedure Manual. 
In addition, approximately 6 further subjects, who meet the criteria for a clinical diagnosis of 
CM, with or without documented growth, will enter Cohort 11 and receive two cycles of AU-011 
treatment (each cycle will be comprised of 3 repeat 80 µg doses, each followed by 2 repeat laser 
applications). Cycle 2 of AU-011 will be administered as 3 repeat 80 µg doses, each followed by 
2 repeat laser applications no earlier than the Week 12 Visit and after resolution of any 
inflammation resulting from the first cycle or when the inflammation is minimal and decreasing 
based on investigator judgement. Cycle 2 should be administered as soon as reasonably possible 
after inflammation has resolved or is minimal and decreasing based on investigator judgement. If 
the fovea is near the tumor edge, an adjustment to the laser procedure should be performed on 
each treatment day of both cycles as outlined in section 8.2.2 and the Injection and Laser Procedure 
Manual. 
The intention is to alternate the enrolment of Cohorts 10 and 11. If during the enrollment of these 
subjects, a subject has just been enrolled into Cohort 11 and a subject with documented growth 
presents, then that subject may instead be enrolled into Cohort 11 rather than Cohort 10 for 
which they would not be eligible due to the presence of documented growth and instead will be 
assigned to receive the first of 2 cycles of AU-011. 


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If 2 subjects experience a DLT during treatment with Cycle 2, as defined in Section 8.4.1., then 
no further subjects will receive Cycle 2 of AU-011 until discussed with the independent ocular 
oncologist and medical monitor and continuation of enrollment is confirmed. 
Subjects with Documented Growth 
Enrollment in Cohorts 10 and 11 was closed following approval of protocol revision 11 (Rev-11) 
at each site. An additional cohort, Cohort 12, of subjects with minimum defined levels of 
documented growth will be initiated to allow assessment of safety and efficacy of 2 cycles of 
AU-011 treatment in this key subgroup of subjects with CM. Since Cohort 12 has the same dose 
as Cohort 11 no safety review will be required. 
Up to 15 subjects, who meet the criteria for a clinical diagnosis of CM with documented growth 
as defined in Inclusion Criteria 5C, will enter Cohort 12 and receive two cycles of AU-011 
treatment (each cycle will be comprised of 3 repeat 80 µg doses, each followed by 2 repeat laser 
applications). Cycle 2 of AU-011 will be administered as 3 repeat 80 µg doses, each followed by 
2 repeat laser applications no earlier than the Week 12 Visit and after resolution of any 
inflammation resulting from the first cycle or when the inflammation is minimal and decreasing 
based on investigator judgement. Cycle 2 should be administered as soon as reasonably possible 
after inflammation has resolved or is minimal and decreasing based on investigator judgement. If 
the fovea is near the tumor edge, an adjustment to the laser procedure should be performed on 
each treatment day of both cycles as outlined in section 8.2.2 and the Injection and Laser Procedure 
Manual. 
If 2 subjects experience a DLT during treatment with Cycle 2, as defined in Section 8.4.1., then 
no further subjects will receive Cycle 2 of AU-011 until discussed with the independent ocular 
oncologist and medical monitor and continuation of enrollment is confirmed. 
Study Methods 
Subjects will be screened for enrollment into the study after providing written informed consent 
between Day -28 and Day 1. Screening procedures include medical history, ophthalmic 
assessments, vital signs, and safety laboratory analyses. To be eligible for study enrollment, 
subjects will have a small CM of ≥ 2.0 and ≤ 3.0 mm in thickness, and largest basal diameter ≤ 
13.0 mm, OR tumor thickness of ≥ 1.2 and ≤ 3.0 mm with documented growth and largest basal 
diameter ≤ 13.0 mm. To be eligible for enrollment in Cohort 12, subjects will have clinically 
diagnosed primary CM with tumor thickness of ≥ 0.5 mm and ≤ 3.0 mm on B-scan ultrasound, a 
largest basal diameter of ≤ 13.0 mm on fundus photos with an estimated tumor volume ≤50 mm3 
associated with documented tumor growth, defined as ≥ 0.4 mm based on intersite measurements 
(clinical site and referring center) or ≥ 0.3 mm based on within site measurements on tumor 
thickness within 2 years of screening. 
Qualified subjects will be enrolled into one of the 12 Cohorts described above. Each subject in 
the first three Cohorts 1-3 and in Cohort 6 will receive a single intravitreal treatment with Light- 
activated AU-011, subjects in Cohort 4 will receive 2 repeat doses, and subjects in Cohorts 5, 7, 
8, 9, 10, 11 and 12 will receive 3 repeat doses. After administration of Light-activated AU-011, 
the CM is exposed to 689 nm laser light. Subjects in Cohorts 6, 8, 9, 10, 11 and 12 will receive 2 
laser applications 30 minutes (± 10 minutes) apart at 6 to 8 hours after each IVT administration 
(after the second injection for these 80 µg cohorts), while the remaining cohorts will receive a 
single laser application at 6 to 8 hours after each IVT administration (after the second injection in 


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the 80 µg cohorts). In addition, Cohorts 10, 11 and 12 will receive Cycle 2 of AU-011 at the 
same dose and regimen no earlier than the Week 12 Visit and after resolution of any 
inflammation resulting from the first cycle or when the inflammation is minimal and decreasing 
based on investigator judgement. Cycle 2 should be administered as soon as reasonably possible 
after inflammation has resolved or is minimal and decreasing based on investigator judgement. If 
the fovea is near the tumor edge, an adjustment to the laser procedure should be performed on 
each treatment day of both cycles as outlined in section 8.2.2 and the Injection and Laser Procedure 
Manual. 
If subjects are discharged during daylight hours, appropriate sun protection, e.g., sunglasses and 
a hat, will be required. 
Study subjects will be required to return for an ocular examination 24 hours ± 4 hours following 
intravitreal administration, followed by 11 visits (Day 8, Day 15, Day 29, Week 6, Week 8, 
Week 12, Week 26, Week 39, Week 52, Week 78, and Week 104). At these visits, subjects will 
be monitored with systemic and ophthalmic assessments. In addition, subjects in both the 2 and 3 
repeat Light-activated AU-011 administration cohorts will have an additional safety visit on Day 
9. Subjects in the 3 repeat Light-activated AU-011 administration cohorts will have an 
additional safety visit at Day 16. Subjects in the observation cohort (Cohort 10) will be seen 
every 3 months (ie, 90 day (+/- 7 days) intervals from the Screening Visit) until tumor growth is 
established and then seen at the schedule described in Section 10 and Appendix 1 until the time 
of receiving Cycle 2, when they will then follow the schedule described in Appendix 4. Subjects 
in the observation cohort in whom tumor growth is not observed during the 2 year study period 
will exit the study at Week 104. Subjects in the repeat cycle of AU-011 cohorts (Cohorts 11 and 
12) will also follow the schedule described in Section 10 and Appendix 1 until the time they 
receive the second cycle of AU-011, when they will then follow the schedule described in 
Appendix 4. 
If the second cycle of AU-011 occurs after Visit 15 (Week 78), subjects will be followed for 26 
weeks post-treatment and then may be rolled into the long-term follow-up study pending subject 
consent. Details regarding the follow-up visit schedule after the second cycle of AU-011 can be 
found in Appendix 4. 
All subjects’ study participation will be for a minimum of 2 years and all subjects in this study 
may then be rolled into the long-term follow-up study pending consent. 
Ocular assessments including Best Corrected Visual Acuity (BCVA) by Early Treatment 
Diabetic Retinopathy Study method (ETDRS), slit lamp biomicroscopy, intraocular pressure 
(IOP), fundoscopy, color fundus photography (FP), fluorescein angiography (FA), B-scan 
ultrasound (B-scan), A-scan ultrasound (A-scan), enhanced depth imaging optical coherence 
tomography (EDI-OCT), optical coherence tomography angiography (OCTA), and visual fields 
will be evaluated during the study. Phlebotomy will be performed at various time points for 
hematology, serum chemistry and anti-drug antibodies (ADA). Concomitant medications and 
adverse events (AEs) will be reviewed through 30 days following the study treatment. After 30 
days, for Cohorts 1 to 9, only AEs or SAEs determined by the Investigator to be related to study 
product and/or study procedures are to be reported. For Cohort 10, 11 and 12 subjects, 
concomitant medications and all adverse events will be reviewed through their last study visit. If 
peri-tumoral whitening/pigmentary changes are seen during the study, additional assessments as 
outlined in Section 10.3.10 should be conducted. Further treatment (additional therapy) for CM 


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will be documented throughout the study. Section 10 provides further details on the conduct of 
the study, study visits, and assessments. 
Ocular imaging, including B-scan, A-scan, FP, FA, EDI-OCT, and OCTA will be read by a 
centralized Independent Reading Center (IRC) to provide consistency and reliability in data 
generated for each subject at each study site. At least two independent readers at the IRC will 
review required screening B-scan images for determination of eligibility and at the predefined 
time points. 
6.2. 
Criteria for Study Termination 
The Sponsor may suspend or terminate the study at any time for any reason. If the Investigator 
suspends or terminates the study at their site, the Investigator will promptly inform the Sponsor 
and the Institutional Review Board (IRB) and provide them with a detailed written explanation. 
The Investigator will also return all study drug and other materials to the Sponsor as required. 
Upon study completion, the Investigator will provide the IRB with notice of closure. 


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7. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
To be eligible for this clinical study, subjects must provide written informed consent and meet all 
of the inclusion criteria and none of the exclusion criteria. 
7.1. 
Subject Inclusion Criteria 
Subjects must: 
1. Be at least 18 years of age of either gender or any race. 
2. Have been informed about the nature and requirements of the study, voluntarily agreed to 
participate in the study, and documented this by signing the Informed Consent Form 
(ICF) before participating in any study-related activities. 
3. Be willing and able to follow all instructions and attend all study visits. 
4. Per the expert opinion of the Investigator, have clinically diagnosed primary CM with no 
known metastatic disease. 
5. Have clinically diagnosed primary CM: 
A. with tumor thickness of ≥ 1.2 mm and ≤ 3.0 mm on B-scan ultrasound and with a 
largest basal diameter of ≤ 13.0 mm on fundus photos associated with tumor growth, 
 
OR 
B.  with tumor thickness of ≥ 2.0 mm and ≤ 3.0 mm on B-scan ultrasound and with a 
largest basal diameter of ≤ 13.0 mm on fundus photos associated with the presence of 
subretinal fluid by OCT AND at least one of the following: 
a. Overlying orange pigment (lipofuscin) on fundus photos 
b. Vision loss 
c. Flashes or floaters 
OR 
C. Criteria for Cohort 12: with tumor thickness of ≥ 0.5 mm and ≤ 3.0 mm on B-scan 
ultrasound, a largest basal diameter of ≤ 13.0 mm on fundus photos with an estimated 
tumor volume ≤50 mm3 associated with tumor growth within 2 years of screening 
(defined as ≥ 0.4 mm increase based on intersite measurements or ≥ 0.3 mm based on 
within site measurements on tumor thickness) 
NOTE: Whenever available at the investigative site or referring site, historical images 
(B-scans and/or color fundus photos) for all subjects should be provided to the 
Independent Reading Center at the time of entry to the study. The investigative site 
should make all reasonable efforts to obtain this information from referring sites. 
6. In the opinion of the treating physician, the subject could be managed by interventional 
therapy, or by cautious observation. 
7. Be treatment-naïve for their primary CM. 


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8. Have a tumor for which the entire extent must be able to be imaged on required fundus 
photography in a single frame and treated by the laser. 
9. If female and capable of becoming pregnant, agree to have pregnancy testing performed 
at screening (must be negative) and if required at Visit 2 (must be negative); must not be 
lactating; and must agree to use a medically acceptable form of birth control before 
administration of the investigational product and for three months after administration of 
the investigational product. Women considered capable of becoming pregnant include all 
females who have experienced menarche and have not experienced menopause (as 
defined by amenorrhea for greater than 12 consecutive months) or have not undergone 
successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral 
oophorectomy). 
10. For women of childbearing potential and for males with sexual partners of childbearing 
potential: Acceptable forms of birth control are spermicide with barrier, oral 
contraceptive, injectable or implantable method of contraception, transdermal 
contraceptive, intrauterine device, or surgical sterilization of partner. For non-sexually 
active females and males, abstinence will be considered an acceptable form of birth 
control. 
11. Be otherwise in good general health, with no significant or uncontrolled medical 
conditions, as determined by the Investigator. 
12. Be able and willing to avoid all prohibited medications for the appropriate washout 
period (See Section 8.3.2). 
 
7.2. 
Subject Exclusion Criteria 
Subjects must not: 
1. Have known contraindications or sensitivities to IRDye®700DX phthalocyanine-based 
dye, or laser in the study eye. 
2. Have any ocular condition in the study eye that, in the Investigator’s opinion, could affect 
the subject's safety or trial parameters. 
3. Have a CM that invades or encompasses the optic nerve that precludes treatment, as 
determined by the investigator and/or shows extraocular extension. 
4. Have metastatic disease confirmed by abdominal and chest imaging within three months 
prior to screening. 
5. Have undergone vitrectomy at any time or have undergone any ocular surgical 
intervention in the study eye within three months before Visit 1, or are planning/will 
require ocular surgery in the study eye prior to the study drug administration. If the 
subject is likely to require cataract surgery in the study eye at any time prior to the Week 
104 visit, he/she should not be enrolled. 
6. Have a history of rhegmatogenous retinal detachment, diabetic retinopathy, or other 
active retinal disease in the study eye unrelated to the CM. 
7. Have any active ocular disease in the study eye (other than CM) that may progress during 
the study and result in a change in vision or loss in vision (e.g., clinically significant 


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corneal dystrophies, keratoconus, glaucoma or clinically significant retinal or macular 
disease). 
8. Have an active ocular infection (bacterial, viral, or fungal). 
9. Use or require use of heparin or low molecular weight heparins within one week of 
treatment. 
10. Use or require use of immunosuppressive or antineoplastic medications within five half- 
lives of Visit 1. Steroids, including inhalation steroids, are permitted. 
11. Have previously received HPV vaccination. 
12. Any active malignancies other than CM, or squamous or basal cell skin cancer. If there is 
evidence of clinical remission for at least one year, the subject’s eligibility may be 
discussed with the medical monitor. 
13. Have any significant illness (e.g., an uncontrolled autoimmune disease, severe 
cardiovascular disease [confirmed by a cardiologist], active infection, etc.) that the 
Investigator determines could interfere with study participation or safety, or put the 
subject at any unnecessary risk. 
14. Have planned or will require systemic surgery during the active study treatment period. 
15. Have used an investigational drug or medical device within 30 days or 5 half-lives of 
Visit 1 or be concurrently enrolled in another investigational product trial. 
 
7.3. 
Withdrawal of Subjects 
7.3.1. 
Subject Discontinuation 
Subject participation is voluntary; any subject may discontinue participation in the study without 
prejudice or may be withdrawn from the study by the Investigator or Sponsor for the following 
reasons: 
• Pregnancy 
• Intolerable toxicity thought to be related to study drug 
• Subject request 
• Inability to comply with trial requirements 
• Conditions requiring treatment intervention not permitted by protocol 
• Intercurrent illness (Investigator’s discretion) 
• Non-compliance/lost to follow-up 
• Discontinuation by Sponsor 
If the subject wishes to withdraw study consent, every effort will be made to encourage the 
subject to return to the study site for a final visit prior to withdrawing consent. 
 
7.3.2. 
Loss to Follow-up 
The study sites will attempt to follow-up on subjects who do not return for scheduled study 
examinations. Sites must make a minimum of three documented attempts via telephone, email, or 
regular mail to contact the subject. If the subject does not reply to any of these attempts, the site 
must send a letter by certified mail (with a request for notification of receipt of delivery) to the 


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subject. If a subject is non-responsive to these follow-up attempts, he/she will be considered to 
be lost to follow-up and the electronic case report form (eCRF) will be updated to note lost to 
follow-up as the reason for discontinuation. 
 
7.3.3. 
Early Subject Termination or Subject Withdrawal 
Subjects who discontinue from the study early for any reason will be asked to undergo Week 
104/Early Termination assessments. If termination occurs before Visit 11 (Week 12), then all 
ophthalmic assessments, including imaging should be performed on both eyes at the Early 
Termination Visit. 
All subjects who discontinue from the study early will be followed for up to 30 days after their 
last administration of study medication for the development of new AEs. 
 
7.3.4. 
Follow-up of Subjects with Adverse Events 
If any study subject has an AE at the time of completion, termination, or withdrawal, the subject 
should be followed until the event has resolved, returned to baseline, or in case of permanent 
impairment, until the condition stabilizes. If in the opinion of the Investigator, the AE or 
laboratory abnormality/ies are not likely to improve because of the underlying disease, the 
Investigator must record his or her reasoning for this decision in the subject’s medical record and 
on the eCRF. 


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8. 
TREATMENT OF SUBJECTS 
8.1. 
Description of Study Drug 
Light-activated AU-011 is a combination product consisting of a drug (AU-011) and a laser 
(Aura Photoactivation System) that delivers 689 nm light to activate the drug once it is bound to 
the tumor cells. AU-011 drug substance is a modified human papillomavirus-derived, empty 
viral like particle conjugated to approximately 200 molecules of a phthalocyanine-based 
photosensitizer IRDye®700DX. AU-011 will be administered via intravitreal injection as a low 
dose (20 µg)  intravitreal injection ( 
µL injection), a medium dose (40 µg) per intravitreal 
injection ( 
µL injection), or a high dose (80 µg) per intravitreal injection ( 
µL 
injections with interim IOP assessment). Refer to Section 4.4. Additional information can be 
found in the IB. 
8.2. 
AU-011 Treatment 
8.2.1. 
Administration of AU-011 
In this clinical trial, AU-011 study drug will be administered by IVT injection and will be 
followed by laser light application (689 nm) to the CM 6 to 8 hours after intravitreal 
administration of AU-011. The maximum concentration of the current AU-011 formulation is 
40 µg in 
µl and as a result, the maximum feasible dose is 80 µg administered as 2 injections 
of 40µg in  
µl. 
Subjects in Cohorts 1 (20 µg single dose), 2 (40 µg single dose) and 3 (80 µg single 
administration given as 2 injections of 40 µg in  µl) will receive one treatment followed by a 
single laser application, subjects in Cohort 4 (40 µg two repeat doses) will receive 2 injections 
one week apart followed by a single laser application, subjects in Cohort 5 (40 µg three repeat 
doses) will receive 3 injections one week apart followed by a single laser application, subjects in 
Cohort 6 (80 µg single dose followed by 2 laser applications) will receive a single dose 
administered as 2 injections of 40 µg in 
µl followed by 2 laser applications, subjects in 
Cohort 7 (80 µg three repeat doses followed by a single laser application) will receive 3 doses 
each administered as 2 injections of 40 µg in 
µl one week apart followed by a single laser 
application, and subjects in Cohorts 8 and 9 (80 µg three repeat doses followed by two laser 
applications) will receive 3 doses each administered as 2 injections of 40 µg in 
µl one week 
apart followed by 2 laser applications. Subjects in cohorts 3, 6, 7, 8 and 9 receiving 80 µg doses 
given as 2 injections of 40 µg in 
µl will have their IOP measured prior to and after each 
injection. IOP must be 21 mm Hg or less before each injection can be given and the maximum 
interval between the two injections is 2 hours. IOP must also be 21 mm Hg or less before the 
patient is discharged from the clinic. 
Subjects enrolled in the observation cohort and after exhibiting tumor growth (Cohort 10), and 
repeat cycle cohorts (Cohorts 11 and 12) will receive 2 cycles of AU-011 at the highest feasible 
and tolerated dose of 3 repeat 80 µg doses, each followed by 2 repeat laser applications. The 
second cycle of AU-011 will be administered no earlier than the Week 12 Visit and after 
resolution of any inflammation resulting from the first cycle or when the inflammation is 
minimal and decreasing based on investigator judgement. Cycle 2 should be administered as 
soon as reasonably possible after inflammation has resolved or is minimal and decreasing based 


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on investigator judgement. However, if 2 subjects experience a DLT during treatment with Cycle 
2, as defined in Section 8.4.1, then no further subjects will receive Cycle 2 of AU-011 until 
discussed with the independent ocular oncologist and medical monitor and continuation of 
enrollment is confirmed. If the fovea is near the tumor edge, an adjustment to the laser procedure 
should be performed on each treatment day of both cycles as outlined in section 8.2.2 and the 
Injection and Laser Procedure Manual. 
All subjects will be monitored with systemic and ophthalmic assessments. If subjects are 
discharged during daylight hours, appropriate sun protection, e.g., sunglasses and a hat, will be 
required. Study subjects will be required to return for an ocular examination 24 hours ± 4 hours 
following administration of AU-011 for slit lamp biomicroscopy, IOP, fundoscopy, assessment 
of any changes in their vision, and AE and concomitant medications review. Cohort 1, 2, and 3 
subjects only will also have B-scan ultrasound performed 24 ± 4 hours following administration 
of AU-011. 
Procedures for intravitreal injection, which will be administered by an ophthalmologist, are 
provided in the study procedures binder. 
 
8.2.2. 
Laser Activation of AU-011 
This study will use the Aura Photoactivation System which will deliver light at 689 nm to the 
CM 6 to 8 hours after the intravitreal administration (after the second intravitreal injection for 
the subjects receiving 80 µg doses) of study drug AU-011. A second laser application will also 
be investigated in this trial to ensure that maximum tumor cell necrosis occurs with each 
administration of Light-activated AU-011. 
The Injection and Laser Procedure Manual provides detailed instructions on the procedures for 
laser application for this study including tumor margin, laser spot size, foveal treatment, and 
specific high-risk tumor situations including but not limited to: 
Subfoveal tumors 
Tumor edge ≤1.0mm from the fovea 
Tumor edge >1.0mm to 2.0mm from the fovea 
Tumor edge >2.0mm to 3.0mm from the fovea 
Tumor edge >3.0mm from the fovea 
Suggested treatment patterns and estimated number of treatment spots for several tumor size 
examples have been updated in the Injection and Laser Procedure Manual in conformance to the 
instructions provided. 
8.3. 
Concomitant Medications 
All concomitant medications taken by the study subjects within seven days prior to the first dose 
of study drug will be documented. Additionally, through 30 days after the completion of study 
treatment, the Investigator or study staff will ask the subject about any new medications he/she is 
taking or has taken after the start of the study drug and this information will be documented in 
the study eCRF. For Cohort 10, 11 and 12 subjects, concomitant medications will be 
documented through their last study visit. Further treatment (additional therapy) for CM will be 
documented throughout the course of the study. 


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The safety committee may, at its discretion, decide to mandate prophylactic use of topical and/or 
systemic corticosteroids at any point in this dose and frequency escalation study if the severity 
and/or time course of ocular inflammation suggests that doing so would be in the best interest of 
study subjects. If any diabetic subjects are prescribed systemic steroids, the site should ensure 
that the subject is willing to check their blood pressure and fasting glucose levels on a daily basis 
during treatment and to inform the study physician immediately of any signs or symptoms that 
suggest either are abnormal. 
Artificial tears may be administered within the immediate 24-hour period prior to study 
treatment and following the study treatment. However, a new, unopened bottle or vial must be 
used. 
 
8.3.1. 
Concomitant Steroid Treatment 
On study Day 1, ie, day of first administration of AU-011 treatment and before the first laser 
administration, the Investigator should begin topical 1% prednisone acetate or difluprednate 
0.05% topical eye drops and an oral prednisone taper or periocular steroid injection. Subtenon’s 
injection of triamcinolone acetonide (40mg/ml) can be given with up to 1 ml delivered as 
tolerated. Oral prednisone starting at 60 mg/day and tapering off (for example, over six to eight 
weeks) can also be used. 
These regimens are intended to be a minimum treatment regimen and the Investigator can treat 
with higher doses than proposed in the guidelines in order to minimize the severity and duration 
of posterior segment inflammation and allow Cycle 2 of AU-011 therapy to be administered at 
12 weeks or as soon as possible thereafter. 
If posterior synechiae develop, the Investigator can also start mydriatric agents like mydriacyl, 
cyclogyl or atropine and miotic inhibitors like phenylephrine. 
In the event of any potential breakthrough inflammation, the Investigator may restart clinically 
appropriate levels of oral prednisone treatment. Additionally, the Investigator may choose to 
taper subjects more quickly than described above. 
If a subject continues to show inflammation during the active treatment period, the Investigator 
should determine the necessity of increasing the oral prednisone dose to 80 mg daily with slow 
taper or hospital admission with 250 mg intravenous methylprednisolone 4 times per day over 3 
days to protect the eye and vision. 
When Cycle 2 or additional therapy of AU-011 is administered, topical prednisone acetate 1% or 
difluprednate 0.05% topical eye drop taper and periocular steroid injection or oral steroid use 
should be instituted on the day of the first AU-011 treatment and before the first laser 
application. The topical steroid eye drop can be tapered and discontinued at the discretion of the 
Investigator. The periocular or oral steroid may consist of a periocular triamcinolone acetonide 
(40mg/ml) injection up to 1 ml as tolerated or an oral steroid taper similar to the oral taper 
described for Cycle 1 of therapy above. These regimens are intended to be a minimum treatment 
regimen and the Investigator can treat with higher doses than proposed in the guidelines, but not 
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8.3.2. 
Prohibited Concomitant Medications 
Heparins or low molecular weight heparins are prohibited within one week prior to AU-011 
intravitreal injections. Immunosuppressive or antineoplastic medications are prohibited within 5 
half-lives of Visit 1. Steroids, including inhalation steroids, are permitted. 
 
8.3.3. 
Additional Therapy 
 
Additional therapy with AU-011 at the maximum tolerated and feasible dose of 3 repeat doses of 
80 µg each followed by two laser applications (treatment regimen) can be provided to: 
• ensure that all subjects are able to receive the maximum tolerated and feasible dose, 
particularly for subjects that were treated with lower doses previously 
• allow additional treatment regimens in subjects that have stable disease (treatment 
extension) 
• allow retreatment in subjects that meet the protocol definition of disease progression 
 
If the fovea is near the tumor edge, an adjustment to the laser procedure should be performed on 
each treatment day as outlined in section 8.2.2 and the Injection and Laser Procedure Manual. 
Subjects may be considered for additional therapy with AU-011 (defined above) after Visit 11 
(Week 12) and only after inflammation from the previous treatment has resolved or when the 
inflammation is minimal and decreasing based on investigator judgement. Additional therapy 
with AU-011 must be approved by the Sponsor on a case-by-case basis prior to the 
initiation of therapy. Alternatively, also after Visit 11 (Week 12 Visit), standard of care 
therapy, including plaque brachytherapy, proton beam radiotherapy or enucleation may be used 
if the subject meets the protocol definition of disease progression or the Investigator judges that 
the disease is progressing per their clinical judgement for increases in tumor thickness or LBD 
that are less than the protocol definition of disease progression. Before additional therapy is 
performed, the following protocol assessments must be collected in the study eye unless 
otherwise noted: ETDRS BCVA (both eyes), slit lamp biomicroscopy, IOP measurement, 
fundoscopy, Fundus photos, EDI-OCT, B-scan ultrasound, A-scan ultrasound, OCTA (Cohorts 6 
to 9 only) and a visual field examination. If these assessments have not been performed at the 
most recent study visit, an unscheduled visit is required to be performed to obtain these 
assessments. 
The criteria for implementing additional therapy due to disease progression is as follows: 
• An increase on B-scan ultrasound of >0.5 mm in melanoma thickness from baseline, not 
due to intralesional hemorrhage/inflammation 
OR 
• An increase on digital fundus photos of >1.0 mm in melanoma diameter from baseline, 
not due to intralesional hemorrhage/inflammation or pigmentary changes 
If additional therapy with AU-011 occurs after Visit 15 (Week 78), subjects will be followed for 
26 weeks post retreatment and then may be rolled into the long-term follow-up study pending 
subject consent. Details regarding the follow-up visit schedule after additional therapy with AU- 
011 can be found in Appendix 4. 


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The Investigator may offer fine needle aspiration biopsy of the melanoma for genetic analysis 
before initiating additional therapy. 
Any progression of the subject’s condition and subsequent treatment must be recorded on the 
appropriate eCRF. 
Details about concomitant steroid treatment for management of anterior and posterior segment 
inflammation are provided in section 8.3.1 and in the study procedures manual. 
At the discretion of the PI, cycloplegic/mydriatic agents may be administered as part of the 
treatment of anterior ocular inflammation. 
8.3.4. 
AU-011 Treatment Criteria for Observation Cohort 
Once tumor growth is established in the observation cohort as described below, subjects will 
receive the first of 2 cycles of AU-011 treatment and the visit schedule for treatment and follow- 
up is described in Section 10 and Appendix 1 of this protocol until Cycle 2 is administered, at 
which time the visit schedule in Appendix 4 will be followed. 
The criteria for confirming tumor growth in subjects in the observation cohort are as follows: 
• A growth rate of 0.5 mm per year (with a minimum detectable increase of 0.15 mm over 
a minimum period of 3 months) in melanoma thickness from baseline or an absolute 
increase of ≥ 0.5 mm during the study period 
OR 
• A growth rate of 1.0 mm per year (with a minimum detectable increase of 0.6 mm over a 
minimum period of 3 months) in melanoma LBD from baseline or an absolute increase 
of ≥ 1.5 mm during the study period 
8.4. 
Dose Escalation Design and Toxicity 
8.4.1. 
DLT Definition 
Dose limiting toxicity[ies] (DLT[s]) is defined as a treatment-related safety event (related to drug 
and/or laser), severe enough to limit dose escalation (increase of dose or frequency of dosing) of 
AU-011. 
8.4.2. 
Dose Escalation / Termination 
Dose escalation to the next higher dose level, repeat dose group, repeat laser application or 
repeat cycle will be implemented only if less than 2 subjects in the prior cohort complete the 
treatment without a DLT. 


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9. 
STUDY DRUG 
9.1. 
Study Drug 
AU-011 drug product is a sterile, 
aqueous solution supplied at a concentration of 
mg per mL of buffered isotonic solution (pH 6.5). Each vial contains 
mL. Additional 
information is provided in the study pharmacy manual. 
9.2. 
Study Drug Packaging, Labeling, and Storage 
AU-011 is supplied in a 
mL, high density plastic, single-use vial; each vial contains a fill 
volume of 
mL. AU-011 will be shipped to clinical sites on dry ice. Once the site receives the 
study drug, it should be immediately stored at frozen temperature (- °C ± 
°C). 
All study drug must be kept in a secure place under appropriate storage conditions. The Sponsor 
or its representatives must be granted access on reasonable request to check drug storage, 
dispensing procedures, and accountability records. 
9.3. 
Study Drug Preparation 
The designated site personnel will prepare AU-011 per the manual provided by the Sponsor. The 
ophthalmologist will administer the study drug as specified in the injection and laser procedure, 
located in the study procedures manual. 
 
9.4. 
Study Drug Accountability 
Each clinical site is responsible for accountability of all used and unused study drug supplies at 
the site. 
The Sponsor or designee will verify receipt of the study drug at the site during monitoring 
visit(s), and will conduct an inventory of remaining clinical trial supplies at the site close-out 
visit. All study drug inventories must be made available for inspection by the monitor, Sponsor, 
or representatives of the aforementioned and regulatory agencies upon request. 
Dispensation and destruction of study drug will be recorded in the source document and drug 
accountability records. Clinical trial supplies must not be returned or destroyed unless the 
Sponsor or its representative has granted prior approval. Refer to the study pharmacy manual for 
additional details. 
9.5. 
Laser System 
The Sponsor will be providing the Aura Photoactivation System to the study sites. The Aura 
Photoactivation System (supplied by a contract manufacturer in accordance with Aura’s 
specification) consists of a laser console and a compatible slit lamp adaptor. The Sponsor will 
also provide each site with a compatible standard slit lamp biomicroscope and a table for the 
equipment. The laser photoactivation system has been tested for compliance to applicable FDA 
laser standards. 
The laser system will be labeled “For investigational use only.” Refer to the laser user manual 
for additional information. 


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10. 
CONDUCT OF STUDY AND STUDY ASSESSMENTS 
10.1. 
Conduct of Study 
10.1.1. 
Screening and Informed Consent 
All subjects will receive a written ICF describing this study and providing sufficient information 
to make an informed decision about participating in this study. Written informed consent must be 
obtained before any protocol specific procedures are performed. 
The Investigator is responsible for ensuring that a careful and thorough informed consent 
procedure is implemented before a subject enters the study and at any time during the study 
should ICF changes be introduced. This includes, but is not limited to: (1) providing a quiet place 
for the subject to read the ICF and allowing ample time for this review; (2) ensuring that 
qualified medical personnel are available to directly answer questions that a subject may have; 
(3) ensuring that each potential study subject understands that his or her medical treatment will 
not be otherwise affected based on the decision whether or not to participate in the study, that his 
or her participation is completely voluntary, and that he or she can opt to stop participation in the 
study at any time for any reason; and (4) ensuring that a full copy of the signed ICF is given to 
the subject to take home for his or her medical records. The process for obtaining informed 
consent should also be noted in the subject’s source documentation. 
In addition, whenever available, historical B-scans and/or color fundus photographs, either from 
the investigative site or the referring site, should be provided to the Independent Reading Center 
for subjects at the time of entry to the study. The investigative site should make all reasonable 
efforts to obtain this information from referring sites. 
Appendix 1 and the sections below describe the procedures that will be performed at each visit. 
Additionally, for the observation cohort visits every 3 months (ie, 90 day (+/- 7 days) intervals 
from the Screening Visit), which occur prior to evidence of tumor growth, the same procedures 
outlined for Visit 6 (Day 15) will be performed with the exception of OCTA and Anti-drug 
Antibody (ADA) testing which is not required. 
 
10.1.2. 
Screening (Visit 1 [Day -28 to Day 1]) 
After providing written informed consent, the following procedures will be performed: 
• Demographic information 
• Eligibility criteria 
• Medical and ophthalmic history 
• Concomitant medication review 
ALL OPHTHALMIC ASSESSMENTS WILL BE PERFORMED ON BOTH EYES AT 
SCREENING AND THEREAFTER ON THE STUDY EYE ONLY THROUGHOUT THE 
STUDY, UNLESS OTHERWISE INDICATED. 
• Vital signs (blood pressure [BP] and pulse) recorded 
• Serum pregnancy test for women of childbearing potential 


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• BCVA using ETDRS performed prior to dilating eyes (BCVA) 
• Slit lamp biomicroscopy 
• IOP measured by applanation or tonopen 
• Fundoscopy 
• Fundus photos 
• FA 
• EDI-OCT of the macular region and in the region of the tumor 
• B-scan 
• A-scan (for sites with diagnostic probes only) – study eye only 
• OCTA of the macular region and in the region of the tumor (Cohorts 6 through 9 
only) 
• Visual field examination 
• Laboratory assessments: Complete Blood Count (CBC) with differential and 
Comprehensive Metabolic Panel (CMP) 
• Blood sample for Anti-drug Antibody (ADA) testing 
10.1.3. 
Single Light-activated AU-011 Administration (or Initial for Repeat) Study 
Treatment (Visit 2 [Day 1]) 
During Visit 2, the following procedures will be performed: 
• Eligibility criteria review 
• Vital signs 
• BCVA (Both Eyes) 
• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 
• Fundus photos 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 
• B-scan 
• Urine pregnancy test for women of childbearing potential (only if Visit 2 occurs more 
than 7 days after Visit 1) 
• Laboratory assessments: CBC with differential and CMP (only if Visit 2 occurs more 
than 7 days after Visit 1) 
• Administration of Light-activated AU-011 treatment 


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− Intravitreal injection of AU-011 study drug (Subjects in cohorts 3, 6, 7, 8, 9, 10 
[after observation of growth], 11 and 12 receiving 80 µg doses administered as 2 
injections of 40 µg in 
µl will have their IOP measured prior to and after each 
injection. IOP must be 21 mm Hg or less before each injection can be given and 
the maximum interval between the two injections is 2 hours. IOP must also be 
21 mm Hg or less before the patient is discharged from the clinic). 
− Laser treatment (single laser applications for cohorts 1, 2, 3, 4, 5 and 7, and two 
laser applications for cohorts 6, 8, 9, 10 [after observation of growth], 11 and 12 
given 6 to 8 hours after intravitreal administration of AU-011). For subjects in 
cohorts 3, 6, 7, 8, 9, 10 [after observation of growth], 11 and 12 receiving 80 µg 
doses administered as 2 injections of 40 µg in 
µl, laser treatment is 6 to 8 
hours after the second injection. If the fovea is near the tumor edge, an adjustment 
to the laser procedure should be performed as outlined in section 8.2.2 and the 
Injection and Laser Procedure Manual. Subjects should remain at the study site after 
intravitreal injection until approximately ½ hour after laser treatment. 
− If subjects are discharged during daylight hours, appropriate sun protection, e.g., 
sunglasses and a hat, will be required. 
− Subjects must return to the study site for additional assessments 24 hours (± 4 
hours) after AU-011 intravitreal administration, refer to Section 10.1.4. 
• Record AEs 
• Record concomitant medications 
If Visit 1 and Visit 2 are within 7 days, the following procedures do not need to be repeated prior 
to AU-011 study drug injection, unless clinically indicated: 
• BCVA (Both Eyes) 
• Fundus photos 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 
• B-scan 
10.1.4. 
Visit 3 (Day 2, 24 hours [± 4 hours] Post-Injection Follow-up) 
Twenty-four hours (± 4 hours) following intravitreal administration of AU-011 study drug, 
subjects are required to return to the study site for the following assessments: 
• Vital signs 
• BCVA (Both Eyes) 
• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 


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• Fundus photos 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 
• B-scan (Cohort 1, 2, and 3 subjects only) 
• Record AEs 
• Record concomitant medications 
10.1.5. 
Visit 4 (Day 8 to Day 9) 
During Visit 4, the following procedures will be performed: 
• Vital signs 
• BCVA (Both Eyes) 
• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 
• Fundus photos 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 
• B-scan 
• A-scan (for sites with diagnostic probes only) 
• Laboratory assessments: CBC with differential and CMP 
• Blood sample for ADA testing (Pre-dose for 2 and 3 repeat Light-activated AU-011 
administration cohort subjects) 
• Record AEs 
• Record concomitant medications 
FOR 2 AND 3 REPEAT LIGHT-ACTIVATED AU-011 ADMINISTRATION 
COHORTS ONLY: 
• Administration of Light-activated AU-011 treatment 
− Intravitreal injection of AU-011 study drug (Subjects in cohorts 7, 8, 9, 10 [after 
observation of growth], 11 and 12 receiving 80 µg doses administered as 2 
injections of 40 µg in 
µl will have their IOP measured prior to and after each 
injection. IOP must be 21 mm Hg or less before each injection can be given and 
the maximum interval between the two injections is 2 hours. IOP must also be 
21 mm Hg or less before the patient is discharged from the clinic). 
− Laser treatment (single laser applications for cohorts 4, 5 and 7, and two laser 
applications for cohorts 8, 9, 10 [after observation of growth], 11 and 12 given 6 


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to 8 hours after intravitreal administration of AU-011). For subjects in cohorts 7, 
8, 9, 10 [after observation of growth], 11 and 12 receiving 80 µg doses 
administered as 2 injections of 40 µg in 
µl, laser treatment is 6 to 8 hours 
after the second injection. If the fovea is near the tumor edge, an adjustment to the 
laser procedure should be performed as outlined in section 8.2.2 and the Injection 
and Laser Procedure Manual. Subjects should remain at the study site after 
intravitreal injection until approximately ½ hour after laser treatment. 
− If subjects are discharged during daylight hours, appropriate sun protection, e.g., 
sunglasses and a hat, will be required. 
− Subjects must return to the study site for additional assessments 24 hours (± 4 
hours) after AU-011 intravitreal administration, refer to Section 10.1.4. 
 
10.1.6. 
Visit 5 (Day 9 to Day 10, 24 hours [± 4 hours] Post-Injection Follow-up for 2 and 
3 Repeat Light-activated AU-011 Administration Cohorts 
Twenty-four hours (± 4 hours) following intravitreal administration of AU-011 study drug, 
subjects are required to return to the study site for the following assessments: 
• Vital signs 
• BCVA (Both Eyes) 
• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 
• Fundus photos 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 
• Record AEs 
• Record concomitant medications 
10.1.7. 
Visit 6 (Day 15 to Day 16) 
During this Visit, the following procedures will be performed: 
• Vital Signs 
• BCVA (Both Eyes) 
• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 
• Fundus photos 
• EDI-OCT 


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• OCTA (Cohorts 6 to 9 only) 
• B-scan 
• Blood sample for ADA testing (Performed pre-dose and required for 3 repeat Light- 
activated AU-011 administration cohort subjects only) 
• Record AEs 
• Record concomitant medications 
FOR 3 REPEAT LIGHT-ACTIVATED AU-011 ADMINISTRATION COHORTS 
ONLY: 
• Administration of Light-activated AU-011 treatment 
− Intravitreal injection of AU-011 study drug (Subjects in cohorts 7, 8, 9, 10 [after 
observation of growth], 11 and 12 receiving 80 µg doses administered as 2 
injections of 40 µg in 
µl given as 
µl injections will have their IOP 
measured prior to and after each injection. IOP must be 21 mm Hg or less before 
each injection can be given and the maximum interval between the two 
injections is 2 hours. IOP must also be 21 mm Hg or less before the patient 
is discharged from the clinic). 
− Laser treatment (single laser applications for cohorts 5 and 7, and two laser 
applications for cohorts 8, 9, 10 [after observation of growth], 11 and 12 given 6 
to 8 hours after intravitreal administration of AU-011). For subjects in cohorts 7, 
8, 9, 10 [after observation of growth], 11 and 12 receiving 80 µg doses 
administered as 2 injections of 40 µg in 
µl, laser treatment is 6 to 8 hours 
after the second injection. If the fovea near the tumor edge, an adjustment to the 
laser procedure should be performed as outlined in section 8.2.2 and the Injection 
and Laser Procedure Manual. Subjects should remain at the study site after 
intravitreal injection until approximately ½ hour after laser treatment. 
− If subjects are discharged during daylight hours, appropriate sun protection, e.g., 
sunglasses and a hat, will be required. 
− Subjects must return to the study site for additional assessments 24 hours (± 4 
hours) after AU-011 intravitreal administration, refer to Section 10.1.4. 
 
10.1.8. 
Visit 7 (Day 16 to Day 17, 24 hours [± 4 hours] Post-Injection Follow-up for 3 
Repeat Light-activated AU-011 Administration Cohorts only) 
Twenty-four hours (± 4 hours) following intravitreal administration of AU-011 study drug, 
subjects are required to return to the study site for the following assessments: 
• Vital signs 
• BCVA (Both Eyes) 
• Slit lamp biomicroscopy 
• IOP 


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• Fundoscopy 
• Fundus photos 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 
• Record AEs 
• Record concomitant medications 
10.1.9. 
Follow-up Visit 8 (Day 29 ± 1 day) 
During this Visit, the following procedures will be performed: 
• Vital signs 
• BCVA (Both Eyes) 
• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 
• Fundus photos 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 
• B-scan 
• A-scan (for sites with diagnostic probes only) 
• Laboratory assessments: CBC with differential and CMP 
• Blood sample for ADA testing 
• Record AEs 
• Record concomitant medications 
10.1.10. 
Follow-up Visit 9 (Week 6 ± 3 days) 
During this Visit, the following procedures will be performed: 
• BCVA (Both Eyes) 
• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 
• Fundus photos 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 


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• Record AEs (For single Light-activated AU-011 administration cohort subjects, only 
study product and/or study procedure related AEs. For 2 and 3 repeat Light-activated 
AU-011 administration cohort subjects, any AE) 
• Record concomitant medications (For 2 and 3 repeat Light-activated AU-011 
administration cohort subjects only) 
 
10.1.11. 
Follow-up Visit 10 (Week 8 ± 3 days) 
During this Visit, the following procedures will be performed: 
• BCVA (Both Eyes) 
• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 
• Fundus photos 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 
• B-scan 
• A-scan (for sites with diagnostic probes only) 
• Record AEs (For single and 2 repeat Light-activated AU-011 administration cohort 
subjects, only study product and/or study procedure related AEs. For 3 repeat Light- 
activated AU-011 administration cohort subjects, any AE.) 
• Record concomitant medications (For 3 repeat Light-activated AU-011 administration 
cohort subjects only) 
 
10.1.12. 
Follow-up Visit 11 (Week 12 ± 3 days) 
During this Visit, ALL OCULAR ASSESSMENTS WILL BE PERFORMED ON BOTH EYES 
UNLESS INDICATED OTHERWISE): 
• BCVA 
• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 
• Fundus photos 
• FA 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 
• B-scan 


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• A-scan (for sites with diagnostic probes only) – study eye only 
• Visual field examination 
• Blood sample for ADA testing 
• Record study product and/or study procedure related AEs. Record all AEs and 
concomitant medications for Cohort 10, 11 and 12 subjects. 
• If applicable, the Investigator may offer fine needle aspiration biopsy of the 
melanoma for genetic analysis before initiating additional therapy. 
10.1.13. 
Follow-up Visit 12 (Week 26 ± 7 days) 
During this Visit, the following procedures will be performed: 
• BCVA (Both Eyes) 
• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 
• Fundus photos 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 
• B-scan 
• A-scan (for sites with diagnostic probes only) 
• Record study product and/or study procedure related AEs. Record all AEs and 
concomitant medications for Cohort 10, 11 and 12 subjects. 
• If applicable, the Investigator may offer fine needle aspiration biopsy of the 
melanoma for genetic analysis before initiating additional therapy. 
 
10.1.14. 
Follow-up Visit 13 (Week 39 ± 7 days) 
During this Visit, the following procedures will be performed: 
• BCVA (Both Eyes) 
• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 
• Fundus photos 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 
• B-scan 


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• A-scan (for sites with diagnostic probes only) 
• Record study product and/or study procedure related AEs. Record all AEs and 
concomitant medications for Cohort 10, 11 and 12 subjects. 
• If applicable, the Investigator may offer fine needle aspiration biopsy of the 
melanoma for genetic analysis before initiating additional therapy. 
 
10.1.15. 
Follow-up Visit 14 (Week 52 ± 7 days) 
During this Visit, the following procedures will be performed: 
• Vital signs 
• BCVA (Both Eyes) 
• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 
• Fundus photos 
• FA 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 
• B-scan 
• A-scan (for sites with diagnostic probes only) 
• Visual field examination 
• Blood sample for ADA testing 
• Record study product and/or study procedure related AEs. Record all AEs and 
concomitant medications for Cohort 10, 11 and 12 subjects. 
• If applicable, the Investigator may offer fine needle aspiration biopsy of the 
melanoma for genetic analysis before initiating additional therapy. 
 
10.1.16. 
Follow-up Visit 15 (Week 78 ± 7 days) 
During this Visit, the following procedures will be performed: 
• BCVA (Both Eyes) 
• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 
• Fundus photos 
• EDI-OCT 


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• OCTA (Cohorts 6 through 9 only) 
• B-scan 
• A-scan (for sites with diagnostic probes only) 
• Record study product and/or study procedure related AEs. Record all AEs and 
concomitant medications for Cohort 10, 11 and 12 subjects. 
• If applicable, the Investigator may offer fine needle aspiration biopsy of the 
melanoma for genetic analysis before initiating additional therapy. 
10.1.17. 
Follow-up Visit 16 (Week 104 ± 7 days), End of Study or Early Termination 
During this Visit (End of Study) or an Early Termination Visit, the following procedures will be 
performed (If Early Termination Visit occurs before Visit 11 (Week 12), then all ophthalmic 
assessments, including imaging should be performed on both eyes): 
• Vital signs 
• BCVA (Both Eyes) 
• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 
• Fundus photos 
• FA 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 
• B-scan 
• A-scan (for sites with diagnostic probes only) 
• Visual field examination 
• Record study product and/or study procedure related AEs. Record all AEs and 
concomitant medications for Cohort 10, 11 and 12 subjects. 
• If applicable, the Investigator may offer fine needle aspiration biopsy of the 
melanoma for genetic analysis before initiating additional therapy. 
• If Early Termination Visit occurs ≤ 30 days following the study treatment: Record 
any AE and record concomitant medications 
 
10.2. 
Safety Assessments 
10.2.1. 
History and Vital Signs 
A medical history will be recorded at Screening. Vital signs (BP seated and pulse) will be 
recorded at Visit 1 (Screening), Visit 2 (Day 1), Visit 3 (Day 2), Visit 4 (Day 8), Visit 6 (Day 


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15), Visit 8 (Day 29), Visit 14 (Week 52), and Visit 16 (Week 104) and at any Early Termination 
Visit. For both 2 and 3 repeat Light-activated AU-011 administration cohort subjects only, 
vital signs will also be recorded at Visit 5 (Day 9) and for the 3 repeat Light-activated AU-011 
administration cohort subjects only, vital signs will also be recorded at Visit 7 (Day 16). 
 
10.2.2. 
Laboratory Assessments 
This study will use a central laboratory for analyzing and reporting hematology (CBC with 
differential), CMP, and ADA results. 
If a situation arises in which the Investigator needs results more quickly than the central 
laboratory can accommodate, the Investigator may use a local laboratory in parallel, e.g., 
pregnancy test results for confirming subject eligibility. 
 
10.2.2.1. Hematology and Differential Panel 
CBC plus differential panel that includes hemoglobin, hematocrit, red blood cells (RBC), white 
blood cells (WBC), WBC differential, and platelets will be performed at Visit 1 (Screening), at 
Visit 2 (Day 1) if Visit 2 occurs more than 7 days after Visit 1, Visit 4 (Day 8), and Visit 8 (Day 
29). 
 
10.2.2.2. Comprehensive Metabolic Panel (CMP) and Electrolyte Panel 
A CMP includes the following: total bilirubin, direct bilirubin, alkaline phosphatase, ALT 
(SGPT), AST (SGOT), GGT, LDH, blood urea nitrogen (BUN), creatinine, glucose, uric acid, 
calcium, phosphorus (or phosphate), total protein, albumin, globulin, triglycerides, cholesterol, 
CK, sodium, potassium, bicarbonate, chloride, and magnesium. Blood samples for a CMP and 
Electrolyte Panel will be performed at Visit 1 (Screening), Visit 2 (Day 1) if Visit 2 occurs more 
than 7 days after Visit 1, Visit 4 (Day 8), and Visit 8 (Day 29). 
10.2.2.3. Pregnancy Test and Contraception Requirements 
For women of childbearing potential, serum pregnancy test will be performed at Visit 1 
(Screening). A central laboratory will be used for analyzing and reporting serum pregnancy 
results. If Visit 2 (Day 1) occurs more than 7 days after Visit 1, urine pregnancy test will be 
performed at Visit 2. If the pregnancy test(s) is positive, the subject will be screen failed. 
Women of childbearing potential and males with sexual partners of childbearing potential must 
agree to use a medically acceptable form of birth control before the first single administration of 
the investigational product and for three months after the last administration of Light-activated 
AU-011 treatment. Women considered capable of becoming pregnant include all females who 
have experienced menarche and have not experienced menopause (as defined by amenorrhea for 
greater than 12 consecutive months) or have not undergone successful surgical sterilization 
(hysterectomy, bilateral tubal ligation, or bilateral oophorectomy). 
Acceptable forms of birth control are spermicide with barrier, oral contraceptive, injectable or 
implantable method of contraception, transdermal contraceptive, intrauterine device, or surgical 
sterilization of partner. For non-sexually active females and males, abstinence will be considered 
an acceptable form of birth control. 


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10.2.2.4. Anti-Drug Antibodies (ADA) 
Anti-drug antibody (ADA) blood samples will be taken at Visit 1 (Screening), Visit 4 (Day 8), 
Visit 8 (Day 29), Visit 11 (Week 12), and Visit 14 (Week 52). For 3 repeat Light-activated AU- 
011 administration cohort subjects only, also performed at Visit 6 (Day 15). 
Study staff will record the visit numbers and dates, and exact times of AU-011 injections and 
blood samples taken in source documents. A central laboratory will be used for analyzing and 
reporting ADA data. 
 
10.2.3. 
Safety Monitoring 
The safety and tolerability of Light-activated AU-011 treatment will be assessed through the 
collection and analysis of AEs, vital signs, ocular examinations, and laboratory tests. All safety 
assessments and protocol specified tests, including occurrence of AEs, intensity/severity, 
relationship to study drug, and treatment or action taken to resolve the event, will be performed 
by qualified study personnel and/or the evaluating physicians. 
For the purposes of safety monitoring, baseline is defined as the pre-dose value at Visit 2 (Day 1) 
or, if no pre-dose Visit 2 (Day 1) result is available, it is the pre-dose test performed closest to 
Visit 2 (Day 1). 
The study medical monitor and independent ocular oncologist will review SAEs and AEs on a 
monthly basis for the early part of the study and thereafter every six months during the follow up 
phase for any trends within and between the cohorts. 
The study data, including any adverse and/or serious adverse events, together with any 
determinations of DLTs and decisions on dose reductions, or dose escalations, will be reviewed 
by the study medical monitor and independent ocular oncologist. 
10.2.3.1. Definitions of Adverse Events 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have to have a causal 
relationship with this treatment. 
Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory 
finding, for example), symptom, or disease temporally associated with the use of a medicinal 
product, whether or not considered related to the medicinal product. 
An AE includes, but is not limited to, the following: 
Any clinically significant worsening of a pre-existing condition other than CM is considered to 
be an AE. However, worsening of CM is considered to be “disease progression” or “lack of 
efficacy” and need not be reported as an AE unless it or the signs and symptoms associated with 
CM are more severe than expected for the subject’s condition. 
An AE occurring from overdose (i.e., a dose higher than that indicated in the protocol) of a study 
drug, whether accidental or intentional. 
The criteria for determining whether an abnormal objective test finding should be reported as an 
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• Test result is associated with accompanying symptoms 
• Test result requires additional diagnostic testing 
• Test result requires significant additional concomitant drug treatment, or other 
therapy or intervention 
• Test result leads to a change in trial dosing or discontinuation of study drug 
• Test result is considered to be an AE by the Investigator or Sponsor 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE. Any abnormal test result that is determined to be an error does not require 
reporting as an AE. 
A clinical diagnosis, rather than the changes in laboratory or other assessment should be 
recorded on the eCRF as appropriate (e.g., anemia versus low hemoglobin value, bundle branch 
block rather than abnormal electrocardiogram (ECG)). 
For Cohorts 1 to 9, from the time the subject receives the single administration (or initial for 
repeat) study treatment until 30 days after the subject completes the study treatment, protocol- 
related events should be recorded as well. For Cohort 10, 11 and 12 subjects, these should be 
recorded until the last study visit for the subject. A protocol-related AE is an AE occurring 
during a clinical study that is not related to the study product, but is considered by the 
Investigator or medical monitor to be related to the research conditions. For example, a 
protocol-related AE may be an event related to a medical procedure required by the protocol. 
10.2.3.2. Serious Adverse Events 
Any adverse experience occurring at any dose that results in any of the following outcomes is 
classified as a serious adverse event (SAE). 
• Results in death 
• Life threatening (see below for definition) 
• Results in persistent or significant disability/incapacity (see below for definition) 
• Requires subject hospitalization or prolongs subject hospitalization (see below for 
definition) 
• Results in a congenital anomaly/birth defect in a neonate/infant 
Additionally, important medical events that may not result in death, be life-threatening, or 
require hospitalization may be considered serious AEs when, based on appropriate medical 
judgment, they may jeopardize the subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition. Examples of such events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in hospitalization, or development of drug dependency or drug 
abuse. 
Life-threatening refers to immediate risk of death as the event occurred per the reporter. A life- 
threatening experience does not include an experience, had it occurred in a more severe form, 
might have caused death, but as it actually occurred, did not create an immediate risk of death. 


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For example, an allergic reaction resulting in angioedema of the face would not be life 
threatening, even though angioedema of the larynx, allergic bronchospasm, or anaphylaxis can 
be fatal. 
Hospitalization is official admission to a hospital. Hospitalization or prolongation of a 
hospitalization constitutes criteria for an AE to be serious; however, it is not in itself considered 
a SAE. In the absence of an AE, a hospitalization or prolongation of a hospitalization should not 
be reported by the PI. This is the case in the following situations: 
• The hospitalization or prolongation of hospitalization is part of a routine procedure 
followed by the center (e.g., stent removal after surgery, or other elective procedures). 
This should be recorded in the study file. 
• Hospitalization for survey visits or annual physicals falls in the same category. 
Disability is defined as a substantial disruption in a person’s ability to conduct normal life 
functions. 
 
10.2.3.3. Adverse Event Recording and Reporting 
Serious Adverse Events (SAEs) should be reported from the time the subject signs the informed 
consent to 30 days after the subject completes the study treatment. Adverse Events (AE) should 
be reported from the time the subject receives the single Light-activated AU-011 administration 
(or initial for repeat) study treatment to 30 days after the subject completes the study treatment. 
After 30 days, for Cohorts 1 to 9, only AEs or SAEs determined by the Investigator to be related 
to study product and/or study procedures are to be reported. Relatedness to Light-activated AU- 
011 treatment and/or study procedures is determined by the Investigator. For Cohort 10, 11 and 
12 subjects, all SAEs and AEs will be reported from the time the subject signs the informed 
consent through their last study visit. All AEs, regardless of severity and whether or not they are 
ascribed to the study treatment, will be recorded in the source documents. All AEs and SAEs for 
subjects who are not screen failures will be recorded on the eCRF. 
Study Investigators must follow-up on all AEs, SAEs, and other reportable events until the 
events have resolved, returned to baseline, or in case of permanent impairment, until the 
condition stabilizes. If, in the opinion of the Investigator, the AE or laboratory abnormality/ies 
are not likely to improve because of the underlying disease, the Investigator must record his or 
her reasoning for this decision in the subject’s source documentation and on the eCRF. Any 
medication or other intervention necessary for the treatment of an AE must be recorded on the 
concomitant medication eCRF. 
All AEs will be characterized by the following criteria: 
• Event term 
• Intensity or severity 
• Relationship to study treatment 
• Outcome 
• Treatment or action taken. 


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Whenever possible, recognized medical terms should be used when recording AEs. 
Colloquialisms and/or abbreviations should not be used. 
If more than one distinct AE occurs, each event should be recorded separately. However, if 
known at the time of reporting, a diagnosis (i.e., disease or syndrome) should be recorded on the 
eCRF rather than individual signs and symptoms (e.g., record congestive heart failure rather than 
dyspnea, rales, and cyanosis). However, if a constellation of signs and/or symptoms cannot be 
medically characterized as a single diagnosis or syndrome at the time of reporting, each 
individual event should be recorded as a separate AE. A diagnosis that is subsequently 
established should be reported as follow-up information. However, signs and symptoms that are 
considered unrelated to an encountered syndrome or disease should be recorded as individual 
AEs (e.g., if congestive heart failure and severe headache are observed at the same time, each 
event should be recorded as an individual AE). 
AEs occurring secondary to other events (e.g., sequelae) should be identified by the primary 
cause; a "primary" event, if clearly identifiable, should represent the most accurate clinical term 
to record as the AE event term. For example: 
Orthostatic hypotension fainting and fall to floorhead traumaneck pain 
The primary event is orthostatic hypotension and the sequelae are fainting, fall, head 
trauma and neck pain. 
 
10.2.3.4. Classification of Adverse Events by Intensity/Severity 
All AEs should be graded by Investigators using the Common Terminology Criteria for Adverse 
Events (CTCAE) version 4.03 (Appendix 3). If the AE is not specifically listed in the CTC 
toxicity criteria (for instance posterior segment inflammation, as opposed to uveitis), use the 
following grades: 
• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 
• Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental Activities of Daily Living (ADL) 
− Instrumental ADL refer to preparing meals, shopping for groceries or clothes, 
using the telephone, managing money, etc. 
• Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self- 
care ADL. 
− Self-care ADL refer to bathing, dressing and undressing, feeding self, using the 
toilet, taking medications, and not bedridden 
• Grade 4: Life-threatening consequences; urgent intervention indicated 
• Grade 5: Death related to AE 
There is a distinction between the severity and the seriousness of an AE. Severity is a 
measurement of intensity; thus, a severe reaction is not necessarily a SAE. For example, a 


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headache may be severe in intensity, but would not be serious unless it met one of the criteria for 
SAEs. 
Expectedness 
All AEs considered related to Light-activated AU-011 will be evaluated as to whether they are 
expected or unexpected, and related to Light-activated AU-011, the laser, and/or both. 
Expectedness will be determined by the Sponsor. 
Expected (anticipated): An AE is expected when the nature, severity, or degree of incidence was 
previously described in the IB. 
Unexpected (unanticipated): An AE is unexpected when the nature, severity, or degree of 
incidence was not previously described in the IB. 
Relatedness 
The Investigator will determine the assessment of the causal relationship of the AE to the study 
product and/or laser treatment. The following terms for assessment of the causality to study 
product or study procedures are to be used: 
• Not related: An event that does not follow a reasonable temporal sequence from 
administration of the study product or procedure, does not follow a known or 
expected response pattern to the suspect product or procedure and that could be 
reasonably explained by the known characteristics of the subject's clinical state. 
• Related: An event that follows a reasonable temporal sequence from administration of 
the study product or procedure, follows a known or expected response pattern to the 
suspected product or procedure and that could not be reasonably explained by the 
known characteristics of the subject’s clinical state. 
Outcome 
The clinical outcome of an AE will be characterized as follows: 
• Ongoing 
• Resolved 
• Resolved with sequelae 
• Death 
• Unknown 
Action Taken with Study Drug or Procedure 
• None 
• Study product or procedure interrupted 
• Study product or procedure discontinued 
10.2.3.5. Serious Adverse Event Reporting 
Serious Adverse Events (SAE) must be reported to the Sponsor as soon as possible and no later 
than 24 hours after the Investigator first learns of the event. The SAE form is to be completed 


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Medical Monitor, 
and submitted by email to Aura Biosciences. For initial reports, Investigators should record all 
case details that can be gathered within the reporting timeframe. Relevant follow-up information 
should be submitted to the Sponsor as soon as it becomes available and/or upon request. For 
some events, the Sponsor or designee or the medical monitor may follow up with the site by 
telephone, fax, electronic mail, and/or a monitoring visit to obtain additional case details deemed 
necessary to appropriately evaluate the event (e.g., hospital discharge summary, consultant 
report, or autopsy report). Reports relating to the subject’s subsequent medical course must be 
submitted to the Sponsor until the event has resolved or, in case of permanent impairment, until 
the event stabilizes and the overall clinical outcome has been ascertained. 
SAE reporting timelines should be followed when reporting a pregnancy or symptomatic 
overdose. 
The SAE report should be sent to the medical monitor and Aura Biosciences via e-mail – 
Safety@aurabiosciences.com. The following contact information (during both business and non- 
business hours) is also available: 
• 
: 
 
• Aura Biosciences, 
Study personnel are free to contact the medical monitor, 
by phone at 
, or by email at 
regarding any SAE or medical concerns. 
Transmission of the SAE report should be confirmed by the site personnel submitting the report. 
Follow-up information for SAEs and information on non-serious AEs that become serious should 
also be reported to the Sponsor as soon as it is available; these reports should be submitted using 
the SAE Report Form. Non-serious AEs that become serious should be reported to the Sponsor 
within 24 hours and recorded on the SAE Report Form. 
10.3. 
Ophthalmic Assessments 
10.3.1. 
Best Corrected Visual Acuity (BCVA) 
The study’s independent visual acuity consultants will certify the visual acuity equipment, 
examination rooms, and examiners before the study begins at each site. Manifest refraction and 
BCVA measurement will be performed according to the standard ETDRS refraction and visual 
acuity testing protocol in both eyes at all visits. 
 
10.3.2. 
Intraocular Pressure (IOP) 
IOP will be measured using applanation or tonopen in the study eye at every study visit and in 
both eyes at Visit 1 (Screening) and Visit 11 (Week 12), and at any Early Termination Visit that 
occurs before Visit 11 (Week 12). In addition, for all 80 µg dose cohorts, IOP must be 21 mm 
Hg or less before each injection and before discharge from the clinic. 
10.3.3. 
Slit Lamp Biomicroscopy and Fundoscopy 
Slit lamp biomicroscopy and fundoscopy will be performed in the study eye at every study visit 
except at Visit 1 (Screening) and Visit 11 (Week 12), and at any Early Termination Visit that 


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occurs before Visit 11 (Week 12), where Slit Lamp Biomicroscopy and Fundoscopy will be 
measured in both eyes. 
10.3.4. 
Fluorescein Angiography (FA) and Color Fundus Photography (Fundus Photos) 
FA will be performed at Visit 1 (Screening), Visit 11 (Week 12), Visit 14 (Week 52), and Visit 
16 (Week 104), and at any Early Termination Visit. Fundus photos will be performed in both 
eyes at Visit 1 (Screening) and Visit 11 (Week 12), and at any Early Termination Visit if that 
occurs before Visit 11 (Week 12). Fundus photos will be taken for the study eye only at all other 
visits including Early Termination that occurs after Visit 11 (Week 12). All FAs and fundus 
photos will be performed using digital fluorescein photography equipment and cameras certified 
by the IRC. The IRC will certify all photographers performing FA and fundus photos before they 
perform any imaging on study subjects. The IRC will provide each site with the protocol for 
image acquisition and transfer. 
The largest basal diameter (LBD) of the CM will be measured on the Fundus Photos at baseline 
and all visits described above. The greatest basal area (GBA) of tumor will also be measured on 
Fundus Photos at the same visits and tumor volume will be derived using the GBA and the 
maximum tumor thickness (measured by B-scan ultrasound) using the formula πr2h/3 where r is 
the radius derived from the GBA and h is the maximum tumor thickness. The criteria to classify 
tumor response (diameter) on Fundus Photos will be: 
Tumor Control: 
• Regression = Any reduction > 0.5 mm in the largest basal diameter (LBD) of the CM 
from baseline 
• Stable Disease (SD) = Maximum LBD of the CM is within ≥ -0.5 mm to ≤ +1.0 mm 
change in diameter from baseline 
Tumor Progression: 
• Progression = Any increase > 1.0 mm in the LBD of the CM from baseline not judged 
by the Investigator to be due to inflammation/swelling, hemorrhage or pigmentary 
changes 
10.3.5. 
Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT) 
The study’s IRC will certify the EDI-OCT machine and technician(s) before the study begins at 
each site. EDI-OCT will be performed in both eyes at Visit 1 (Screening) and Visit 11 (Week 
12), and at any Early Termination that occurs before Visit 11 (Week 12) and in the study eye 
only at all other visits including Early Termination that occurs after Visit 11 (Week 12). All 
images will be sent to the IRC for assessment throughout the study and in accordance with the 
IRC-provided protocol. 
10.3.6. 
Optical Coherence Tomography Angiography (OCTA) 
OCTA will be recorded at sites with OCTA imaging systems in Cohorts 6 through 9. The study’s 
IRC will certify the OCTA machine and technician(s) before the study begins at each site. OCTA 
will be performed in both eyes at Visit 1 (Screening) and Visit 11 (Week 12), and at any Early 
Termination that occurs before Visit 11 (Week 12) and in the study eye only at all other visits 


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including Early Termination that occurs after Visit 11 (Week 12). All images will be sent to the 
IRC for assessment throughout the study and in accordance with the IRC-provided protocol. 
10.3.7. 
B-scan Ultrasound 
B-scan ultrasound (B-scan) will be performed in both eyes at Visit 1 (Screening) and Visit 11 
(Week 12), and at any Early Termination Visit if that occurs before Visit 11 (Week 12) and in 
the study eye only at Visit 2 (Day 1), Visit 3 (Day 2) for cohorts 1, 2 and 3 only, Visit 4 (Day 8), 
Visit 6 (Day 15), Visit 8 (Day 29), Visit 10 (Week 8), Visit 12 (Week 26), Visit 13 (Week 39), 
Visit 14 (Week 52), Visit 15 (Week 78), Visit 16 (Week 104), and at any Early Termination that 
occurs after Visit 11 (Week 12). Ultrasound technicians will be certified by the IRC prior to 
study initiation based on adherence to IRC provided imaging acquisition and transfer protocols. 
Tumor thickness eligibility for the study is determined by B-scan measurement. 
Criteria to classify tumor response (thickness) on B-scan will be: 
Tumor Control: 
• Complete Response (CR) = Entire tumor is a flat lesion and of equal (or less) 
thickness to the surrounding choroid 
• Regression = Any reduction > 0.5 mm in the maximum thickness of the CM from 
baseline 
• Stable Disease (SD) = Maximum thickness of the CM is within ≥ -0.5 mm to ≤ +0.5 
mm change from baseline 
Tumor Progression: 
• Progression = Any increase > 0.5 mm in the maximum thickness of the CM from 
baseline not judged by the Investigator to be due to inflammation/swelling or 
hemorrhage 
10.3.8. 
A-scan Ultrasound 
A-scan ultrasound (A-scan) will be recorded in the study eye at sites with diagnostic probes. The 
amplitude of the internal reflectivity of the lesion will be recorded at Visit 1 (Screening), Visit 4 
(Day 8), Visit 8 (Day 29), Visit 10 (Week 8), Visit 11 (Week 12), Visit 12 (Week 26), Visit 13 
(Week 39), Visit 14 (Week 52), Visit 15 (Week 78), Visit 16 (Week 104), and at any Early 
Termination Visit. Ultrasound technicians will be certified by the IRC prior to enrollment of 
subjects in to the sub-study, based on adherence to IRC provided imaging acquisition and 
transfer protocols. 
10.3.9. 
Visual Field Examination 
Visual field assessment will be performed using automated perimetry testing (e.g., Humphrey 
24-2 SITA standard). Visual field examinations will be performed in both eyes at Visit 1 
(Screening) and Visit 11 (Week 12), and at any Early Termination Visit that occurs before Visit 
11 (Week 12) and in the study eye only at Visit 14 (Week 52), Visit 16 (Week 104), and any 
Early Termination Visit that occurs after Visit 11 (Week 12). 


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10.3.10. 
Additional Assessments 
If peri-tumoral whitening/pigmentary changes are seen at any time during the study, the 
Investigators should notify the sponsor and the additional assessments outlined below should be 
conducted if the required equipment is available at the Investigational site: 
1. Wide field fundus autofluorescence (FAF) over lesion and extent of whitening 
2. Single line scan OCT images oversampled at least 50 times with EDI on, including normal 
retina, whitening and tumor 
3. Indocyanine green (ICG) angiography 
4. OCTA in the area of retinal whitening 
These assessments should be conducted at the visit that the changes are first observed and at 
scheduled visits through 26 weeks (as outlined in Appendix 1) from the last treatment day for 
that cycle. If changes were seen with the first cycle of treatment and there are further 
changes/increases observed during the second cycle, the additional assessments should be 
conducted at the visit when observed and at scheduled visits through 26 weeks (as outlined in 
Appendix 4) from the last treatment day of second cycle. 
 
10.4. 
General Methodology 
 
Since this is an exploratory study, no formal hypothesis testing will be performed. Descriptive 
statistics will be used to tabulate and summarize efficacy and safety outcomes. Background and 
demographic characteristics will be presented. Continuous variables will be summarized by 
descriptive statistics (sample size, mean, standard deviation, median, minimum and maximum). 
Discrete variables will be summarized by frequencies and percentages. 
Safety assessments will be made at all study visits and both safety and tolerability will be 
evaluated by assessing the incidence of DLTs (as defined in Section 8.4.1), AEs and the 
incidence of SAEs. 
AEs, SAEs, and other findings will be summarized by presenting the percentages of subjects 
with each event for each treatment group. When relevant, the time course of AEs will be 
presented. 
All safety analyses will be presented by dose group and over all subjects. Safety analyses will 
summarize subjects by the treatment received. 
The safety analysis will summarize ocular treatment-emergent AEs (TEAEs) in the study eye for 
all treated subjects using discrete summaries at the subject- and event-level by system organ 
class and preferred term. A TEAE will be defined as occurring on or after the day that treatment 
is initiated. An additional analysis will investigate ocular AEs for the non-study eye. Non-ocular 
TEAEs will be summarized using discrete summaries at the subject- and event-level by system 
organ class and preferred term. Treatment-related ocular and non-ocular TEAEs will be 
summarized similarly. Ocular and non-ocular TEAEs will also be summarized by severity or 
toxicity grade. Additionally, TEAEs will be summarized by treatment schedule as deemed 
necessary to better understand the safety profile. 
The presence or absence of anti-drug antibodies will be summarized by treatment group. 


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10.5. 
Efficacy 
Since this is a single arm, exploratory study, no formal hypothesis testing will be performed. 
Efficacy will be assessed at the Week 12, 26 39, 52, 78 and 104 visits for any potential tumor 
response and changes in ETDRS best corrected visual acuity (BCVA). This will include change 
from baseline at each visit in tumor thickness by ultrasound and largest basal diameter by digital 
fundus photography. The proportion of subjects who meet the definition of stable disease (do not 
meet the definition of disease progression) will also be reported for each visit using change in 
tumor thickness and for changes in largest basal diameter. Change from baseline in ETDRS 
BCVA at Week 12 and at each subsequent visit will include changes in letter score and the 
proportion of subjects who lose or gain 5, 10 or 15 letters. 
 
Exploratory analyses will be performed for change in internal reflectivity of tumors by A-scan 
ultrasound at each visit and macular changes (foveal avascular zone and vessel density) by 
OCTA at each visit. 
Background and demographic characteristics will be presented. Continuous variables will be 
summarized by descriptive statistics (sample size, mean, standard deviation, median, minimum 
and maximum). Discrete variables will be summarized by frequencies and percentages. 
 
Efficacy and safety will be analyzed at various intervals after the first 2 cohorts have completed 
12 months of follow-up and then at further intervals as subsequent cohorts reach similar 
milestones. Specific details of the timing of such analyses will be included in the Statistical 
Analysis Plan. 


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11. 
SOURCE DATA/DOCUMENTS 
11.1. 
Study Monitoring 
The Investigator will permit monitoring, quality audits, and inspections by the government 
regulatory authorities, and the Sponsor or its representative(s) of all study related documents 
(e.g., source documents, regulatory documents, data collection instruments, eCRFs). 
Study monitoring involves the following elements: 
• Aura Biosciences personnel, or designee, may meet with Investigators prior to the 
initiation of the study in order to review the adequacy of the subject population, 
facilities, and equipment with respect to the needs of the study, and to familiarize the 
Investigator and support staff with the study protocol. 
• Aura Biosciences personnel, or designee, may meet with the Investigators at the time 
enrollment is initiated in order to ensure that subjects are being properly selected, that 
the methods described in the study protocol are thoroughly understood by the 
Investigator, and that study data are being correctly recorded. 
• Aura Biosciences personnel, or designee, may visit the clinical site at any time during 
the course of the study to review and/or collect completed eCRFs. Additionally, 
telephone consultation will occur as necessary during the course of the study to 
ensure the proper progress and documentation of the study findings. 
• Aura Biosciences personnel will review protocol deviations regularly. 
11.2. 
Audits and Inspections 
Authorized representatives of Aura Biosciences, a regulatory authority, an Independent Ethics 
Committee, or an IRB may visit the site to perform audits or inspections, including source data 
verification. The purpose of an audit or inspection is to systematically and independently 
examine all study-related activities and documents to determine whether these activities were 
conducted, and data were recorded, analyzed, and accurately reported according to the protocol, 
Good Clinical Practice (GCP) guidelines of the International Conference on Harmonization 
(ICH), and any applicable regulatory requirements. The Investigator should contact Aura 
Biosciences immediately if contacted by a regulatory agency about an inspection. 
 
11.3. 
Institutional Review Board (IRB) 
The Investigator must obtain IRB approval for the investigation. Initial IRB approval, and all 
materials approved by the IRB for this study including the subject consent form and recruitment 
materials must be maintained by the Investigator and made available for inspection. 


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12. 
QUALITY CONTROL AND QUALITY ASSURANCE 
The eCRFs will be reviewed by Aura Biosciences or designee. All data on eCRFs will be 100% 
source-verified by office-based monitoring and during site visits for accuracy and completeness 
by a clinical monitor. All data captured by the EDC system will be transferred through an 
electronic interface into a study database for management, analysis, and reporting. Any other 
data (eg, laboratory results) will also be transferred into the database. Upon completion of data 
collection, the database will receive a quality assurance (QA) check to ensure acceptable 
accuracy and completeness. 


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13. 
ETHICS 
13.1. 
IRB Review 
The study protocol, subject information and consent form, the IB, any subject diary card or 
written instructions to be given to the subject, available safety information, subject recruitment 
procedures (e.g., study website), information about payments and compensation available to the 
subjects and documentation evidencing the Investigator’s qualifications should be submitted to 
the IRB for review and approval according to local regulations, prior to the study start. The 
written approval should identify all documents reviewed by name and version. 
Changes in the conduct of the study or planned analysis will be documented in a protocol 
amendment. The Investigator must submit and, where necessary, obtain IRB and/or Sponsor 
approval for all subsequent protocol amendments and changes to the ICF or changes of the 
investigational site, facilities or personnel. The Investigator should notify the IRB of protocol 
deviations or SAEs occurring at the site and other AE reports received from the Sponsor in 
accordance with local procedures. 
Safety updates for Light-activated AU-011 will be prepared by the Sponsor or its representative 
as required, for submission to the relevant IRB. 
 
13.2. 
Ethical Conduct of the Study 
This study will be conducted in compliance with the protocol, principles set forth in the 
Declaration of Helsinki (1998 version applicable for study sites in the EU), ICH Guideline E6 for 
GCP (CPMP/ICH/135/95 Jan 1997), and the U.S. Code of Federal Regulations (CFR) Title 21, 
parts 50, 54 56, and 312. 
Appendix 2 provides more detail about the Sponsor’s commitments to clinical research and to 
this study. 
 
13.3. 
Written Informed Consent 
Informed consent is a process by which a subject voluntarily confirms his or her willingness to 
participate in a particular trial, after having been informed of all aspects of the trial that are 
relevant to the subject's decision to participate. Informed consent is documented by means of a 
written, signed and dated ICF. 
The ICF will be submitted for approval to the IRB that is responsible for review and approval of 
the study. Each consent form must include all of the relevant elements currently required by the 
national regulatory body, as well as local county authority or state regulations. 
Before recruitment and enrollment into the trial, each prospective candidate will be given a full 
explanation of the trial. Once the essential information has been provided to the prospective 
candidate, and the Investigator is sure that the individual candidate understands the implications 
of participating in this trial, the candidate will be asked to give consent to participate in the trial 
by signing an ICF. A notation that written informed consent has been obtained will be made in 
the subject’s medical record. A copy of the ICF, to include the subject’s signature, will be 
provided by the Investigator to the subject. 


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If an amendment to the protocol substantially alters the trial design or the potential risks to the 
subjects, the subject’s consent to continue participation in the trial should be obtained. 
13.4. 
Subject Confidentiality 
Confidentiality of subject’s personal data will be protected in accordance with the Health 
Insurance Portability and Accountability Act of 1996 (HIPAA) and national data protection laws, 
as applicable. HIPAA regulations require that, in order to participate in the trial, a subject must 
sign an authorization from the trial that he or she has been informed of following: 
• What protected health information (PHI) will be collected from subjects in this trial; 
• Who will have access to that information and why; 
• Who will use or disclose that information; 
• That health information may be further disclosed by the recipients of the information, 
and that if the information is disclosed the information may no longer be protected by 
federal or state privacy laws; 
• The information collected about the research trial will be kept separate from the 
subject’s medical records, but the subject will be able to obtain the research records 
after the conclusion of the trial; 
• Whether the authorization contains an expiration date; and 
• The rights of a research subject to revoke his or her authorization. 
In the event that a subject revokes authorization to collect or use his or her PHI, the Investigator, 
by regulation, retains the ability to use all information collected prior to the revocation of subject 
authorization. For subjects that have revoked authorization to collect or use PHI, attempts should 
be made to obtain permission to collect at least vital status (i.e., that the subject is alive) at the 
end of their scheduled trial period. 
In compliance with ICH GCP guidelines, it is a requirement that the Investigator and institution 
permit authorized representatives of Sponsor, the regulatory authorities and the IRB direct access 
to review the subject’s original medical records at the site for verification of trial-related 
procedures and data. 
Measures to protect confidentiality include: only a unique trial number and initials will identify 
subjects on the eCRF or other documents submitted to the Sponsor. This information, together 
with the subject’s date of birth, will be used in the database for subject identification. Subject 
names or addresses will not be entered on the eCRF or in the database. No material bearing a 
subject’s name will be kept on file by the Sponsor. Subjects will be informed of their rights 
within the ICF. 


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14. 
DATA HANDLING AND RECORDKEEPING 
14.1. 
Data Collection 
The eCRF is the primary data collection instrument for the trial. eCRFs will be kept current to 
enable the monitor to review the subjects’ status throughout the course of the trial. In order to 
maintain confidentiality, only the study number, subject number and date of birth will identify 
the subject on the eCRF. All data requested on the eCRF must be supported by and be consistent 
with the subject’s source documentation. 
Source documents are the original documents, data, records and certified copies of original 
records of clinical findings, observations and activities from which the subject’s eCRF data are 
obtained. These can include, but are not limited to, hospital records, clinical and office charts, 
laboratory, medico-technical department and pharmacy records, diaries, microfiches, ECG 
traces, copies or transcriptions certified after verification as being accurate and complete, 
photographic negatives, microfilm or magnetic media, X-rays, and correspondence. 
All missing data must be explained. When a required laboratory test, assessment, or evaluation 
has not been done or an “Unknown” box is not an option on the eCRF, a note should be created 
verifying that the field was “Not Done” or “Unknown”. For any entry errors made, the error(s) 
must be corrected, and a note explaining the reason for change should be provided. 
The Principal Investigator will sign and date the subject eCRF casebook indicating that the data 
on the eCRF have been assessed, once all data for that subject is final. 
 
14.2. 
Study Documentation and Retention of Records 
All study-related records must be maintained for at least 2 years after a marketing application is 
approved for the drug; or if an application is not approved for the drug, until at least 2 years after 
shipment and delivery of the drug for investigational use is discontinued and FDA/health 
authorities or regulatory agencies have been notified. The Sponsor will notify the principal 
Investigator when records are no longer needed. The Investigator will not discard any records 
without notifying the Sponsor. If the Investigator moves from the current investigational site, the 
Sponsor should be notified in writing or by email of the name of the person who will assume 
responsibility for maintenance of the records at the investigational site or the new address at 
which the records will be stored. The Investigator will notify the Sponsor as soon as possible in 
the event of accidental loss or destruction of any study documentation. 
14.3. 
Amendments to the Protocol 
Amendments to the protocol shall be planned, documented, and signature authorized prior to 
implementation. 
If an amendment to the protocol is required, the amendment will be originated and documented 
by the Sponsor (or its representative). The written amendment must be reviewed and approved 
by the Sponsor, and submitted to the IRB for approval. 
Amendments specifically involving change to trial design, risk to subject, increase to dosing or 
exposure, subject number increase, addition or removal of new tests or procedures, shall be 
reviewed and approved by the appropriate IRB. 


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The amendment will be submitted formally to regulatory authorities by the Sponsor as 
applicable, after IRB approval and specifically when an increase to dosing or subject exposure 
and/or subject number has been proposed; or, when the addition or removal of an Investigator is 
necessitated. 


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15. 
DISCLOSURE AND PUBLICATION POLICY 
All information provided regarding the trial, as well as all information collected/documented 
during the course of the trial, will be regarded as confidential. The Sponsor reserves the right to 
release literature publications based on the results of the trial. Results from the trial will be 
published/presented as per the Sponsor’s publication strategy. 
Inclusion of the Investigator in the authorship of any multi-center publication will be based upon 
substantial contribution to the design, analysis, interpretation of data, drafting and/or critically 
revising any manuscript(s) derived from the trial. The Investigator acknowledges that the trial is 
part of a multi-center trial and agrees that any publication by the Investigator of the results of the 
trial conducted at his/her research site shall not be made before the first multi-center publication. 
In the event there is no multi-center publication within fifteen (15) months after the trial has been 
completed or terminated at all trial sites, and all data has been received, the Investigator shall 
have the right to publish its results from the trial, subject to the notice requirements described 
herein and subject to acknowledgement of the Sponsor as appropriate. Investigator shall provide 
the Sponsor thirty (30) days to review a manuscript or any poster presentation, abstract or other 
written or oral material which describes the results of the trial for the purpose only of 
determining if any confidential or patentable information is disclosed thereby. If the Sponsor 
requests in writing, the Investigator shall withhold any publication or presentation an additional 
sixty (60) days solely to permit the Sponsor to seek patent protection. 


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16. 
LIST OF REFERENCES 
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Bishop KD, Oslzewski AJ. Epidemiology and survival outcomes of ocular and mucosal 
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Schmidt-Pokrzywniak A, Jockel K-H, Bornfeld N, Sauerwein W, Stang A. Positive interaction 
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Oncolytic viruses for cancer therapy. OncoImmunology 2013;2(6):e24612. 
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17. 
APPENDICES 


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APPENDIX 1. SCHEDULE OF ASSESSMENTS 
 
Screening 
Active Period 
Follow-up Period 
End of Study 
or Early 
Termination 
Assessment 
Visit 1 
D -28 
to 1 
Visit 
2 
D1 
Visit 
3 
D2 
± 
4H 
Visit 
4 
D8 
+ 
1D 
Visit 
5 
D9 
± 
4H 
Visit 
6 o 
D15 
+ 1D 
Visit 
7 
D16 
± 
4H 
Visit 
8 
D29± 
1D 
Visit 9 
W6 ± 
3D 
Visit 
10 
W8 ± 
3D 
Visit 11 
W12 ± 
3D 
Visit 12 
W26 ± 
7D 
Visit 
13 
W39 
± 
7D 
Visit 
14 
W52 
± 
7D 
Visit 
15 
W78 
± 7D 
Visit 16 
W104 ± 7D 
or 
Early 
Termination 
Informed consent 
X 
Eligibility review 
X 
X 
Demographics 
X 
Medical and ophthalmic 
history 
X 
Vital signsa 
X 
X 
X 
X 
Xj 
X 
Xk 
X 
X 
X 
Pregnancy test 
X 
Xb 
Laboratory assessments (CBC 
with differential and CMP) 
Xc 
Xc 
Xc 
Xc 
Light-activated AU-011 
treatment 
Xd 
Xj 
Xk 
ADA samples 
X 
X 
Xk 
X 
X 
X 
BCVA 
X 
X e 
X 
X 
Xj 
X 
Xk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Slit lamp biomicroscopyf 
X 
X 
X 
X 
Xj 
X 
Xk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IOPf 
X 
X 
X 
X 
Xj 
X 
Xk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Fundoscopyf 
X 
X 
X 
X 
Xj 
X 
Xk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Fundus photosf 
X 
Xe 
X 
X 
Xj 
X 
Xk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FAf 
X 
X 
X 
X 
EDI-OCTf 
X 
Xe 
X 
X 
Xj 
X 
Xk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
OCTAf, p 
X 
Xe 
X 
X 
Xj 
X 
Xk 
X 
X 
X 
X 
X 
X 
X 
X 
X 
B-scanf 
X 
Xe 
Xl 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
A-scan (study eye only) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Visual field examf 
X 
X 
X 
X 
AE reviewq 
Xq 
X 
X 
X 
Xj 
X 
Xk 
X 
Xm 
Xn 
Xh,q 
Xh,q 
Xh,q 
Xh,q 
Xh,q 
Xh,i,q 
Concomitant medication 
reviewq 
X 
X 
X 
X 
Xj 
X 
Xk 
X 
Xj 
Xk 
Xq 
Xq 
Xq 
Xq 
Xq 
Xg,q 


Clinical Protocol, Rev-15 
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aVital signs include BP seated and pulse. 
bSerum pregnancy test will be performed at Visit 1. If Visit 2 occurs more than 7 days after Visit 1, then urine pregnancy test will be performed at Visit 2. 
cCBC with differential includes hemoglobin, hematocrit, red blood cells (RBC), white blood cells (WBC), WBC differential, and platelets. CMP includes total bilirubin, direct 
bilirubin, alkaline phosphatase, ALT (SGPT), AST (SGOT), GGT, LDH, blood urea nitrogen (BUN), creatinine, glucose, uric acid, calcium, phosphorus (or phosphate), total 
protein, albumin, globulin, triglycerides, cholesterol, CK, sodium, potassium, bicarbonate, chloride, and magnesium. If Visit 2 occurs more than 7 days after Visit 1, then 
laboratory assessments will be repeated at Visit 2. 
dSubjects should remain at the study site following intravitreal injection until approximately ½ hour after laser treatment. If subjects are discharged during daylight hours, 
appropriate sun protection, e.g., sunglasses and a hat, will be required. 
eIf Visit 1 and Visit 2 are within 7 days, the following procedures do not need to be repeated prior to AU-011 study drug injection, unless clinically indicated: BCVA, fundus 
photos, EDI-OCT, OCTA, and B-scan. 
fFA and Fundus photos, EDI-OCT, OCTA, B-scan, Visual Field, IOP, Slit lamp and Fundoscopy will be performed in both eyes at Visit 1 (Screening) and Visit 11 (Week 12), and 
at any Early Termination Visit if that occurs before Visit 11 (Week 12), and in the study eye only at all remaining visits where applicable for each assessment. 
gIf Early Termination Visit occurs ≤ 30 days following study treatment. 
hStudy product and/or study procedure related AEs only for Cohorts 1 to 9. 
iAny AE for up to 30 days after the last AU-011 treatment if Early Termination Visit occurs ≤ 30 days following study treatment. 
jFor 2 and 3 Repeat Light-activated AU-011 administration cohort subjects only 
kFor 3 Repeat Light-activated AU-011 administration cohort subjects only 
lFor Cohort 1, 2 and 3 subjects only 
mFor Single Light-activated AU-011 administration cohort subjects, only study product and/or study procedure related AEs. For 2 and 3 Repeat Light-activated AU-011 
administration cohort subjects, any AE. 
nFor Single Light-activated AU-011 administration cohort and 2 Repeat Light-activated AU-011 administration cohort subjects, only study product and/or study procedure related 
AEs. For 3 Repeat Light-activated AU-011 administration cohort subjects, any AE. 
oFor the observation cohort (Cohort 10) every 3 month visits (i.e. 90 day (+/- 7 days) intervals from the Screening Visit) prior to evidence of tumor growth, all procedures outlined 
for Visit 6 (Day 15) will be performed with the exception of OCTA and Anti-drug Antibody (ADA) testing which is not required. 
pFor Cohort 6, 7, 8, and 9 subjects only 
qFor Cohort 10, 11, and 12 subjects, all SAEs and AEs and concomitant medications will be reported from the time the subject signs the informed consent through their last study 
visit. 


Clinical Protocol, Rev-15 
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AU-011 
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APPENDIX 2. SPONSOR’S COMMITMENTS 
The Sponsor is committed to: 
 
1. Complying with all applicable health authority regulations governing the conduct of 
clinical research studies, including the U.S. Food and Drug Administration. 
2. Protecting the rights, health, safety and welfare of study subjects. 
3. Informing the clinical Investigators of any new information about the study which may 
affect the health, safety or welfare of the subjects, or may influence their decision to 
continue participation in the study. 
4. Providing the clinical Investigators with the study protocol, and access to electronic 
CRFs on which to document the study evaluation variables for each subject entered into 
the study. 
5. Providing the statistical analysis and study report writing resources necessary to complete 
reporting of the study results. 
6. Ensuring equity of consideration among all Investigators in multicenter studies in all 
matters of publications, meeting presentations, etc. 
7. Certifying that IRB/EC approval of the protocol and Investigator’s Agreement will be 
completed prior to treatment at an investigational site. 


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AU-011 
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APPENDIX 3. COMMON TECHNICAL CRITERIA FOR ADVERSE 
EVENTS (CTCAE) 
 
Refer to CTCAE, Version 4, published May 28, 2009 (v4.03: June 14, 2010) 
Online resources are available at http://evs.nci.nih.gov/ftp1/CTCAE/About.html and include the 
following documents provided in different formats: 
• The file named “CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf” provides the 
most recent release of core terminology and is available as a PDF document in 
traditional small booklet format. 
• The file name “CTCAE4.03_2010-06-14_QuickReference_8.5x11.pdf” provides the 
most recent release of core terminology and is available as a PDF document in letter- 
sized format. 


Clinical Protocol, Rev-15 
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AU-011 
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APPENDIX 4. AU-011 ADDITIONAL THERAPY AND SECOND CYCLE 
(COHORTS 10, 11 & 12) VISIT SCHEDULE 
If the Investigator elects to give additional therapy with AU-011 as outlined in Section 8.3.3 then 
the following visit schedule and assessments must be performed. Similarly, the same visit 
schedule will be used for the second cycle of AU-011 for Cohorts 10, 11 and 12. Concomitant 
steroid treatment as outlined in section 8.3.1 should be administered with additional therapy or 
second cycle of AU-011. Prior to additional therapy and second cycle with AU-011, subjects 
must have provided informed consent and women of child-bearing potential must undergo a 
urine pregnancy test. 
Subjects will be assessed for safety 24 hours after each AU-011 administration and at 2 weeks, 4 
weeks, 12 weeks, and 26 weeks after completion of additional therapy with AU-011. Additional 
unscheduled visits may occur at the discretion of the investigator. If a protocol defined visit is 
scheduled to occur within 1 week of either the 4 week, 12 week or 26 week post additional 
therapy or second cycle follow-up visit, only one visit is required and the visit should be 
recorded as the protocol defined visit and all the assessments of that visit should be performed. 
After the 26 week post additional therapy or second cycle follow-up visit, remaining study visits 
will be conducted per the visit schedule in Section 10 and Appendix 1. If any post additional 
therapy, or second cycle follow-up visit will occur after the planned Week 104 End of Study 
Visit, the 26 week post additional therapy, or second cycle follow-up visit should be recorded as 
the Week 104 End of Study Visit. 
AU-011 Additional Therapy or Second Cycle 1, 2 & 3 
The following procedures will be performed: 
• Informed Consent Form Amendment Review and Consent 
• Vital signs 
• BCVA (Both Eyes) 
• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 
• Fundus photos 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 
• B-scan 
• Blood sample for ADA testing (prior to AU-011 administration) 
• Urine pregnancy test for women of childbearing potential (prior to first AU-011 
administration) 
• Administration of Light-activated AU-011 treatment 


Clinical Protocol, Rev-15 
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− Intravitreal injection of AU-011 study drug (Highest established safe dose at the 
time of the retreatment request will be offered). The subject will receive 80 µg 
doses administered as 2 injections of 40 µg in 
µl and the subject’s IOP will be 
measured prior to and after each injection. IOP must be 21 mm Hg or less before 
each injection can be given and the maximum interval between the two 
injections is 2 hours. IOP must also be 21 mm Hg or less before the patient 
is discharged from the clinic). 
− Laser treatment (Highest safe regimen at the time of the retreatment request will 
be offered and given 6 to 8 hours after intravitreal administration of AU-011). As 
the subject will receive 80 µg doses administered as 2 injections of 40 µg in 
µl, the two laser treatments will be administered 6 to 8 hours after the second 
injection 30 minutes (±10 minutes) apart. If the fovea is near the tumor edge, an 
adjustment to the laser procedure should be performed on each treatment day as 
outlined in section 8.2.2 and the Injection and Laser Procedure Manual. Subjects 
should remain at the study site after intravitreal injection until approximately ½ 
hour after laser treatment. 
− If subjects are discharged during daylight hours, appropriate sun protection, e.g., 
sunglasses and a hat, will be required. 
• Record AEs 
• Record concomitant medications 
 
24 hour Post Additional Therapy or Second Cycle Follow-Up (1 Day after AU-011 
treatment) 
The following procedures will be performed: 
• Vital Signs 
• BCVA (Both Eyes) 
• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 
• Fundus photos 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 
• Record AEs 
• Record concomitant medications 
 
2-Week Post Additional Therapy or Second Cycle Follow-Up (14 to 15 days after last AU- 
011 treatment) 


Clinical Protocol, Rev-15 
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The following procedures will be performed: 
• BCVA (Both Eyes) 
• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 
• Fundus photos 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 
• B-scan 
• Blood sample for ADA testing 
• Record AEs 
• Record concomitant medications 
 
4-Week Post Additional Therapy or Second Cycle Follow-Up (4 weeks +/- 1 day after last 
AU-011 treatment) 
The following procedures will be performed: 
• BCVA (Both Eyes) 
• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 
• Fundus photos 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 
• B-scan 
• Blood sample for ADA testing 
• Record AEs 
• Record concomitant medications 
 
12-Week Post Additional Therapy or Second Cycle Follow-Up (12 weeks +/- 3 days after 
last AU-011 treatment) 
The following procedures will be performed: 
• BCVA (Both Eyes) 


Clinical Protocol, Rev-15 
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AU-011 
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Aura Biosciences, Inc. 
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• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 
• Fundus photos 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 
• B-scan 
• Blood sample for ADA testing 
• Record study product and/or study procedure related AEs. Record all AEs and 
concomitant medications for Cohort 10, 11 and 12 subjects. 
 
26 Week Post Additional Therapy or Second Cycle Follow-Up (26 weeks +/- 7 days after 
last AU-011 treatment) 
The following procedures will be performed: 
• BCVA (Both Eyes) 
• Slit lamp biomicroscopy 
• IOP 
• Fundoscopy 
• Fundus photos 
• EDI-OCT 
• OCTA (Cohorts 6 through 9 only) 
• B-scan 
• Blood sample for ADA testing 
• Record study product and/or study procedure related AEs. Record all AEs and 
concomitant medications for Cohort 10, 11 and 12 subjects. 
After the 26 week post additional therapy or second cycle follow-up visit, remaining study visits 
will be conducted per the visit schedule in Section 10 and Appendix 1. If additional therapy or 
second cycle with AU-011 occurs after Visit 15 (Week 78), subjects will be followed for 26 
weeks post treatment and then may be rolled into the long-term follow-up study pending subject 
consent. 


Aura Biosciences, Inc. 
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Clinical Protocol, Rev-15 
AU-011 
AU-011-101, 21 Feb 2020 
IND 121,893 
 
AU-011 Additional Therapy or Second Cycle Schedule of Assessments 
 
Assessment 
Treatment 
1 
24 Hr Post 
Treatment 
Follow-up 
Treatment 
2 
24 Hr Post 
Treatment 
Follow-up 
Treatment 
3 
24 Hr Post 
Treatment 
Follow-up 
2-Week Post 
Treatment 
Follow up 
4-Week Post 
Treatment 
Follow up 
12-Week Post 
Treatment 
Follow up 
26-Week 
Post 
Treatment 
Follow up 
Informed consent 
Xc 
Vital signs 
X 
X 
X 
X 
X 
X 
Pregnancy test 
Xa 
Light-activated 
AU-011 treatment 
X 
X 
X 
ADA samples 
X 
X 
X 
X 
X 
X 
X 
BCVA 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Slit lamp 
biomicroscopy 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
IOP 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Fundoscopy 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Fundus photos 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
EDI-OCT 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
OCTA 
Xd 
Xd 
Xd 
Xd 
Xd 
Xd 
Xd 
Xd 
Xd 
Xd 
B-scan 
X 
X 
X 
X 
X 
X 
X 
AE reviewe 
X 
X 
X 
X 
X 
X 
X 
X 
Xb,e 
Xb,e 
Concomitant 
medication reviewe 
X 
X 
X 
X 
X 
X 
X 
X 
Xe 
Xe 
aIn women of child bearing potential only. 
bRecord study product and/or study procedure related AEs only for subjects in Cohorts 1 to 9. 
cIf informed consent not previously obtained on protocol amendment Rev-7 or later 
dCohorts 6 through 9 only 
eFor Cohort 10, 11, and 12 subjects, all SAEs and AEs and concomitant medications will be reported from the time the subject signs the informed consent through their last study 
visit. 
 
 
 
 
 
 
 

SAP_001.pdf: 
Aura Biosciences, Inc. - AU-011-101 
Version: 7.0 
'!11001 
AOOING VALUE TO CLINICAL DATA 
Confidential 
Statistical Analysis Plan 
SPONSOR: 
Aura Biosciences Inc. 
PROTOCOL TITLE: 
A Phase 1b/2 Open-label, Ascending Single and Repeat Dose 
Clinical Trial Designed to
Evaluate the safety and efficacy 
of Light-activated
AU-011
for
the
Treatment
of
Subjects 
with Small Primary Choroidal Melanoma 
NCT03052127
STUDY CODE: 
AU-011-101 
For IDDI: 
Author: 
- Senior Biostatistician
Reviewer: 
- Director, Biostatistical Services
For Sponsor: 
Approver: 
, Senior Director, Clinical Operations 
Approvers ( outside of the Vault): 
- Executive Medical Director, Clinical Development & Medical Affairs
Aura Biosciences - AU-011-101 - SAP 
TPL N°: TPL SA-02-01 
Of SOP SA-02.07 
TPL Effective Date: 31 Mar 2016 
Page 1 of 34 
TPL Version: OS 
Approved in Vault: 9/22/2021 
NCT03052127


 
 
 
Confidential 
 
Aura Biosciences – AU-011-101 - SAP                                                                       Page 2 of 34 
 
TPL N°: TPL SA-02-01 
TPL Version: 05 
Of SOP SA-02.07 
TPL Effective Date: 31 Mar 2016 
 
Table of Contents 
 
1 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ................................... 4 
2 
INTRODUCTION ............................................................................................... 6 
3 
STUDY DESIGN AND OBJECTIVES .................................................................... 7 
3.1 
Study Objectives.......................................................................................... 7 
3.1.1 
Primary Objective .................................................................................. 7 
3.1.2 
Secondary Objectives ............................................................................ 7 
3.2 
Study Design ............................................................................................... 7 
3.3 
Sample Size Justification ............................................................................. 11 
4 
GENERAL ANALYSIS DEFINITIONS ................................................................ 12 
4.1 
Study Period and Visit Window Definitions ..................................................... 12 
4.1.1 
Study Periods ..................................................................................... 12 
4.1.2 
Visit Windows ..................................................................................... 12 
4.2 
Planned analyses ....................................................................................... 12 
4.3 
Definition of Populations ............................................................................. 13 
4.3.1 
Intention-To-Treat Population ............................................................... 13 
4.3.2 
Efficacy Evaluable Population ................................................................ 13 
4.3.3 
Safety Population ................................................................................ 13 
4.4 
Subgroup Definitions .................................................................................. 13 
4.5 
Treatment Assignment and Treatment Cohorts .............................................. 13 
4.5.1 
Description of Study Drug .................................................................... 13 
4.5.2 
Administration of AU-011 ..................................................................... 14 
4.5.3 
Laser Activation of AU-011 ................................................................... 14 
4.5.4 
Treatment Cohorts .............................................................................. 15 
4.6 
Calculated Variables ................................................................................... 15 
4.7 
Partial Dates ............................................................................................. 15 
4.8 
Methods To Be Used For Handling Missing Data ............................................. 16 
4.9 
Changes to Analyses Specified in the Protocol ............................................... 16 
5 
STUDY SUBJECTS ........................................................................................... 16 
5.1 
Disposition of Subjects ............................................................................... 16 
5.2 
Protocol Deviations .................................................................................... 16 
6 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS ............................ 16 
7 
PRIOR AND CONCOMITANT TREATMENT ........................................................ 17 
7.1 
Prior and Concomitant Medications ............................................................... 17 
7.2 
Prior and Concomitant Procedures/Surgeries ................................................. 17 
8 
EFFICACY EVALUATION ................................................................................. 18 
8.1 
Tumor Response ........................................................................................ 18 
8.1.1 
Maximum Thickness and LBD Tumor Response Criteria ............................ 19 
8.1.2 
Investigator Determination of Progression .............................................. 20 
8.1.3 
Adverse Events of Pigmentary Changes .................................................. 20 
8.1.4 
Subjects Receiving Standard of Care ..................................................... 21 
8.1.5 
Maximum Tumor Thickness by B-scan Ultrasound ................................... 21 
8.1.6 
Largest Basal Diameter by Fundus Photography ...................................... 21 
8.1.7 
Tumor Reponse by B-scan Ultrasound and Largest Basal Diameter by Fundus 
Photography .................................................................................................... 21 
8.1.8 
Tumor thickness growth rate ................................................................ 21 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
Approved in Vault: 9/22/2021


 
 
 
Confidential 
 
Aura Biosciences – AU-011-101 - SAP                                                                       Page 3 of 34 
 
TPL N°: TPL SA-02-01 
TPL Version: 05 
Of SOP SA-02.07 
TPL Effective Date: 31 Mar 2016 
 
8.2 
Best Corrected Visual Acuity by ETDRS Protocol ............................................. 21 
8.3 
Sensitivity Analyses ................................................................................... 22 
8.4 
Exploratory Analyses .................................................................................. 22 
8.4.1 
Subretinal Fluid by EDI-OCT ................................................................. 23 
8.4.2 
Orange Pigmentation on Tumor by Color Fundus Photography .................. 23 
8.4.3 
Other B-scan Ultrasound Data ............................................................... 23 
8.4.4 
Capillary Density by OCTA .................................................................... 23 
9 
SAFETY EVALUATION ..................................................................................... 23 
9.1 
Extent of Exposure ..................................................................................... 23 
9.2 
Dose Limiting Toxicities .............................................................................. 24 
9.3 
Adverse Events .......................................................................................... 24 
9.4 
Deaths and Serious Adverse Events ............................................................. 25 
9.5 
Clinical Laboratory Determination ................................................................ 25 
9.6 
Vital Signs, Physical Findings and Other Observations Related to Safety ........... 26 
9.6.1 
Vital Signs .......................................................................................... 26 
9.6.2 
Slit Lamp Biomicroscopy ...................................................................... 26 
9.6.3 
Visual Field Exam ................................................................................ 27 
9.6.4 
Tonometry ......................................................................................... 27 
9.6.5 
Fundoscopy ........................................................................................ 27 
9.6.6 
Anti-Drug Antibodies ........................................................................... 27 
9.6.7 
Additional Therapy .............................................................................. 27 
10 
INTERIM ANALYSIS .................................................................................... 27 
11 
APPENDICES .............................................................................................. 28 
11.1 
Schedule of Assessments ............................................................................ 28 
11.2 
Definition of Visit Windows in Reporting ........................................................ 30 
11.3 
List of Tables/Graphs/Listings ...................................................................... 31 
11.3.1 
List of Statistical Tables ....................................................................... 31 
11.3.2 
List of Graphs ..................................................................................... 34 
11.3.3 
List of Derived Data Listings ................................................................. 34 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
Approved in Vault: 9/22/2021


 
 
 
Confidential 
 
Aura Biosciences – AU-011-101 - SAP                                                                      Page 4 of 34 
 
TPL N°: TPL SA-02-01 
TPL Version: 05 
Of SOP SA-02.07 
TPL Effective Date: 31 Mar 2016 
 
1 
List of Abbreviations and Definition of Terms 
 
Abbreviation 
Term 
 
 
A-scan 
A-scan ultrasonography 
ADA 
Anti-Drug Antibodies 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Transaminase 
ATC 
Anatomical Therapeutic Chemical 
AU-011 
A modified human papillomavirus-derived, empty viral like particle 
(VLP) conjugated to approximately 200 molecules of photosensitizer 
IRDye® 700DX 
B-scan 
B-scan ultrasonography 
BCVA 
Best Corrected Visual Acuity 
BP 
Blood Pressure 
BUN 
Blood Urea Nitrogen 
CBC 
Complete Blood Count 
CK 
Creatine Kinase 
CM 
Choroidal Melanoma 
CMP 
Comprehensive Metabolic Panel 
CTC 
Common Toxicity Criteria 
DG 
Documented Growth 
DLT 
Dose Limiting Toxicity 
DP 
Disease Progression 
eCRF 
Electronic Case Report Form 
EDI-OCT 
Enhanced Depth Imaging Optical Coherence Tomography 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
FA 
Fluorescein Angiography 
GGT 
Gamma-Glutamyltransferase 
ICH 
International Conference on Harmonization 
IOP 
Intraocular Pressure 
ITT 
Intention-To-Treat 
IVT 
Intravitreal 
LBD 
Largest Basal Diameter 
LDH 
Lactate Dehydrogenase 
LLN 
Lower limit of normal 
LOCF 
Last Observation Carried Forawrd 
MAD 
Multiple Ascending Dose 
MCV 
Mean Corpuscular Volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
Approved in Vault: 9/22/2021


 
 
 
Confidential 
 
Aura Biosciences – AU-011-101 - SAP                                                                      Page 5 of 34 
 
TPL N°: TPL SA-02-01 
TPL Version: 05 
Of SOP SA-02.07 
TPL Effective Date: 31 Mar 2016 
 
Min 
Minute 
mmHG 
Millimeter of Mercury 
μg 
Microgram 
μL 
Microliter 
n 
Number of non-missing values 
NCI 
National Cancer Institute 
NCI-CTC 
National Center Institute - Common Terminology Criteria 
nm 
Nanometer 
OCTA 
Optical Coherence Tomography Angiography 
OD 
Right eye 
OS 
Left eye 
OU 
Both eyes 
PR 
Partial Response 
PSC 
Posterior Subcapsular Cataract 
PT 
Preferred Term 
RBC 
Red Blood Cells 
SAD 
Single Ascending Dose 
SAE 
Serious Adverse Event 
SAF 
Safety 
SAP 
Statistical Analysis Plan 
SD 
Stable Disease 
SGOT 
Serum Glucose-Oxaloacetic Transaminase 
SGPT 
Serum Glucose-Pyruvic Transaminase 
SOC 
System Organ Class 
TE 
Treatment-Emergent 
TEAE 
Treatment-Emergent Adverse Event 
ULN 
Upper limit of normal 
WBC 
White Blood Cells 
WHO 
World Health Organization 
 
 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
Approved in Vault: 9/22/2021


 
 
 
Confidential 
 
Aura Biosciences – AU-011-101 - SAP                                                                      Page 6 of 34 
 
TPL N°: TPL SA-02-01 
TPL Version: 05 
Of SOP SA-02.07 
TPL Effective Date: 31 Mar 2016 
 
2 
Introduction 
This original Statistical Analysis Plan (SAP) V1.0 was written for Study AU-011-101 
conducted in subjects with small to medium primary choroidal melanoma on the basis of 
Clinical Protocol Rev-7, 25 May 2018. The International Conference on Harmonization 
(ICH) guideline E3 “Structure and Content of Clinical Study Reports” was used as a guide 
to the writing of the plan. 
The revision of the SAP was made on the basis of Clinical Protocol Protocol Rev-15, 21 
Feb. 2020. 
An overview of the changes made in the SAP v2.0: 
 
Revision of primary objective and secondary objectives. 
 
Addition of Expansion cohort (Cohort 9), Observational cohort (Cohort 10), and 2 
Cycles of AU-011 cohorts (Cohort 11 and Cohort 12) 
 
The 2nd Interim Analysis was decided to be cancelled.  
 
Number of subjects in the study increased from 45 to 60.  
 
Number of study sites in the study increased from 10 to 15. 
 
Addition of the definitions of subgroups, and subgroup analyses.  
 
Revision of the definitions of Tumor control, Partial response and disease 
progression.  
 
Addition of tumor growth rate analysis. 
 
The final analysis would be performed after all subjects complete the Week 52 Visit. 
An overview of the changes made in the SAP v3.0: 
 
Revision of tumor response assessment to consider various factors that could have 
impacted the determination of tumor response. 
 
Addition of a new analysis population: Efficacy Evaluable population, to exclude 
subjects from site 009 due to significant GCP deviations. 
 
Addition of analyses of ocular TEAEs related study drug/injection procedure/laser. 
An overview of the changes made in the SAP v4.0: 
 
Redefined the ITT population (instead of the Efficacy Evaluable population) as the 
primary population for efficacy analysis.  
 
Revision of the criteria for subjects with an AE of pigmentary changes in the 
determination of tumor response. 
 
Addition of analyses of tumor response and visual acuity for site 009 subjects only. 
 
Addition of analyses of subjects with visual acuity preservation. 
An overview of the changes made in the SAP v5.0 (after the 1st DB lock on 25 Aug. 2021): 
 
More details/clarification of rules given specifically for tumor response analysis at 
Month 12 LOCF and Last Visit.  
 
Revision of the criteria for visual acuity failure for consistency with the overall 
definition when data are not available at both Week 39 and Week 52. 
 
 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 8 of 34 
 
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*Alternating enrollment Cohort 10 & 11 will be closed with this revision(Rev-11) and subjects will be enrolled in 
Cohort 12. 
Single Ascending Dose (SAD) Cohorts 
Three subjects will receive a single intravitreal (IVT) injection of Light-activated AU-011 
low dose (20 µg in 
 µL).  The injection is followed 6 to 8 hours later by exposure to 689 
nm laser light.  No more than one subject may be treated per day, and the treated subject 
must complete his/her 24-hour post-treatment visit with no safety issues before the next 
subject in a given cohort may be treated. 
If all 3 subjects in the low dose group complete treatment without any dose limiting toxicity 
(DLT), escalation to the medium dose level (40 µg in 
 µL) group will be initiated.  If a 
DLT is observed in 1 subject in the low dose group, this group will be expanded to 6 
subjects. Dose escalation will not be allowed if 2 or more subjects in the low dose group 
experience a treatment-related DLT. Instead, if 2 or more subjects in the low dose group 
experience a treatment-related DLT, dose reduction to 10 µg in 
 µL may be considered 
for enrolling an additional 3 subjects. 
One week after the last subject in the low dose group completes treatment, the study 
medical monitor and independent ocular oncologist will review safety data for all subjects 
in the low dose group. After review and confirmation that the data support proceeding to 
treatment with the medium dose group, three subjects will receive a single IVT injection 
of Light-activated AU-011 medium dose (40 µg in 
 µL). The injection is followed 6 to 8 
hours later by exposure to 689 nm laser light.  
If all 3 subjects in the medium dose group complete treatment without any dose limiting 
toxicity (DLT), escalation to the high dose level group will be initiated. If a DLT is observed 
in 1 subject in the medium dose group, this group will be expanded to 6 subjects. If 2 or 
more subjects in the medium dose group experience a DLT after their treatment, this will 
confirm that the low dose level is the maximum feasible dose (due to formulation limits). 
One week after the last subject in the medium dose group completes treatment, the study 
medical monitor and an independent ocular oncologist will review safety data for all 
subjects in the medium dose group. After review and confirmation that the data support 
proceeding to treatment with the high dose group, three subjects will receive a single dose 
of Light-activated AU-011 high dose (80 µg administered as 2 injections of 40 µg in 
 
µL not more than two hours apart). The second injection is followed 6 to 8 hours later by 
exposure to 689 nm laser light. If a DLT is observed in 1 subject in the high dose group, 
this group will be expanded to 6 subjects. If 2 or more subjects in the high dose group 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 9 of 34 
 
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experience a DLT after their treatment, this will confirm that the medium dose level is the 
maximum feasible dose and the dose chosen for the repeat dose phase of the study will 
drop to one dose below the maximum feasible dose of 40 µg and the lower dose of 20 µg 
will be given as repeat doses. 
Multiple Ascending Dose (MAD) Cohorts 
One day after the last subject in the high dose group completes treatment, the study 
medical monitor and independent ocular oncologist will review safety data for all subjects 
and recommend proceeding to the repeat dose phase of the study. After review and 
confirmation that the data support proceeding to repeat dose regimens, 3 subjects will 
receive an IVT injection of 40 µg in 
 µL of Light-activated AU 011 as 2 repeat doses 1 
week apart. Each injection is followed 6 to 8 hours later by exposure to 689 nm laser light. 
If all 3 subjects in this 2 repeat 40 µg dose group complete treatment without any dose 
limiting toxicity (DLT) after 2 injections, then this regimen may be investigated further in 
subsequent studies.  If a DLT is observed in 1 subject in this 2 repeat 40 µg dose group, 
this group will be expanded to 6 subjects. If 2 or more subjects in this 2 repeat 40 µg dose 
group experience a DLT after their treatment, this will confirm that a lower repeat dose 
regimen should be investigated. 
One day after the last subject in the 2 repeat 40 µg dose group completes treatment, the 
study medical monitor and independent ocular oncologist will review safety data for all 
subjects and identify whether it is safe to evaluate 3 repeat 40 µg doses in the next cohort 
of the study. 
After review and confirmation that the data support proceeding to a 3 repeat 40 µg dose 
regimen, 3 subjects will receive an IVT injection of 40 µg in 
 µL of Light-activated AU-
011 as 3 repeat doses 1 week apart. Each injection is followed 6 to 8 hours later by 
exposure to 689 nm laser light. 
If all 3 subjects in this 3 repeat 40 µg dose group complete treatment without any dose 
limiting toxicity (DLT) after 3 injections, escalation to the next dose cohort will be initiated.  
If a DLT is observed in 1 subject in this 3 repeat 40 µg dose group, this group will be 
expanded to 6 subjects. If 2 or more subjects in this 3 repeat 40 µg dose group experience 
a 
DLT 
after 
their 
treatment, 
this 
will 
confirm 
that a 
fewer 
number 
of repeat administrations, or a lower dose at each administration should be investigated. 
One day after the last subject in the 3 repeat 40 µg dose group completes treatment, the 
study medical monitor and independent ocular oncologist will review safety data for all 
subjects and identify the maximum feasible dose for continued evaluation in the repeat 
dose phase of the study. After review and confirmation that the data support proceeding, 
an 80 µg single dose repeat laser regimen will be initiated. Three subjects will receive IVT 
administration of 80 µg of Light-activated AU-011 administered as 2 injections of 40 µg in 
 µL (not more than 2 hours apart)  followed by two 689 nm laser applications 30 
minutes (± 10 minutes) apart, with the first of the 2 laser applications occurring 6 to 8 
hours after the second injection.  
If all 3 subjects in this 80 µg single dose followed by 2 laser applications dose group 
complete treatment without any dose limiting toxicity (DLT), then the study may progress 
to the next cohort. If a DLT is observed in 1 subject in this 2 repeat laser applications 
following 80 µg single dose group, this group will be expanded to 6 subjects. If 2 or more 
subjects in this 2 repeat laser applications following 80 µg single dose group experience a 
DLT after their treatment, this will confirm that a lower dose followed by repeat laser 
regimen, or a repeat dose followed by single laser application, should be investigated 
further. 
One day after the last subject in the 2 repeat laser applications following 80 µg single dose 
group completes treatment, the study medical monitor and independent ocular oncologist 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 10 of 34 
 
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will review safety data for all subjects and identify whether it is safe to evaluate repeat 
laser applications after each of 3 repeat doses of 80 µg in the study.  
After review and confirmation that the data support proceeding to the 3 repeat 80 µg dose 
regimen followed by a single laser application, 3 subjects will receive an IVT administration 
of 80 µg of Light-activated AU-011 administered as 2 injections of 40 µg in 
 µL (not 
more than 2 hours apart) as 3 repeat doses one week apart. Each administration is 
followed 6 to 8 hours (after the second injection) later by exposure to 689 nm laser light. 
One day after the last subject in the 3 repeat 80 µg dose group, followed by a single laser 
application, completes treatment and 4 weeks after the last subject in the 80 µg single 
dose followed by 2 laser applications dose group complete treatment, the study medical 
monitor and independent ocular oncologist will review safety data for all subjects and 
identify whether it is safe to evaluate 3 repeat doses of 80 µg, each followed by 2 repeat 
laser applications, in the next cohort of the study. 
After review and confirmation that the data support proceeding to repeat laser applications 
after each of 3 repeat 80 µg doses, 3 subjects will receive an IVT administration of 80 µg 
of Light-activated AU-011 administered as 2 injections of 40 µg in 
 µL (not more than 
2 hours apart) as 3 repeat doses one week apart. Each administration is followed 6 to 8 
hours (after the second injection) later by 2 exposures to 689 nm laser light 30 minutes 
(± 10 minutes) apart.  
If all 3 subjects in this group, who receive 3 repeat 80 µg doses, each followed by 2 repeat 
laser applications, complete treatment and have been followed for 4 weeks without any 
dose limiting toxicity (DLT) after 3 weekly administrations, then this dose and regimen will 
be considered the maximum feasible dose and investigated in the expanded cohort. If a 
DLT is observed in 1 subject in this 3 repeat 80 µg dose with 2 repeat laser applications 
group, this group will be expanded to 6 subjects. If 2 or more subjects in this 3 repeat 80 
µg dose with 2 repeat laser applications group experience a DLT after their treatment, this 
will confirm that a fewer number of repeat administrations of either Light-activated 
AU-011 or laser, or both, or a lower dose of Light-activated AU-011 at each 
administration should be investigated further.  
Four weeks after the final treatment of the final subject in this cohort, a review of the 
safety data (including EDI-OCT) by the study medical monitor and independent ocular 
oncologist will occur. If safety is confirmed, the 3 repeat 80 µg dose with 2 repeat laser 
applications will be considered the maximum feasible and tolerated dose and this regimen 
will be expanded by up to 12 additional subjects in Cohort 9. 
Repeat Cycle and Observation Cohorts 
Once the last subject in the expansion cohort has been enrolled and safety of the maximum 
safe and feasible dose is confirmed, approximately 6 additional subjects, who fulfil the 
criteria for the clinical diagnosis of CM, but without documented growth, will be enrolled 
into an observation cohort (Cohort 10). These subjects will be assessed every 3 months 
(ie, 90 day (+/- 7 days) intervals from the Screening Visit) until tumor growth of the CM 
lesion is established (as defined in Protocol Section 8.3.4.) and at which time will then 
receive treatment with AU-011, as 3 repeat 80 μg doses, each followed by 2 repeat laser 
applications and move to the same visit schedule as subjects entering the trial and 
receiving treatment with AU-011 immediately. These subjects will receive Cycle 2 of AU-
011 administered as 3 repeat 80 μg doses, each followed by 2 repeat laser applications no 
earlier than the Week 12 Visit and after resolution of any inflammation resulting from the 
first cycle or when the inflammation is minimal and decreasing based on investigator 
judgement. Cycle 2 should be administered as soon as reasonably possible after 
inflammation has resolved or is minimal and decreasing based on investigator judgement. 
 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 11 of 34 
 
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In addition, approximately 6 additional subjects, who meet the criteria for a clinical 
diagnosis of CM, with or without documented growth, will enter Cohort 11 and receive two 
cycles of AU-011 treatment (each cycle will be comprised of 3 repeat 80 μg doses, each 
followed by 2 repeat laser applications). Cycle 2 of AU-011 will be administered as 3 repeat 
80 μg doses, each followed by 2 repeat laser applications no earlier than the Week 12 Visit 
and after resolution of any inflammation resulting from the first cycle or when the 
inflammation is minimal and decreasing based on investigator judgement. Cycle 2 should 
be administered as soon as reasonably possible after inflammation has resolved or is 
minimal and decreasing based on investigator judgement. 
 
The intention is to alternate the enrolment of Cohorts 10 and 11. If during the enrollment 
of these subjects, a subject has just been enrolled into Cohort 11 and a subject with 
documented growth presents, then that subject may instead be enrolled into Cohort 11 
rather than Cohort 10 for which they would not be eligible due the to the presence of 
documented growth and instead will be assigned to receive the first of 2 cycles of AU-011. 
 
If 2 subjects experience a DLT during treatment with Cycle 2, then no further subjects will 
receive Cycle 2 of AU-011 until discussed with the independent ocular oncologist and 
medical monitor and continuation of enrollment is confirmed. 
Subjects with Documented Growth 
Enrollment in Cohorts 10 and 11 was closed following approval of protocol revision 11 
(Rev-11) at each site. An additional cohort, Cohort 12, of subjects with minimum defined 
levels of documented growth will be initiated to allow assessment of safety and efficacy of 
2 cycles of AU-011 treatment in this key subgroup of subjects with CM. Since Cohort 12 
has the same dose as Cohort 11, no additional safety review will be required prior to 
initiating this cohort. 
Up to 15 subjects, who meet the criteria for a clinical diagnosis of CM with documented 
growth (as defined in Protocol Inclusion Criteria 5C) will enter Cohort 12 and receive two 
cycles of AU-011 treatment (each cycle will be comprised of 3 repeat 80 μg doses, each 
followed by 2 repeat laser applications). Cycle 2 of AU-011 will be administered as 3 repeat 
80 μg doses, each followed by 2 repeat laser applications no earlier than the Week 12 Visit 
and after resolution of any inflammation resulting from the first cycle or when the 
inflammation is minimal and decreasing based on investigator judgement. Cycle 2 should 
be administered as soon as reasonably possible after inflammation has resolved or is 
minimal and decreasing based on investigator judgement. 
If 2 subjects experience a DLT during treatment with Cycle 2, then no further subjects will 
receive Cycle 2 of AU-011 until discussed with the independent ocular oncologist and 
medical monitor and continuation of enrollment is confirmed. 
3.3 
Sample Size Justification 
No formal sample size calculation was performed for this ascending single and repeat dose 
and cycle phase 1b/2 study. Approximately 60 subjects with small primary CM will be 
enrolled and treated with Light-activated AU-011 at 3 dose levels and repeat dose 
regimens and cycles of Light-activated AU-011 and one or two laser applications. 
The study was designed to investigate at least 3 subjects at each treatment level and 
expand to investigate an additional 6 subjects at the maximum feasible dose. Provisions 
for expanding cohorts based on observed DLTs were also provided as per the study design 
section above. 
 
 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 12 of 34 
 
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4 
General Analysis Definitions 
Data will be analyzed using SAS (Version 9.4 or later). 
No tests of significance will be carried out to compare cohorts on baseline data because 
any observed differences between them must be attributed to chance. 
Since this is an exploratory study, no formal hypothesis testing will be performed. 
Descriptive statistics will be used to tabulate and summarize baseline, efficacy and safety 
outcomes.  
Descriptive statistics will be tabulated as follows:  
 
Categorical data will be summarized in contingency tables presenting frequencies 
and percentages. 
 
Continuous data will be summarized using number of non-missing values (n), 
mean, standard deviation, median, minimum and maximum values. 
The tables will be created by cohort and overall, in the order as listed in Section 4.5.4. In 
addition, a subtotal of dose escalation cohorts (Cohort 1 to 8) and a subtotal of the 
expansion cohorts (Cohort 9 to 12) will be included in all the relevant tables. 
Listings with individual values will be provided for all data presented in the tables. 
4.1 
Study Period and Visit Window Definitions 
4.1.1 Study Periods 
The study consists of 3 periods: screening, active period and follow-up period. Results will 
be presented by visit and not by period. 
4.1.2 Visit Windows 
The schedule of study assessments can be found in Appendix 11.1 of this SAP. 
Missing scheduled visit will be substituted by an unscheduled or early withdrawal visit 
occurring within each follow-up visit window. If there are multiple unscheduled or early 
withdrawal visits occurring within the window, the closest one within the visit window will 
be used. If no unscheduled or early withdrawal visit occurred within the window, the visit 
will be considered as missing. The details are tabulated in Appendix 11.2. 
An exception to this visit-window algorithm is the analysis of the “Last Visit”. For all “Last 
Visit” time-point analyses, a subject’s last non-missing endpoint assessment will be used 
for the analysis, regardless of if the visit falls within a particular visit window or not.  
4.2 
Planned analyses 
Two interim analyses are planned: 1) after the first 2 cohorts (SAD cohorts) have 
completed 12 months of follow-up (Visit 14); and 2) after all subjects complete Week 12 
visit (Visit 11). 
The final analysis will be performed when all enrolled subjects will have completed the End 
of Study visit or the Early Termination visit, if early discontinued from study. 
Note on SAP V2.0:  
1) One interim analysis was performed for the '01AUG2018 Deliverable".  
2) No further interim analyses are going to be done. 
3) Due to the early termination of the study, the final analysis will be performed after 
all subjects complete the Week 52 Visit. 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 13 of 34 
 
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4.3 
Definition of Populations 
4.3.1 Intention-To-Treat Population  
The Intention-To-Treat (ITT) population will consist of all enrolled subjects, whether or not 
they receive one administration of study treatment.  
This is the primary population for the efficacy analysis. 
4.3.2 Efficacy Evaluable Population  
The Efficacy Evaluable population will consist of ITT population subjects, excluding subjects 
from site 009, who have been excluded based on site audit findings.  
This population will be used as a sensitivity analysis for efficacy. 
4.3.3 Safety Population  
The Safety population will include all subjects who received at least one administration of 
study treatment. Subjects will be analyzed according to the treatment that they actually 
received. 
This is the primary population for the safety analysis. 
4.4 
Subgroup Definitions 
The following subgroups are defined for additional characterization of efficacy and/or 
safety of AU-011:  
 Subjects with documented growth (DG): defined as subjects who had any amount 
of documented growth on tumor thickness 
 Phase 3 Eligible (Ph3 Elig): defined as subjects with entry criteria similar to planned 
phase 3 critieria 
o 
Subjects with tumor thickness of ≥0.5 mm and ≤3.0 mm on B-scan ultrasound, 
a largest basal diameter of ≤13.0 mm on fundus photos with an estimated tumor 
volume ≤50 mm3 and tumor growth of ≥0.3 mm on tumor thickness within 2 
years of screening 
 Phase 3 Eligible Therapeutic Regimen at 2 cycles (Ph3 Elig TR2C) 
o 
Phase 3 Eligible subjects who received 2 cycles of AU-011 treatment, each cycle 
comprised of three weekly treatments with 80µg x 2 laser applications 
 Phase 3 Eligible - High Risk for Vision Loss (Ph3 Elig HRVL) 
o 
Phase 3 Eligible subjects with tumor ≤3.0 mm from the fovea or optic disc 
4.5 
Treatment Assignment and Treatment Cohorts 
4.5.1 Description of Study Drug 
Light-activated AU-011 is a combination product consisting of a drug (AU-011) and a laser 
(Aura Photoactivation system) that delivers 689 nm light to activate the drug once it is 
bound to the tumor cells. AU-011 drug substance is a modified human papillomavirus-
derived, empty viral like particle (VLP) conjugated to approximately 200 molecules of a 
phthalocyanine-based photosensitizer IRDye®700DX. AU-011 drug product is a sterile, 
pale blue aqueous solution supplied at a concentration of 0.4 mg per mL of buffered 
isotonic solution (pH 6.5). AU-011 is supplied in a 
 mL, high density plastic, single-use 
vial; each vial contains a fill volume of 
 mL.  
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 14 of 34 
 
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4.5.2 Administration of AU-011 
In this clinical trial, AU-011 study drug will be administered by IVT injection and will be 
followed by laser light application (689 nm) to the CM 6 to 8 hours after administration of 
AU-011. The maximum concentration of the current AU-011 formulation is 40 µg in 
 
µl and as a result, the maximum feasible dose is 80 µg administered as  injections of 
40µg in 
 µl.  
AU-011 will be administered via IVT injection as a low dose (20 µg) per IVT injection (
 
µL injection), a medium dose (40 µg) per IVT injection (
 µL injection), or a high dose 
(80 µg) per IVT injection (
 µL injections with interim IOP assessment). 
Subjects in cohorts 1 (20 µg single dose), 2 (40 µg single dose) and 3 (80 µg single 
administration given as  injections of 40 µg in 
µl) will receive one treatment followed 
by a single laser application, subjects in cohort 4 (40 µg two repeat doses) will receive  
injections one week apart followed by a single laser application, subjects in cohort 5 (40 µg 
three repeat doses) will receive  injections one week apart followed by a single laser 
application, subjects in cohort 6 (80 µg single dose followed by 2 laser applications) will 
receive a single dose administered as  injections of 40 µg in 
 µl followed by 2 laser 
applications, subjects in cohort 7 (80 µg three repeat doses followed by a single laser 
application) will receive 3 doses each administered as  injections of 40 µg in 
 µl one 
week apart followed by a single laser application, and subjects in cohorts 8 and 9 (80 µg 
three repeat doses followed by two laser applications) will receive 3 doses each 
administered as 
 injections of 40 µg in 
 µl one week apart followed by 2 laser 
applications.  Subjects in cohorts 3, 6, 7, 8 and 9 receiving 80 µg doses given as 
 
injections of 40 µg in 
 µl will have their IOP measured prior to and after each injection. 
IOP must be 21 mm Hg or less before each injection can be given and the maximum 
interval between the two injections is 2 hours. IOP must also be 21 mm Hg or less before 
the subject is discharged from the clinic. 
Subjects enrolled in the observation cohort and after exhibiting tumor growth (Cohort 10), 
and repeat cycle cohorts (Cohorts 11 and 12) will receive 2 cycles of AU-011 at the highest 
feasible and tolerated dose of 3 repeat 80 µg doses, each followed by 2 repeat laser 
applications. The second cycle of AU-011 will be administered no earlier than the Week 12 
Visit and after resolution of any inflammation resulting from the first cycle or when the 
inflammation is minimal and decreasing based on investigator judgement. Cycle 2 should 
be administered as soon as reasonably possible after inflammation has resolved or is 
minimal and decreasing based on investigator judgement. However, if 2 subjects 
experience a DLT during treatment with Cycle 2, then no further subjects will receive Cycle 
2 of AU-011 until discussed with the independent ocular oncologist and medical monitor 
and continuation of enrollment is confirmed. If the fovea is within 2 mm of the tumor edge 
or edge of the clinical margin of the tumor, an adjustment to the laser procedure should 
be performed on each treatment day of both cycles (as outlined in the Protocol section 
8.2.2). 
4.5.3 Laser Activation of AU-011 
This study will use the Aura Photoactivation System which will deliver light at 689 nm to 
the CM 6 to 8 hours after the IVT administration (after the second IVT injection for the 
subjects receiving 80 µg doses) of study drug AU-011. A second laser application will also 
be investigated in this trial to ensure that maximum tumor cell necrosis occurs with each 
administration of Light-activated AU-011. The study procedures binder provides detailed 
instructions on the procedures for laser application for this study. 
 
 
 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 15 of 34 
 
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4.5.4 Treatment Cohorts 
The treatment cohorts are defined as follow: 
Dose Escalation cohorts: 
 
Cohort 1: 20 µg x 1 laser, Single      
 
Cohort 2: 40 µg x 1 laser, Single 
 
Cohort 3: 80 µg x 1 laser, Single 
 
Cohort 4: 40 µg x 1 laser, 2XQ. Wk    
 
Cohort 5: 40 µg x 1 laser, 3XQ. Wk    
 
Cohort 6: 80 µg x 2 lasers, Single 
 
Cohort 7: 80 µg x 1 laser, 3XQ. Wk     
 
Cohort 8: 80 µg x 2 lasers, 3XQ. Wk 
Expansion cohorts: 
 
Cohort 9: 80 µg x 2 Lasers, 3XQ. Wk  
 
Cohort 10: Observational cohort - No documented growth 
 
Cohort 11: 2 Cycles of AU-011 – With or without documented growth 
 
Cohort 12: 2 Cycles of AU-011 – Documented growth 
4.6 
Calculated Variables 
 
Study day 1 is defined as the day when first study treatment was received. 
 
The baseline is defined as the last assessment done before or on study day 1. For 
instance, if data was collected at screening and Day 1, then the Day 1 value will be 
used for baseline 
 
Time since diagnosis of CM (months) = (month and year of screening – month and 
year of diagnosis). 
Assessments done on the date of study treatment administration are assumed to take 
place before the administration, unless specified otherwise. 
4.7 
Partial Dates 
Missing or incomplete dates will not be imputed at the data level. However, assumptions 
for missing or partial dates for important variables will be made to allow inclusion of 
appropriate data records in the analyses. In general, the assumptions about the missing 
or partial dates, when needed, are made conservatively to avoid overestimation of 
treatment effects and underestimation of adverse effects. 
If a medication, procedure or surgery date is missing or partial, so it cannot be determined 
whether it was taken prior or concomitantly, it will be considered both as a prior and a 
concomitant medication, procedure or surgery. 
If the partial AE onset date information does not indicate whether the AE started prior to 
treatment or after treatment, the AE will be classified as started after treatment. 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 16 of 34 
 
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4.8 
Methods To Be Used For Handling Missing Data 
When summarizing categorical variables, subjects with missing data are generally not 
included in the calculations of percentages unless otherwise specified. When needed, the 
category of “Missing” is created and the number of subjects with missing data is presented. 
When summarizing continuous variables, subjects with missing data are not included in 
calculations. No imputations are made.  
4.9 
Changes to Analyses Specified in the Protocol 
The tumor response categories criteria specified in Section 8.1 of this SAP are different 
than what is provided in the Sections 10.3.6 and 10.3.7 of the Protocol (Rev-15, 21 Feb. 
2020). The tumor response categories and criteria provided in this SAP will be used. 
5 
Study Subjects 
5.1 
Disposition of Subjects 
The number of subjects in each population will be tabulated by cohort (defined in Section 
0), overall and subgroups (defined in Section 4.4). 
The frequency of subjects treated, of subjects who completed the study treatment per 
protocol and of subjects who discontinued the study early will be given by cohort and 
overall for the ITT population. The primary reason for early discontinuation of study will 
be summarized. The details of the ‘other reason’ will be included in the listing. 
5.2 
Protocol Deviations 
All protocol deviations will be assessed and identified by the sponsor. The major protocol 
deviations will be summarized for each cohort and overall for the ITT population. The 
details will be listed by subject and cohort. Listing of all in- and exclusion criteria not met 
will be provided by cohort separately. 
6 
Demographic and other Baseline Characteristics 
Descriptive statistics with respect to demographics and subject characteristics at baseline 
will be displayed by cohort, overall, and subgroups (as needed, defined in Section 4.4) for 
the ITT population.  
The variables to be summarized are: 
 
Age, gender, race, ethnicity 
 
Iris color, study eye,  
 
Tumor lesion thickness, tumor largest basal diameter, distance from the fovea, 
distance from the nerve, Risk factors 
 
History of Primary Choroidal Melanoma: 
o 
Eye affected (OS/OD/OU) 
o 
Time since diagnosis of CM (months) 
o 
Prior Treatment for CM (Yes/No) 
 
Vital signs: pulse, systolic and diastolic blood pressure (seated) 
 
Anti-drug antibody (ADA) sample 
 
Visual acuity score both in the study eye and in the fellow eye 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
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 
Ophthalmic history (other than primary CM) both in the study eye and in the fellow 
eye 
 
Medical history (other than ophthalmic history) 
Medical and ophthalmic history will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) version 20.0 and will be tabulated by system organ class (SOC) and 
preferred term (PT) by cohort and overall for the ITT population. Multiple occurrences of 
the same preferred term in one subject will be counted only once. Summary tables will be 
sorted alphabetically by SOC then by PT within SOC based on descending frequency in the 
‘overall’ column. 
Other baseline data, for example, childbearing potential and contraception, serum 
pregnancy test, etc, will be provided in a data listing. 
7 
Prior and Concomitant Treatment 
Prior and concomitant treatments will be summarised and listed for the ITT population.  
7.1 
Prior and Concomitant Medications 
Prior and concomitant medications will be classified according to World Health Organization 
Drug Dictionary (Version 2017-March). 
The number and percentage of subjects receiving a prior or concomitant medication will 
be displayed by first level Anatomical Therapeutic Chemical class (ATC 1) and fourth level 
Anatomical Therapeutic Chemical class (ATC 4) by cohort and overall for the safety 
population. 
Medications will be reported as prior when they start before the first day of study 
treatment. Medications will be reported as concomitant when they start before, on or after 
first day of study treatment and continue afterwards. Medications started before the first 
day of study treatment and continuing afterwards will be reported both as prior and 
concomitant. In case of missing or partial start/stop date, rules defined in section 4.7 will 
be applied to identify prior and/or concomitant medications. 
Prior and concomitant medication summaries will be sorted alphabetically by ATC 4 class 
within ATC 1 class. 
A listing of all medications recorded on the prior and concomitant medications eCRF page 
will provide details including indication, start and stop dates and when available, dose, 
route, frequency. 
7.2 
Prior and Concomitant Procedures/Surgeries 
Prior and concomitant procedures and surgeries will be coded using MedDRA version 20.0. 
The number and percentage of subjects undergoing a prior or concomitant procedure or 
surgery will be displayed by system organ class and preferred term by cohort and overall 
for the safety population. 
Procedures and surgeries will be reported as prior when they start before the first day of 
study treatment. Procedures and surgeries will be reported as concomitant when they start 
before, on or after first day of study treatment and continue afterwards. Procedures and 
surgeries started before the first day of study treatment and continuing afterwards will be 
reported both as prior and concomitant. In case of missing or partial date, rules defined 
in section 4.7 will be applied to identify prior and/or concomitant procedures and surgeries. 
Prior and concomitant procedures and surgeries summaries will be sorted alphabetically 
by SOC then by PT within SOC based on descending frequency in the ‘overall’ column. 
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 18 of 34 
 
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A listing of all procedures and surgeries recorded on the prior and concomitant procedures 
and surgeries eCRF page will provide details including indication, eye, and start and stop 
dates. 
8 
Efficacy Evaluation  
Efficacy will be assessed at each visit for any potential tumor response based on imaging-
based assessments, and changes in Early Treatment Diabetic Retinopathy Study (ETDRS) 
BCVA. No formal hypothesis testing will be performed in this study. 
For imaging-based measurements, e.g. B-scan, OCTA, etc, as there are 2-3 readers and 
multiple values are available, and no adjudication will be conducted, a general convention 
will be followed: For the continuous variables, the average will be taken as the final value 
for analysis. For the categorical variables, if there are two like responses available, it will 
be the final response. And when all responses differ, the most conservative response will 
be taken as the final response. 
Efficacy analyses will be performed by cohort, overall and for subgroups (defined in Section 
4.4) on ITT population. Some efficacy analyses will also be performed on Efficacy Evaluable 
population as sensitivity analyses (see more details in Section 8.3). 
8.1 
Tumor Response 
Three different methods of determining tumor response will be applied. The rationale for 
using these 3 methods is to describe the data taking into consideration various factors (ie, 
criteria as stated below) that could have impacted the determination of tumor response. 
The following four criteria will be considered for tumor response assessment: 
a) The maximum thickness and LBD as defined in Section 8.1.1  
b) The investigator determination of the subject meeting protocol defined disease 
progression criteria as defined in Section 8.1.2 
c) The subject having an AE of Pigmentary Changes as defined in Section 8.1.3. 
d) The subject receiving standard of care 
The 3 different methods for determining tumor response are:  
1. Based on maximum thickness and LBD and subject receiving Standard of Care 
Tumor response (PR, SD, or DP) will be based on the algorithm as defined in Section  
8.1.1, with the modification that Investigator determination mentioned in DP definition will 
not be considered and if a subject receives standard of care they will be considered as 
having met the disease progression (DP) criteria from the date standard of care was 
administered.  
Note that for the Month 12 LOCF and Last Visit timepoints: 
 
If a patient receives standard of care prior to their Month 12 Visit, the subject will 
be considered as having met DP, even if the LBD and/or tumor thickness 
assessments are being LOCF’d from a time-point previous to the SOC being 
administered.  
 
Similarly, if a patient receives standard of care prior to their Last Visit, the subject 
will be considered as having met DP, even if the LBD and/or tumor thickness 
assessments are being LOCF’d from a time-point previous to the SOC being 
administered.  
2. Based on maximum thickness and LBD, subject receiving Standard of Care, and 
Investigators determination of progression 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 19 of 34 
 
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Tumor response (PR, SD, or DP) will be based on the algorithm defined method 1 above 
with the addition of the Investigator determination of progression criteria provided in 
Section 8.1.2. 
3. Based on maximum thickness and LBD, subject receiving Standard of Care, 
Investigators determination of progression, and adverse events of pigmentary changes 
Tumor response (PR, SD, or DP) will be based on the algorithm defined method 1 with the 
additional criteria of both Investigator determination (Section 8.1.2) and AE of pigmentary 
changes provided in (Section 8.1.3). 
As this method accounts for the Investigator determination of progression per protocol 
sections 10.3.4 and 10.3.7, it will be considered the primary method for describing the 
results in the clinical study report.  
For each of these 3 methods of determining tumor response, the tumor response results 
will be presented at each visit, as well as an overall summary table. The overall summary 
table will present the results at Month 12 using last observation carried forward (LOCF) as 
well as the subject’s last visit, including follow-up.  For the overall summary table, the 
table will provide which of the LBD and maximum thickness criteria were met for the 
response (or both) as well as a category for “Treated with standard of care prior to 
Progression” (i.e., this category will be for subjects who were treated with standard of care 
prior to reaching the progression criteria).  
An additional summary of the Summary of Tumor Response Tables (3 tables for Methods 
1-3) including just site 009 (i.e., the site excluded from the Efficacy Evaluable Population) 
will be performed.  
8.1.1 Maximum Thickness and LBD Tumor Response Criteria 
All tumors will be assessed for thickness by B-scan ultrasound and for largest basal 
diameter (LBD) by Fundus Photos.   
Criteria to classify tumor response will be: 
 
Partial Response (PR): 
o 
Any reduction > 0.5 mm in the maximum thickness of the CM from baseline 
(B-scan) and no progression (ie, and increase <1.0 mm) based on LBD 
(Fundus Photos), OR 
o 
Any reduction > 0.5 mm in the LBD of the CM from baseline (Fundus Photos) 
and no progression (ie, and increase <0.5 mm) based on tumor thickness 
(B-scan) 
 
Stable Disease (SD):  
o 
Maximum thickness of the CM is within -0.5 mm to +0.5 mm (inclusive) 
change from baseline (B-scan), AND 
o 
Maximum LBD of the CM is within  -0.5 mm to  +1.0 mm (inclusive) 
change in diameter from baseline (Fundus Photos) 
 
Disease Progression: 
o 
Any increase > 0.5 mm in the maximum thickness of the CM from baseline 
not judged by the Investigator to be due to inflammation/swelling or 
hemorrhage (B-scan), OR 
o 
Any increase > 1.0 mm in the LBD of the CM from baseline not judged by 
the Investigator to be due to inflammation/swelling, hemorrhage or 
pigmentary changes (Fundus Photos) 
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 20 of 34 
 
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Missing LBD or maximum thickness values:   
If both the LBD and maximum thickness values at a visit are missing, the tumor response 
will be set to missing for that visit. 
If 1 of the 2 measurements is missing, the tumor response will be determined by just 
considering criteria as applied to the non-missing measurement. (note: this rule does not 
apply to the Month 12 LOCF and Last Visit endpoints where an LOCF algorithm for both 
tumor thickness and LBD will be applied, as described below).  
Additionally, the following LOCF algorithm for tumor thickness and LBD will be applied for 
tumor response relative the Month 12 LOCF and Last Visit endpoints only (i.e., this LOCF 
algorithm does not apply to the individual visits, only the Month 12 LOCF and Last Visit 
timepoints). 
 
If a subject is missing a tumor thickness and/or their LBD assessments as a 
scheduled visit, an LOCF approach will be used to impute the missing data from the 
previous visits (ie, an LOCF approach will be applied to the tumor thickness and 
separately an LOCF approach will be applied to the LBD). If a patient has no non-
missing post-baseline visits, the baseline value will be used. The assessment of 
tumor response (i.e., as described above) will be applied using the LOCF’d tumor 
thickness and LBD values.  
8.1.2 Investigator Determination of Progression 
The investigator determination of progression is based on the corresponding Investigator 
judgement of progression eCRF question: 
Did the subject meet the protocol defined disease progression criteria and not yet 
receive additional therapy with standard of care (plaque brachytherapy, proton beam 
radiotherapy or enucleation) or additional therapy with AU-011 since the previous 
visit? (Yes/No Response). 
If the Response to this eCRF question is “No” and the subject met the criteria for disease 
progression (DP) based on the maximum thickness and LBD criteria defined in Section 
8.1.1, then the tumor response will be classified as Stable Disease (SD).  
Note that if a subject has started standard of care, they will be considered as having met 
the disease progression (DP) criteria from the date standard of care was administered.   
Missing Investigator judgement of progression:   
If the subject is missing the Investigator judgement of progression for a visit, the values 
from the subject’s next non-missing Investigator judgement of progression will be used. 
If the subject does not have a next non-missing assessment (i.e., there are no subsequent 
assessments or they are all missing), the determination of the tumor response category 
will be based on the LBD and maximum thickness criteria values only (i.e., without 
consideration of the Investigator judgement of progression). 
8.1.3 Adverse Events of Pigmentary Changes 
For any disease progression (DP) tumor responses due to LBD defined in Method 1 (i.e., 
based on only meeting the LBD criterion, not based on meeting either the tumor thickness 
criterion or subject receiving Standard of Care), if the subject has an AE of pigmentary 
changes in the eye being assessed and the Investigator response to eCRF question is “No” 
per section 8.1.2 on or after the start date of this AE, then the tumor response will be 
classified as stable disease (SD).  
An AE of pigmentary changes is any AE where the Preferred Term (PT) is “Retinal 
depigmentation” or “Retinal pigment epitheliopathy”.  
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 21 of 34 
 
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8.1.4 Subjects Receiving Standard of Care 
The date of the subject receiving standard of care will be from the Prior and Concomitant 
Procedure/Surgery eCRF page. Standard of Care includes the eye procedures categorized 
as: ‘Radiotherapy to eye’, ‘Brachytherapy to eye’ or ‘Photodynamic therapy’ (i.e., 
dictionary derived terms). 
8.1.5 Maximum Tumor Thickness by B-scan Ultrasound 
Descriptive statistics for change from baseline in maximum tumor thickness as measured 
by B-scan ultrasound in the study eye will be summarized at each visit by cohort, overall 
and for subgroups (defined in Section 4.4). 
8.1.6 Largest Basal Diameter by Fundus Photography 
Descriptive statistics for change from baseline in largest tumor basal diameter as 
measured by color fundus photography in the study eye will be summarized at each visit 
by cohort, overall and for subgroups (defined in Section 4.4).   
8.1.7 Tumor Reponse by B-scan Ultrasound and Largest Basal Diameter by 
Fundus Photography 
Number and percentage of subjects with tumor control (PR and SD) on both tumor 
thickness and LBD and tumor progression on either tumor thickness or LBD in the study 
eye will be summarized at each visit by cohort, overall and for subgroups defined in Section 
4.4. Definitions in Section 8.1 will be used. 
8.1.8 Tumor thickness growth rate 
Tumor thickness growth rates after treatment will be compared to historical growth rates 
in subjects with documented growth and other subgroups defined in section 4.4 using a 
mixed model repeated measures (MMRM) analysis. These analyses will be provided in a 
separate report by the sponsor.  
8.2 
Best Corrected Visual Acuity by ETDRS Protocol 
The BCVA score or visual acuity score using the Early Treatment of Diabetic Retinopathy 
Study (ETDRS) protocol will be determined for each subject in each eye at each visit. The 
observed visual acuity score in the study eye will be used for the analyses.  
Descriptive statistics for visual acuity score as well as for change from baseline in visual 
acuity score will be presented for each visit up to the Week 52 visit and at the end of study 
visit by cohort, overall and for subgroups (defined in Section 4.4).  
Number and percentage of subjects with a 5, 10 or 15 letter gain or loss at each visit up 
to the Week 52 visit and at the end of study visit will also be included by cohort and overall. 
Number and percentage of subjects with visual acuity preservation (ie, not meeting visual 
acuity failure criteria as defined below) over 52 weeks will also be included overall and for 
subgroups (defined in Section 4.4).  
Visual acuity failure is defined as having a ≥ 15 letter loss at Week 39 or Week 52 
confirmed at the next visit excluding visits occurring post-SOC. Additional details are 
provided below:  
 
A ≥ 15 letter loss at Week 39 and confirmed at Week 52 (or at the next visit after 
Week 52 with non-missing data [regardless of the visit windowing algorithm as 
described in Section 4.1.2] if the subject’s visual acuity data is missing at the 
Week 52 visit or the Week 52 visit did not occur). The data after a subject 
receives standard of care (SOC) is excluded (i.e., censored) from determination 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 22 of 34 
 
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of visual acuity failure. If there is no subsequent confirmatory visit data is 
available after Week 39 then the subject is counted as a visual acuity failure.  
 
If the subject does not meet the ≥ 15 letter loss criterion at Week 39 but does 
meet the ≥ 15 letter loss criterion at Week 52, then the subject’s next visit after 
Week 52 with non-missing data (regardless of the visit windowing algorithm as 
described in Section 4.1.2) will be the confirmatory visit (i.e., the subject will be 
counted as a visual acuity failure if the subject’s confirmatory visit also is a ≥ 15 
letter loss). The data after a subject receives standard of care (SOC) is excluded 
(i.e., censored) from determination of visual acuity failure. If there is no 
subsequent confirmatory visit data is available after Week 52 then the subject is 
counted as failure. 
 
If SOC occurs before Week 39, the subject’s 2 most recent visits available before 
SOC (with non-missing visual acuity data), regardless of the visit windowing 
algorithm as described in Section 4.1.2, will be used. If both visit assessments 
indicate the loss is ≥ 15 letters at this visit the subject will be counted as a visual 
acuity failure, otherwise the subject will not be counted as a visual acuity failure 
 
If both Week 39 and Week 52 visits are missing, the subject’s 2 most recent 
visits before Week 39 (and before receiving SOC), regardless of the visit 
windowing algorithm as described in Section 4.1.2, with non-missing values will 
be used. If both visit assessments indicate the loss is ≥ 15 letters the subject will 
be counted as a visual acuity failure, otherwise the subject will not be counted as 
a visual acuity failure. 
 
If a subject does not have any post-treatment visual acuity data, the subject will 
not be counted as a visual acuity failure.  
An additional summary of the following two tables including just site 009 (i.e., the site 
excluded from the Efficacy Evaluable Population) will be performed: 
 
Summary of Best Corrected Visual Acuity (ETDRS Letters) and Change from 
Baseline by Visit 
 
Number and percentage of subjects with visual acuity preservation (i.e., as defined 
above) 
8.3 
Sensitivity Analyses 
The following sensitivity analyses will be performed: 
 
The maximum tumor thickness and largest basal diameter endpoints (i.e., as 
described in Sections 8.1.5 and 8.1.6, respectively) will be summarized on ITT 
population excluding post-standard of care data (i.e. all data after receiving 
standard of care will be excluded for the standard of care subjects). 
 
BCVA data (Section 8.2) will be summarized on ITT population excluding post-
standard of care data. Number and percentage of subjects with a 5, 10 or 15 letter 
gain or loss at each visit up to the Week 52 visit and at the end of study visit will 
also be provided for: 1) Efficacy Evaluable population; 2) Efficacy Evaluable 
population excluding post-standard of care data. 
 
Tumor response (section 8.1.7) will be summarized on Efficacy Evaluable 
population. 
8.4 
Exploratory Analyses 
Exploratory analyses will be performed for all other relevant parameters from EDI-OCT, 
color fundus photography, fluorescein angiography, and B-scan ultrasound.  
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 23 of 34 
 
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Internal reflectivity of tumors by A-scan ultrasound and macular changes (foveal avascular 
zone and vessel density) by OCTA will be summarized at each visit as a sub-study for sites 
with A-scan diagnostic probes and OCTA devices. 
These analyses will be performed on ITT population. 
8.4.1 Subretinal Fluid by EDI-OCT 
Shift tables presenting number and percentage of subjects with or without 
(presence/absence) subretinal fluid as measured by EDI-OCT in the study eye from 
baseline to each post-baseline visit will be produced by cohort and overall for the ITT 
population.  
Descriptive statistics for change from baseline in central retinal thickness as measured by 
EDI-OCT in the study eye will be summarized for each visit by cohort and overall for the 
ITT population. 
OCT is primary measurement for subretinal fluid. 
8.4.2 Orange Pigmentation on Tumor by Color Fundus Photography 
Shift tables presenting number and percentage of subjects with or without 
(presence/absence) orange pigmentation on tumor as measured by color fundus 
photography in the study eye from baseline to each post-baseline visit will be produced 
by cohort and overall for the ITT population.  
Other fundus photography assessments data, i.e. Tumor Melanosis, Greatest Basal Area, 
Distance From Fovea, and Distance From Nerve Edge, will be summarized. And for 
categorical parameters, shift tables reflecting the changes from baseline will be produced 
at each visit by cohort and overall for the ITT population.    
8.4.3 Other B-scan Ultrasound Data 
Frequency distribution of Shape of Tumor (Dome, Collar button, Multi-lobe, Irregular, Flat, 
Other); Apical sub-retinal fluid (none, mild, moderate, significant); and Vitreous opacity 
(none, mild, moderate, dense, undetermined) will be tabulated for each visit by cohort 
and overall for the ITT population. 
8.4.4 Capillary Density by OCTA 
Descriptive statistics of foveal avascular zone area, and vessel density in the study eye for 
the actual values and change from baseline values will be summarized for baseline, at 
week 26, 52 and week 104 visits by cohort and overall for the ITT population. 
9 
Safety Evaluation 
Safety analyses will be performed by cohort and overall for the safety population. 
The main safety analyses will be based on all available data regardless of additional 
therapy. 
9.1 
Extent of Exposure 
Number and percentage of subjects administered with AU-011, who received full dose of 
AU-011 (Yes/No), Light activated (Yes/No), administered with first laser treatment 
(Yes/No, if applicable), administered with second laser treatment (Yes/No, if applicable), 
will be summarized at Day 1, Day 8 and Day 15 visits. 
Details of the treatment administration for each individual subject will be provided in a 
data listing. 
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 24 of 34 
 
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9.2 
Dose Limiting Toxicities 
Dose limiting toxicity[ies] (DLT[s]) is defined as a drug-related safety event, severe 
enough to limit dose escalation (increase of dose or frequency of dosing) of AU-011.  
Number and percentage of subjects with DLTs will be tabulated by cohort and overall for 
the safety population. 
9.3 
Adverse Events 
Adverse events (AEs) will be coded using the MedDRA Version 20.0 and will be graded 
according to the National Center Institute Common Terminology Criteria for AEs (NCI-
CTCAE criteria [v4.03]). Uncoded terms will be presented under “SOC uncoded”, with their 
reported term. 
Related AEs are defined as events with a relationship to study treatment equal to ‘related’ 
or with missing relationship. All AEs related to study drug, related to injection procedure, 
and related to laser administration will be reported separately. 
Adverse events in this section will be tabulated if they are treatment-emergent (TE). Non-
TE adverse events will only be included in listing of all adverse events. Adverse events 
which begin on or after the day the treatment is initiated will be considered as treatment-
emergent adverse events (TEAEs). Missing or partial AE start date will be estimated in 
order to include events in summary tables in case of doubt (see section 4.7 for more 
details). 
Ocular TEAEs are those TEAEs reported as occurring in the eye(s). 
All tabulations of adverse events will be presented by cohort, overall, and subgroups 
(defined in Section 4.4). 
An overall summary table of AEs will present the number and percentage of subjects with 
at least one: 
 
TEAE 
 
Serious AE (SAE) 
 
Related SAE – broken out by study drug, injection procedure and laser related 
 
Ocular TEAE in the study eye 
 
Related ocular TEAE in the study eye – broken out by study drug, injection 
procedure and laser related 
 
Ocular TEAE in the fellow eye 
 
Related ocular TEAE in the fellow eye – broken out by study drug, injection 
procedure and laser related 
 
Non-ocular TEAE 
 
Related non-ocular TEAE – broken out by study drug, injection procedure and laser 
related  
 
Fatal AE 
Tabulations of the number of subjects who experienced TEAEs as well as number of events 
will be presented by system organ class and preferred term (in descending frequency by 
SOC and by PT within each SOC). Subjects will only be counted once for each preferred 
term. In case a subject experienced the same event more than once, the event will be 
counted only once. 
The following tabulations will be presented: 
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 25 of 34 
 
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 
All TEAEs 
 
Ocular TEAEs in the study eye 
 
Related ocular TEAEs in the study eye – broken out by study drug, injection 
procedure and laser related. Three additional tabulations include:  
o 
Related to study drug and/or injection procedure and/or laser 
o 
Related to study drug and/or laser  
o 
Related to injection procedure that are not related to study drug or laser 
 
Ocular TEAEs in the fellow eye 
 
Related ocular TEAEs in the fellow eye – broken out by study drug, injection 
procedure and laser related, if relevant 
 
Non-ocular TEAEs 
 
Related non-ocular TEAEs – broken out by study drug, injection procedure and laser 
related 
In addition, tabulations of the number of subjects who experienced TEAEs as well as 
number of events will be presented by system organ class, preferred term and worst 
severity. Subjects will only be counted once for each preferred term. In case a subject 
experienced the same event more than once, the event with the worst severity will be 
counted in the summary. 
The following tabulations will be presented: 
 
All TEAEs 
 
Ocular TEAEs in the study eye 
 
Related ocular TEAEs in the study eye – broken out by study drug, injection 
procedure and laser related. Three additional tabulations include:  
o 
Related to study drug and/or injection procedure and/or laser 
o 
Related to study drug and/or laser  
o 
Related to injection procedure that are not related to study drug or laser 
 
Related non-ocular TEAEs – broken out by study drug, injection procedure and laser 
related 
Listing of all adverse events by cohort will be provided including the subject identifier, age, 
race, sex, reported term, preferred term, start date (Study Day of Start), stop date (Study 
Day of Stop), duration, TEAE (Yes/No), DLT (Yes/No), serious (Yes/No), associated eye 
(OD/OS/OU), 
severity 
(Mild/Moderate/Severe/Life-Threatening/Death), 
relationships 
(Related/Not Related to each of study drug, injection procedure, and laser administration), 
outcome, action taken. The adverse event listing will be sorted by treatment arm, subject 
identifier, start date, and reported term.  
9.4 
Deaths and Serious Adverse Events  
SAEs, related SAEs and fatal AEs will be summarized by system organ class and preferred 
term. In addition, listings of SAEs and fatal AEs will be provided, similarly to the listing of 
all AEs. 
9.5 
Clinical Laboratory Determination 
Clinical laboratory parameters will be graded (as applicable) using the NCI-CTC version 
4.03. Laboratory parameters which cannot be graded will be given the designation of 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 26 of 34 
 
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‘Normal’ or ‘Abnormal’, where ‘Abnormal’ is defined as outside of the normal range of [LLN, 
ULN]. Parameters to be summarized are as follows:  
 
Hematology and Differential Panel: Hemoglobin, hematocrit, Red Blood Cells 
(RBC), White Blood Cells (WBC), WBC differential, platelets, Mean Corpuscular 
Volume (MCV). 
 
Biochemistry and electrolytes: Total bilirubin, direct bilirubin, alkaline 
phosphatase, ALT (SGPT), AST (SGOT), GGT, LDH, blood urea nitrogen (BUN), 
creatinine, glucose, uric acid, calcium, phosphorus (or phosphate), total protein, 
albumin, globulin, triglycerides, cholesterol, CK, sodium, potassium, bicarbonate, 
chloride, and magnesium 
For continuous laboratory parameters, summaries of the values and changes from baseline 
will be presented for each visit by parameter.  
Where applicable, the shift from baseline NCI-CTC grade to worst post-baseline NCI-CTC 
grade will be presented for each parameter. This summary will include all scheduled and 
unscheduled post-baseline visits in the derivation of worst post-baseline grade.  
For parameters without NCI-CTC grading, the shift from baseline abnormality 
categorization (‘Normal’, ’Abnormal’) to worst post-baseline abnormality categorization 
(‘Normal’, ’Abnormal’) will be presented for each parameter. This summary will include all 
scheduled and unscheduled post-baseline visits in the derivation of the worst post-baseline 
abnormality categorization. 
9.6 
Vital Signs, Physical Findings and Other Observations Related to 
Safety 
9.6.1 Vital Signs 
Descriptive statistics for the actual values and change from baseline values of the vital 
signs parameters will be summarized at each visit by cohort and overall for the safety 
population. The vital sign parameters to be summarized are Systolic Blood Pressure 
(mmHg), Diastolic Blood Pressure (mmHg) and Pulse Rate (beats/min). 
9.6.2 Slit Lamp Biomicroscopy 
Number and percentage of subjects with normal/abnormal slit lamp biomicroscopy exam 
in the study eye will be summarized for Motility, Lids/Lacrimal/Lashes, Conjunctiva/Sclera, 
Cornea, Iris, Pupils, Optic Nerve and Retina parameters at each visit by cohort and overall 
for the safety population. 
Number and percentage of subjects with anterior chamber activity (cells: 0, Trace, 1+, 
2+, 3+, 4+) in the study eye will be summarized at each visit by cohort and overall for 
the safety population. 
Number and percentage of subjects with lens status aphakic/pseudo-phakic/phakic as well 
as complete grade nuclear, posterior subcapsular cataract (PSC) and cortical (0, 1, 2, 3, 
4), if phakic, and vitreous haze (0, 1+, 2+, 3+, 4+) in the study eye will be summarized 
at each visit by cohort and overall for the safety population. 
The shift from baseline to week 12, week 52 and week 104 visits for each parameter in 
the study eye will be presented by cohort and overall for the safety population. 
 
 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 27 of 34 
 
TPL N°: TPL SA-02-01 
TPL Version: 05 
Of SOP SA-02.07 
TPL Effective Date: 31 Mar 2016 
 
9.6.3 Visual Field Exam 
Results of automated perimetry exam in the study eye and the fellow eye will be provided 
in a data listing for the safety population. 
9.6.4 Tonometry 
Descriptive statistics of the IOP in the study eye for the actual values and change from 
baseline values will be summarized at each visit by cohort and overall for the safety 
population. In case of multiple post-baseline values, only the first value will be taken into 
account at each visit. All values will be included in the data listing. 
9.6.5 Fundoscopy 
Number and percentage of subjects with normal/abnormal fundoscopy exam in the study 
eye will be summarized for each visit by cohort and overall for the safety population. The 
shift from baseline to week 12, week 52 and week 104 visits for fundoscopy exam in the 
study eye will be presented by cohort and overall for the safety population. 
9.6.6 Anti-Drug Antibodies  
Number and percentage of subjects with positive/negative ADA test result will be 
summarized at each timepoint by cohort and overall for the safety population. 
9.6.7 Additional Therapy 
Some subjects may receive additional therapies with AU-011 or standard care after Visit 
11 (Week 12) if the Investigator determines that ocular melanoma has progressed and 
further treatment (additional therapy) is required. Number and percentage of those 
subjects who receive AU-011 will be summarized by original cohorts and overall. The 
highest established safe dose and regimen of drug and laser that was given at the time of 
the request will also be present. 
Number and percentage of subjects receiving additional therapy other than AU-011 will be 
summarized by cohort and overall for the safety population. Details of the treatment 
administration for each individual subject will be provided in a data listing. 
10 
Interim Analysis  
Two interim analyses were planned to summarize the safety and efficacy results of AU-
011 as mentioned in Section 4.2. 
One interim analysis was performed for the '01AUG2018 Deliverable". It has been decided 
that no additional interim analysis will be performed. 
 
 
 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
Approved in Vault: 9/22/2021


 
 
 
Confidential 
 
Aura Biosciences – AU-011-101 - SAP                                                                      Page 28 of 34 
 
TPL N°: TPL SA-02-01 
TPL Version: 05 
Of SOP SA-02.07 
TPL Effective Date: 31 Mar 2016 
 
11 
Appendices 
11.1   Schedule of Assessments 
 
 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
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Confidential 
 
Aura Biosciences – AU-011-101 - SAP                                                                      Page 29 of 34 
 
TPL N°: TPL SA-02-01 
TPL Version: 05 
Of SOP SA-02.07 
TPL Effective Date: 31 Mar 2016 
 
  
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
Approved in Vault: 9/22/2021


 
 
 
Confidential 
 
Aura Biosciences – AU-011-101 - SAP                                                                      Page 30 of 34 
 
TPL N°: TPL SA-02-01 
TPL Version: 05 
Of SOP SA-02.07 
TPL Effective Date: 31 Mar 2016 
 
11.2 Definition of Visit Windows in Reporting 
The definition of visit label and visit windows in reporting are described in the table below. 
 
Study 
Period 
Visit Label 
Definition [Day window]  
Screening Visit 1 
= Subject screening date; nominally 1 to 28 days prior to the first AU-011 
treatment.  
‘Day 1’ - ‘Date of assessment’ = [1 to 28]. Alternatively, this is the 
assessment before the first treatment date.  
Active 
Period 
Visit 2 - D1 
(Baseline) 
= An assessment with the same date as recorded on the  
Day 1 Administration CRF  
Target date = 1 
Visit 3 – D2 
= An assessment where ‘Date of assessment’ – ‘Day 1’ + 1 = 2  
Target date = 2 
Visit 4 – D8 
= An assessment where ‘Date of assessment’ – ‘Day 1’ + 1 = [8 - 9] 
Target date = 8 
Visit 5 – D9 
= An assessment where ‘Date of assessment’ – ‘Day 1’ + 1 = [9 - 10] 
Target date = 9. Alternatively, this is the assessment one day after Visit 
4 – D8. 
Visit 6 - D15 
= An assessment where ‘Date of assessment’ – ‘Day 1’ + 1 = [15 - 16] 
Target date = 15 
Visit 7 - D16 
= An assessment where ‘Date of assessment’ – ‘Day 1’ + 1 = [15 - 17] 
Target date = 16. Alternatively, this is the assessment one day after 
Visit 6 – D15. 
Follow-up 
Period 
 
 
Visit 8 – D29 
= An assessment where ‘Date of assessment’ – ‘Day 1’ + 1 = [22 - 36]  
Target date = 29 
Visit 9 – W6 
= An assessment where ‘Date of assessment’ – ‘Day 1’ + 1 = [37 - 50]  
Target date = 43 
Visit 10 – W8 
= An assessment where ‘Date of assessment’ – ‘Day 1’ + 1 = [51 - 64] 
Target date = 57 
Visit 11 – W12 
= An assessment where ‘Date of assessment’ – ‘Day 1’ + 1 = [65 - 113]  
Target date = 85 
Visit 12 – W26 
= An assessment where ‘Date of assessment’ – ‘Day 1’ + 1 = [155 - 211]  
Target date = 183 
Visit 13 – W39 
= An assessment where ‘Date of assessment’ – ‘Day 1’ + 1 = [246 - 302]  
Target date = 274 
Visit 14 – W52 
= An assessment where ‘Date of assessment’ – ‘Day 1’ + 1 = [337 - 393]  
Target date = 365 
Visit 15 – W78 
= An assessment where ‘Date of assessment’ – ‘Day 1’ + 1 = [463 - 631]  
Target date = 547 
End of 
Study 
Visit 16 – 
W104 
= An assessment where ‘Date of assessment’ – ‘Day 1’ + 1 = [700 - 756]  
Target date = 728 
 
 
 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 32 of 34 
 
TPL N°: TPL SA-02-01 
TPL Version: 05 
Of SOP SA-02.07 
TPL Effective Date: 31 Mar 2016 
 
14.2.3.2.1 
Sensitivity Analysis - Summary of Visual Acuity Score (ETDRS Letters) and 
Change from Baseline by Visit – Study Eye - ITT Population excluding all Post-
standard of care data 
14.2.3.2.2 
Sensitivity Analysis - Proportion of Subjects with 5, 10, 15 Letters Gain/Loss of 
Vision by Visit – Study Eye - ITT Population excluding all Post-standard of care 
data 
14.2.3.2.3 
Sensitivity Analysis - Proportion of Subjects with 5, 10, 15 Letters Gain/Loss of 
Vision by Visit – Study Eye – Efficacy Evaluable Population  
14.2.3.2.4 
Sensitivity Analysis - Proportion of Subjects with 5, 10, 15 Letters Gain/Loss of 
Vision by Visit – Study Eye – Efficacy Evaluable Population excluding all Post-
standard of care data 
14.2.3.3.1 
Sensitivity Analysis - Summary Of Tumor Response (Method 1) – Study Eye - 
EFFICACY EVALUABLE Population 
14.2.3.3.2 
Sensitivity Analysis - Summary Of Tumor Response (Method 2) – Study Eye - 
EFFICACY EVALUABLE Population 
14.2.3.3.3 
Sensitivity Analysis - Summary Of Tumor Response (Method 3) – Study Eye - 
EFFICACY EVALUABLE Population 
14.2.3.3.4 
Sensitivity Analysis - Summary Of Overall Tumor Response (Method 1) – Study 
Eye - EFFICACY EVALUABLE Population 
14.2.3.3.5 
Sensitivity Analysis - Summary Of Overall Tumor Response (Method 2) – Study 
Eye - EFFICACY EVALUABLE Population 
14.2.3.3.6 
Sensitivity Analysis - Summary Of Overall Tumor Response (Method 3) – Study 
Eye - ITT Population 
14.2.4.1 
Summary of Subretinal Fluid by EDI-OCT (Shift Table) – Study Eye – ITT 
Population 
14.2.4.2 
Summary Of Central Retinal Thickness By EDI-OCT – Study Eye – ITT 
Population 
14.2.5.1 
Summary of Orange Pigmentation on Tumor as Measured by Fundus 
Photography (Shift Table) – Study Eye – ITT Population 
14.2.5.2 
Summary of Tumor Melanosis as Measured by Fundus Photography (Shift 
Table) – Study Eye – ITT Population 
14.2.5.3 
Summary Of Greatest Basal Area By Fundus Photography – Study Eye – ITT 
Population 
14.2.5.4 
Summary Of Distance From Fovea By Fundus Photography – Study Eye – ITT 
Population 
14.2.5.5 
Summary Of Distance From Nerve Edge By Fundus Photography – Study Eye – 
ITT Population 
14.2.6.1 
Summary of Macular Edema Leakage by FA – Study Eye – ITT Population 
14.2.6.2 
Summary of Apical Sub-retinal Fluid by B-Scan – Study Eye – ITT Population 
14.2.6.3 
Summary of Vitreous Opacity by B-Scan – Study Eye – ITT Population 
14.2.6.4 
Summary Of Shape Of Tumor by B-Scan - Study Eye – ITT Population 
14.2.6.5 
Summary Of Foveal Avascular Zone Area by Octa - Study Eye – ITT 
Population 
14.2.6.6 
Summary of Vessel Density by OCTA – Study Eye - ITT Population 
14.3.1.1 
Extent of Exposure – AU-011 and Laser – SAF Population 
14.3.1.2 
Summary Of Additional Treatment – SAF Population 
14.3.1.3 
Summary of Dose Limiting Toxicities – SAF Population 
14.3.2.1 
Overview of Treatment-emergent Adverse Events (TEAE) – SAF Population 
14.3.2.2 
Treatment-Emergent Adverse Events by System Organ Class and Preferred 
Term – SAF Population 
14.3.2.3.1 
Ocular Treatment-Emergent Adverse Events by System Organ Class and 
Preferred Term – Study Eye – SAF Population 
14.3.2.3.2-7 
Related Ocular Treatment-Emergent Adverse Events by System Organ Class 
and Preferred Term – Study Eye – SAF Population 
14.3.2.4.1 
Ocular Treatment-Emergent Adverse Events by System Organ Class and 
Preferred Term – Fellow Eye – SAF Population 
14.3.2.4.2-4 
Related Ocular Treatment-Emergent Adverse Events by System Organ Class 
and Preferred Term – Fellow Eye – SAF Population 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
Approved in Vault: 9/22/2021


 
 
 
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Aura Biosciences – AU-011-101 - SAP                                                                      Page 33 of 34 
 
TPL N°: TPL SA-02-01 
TPL Version: 05 
Of SOP SA-02.07 
TPL Effective Date: 31 Mar 2016 
 
14.3.2.5.1 
Non-Ocular Treatment-Emergent Adverse Events by System Organ Class and 
Preferred Term – SAF Population 
14.3.2.5.2-4 
Related Non-Ocular Treatment-Emergent Adverse Events by System Organ 
Class and Preferred Term – SAF Population 
14.3.2.6.1 
Treatment-Emergent Adverse Events by Worst Severity, by System Organ Class 
and Preferred Term– SAF Population 
14.3.2.6.2 
Ocular Treatment-Emergent Adverse Events by Worst Severity, by System 
Organ Class and Preferred Term – Study Eye – SAF Population 
14.3.2.6.3-8 
Related Ocular Treatment-Emergent Adverse Events by Worst Severity, by 
System Organ Class and Preferred Term – Study Eye – SAF Population 
14.3.2.7.1-3 
Related Non-Ocular Treatment-Emergent Adverse Events by Worst Severity, by 
System Organ Class and Preferred Term – SAF Population 
14.3.3.1 
Serious Adverse Events by System Organ Class and Preferred Term – SAF 
Population 
14.3.3.2-4 
Related Serious Adverse Events by System Organ Class and Preferred Term – 
SAF Population 
14.3.3.5 
Adverse Events Leading to Death by System Organ Class and Preferred Term – 
SAF Population 
14.3.4.1 
Hematology: Values and Changes from Baseline by Visit – SAF Population 
14.3.4.2 
Biochemistry: Values and Changes from Baseline by Visit – SAF Population 
14.3.4.3 
Hematology – Shift From Baseline NCI-CTC Grade To Worst Post-Baseline NCI-
CTC Grade  
14.3.4.4 
Biochemistry – Shift From Baseline NCI-CTC Grade To Worst Post-Baseline NCI-
CTC Grade  
14.3.5.1 
Vital Signs - Values and Change from Baseline by Visit – SAF Population 
14.3.5.2 
Summary of Intraocular Pressure (IOP) at each Visit – Study Eye - Safety 
Population 
14.3.5.3 
Summary of Intraocular Pressure (IOP) Increase on Treatment Days – Study 
Eye - Safety Population 
14.3.6.1.1-8 
 
Slit Lamp Biomicroscopy Exam: Descriptive Statistics (Frequencies) by Visit – 
Study Eye – SAF Population 
--- For Parameters: Motility, Lids/Lacrimal/Lashes, Conjunctiva/Sclera, Cornea, 
Iris, Pupils, Optic Nerve and Retina 
14.3.6.2.1-4 
Slit Lamp Biomicroscopy Exam: Descriptive Statistics (Frequencies) by Visit – 
Study Eye – SAF Population 
--- For Parameters: Anterior Chamber Activity , Vitreous Haze, Lens Status, 
Lens Status - Phakic 
14.3.6.3.1-8 
Slit Lamp Biomicroscopy Exam: Shift from Baseline to Week 12, 52 and 104 – 
Study Eye – SAF Population 
--- For Parameters: Motility, Lids/Lacrimal/Lashes, Conjunctiva/Sclera, Cornea, 
Iris, Pupils, Optic Nerve and Retina 
14.3.6.4.1-3 
Slit Lamp Biomicroscopy Exam: Shift from Baseline to Week 12, 52 and 104 – 
Study Eye – SAF Population 
--- For Parameters: Anterior Chamber Activity , Vitreous Haze, Lens Status 
14.3.7.1 
Fundoscopy Exam: Descriptive Statistics (Frequencies) by Visit – Study Eye – 
SAF Population 
14.3.7.2 
Fundoscopy Exam: Shift from Baseline to Week 12, 52 and 104 – Study Eye – 
SAF Population 
14.3.7.3 
Anti-Drug Antibodies: Descriptive Statistics (Frequencies) by Timepoint – SAF 
Population 
 
 
 
 
 
 
Aura Biosciences, Inc. - AU-011-101                                                                   Version: 7.0
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