A Phase 1a/1b Dose Escalation and Expansion Trial of TTI-621, a Novel Biologic Targeting CD47, in Subjects With Relapsed or Refractory Hematologic Malignancies and Selected Solid Tumors
Phase: PHASE1
Conditions: Hematologic Malignancies, Solid Tumor
Sponsor: Pfizer

PPD 
 
 
 
CLINICAL PROTOCOL TTI-621-01 
A Phase 1a/1b Dose Escalation and Expansion Trial of 
TTI-621, a Novel Biologic Targeting CD47, in Subjects with 
Relapsed or Refractory Hematologic Malignancies and 
Selected Solid Tumors 
 
Investigational Product 
TTI-621 (SIRPα-IgG1 Fc) 
Protocol Number 
TTI-621-01 
Development Phase 
1a/1b 
CCI 
 
Confidentiality Statement 
This document contains confidential information that is the property of Trillium Therapeutics Inc. (Trillium) 
and may not be disclosed to anyone other than the recipient Investigator, clinical staff, and members of the 
Institutional Review Board/Independent Ethics Committee. This information cannot be used for any purpose 
other than the clinical research program without the prior written consent of Trillium. 

TTI-621 
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Clinical Protocol TTI-621-01 
20 February, 2019 
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SYNOPSIS 
 
TITLE: 
A Phase 1a/1b Dose Escalation and Expansion Trial of TTI-621, a Novel Biologic Targeting CD47, in 
Subjects with Relapsed or Refractory Hematologic Maligna ncies and Selected Solid Tumors 
PROTOCOL NUMBER:  TTI-621-01 
PHASE OF DEVELOPMENT:  1a/1b 
INVESTIGATORS AND STUDY CENTERS: This is a multicenter trial. 
OBJECTIVES: 
Phase 1a Escalation 
The primary objective of the escalation phase of the study is to characterize the safety profile and dose - 
limiting toxicities (DLT) of TTI-621 in order to identify the maximum tolerated dose (MTD) in subjects 
with advanced relapsed or refractory lymphomas. 
Secondary objectives include characterization of the pharmacokinetics (PK), pharmacodynamics (PD), and 
development of antidrug antibodies (ADA). 
Phase 1b Expansion (Part 2 and 3) 
The primary objective of the expansion phase of the study is to further characterize the safety of TTI-621 in 
an expanded number of primary hematologic malignancies and selected solid tumors and to evaluate the 
safety of individual subject TTI-621 dose intensification. 
Secondary objectives include further characterization of the PK, PD, and development of ADA; and to gain 
preliminary evidence of the anti-tumor activity of TTI-621 in subjects with a variety of hematologic 
malignancies and selected solid tumors. In addition, the safety of TTI-621 will be evaluated in combination 
with other anti-cancer agents. 
Phase 1b Dose Optimization (Part 4) 
The primary objective of the dose optimization phase is to further evaluate the safety and tolerability of TTI- 
621 at dose levels higher than the initially recommended phase 1b dose of 0.2 mg/kg (as determined during 
phase 1a dose escalation) and the MTD and/or recommended phase 2 dose will be re-assessed per revised 
DLT criteria following a 3+3 dose escalation schema. The DLT criteria are revised based on the totality of 
safety data collected thus far from the phase 1a and 1b dose expansion phase of the study. The starting dose 
for this further dose evaluation will be the highest dose of TTI-621 evaluated (0.5 mg/kg) during phase 1b 
dose expansion following dose intensification regimens permissible per protocol (Part 3). 
Secondary objectives include characterization of the PK, PD, immunogenicity, and preliminary evidence of 
antitumor activity of TTI-621 in patients with relapsed and/or refractory CTCL at higher dose levels of TTI- 
621. 

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Clinical Protocol TTI-621-01 
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TEST PRODUCT, DOSE, AND MODE OF ADMINISTRATION: 
TTI-621 (SIRPα-IgG1 Fc) is a soluble recombinant fusion protein created by directly linking the sequences 
encoding the N-terminal CD47 binding domain of human signal regulatory protein alpha (SIRPα) with the 
Fc domain of human immunoglobulin (IgG1). TTI-621 acts by binding human CD47 and preventing it from 
delivering an inhibitory “do not eat” (antiphagocytic) signal to macrophages. 
TTI-621 drug product is formulated in 10 mM sodium phosphate and 150 mM sodium chloride at a pH of 
7.4, supplied in single-use vials containing 5.0 mL of sterile preservative-free liquid at a concentration of 
10 mg/mL. 
The required dose of TTI-621 is to be diluted in 250 mL of 0.9% sodium chloride for injection USP and 
administered IV over 60 minutes at assigned dose levels as determined by sequential cohort assignment. 
STUDY DESIGN AND METHODOLOGY: 
This is a multicenter, open-label, phase 1a/1b trial of TTI-621 in subjects with relapsed or refractory 
hematologic malignancies and selected solid tumors that will be conducted in 4 parts. In the dose escalation 
phase (Part 1), subjects with advanced lymphomas will be enrolled in sequential dose cohorts to receive 
TTI-621 once weekly to characterize safety, tolerability, PK, and the maximum-tolerated dose (MTD). In 
the expansion phase (Part 2), subjects with a variety of hematologic malignancies and selected solid tumors 
will be treated at the recommended dose of TTI-621 as determined in phase 1a (Part 1) to further define 
safety and to characterize efficacy. In the expansion phase (Part 3), based on preliminary observations of 
response, 2 cohorts of subjects (1 cohort with cutaneous T-cell lymphoma (CTCL) and 1 cohort with 
peripheral T-cell lymphoma (PTCL)), will be evaluated separately for the potential to be further studied 
using the Simon 2-stage design. 
In the phase 1b dose optimization of the study (Part 4), further dose escalation of TTI -621 will be pursued in 
patients with relapsed and/or refractory CTCL following a 3+3 escalation design and using a revised DLT 
criteria. The major revision to the DLT criteria as used in phase 1a relates to Grade 4 thrombocytopenia. The 
safety data collected thus far from phase 1a and ongoing phase 1b expansion (by data cut-off of 01 October, 
2018) showed that related ≥ Grade 3 thrombocytopenia and platelet count decreased occurred in 11% and 
9% of patients respectively. Thrombocytopenia appeared to be transient and in general recovered within a 
week prior to the next dosing. Thrombocytopenia was not found to be associated with increased incidence of 
bleeding and had limited impa ct on the study drug delivery (See Section 1.8.4 for details). Based on the 
data, Grade 4 thrombocytopenia will be revised to qualify as a DLT only when the event lasts longer than 72 
hours. 
A Safety Review Committee (SRC) oversees the safety of all phases of the study. During the phase 1b dose 
optimization part (Part 4) of the study, the SRC convenes at appropriate intervals to review all available 
safety data in a cohort, cumulative information from all dosed subjects, and any new preclinical information 
as in phase 1a. The SRC renders decisions on dose escalation and other safety aspects of the study. All 
actions of the SRC are documented in written minutes. During phase 1b dose expansion phase (Part 2 and 
3), any significant safety and tolerability issues observed based on medical monitoring and 
pharmacovigilance signal detection can be discussed at SRC for recommendation on any actions to be taken. 
The SRC can also convene to discuss any individual patient cases brought forth for advice by the treating 
investigators or the sponsor. The SRC will extend its responsibility under Amendment 9 to review both 
safety and efficacy data to recommend a decision as to whether or when to proceed the Part 3 CTCL and 
PTCL cohorts to next stage per the Simon’s 2-stage design and in collaboration with the timing of the Part 4 
dose optimization phase of the study. The membership of the SRC may vary between different phases of 
the study and will be documented in the Safety Committee Charter document. 
Phase 1a Escalation (completed, as of amendment 9) 
A minimum of 3 subjects will be treated in each cohort in a conventional 3 + 3 design, starting at Cohort 1. 
Given the potential risk for cytokine release syndrome, the first subject in each dosing cohort will be treated 
and observed for 72 hours before the next subject can receive their first infusion of TTI-621. (Cohort 0 
represents a contingency de-escalation dose level in the event that tolerance issues are encountered in 
Cohort 1). Subjects will receive TTI-621 at the assigned dose once weekly for 3 weeks of 
treatment/observation for DLT assessment as defined in the protocol. If DLT is encountered in 1 of 
3 subjects within a particular cohort, 3 additional subjects will be treated at that dose level. Otherwise, 

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Clinical Protocol TTI-621-01 
20 February, 2019 
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enrollment will proceed sequentially through the predefined cohorts. Based on the incidence of DLT, the 
MTD will be determined. 
Phase 1b Expansion (ongoing, as of amendment 9) 
In the expansion phase of the study (Part 2), the safety and preliminary anti-tumor activity of TTI-621 
monotherapy at the recommended dose of TTI-621 as identified in the escalation phase were explored in up 
to 40 subjects per cohort type, as outlined in the table below. These cohorts included: indolent B-cell 
lymphoma (IBCL), aggressive B-cell lymphoma (ABCL), T-cell lymphoma (TCL), Hodgkin lymphoma 
(HL), chronic lymphocytic leukemia (CLL), multiple myeloma (MM), acute myeloid leukemia (AML), 
acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS), myeloproliferative neoplasms 
(MPN), and small cell lung cancer (SCLC). A cohort of subjects with CD20-positive malignancies were 
enrolled and treated with TTI-621 in combination with rituximab. In addition, a cohort of subjects with 
classic HL (cHL) were treated with TTI-621 in combination with nivolumab. Intrasubject dose- 
intensification after initial exposure to the recommended dose from phase 1a may be permitted at 
investigator discretion during the course of the study. 
An overview of monotherapy and combination treatments administered in the expansion phase (Part 2 and 
3) is provided in the table below. Starting doses of TTI-621 are shown; intrasubject dose-intensification may 
be permitted as outlined in Section 6.5.4. 
As of Amendment 9: 
Dose expansion: 
Part 2 
• 
The following monotherapy cohorts are closed to future enrollment: IBCL, ABCL, HL, CLL, 
MDS, MPN, SCLC, AML,MM, TCL and ALL 
• 
The cohorts with TTI-621 in combination with rituximab or nivolumab for subjects with CD20+ 
malignancies, and cHL, respectively, will remain open for enrollment until the planned slots are 
filled 
Part 3 
• 
Two cohorts are ongoing : CTCL and PTCL (consisting of T- and NK-cell neoplasms per WHO 
definition (Swerdlow et al., 2016) with overall response in each of the 2 cohorts (CTCL and PTCL) 
evaluated separately using the Simon 2-stage design 
• 
Dose intensification to a maximum of 0.5 mg/kg/week will be required for all newly enrolled 
subjects per Section 6.5.4. following a ramp-up schedule (2 weeks of study treatment at 0.2 mg/kg 
followed by dose intensification between week 3 and week 8 at increments of 0.1 mg/kg/week as 
tolerated up to maximum dose of 0.5 mg/kg/week) 
In summary, as of Protocol Amendment 9, enrollment will be limited to the following disease types: CD20+ 
NHL (in combination with rituximab), cHL (in combination with nivolumab), CTCL and PTCL. 

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Clinical Protocol TTI-621-01 
20 February, 2019 
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Expansion 
Cohort (n) 
TTI-621 
Starting 
Dose 
(mg/kg/wk) 
Combination 
Partner Dose 
Mandatory Dose 
Intensification 
Starting at Week 3 
increase by 
0.1 mg/kg/wk 
increments up to a 
maximum of 
0.5 mg/kg/wk 
Monotherapy 
IBCL (closed) 
0.2 
NA 
closed 
ABCL (closed) 
0.2 
NA 
closed 
HL (closed) 
0.2 
NA 
closed 
TCL (closed) 
0.2 
NA 
closed 
CTCL (up to 35) 
0.2 
NA 
Yes 
PTCL (up to 35) 
0.2 
NA 
Yes 
CLL (closed) 
0.2 
NA 
closed 
ALL (closed) 
0.2 
NA 
closed 
MM (closed) 
0.2 
NA 
closed 
AML (closed) 
0.2 
NA 
closed 
MDS (closed) 
0.2 
NA 
closed 
MPN (closed) 
0.2 
NA 
closed 
SCLC (closed) 
0.2 
NA 
closed 
Combination 
Therapy 
Rituximab combination: 
CD20-positive malignancy 
(up to 40) 
0.1 
375 mg/m2/wk 
for up to 8 cyclesa 
Yes 
Nivolumab combination: 
cHL 
(up to 15) 
0.1 
per FDA approved 
package insert for 
cHLb 
Yes 

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Clinical Protocol TTI-621-01 
20 February, 2019 
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Planned Dose Escalation Levels 
TTI-621 dose (mg/kg) 
 DLT evaluation period 
 
 
Level 
N 
Week 1 b 
Week 2 
Week 3 
0 
3 (+ 3) 
0.2 
0.5 
0.5 
1a 
3 (+ 3) 
0.5 
0.5 
0.5 
2 
3 (+ 3) 
0.7 
0.7 
0.7 
3 
3 (+ 3) 
1.0 
1.0 
1.0 
4 
3 (+ 3) 
1.4 
1.4 
1.4 
a Level 1 = starting dose 
b If de-escalation to Level 0 is required, all subsequent cohorts will start with a priming dose of 0.2 mg/kg at week 1 
followed by the respective dose level escalation increments (to 0.7, 1.0, 1.4 mg/kg) at week 2 or subsequent weeks, as 
applicable, based on SRC decision. 
The selection of the starting dose level and planned escalation cohorts will be guided by the dose 
intensification experience collected so far during the phase 1b expansion phase of this study. As of 26 
November 2018, in Part 2, 12 T Cell Lymphoma patients were initially dosed at the recommended dose of 
0.2 mg/kg and then dose intensified up to 0.5 mg/kg at the investigator discretion (ID). In Part 3 (A8), 14 T 
Cell Lymphoma patients have been treated per protocol-defined ramp-up schedule (2 weeks of study 
treatment at 0.2 mg/kg followed by dose intensification between week 3 and week 8 at increments of 0.1 
mg/kg/week as tolerated up to maximum dose of 0.5 mg/kg/week). Among these patients who were exposed 
to 0.5 mg/kg of TTI-621, 22 patients (11 ID; 11 A8) had both pre and post-dose platelet assessments on 
W1D1 after receiving TTI-621 0.2 mg/kg. A total of 17/22 patients (11 ID; 6 A8) had both pre and post- 
dose platelet assessments at Weeks 5-30 after receiving 0.5mg/kg. Median pre- and post-dose platelet 
values following 0.2mg/kg and 0.5 mg/kg doses were 257/123, and 234/188, respectively. Grade 4 post-dose 
platelet levels occurred in 1 patient each following 0.2 mg/kg and 0.5 mg/kg TTI -621 doses; 5% (1/22) 
versus 6% (1/17), respectively (See Section 1.8.4). In addition, related adverse events (AEs) were generally 
comparable or less frequent following 0.5 vs. 0.2 mg/kg doses. 
In the starting dose cohort (0.5 mg/kg), the first 3 patients will be treated sequentially to allow close 
monitoring of toxicity and timely dose adjustment if needed. The third patient will not start the study 
treatment until the first and second patient, respectively, have completed the initial two weeks of study 
treatment and had no observation of treatment-emergent adverse events (TEAE) meeting DLT criteria. If the 
first or second patient experiences a DLT event within the first two weeks of treatment, de-escalation to 
Level 0, a priming dosing regimen, will be considered per SRC discussion and decision. A priming regimen 
refers to a dosing regimen that involves a lower priming dose used during the initial week(s) of treatment 
followed by further dose escalation to a higher and sta ble dose for continued use throughout the course of 
the study. At Level 0, patients will be dosed at 0.2 mg/kg for the first week and then receive a stable dose of 
0.5 mg/kg for the remainder of the study. 
If Level 0 is determined to be tolerable per 3+3 schema, further escalation of doses beyond 0.5 mg/kg in 
Week 2 and beyond will be considered, as part of the priming dosing regimen. The same dose escalation 
increment (to 0.7, 1.0, and 1.4 mg/kg) may be followed after the initial week of exposure to 0.2 mg/kg. 
A DLT is defined in phase 1b dose optimization (Part 4) as any of the following TEAEs that occur during 
the 3-week DLT period (including pre-dose tests on Day 22) and that are considered at least possibly related 
to study treatment by the investigator. Note that any AEs for which the relationship to study trea tment 
cannot be ruled out should be considered possibly related: 
• 
Grade 4 thrombocytopenia (<25 × 109/L) lasting >72 hours or a platelet count ≤10 × 109/L at any 
time 
• 
≥ Grade 3 thrombocytopenia with bleeding (except epistaxis or gingival bleeding that is less than 
24 hours in duration and does not require medical intervention, or normal menses) or requiring 
platelet transfusions 

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Clinical Protocol TTI-621-01 
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• 
Grade 4 anemia, unexplained by underlying disease 
• 
Grade 4 neutropenia lasting >72 hours 
• 
Grade 3 febrile neutropenia lasting >72 hours 
• 
Grade 4 febrile neutropenia 
• 
Grade 3 or higher non-hematologic toxicity with the following exceptions: 
o 
Grade 3 nausea and/or vomiting lasting <72 hours with standard supportive care 
o 
Transient Grade 3 fatigue lasting ≤72 hours 
o 
Transient asymptomatic Gra de 3 laboratory abnormalities considered not clinically significant 
following agreement between investigators and the sponsor's medical monitor and that last <72 
hours with standard supportive care 
• 
Other ≥ Grade 2 TTI-621-related non-hematologic toxicities that, in the opinion of the investigator, 
require a dose reduction or discontinuation of TTI-621 
The major revision of the DLT criteria in comparison to those in phase 1a is that Grade 4 thrombocytopenia 
is no longer a DLT unless it lasts for more than 72 hours. This revision is based on a safety analysis of 179 
patients by a data cut of 01 October, 2018. The majority of patients (143; 80%) had abnormal platelet counts 
reported at 1 or more timepoints post-dose, with 49 subjects (27%) experiencing Grade 4 decreases, 
including both TTI-621-induced events, and events resulting from the underlying hematologic malignancies. 
As shown in Figure 1-3 (See Section 1.8.4), reduced platelet counts that occurred on dosing days generally 
recovered within the week prior to the next dose. Overall, pre-infusion platelet counts remained stable over 
the course of the study. Due to the transient and reversible nature of the thrombocytopenia, no apparent 
increase in the incidence of bleeding has been observed on study (Table 1-1, Section 1.8.4). A total of 
24/179 subjects (13%) experienced a treatment-emergent bleeding event in Study TTI-621-01 (see Table 
1-1, Section 1.8.4). Overall, 20/179 subjects (11%) experienced Grade 1 or 2 events and 4 subjects (2%) had 
Grade 3 events. Grade 3 hemorrhage events were considered treatment-related for 3 subjects (2%). No 
Grade 4 hemorrhage events were reported. Therefore, relaxing the original DLT criteria is appropriate after 
the clinical significance of thrombocytopenia is better a ssessed with an expanded safety data set. 
The MTD is defined as the dose level immediately below the lowest dose that at which 2 or more of either 3 
or 6 patients experienced a DLT during the 3-week DLT period. At least 6 patients must be treated at the 
putative MTD, with no more than 1 incidence of DLT. AEs that occur after the 3-week DLT period or 
cumulative toxicities will be considered in the final designation of MTD. 
If MTD is not reached after completion of all planned dose escalation levels, a decision will be made in 
consultation with the SRC, to either continue further escalation at a maximal 50% escalation increment, or 
dose escalation will be halted. A maximum assessed dose (MAD) could be used in lieu of the MTD. The 
SRC will review the totality of the safety, tolerability, PK, PD, and preliminary efficacy data (if available) 
before making this decision. 
In addition to MTD/MAD determination, SRC will review the totality of cumulative toxicity and tolerability 
data in balance against the PK, PD and preliminary efficacy data. If a biologically active dose appears to be 
lower than MTD/MAD or if the MTD/MAD results in dose modification due to tolerability that limits 
continued dose exposure and in turn compromise the potential efficacy gain, a recommended phase 2 dose 
of TTI-621 lower than MTD/MAD can be determined for future single agent studies. Minimally 6 patients 
will need to be evaluated at the recommended phase 2 dose before formal designation. 
After MTD/MAD or recommended phase 2 dose (if different from MTD/MAD) is determined, an additional 
6 patients will be enrolled and treated at this dose level to form a safety expansion cohort of a total of 12 
patients (including the 6 patients treated at the designated phase 2 dose before the dose selection). 
Preliminary efficacy will also evaluated in this cohort of patients. 
The initiation of phase 1b dose optimization will occur after the closure of enrollment to Stage 1 of Part 3 
CTCL cohort per Simon’s 2-stage design. The proceeding of the Part 3 CTCL and PTCL cohort will follow 
the criteria as described per Simon’s 2 stage design (Amendment 8). Other effica cy measures such as 
durability of response and disease control, safety signals in balance of clinical benefit, and evolving 
competitive landscape that impact the desirable efficacy assumption used in the Simon’s 2 -stage design, 
may influence the decision by the sponsor whether to proceed these cohorts to Stage 2. 
Additionally, in the context of Part 4 dose optimization introduced in Amendment 9, the following options 
will be considered and decisions regarding whether and/or when to proceed with the two Part 3 cohorts to 

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Clinical Protocol TTI-621-01 
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Stage 2 in relation to Part 4 dose optimization cohort will be made in a data -driven manner. Under this 
circumstance, SRC will review and discuss both safety and efficacy data and make recommendation to 
sponsor for final decision. 
• 
Proceeding to Stage 2 may be halted until the completion of the phase 1b dose optimization (Part 
4). At that time, the efficacy from Stage 1 in the Part 3 CTCL cohort will be assessed against that 
of the safety expansion cohort (when available) in CTCL patients in Part 4. The decision regarding 
which dose regimen to use for further clinical evaluation of single-agent TTI-621 in CTCL, PTCL, 
and/or other indications (the ramp-up schedule used in Part 3 vs selected dose regimen in Part 4) 
will depend on safety and the efficacy signal observed in association with these two dose regimens 
in CTCL. If the selected dose regimen in Part 4 is chosen, the sponsor may decide to stop the 
Simon’s 2 stage study plan and choose another form of continued evaluation including but not 
limited to starting a new study. 
• 
Proceeding to Stage 2 may occur in parallel to Part 4 dose optimization. This option may be 
considered when the efficacy signal from Stage 1 not only surpasses the minimal response criteria 
per the Simon’s 2-stage design but presents higher probability of surpassing the target response rate 
of 30% overall response rate (ORR). This parallel option is particularly amenable to the scenario 
where the Stage 2 of Part 3 PTCL cohort is proceeding together with Part 4 dose optimization in 
Part 4 due to different target patient populations for the two parallel cohorts. 

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MAJOR ELIGIBILITY CRITERIA: 
Phase 1a Escalation 
Histologically  documented, measurable, advanced lymphomas, transfusion -independence 
Phase 1b Expansion (Part 2 and 3) 
Advanced malignancy: IBCL, ABCL, cHL, AML, ALL, MDS, MPN, SCLC, PTCL and CTCL; measurable 
disease who have relapsed or are refractory following at least 2 prior systemic therapeutic attempts (1 prior 
systemic attempt for PTCL). For CTCL, extracorporal photochemotherapy (ECP) will be considered a 
systemic therapy. Local radiation and topical agents are not systemic therapies. 
Note: the following monotherapy cohorts have been closed to future enrollment: IBCL, ABC L, HL, CLL, 
MDS, MPN, SCLC, AML, MM, T Cell and ALL. 
Phase 1b dose optimization (Part 4) 
Histologically confirmed diagnosis of CTCL (both Mycosis Fungoides and Sezary Syndrome): 
• 
Failed at least 2 prior systemic therapies for CTCL (Systemic therapy does not include local 
radiation therapy or topical agents) 
• 
Malignancy is measurable per global CTCL criteria (Olsen, 2011) 
• 
History of histologically-documented diagnosis of CTCL stage IB to IVB (Olsen, 2011) 
All subjects 
• 
Previously progressed on, or currently progressing on standard anticancer therapy or for whom no 
other approved conventional therapy exists; male or female 18 years or older; Eastern Cooperative 
Oncology Group (ECOG) status of 0, 1, or 2; adequate hematologic, hepatic, renal, and coagulation 
function; fresh or archived tumor tissue available for immunohistochemistry; recovery from prior 
treatments and/or surgeries; no history of hemolytic anemia or bleeding diathesis. 
• 
Subjects with AML M3 using the French American British (FAB) classification (i.e., acute 
promyelocytic leukemia [APL]) are excluded from this trial. 
PLANNED SAMPLE SIZE: 
Eighteen subject enrolled in phase 1a , and up to approximately 285 for the entire study including 
approximately 25 subjects in phase 1b dose optimization phase (Part 4). 

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Clinical Protocol TTI-621-01 
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TREATMENT PROCEDURES: 
Subjects in the escalation phase will receive the assigned dose level of TTI -621 once weekly. TTI-621 will 
be infused in 250 mL of normal saline over 60 minutes. Vital signs will be measured and subjects will be 
monitored for possible infusion reactions. In the absence of disease progression, subsequent TTI -621 doses 
may be delivered if both clinical and laboratory AEs have resolved to Grade 1 or better (or to baseline grade 
if pre-existing) with the exceptions listed in Section 6.5. 
Subjects in the expansion phase Part 2 will receive TTI-621 using the initial monotherapy MTD dose as 
identified in the escalation phase (0.2 mg/kg) as a starting dose. Subjects in the combina tion treatment 
cohorts will receive a starting dose of 0.1 mg/kg TTI-621 together with the combination partner agent. 
Subjects will receive the assigned dose level of TTI-621 once weekly. Subsequent TTI-621 doses will be 
delivered if both clinical and laboratory AEs have resolved per Section 6.5.3. Dose delays and/or reductions 
in individual subjects may be instituted as appropriate. 
All newly enrolled subjects in the expansion phase Part 3 will undergo dose intensification weekly to a 
maximum dose of 0.5 mg/kg/week as tolerated in 0.1 mg/kg/week increments starting at Week 3. Dose 
modifications for TTI-621 should be instituted per Section 6.5. 
Subjects in the phase 1b dose optimization phase (Part 4) will be enrolled in additional TTI-621 dose 
escalation cohorts, starting with level 1 (dose of 0.5 mg/kg) given once weekly. Following a 3+3 escalation 
design and using a revised DLT criteria, enrollment will continue through level 2 (starting dose of 0.7 
mg/kg), level 3 (starting dose of 1.0 mg/kg) and level 4 (starting dose of 1.4 mg/kg) respectively. In the 
starting dose cohort (0.5 mg/kg), the first 3 patients will be treated sequentially to allow close monitoring of 
toxicity and timely dose adjustment if needed. The second and third patient will not start the study treatment 
until the first and second patient, respectively, have completed the initial 2 weeks of study treatment and had 
no observation of TEAEs meeting DLT criteria. If a DLT is noted in level 1, there may be de-escalation to 
level 0 (priming dose of 0.2 mg/kg at week 1 followed by 0.5 mg/kg at subsequent doses) with progression 
through Levels 2, 3 and 4 using the dose priming approach of 0.2 mg/kg at week 1 followed by the 
respective level dose regimens at subsequent weeks. 
Treatment for all parts of the study (Part 1-4) may continue until disease progression, unacceptable toxicity, 
or other reason for treatment discontinuation. For phase 1b expansion Parts 2 -4, for patients who have been 
given weekly infusion of TTI-621 for more than a year and are receiving clinical benefit (objective response 
or clinically meaningful long-term stable disease), investigators may exercise their discretion to reduce the 
dosing frequency from weekly to bi-weekly following the discussion and approval from the sponsor or 
designees. 
STUDY TESTS AND OBSERVATIONS: 
Standard safety measurements include physical exam and body weight, ECOG score, clinical AEs, 
laboratory variables (hematology, serum chemistries, urinalysis, and coagulation), electrocardiogram (ECG), 
and vital signs. Additional safety tests relevant to the biology of TTI-621 include evaluation of the 
incidence of antibodies to TTI-621. Quality of life (QOL) will be measured by the FACT-G questionnaire, 
(all tumor types), and using the SKINDEX29 questionnaire (subjects with CTCL). 
Disease assessments will be performed as per Appendix D. Table 3. Blood will be taken serially for PK 
assessment. Additional blood samples will be taken for PD and biomarkers such as flow cytometric 
assessment of leukocyte subpopulations, receptor occupancy, and soluble cytokines/chemokines. 

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STUDY ENDPOINTS: 
Phase 1a Escalation 
• 
Primary: incidence and severity of AEs 
• 
Secondary: PK profile, PD, ADA 
Phase 1b Expansion (Part 2 and 3) 
• 
Part 2 and 3 Primary: incidence and severity of AEs 
• 
Part 2 and 3 Secondary: PK profile, PD, ADA, ORR, duration of response (DOR), and 
progression-free survival (PFS) 
• 
Part 3 endpoints: CTCL and PTCL: organ system ORR - 2 analyses within each cohort 
Phase 1b Expansion Dose Optimization (Part 4) 
• 
Primary: incidence and severity of AEs 
• 
Secondary: PK, PD, ADA, ORR, DOR, organ system overall response rate (Olsen, 2011) 
STATISTICAL METHODS: 
Safety Analyses 
Safety analyses will be conducted using all dosed subjects. The results of the safety analyses will be 
presented by study phase. For the escalation phase, tabulations will be provided by dose cohort and overall. 
For the expansion phase, tabulations will be provided by disease cohort and overall. Some safety analyses 
may be performed based on all treated subjects combined. 
TEAEs reported during the study will be tabulated and listed by MedDRA System Organ Class and 
preferred term. Tables will display number and percentage of subjects with the event for the following 
categories: all AEs, events considered related to study drug, events by severity, DLT, events occasioning 
treatment modification, and serious adverse events (SAEs). For the escalation phase, the observed DLT rate 
in each dose cohort will be calculated by the crude proportion of subjects who experienced DLT, 
accompanied with a 95% exact binomial CI. 
Hematology and serum chemistries will be summarized using conventional summary statistics (mean, 
standard deviation, median, and range) for the following: baseline value, minimum and maximum post 
baseline values, average post baseline value, and last post baseline value. Standard shift tables will also be 
prepared presenting worst post baseline toxicity grade vs baseline. Incidence of subjects with ADA will be 
summarized descriptively. Laboratory values acquired during the immediate post-infusion period will be 
presented separately. 
Vital signs and ECG results will be summarized in a descriptive manner by calculating the mean, standard 
deviation, median, and range by time point in the same manner described for laboratory va lues. 
Pharmacokinetic Analyses 
PK parameters of TTI-621 will be calculated from concentration-time data using noncompartmental 
analyses. Parameters may include, as appropriate, AUC0–τ, AUC0–∞, Cmax, Tmax, t1/2, clearance, and 
volume of distribution. Results will be reported using conventional summary statistics. The relationship 
between TTI-621 exposure and various safety indices will be assessed. All final PK analyses will be 
defined in the final PK analysis plan and/or final Statistical Analysis Plan (SAP) as appropriate. 

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Efficacy Analyses 
Efficacy analyses will be conducted using the Full Analysis Set and, where appropriate, the Per-protocol 
Set; in addition, the ORR will also be presented for the Response-Evaluable Set and will be estimated for 
each cohort evaluated in the expansion pha se using disease-specific response criteria. The DOR will be 
calculated for a subject who achieves response, and is defined as the number of weeks from the start dat e of 
the response (and subsequently confirmed) to the first date recurrent or progressive disease is documented ; 
subjects who are ongoing at the time of the analysis will have the last study visit date included as a censored 
value for the Kaplan-Meier analysis. If a subject dies, irrespective of cause, without documentation of 
recurrent or progressive disease beforehand, then the date of death will be used to denote the response end 
date. PFS is defined as the number of weeks from the date of the first dose of study drug to the earliest of 
documented recurrent or progressive disease or death due to any cause without prior progression . DOR and 
PFS will be summarized descriptively using the Kaplan-Meier method with 95% CI calculated using 
Greenwood’s formula. Median follow-up for each endpoint will be estimated according to the Kaplan-Meier 
estimate of potential follow-up. The PFS rate at selected landmarks (e.g., 6 months) and corresponding 95% 
CIs will be estimated using the Kaplan-Meier method. Greenwood’s formula will be used to calculate the 
standard errors of the Kaplan-Meier estimate and upper and lower limits of the 95% CI. 
Pharmacodynamic measurements and biomarkers will be summarized using summary statistics and may be 
displayed graphically as appropriate. Subgroup analyses, which will be pre-specified in the SAP, may be 
conducted in the expansion phase of the study to explore the relationship between measures of anti-tumor 
activity and selected baseline biomarkers. 
Phase 1b Part 3-Specific Analyses 
Each of the 2 additional cohorts (CTCL and PTCL) will be evaluated separately for the potential to be 
further studied using the Simon 2-stage design. For the first stage, a total of 18 response-evaluable subjects 
will be reviewed in each cohort; if 2 or fewer responders are observed, enrollment in the respective cohort 
will be terminated. Otherwise, enrollment will continue to the second stage and an additional 17 subjects 
will be enrolled for a total of 35 response-evaluable subjects per cohort. At the end of the second stage, if 6 
or fewer responders per cohort are observed, the drug will be rejected for further testing in this indication. 
The safety and efficacy assessments outlined above will be summarized for each cohort separately . If more 
than the required number of response-evaluable patients are available (i.e., >18 or >35), the first 18 or 35, 
respectively, would be used. 

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TABLE OF CONTENTS 
SYNOPSIS ............................................................................................................... 2 
1. 
INTRODUCTION .................................................................................................. 21 
1.1 
Hematologic Malignancies ......................................................................... 21 
1.2 
Cutaneous T-cell Lymphoma ..................................................................... 21 
1.3 
Peripheral T-cell Lymphoma ...................................................................... 22 
1.4 
CD47 and SIRPα ........................................................................................ 23 
1.5 
Regulation of Phagocytic Activity ............................................................. 23 
1.6 
TTI-621 ...................................................................................................... 24 
1.6.1 Mechanism of Action ..................................................................... 24 
1.6.2 Chemistry and Description ............................................................. 25 
1.6.3 Nonclinical Pharmacodynamics ..................................................... 26 
1.6.4 Nonclinical Pharmacokinetics ........................................................ 27 
1.6.5 Toxicology ..................................................................................... 28 
1.7 
Anticipated or Possible Risks in Human Subjects ..................................... 29 
1.8 
Rationale for Selection of Doses ................................................................ 31 
1.8.1 TTI-621 Monotherapy .................................................................... 31 
1.8.2 Combination Therapy Cohorts ....................................................... 32 
1.8.3 Rationale for Intrasubject Dose-Intensification ............................. 32 
1.8.4 Rationale for Phase 1b Dose Optimization (Part 4) ....................... 33 
2 
STUDY OBJECTIVES .......................................................................................... 36 
2.1 
Phase 1a Dose Escalation ........................................................................... 36 
2.2 
Phase 1b Dose Expansion (Part 2 and Part 3) ............................................ 36 
2.3 
Phase 1b Dose Expansion (Dosing Optimization, Part 4) .......................... 37 
3 
INVESTIGATIONAL PLAN ................................................................................ 38 
3.1 
Overall Study Design ................................................................................. 38 
3.2 
Phase 1a Escalation (Completed) ............................................................... 39 
3.2.1 Dose Advancement and MTD Determination ................................ 39 
3.2.2 Definition of Maximum Tolerated Dose ........................................ 41 
3.3 
Phase 1b Expansion .................................................................................... 41 
3.3.1 Phase 1b - Part 2 and Part 3 ........................................................... 41 
3.3.2 Phase 1b Dose Optimization Part 4 (to be enrolled as of 

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Amendment 9) ............................................................................... 43 
3.3.3 Definition of Dose-limiting Criteria for Phase 1b Part 4 
(Amendment 9) .............................................................................. 45 
3.4 
Safety Review Committee .......................................................................... 46 
3.5 
Number of Subjects .................................................................................... 47 
3.6 
Investigational Sites ................................................................................... 47 
3.7 
Study Duration ........................................................................................... 47 
4 
SELECTION OF STUDY POPULATION ........................................................... 48 
4.1 
Inclusion Criteria ........................................................................................ 48 
4.2 
Exclusion Criteria ....................................................................................... 52 
5 
ENROLLMENT PROCEDURES .......................................................................... 54 
6 
TREATMENT PROCEDURES ............................................................................. 54 
6.1 
Investigational Product ............................................................................... 54 
6.2 
Method of Assigning Subjects to Treatment Groups ................................. 54 
6.3 
Treatments Administered (All Phases) ....................................................... 55 
6.3.1 Dosing Instructions ........................................................................ 55 
6.4 
Treatments Administered – Expansion Phase ............................................ 56 
6.4.1 TTI-621 Monotherapy .................................................................... 56 
6.4.2 TTI-621 plus Rituximab Combination Cohort ............................... 56 
6.4.3 TTI-621 plus Nivolumab Combination Cohort .............................. 57 
6.5 
Dose Modifications (Amendment 9) ......................................................... 58 
6.5.1 General Principles .......................................................................... 58 
6.5.2 Criteria for Retreatment and Dose Delays ..................................... 59 
6.5.3 Dose Modification Guidelines for TTI-621-related toxicities ....... 60 
6.5.4 Intrasubject Dose Intensification (Phase 1b dose expansion Part 3) 
. ....................................................................................................... 63 
6.6 
Intra-patient Dose Reduction and Escalation (Phase 1b Dose Optimization 
Part 4: DLT evaluation period) .................................................................. 63 
6.7 
Management of Clinical Events ................................................................. 64 
6.8 
Concomitant Medications and Treatment .................................................. 65 
6.8.1 Required Concomitant Treatments ................................................ 65 
6.8.2 Allowed Concomitant Treatments ................................................. 65 
6.8.3 Prohibited Concomitant Treatments .............................................. 66 
6.9 
Removal of Subjects from Therapy or Assessment ................................... 67 

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7 
TESTS AND EVALUATIONS ............................................................................. 68 
7.1 
Screening Period ........................................................................................ 68 
7.2 
Day 1 Pre-infusion ..................................................................................... 70 
7.3 
Day 1 Post-TTI-621 infusion (see Table 7-1) ............................................ 71 
7.4 
Week 2 ....................................................................................................... 73 
7.5 
Week 3 ....................................................................................................... 74 
7.6 
TTI-621 Intrasubject Dose Intensification – Additional Assessments Every 
Week of Dose Intensification (only applicable to Part 3) .......................... 75 
7.7 
Week 4 ....................................................................................................... 75 
7.8 
Week 5-7 .................................................................................................... 77 
7.8.1 Week 5 (Part 4 only) ...................................................................... 77 
7.8.2 Week 6 (Part 4 only) ...................................................................... 77 
7.8.3 Week 7 (Part 4 only) ...................................................................... 78 
7.9 
Week 8 ....................................................................................................... 78 
7.10 
Weeks 9 and Higher ................................................................................... 79 
7.10.1 Phase 1b Part 3 ............................................................................... 79 
7.10.2 Phase 1b Part 4 ............................................................................... 81 
7.11 
End-of-Treatment Visit .............................................................................. 82 
7.12 
Safety Follow-up Visit ............................................................................... 83 
7.13 
Long-term Follow-up (Expansion Phase Only) .......................................... 84 
7.14 
Procedures for Special Tests ...................................................................... 84 
7.14.1 Disease Assessment ........................................................................ 84 
7.14.2 PK .................................................................................................. 86 
CCI 
 
8 
PLANNED ANALYSES ....................................................................................... 89 
8.1 
Study Endpoints ......................................................................................... 89 
8.1.1 Escalation Phase ............................................................................. 89 
8.1.2 Expansion Phase, Part 2 and Part 3 ................................................ 89 
8.1.3 Expansion Phase, Part 4 ................................................................. 89 
8.2 
Analysis Populations .................................................................................. 90 
8.3 
Determination of Sample Size .................................................................... 91 
8.4 
Statistical Methods ..................................................................................... 93 
8.4.1 Subject Disposition ........................................................................ 93 

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8.4.2 Demographics and Baseline Characteristics ................................... 94 
8.4.3 Extent of Exposure ......................................................................... 94 
8.4.4 Safety Analyses .............................................................................. 94 
8.4.5 PK Analyses ................................................................................... 96 
8.4.6 Efficacy Analyses ........................................................................... 96 
8.4.7 
CTCL and PTCL Cohorts ............................................................. 97 
CCI  
9 
ADVERSE EVENTS AND SAFETY REPORTING ............................................ 99 
9.1 
Grading and Severity of Adverse Events ................................................... 99 
9.2 
Adverse Event Attribution ....................................................................... 100 
9.3 
Serious Adverse Event Reporting ............................................................ 100 
9.4 
Reporting Periods for Adverse Events and Serious Adverse Events ....... 101 
9.5 
Adverse Events of Special Interest ........................................................... 102 
10 
ETHICAL AND ADMINISTRATIVE CONSIDERATIONS ............................ 105 
10.1 
Regulatory Authority Approval ............................................................... 105 
10.2 
Ethics Approval ........................................................................................ 105 
10.3 
Informed Consent and Protected Health Information .............................. 105 
10.4 
Clinical Supplies ...................................................................................... 106 
10.5 
Data Management and Study Monitoring ................................................ 106 
10.6 
Records Retention .................................................................................... 106 
11 
REFERENCES ..................................................................................................... 108 
12 
APPENDICES ...................................................................................................... 111 
Appendix A. Definitions of Indolent vs Aggressive B-cell Lymphomas and T 
cell lymphomas* ...................................................................................... 112 
Appendix B.  Eastern Cooperative Oncology Group Performance Scale ........... 114 
Appendix C.  Grading Scale for Skin Symptoms of Graft-vs-host Disease ....... 115 
Appendix D.  Summary of Tests and Observations ........................................... 116 
Appendix D. Table 1. Phase 1b - Part 2 and 3: Schedule of Assessments 
(additional assessments as clinically indicated) ....................................... 116 
Appendix D. Table 2. Phase 1b - Part 4 Dose Optimization: Schedule of 
Assessments ............................................................................................. 120 
Appendix D. Table 3. Response Assessments by Malignancy Type ................ 124 
Appendix E. Cockcroft-Gault Equation for Calculating Estimated Creatinine 

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Clearance .................................................................................................. 126 
Appendix F. Expansion Phase 1b Part 4 Dose Regimen Scenarios for 
Hematology, PK and Receptor Occupancy (blood) ................................. 127 
Appendix G.  Principal Investigator’s Signature Page ....................................... 128 
Appendix H.  Document History Summary of Changes .................................... 129 
 
LIST OF FIGURES 
Figure 1-1: Proposed TTI-621 Mechanism of Action ....................................................... 25 
Figure 1-2: Schematic of TTI-621 ..................................................................................... 25 
Figure 1-3: Pre-dose Platelet Counts During Week 1 ....................................................... 34 
Figure 1-4: Pre and Post-Dose Platelet Levels following 0.2 and 0.5 mg/kg TTI-621 ..... 35 
 
LIST OF TABLES 
Table 1-1: Treatment-Emergent Bleeding AEs (Safety Analysis Set) ............................... 36 
Table 3-1: TTI-621 Dose Levels by Cohort ....................................................................... 40 
Table 3-2: Dose Escalation Rules ....................................................................................... 41 
Table 3-3: Disease Cohorts and Schedule of Treatments Administered ............................ 43 
Table 3-4: Planned Dose Escalation Levels ....................................................................... 44 
Table 6-1: Dose Modifications for Dose 2 and Subsequent Doses .................................... 61 
Table 7-1: Week 1 Temporal Summary of Infusion and Post-infusion Assessments ........ 72 
Table 7-2: Summary of Pharmacokinetic Sampling Times ............................................... 87 
Table 8-1: 95% Lower Confidence Limits for Response Rate........................................... 92 

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DEFINITIONS OF ABBREVIATIONS AND TERMS 
Abbreviation 
or Term 
Definition 
ABCL 
aggressive B-cell lymphoma 
ADA 
antidrug antibodies 
ADa M 
Analysis Dataset Model 
AE 
adverse event 
ALCL 
anaplastic large-cell lymphoma 
ALL 
acute lymphoblastic leukemia 
ALT 
alanine aminotransferase 
AML 
acute myeloid leukemia 
ANC 
absolute neutrophil count 
AP/BP 
accelerated phase/blast phase 
APL 
acute promyelocytic leukemia 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
auto-SCT 
autologous stem cell transplantation 
BUN 
blood urea nitrogen 
BV 
brentuximab vedotin 
CD47 
transmembrane protein and the target of TTI-621 
CFR 
Code of Federal Regulations 
cHL 
classic Hodgkin Lymphoma 
CI 
confidence interval 
CLL 
chronic lymphocytic leukemia 
Cmax 
maximum concentration 
CMML 
chronic myelomonocytic leukemia 
CMR 
complete metabolic response 
CP 
chronic phase 
CR 
complete response/remission 
CRF 
case report form 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTCL 
cutaneous T-cell lymphoma 
DIPSS 
Dynamic International Prognostic Scoring System 
DLT 
dose-limiting toxicity 
DNMT1 
DNA methyl transferase 1 
DOR 
duration of response 
EC 
Ethics Committee 
EC50 
effective concentration at one-half of the maximal response is obtained 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
ECP 
extracorporal photochemotherapy 

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Abbreviation 
or Term 
Definition 
EOI 
end of infusion 
EOT 
end of treatment 
ET 
essential thrombocythemia 
FAB 
French American British 
Fc 
region of an immunoglobulin molecule 
FDA 
Food and Drug Administration 
FLC 
free light chains 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
HL 
Hodgkin lymphoma 
HLA 
human leukocyte antigen 
HNSTD 
highest non-severely toxic dose 
HSCT 
hematopoietic stem cell transplantation 
IBCL 
Indolent B-cell lymphoma 
ICH 
International Conference on Harmonisation 
ID 
investigator's discretion 
IFN 
interferon 
IgG1 
immunoglobulin G1 
IMID 
immunomodulatory drug 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
IRR 
infusion-related reaction 
IV 
intravenous(ly) 
LCL 
lower confidence limit 
LDH 
lactate dehydrogenase 
MABEL 
minimal anticipated biological effect level 
MAD 
maximum assessed dose 
MDS 
myelodysplastic syndrome 
MedDRA 
Medical Dictionary for Regulatory Activities 
MF 
Mycosis Fungoides 
MM 
multiple myeloma 
MPN 
myeloproliferative neoplasms 
MPN-AP/BP 
accelerated phase/blast phase myeloproliferative neoplasm 
MPN/MDS 
myeloproliferative/myelodysplastic overlap neoplasms 
MRD 
minimal residual disease 
MTD 
maximum tolerated dose 
NCI 
National Cancer Institute 
NHL 
non-Hodgkin lymphoma 
NOS 
not otherwise specified 
ORR 
objective/overall response rate 

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Abbreviation 
or Term 
Definition 
OS 
overall survival 
PCR 
polymerase chain reaction 
PD 
pharmacodynamics 
PD-1 
programmed  death-1 
PD-L 
programmed death ligand 
PET 
probability of early termination 
PFS 
progression-free survival 
PK 
pharmacokinetics 
PMR 
partial metabolic response 
Post-ET 
post-essential thrombocythemia 
Post-PV 
post-polycythemia vera 
PR 
partial response/partial remission 
PTCL 
peripheral T-cell lymphoma 
PV 
polycythemia vera 
Q 
every (e.g., Q2 weeks = once every 2 weeks) 
QOL 
quality of life 
RAEB 
refractory anemia with excess blasts 
RBC 
red blood cell 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
subcutaneous(ly) 
SCLC 
small cell lung cancer 
SDTM 
Study Data Tabulation Model 
SFU 
safety follow-up 
SIRPα 
signal regulatory protein alpha 
SIRPα-IgG1 
fusion protein consisting of the binding domain for CD47 (SIRPα) and a region of 
Fc 
human IgG1 (Fc) 
SRC 
safety review committee 
SS 
Sézary syndrome 
t½ 
terminal half-life 
TEAE 
treatment-emergent adverse event 
TCL 
T-cell lymphoma 
Tmax 
time of maximum concentration 
TSH 
thyroid-stimulating hormone 
TTI-621 
investigational product (SIRPα-IgG1 Fc) 
ULN 
upper limit of normal 
WBC 
white blood cell 

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1. INTRODUCTION 
 
1.1 Hematologic Malignancies 
 
Non-Hodgkin lymphoma (NHL), which together with Hodgkin lymphoma (HL) comprises 
the broad class of malignant lymphomas, is the most prevalent hematologic malignancy in 
the US, representing approximately 4% of all malignancies in both incidence and deaths 
per year (National Cancer Institute, 2015). Approximately 72,000 new cases of NHL will 
be diagnosed in 2015 and approximately 20,000 patients will die of their disease (Siegel et 
al., 2015). 
 
NHL is further subdivided into two distinct prognostic groups: indolent and aggressive 
lymphomas. Indolent or low-grade subtypes have a relatively good prognosis with a 
median survival as long as 20 years; however, patients presenting with advanced disease 
are generally not curable with standard therapies. Patients with early-stage indolent NHL 
can often obtain disease control with radiation therapy alone, while patients with advanced 
disease often require systemic chemotherapy. 
 
Aggressive or high-grade NHL often presents clinically in a more symptomatic manner 
than indolent lymphoma, but a considerable number of these patients can be cured using 
intensive combination chemotherapy regimens. The standard treatment for patients with 
aggressive lymphoma who do not obtain a complete response with frontline treatment — 
or for those who relapse — is intensive salvage chemotherapy followed by autologous stem 
cell transplantation (auto-SCT). Not all patients are suitable candidates for this aggressive 
treatment option. In addition, relapsed or progressive disease after auto-SCT occurs in 
more than 50% of patients with NHL (Philip et al., 1995); for these patients, prognosis is 
poor, with a median overall survival of 7 to 11 months (Paltiel et al., 2003). Currently there 
is no consensus treatment for patients who have relapsed or refractory disease after auto- 
SCT. 
 
Across the disease spectrum, malignant lymphoma continues to represent an unmet 
medical need. Given the few treatment options available for patients with relapsed or 
refractory lymphoma, novel therapies providing clinical benefit are needed. 
 
1.2 Cutaneous T-cell Lymphoma 
 
Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of extranodal 
lymphomas, which includes the 2 main subtypes, mycosis fungoides (MF) and Sézary 
syndrome (SS). Categorization of CTCL is based on the International Society for 
Cutaneous Lymphomas/European Organization for Research and Treatment of Cancer 

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(ISCL/EORTC) classification system (Olsen et al., 2011), which stratifies risk based on 
tumor, node, metastasis, and blood (TNMB) staging and provides prognostic information, 
with limited-stage disease conferring the longest median overall survival. Skin-directed 
therapies are preferred in the management of limited-stage disease, whereas advanced- 
stage disease requires systemic therapies. CTCL is characterized by variable CD30 over- 
expression; therefore, recently approved therapies include the CD30-directed antibody- 
drug conjugate brentuximab vedotin (BV). In an open-label, randomized phase 3 trial, BV 
was associated with an improved 4-month overall response rate (ORR) compared to 
physician’s choice of therapy (4-month ORR of 56.3% versus 12.5%) (Prince et al., 2017). 
CTCL however, remained a resistant malignancy with a median PFS of 16.7 months in the 
BV arm, and 38/64 patients in the BV arm received subsequent anti-cancer therapy. 
 
In a global, open-label, randomized trial in patients with previously treated CTCL, the 
anti-CCR4 antibody, mogamulizumab, demonstrated an improved ORR versus the histone 
deacetylase inhibitor, vorinostat (28% versus 4.8%, respectively), with the most 
pronounced improved ORR in patients with SS (37% [mogamulizumab] vs 2.3% 
[vorinostat]) (Kim et al., 2017). The median PFS was 7.7 months vs 3.1 months for 
mogamulizumab and vorinostat, respectively. 
 
Other approved therapies for CTCL include bexarotene, vorinostat, romidepsin and 
pralatrexate with ORRs of approximately 20-30%. As demonstrated by the aforementioned 
clinical trials, novel therapeutic options are needed for patients whose CTCL recurs 
following approved therapies. Preliminary data with TTI-621 in both the intravenous and 
intratumoral studies suggests that CD47 blockade with an IgG1 Fc decoy agent may 
provide a therapeutic option for those with advanced and large-cell transformed disease, 
with several highly refractory patients experiencing objective responses in the phase 1b 
T-cell cohort. 
 
1.3 Peripheral T-cell Lymphoma 
 
Aggressive peripheral T-cell lymphomas (PTCLs) per WHO 2016 classification, can be 
subdivided into those of primarily nodal origin and those that typically present in specific 
extranodal sites and are often associated with characteristic clinical syndromes (Swerdlow 
et al., 2016). Anaplastic large-cell lymphoma (ALCL) is the one of the more common types 
of aggressive PTCL. In 65% of cases, ALCL is characterized by the ALK mutation which 
impacts survival. In the 1314 patient experience of The International Peripheral T-Cell 
Lymphoma Project, Savage and colleagues reported that the 5-year OS (70% vs. 49%) and 
5-year failure-free survival (60% vs. 36%) both favored patients with ALK-positive ALCL 
(Savage et al., 2008). Additionally, they found that the 5-year failure-free survival rate for 
ALK-negative ALCL was superior when compared with PTCL not otherwise specified 

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(NOS): 36% vs 20%; p=0.012, with an OS of 49% vs 32%; p=0.032. PTCL-NOS is 
characterized by aggressive disease, short duration of response, and poor overall survival. 
A recent review concluded that PTCL patients with recurrent disease display a “dismal 
prognosis with their therapy representing an unmet medical need as best treatment strategy 
is yet to be determined” (Broccoli and Zinzani, 2017). Preliminary results with TTI-621 
have demonstrated anti-tumor activity in several patients with a variety of subtypes of 
relapsed or refractory PTCL. 
 
1.4 CD47 and SIRPα 
 
CD47 is a cell-surface protein expressed on multiple normal cell types and often at high 
levels on many malignant tumor cells. CD47 interacts with several different proteins and 
is involved in a wide variety of physiologic processes including platelet and neutrophil 
activation, T-cell function, regulation of vascular signaling by nitric oxide, inhibition of 
dendritic cell activity, and inhibition of monocyte activation. CD47 binds to signal 
regulatory protein alpha (SIRPα) on the surface of macrophages thereby transmitting a 
signal that inhibits the ability of macrophages to phagocytose the cell (Weiskopf and 
Weissman, 2015). 
 
SIRPα is a transmembrane glycoprotein receptor consisting of 3 extracellular 
immunoglobulin-like domains and a cytoplasmic tail that triggers phosphatase-mediated 
signaling. SIRPα is found on macrophages, monocytes, granulocytes, dendritic cells, and 
neurons (Adams et al., 1998). 
 
1.5 Regulation of Phagocytic Activity 
 
Macrophage-mediated phagocytosis is regulated by both positive and negative signals. 
Normally, macrophages recognize pro-phagocytic signals that are present on tumor cells 
and absent on normal cells that trigger engulfment and destruction. CD47, which transmits 
an anti-phagocytic signal through SIRPα, is an important mechanism by which malignant 
cells escape immune-mediated clearance. Although the precise mechanism by which the 
CD47-SIRPα axis inhibits phagocytosis is not fully understood, it is thought to involve 
deactivation of the contractile cytoskeletal activity involved in pulling the target cell into a 
macrophage for ingestion (Tsai and Discher, 2008). 
 
High levels of CD47 have been found to correlate with poor clinical prognosis in patients 
with a number of cancer types, including most hematologic malignancies (Chao et al., 
2011; Chao et al., 2010; Jaiswal et al., 2009; Majeti et al., 2009). For example, OS was 
significantly lower for patients with diffuse large B-cell lymphoma and mantle cell 
lymphoma who had elevated CD47 expression. Similarly,  patients with chronic 

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lymphocytic leukemia (CLL) that expressed high levels of CD47 experienced a 
significantly worse event-free survival compared with those whose tumor expressed lower 
expression levels (Chao et al., 2010). 
 
Phagocytosis of tumor cells, including small cell lung cancer (SCLC) cells, may be 
experimentally increased by disrupting the CD47-SIRPα interaction by means of anti- 
CD47 antibodies. Several developmental programs are underway to explore this possible 
therapeutic approach. In addition, CD47 blockade has been shown to augment rituximab 
potency in preclinical models (Chao et al., 2010). Preclinical studies have also 
demonstrated that the combination of a CD47 antagonist with programmed death-ligand 
(PD-L)-1 blockade resulted in tumor control and increased survival compared with either 
agent alone (Sockolosky et al., 2016). 
 
1.6 TTI-621 
 
Trillium Therapeutics Inc. (Trillium) is developing TTI-621 (SIRPα-IgG1 Fc), a soluble 
recombinant fusion protein created by combining the sequences encoding the N-terminal 
portion of human SIRPα with the Fc region of human IgG1. The SIRPα region interacts 
with its ligand CD47, while the Fc region binds to macrophage Fcγ receptors. TTI-621 
functions as a decoy receptor, binding CD47 on the surface of the tumor cells and blocking 
its anti-phagocytic signal, allowing the macrophage to ingest the malignant cell. The Fc 
region of TTI-621 may also assist in the activation of macrophages through engagement of 
Fcγ receptors. 
 
1.6.1 Mechanism of Action 
 
The proposed mechanism of action for TTI-621 is illustrated in Figure 1-1. Tumor cells 
express high levels of the CD47 “do not eat” signal, which suppresses phagocytosis 
by engaging SIRPα on the surface of macrophages, overriding any pro-phagocytic 
(“eat”) signals (Step A). The decoy receptor TTI-621 binds to CD47 on the surface of 
tumor cells (Step B) and engages activating Fc-gamma receptors on macrophages 
(Step C). The combination of CD47 blockade and activating signals triggers 
macrophage phagocytosis of tumor cells (Step D). Macrophages then process the 
internalized tumor cells, resulting in the presentation of tumor antigen peptide-MHC 
complexes at the cell surface (Step E), triggering T cell activation and tumor cell 
destruction (Step F). Thus, blockade of CD47 by TTI-621 is proposed to activate both 
the innate and adaptive immune systems. 

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Figure 1-1: Proposed TTI-621 Mechanism of Action 
 
 
 
 
 
1.6.2 Chemistry and Description 
 
TTI-621, which has a molecular weight of 76,677 daltons, is a homodimer consisting 
of identical polypeptides each containing 345 amino acids and linked by a disulfide 
bond (Figure 1-2). The protein is glycosylated through N-linkage. TTI-621 is expressed 
and secreted by a genetically engineered Chinese Hamster Ovary cell line. 
Figure 1-2: Schematic of TTI-621 
 
TTI-621 consists of the N-terminal domain of human SIRPα (red) linked to a human IgG1 Fc region (blue). The 
hinge and inter-chain disulfide bonds are represented in black. 

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TTI-621 as formulated for clinical trial use is described in Section 6.1. Additional 
information is found in the Investigator’s Brochure. 
 
1.6.3 Nonclinical Pharmacodynamics 
 
TTI-621 bound to human hematopoietic tumor cell lines and primary tumor samples 
with an effective half-maximal concentration (EC50) of 14–807 nM (1–62 μg/mL). 
Comparable binding was also observed on normal human white blood cells and 
platelets, although there was extremely low binding to human red blood cells (RBCs) 
despite their abundant expression of CD47. This unusually low level of binding may 
be a consequence of CD47 association with the RBC cytoskeleton and resulting lack 
of membrane mobility, which may preclude the formation of high-affinity 
TTI-621:CD47 clusters on the RBC surface. 
 
TTI-621 cross-reacts with CD47 from cynomolgus macaques (97.6% amino acid 
sequence homology to humans) and binds strongly to monkey RBCs. This makes the 
cynomolgus monkey a suitable model for studying the pharmacology and toxicology 
of TTI-621. TTI-621 did not bind rat or mouse cells, which is consistent with the 
known species selectivity of human SIRPα. 
 
The ability of TTI-621 to promote macrophage-mediated destruction of human tumor 
cells was assessed in vitro. TTI-621 was shown to potently trigger the phagocytosis of 
a variety of hematopoietic tumor cell lines and primary patient samples. The biological 
activity of TTI-621 in this system occurred at an average concentration of 11 nM 
(0.84 μg/mL), representing the anticipated active dose of TTI-621. TTI-621 did not 
provoke the phagocytosis of normal blood-derived monocytes. This specificity for 
cancer cells likely results from the expression of requisite pro-phagocytic signals on 
malignant cells that are absent on normal cells. 
 
TTI-621 was evaluated in an in vivo acute myeloid leukemia (AML) xenograft model 
in which patient-derived tumor cells were injected directly into the femur of 
preconditioned NOD.SCID mice. Antileukemic activity was observed in 4 of 5 AML 
samples tested. Profound reductions in tumor burden were observed in animals 
receiving 5 mg/kg TTI-621, with partial anti-tumor activity at 0.2 and 1 mg/kg doses. 
 
The presence of CD47 on non-tumor tissue has the potential to bind SIRPα-IgG1 Fc 
and remove it from circulation (an antigen sink effect). Since TTI-621 does not cross- 
react with mouse CD47, it would not model the antigen sink effect that might 
ordinarily occur. Hence, a mouse surrogate fusion protein (TTI-508) was generated 
using the SIRPα sequence from NOD mice. This surrogate binds both mouse and 

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human CD47 and contains a mouse IgG2aFc region that allows for homologous Fc- 
Fcγ receptor interactions in mice. TTI-508 induced macrophage phagocytosis of a 
human tumor cell line in vitro with similar potency to TTI-621. In vivo, TTI-508 was 
highly active in the AML xenograft model, dramatically reducing tumor burden at a 
1 mg/kg dose and exerting a partial effect at 0.2 mg/kg. TTI-508 was also highly 
efficacious in human B-cell lymphoma xenograft models when dosed at 10 mg/kg. 
 
Collectively, the primary pharmacology studies demonstrated the following: 
• TTI-621 bound to human CD47+ tumor cells with EC50 values ranging from 
14–807 nM (1–62 µg/mL) with nanomolar affinity. 
• TTI-621 induced macrophage-mediated phagocytosis of a range of 
hematologic tumor cells but not of normal cells. 
• TTI-621 bound strongly to cynomolgus monkey RBCs despite an inherently 
weaker binding affinity to monkey CD47. 
• TTI-621 bound weakly to human RBCs but did not induce hemolysis or 
agglutination of human RBCs in vitro. 
 
Secondary pharmacology studies of TTI-621 demonstrated the following: 
• TTI-621 induced antibody-dependent cellular cytotoxicity (ADCC) of human 
tumor target cell lines but did not mediate complement-dependent lysis. 
• TTI-621 was not directly cytotoxic to human tumor cell lines at 
concentrations up to 10 μM (767 μg/mL) and did not induce direct hemolysis 
of monkey or human RBC. 
• TTI-621 did not provoke significant in vitro release of IL-2, IL-4, IL-10, IFN- 
γ or TNF-α, but did induce IL-6 and IL-8 release at levels above background 
in a minority of donor blood samples. 
• TTI-621 bound strongly to human platelets but had no effect on platelet 
aggregation. Additionally, TTI-621 on its own did not affect the activation of 
human or monkey platelets. No inhibitory effect on agonist-induced platelet 
activation was observed for either species. 
 
Additional information is found in the Investigator’s Brochure. 
 
1.6.4 Nonclinical Pharmacokinetics 
 
Pharmacokinetic (PK) investigations were conducted in conjunction with both the 
Good Laboratory Practice (GLP) and non-GLP primate toxicology studies. Across all 
studies, TTI-621 doses ranged from 0.5 to 12.5 mg/kg. Dosing was intravenous (IV) 
with the exception of 1 cohort of male monkeys given TTI-621 subcutaneously (SC) 
in Study 5001009. In general, both maximum blood concentration (Cmax) and area 

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under the curve (AUC)0–∞ increased in a more-than-dose-proportional manner. Mean 
terminal half-life (t1/2) values between all cohorts after the Day 1 dose were extremely 
variable, ranged from 35.2 to 156 hours, or approximately 1.5 to 6.5 days. The 
variation in t1/2 between cohorts did not appear to be a function of dose. SC dosing led 
to lower Cmax and AUC0–∞ and longer time to Cmax (Tmax) values compared with IV 
dosing; however, t1/2 and other parameters were similar between SC and IV 
administration. 
 
Trends in the PK parameters of later time points were inconsistent and variable relative 
to Day 1, which was likely a consequence of the development of antidrug antibodies 
(ADA) in the majority of animals. 
 
Additional information may be found in the Investigator’s Brochure. 
 
1.6.5 Toxicology 
 
The toxicology program consisted of 5 studies: 3 non-GLP pilot dose-finding studies 
and 2 GLP IND-enabling studies, all conducted in cynomolgus monkeys. 
 
A total of 86 monkeys were dosed with TTI-621 in these toxicology studies. TTI-621 
was administered either via a 1-hour IV infusion or a SC injection over a range of 
concentrations between 0.5 mg/kg and 12.5 mg/kg. The IV dosing regimens tested 
across studies ranged from twice weekly to once every 2 weeks, while the SC dosing 
regimens ranged from 3 times weekly to once every 2 weeks. The majority of animals 
at the lower doses (0.5, 1, 1.25, 1.5 and 3 mg/kg) tolerated treatment well. There were 
no test article effects at the injection/infusion site and no measurable effects on the 
cardiovascular, respiratory, ophthalmologic, or nervous systems. Isolated animals at 
higher doses displayed clinical symptoms including hypo-activity, pallor, anorexia 
with or without weight decrease, general debility, and hypothermia. 
 
Treatment-emergent and dose-related anemia — sometimes profound but reversible 
— was a consistent laboratory finding and many of the above clinical symptoms were 
attributed to effects of TTI-621 on the RBC compartment. These effects on clinical 
pathology demonstrated reversibility during the recovery phase. Six of the 86 animals 
receiving TTI-621 at doses ≥3mg/kg were pre-terminally sacrificed due to severe 
anemia (N=4) or hemorrhage (N=2). Anemia was not unexpected, as TTI-621 binds 
strongly to cynomolgus RBCs and CD47 is speculated to regulate the normal 
homeostatic clearance of RBCs by macrophages. Blockade of CD47 may therefore 
accelerate this clearance, as observed with CD47-blocking antibodies in non-human 

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primates. TTI-621 shows only minimal binding to human RBCs, and therefore the 
anemia observed in monkeys is thought to be less likely to occur in human subjects. 
 
The highest non-severely toxic dose (HNSTD) for once-weekly IV dosing was 
determined to be 1 mg/kg, with anemia as the most consistent treatment-related effect. 
TTI-621 exhibits minimal binding to human RBCs in vitro; hence, significant anemia 
is not expected. However, the risk of treatment-emergent anemia in the clinical studies 
cannot be ruled out. 
 
Additional information with descriptions of each study is found in the Investigator’s 
Brochure. 
 
1.7 Anticipated or Possible Risks in Human Subjects 
 
Summary of Dose-Escalation Safety Data 
 
Data from the first 18 subjects enrolled in the dose-escalation phase of the study show that 
TTI-621 has been reasonably well tolerated. Transient, dose-dependent decreases in 
platelets without clinical sequelae occurred in the hours following infusion in the majority 
of subjects exposed to TTI-621. Thrombocytopenia was relatively brief with recovery to 
baseline platelet counts by the next weekly dose and appeared attenuated with weekly TTI- 
621 exposure. Other Grade 3/4 cytopenias (monocytes, neutrophils, and lymphocytes) 
were also frequently observed; all were transient and resolved without sequelae. 
 
The majority of subjects experienced mild to moderate infusion-related reactions (IRRs) 
that typically occurred after the first TTI-621 infusion only. IRRs were reported across all 
dose cohorts with no obvious dose relationship and occurred despite premedication with 
an antihistamine and acetaminophen. 
 
Three subjects experienced reversible Grade 3 hypophosphatemia in the days following 
their first infusion of TTI-621. Hypophosphatemia in 1 of the 3 subjects was considered 
related to TTI-621 and was therefore reported as a DLT. The event rapidly resolved without 
intervention. Hypophosphatemia was considered unrelated to TTI-621 in the other 
2 subjects and their phosphate levels were corrected by oral phosphate. 
 
No subjects in either the 0.05 mg/kg/week or 0.1 mg/kg/week dose groups experienced 
dose-limiting toxicity (DLT). However DLTs were reported for 2 of 5 subjects treated at 
the 0.3 mg/kg/week dose: 1 subject with Grade 4 thrombocytopenia and 1 subject with 
Grade 4 thrombocytopenia and Grade 3 elevated alanine aminotransferase/aspartate 
aminotransferase (ALT/AST). Upon review of cumulative adverse events (AEs) and 
laboratory values, the Safety Review Committee (SRC) recommended proceeding with 

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enrollment at an intermediate dose level of 0.2 mg/kg TTI-621 (Cohort 2a), and to dose 
reduce all subjects participating in the 0.3 mg/kg cohort to the 0.2 mg/kg dose level (one 
subject was dose reduced to the 0.1 mg/kg dose level). 
 
Seven subjects were subsequently enrolled in Cohort 2a, 6 of whom were DLT evaluable. 
One of the 6 DLT-evaluable subjects experienced a DLT of Grade 3 hypophosphatemia; 
therefore, the SRC declared 0.2 mg/kg as the MTD and enrollment to the expansion phase 
is currently underway. Similarly, a dose of 0.2 mg/kg/week in combination with rituximab 
was initially recommended for subjects enrolled in the combination treatment arm; 
however 1 subject treated with TTI-621 experienced an SAE of Grade 3 gastrointestinal 
bleed; therefore, current subjects receive an initial dose of 0.1 mg/kg TTI-621 administered 
together with the combination partner agent. 
 
Safety Update 
 
As of a data cutoff date of 01 October, 2018, a total of 179 subjects (177 unique 
individuals) had been enrolled in Study TTI-621-01: 18 subjects were enrolled in the 
dose-escalation phase and 161 subjects had been enrolled in the expansion phase. Two 
subjects were re-enrolled on Study TTI-621-01; these subjects were originally enrolled and 
treated in the dose-escalation phase of the study and were subsequently enrolled and treated 
in the expansion phase. Two additional subjects with CTCL who participated in Study 
TTI-621-02 and received local intratumoral treatment with TTI-621 in cutaneous lesions, 
enrolled on Study TTI-621-01 to receive systemic TTI-621 after completing treatment on 
Study TTI-621-02. 
 
Overall, 166/179 subjects (93%) enrolled in Study TTI-621-01 experienced at least 1 
treatment emergent adverse event (TEAE). TEAEs in 134/179 subjects (75%) were 
considered related to TTI-621 treatment by Investigators. The most frequently reported 
TEAEs were infusion-related reactions in 72 subjects (40%), chills in 33 subjects (18%), 
fatigue in 26 subjects (15%), thrombocytopenia in 26 subjects (15%), nausea in 21 subjects 
(12%), platelet count decreased in 20 subjects (11%), anemia in 18 subjects (10%), and 
pyrexia in 18 subjects (10%). A total of 59 subjects (33%) experienced a ≥ Grade 3 TEAE 
that was considered related to TTI-621. The most frequently reported treatment-related ≥ 
Grade 3 TEAEs were thrombocytopenia in 19 subjects (11%), platelet count decreased in 
16 subjects (9%), anemia in 11 subjects (6%), neutropenia in 7 subjects (4%), neutrophil 
count decreased in 6 subjects (3%), white blood cell count decreased in 4 subjects (2%), 
and infusion-related reaction in 3 subjects (2%). All other treatment-related ≥ Grade 3 
TEAEs were reported for ≤2 subjects. 

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Infusion-related reactions have been frequently reported in this study. The majority of 
reactions were Grade 1 or 2 and were reported across all dose cohorts with no obvious dose 
relationship and occurred despite premedication with an antihistamine and acetaminophen. 
Three subjects in the expansion cohorts of this study experienced ≥ Grade 3 infusion- 
related reactions; 2 of these events were reported as SAEs and resulted in TTI-621 
discontinuation for 1 subject. 
 
Thrombocytopenia/platelet count decreased were the most frequently reported ≥Grade 3 
related TEAEs, occurring in 19/179 (11%) and 16/179 (9%) of subjects respectively. 
Thrombocytopenia/platelet count decreased occurred within 24 hours following infusion 
in majority of patients exposed to IV administration of TTI-621. Reduced platelet counts 
appeared transient and generally recovered within a week prior to the next dosing. Overall, 
pre-infusion platelet counts remained stable over the course of the study and no clinical 
sequela was observed (See Section 1.8.4). 
 
Grade 3/4 cytopenias, including decreased monocytes, neutrophils, and lymphocytes, were 
observed and reported as laboratory abnormalities as well as TEAEs. 
 
Treatment-related, Grade 3 or higher anemia was reported in 11 subjects receiving IV TTI- 
621. All events occurred in subjects with primary hematologic malignancies in which 
anemia is frequently caused by the malignancy itself (AML/MDS/MPN). No serious events 
of anemia were reported and anemia did not appear to be associated with increased 
destruction of erythrocytes. 
 
See Section 9.5 for further details of anticipated risks and AEs of special interest. 
 
1.8 Rationale for Selection of Doses 
 
1.8.1 TTI-621 Monotherapy 
 
The selection of the TTI-621 starting dose in human subjects was determined using a 
conventional HNSTD approach. The HNSTD for once-weekly administration of TTI- 
621 in the GLP toxicology study was 1 mg/kg. Using the standard 1/6 safety factor 
and applying a 0.32 multiple to convert the cynomolgus monkey mg/kg into a human 
equivalent dose resulted in a starting dose of 0.053 mg/kg. Thus, a starting dose of 
0.05 mg/kg was proposed for this study. A similar starting dose was determined using 
a conservative minimum anticipated biological effect level (MABEL) calculation 
based on 10% receptor occupancy of human platelets (see Investigator Brochure). 

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1.8.2 Combination Therapy Cohorts 
 
As outlined in Section 1.7, the starting dose for subjects in the TTI-621 plus rituximab 
expansion cohort is 0.1 mg/kg TTI-621 given weekly in combination with 375 mg/m2 
rituximab. This dose of rituximab is the standard approved dose for patients with 
previously 
untreated 
NHL 
when 
given 
in 
combination 
with 
CHOP 
(cyclophosphamide, doxorubicin, vincristine, prednisone) or other anthracycline- 
based regimens (Rituxan® [rituximab] package insert. San Francisco, CA: Genentech; 
and Rituxan® [rituximab] product monograph. Mississauga, Ontario: Hoffmann-La 
Roche Ltd.). There is no standard dose or schedule of rituximab in the 
relapsed/refractory setting; however, the selected dose and schedule has been safely 
and effectively employed in combination with various single- and multi-agent 
chemotherapy regimens for this patient population. 
 
The starting dose for subjects in the combination TTI-621 plus nivolumab expansion 
cohort is 0.1 mg/kg TTI-621 given weekly in combination with 3 mg/kg nivolumab 
given every 2 weeks or at a fixed dose as per the approved package insert for patients 
with HL (OPDIVO® [nivolumab]. Princeton, NJ: Bristol-Myers Squibb Company and 
OPDIVO® [nivolumab] product monograph. Montreal, Canada: Bristol-Myers 
Squibb Canada). 
 
1.8.3 Rationale for Intrasubject Dose-Intensification 
 
In vitro studies suggest that increased CD47 receptor occupancy by TTI-621 is 
associated with increased macrophage-mediated phagocytosis of tumor cells— 
providing rationale for further dose intensification of TTI-621, as tolerated. Clinically, 
reversible thrombocytopenia has reliably and rapidly occurred after TTI-621 
infusions. However, thrombocytopenia recovered without active management within 
a week and was asymptomatic (See Section 1.8.4). In Part 2, as of Amendment 6, intra- 
subject dose intensification was made permissible at investigator’s discretion after 
initial treatment at the recommended dose of 0.2 mg/kg determined during phase 1a 
dose escalation. 
 
As of 01 October 2018, TTI-621 dose intensification per Investigator discretion has 
been employed for 46 subjects enrolled on Study TTI-621-01. The most common 
treatment-related ≥ Grade 3 events, occurring in ≥ 2 patients experienced by these 
subjects following dose intensification were limited to Grade 3 or higher platelet count 
decreased (17.4%), anemia (8.7%), thrombocytopenia (4.3%), neutropenia (4.3%), 
neutrophil count decreased (4.3%) and white blood cell count decreased (4.3%). 

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Platelet decrease did not appear worse after dose intensification up to 0.5 mg/kg 
(Section 1.8.4). For these reasons, in Part 3, all patients in CTCL and PTCL cohorts 
will receive a standardized dose ramp-up regimen which includes initial two-weeks of 
0.2 mg/kg treatment followed by cautious intrasubject dose intensification at an 
increment of 0.1 mg/kg per week up to 0.5 mg/kg within 5-8 weeks. Details regarding 
when dose intensification should be delayed or stopped due to AEs are is provided in 
Section 6.5.4. 
 
 
1.8.4 Rationale for Phase 1b Dose Optimization (Part 4) 
 
During phase 1a dose escalation (Part 1), weekly infusion of TTI-621 at 0.2 mg/kg 
was determined to be the MTD per 3+3 dose escalation as planned. Two Grade 4 
events of asymptomatic thrombocytopenia were observed in 2/3 patients dosed at 0.3 
mg/kg. Per the DLT criteria in phase 1a, these two events were determined to be a 
DLT which led to the conclusion that 0.3 mg/kg exceeded MTD. The majority of the 
patients treated during Phase 1b dose expansion Part 2 received weekly infusions of 
0.2 mg/kg TTI-621. Based on a safety analysis of 179 patients by a data cut of 01 
October, 2018, the majority of patients (143; 80%) had abnormal platelet counts 
reported at 1 or more timepoints post dose, with 49 subjects (27%) experiencing Grade 
4 decreases, including both TTI-621-induced events, and events resulting from the 
underlying hematologic malignancies. As shown in Figure 1-3, platelet counts 
decreased acutely on dosing days but generally recovered within the week prior to the 
next dose. Overall, pre-infusion platelet counts remained stable over the course of the 
study. Additionally, due to the transient and reversible nature of the thrombocytopenia, 
no apparent increase in the incidence of bleeding has been observed on study. A total 
of 24/179 subjects (13%) experienced a treatment-emergent bleeding event (see Table 
1-1). 
 
Overall, 20/179 subjects (11%) experienced Grade 1 or 2 events and 4 subjects (2%) 
had Grade 3 bleeding events. Grade 3 hemorrhage events were considered treatment- 
related for 3 subjects (2%). No Grade 4 hemorrhage events were reported. Therefore, 
based on the expanded safety data in which the clinical significance of 
thrombocytopenia is now better understood, the original DLT criteria have been 
reassessed and revised. The major revision of the DLT criteria in comparison to those 
in Phase 1a is that Grade 4 thrombocytopenia is no longer a DLT unless it lasts for 
more than 72 hours. With this revision, the two original DLT events of Grade 4 
thrombocytopenia would no longer be qualified as DLTs, so 0.3 mg/kg should not 
have exceeded MTD. Therefore, further dose escalation per revised DLT criteria to re- 
define MTD or recommended Phase 2 dose is warranted. This effort is further justified 
by the safety data collected thus far from selected patients who dose intensified on 

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study to doses higher than 0.2 mg/kg during phase 1b expansion. Exposure to higher 
doses up to 0.5 mg/kg appeared to be tolerable. 
 
The selection of the starting dose level and planned escalation cohorts are guided by 
the dose intensification experience collected so far during the phase 1b expansion 
phase of this study. As of 26 November 2018, in Part 2, 12 T Cell Lymphoma patients 
were initially dosed at the recommended dose of 0.2 mg/kg and then dose intensified 
up to 0.5 mg/kg at the investigator discretion (ID). In Part 3 (A8), 14 T Cell Lymphoma 
patients have been treated per protocol-defined ramp-up schedule (2 weeks of study 
treatment at 0.2 mg/kg followed by dose intensification between week 3 and week 8 
at increments of 0.1 mg/kg/week as tolerated up to maximum dose of 0.5 mg/kg/week). 
Among these patients who were exposed to 0.5 mg/kg of TTI-621, 22 patients (11 ID; 
11 A8) had both pre and post-dose platelet assessments on W1D1 after receiving TTI- 
621 0.2 mg/kg. A total of 17/22 patients (11 ID; 6 A8) had both pre and post -dose 
platelet assessments at Weeks 5-30 after receiving 0.5mg/kg. Median pre- and post- 
dose platelet values following 0.2mg/kg and 0.5 mg/kg doses were 257/123, and 
234/188, respectively. Grade 4 post-dose platelet levels occurred in 1 patient each 
following 0.2 mg/kg and 0.5 mg/kg TTI-621 doses; 5% (1/22) versus 6% (1/17), 
respectively. In addition, related AEs were generally comparable or less frequent 
following 0.5 vs. 0.2 mg/kg doses. 
 
Figure 1-3: Pre-dose Platelet Counts During Week 1 
 
300 
 
250 
 
200 
 
150 
 
100 
 
50 
 
0 
Day 
Patients (n) 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
171 
157 
152 
162 
 
Graph shows that the 0.2 mg/kg dose level, platelet counts decreased acutely on week 1 dosing days but 
generally recovered within the week prior to the next dose. 
Median Platelet Counts 
 
 
 
 
 
Platelets (x 109/L) 

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Figure 1-4: Pre and Post-Dose Platelet Levels following 0.2 and 0.5 mg/kg TTI-621 
 
 
Patients with pre and post-dose platelet levels following administration of TTI-621 at 0.5 mg/kg had previously 
been treated at 0.2 mg/kg. Platelet values on the left side of the figure are from patients dosed at 0.2 mg/kg. Platelet 
values on the right side of the figure are from those patients that had their dose incrementally increased up to 
0.5 mg.kg 

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Table 1-1: Treatment-Emergent Bleeding AEs (Safety Analysis Set) 
 
Bleeding Adverse Event 
n (%) 
Adverse Event Severity 
Total 
n=179 
Grade 1 
NR 
R 
Grade 2 
NR 
R 
Grade 3 
NR 
R 
Subjects with any bleeding TEAE 
11 (6) 
9 (5) 
3 (2) 
0 
2 (1) 
3 (2) 
24 (13) 
Epistaxis 
4 (2) 
5 (3) 
0 
0 
0 
2 (1) 
11 (6) 
Gastrointestinal haemorrhage 
0 
0 
0 
0 
2 (1) 
1 (1) 
2 (1) 
Petechiae 
2 (1) 
0 
0 
0 
0 
0 
2 (1) 
Anal haemorrhage 
1 (1) 
0 
0 
0 
0 
0 
1 (1) 
Ecchymosis 
0 
0 
1 (1) 
0 
0 
0 
1 (1) 
Haematochezia 
1 (1) 
0 
0 
0 
0 
0 
1 (1) 
Haematoma 
1 (1) 
0 
0 
0 
0 
0 
1 (1) 
Haematuria 
1 (1) 
1 (1) 
0 
0 
0 
0 
1 (1) 
Haemoptysis 
1 (1) 
0 
0 
0 
0 
0 
1 (1) 
Haemorrhage 
0 
1 (1) 
0 
0 
0 
0 
1 (1) 
Menorrhagia 
0 
1 (1) 
0 
0 
0 
0 
1 (1) 
Periorbital haematoma 
1 (1) 
0 
0 
0 
0 
0 
1 (1) 
Purpura 
0 
1 (1) 
0 
0 
0 
0 
1 (1) 
Rectal haemorrhage 
1 (1) 
0 
0 
0 
0 
0 
1 (1) 
Thrombotic thrombocytopenic purpura 
0 
0 
1 (1) 
0 
0 
0 
1 (1) 
Vaginal haemorrhage 
0 
0 
1 (1) 
0 
0 
0 
1 (1) 
Source: Dynamic Data Listings 19OCT2018 
NR, not related; R, Related 
 
2 
STUDY OBJECTIVES 
 
2.1 Phase 1a Dose Escalation 
 
The primary objective of the escalation phase of the study is to characterize the safety 
profile and DLT of TTI-621 in order to identify the MTD and/or the optimal dose in adult 
subjects with advanced relapsed or refractory lymphomas. 
 
Secondary objectives include characterization of the PK of TTI-621, development of ADA, 
and pharmacodynamics (PD) through various biomarker studies. 
 
2.2 Phase 1b Dose Expansion (Part 2 and Part 3) 
 
The primary objective of the expansion phase of the study is to further characterize the 
safety of TTI-621 in an expanded number of primary hematologic malignancies and 
selected solid tumors, and to evaluate the safety of individual subject TTI-621 dose 
intensification. 

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Secondary objectives include additional characterization of PK, PD, and development of 
ADA; and to gain preliminary evidence of the anti-tumor activity of TTI-621 in subjects 
with a variety of hematologic malignancies and selected solid tumors. In addition, the 
safety of TTI-621 will be evaluated in combination with other anti-cancer agents. 
 
2.3 Phase 1b Dose Expansion (Dosing Optimization, Part 4) 
 
The primary objective of the dose optimization phase is to further evaluate the safety and 
tolerability of TTI-621 at dose levels higher than the initially recommended phase 1b dose 
of 0.2 mg/kg (as determined during phase 1a dose escalation) and the MTD and/or 
recommended phase 2 dose will be re-assessed per revised DLT criteria following a 3+3 
dose escalation schema. The DLT criteria are revised based on the totality of safety data 
collected thus far from the phase 1a and 1b dose expansion phase of the study. The starting 
dose for this further dose evaluation will be the highest dose of TTI-621 evaluated (0.5 
mg/kg) during phase 1b dose expansion following dose intensification regimens 
permissible per protocol (Part 2 and Part 3). 
 
Secondary objectives include characterization of the PK, PD, immunogenicity, and 
preliminary evidence of antitumor activity of TTI-621 in patients with relapsed and/or 
refractory CTCL at higher dose levels of TTI-621. 

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3 
INVESTIGATIONAL PLAN 
 
3.1 Overall Study Design 
 
Study TTI-621-01 is a multicenter, open-label, phase 1a/1b trial of TTI-621 in subjects 
with relapsed or refractory hematologic malignancies and selected solid tumors; the study 
will be conducted in 4 parts. 
 
Part 1: In the dose escalation phase, subjects with advanced relapsed or refractory 
lymphomas will be enrolled in sequential cohorts to receive escalating dose levels of 
TTI-621 as outlined in Table 3-1 for the purpose of characterizing safety, tolerability, and 
identifying the MTD and/or the optimal dose. 
 
Part 2: In the expansion phase, Part 2, subjects with a broader variety of hematologic 
malignancies and selected solid tumors will be treated at a TTI-621 dose based on the 
putative optimal dose in order to further define safety, characterize the efficacy, and 
evaluate the safety of individual subject TTI-621 dose intensification. A cohort of subjects 
with CD20-positive malignancies will also be enrolled and treated with TTI-621 plus 
rituximab to characterize the safety and efficacy of the combination. Similarly, a cohort of 
subjects with classic HL (cHL) will be treated with TTI-621 plus nivolumab to characterize 
the safety and efficacy of the combination. The phases of the study are described in more 
detail below. 
 
Part 3: In the expansion phase, Part 3, based upon preliminary observations of response, 
2 cohorts (subjects with CTCL and PTCL), will be evaluated separately, using the Simon 
2-stage design, for the potential to be further studied. 
 
As of November 1, 2016, the MTD/optimal dose for TTI-621 monotherapy was determined 
by the SRC to be 0.2 mg/kg. The starting dose of TTI-621 to be administered in 
combination with other agents is 0.1 mg/kg (see Section 1.8 for details of DLTs and cohort 
advancement and Section 6.4 for further dosing information). In vitro studies suggest that 
increased CD47 receptor occupancy by TTI-621 is associated with increased macrophage- 
mediated phagocytosis of tumor cells. The observation that the degree of thrombocytopenia 
has been attenuated with subsequent doses for many subjects who were not platelet 
transfusion-dependent suggests compensatory increases in marrow platelet production that 
may enable safe intrasubject dose intensification. Therefore, under phase 1b Part 3 dose 
intensification will be required for all newly enrolled subjects starting at Week 3, in 0.1 
mg/kg weekly increments, to a maximum of 0.5 mg/kg/week (see Section 6.5.4 for details). 
 
Part 4: In the dose optimization phase, Part 4, the safety and tolerability of TTI-621 at 
higher dose levels beyond the initially recommended phase 1b dose of 0.2 mg/kg (as 

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determined during phase 1a dose escalation) and the highest dose of TTI-621 evaluated 
(0.5 mg/kg) during phase 1b dose expansion following dose intensification permissible per 
protocol, will be evaluated. This phase 1b dose optimization phase will aim at re-defining 
MTD and/or recommended phase 2 dose following 3+3 dose escalation schema and a 
revised DLT criteria based on the totality of safety data collected thus far from phase 1a 
and 1b dose expansion phase of the study. 
 
The major revision to the DLT criteria as used in phase 1a relates to Grade 4 
thrombocytopenia. The safety data collected thus far from phase 1a and ongoing phase 1b 
expansion (by data cut-off of 01 October, 2018) showed that ≥ Grade 3 related 
thrombocytopenia and platelet count decrease occurred in 11% and 9% of patients 
respectively. Thrombocytopenia appeared to be transient and in general recovered within 
a week prior to the next dosing. Thrombocytopenia was not found to be associated with 
increased incidence of bleeding and had limited impact on the study drug delivery. Based 
on the data, Grade 4 thrombocytopenia will be revised to qualify as a DLT only when the 
event lasts longer than 72 hours. Subject data obtained from the phase 1b Part 3 CTCL and 
PTCL cohorts stage 1 will be evaluated per Simon 2-stage criteria previously established. 
 
In phase 1b dose optimization of the study (Part 4), further dose escalation of TTI-621 will 
be pursued in patients with relapsed and/or refractory CTCL following a 3+3 escalation 
design and using a revised DLT criteria. Dose optimization will proceed following review 
of the data obtained from the phase 1b Part 3, stage 1 cohorts of CTCL and PTCL subjects. 
 
 
3.2 Phase 1a Escalation (Completed) 
 
3.2.1 Dose Advancement and MTD Determination 
 
A minimum of 3 subjects will be treated in each dose cohort in a conventional 3 + 3 
design (Table 3-1) starting at Cohort 1. Given the potential risk for cytokine release 
syndrome, the first subject in each dosing cohort will be treated and observed for 
72 hours before the next subject can receive their first infusion of TTI-621. Cohort 0 
represents a contingency de-escalation dose level in the event that tolerance issues are 
encountered in Cohort 1. Treatment for an individual subject is described in Section 
6.3. 

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Cohort 
N 
Dose (once weekly) 
0 
3 (+ 3) 
0.01 mg/kg 
1 
3 (+ 3) 
0.05 mg/kg 
2 
3 (+ 3) 
0.1 mg/kg 
3 
3 (+ 3) 
0.3 mg/kg 
4 
3 (+ 3) 
1 mg/kg 
5 
3 (+ 3) 
3 mg/kg 
6 
3 (+ 3) 
10 mg/kg 
 
 
Table 3-1: TTI-621 Dose Levels by Cohort 
 
 
Subjects will receive TTI-621 at the assigned dose once weekly for a planned 3 weeks 
of treatment/observation for DLT assessment. In the absence of DLT (as defined in 
Section 3.2.2) in 3 evaluable subjects within a cohort, dose advancement will proceed 
through the successive cohorts. All subjects in each dose cohort must have completed 
the DLT observation period before the next dose cohort commences treatment. 
 
Subjects will be considered evaluable for DLT if they received all 3 weekly doses 
within the specified treatment/observation period or if they experienced an AE 
meeting the criteria for DLT during that time. Those who drop out of the study during 
the first 3 weeks for reasons other than toxicity or who experience a delay in dosing 
of more than 3 days for reasons other than DLT are considered unevaluable for DLT 
and will be replaced with a new subject enrollment. For subjects who experienced a 
treatment delay, the DLT observation period will extend 7 days beyond the third dose 
of TTI-621. 
 
If DLT as defined below is encountered in 1 subject within a particular dose cohort, 
additional subjects will be treated in that cohort as outlined in Table 3-2. Based on the 
incidence of DLT, the MTD will be determined. Depending upon the tolerance at a 
particular dose level, intermediate dose levels may be studied to more closely 
characterize DLT and more accurately identify the MTD as recommended by the 
Safety Review Committee (SRC). 

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Proceed with enrollment in next cohort 
Enroll 3 additional subjects in current cohort 
Proceed with enrollment in next cohort 
Do not escalate; enroll 3 additional subjects in 
previous cohort or new intermediate dose level 
Do not escalate; enroll 3 additional subjects in 
previous cohort or new intermediate dose level 
of 3 subjects 
of 3 subjects 
1 of 6 subjects 
≥ 2 of 6 subjects 
 
≥ 2 of 3 subjects 
If DLT was observed 
in: 
Then: 
 
 
Table 3-2: Dose Escalation Rules 
 
 
Individual subjects may continue receiving additional TTI-621 treatment until disease 
progression, unacceptable toxicity, or other reason for treatment discontinuation. As 
of Protocol Amendment 6, intrasubject dose escalation may be employed for active 
subjects in the dose-escalation phase of the study (see Section 1.8.3). 
 
 
3.2.2 Definition of Maximum Tolerated Dose 
 
The MTD is defined as the dose level immediately below that in which 2 or more of 
either 3 or 6 subjects experienced DLT during the first 3 weeks of treatment. At least 
6 subjects must be treated at the putative MTD, with no more than 1 incident of DLT. 
AEs that manifest after the 3-week DLT observation period or cumulative toxicities 
will be considered in the final definition of MTD. 
 
The final determination of the optimal dose for further use in the expansion phase may 
or may not be synonymous with the MTD but will consider both acute and cumulative 
toxicities; the incidence of required dose delays, reductions, and discontinuations; and 
the overall facility of administration in clinical practice. 
 
 
3.3 Phase 1b Expansion 
 
3.3.1 Phase 1b - Part 2 and Part 3 
 
In Part 2 of the expansion phase of the study, the safety and preliminary anti-tumor 
activity of TTI-621 monotherapy at the optimal dose identified in the escalation phase 
will be explored in 12–15 subjects per cohort type, as outlined in Table 3-3 below. 
These cohorts include: indolent B-cell lymphomas (IBCL; see Appendix A), 
aggressive B-cell lymphomas (ABCL; see Appendix A), T-cell lymphoma (TCL), HL, 

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CLL, ALL, multiple myeloma (MM), AML, MDS, myeloproliferative neoplasms 
(MPN), and SCLC. A cohort of subjects with CD20-positive malignancies will also 
be enrolled and treated with TTI-621 in combination with rituximab. Similarly, a 
cohort of subjects with cHL will be treated with TTI-621 plus nivolumab. If 
preliminary evidence of clinical benefit is observed in association with acceptable 
tolerability, one or more hematologic disease-specific cohorts may be expanded to a 
maximum of 40 subjects (see Section 8.3 for details). In the rare instance that a subject 
has more than one malignancy, the subject will be assigned to a single cohort based 
upon the Investigator’s assessment of the subject’s greatest clinical need. 
 
In Part 3 of the expansion phase of the study, the safety and preliminary anti-tumor 
activity of TTI-621 monotherapy will be further explored in two cohorts of CTCL and 
PTCL subjects ((consisting of T- and NK-cell neoplasms per WHO definition 
(Swerdlow et al., 2016)), starting with the optimal dose identified in the escalation 
phase. Dose intensification to a maximum of 0.5 mg/kg/week will be required for all 
newly enrolled subjects per Section 6.5.4, following a ramp-up schedule (2 weeks of 
study treatment at 0.2 mg/kg followed by dose intensification between week 3 and 
week 8 at increments of 0.1 mg/kg/week as tolerated up to maximum dose of 0.5 
mg/kg/week). The overall response in each of the 2 cohorts (CTCL and PTCL) will be 
evaluated separately using the Simon 2-stage design. 
 
As of Protocol Amendment 9, enrollment will be limited to the following disease 
types: CD20+ NHL (in combination with rituximab), cHL (in combination with 
nivolumab), CTCL and PTCL. 
 
Treatment may continue until evidence of unequivocal disease progression is seen (see 
Section 7.14.1), unacceptable toxicity, or other reason for treatment discontinuation. 
For patients who have been given weekly infusion of TTI-621 for more than a year 
and are receiving clinical benefit (objective response or clinically meaningful long- 
term stable disease), investigators may exercise their discretion to reduce the d osing 
frequency from weekly to bi-weekly following the discussion and approval from the 
sponsor or designees. 
 
An overview of monotherapy and combination treatments administered in the 
expansion phase is provided in Table 3-3. Starting doses of TTI-621 are shown; 
intrasubject dose-intensification is required as outlined in Section 6.5.4. 

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Table 3-3: Disease Cohorts and Schedule of Treatments Administered 
in the Expansion Phase Part 2 and Part 3 
Expansion 
Cohort 
TTI-621 
Starting Dose 
(mg/kg/wk) 
Combination 
Partner Dose 
Monotherapy 
IBCL (closed) 
0.2 
NA 
ABCL (closed) 
0.2 
NA 
TCL (closed) 
0.2 
NA 
CTCL 
0.2 
NA 
PTCL 
0.2 
NA 
HL (closed) 
0.2 
NA 
CLL (closed) 
0.2 
NA 
ALL (closed) 
0.2 
NA 
MM (closed) 
0.2 
NA 
AML (closed) 
0.2 
NA 
MDS (closed) 
0.2 
NA 
MPN (closed) 
0.2 
NA 
SCLC (closed) 
0.2 
NA 
Combination 
Therapy 
Rituximab combination: 
CD20-positive malignancy 
0.1 
375 mg/m2/wk 
for up to 8 cyclesa 
Nivolumab combination: cHL 
0.1 
per FDA approved package 
insert for cHLb 
NA: not applicable 
a Subjects may continue on TTI-621 monotherapy upon completion of combination partner regimen/unacceptable 
toxicity to the combination regimen 
b Subjects who have unacceptable toxicity to the combination regimen may continue to receive 
TTI-621 monotherapy 
 
 
3.3.2 Phase 1b Dose Optimization Part 4 (to be enrolled as of Amendment 9) 
 
A minimum of 3 patients will be treated in each cohort sequentially in a 3 + 3 design. 
The planned dose escalation levels are shown in Table 3-4. Patients will receive once 
weekly dosing of TTI-621 at the dose levels in their assigned cohort regimen (Week 1 
given on Day 1, Week 2 given on Day 8, and Week 3 given on Day 15). The DLT 
observation period is 21 days. Patients will be considered evaluable for DLT if they 
receive all 3 weekly doses within the DLT evaluation period or if they experience an 
AE meeting DLT criteria during that time. If a patient experiences a non-DLT event 
that requires a dose to be held per dose modification guideline (Section 6.5), the DLT 
evaluation period can be extended to 28 days. If a DLT occurs in 1 of 3 patients within 
a cohort, 3 additional patients will be treated at that cohort regimen. In the absence of 
DLT, enrollment will proceed sequentially through the planned dose levels. 

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Alternative dose escalation including evaluation of intermediate doses, expansion of 
an existing dose level, evaluation of alternative regimens/schedules including a dose 
ramp-up design following different dose intensification increments and schedule, and 
modification of dosing frequency and/or IV infusion rate are all permissible if 
supported by the evolving data and a SRC decision. All patients in each cohort must 
have completed the 21-day DLT period before the next cohort begins treatment. The 
MTD of TTI-621 will be the dose below the one in which ≥2 DLTs are observed 
among 6 treated patients. 
Table 3-4: Planned Dose Escalation Levels 
 
Level 
N 
TTI-621 dose (mg/kg) 
DLT evaluation period 
Week 1b 
Week 2 
Week 3 
0 
3 (+ 3) 
0.2 
0.5 
0.5 
1a 
3 (+ 3) 
0.5 
0.5 
0.5 
2 
3 (+ 3) 
0.7 
0.7 
0.7 
3 
3 (+ 3) 
1.0 
1.0 
1.0 
4 
3 (+ 3) 
1.4 
1.4 
1.4 
a Level 1 = starting dose 
b If de-escalation to level 0 is required, all subsequent cohorts will start with a priming dose of 0.2 
mg/kg at week 1 followed by the respective dose level escalation increments (0.7, 1.0, 1.4 mg/kg) at 
week 2 or subsequent weeks, as applicable, based on SRC decision. 
 
In the starting dose level (0.5 mg/kg), the first 3 patients will be treated sequentially 
to allow close monitoring of toxicity and timely dose adjustment if needed. The third 
patient will not start the study treatment until the first and second patient, respectively, 
have completed the initial two weeks of study treatment and had no observation of 
TEAEs meeting DLT criteria. If the first or second patient experiences a DLT event 
within the first two weeks of treatment, de-escalation to Level 0, a priming dosing 
regimen, will be considered per SRC discussion and decision. A priming regimen 
refers to a dosing regimen that involves a lower priming dose used during the initial 
week(s) of treatment followed by further dose escalation to a higher and stable dose 
for continued use throughout the course of the study. At Level 0, patients will be dosed 
at 0.2 mg/kg for the first week and then receive a stable dose of 0.5 mg/kg for the 
remainder of the study. 
 
If Level 0 is determined to be tolerable per 3+3 schema, further escalation of doses 
beyond 0.5 mg/kg in Week 2 and beyond will be considered, as part of the priming 
dosing regimen. The same dose escalation increment (to 0.7, 1, and 1.4 mg/kg) may 
be followed after the initial week of exposure to 0.2 mg/kg. 

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The MTD is defined as the dose level immediately below the lowest dose that at which 
2 or more of either 3 or 6 patients experienced a DLT during the 3-week DLT period. 
At least 6 patients must be treated at the putative MTD, with no more than 1 incidence 
of DLT. AEs that occur after the 3-week DLT period or cumulative toxicities will be 
considered in the final designation of MTD. 
 
If MTD is not reached after completion of all planned dose escalation levels, a decision 
will be made in consultation with the SRC (see Section 3.4), to either continue further 
escalation at a maximal 50% escalation increment, or d ose escalation will be halted. 
A maximum assessed dose (MAD) could be used in lieu of the MTD. The SRC will 
review the totality of the safety, tolerability, PK, PD, and preliminary efficacy data (if 
available) before making this decision. 
 
In addition to MTD/MAD determination, SRC will review the totality of cumulative 
toxicity and tolerability data in balance against the PK, PD and preliminary efficacy 
data. If a biologically active dose appears to be lower than MTD/MAD or if the 
MTD/MAD results in dose modification due to tolerability that limits continued dose 
exposure and in turn compromise the potential efficacy gain, a recommended phase 2 
dose of TTI-621 lower than MTD/MAD can be determined for future single agent 
studies. Minimally 6 patients will need to be evaluated at the recommended phase 2 
dose before formal designation. 
 
After MTD/MAD or recommended phase 2 dose (if different from MTD/MAD) is 
determined, an additional 6 patients will be enrolled and treated at this dose level to 
form a safety expansion cohort of a total of 12 patients (including the 6 patients treated 
at the designated phase 2 dose before the dose selection). Preliminary efficacy will 
also evaluated in this cohort of patients. 
 
3.3.3 Definition of Dose-limiting Criteria for Phase 1b Part 4 (Amendment 9) 
 
Dose-limiting toxicity is defined as any of the following TEAEs that occur during the 
21-day DLT treatment/observation period (including the pre-dose tests on Day 
22/Week 4 Day 1) and that are considered at least possibly related to study treatment 
by the investigator. Note that any AEs for which the relationship to study treatment 
cannot be ruled out should be considered possibly related: 
 
Hematologic toxicity 
• Grade 4 thrombocytopenia (<25 × 109/L) lasting >72 hours or a platelet count 
≤10 × 109/L at any time 

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• ≥ Grade 3 thrombocytopenia with bleeding (except epistaxis or gingival 
bleeding that is less than 24 hours in duration and does not require medical 
intervention, or normal menses) or requiring platelet transfusions 
• Grade 4 anemia, unexplained by underlying disease 
• Grade 4 neutropenia lasting >72 hours 
• Grade 3 febrile neutropenia lasting >72 hours 
• Grade 4 febrile neutropenia 
 
Non-hematologic toxicity 
• Grade 3 or higher non-hematologic toxicity with the following exceptions: 
o Grade 3 nausea and/or vomiting lasting <72 hours with standard 
supportive care 
o Transient Grade 3 fatigue lasting ≤72 hours 
o Transient asymptomatic Grade 3 laboratory abnormalities considered 
not clinically significant following agreement between investigators 
and the sponsor's medical monitor and that last <72 hours with standard 
supportive care 
• Other ≥ Grade 2 TTI-621-related non-hematologic toxicities that, in the 
opinion of the investigator, require a dose reduction or discontinuation of TTI- 
621 
 
3.4 Safety Review Committee 
 
A SRC oversees the safety of all phases of the study. During the phase 1b dose optimization 
(Part 4) of the study, the SRC convenes at appropriate intervals (when all 3 or 6 subjects 
in a given cohort are evaluable for DLT determination) to review all available safety data 
in a cohort, cumulative information from all dosed subjects, and any new preclinical 
information, as in phase 1a. The SRC renders decisions on dose escalation and other safety 
aspects of the study. All actions of the SRC are documented in written minutes. 
 
During phase 1b dose optimization (Part 2 and Part 3), any significant safety and 
tolerability issues observed based on medical monitoring and pharmacovigilance signal 
detection can be discussed at SRC for recommendation on any actions taken. The SRC can 
also convene to discuss any individual patient cases brought forth for advice by the treating 
investigators or the sponsor. The SRC will extend its responsibility under Amendment 9 to 
review both safety and efficacy data to recommend a decision as to whether or when to 
proceed with the Part 3 CTCL and PTCL cohorts to next stage per the Simon’s 2-stage 
design in parallel to the Part 4 dose optimization phase of the study. The membership of 
the SRC may vary between different phases of the study and will be documented in the 
SRC Safety Committee Charter. 

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During phase 1a, the SRC consisted of the Chief Medical Officer/Medical Monitor, Head 
of Clinical Operations, all enrolling Investigators, and other Sponsor personnel as 
appropriate. Under Amendment 9, the SRC will involve all enrolling investigators in the 
data review and discussion but due to the size of the participating sites, only selected 3-5 
investigators will function as the official members of the SRC and will therefore have the 
voting right. All discussions and decisions of the SRC will be documented in writing. 
 
3.5 Number of Subjects 
 
The dose escalation portion of the study is estimated to enroll up to 36 subjects with an 
advanced lymphoma. The dose expansion phase 1b (Part2) will enroll 12–15 subjects per 
cohort type. If preliminary evidence of clinical benefit is observed in association with 
acceptable tolerability, one or more hematologic disease-specific cohorts may be expanded 
up to a maximum of 40 subjects. For the dose expansion phase 1b (Part 3), the number of 
subjects in the CTCL and PTCL cohorts will be enrolled based upon a Simon optimal 2- 
stage design with a maximum of 35 subjects in each cohort. 
 
In addition, approximately 25 subjects will be enrolled for the phase 1b dose optimization 
(Part 4). The total number of subjects enrolled in the study is approximately 285 subjects 
(see Section 8.3 for details). 
 
3.6 Investigational Sites 
 
Approximately 20 institutions will enroll subjects into this study. 
 
3.7 Study Duration 
 
The dose-escalation phase of the study is expected to run for approximately 18 months and 
the expansion phase of the study for approximately 5 years. 

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4 
SELECTION OF STUDY POPULATION 
 
Potential subjects must sign an informed consent form before any study-specific screening 
tests may be conducted. Screening tests are described in Section 7.1. 
 
4.1 Inclusion Criteria 
 
Phase 1a Escalation (Completed and now Closed) 
1. Histologically documented, advanced lymphoma after the failure of at least 
2 prior therapies with at least one site of measurable disease (≥ 1.5 cm in the long 
axis or ≥ 1.0 cm in both the long and short axis). Additionally, subjects with NHL 
(indolent and aggressive B-cell lymphomas) should have failed CD20-targeted 
therapy. 
 
2. Adequate hematologic status (in the absence of transfusion and growth factor 
support for at least 28 days), defined as: 
o absolute neutrophil count (ANC) ≥ 1.5 x 109/L 
o platelets ≥ 75 x 109/L 
o hemoglobin ≥ 10 g/dL 
Phase 1b Expansion (Selected Cohorts Currently Open for Parts 2 and 3) 
1. Advanced measurable malignancy documented by histology, cytology, flow 
cytometry, fluorescent in situ hybridization (FISH) or polymerase chain reaction 
(PCR) methodology in one of the following categories: 
 
o (closed) Small cell lung cancer (SCLC) (measurable disease by the 
Response Evaluation Criteria in Solid Tumors [RECIST], Version 1.1) 
o Histologically documented, advanced lymphoma after the failure of at 
least 2 prior systemic therapies with at least one site of measurable disease 
(≥ 1.5 cm in the long axis or ≥ 1.0 cm in both the long and short axis). 
Additionally, subjects with CD20-positive NHL (indolent and aggressive 
B-cell lymphomas) should have failed CD20-targeted therapy 
o Indolent B-cell lymphoma (see Appendix A) 
o Aggressive B-cell lymphoma (see Appendix A) 
o Classic Hodgkin lymphoma 
▪ Patients with cHL should have failed at least one 
checkpoint inhibitor therapy before enrolling to the 
nivolumab combination cohort 
o Peripheral T-cell lymphoma ([PTCL] as defined by mature T- and NK-cell 
neoplasms per WHO and CTCL, see Appendix A), having failed at 
least 1 prior systemic therapy. Subjects with PTCL must have at least 

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1 site of measurable disease (≥ 1.5 cm in the long axis or ≥ 1.0 cm in both 
the long and short axis) 
o CTCL (both MF and SS): 
o Failed at least 2 prior systemic therapies for CTCL. Systemic 
therapy does not include local radiation therapy or topical agents 
o Malignancy is measurable per global CTCL criteria (Olsen, 2011) 
o History of histologically-documented diagnosis of CTCL stage IIB 
to IVB (Olsen, 2011) 
o (closed) B-cell or T-cell acute lymphoblastic leukemia (ALL): 
o First or greater bone marrow relapse from complete remission, or 
o Any bone marrow relapse after allogeneic transplant, or 
o Absence of complete remission after 2 induction attempts 
employing standard regimens, or 
o Ph+ B-ALL if subjects are intolerant to or ineligible to receive 
tyrosine kinase inhibitor therapy or have progressed after at least 
one line of this therapy 
o (closed) CLL: subjects should have failed at least 2 prior therapies, 
including CD20-targeted therapy 
o (closed) Multiple myeloma (MM): subjects should have failed at least 
3 prior therapies, including an immunomodulatory drug (IMID) and 
proteasome inhibitor-based therapy and have measurable disease as 
defined as 1 or more of the following: 
o serum M-protein > 0.5g/dl and/or 
o urine M-protein > 200 mg/24 hours and/or 
o in subjects who do not meet these criteria, serum free light chains 
(FLC) > 100 mg/L (involved light chain) and abnormal ratio (FLC 
kappa/FLC lambda) 
o biopsy-proven plasmacytoma 
o (closed) AML, with the exception of AML M3 using the French American 
British (FAB) classification (i.e., acute promyelocytic leukemia [APL]): 
o  (closed) MDS of WHO classifications RAEB-1 (refractory anemia with 
excess blasts) and RAEB-2 
o (closed) BCR/ABL1-negative myeloproliferative neoplasm (MPN) or 
myeloproliferative/myelodysplastic overlap neoplasm (MPN/MDS) per 
the revised 2016 WHO criteria, including: 
o chronic phase (CP) (defined as peripheral blood and bone marrow 
<10% blasts) primary myelofibrosis or post-essential 

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thrombocythemia (post-ET) or post-polycythemia vera (post-PV) 
myelofibrosis 
▪ if the diagnosis is Myelofibrosis-CP, must have Dynamic 
International Prognostic Scoring System (DIPSS) 
intermediate-2/high risk disease (Passamonti et al., 2010) 
and either be: 1) intolerant/resistant to ruxolitinib or 2) 
ineligible for ruxolitinib therapy, as determined by the 
treating Investigator 
o accelerated phase/blast phase MPN (MPN-AP/BP) (defined as 
either a peripheral blood or bone marrow with ≥10% blasts) 
▪ if the diagnosis is MPN-AP/BP, must have 
progressive/resistant disease after treatment with a DNA 
methyl transferase 1 (DNMT1) inhibitor therapy (e.g. 
azacitidine or decitabine), as determined by the treating 
Investigator 
o chronic myelomonocytic leukemia (CMML) -1 or 2 characterized 
by 
▪ >1x109/L monocytes and 2-19% blasts in peripheral blood 
or Auer rods and 
▪ dysplasia in ≥ 1hematopoietic line and 5-19% marrow 
blasts or Auer rods 
o (closed) Subjects with MPN or MPN/MDS must not be eligible to proceed 
with hematopoietic stem cell transplantation (HSCT) and must have: 
o for MPN, an indication to treat with cytoreductive drugs (e.g. 
hydroxyurea, anagrelide, interferon, ruxolutinib, etc.), according to 
the judgment of the treating physician 
o for MPN, documentation of inadequate response or intolerance to 
first line therapy, which includes at least one cytoreductive drug 
(e.g. hydroxyurea, anagrelide, interferon, ruxolutinib, etc.) 
o for CMML, documentation of inadequate response or intolerance 
to first line therapy, which includes at least one hypomethylating 
agent 
2. Hematologic status as follows (transfusions not permissible to achieve these 
levels within 14 days prior to the first dosing of study drug): 
o ANC ≥ 1 x 109/L (not applicable to subjects with AML, ALL, MDS, or 
MPN/MDS) 
o platelets ≥ 75 x 109/L (≥50 x 109/L if the patient has bone marrow 
involvement) 
o hemoglobin ≥ 9 g/dL 

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Phase 1b Expansion (Dose Optimization Part 4) 
 
1. Histologically confirmed diagnosis of CTCL (both Mycosis Fungoides and 
Sezary Syndrome): 
o Failed at least 2 prior systemic therapies for CTCL (systemic therapy does 
not include local radiation therapy or topical agents) 
o Malignancy is measurable per global CTCL criteria (Olsen, 2011) 
o History of histologically-documented diagnosis of CTCL stage IB to IVB 
(Olsen, 2011) 
 
3. Hematologic status as follows (transfusions not permissible to achieve these 
levels within 14 days prior to the first dosing of study drug): 
o ANC ≥ 1 x 109/L 
o platelets ≥ 75 x 109/L 
o hemoglobin ≥ 9 g/dL 
 
Both Phases 
1. Male or female 18 years of age or older 
 
2. Availability of fresh or archived tumor tissue for immunohistochemical studies. 
Archival tissue may be used provided it was obtained subsequent to the last prior 
anti-cancer therapy. For subjects with SS, peripheral blood is acceptable. 
 
3. Relapsed or refractory disease that has previously progressed on, or is currently 
progressing on standard anticancer therapy or for whom no other approved 
conventional therapy exists 
 
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 
(see Appendix B) 
 
5. Adequate coagulation function, defined as: 
o International Normalized Ratio (INR) < 1.5 x the upper limit of normal 
(ULN) for that laboratory 
o partial thromboplastin time < 1.5 x ULN 
o subjects receiving anticoagulation therapy must be on a stable dose with 
monitoring studies within therapeutic range per local institutional 
standards 
6. Adequate hepatic function, defined as: 

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o total bilirubin < 1.5 x ULN unless considered due to Gilbert’s disease 
o alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 
< 1.5 x ULN or < 3 x ULN with documented liver metastases 
7. Adequate renal function, defined as estimated serum creatinine clearance 
> 30 mL/minute calculated using the Cockcroft-Gault equation (see Appendix E). 
 
8. Recovery from the toxicities of previous anticancer drugs or radiotherapy to 
Grade 0 or 1 (or to baseline grade if condition was pre-existing) 
 
9. Commitment from male and female subjects of reproductive potential to use, from 
the time of screening through 60 days after the last dose of TTI-621, either: 
o one highly effective method of contraception, including hormonal 
contraceptives (e.g., combined oral contraceptives, patch, vaginal ring, 
injectables, and implants), intrauterine device (IUD) or intrauterine system 
(IUS), vasectomy, or tubal ligation 
OR 
o at least 2 effective methods of contraception, including male condom, 
female condom, cervical cap, diaphragm, or contraceptive sponge 
OR 
o abstain from sex during study participation and for 60 days after the last 
dose of TTI-621 
 
4.2 Exclusion Criteria 
 
Both Phases 
1. (AML cohort closed) AML M3 by FAB classification (APL) 
 
2. Known, current central nervous system disease involvement or untreated brain 
metastases 
 
3. Investigational agent or any anticancer drug within 14 days prior to planned start 
of treatment (with the exception of hydroxyurea in subjects with MPN, 
MPN/MDS, ALL or AML; see Section 6.8.2) 
 
4. Allogeneic transplant within 30 days prior to the planned start of treatment or 
subjects with active graft-vs-host disease with the exception of Grade 1 skin 
involvement (see Appendix C) 
 
5. Prior anti-CD47 therapy, with the exception of prior TTI-621 therapy delivered 
intratumorally only 
 
6. Major surgery within 28 days prior to planned start of treatment 

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7. Use of irreversible antiplatelet/anticoagulant agents within 7 days prior to planned 
start of treatment (except subjects with thrombocytosis where low dose aspirin is 
being used to reduce the risk of thrombosis); use of low dose aspirin 
(≤81 mg/day) and selected, reversible anticoagulants are permitted (low molecular 
weight heparin, heparin, warfarin and dabigatran) 
8. History of hemolytic anemia or bleeding diathesis 
 
9. Uncontrolled infection requiring systemic antibiotics/antivirals/antifungals 
 
10. Chronic use of systemic corticosteroids of more than 20 mg per day of prednisone 
or equivalent; enrollment of post-transplant subjects who are on corticosteroids 
for graft-vs-host disease prophylaxis requires approval of the Medical Monitor. 
CTCL patients who are on a stable dose of medium or low potency topical 
corticosteroids for at least 4 weeks prior to study entry may continue its use on 
study at the same dose. 
 
11. Known hypersensitivity to any component of study drug 
 
12. Positive serum pregnancy test in females of child-bearing potential or current 
breastfeeding 
 
13. Significant cardiovascular disease such as symptomatic congestive heart failure 
(New York Heart Association Class III or IV), symptomatic coronary artery 
disease, myocardial infarction within the last 6 months, unstable arrhythmia 
requiring treatment, unstable angina, or prolonged QTc interval 
> 480 milliseconds (Grade 2 or higher) (QTc interval calculation at the discretion 
of the Investigator) 
 
14. Active hepatitis B or C or a history of HIV infection 
 
15. Other significant medical condition unrelated to the primary malignancy that 
would compromise subject’s safety or ability to comply with protocol 
requirements 
16. Inability for the subject to complete protocol requirements, such as geographic 
considerations, psychiatric disorders, or other compliance concerns 
17. Prior Grade 4 rituximab infusion-related reaction (rituximab combination arm 
only) 
18. Active autoimmune disease or history of autoimmune disease that might recur 
(nivolumab combination arm only); subjects with vitiligo or type I diabetes 
mellitus or residual hypothyroidism due to autoimmune thyroiditis only requiring 
hormone replacement are permitted to enroll 

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5 
ENROLLMENT PROCEDURES 
 
At the time a prospective subject signs the informed consent form, a unique subject number 
will be assigned and Part 1 of the Registration/Enrollment Form completed and sent to the 
Sponsor or designee. Subjects will be screened for eligibility according to the criteria 
outlined in Section Error! Reference source not found.. 
 
Phase 1b Dose Expansion Phase (Part 2 and 3) 
Once a subject is deemed eligible, Part 3 of the Registration/Enrollment Form will be 
completed and sent to the Sponsor or designee. 
 
Phase 1b Dose Optimization Phase (Part 4) 
Once a subject is deemed eligible, Part 3 of the Registration/Enrollment Form will be 
completed and sent to the Sponsor or designee, at which time the TTI-621 dose level will 
be assigned. Additional instructions may be found in the separate Study Manual. 
 
6 
TREATMENT PROCEDURES 
 
6.1 Investigational Product 
 
TTI-621 is formulated as a sterile, clear, preservative-free liquid concentrate in 10 mM 
sodium phosphate, 150 mM sodium chloride, and water for injection, with pH adjusted to 
7.4. Formulated TTI-621 is supplied in single-use vials containing 5.0 mL solution at a 
concentration of 10 mg/mL. TTI-621 may be stored at –20°C or colder and should be 
protected from light in a secure storage facility with limited access. 
 
Additional information on the drug product may be found in the Investigator’s Brochure; 
accountability instructions are in the Pharmacy Manual. 
 
6.2 Method of Assigning Subjects to Treatment Groups 
 
Subjects in the escalation phase of the study will be sequentially assigned to TTI-621 dose 
cohorts at the time of enrollment as described in Section 3.2.1. For the expansion phase of 
the study, subjects will receive treatment based on the dose selected from the escalation 
phase, unless otherwise specified (see Section 3.3). 

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6.3 Treatments Administered (All Phases) 
 
6.3.1 Dosing Instructions 
 
General 
Premedication with an antihistamine and acetaminophen is required for all subjects 
prior to infusion of TTI-621. 
 
TTI-621 will be thawed at room temperature and the required dose diluted into 250 mL 
of 0.9% sodium chloride for injection USP as further described in the Pharmacy 
Manual. If not used immediately, the prepared infusate may be stored as described in 
the Pharmacy Manual. The assigned dose of TTI-621 will be administered IV over 
60 minutes (see Section 6.4.1 for expansion phase instructions). The start of the 
infusion (Time 0) is defined as after priming, immediately before commencement of 
the infusion. End of infusion is defined as the time immediately after the flush. 
 
Vital signs will be monitored as outlined in Section 7. 
 
The individual dose is determined based on the subject’s current body weight. Body 
weight can be rounded per institutional procedures when calculating doses. Body 
weight will be taken weekly through Week 8, then every other week (Weeks 10, 12, 
etc.) After Week 8, the weight taken at the prior visit may be used to calculate dose 
(e.g. weight at Week 8 used for Week 9 dosing). 
 
Each subject will receive TTI-621 in accordance with the assigned dose until disease 
progression, unacceptable toxicity, or other reasons for treatment discontinuation 
occur. For patients who have been given weekly infusion of TTI-621 for more than a 
year and are receiving clinical benefit (objective response or clinically meaningful 
long-term stable disease), investigators may exercise their discretion to reduce the 
dosing frequency from weekly to bi-weekly following the discussion and approval 
from the sponsor or designees. In the context of treatment discontinuation, 
unacceptable toxicity will include any Grade 4 TTI-621-related nonhematologic 
toxicity or a TTI-621-related toxicity that requires a dose delay of more than 3 weeks. 
 
In the absence of disease progression, subsequent TTI-621 doses may be delivered 
based upon subject’s clinical status with dose modifications per Section 6.5. 

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6.4 Treatments Administered – Expansion Phase 
 
An overview of treatments administered for the monotherapy and combination therapy 
cohorts for Part 2 and Part 3, is provided in Table 3-3. Additional details are provided in 
the sections below. 
 
6.4.1 TTI-621 
Monotherapy 
Phase 1b – Part 2 and Part 3 
Subjects enrolled in these cohorts will receive a starting dose of 0.2 mg/kg/week 
TTI-621. For Part 3, intrasubject TTI-621 dose-intensification is required for newly 
enrolled subjects. All subjects will receive a dose ramp-up regimen which includes 
initial two-weeks of 0.2 mg/kg treatment followed by intrasubject dose intensification 
at an increment of 0.1 mg/kg per week up to 0.5 mg/kg within 5-8 weeks. Details 
regarding when dose intensification should be delayed or stopped due to AEs are 
provided in Section 6.5.3. 
 
Phase 1b Dose Optimization - Part 4 
 
Subjects in the phase 1b dose optimization phase (Part 4) will undergo dose escalation 
of TTI-621, starting with Level 1 (dose of 0.5 mg/kg) per dose escalation plan (See 
Table 3-4, Section 3.3.2) given once weekly. Following a 3+3 escalation design and 
using a revised DLT criteria, enrollment will continue through Level 2 (starting dose 
of 0.7 mg/kg), Level 3 (starting dose of 1.0 mg/kg) and Level 4 (starting dose of 1.4 
mg/kg) respectively. In the starting dose cohort (0.5 mg/kg), the first 3 patients will be 
treated sequentially to allow close monitoring of toxicity and timely dose adjustment 
if needed. The second and third patient will not start the study treatment until the first 
and second patient, respectively, have completed the initial 2 weeks of study treatment 
and had no observation of TEAEs meeting DLT criteria. If a DLT is noted in Level 1, 
there may be de-escalation to Cohort 0 (priming dose of 0.2 mg/kg at week 1 followed 
by 0.5 mg/kg at subsequent doses) with progression through Levels 2, 3 and 4 using 
the dose priming approach of 0.2 mg/kg at week 1 followed by the respective level 
dose regimens at subsequent weeks. 
 
6.4.2 TTI-621 plus Rituximab Combination Cohort 
 
Subjects enrolled in this cohort will receive a starting dose of 0.1 mg/kg TTI-621 in 
combination with 375 mg/m2 rituximab given weekly (1 cycle) for up to 8 cycles 
according  to  the  institutional  standard  of  care.  Intrasubject  TTI-621  dose- 

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intensification is required for newly enrolled subjects as outlined in Section 6.5.4. 
Subjects who complete 8 cycles of combination therapy or those who have 
unacceptable toxicity to the combination therapy prior to completion of 8 cycles may 
continue to receive TTI-621 as a single agent. 
 
All subjects receiving the TTI-621 plus rituximab combination will have previously 
received rituximab and are thus less likely to experience the typical “first dose” 
infusion reactions upon re-exposure to rituximab. For subjects in this combination 
cohort, if rituximab is given on the same day as TTI-621, at least 60 minutes must 
elapse between completion of the rituximab infusion and initiation of the TTI-621 
infusion. Rituximab may also be given the day before TTI-621 infusion, particularly 
for subjects who have a history of Grade 2 or 3 rituximab infusion-related reactions. 
Any rituximab infusion-related reactions must be Grade 2 or lower and have fully 
resolved to initiate the TTI-621 infusion on the same day. Any rituximab infusion- 
related reactions that do not meet these criteria must be discussed with the Medical 
Monitor to determine optimal next steps. Subjects who have had a prior Grade 4 
rituximab infusion reaction will not be included in the combination TTI-621 plus 
rituximab cohort. 
 
6.4.3 TTI-621 plus Nivolumab Combination Cohort 
 
Subjects enrolled in this cohort will receive a starting dose of 0.1 mg/kg/week TTI-621 
in combination with nivolumab at 3mg/kg given every 2 weeks or a fixed dose per 
current FDA approved package insert for cHL. Intrasubject TTI-621 dose- 
intensification is required for newly enrolled subjects as outlined in Section 6.5.4. 
Subjects who have unacceptable toxicity to nivolumab may continue to receive 
TTI-621 as a single agent. 
 
For subjects in this combination cohort, if nivolumab is given on the same day as 
TTI-621, at least 60 minutes must elapse between completion of the nivolumab 
infusion and initiation of the TTI-621 infusion. Nivolumab may also be given the day 
before TTI-621 infusion. Any nivolumab infusion-related reactions must be Grade 2 
or lower and have fully resolved to initiate the TTI-621 infusion on the same day. Any 
nivolumab infusion-related reactions that do not meet these criteria must be discussed 
with the Medical Monitor to determine optimal next steps. 

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6.5 Dose Modifications (Amendment 9) 
 
This section below will be used for the entire phase 1b expansion phase per Amendment 
9, including both part 2, part 3 and the dose optimization phase part 4, except where 
otherwise noted. 
 
6.5.1 General Principles 
 
Patients will be evaluated according to the Schedule of Assessments (See Appendix 
D. Table 1 and Appendix D. Table 2) for possible toxicities that may have occurred 
after the previous dose(s). Toxicities are to be assessed according to the NCI CTCAE 
version 4.03. All toxicities that occur during the study will be actively managed 
following the standard of care per local institutional practice unless otherwise 
specified in the protocol. The investigator should try to the best of his/her ability to 
assess whether an AE is related or possibly related to study drug, and dosing actions 
of TTI-621 will then be considered accordingly. 
 
In general, patients who have the TTI-621 dose held due to treatment-related or 
possibly related AE may resume study drug after resolution of the AE, at the same 
dose level or at a reduced level (dose reduction) by at least 1 dose level. When a dose 
reduction occurs, the TTI-621 dose will be reduced to the next lower dose either by 
following the ramp-up dosing regimen in Part 3 or on the established safe dose during 
phase 1b dose optimization part 4. If the initial dose adjustment does not provide 
sufficient relief, the dose of TTI-621 can be further reduced if the investigator 
considers that the patient is benefiting from study treatment and may benefit at a 
further dose reduced dose level of TTI-621. When a dose reduction of TTI-621 is 
required due to toxicity, no dose re-escalation will be permitted. If TTI-621 dosing is 
delayed for > 21 days for TTI-621-related or possibly related toxicities despite 
supportive treatment per standard clinical practice or more than 2 dose reductions are 
required in a patient, the investigator should consider discontinuing the patient from 
study treatment, unless the investigator, after risk-benefit assessment, considers that 
the patient may benefit from continued study treatment after resolution of AEs and 
when the re-treatment criteria are satisfied per Section 6.5.2. The patient will continue 
to be followed for 30 days after the last administration of TTI-621. 
 
Patients who experience a DLT (during DLT evaluation period) or a DLT-like toxicity 
within the first 21 days of treatment, generally, require that treatment with TTI-621 be 
permanently discontinued. The patient will be followed until resolution or stabilization 
of the event. The investigator and medical monitor will decide on a case-by-case basis 
if it is in the patients’ best interest to continue the study treatment. If continuation of 

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treatment is in the patients’ best interest, the dose of TTI-621 will be reduced by at 
least 1 dose level upon resumption of treatment following recovery of the toxicity or 
toxicities to a level that satisfies the retreatment criteria (see Section 6.5.2). The 
discussion and decision will be documented. 
 
In managing toxicities, dose modification guidelines should be followed closely. 
However, based on the evolving safety data of TTI-621 and/or individual patient cases, 
alternative dose modifications may be recommended after discussion between the 
investigator and medical monitor to maximize exposure of study treatment while 
protecting patient safety. In principle, dose modification is only required per guidance 
as described below when the AE is determined to be related to the study drug. However, 
when non-study-drug related AEs, in the investigator’s assessment, would likely result 
in a medical condition where continuous dosing would add unwanted physical burden 
and stress to the patient, temporarily withholding the study drug is allowed. 
Discussions between the investigator and medical monitor are highly encouraged in 
these instances. 
 
6.5.2 Criteria for Retreatment and Dose Delays 
 
TTI-621 is given as weekly infusions. Before each TTI-621 dose can be delivered, the 
patients’ ANC must be ≥ 1 x109/L and the platelet count must be ≥ 75 x109/L or 
baseline. In addition, all other toxicity considered to be related to treatment with TTI- 
621 must have resolved to ≤Grade 1 or to the patient’s baseline values with the 
exceptions listed below. If other AEs, not listed below, resolve to a level that is 
determined to be acceptable (and ≤Grade 2) for TTI-621, re-dosing is allowed based 
on a benefit-risk assessment by the investigator and medical monitor on a case by case 
basis. The decision will be documented. 
 
Exceptions: 
• Grade 2 gastrointestinal symptoms such as nausea, vomiting, and diarrhea that 
are easily treatable 
• Grade 2 fatigue or other constitutional symptoms 
• Grade 2 lymphopenia, neutropenia, and/or leukopenia in the absence of 
opportunistic infection 
• Grade 2 thrombocytopenia in the absence of clinically meaningful bleeding 
• Grade 2 anemia in the absence of shortness of breath and/or congestive heart 
failure 
• Transient asymptomatic ≤Grade 3 laboratory abnormalities that is manageable 
with standard supportive care and considered not clinically significant 
following agreement between investigators and the sponsor or designees. 

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If the patient fails to meet the above-cited criteria for retreatment, initiation of the next 
dose of TTI-621 should be delayed for 1 week. At the end of that time, the patient 
should be re-evaluated to determine whether the criteria for retreatment have been met. 
If toxicity does not resolve by three weeks then the patient will be considered for 
removal from the study. If, in the opinion of the investigator and the medical monitor, 
it is in the patients’ best interest to continue treatment with TTI-621 then the dose of 
TTI-621 should be reduced by at least 1 dose level after recovery of the toxicity or 
toxicities in question. In such circumstances, when a dose reduction of TTI-621 is 
required, no re-escalation of dose will be permitted. 
 
6.5.3 Dose Modification Guidelines for TTI-621-related toxicities 
 
Please refer to Table 6-1 for dose delay and reduction recommendations for 
hematologic and non-hematologic toxicities. When the dose of TTI-621 is withheld 
based on the following criteria outlined below, clinical and laboratory re-evaluation 
should be repeated at least weekly or more frequently at investigator discretion 
following standard of care practice until the toxicity resolves to ≤ Grade 1 or baseline 
or to a level assessed to be acceptable per Section 6.5.1 and Section 6.5.2 and/or by 
the investigator upon agreement from the medical monitor. Upon recovery, TTI-621 
may be reinitiated either at the same dose level or at a reduced dose level. In events 
where there are transient lab value abnormalities that, based on investigator 
assessment, are not clinically significant or related to disease and not the study drug, 
continuation of therapy without following the dose modification guideline is 
permissible upon discussion with the sponsor medical monitor. 

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Table 6-1: Dose Modifications for Dose 2 and Subsequent Doses 
Clinical Scenario 
Action 
Grade 3 thrombocytopenia or Grade 4 
thrombocytopenia lasting ≤ 72 hours* 
Continue TTI-621 at the same dose when the re-treatment criterion 
(≥75 x109/L or baseline) is met; no dose intensification until no 
occurrence of the same event at the re-challenge of the same dose 
(Part 3). 
Grade 4 thrombocytopenia (platelet <25 × 
109/L) lasting >72 hours* or a platelet 
count ≤10 × 109/L at any time 
Delay TTI-621 dosing until the re-treatment criterion (≥75 x109/L 
or baseline) is met; transfuse platelet prophylactically against 
bleeding when platelet <10K per ASCO practice guideline; Then 
resume TTI-621: 
• 
at the same dose if dose delay for 1 week; 
• 
at a reduced dose by 1 dose level if dose delay for > 1 week; 
• 
at a reduced dose by 1 dose level if the event recurs 
Dose intensification can occur only when there is no occurrence of 
the same event upon re-dosing of TTI-621 at the same dose for two 
consecutive weeks. When dose reduction occurs, no further dose 
intensification will be allowed (Part 3). 
≥ Grade 3 thrombocytopenia (platelet <50 
× 109/L) with clinical bleeding (more than 
easily  controlled  epistaxis,  mild  gum 
bleeding or menses) 
Delay TTI-621 dosing until the re-treatment criterion (≥75 x109/L 
or baseline) is met, and then resume TTI-621 at a reduced dose by 
1 dose level. No further dose intensification (Part 3) will  be 
allowed. 
Grade 4 neutropenia (ANC <500/mm 3) 
lasting >72 hours* (unexplained by 
underlying disease) 
Delay TTI-621 dosing when the re-treatment criterion (ANC 
>1000/mm3) is met then resume TTI-621: 
• 
at the same dose if dose delay for 1 week 
• 
at a reduced dose by 1 dose level if dose delay for >1 week; 
• 
at a reduced dose by 1 dose level if the event recurs 
Dose intensification (Part 3) can occur only when there is no 
occurrence of the same event upon re-dosing of TTI-621 at the 
same dose for two consecutive weeks. When dose reduction 
occurs, no further dose intensification will be allowed. 
Grade  3 
febrile 
neutropenia  lasting 
>72 hours*; or Grade 3 neutropenia with 
any clinical evidence of infection; or 
Grade 4 febrile neutropenia 
Delay TTI-621 dosing until  the re-treatment criterion  (ANC 
>1000/mm3) is met, then resume TTI-621 at a reduced dose by 1 
dose level. When dose reduction occurs, no further dose 
intensification will be allowed (Part 3). 

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Grade 
3 
infusion 
reaction 
(infusion 
reactions lasting up to 24 hours including 
fevers, rigors, 
headaches, 
hypotension, 
dyspnea, and urticaria related to TTI-621) 
The current infusion should be stopped promptly and standard 
care management administered. The medical monitor should be 
informed about the occurrence of the Gr3 event and one of the 
following options will be discussed following case-by-case 
assessment between the investigator and the medical monitor: 
• 
Restarting the infusion after medical intervention and after 
the patient’s condition has stabilized with additional 
supportive care medications, 
• 
Terminating the current infusion, but re-challenging at the 
next weekly dose. At the re-challenge, the patient should 
receive premedication with corticosteroid per standard 
institution practice and/or established guidelines (Roselló et 
al., 2017); a slower rate of infusion and/or a lower dose of 
TTI-621 should be considered. 
• 
Permanently discontinuing the study treatment. Do not 
intensify dose (Part 3) 
Grade 4 infusion reaction (anaphylaxis or 
other life-threatening reactions lasting 
more than 24 hours) 
Permanently discontinue TTI-621 
Grade 3 or greater non-hematologic 
toxicity related to TTI-621 with the 
following exceptions: 
• 
Grade 3 nausea and/or vomiting 
lasting <72 hours with standard 
supportive care 
• 
Transient Grade 3 fatigue lasting 
≤72 hours 
• 
Transient asymptomatic Grade 3 
laboratory abnormalities that last 
<72 hours with standard 
supportive care and considered 
not clinically significant 
following agreement between 
investigators and the sponsor or 
designees. 
For Grade 3 events, delay TTI-621 dosing until the re-treatment 
criteria is met, then resume TTI-621 at a reduced dose by 1 dose 
level. 
No dose reduction is required for the exceptions listed. 
For Grade 4 events, discontinuation of TTI-621 should be 
considered. If, per investigator’s assessment, it is in the patient’s 
best interest to continue the treatment, TTI-621 treatment can be 
resumed when the AE resolves to a level that meets the re- 
treatment criteria 
Do not intensify dose (Part 3) 
Grade 3 or greater non-hematologic 
toxicity NOT related to TTI-621 
Investigator’s discretion to withhold or decrease dose of TTI- 
621. Do not intensify dose of TTI-621 until the resolution of the 
AEs to Grade 1, baseline, or a level (must be ≤ Grade 2) 
determined to be acceptable per investigator assessment (Part 3) 

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Grade 3 anemia 
Delay TTI-621 dosing until resolution to ≤ Grade 1 or baseline, 
then resume TTI-621 treatment: 
• 
at the same dose if dose delay for 1 week; 
• 
at a reduced dose by 1 dose level if dose delay for > 1 
week; 
• 
at a reduced dose by 1 dose level if the event recurs 
• 
Dose intensification can occur only when there is no 
occurrence of the same event upon re-dosing of TTI-621 
at the same dose for two consecutive weeks. When dose 
reduction occurs, no further dose intensification will be 
allowed (Part 3). 
Grade 4 anemia 
Discontinuation of TTI-622 should be considered. If it is in the 
patient’s best interest to continue TTI-622 per investigator 
assessment, withhold dose until resolved to ≤ Grade 1 or baseline, 
then reduce by 1 dose level. 
* When Grade 4 thrombocytopenia, Grade 4 neutropenia, or Grade 3 febrile neutropenia is first observed, hematology 
labs need to be repeated before the next scheduled visit to allow assessment of whether the event lasts for > 72 hours and 
additionally as clinically indicated per investigator discretion following standard institutional practice. 
 
6.5.4 Intrasubject Dose Intensification (Phase 1b dose expansion Part 3) 
 
For phase 1b Part 3, intrasubject dose intensification will be as follows: 
 
Newly enrolled subjects: Dose intensification will start at Week 3 for subjects when 
the prior TTI-621 dose was associated with Grade 2 or lower treatment-related AEs. 
From Week 3 to Week 8, subsequent weekly doses of TTI-621 will be increased in 
0.1 mg/kg/week increments as tolerated (Grade 2 or lower treatment-related AEs) and 
not to exceed a maximum dose of 0.5 mg/kg/week. After Week 9, additional dose 
intensification is not permitted. 
 
Previously enrolled subjects: For previously enrolled subjects, dose intensification 
up to a maximum of 0.5 mg/kg/ week is at the investigator’s discretion and should start 
at Week 3 if the prior TTI-621 dose was associated with Grade 2 or lower treatment- 
related AEs. More guidance on when to dose intensify in occurrence of AEs is 
provided in Table 6-1. 
 
6.6 Intra-patient Dose Reduction and Escalation (Phase 1b Dose Optimization 
Part 4: DLT evaluation period) 
 
Intra-patient dose reductions of TTI-621 are not permitted in the DLT evaluation period 
(Week 1-3) in the phase 1b dose optimization unless the patient experiences a DLT 
attributed to TTI-621. If a patient experiences a DLT during the first 21 days, treatment 
should be held and the event counted toward the assessment of MTD for the given cohort. 
These patients may continue in the study upon resolution of the toxicity at a reduced dose 

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level. Patients who receive a reduced dose of TTI-621 during the DLT evaluation period 
for reasons other than DLT will be replaced. 
 
During phase 1b dose optimization, when the MTD or recommended phase 2 dose of TTI- 
621 is determined, all patients who have received TTI-621 at a dose lower than the 
recommended dose for a minimum of 4 weeks may dose escalate to the recommended dose 
in the absence of PD or unacceptable treatment-related toxicity at the investigator’s 
discretion and with the medical monitor’s approval. Patients for whom an increase in the 
dose of TTI-621 is being considered must have TEAEs resolve to ≤Grade 1 or baseline or 
to a level that is acceptable to the investigator (non-hematologic toxicity must be ≤Grade 
2, hematologic toxicities must be recovered to levels above the minimum requirement for 
TTI-621 dosing). 
 
 
6.7 Management of Clinical Events 
 
Infusion-Related Reactions (IRR) 
 
Premedication with an antihistamine and acetaminophen is required for all subjects prior 
to infusion of TTI-621. During and immediately after infusion, patients will be closely 
monitored for signs and symptoms of allergic reactions. In the event of a reaction of any 
severity during the infusion itself, the infusion should be stopped and standard institutional 
supportive care administered. 
 
Grade 1 or 2: If the reaction was Grade 1 or 2 in severity and the signs and symptoms have 
fully resolved, the infusion may be restarted. Any patient who experiences a Grade 2 
allergic reaction must receive premedication with corticosteroids per standard institutional 
supportive care prior to receiving subsequent infusions. 
 
Grade 3: If a patient experiences a Grade 3 IRR, the investigator may consider the 
following: 1) restarting the infusion after medical intervention and after the patient’s 
condition has stabilized with additional supportive care medications, 2) terminating the 
current infusion, but re-challenging at the next weekly dose, or 3) permanently 
discontinuing the study treatment. When re-challenge occurs, the patient should receive 
pre-medication with corticosteroid per standard institutional practice, and a slower infusion 
rate and/or a reduced dose of TTI-621 should be considered. The investigator and medical 
monitor will decide to continue treating patients who experienced a Grade 3 IRR on a case- 
by-case basis. As with all AEs of special interest, the medical monitor should be apprised 
of any Grade 3 or higher infusion reaction that occurs during the study. 

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Grade 4: If the allergic reaction was Grade 4, the patient will be permanently discontinued 
from treatment. 
 
Thrombocytopenia 
 
Blood counts should be monitored regularly as outlined in the protocol with additional 
testing obtained according to standard clinical practice. Administration of TTI-621 should 
be modified per dose modification guidance in the protocol when thrombocytopenia occurs 
(see Section 6.5.3). Platelet transfusion is allowed to manage severe thrombocytopenia to 
prevent and minimize bleeding according to the American Society of Hematology 
Transfusion guidelines or American Society Clinical Oncology platelet transfusion 
guideline. Per these guidelines, the platelet count threshold for prophylactic platelet 
transfusion is <10,000 × 109/L. Investigators are advised to consider individual patients’ 
bone marrow function, underlining disease, medical history, concomitant medication, and 
concurrent conditions and decide how to clinically manage thrombocytopenia. 
 
6.8 Concomitant Medications and Treatment 
 
6.8.1 Required Concomitant Treatments 
 
All subjects must be premedicated with an antihistamine and acetaminophen prior to 
infusion of TTI-621. For subjects in the combination cohorts, premedication with an 
antihistamine and acetaminophen should be given prior to the combination agent 
infusion and must be repeated if the infusions of the combination agent and TTI-621 
are separated by more than 4 hours. 
 
6.8.2 Allowed Concomitant Treatments 
 
The Investigator is permitted to use standard supportive care for symptom control or 
drug-related toxicity; this might include analgesics, antiemetics, electrolyte 
replacement, topical steroids, hydration, and/or blood product transfusions. Other 
prescribed medications for non-neoplastic conditions are allowed, as well as vitamins 
and nutritional supplements. Chronic use of steroid above a daily equivalent dose of 
20 mg prednisone is not permitted on study with the exception of CTCL patients who 
had been on a stable dose of medium or low-potency topical steroid for 4 weeks before 
the first dosing of the study drug. These patients can continue to use the same dose of 
topical steroid for symptom control on study. 
 
Use of selected reversible anticoagulants (low molecular weight heparin, heparin, 
warfarin or dabigatran) for prevention or treatment of thrombosis is permitted per the 

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2017 National Comprehensive Cancer Network (NCCN) guidelines, “Cancer- 
Associated Venous Thromboembolic Disease”, with dose adjustments for 
thrombocytopenia per local institutional guidelines, with maintenance of platelet count 
>50x109/L or per local institutional standard. Use of low dose aspirin (≤81 mg day) is 
permitted for control of malignant thrombocytosis. 
 
Myeloid growth factors are permitted for rescue from treatment-emergent Grade 3 or 
4 neutropenia. Likewise, erythropoiesis-stimulating or megakaryopoiesis-stimulating 
agents may be used for treatment-emergent anemia or thrombocytopenia, respectively. 
 
Palliative radiotherapy of limited scope (ie, not exposing a significant amount of 
marrow) for the purpose of symptom relief may be permitted after consultation with 
the Medical Monitor and will not preclude continuation of TTI-621 administration. 
 
6.8.3 Prohibited Concomitant Treatments 
 
No other systemic anticancer modalities (including cytotoxic, immunomodulatory, 
biological, ECP, topical anti-neoplastics or hormonal agents) or additional 
investigational agents are permitted with the following exceptions in the expansion 
phase only: 
 
• In subjects with CTCL, chronic use of steroid above a daily equivalent dose of 
20 mg prednisone is not permitted on study with the exception of CTCL 
patients who had been on a stable dose of medium or low-potency topical 
steroid for 4 weeks before the first dosing of the study drug. These patients can 
continue to use the same dose of topical steroid for symptom control on study. 
 
Ongoing requirement for systemic corticosteroids of greater than 20 mg prednisone or 
equivalent is cause for exclusion at screening; the required initiation of corticosteroids 
during treatment (other than for treatment of an acute symptom) must be discussed 
with the Medical Monitor and tapered back to 20 mg prednisone or equivalent per day 
as soon as clinically feasible. 
 
Use of irreversible anticoagulants is not permitted at any time during the study. 
 
Requirement for surgery during treatment will occasion either TTI-621 treatment 
delay or discontinuation and will be handled case-by-case between the Investigator 
and Medical Monitor. 

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6.9 Removal of Subjects from Therapy or Assessment 
 
Subjects will be counseled that they are free to withdraw from the study at any time. Over 
the course of the study, the Investigator and/or the Sponsor may withdraw a subject from 
treatment for any of the reasons listed below: 
 
• disease progression (see Section 7.14.1) 
• unacceptable toxicity, including any treatment-emergent Grade 4 nonhematologic 
toxicity considered related to TTI-621 
• intercurrent illness compromising ability to fulfill protocol requirements 
• requirement for alternative treatment in the opinion of the Investigator 
• significant noncompliance to protocol 
• withdrawal of consent by the subject 
• administrative reason (eg, termination of the study by the Sponsor) 
• loss to follow-up 
• death 
 
The Sponsor should be notified of the withdrawal and its reason(s). When a subject 
withdraws from treatment, all safety data normally required at the end of the study (ie, the 
end-of-treatment visit, end of study, and safety follow-up) will be obtained if possible as 
outlined in Sections 7.11–7.12. 

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CCI 
7 
TESTS AND EVALUATIONS 
 
All required observations with their schedules are summarized in Appendix D. Table 1 
(Part 2 and 3) and Appendix D. Table 2 (Part 4). Unless otherwise stated, the assessments 
below pertain to patients enrolled in both Part 3 and Part 4 of the study. Concomitant 
medications will be recorded from the time of informed consent through the safety follow - 
up visit. AEs will be recorded from the start of the first dose of study treatment through the 
safety follow-up visit (see Section 9.4). 
 
Routine laboratory assessments, such as serum chemistries, hematology, coagulation and 
urinalysis, will be performed locally. In order to minimize required blood volume, pediatric 
tubes are suggested (but not required) for hematology and serum chemistries. 
 
Special tests such as PK, ADA, and pharmacodynamic/biomarker samples will be 
performed centrally or as individually indicated. Additional information on the handling 
and processing of these samples may be found in the separate Laboratory Manual. 
 
For subjects enrolled in the phase 1b expansion part of the study parts 2-4, there is a 
window of ± 2 days (2 days early or 2 days later) for any scheduled treatment days to permit 
holidays, travel, clinic scheduling and other delays from Week 2 and beyond. If the actual 
visit occurs greater than 2 days from the planned visit, that planned visit will be considered 
to have been missed and subjects should proceed with the next planned visit. All response 
assessments have an allowable window of ± 1 week. Fresh biopsies, photographs and TCR 
Vβ whole blood collections also have a ± 1 week allowable window to align with response 
assessments. 
 
 
 
 
 
 
7.1 Screening Period 
 
Informed consent may be obtained within 30 days prior to Day 1, after which it is 
recommended that the subject be re-consented. The following procedures will be 
performed after written informed consent has been obtained and within 14 days prior to the 
planned start of treatment unless otherwise noted: 
• physical examination including review of systems (breast/chest, extremities, 
head/ears/eyes/nose/throat, lymph nodes, musculoskeletal, pulmonary and 
skin), and height 
• body weight 

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• ECOG performance status (see Appendix B) 
• vital signs including heart rate, respiratory rate, and body temperature 
• baseline disease assessment as indicated for the specific primary malignancy 
(see Section 7.14.1 and Appendix D. Table 3) within 28 days prior to the 
planned start of treatment. CTCL: mSWAT, CAILS (local disease only) and 
central photographs. 
o Leukemia and lymphoma with marrow involvement: bone marrow 
aspirate for routine morphology, flow cytometry, CD47 expression and 
receptor occupancy (not required for Part 4) 
o CTCL: photographs of tumor lesions will be captured at the clinical 
site(s) using standardized photographic equipment, methodologies and 
services provided by Canfield Scientific, Inc. (Parsippany, New 
Jersey). Further detail for study photography will be provided in the 
supplied Canfield User Manual 
• CTCL and PTCL (Part 3 only): Radiographic disease assessments for CTCL 
and PTCL will be submitted for central review (central results are not required 
for enrollment). Please refer to the Imaging Manual. Part 4 will not require 
submission of scans for central review in real time but retrospective 
submissions might be requested by sponsor. 
• CTCL and PTCL (Part 3 only): Tumor tissue will be submitted for central 
review for subjects with CTCL (not including SS) and PTCL to confirm the 
diagnosis (central disease confirmation not required for enrollment). For 
subjects with SS, peripheral blood is acceptable. Archival tissue may be 
provided. Refer to the Laboratory Manual for additional details. 
• resting 12-lead ECG 
• hepatitis B (HBsAg and HBcAb) and C (HCV Ab) panel 
• serum pregnancy test for women of childbearing potential 
• serum chemistries, including alkaline phosphatase, albumin, ALT, AST, 
bilirubin (direct, indirect, and total), blood urea nitrogen (BUN), creatinine, 
glucose, lactate dehydrogenase (LDH), total protein, uric acid, and 
electrolytes (sodium, potassium, calcium, chloride, bicarbonate, phosphorus) 
• hematology, including WBC with 5-part automated differential, hemoglobin, 
RBC, absolute reticulocytes, platelets 
• coagulation panel (prothrombin time, partial thromboplastin time, INR, and 
plasma fibrinogen) 
• thyroid-stimulating hormone (TSH; only for subjects in the nivolumab 
combination cohort) 
• Tumor tissue for biomarker analysis: fresh tumor biopsy tissue, if feasible, to 
be performed for all patients. If tumor biopsy is not feasible archival tissue is 

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acceptable. For subjects with SS, peripheral blood is acceptable, if a fresh 
biopsy is not possible. Refer to the Laboratory Manual for additional details. 
The following complete historical subject information will be captured prior to Day 1: 
• medical history 
• history of malignancy, including histologic or cytologic confirmation of the 
primary malignancy, primary diagnosis date, prior treatments for the 
malignancy, and documentation of prior response and relapse status 
• ongoing medications including those administered within 14 days prior to the 
planned start of treatment 
• QOL via FACT-G questionnaire (all tumor types) and SKINDEX29 
questionnaire (subjects with CTCL) 
 
7.2 Day 1 Pre-infusion 
 
For the TTI-621 monotherapy cohorts, the procedures listed below will be performed at 
the indicated time relative to the infusion of TTI-621. For subjects in the combination 
cohorts, the procedures below will be performed relative to the infusion of the combination 
partner. Except where noted, these assessments can be performed up to 24 hours pre- 
infusion. Baseline testing are assessments preformed within 3 days prior to or on Day 1 
pre-dose. Subjects with screening laboratories within 3 days prior to dosing for a particular 
variable need not repeat the test on Day 1. To proceed with Day 1 infusion, subjects should 
meet eligibility criteria. 
 
• symptom driven physical examination (as before) and ECOG score 
• body weight 
• vital signs prior to infusion (performed per the institutional standard of care) 
• resting 12-lead ECG within 60 minutes prior to infusion (± 30 minutes) 
• serum chemistries (as before) 
• hematology (as before) 
• serum for PK 30 minutes pre-infusion (see Section 7.14.2) 
• biomarkers (± 15 minutes; see Laboratory Manual for details of sample 
splitting, preparation, and shipping) 
o serum for cytokine/chemokine panel (not required for Part 4). 
o serum for anti-tumor antibodies (not required for Part 4). 
o whole blood TCR Vβ sequencing (not required for Part 4). 
o whole blood for receptor occupancy 

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o whole blood for innate and adaptive response assay (not required for 
Part 4). 
• serum for ADA prior to infusion (± 15 minutes) 
• urinalysis (color, appearance, specific gravity, pH, glucose, bilirubin, ketones, 
occult blood, protein) 
• coagulation for Part 4 only 
 
Subjects in the combination cohorts will also undergo the following additional 
assessments. These assessments are to be done after the combination partner infusion and 
prior to the TTI-621 infusion: 
 
• vital signs 60 minutes (± 15 minutes) after completion of the combination 
partner infusion (only if the combination partner and TTI-621 are 
administered more than 60 minutes apart); performed per the institutional 
standard of care 
• vital signs prior to TTI-621 infusion ; performed per the institutional standard 
of care 
 
7.3 Day 1 Post-TTI-621 infusion (see Table 7-1) 
 
• vital signs at completion of infusion (approximately 60 minutes after Time 0 
[± 15 minutes]) and 2 and 4 hours after Time 0 [± 15 minutes]) 
• 12-lead ECG within approximately 30 minutes of the completion of infusion 
(i.e., 60–90 minutes after Time 0) 
• Serum for PK: 
o For Part 3: at completion of infusion (approximately 60 minutes after 
Time 0), 2 hours and 4 hours after Time 0, Day 2 (approximately 24 
hours after Time 0). See Table 7-2 and Appendix D. Table 2. 
o For Part 4: at completion of infusion (approximately 60 minutes after 
Time 0), 2 hours, 4 hours after Time 0, Day 2 (approximately 24 hours 
after Time 0) and Day 4 (approximately 72 hours after Time 0). See 
Table 7-2 and Appendix D. Table 2. If a priming regimen is used, see 
Appendix F for revised sampling timepoints. 
• Hematology: 
o For Part 3: - at completion of infusion (approximately 60 minutes after 
Time 0), 2 hours, and 4 hours after Time 0 (± 15 minutes). 
o For Part 4: at completion of infusion (approximately 60 minutes after 
Time 0), 2 hours, 4 hours after Time 0 (± 15 minutes), Day 2 
(approximately 24 hours after Time 0) and Day 4 (approximately 72 

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hours after Time 0), see Appendix D. Table 2. If a priming dose is 
used, see Appendix F for revised sampling timepoints. 
• biomarkers (± 15 minutes; see Laboratory Manual for details of sample 
splitting, preparation, and shipping): 
o serum for cytokine/chemokine panel at completion of infusion 
(approximately 60 minutes after Time 0) and 4 hours after Time 0, 
(not required for Part 4). 
o whole blood for receptor occupancy at completion of infusion 
(approximately 60 minutes after Time 0) 
• AEs 
• concomitant medications 
 
Table 7-1: Week 1 Temporal Summary of Infusion and Post-infusion Assessments 
 
T = 0 
T 0–60 
min 
T + 60 min 
T + 2 hr 
T + 4 hr 
T + 24 hr 
T + 72 hr 
Start TTI- 
621 
infusion 
End infusion 
- - - - - - - - - - - Monitor for infusion reactions - - - - - - - - - - - 
- 
Vital signs 
Vital signs 
Vital signs 
ECG 
Receptor 
occupancy 
Pharmacokin. 
Pharmacokin. 
Pharmacokin. 
Hematology 
Hematology 
Hematology 
Cytokines/ 
 
 Cytokines/ 
chemokines 
chemokines 
(Part 3 only) 
(Part 3 only) 
Pharmacokin. 
Hematology 
(Part 4 only) 
Pharmacokin. 
(Part 4 only) 
Hematology 
(Part 4 only) 

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7.4 Week 2 
 
On Day 1 of Week 2 (Day 8 of treatment), the below tests and observations will be 
performed. For the TTI-621 monotherapy cohorts, assessments will be performed at the 
indicated time relative to the infusion of TTI-621. For subjects in the combination cohorts, 
assessments will be performed relative to the infusion of the combination partner, as 
applicable. All of these assessments can be performed up to 24 hours pre-infusion, with the 
exception of vital signs, PK, and biomarkers. Post-infusion procedures will be relative to 
the TTI-621 infusion. 
 
• symptom-driven physical examination and ECOG score 
• body weight 
• vital signs prior to infusion and at completion of infusion (60 minutes after 
Time 0 [(± 15 minutes]). For subjects in the combination cohorts, the latter 
timepoint (60 minutes after Time 0) is to be done only if the combination 
partner and TTI-621 are administered more than 60 minutes apart; performed 
per the institutional standard of care. For subjects under Part 4, vitals are not 
required at end of infusion. Refer to Appendix D. Table 2. 
• biomarkers (± 15 minutes; see Study Manual for details of sample splitting, 
preparation, and shipping): 
o serum for cytokine/chemokine panel (pre-dose), not required for Part 4 
o whole blood for receptor occupancy (pre-dose) for Part 3 and 4. For 
Part 4, if a priming dose is used see Appendix F for revised sampling 
timepoints. 
• Serum for PK: 
o For Part 3 and Part 4: serum for PK trough levels (pre-dose). See 
Appendix D. Table 1 and Appendix D. Table 2. If a priming regimen 
is used, see Appendix F for revised sampling timepoints. 
• Hematology: 
o For Part 3: pre-dose (results must be available prior to start of 
infusion). Further hematologic monitoring should be instituted at the 
discretion of the treating Investigator. 
o For Part 4: pre-dose (results must be available prior to start of 
infusion) and 4 hours after Time 0 (± 15 minutes). Day 2 
(approximately 24 hours after Time 0) assessments are required if 
clinically indicated, in the event that ≥ Grade 4 thrombocytopenia is 
observed on day 1 or there are any other clinical conditions indicated 
for a follow-up lab at the investigator discretion. Further hematologic 
monitoring should be instituted at the discretion of the treating 

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Investigator. If a priming dose is used, see Appendix F for revised 
sampling timepoints. 
• serum chemistries 
• AEs 
• concomitant medications 
• coagulation panel only for Part 4 
7.5 Week 3 
 
On Day 1 of Week 3 (Day 15 of treatment), the below tests and observations will be 
performed. For the TTI-621 monotherapy cohorts, assessments will be performed at the 
indicated time relative to the infusion of TTI-621. For subjects in the combination cohorts, 
assessments will be performed relative to the infusion of the combination partner, as 
applicable. All of these assessments can be performed up to 24 hours pre-infusion, with the 
exception of PK and vital signs. For Part 3 only, if intrasubject dose intensification occurs 
at this visit please also refer to Section 7.6 for additional assessments. 
 
• symptom driven physical examination and ECOG score 
• body weight 
• vital signs prior to infusion and at completion of infusion (60 minutes after 
Time 0) [(± 15 minutes]). For subjects in the combination cohorts, the latter 
timepoint (60 minutes after Time 0) is to be done only if the combination 
partner and TTI-621 are administered more than 60 minutes apart; performed 
per the institutional standard of care. For subjects under Part 4, vitals are not 
required at end of infusion. Refer to Appendix D. Table 2. 
• Serum for PK: 
o For Part 3: serum for PK trough levels (pre-dose) 
o For Part 4: serum for PK trough levels (pre-dose). If a priming dose is 
used see Appendix F for revised sampling timepoints. 
• Hematology: 
o For Part 3: pre-dose (results must be available prior to start of 
infusion). Further hematologic monitoring should be instituted at the 
discretion of the treating Investigator. 
o For Part 4: pre-dose (results must be available prior to start of 
infusion) and 4 hours after Time 0 (± 15 minutes). Day 2 
(approximately 24 hours after Time 0) assessments are required if 
clinically indicated, in the event that ≥ Grade 4 thrombocytopenia is 
observed on day 1 or there are any other clinical conditions indicated 
for a follow-up lab at the investigator discretion. Further hematologic 

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monitoring should be instituted at the discretion of the treating 
Investigator. If a priming dose is used, see Appendix F for revised 
sampling timepoints. 
• serum chemistries 
• AEs 
• concomitant medications 
• coagulation panel only for Part 4 
• biomarkers (± 15 minutes; see Study Manual for details of sample splitting, 
preparation, and shipping): 
o For Part 4: If a priming dose is used additional whole blood for 
receptor occupancy is required. See Appendix F for additional 
sampling timepoints. 
 
 
7.6 TTI-621 Intrasubject Dose Intensification – Additional Assessments Every 
Week of Dose Intensification (only applicable to Part 3) 
 
For subjects who are dose intensified at Week 3 through Week 8, the following assessments 
are required on Day 1, only if not already part of the scheduled weekly visit. For the TTI- 
621 monotherapy cohorts, assessments will be performed at the indicated time relative to 
infusion of TTI-621. For subjects in the combination cohorts, pre-infusion assessments will 
be performed relative to the start of the combination partner infusion, as applicable. 
 
• serum for PK at end of infusion and 4 hours after Time 0 (see Table 7-2) 
• whole blood for receptor occupancy: pre-infusion and at end of infusion 
(approximately 60 minutes after Time 0, ± 15 minutes) 
• hematology at 4 hours after Time 0. Additional hematologic monitoring should be 
instituted at the discretion of the treating Investigator. 
• serum chemistries at 4 hours after Time 0 
 
7.7 Week 4 
 
On Day 1 of Week 4 (Day 22 of treatment), the below tests and observations will be 
performed. For the TTI-621 monotherapy cohorts, assessments will be performed at the 
indicated time relative to the infusion of TTI-621. For subjects in the combination cohorts, 
assessments will be performed relative to the infusion of the combination partner, as 
applicable. All of these assessments can be performed up to 24 hours pre-infusion, with the 
exception of vital signs and PK. For Part 3 only, if intrasubject dose intensification occurs 
at this visit please also refer to Section 7.6 for additional assessments. 

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• symptom driven physical examination and ECOG score 
• body weight 
• vital signs prior to infusion and at completion of infusion (60 minutes after 
Time 0 [(± 15 minutes]). For subjects in the combination cohorts, the latter 
timepoint (60 minutes after Time 0) is to be done only if the combination 
partner and TTI-621 are administered more than 60 minutes apart; performed 
per the institutional standard of care. For subjects under Part 4 vitals are not 
required at end of infusion. Refer to Appendix D. Table 2. 
• urine or serum pregnancy test for women of childbearing potential 
• Serum for PK: 
o For Part 3: serum for PK trough levels (pre-dose) 
o For Part 4: serum for PK trough levels (pre-dose). If a priming 
regimen is used see Appendix F for revised sampling timepoints. 
• Hematology: 
o For Part 3: pre-dose (results must be available prior to start of 
infusion). Further hematologic monitoring should be instituted at the 
discretion of the treating Investigator. 
o For Part 4: pre-dose (results must be available prior to start of 
infusion). Further hematologic monitoring should be instituted at the 
discretion of the treating Investigator. If a priming regimen is used, see 
Appendix F for revised sampling timepoints. 
• serum chemistries 
• serum for ADA 
• AEs 
• concomitant medications 
• coagulation panel only for Part 4 
• resting 12-lead ECG within 60 minutes prior to infusion (± 30 minutes) only 
for Part 4 
• biomarkers (± 15 minutes; see Study Manual for details of sample splitting, 
preparation, and shipping): 
o For Part 4: If a priming dose is used additional whole blood for 
receptor occupancy is required. See Appendix F for additional 
sampling timepoints. 

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7.8 Week 5-7 
 
On Day 1 of Week 5, the below tests and observations will be performed. For the TTI-621 
monotherapy cohorts, assessments will be performed at the indicated time relative to the 
infusion of TTI-621. For subjects in the combination cohorts, assessments will be 
performed relative to infusion of the combination partner, as applicable. All assessments 
can be performed up to 24 hours pre-infusion, with the exception of PK. For Part 3 only, 
if intrasubject dose intensification occurs at this visit please also refer to Section 7.6 for 
additional assessments. 
 
• symptom driven physical examination and ECOG score 
• vital signs, performed per the institutional standard of care 
• body weight 
• Part 3 and Part 4: hematology (results must be available prior to study drug). 
For Part 4, if a priming dose is required see Appendix F. 
• Part 3 and Part 4: serum for PK trough levels (pre-dose). For Part 4, if a priming 
dose is required see Appendix F. 
• AEs 
• concomitant medications 
 
 
7.8.1 Week 5 (Part 4 only) 
 
The following assessments are also required in addition to the week 5 assessments 
specified above, for Part 4 only. 
• biomarkers (± 15 minutes; see Study Manual for details of sample splitting, 
preparation, and shipping): 
o For Part 4: If a priming dose is used additional whole blood for 
receptor occupancy is required. See Appendix F for additional 
sampling timepoints. 
 
7.8.2 Week 6 (Part 4 only) 
 
The following assessments are also required in addition to the week 6 assessments 
specified above, for Part 4 only. 
• Serum for PK – at completion of infusion (approximately 60 minutes after 
Time 0), 2 hours and 4 hours after Time 0 (± 15 minutes), Day 2 
(approximately 24 hours after Time 0) and Day 4 (approximately 72 hours after 
Time 0). See Table 7-2. 

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• Whole blood for receptor occupancy – pre-dose and at end of infusion 
(approximately 60 minutes after Time 0) 
 
7.8.3 Week 7 (Part 4 only) 
 
The following assessments are also required in addition to the week 7 assessments 
specified above, for Part 4 only. 
• Whole blood for receptor occupancy pre-dose 
 
7.9 Week 8 
 
The below tests and observations will be performed on Day 1 of Week 8 unless otherwise 
stated. For subjects in the monotherapy cohorts, the procedures listed below will be 
performed at the indicated time relative to TTI-621 infusion. For subjects in the 
combination cohorts, pre-infusion procedures will be relative to the combination agent 
infusion, where applicable. Post-infusion procedures will be relative to the TTI-621 
infusion. All assessments can be performed up to 24 hours pre-infusion, with the exception 
of PK and biomarkers. 
 
• symptom driven physical examination and ECOG score 
• vital signs, performed per the institutional standard of care 
• body weight 
• disease assessment at the end of the week (see Appendix D. Table 3) 
o For CTCL and PTCL subjects, central submission of radiographic 
disease assessments is required. Part 4 will not require submission of 
scans for central review in real time but retrospective submissions 
might be requested by sponsor. 
o CTCL subjects only: mSWAT, CAILS (if applicable) and photographs 
• Fresh tumor sample from an identified target lesion (CTCL subjects: required 
if feasible to perform biopsy, all other tumor types: optional). 
• Peripheral blood and blood smear for central pathology review (See Appendix 
D. Table 3). Refer to the Laboratory Manual for additional details; not 
required for Part 4 
• resting 12-lead ECG 
• Post-dose: QOL by FACT-G (all subjects) and SKINDX29 (CTCL only) 
• urine or serum pregnancy test for women of childbearing potential 
• serum chemistries 

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• hematology (results must be available prior to start of infusion). Further 
hematologic monitoring should be instituted at the discretion of the treating 
investigator. 
• serum for PK (see Table 7-2): 
o Part 3: trough levels pre-infusion and completion of infusion 
(approximately 60 minutes after the start of infusion [i.e., Time 0]), 
2 hours and 4 hours after Time 0, Day 2 (approximately 24 hours after 
Time 0), and Day 4 (approximately 72 hours after Time 0) 
o Part 4: trough levels pre-infusion 
• biomarkers (± 15 minutes; see Study Manual for details of sample preparation 
and shipping): 
o bone marrow aspirate for receptor occupancy (only for subjects with 
bone marrow based disease), to align with the response assessments. 
Not required for Part 4 
o serum for cytokine/chemokine panel pre-infusion, at completion of 
infusion (approximately 60 minutes after Time 0), 4 hours after Time 
0, and Day 2 (approximately 24 hours after Time 0); not required for 
Part 4. 
o Part 3: whole blood for receptor occupancy pre-infusion and at 
completion of infusion (approximately 60 minutes after Time 0); not 
required for Part 4. 
o whole blood for innate and adaptive response assay pre-infusion, not 
required for Part 4 
o whole blood for TCR Vβ sequencing pre-infusion, not required for 
Part 4 
• urinalysis (Part 3 only) 
• coagulation (Part 4 only) 
• serum for ADA analysis 
• AEs 
• concomitant medications 
 
7.10 Weeks 9 and Higher 
 
7.10.1 Phase 1b Part 3 
 
The following assessments are applicable for Part 3. 

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For subjects in the monotherapy cohorts, the procedures listed below will be 
performed at the indicated time relative to the infusion of TTI-621. For subjects in the 
combination cohorts, pre-infusion procedures will be relative to the combination agent 
infusion, where applicable. Post-infusion procedures will be relative to the TTI-621 
infusion. All assessments can be performed up to 24 hours pre-infusion, with the 
exception of PK and biomarkers. The below testing intervals represent a minimum; 
subjects with an ongoing abnormality should be monitored more frequently as 
clinically indicated. 
 
• symptom driven physical examination and ECOG score Day 1 of Week 12 
and every 4 weeks thereafter 
• vital signs, performed per the institutional standard of care 
• body weight measured every other week (Week 10, 12, etc.). After Week 8, 
the weight taken at the prior visit may be used to calculate dose (e.g. weight at 
Week 8 used for Week 9 dosing) 
• disease assessment (see Appendix D. Table 3) at the end of Weeks 16 and 24, 
followed by every 12 weeks (Weeks 36, etc.) or at the point that clinical 
progression is observed or suspected. 
o For CTCL and PTCL subjects, central submission of radiographic 
disease assessments is required. 
o CTCL subjects only: mSWAT, CAILS (if applicable) and photographs 
at time of disease assessments 
o Peripheral blood and blood smear for central pathology review for SS 
subjects only. Refer to the Laboratory Manual and to Appendix D. 
Table 3 for additional details. 
• Week 16 pre-infusion: fresh tumor sample from an identified target lesion for 
CTCL subjects only 
• resting 12-lead ECG Day 1 of Weeks 16 and 24 
• QOL by FACT-G (all subjects) and SKINDX29 (CTCL only): post-dose on 
Week 16 and 24, and then every 12 weeks thereafter 
• urine or serum pregnancy test for women of childbearing potential Day 1 of 
Week 12 and every 4 weeks thereafter 
• serum chemistries Day 1 of Week 12 and every 4 weeks thereafter 
• hematology Day 1 of every week (results must be available prior to start of 
infusion). Further hematologic monitoring should be instituted at the 
discretion of the treating investigator. 

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• serum for PK (see Table 7-2): 
o Day 1 of Week 9 and every week through Week 16 inclusive: trough 
level (pre-infusion) 
• biomarkers (± 15 minutes; see Study Manual for details of sample preparation 
and shipping): 
o Day 1 of Week 9 (pre-infusion): serum for cytokine/chemokine panel 
o Day 1 of Week 16 (pre-infusion): whole blood TCR Vβ sequencing 
o Day 1 of Week 16 only (pre-infusion): anti-tumor antibodies 
o Day 1 of Week 9 (pre-infusion): whole blood for receptor occupancy 
• TSH on Day 1 of Week 12 and every 12 weeks thereafter (only for subjects in 
the nivolumab combination cohort) 
• serum for ADA analysis pre-infusion on Day 1 of Week 12 and every 4 weeks 
• AEs 
• concomitant medications 
 
7.10.2 Phase 1b Part 4 
 
The following assessments are applicable for patients under Part 4. Refer to Appendix 
D. Table 2. The procedures listed below will be performed at the indicated time 
relative to the infusion of TTI-621. All assessments can be performed up to 24 hours 
pre-infusion, with the exception of PK and biomarkers. 
 
• Day 1 of Week 12, and every 4 weeks thereafter: 
o coagulation, symptom driven from week 16 onward 
o resting 12-lead ECG 
o urine or serum pregnancy test for women of childbearing potential 
o serum chemistries 
• body weight measured every other week (Week 10, 12, etc.). After Week 8, 
the weight taken at the prior visit may be used to calculate dose (e.g. weight at 
Week 8 used for Week 9 dosing) 
• vital signs pre-infusion, performed per the institutional standard of care 
weekly 
• disease assessment (see Appendix D. Table 3) at the end of Weeks 16 and 24, 
followed by every 12 weeks (Weeks 36, etc.) or at the point that clinical 
progression is observed or suspected. 

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o central submission of radiographic disease assessments is not required 
for central review in real time but retrospective submissions might be 
requested by sponsor. 
o mSWAT, CAILS (if applicable) and photographs 
o QOL by FACT-G and SKINDX29 
• hematology Day 1 of every week (results must be available prior to start of 
infusion). Further hematologic monitoring should be instituted at the 
discretion of the treating investigator. 
• symptom driven physical examination/ECOG score Day 1 of every week 
• AEs 
• concomitant medications 
• serum for PK (see Table 7-2): 
o Day 1 of Week 9 and every week through Week 16 inclusive: trough 
level (pre-infusion) 
• biomarkers (± 15 minutes; see Study Manual for details of sample preparation 
and shipping): 
o Week 16 pre-infusion: fresh tumor sample if feasible from the same 
lesion as screening or from a nearby lesion for CTCL subjects only 
o whole blood for receptor occupancy pre-infusion on Day 1 of Week 12 
and 16. 
• serum for ADA analysis pre-infusion on Day 1 of Week 12 and every 4 weeks 
 
7.11 End-of-Treatment Visit 
 
Within 1 week following the final dose of TTI-621 (or at the time of premature 
discontinuation of treatment), the following procedures will be performed: 
 
• physical examination and ECOG score 
• body weight 
• vital signs 
• disease assessment (if not performed within the last 8 weeks) 
• QOL by FACT-G (all subjects) and SKINDX29 (CTCL only) 
• resting 12-lead ECG 
• serum for PK 
• serum chemistries 
• hematology 

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• coagulation panel 
• TSH (only for subjects in the nivolumab combination cohort) 
• urinalysis 
• serum for ADA analysis 
• biomarkers (see Study Manual for details of sample preparation and shipping): 
o serum for cytokine/chemokine panel (not required for Part 4) 
o whole blood for innate and adaptive response assay (not required for 
Part 4) 
• AEs 
• concomitant medications 
• peripheral blood and blood smear for central pathology for SS patients (Part 3 
only). Refer to the Laboratory Manual and to Appendix D. Table 3 for 
additional information. 
 
7.12 Safety Follow-up Visit 
 
Approximately 30 days after the final dose of TTI-621 (± 2 days), the following will 
be performed. If treatment-emergent abnormalities are present at the end-of-treatment 
visit, repeat pertinent labs or studies: 
 
• symptom driven physical examination and ECOG score 
• body weight 
• vital signs 
• serum chemistries 
• hematology 
• TSH (only for subjects in the nivolumab combination cohort) 
• serum for ADA analysis; subjects who are seropositive at safety follow-up, 
should be monitored at least quarterly for 1 year post study to assess 
persistence of antibodies 
• status of unresolved AEs 

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7.13 Long-term Follow-up (Expansion Phase Only) 
 
For a period of 1 year following the safety follow-up visit, subjects treated in the 
expansion phase will be contacted at least quarterly (±1 week) via routine clinic visit 
and/or telephone call to assess the following: 
 
• subsequent anticancer therapies 
• status of any ongoing/chronic AEs that were treatment-emergent 
• persistence of ADA in those subjects who seroconverted 
• date of disease progression (if not documented on study) 
• survival status 
 
7.14 Procedures for Special Tests 
 
7.14.1 Disease Assessment 
 
Disease assessments for individual malignancy types are detailed in Appendix D. 
Table 3. 
 
Response Criteria 
Tumor response assessment for lymphomas (including PTCL) in both the escalation 
and expansion phases will utilize the Lugano Classification (Cheson et al., 2014), 
including the 2016 refinement of these criteria (Cheson et al., 2016). A response will 
be defined as an objective status of partial remission (PR) or complete remission (CR) 
for subjects evaluated by computed tomography (CT)-based criteria and complete 
metabolic response (CMR) or partial metabolic response (PMR) for subjects evaluated 
by positron emission tomography -CT based criteria. For CTCL, a response will be 
defined as PR or CR in any of the organ systems individually (skin, viscera, blood or 
lymph nodes). Additionally, a global response incorporating each organ system will 
be compiled per the Olsen criteria (Olsen et al., 2011). Radiographic disease 
assessments for CTCL and PTCL will be submitted for central review for those 
subjects enrolled to phase 1b Part 3. The subjects enrolled to phase 1b Part 4 will not 
require submission of scans for central review in real time but might be requested by 
sponsor retrospectively. 
For the additional malignancies in the expansion phase, the following classification 
systems will be employed: 
 
• AML and ALL – Revised Recommendations of the International Working 
Group for trials in AML (Cheson et al., 2003) 

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• CLL – International Workshop on CLL update of the NCI 1996 Guidelines 
(Hallek et al., 2008) 
• MDS/MPN – An International Consortium Proposal of Uniform Response 
Criteria for Myelodysplastic/Myeloproliferative Neoplasms (MDS/MPN) in 
Adults (Savona et al., 2015) 
• Multiple Myeloma – International Uniform Response Criteria for Multiple 
Myeloma (Durie et al., 2006) 
• CTCL – Clinical Endpoints and Response Criteria in Mycosis Fungoides and 
Sezary Syndrome (Olsen et al., 2011) 
• SCLC – Adaptation of the Immune-Related Response Criteria: irRECIST 
(Bohnsack et al., 2014) 
 
 
 
Pseudoprogression or Indeterminate Response 
 
Some therapeutic agents, particularly immunotherapeutics, display different patterns 
of anti-tumor response, which may include a period of increasing tumor burden 
followed by a response, stable disease followed by slow decline in tumor burden, or 
even a response in the presence of new lesions (Cheson et al., 2016; Chow, 2013; 
Wolchok et al., 2009). Immune-mediated responses may take longer to manifest than 
those from cytotoxic agents. In other cancer settings, a phenomenon called “tumor 
flare” or pseudoprogression has also been described, in which increased contrast 
enhancement and hyperintensity is observed on posttreatment MRI scans (fluid - 
attenuated inversion recovery, or FLAIR) which represents a biologic effect on the 
tumor and its microenvironment and which stabilizes or diminishes over time 
(Batchelor, 2012). 
 
In order to avoid falsely assigning disease progression during the expansion phase of 
the study, a subject whose radiologic disease assessment is indicative of progression 
may, at the discretion of the Investigator and Medical Monitor, be considered 
“Indeterminate” in the case report forms and continue on treatment pending a repeat 
scan 4 to 6 weeks later, if all of the following criteria are met: 
 
• absence of symptomatic or clinical progression 
• stable performance status 
• adequate tolerance to TTI-621 therapy 
• treating beyond progression does not delay an intervention felt to be in the 
subject’s best interest 

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If the second confirmatory scan indicates unequivocal disease progression, the subject 
will be discontinued from treatment. The date of the first scan indicating progression 
will be used for analysis purposes. If however the second scan indicates a reduction in 
tumor burden or stable disease from the baseline scan, the subject may continue on 
treatment in the absence of unacceptable toxicity or other reason for treatment 
discontinuation. 
 
Notwithstanding, the Investigator is free to remove the subject from treatment at any 
time during the study if it is felt to be in the subject’s best interest. 
 
7.14.2 PK 
 
In both the escalation and expansion phases (Part 2), serial blood sampling will take 
place in conjunction with the first and sixth weekly infusion of TTI-621 (i.e., Days 1 
and 36 of study) to estimate the PK profile of TTI-621. Subsequent sampling after the 
first week will be limited to “trough” levels (30 minutes pre-dose). A sample will also 
be taken at EOT. 
 
For phase 1b Part 3 only, serial blood sampling will take place in conjunction with the 
first and eighth weekly infusion of TTI-621, a time at which mandatory intra-subject 
dose intensification for newly enrolled subjects is anticipated to be completed. This 
sampling will be performed to evaluate the PK profile of TTI-621 following dose- 
intensification, and after repeat dosing. Subsequent sampling will be limited to 
"trough" levels at Week 9 through Week 16 inclusive. A sample will also be taken at 
EOT. 
 
For phase 1b Part 4, for subjects enrolled in cohorts without priming doses, serial 
blood sampling will take place in conjunction with the first and sixth weekly infusion 
of TTI-621(i.e., Days 1 and 36 of study) to estimate the PK profile of 
TTI-621 with further dosing optimization. For subjects enrolled in cohorts with 
priming dose regimen under phase 1b Part 4 receiving a single priming dose on Week 
1, serial blood sampling will take place on Week 2, following administration 
of the highest stable dose and on the sixth weekly infusion of TTI-621 to estimate the 
PK profile of TTI-621 with further dosing optimization. Subsequent sampling for all 
phase 1b Part 4 cohorts, will be limited to "trough" levels at Week 9 through Week 16 
inclusive. A sample will also be taken at EOT. 
 
If there is a delay in infusion administration (i.e., duration of TTI-621 infusion is 
greater than 60 minutes), the end-of-infusion PK sample should be drawn at the time 
the infusion is complete (prior to flush). However, all subsequent timepoints should 

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not be adjusted and should be collected relative to the start of TTI-621 infusion as 
summarized in Table 7-2. 
 
Whole blood will be collected at each time point and prepared as outlined in the 
separate Laboratory Manual. 
 
 
 
 
 
 
 
 
 
 
Table 7-2: Summary of PK Sampling Times 
 
Week 
Day 
Nominal Time 
Allowable 
Time 
Window 
N 
1 
Pre-infusion (within 30 min) 
± 15 min 
1 
EOI (60 min)§ 
+5 min 
1 
T + 2 hr§ 
± 15 min 
1 
T + 4 hr§ 
± 15 min 
N 
2 
T + 24 hr§ 
± 6 hrs 
N 
4 
T + 72 hr§ 
± 24 hrs 
N 
1 
trough (30 min pre-infusion) 
± 15 min 
EOT 
Within 1 week following final 
dose 
EOI = immediately after the end of infusion (i.e., prior to flush) 
EOT = end of treatment 
N = any week where the listed timepoints are applicable 
§ Relative to the start of first TTI-621 infusion 
 
 
CCI 
 
 
 
 
 
 
 
 

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• 
CCI 
 
 
 
 
 
 

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8 
PLANNED ANALYSES 
 
A separate Statistical Analysis Plan will provide final specific details on the analytical 
methods and data displays. 
 
8.1 Study Endpoints 
 
8.1.1 Escalation Phase 
 
Primary 
o Incidence and severity of AEs 
Secondary 
o PK profile, PD, ADA 
 
8.1.2 Expansion Phase, Part 2 and Part 3 
 
Primary 
o Incidence and severity of AEs 
Secondary 
o PK profile, PD, ADA 
o Overall response rate, duration of response, and progression-free survival 
o Part 3: CTCL and PTCL: organ system overall response rate – 2 analyses 
within each cohort 
 
8.1.3 Expansion Phase, Part 4 
 
Primary 
o Incidence and severity of AEs 
Secondary 
o PK profile, PD, ADA 
o Overall response rate and duration of response 
o CTCL: organ system overall response rate 

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8.2 Analysis Populations 
 
Safety Analysis Set 
 
The Safety Analysis Set will be used for the analysis of safety data in this study and will 
consist of all subjects who receive at least 1 dose of TTI-621. 
 
Full Analysis Set 
 
The Full Analysis Set will serve as the primary population for all efficacy-related data, 
with the exception of the analysis of overall response, for which the Response-Evaluable 
Set will be primary, and the Full Analysis Set will be secondary. The Full Analysis Set is 
a subset of all enrolled subjects, with subjects excluded for the following reasons: 
• failure to receive at least 1 dose of TTI-621 
• lack of baseline data for those analyses that require baseline data 
Response-Evaluable Set 
 
The Response-Evaluable Set will serve as the primary population for the analysis of overall 
response. The Response-Evaluable Set is a subset of the Full Analysis Set, with subjects 
excluded if they have no post-baseline assessment of overall response. 
 
Per-protocol Set 
 
A supportive analysis may be performed by excluding subjects with important deviations 
from the protocol that may substantially affect the results of the primary efficacy analyses. 
The final determination on protocol violations, and thereby the composition of the Per- 
protocol Set, will be made prior to locking the clinical database and final analysis and will 
be documented in the statistical analysis plan (SAP). 
 
PK-evaluable Set 
 
The PK-evaluable Set consists of treated subjects with adequate blood sampling to estimate 
at least 1 PK parameter. 

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8.3 Determination of Sample Size 
 
Escalation Phase 
 
Up to 6 subjects may be enrolled in each dose cohort evaluated during the escalation phase. 
The minimum number of subjects enrolled in each cohort and the dose-step increments 
between adjacent cohorts will be based on a standard 3 + 3 dose escalation scheme (Section 
3.2). A maximum of 36 subjects will be enrolled between up to 6 dose cohorts. The actual 
number enrolled is dependent upon the observed safety profile, which will determine the 
number of subjects per dose cohort, as well as the number of dose escalations required to 
achieve the MTD. 
 
Expansion Phase 
 
For the purpose of broadly characterizing preliminary anti-tumor activity, a 95% one-sided 
confidence interval will be calculated according to Table 8-1 for each cohort of 12 to 
15 subjects evaluated. The original number of subjects was chosen largely based on 
clinical and feasibility considerations in light of the number of distinct cohorts to be 
evaluated. Although the number of subjects to be enrolled in an individual cohort is limited, 
the number of responses and any other indicators of clinical benefit that are observed within 
a cohort can be used to assess in a preliminary manner whether the true overall response 
rate is either unacceptably low or sufficiently high to warrant further evaluation in this or 
a future study. For example, if 12 subjects are enrolled within a cohort, the probability of 
observing no responses is low (i.e., < 1%) when the true overall response rate is 40% or 
higher. Similarly, the probability of observing 3 or more responses is high (i.e., 92%) when 
the true overall response rate is 40% or higher. When the true overall response rate is only 
10%, the probability of observing 3 or more responses is 11%. 
 
After a preliminary evaluation of both the tolerability of treatment and any early signs of 
clinical benefit as characterized by overall response rate, prolonged progression-free 
intervals, or clearance of minimal residual disease, a hematologic disease cohort may be 
expanded (and, if appropriate, further refined by disease characteristics) to a maximum of 
40 subjects to further evaluate clinical benefit. 

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Table 8-1: 95% Lower Confidence Limits for Response Rate 
 
Number of Responses 
Number of 
Subjects 
3 
4 
5 
6 
7 
8 
10 
9% 
15% 
22% 
30% 
39% 
49% 
11 
8% 
14% 
20% 
27% 
35% 
44% 
12 
7% 
12% 
18% 
25% 
32% 
39% 
13 
7% 
11% 
17% 
22% 
29% 
35% 
14 
6% 
10% 
15% 
21% 
26% 
33% 
15 
6% 
10% 
14% 
19% 
24% 
30% 
 
For the phase 1b portion (Part 2) of the study, the cohort size for selected cohorts has been 
increased to 40 subjects. This is to improve the precision of the overall response rate (ORR) 
estimate. For example, for an ORR of 30%, in 10 subjects, the lower confidence limit 
(LCL) of a 95% one-sided confidence interval is 8.7%, or a distance of 21.3% (30-8.7) 
from the ORR. When the sample size is increased to 40 for the same ORR, the LCL is 
18.3%, or a distance of 11.7% (30-18.3) from the ORR. This anticipated improvement in 
the precision of the point estimate will be particularly important given the relative 
heterogeneity of the enrolled population. 
 
Expansion Phase Part 3: CTCL and PTCL Cohorts 
 
For the phase 1b (Part 3) expansion cohorts for CTCL and PTCL, the cohort size has been 
selected based upon a Simon optimal 2-stage design, with the low and high boundaries of 
the response rate being 10% (not effective) and 30% (warrants further study) respectively, 
and a power of 90% and an alpha of 0.05. The calculations were performed using PASS 
14 (NCSS, 2015) and the Optimum design chosen. The total sample size is 35 subjects per 
cohort under the scenario described below. For the first stage, a total of 18 subjects will be 
enrolled in each cohort. At the end of Stage 1, if 2 or fewer responders are observed per 
cohort, enrollment in this cohort will be terminated, otherwise, enrollment will proceed to 
the second stage and an additional 17 subjects will be enrolled per cohort for a total of 35 
subjects per cohort. At the end of the second stage, if 6 or fewer responders are observed 
per cohort, the drug will be rejected for further testing in this indication. The probability 
of early termination (PET) = 0.734 at the end of the first stage if the true response rate is 
less than 10%. 

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N1 
R1 
PET 
N 
R 
Average 
N 
Alpha Beta 
18 
2 
0.734 
35 
6 
22.53 
0.047 
0.098 
 
Part 4 - Phase 1b Dose Optimization 
 
Up to 6 DLT evaluable subjects may be enrolled at each dose level evaluated during the 
escalation phase. The number of subjects enrolled at each dose level and the dose-step 
increments between adjacent dose levels will be based on a 3 + 3 dose escalation scheme 
(Section 3.2.2). Once the MTD or a recommended dose is estimated (with the required six 
DLT-evaluable patients at that dose level), an additional six patients will be treated at that 
dose level (for a total of twelve patients). These additional patients will allow further 
examination of the safety and tolerability of the dose and a preliminary examination of the 
efficacy of the dose. With twelve patients, if the observed response rate is 33%, the lower 
bound of a two-sided 90% confidence interval would be 0.12. The maximum width of the 
90% CI would be 0.51. 
 
We expect to accrue approximately 25 patients in Part 4. The actual number required will 
depend upon the observed safety profile, which will determine the number of subjects per 
dose level, as well as the number of dose escalations required to achieve the MTD or the 
recommended dose. 
 
8.4 Statistical Methods 
 
The statistical analyses performed for this study will be presented by study phase. For the 
escalation phase, tabulations will be provided by dose cohort and overall. For the expansion 
phase, tabulations will be provided by disease cohort and overall. Some analyses may be 
performed based on the dose escalation and expansion phases combined. 
 
The statistical analyses will be performed using SAS® version 9.2 or later (SAS Institute 
Inc, Cary NC). Programming specifications will be prepared which describe the datasets 
and variables created for this study. The datasets will be prepared using the most recent 
version of CDISC’s Study Data Tabulation Model (SDTM) and Analysis Dataset Model 
(ADaM). The source SDTM and ADaM datasets from which a statistical analysis is 
performed (including interim safety reviews) will be archived with the Sponsor. 
 
8.4.1 Subject Disposition 
 
The number of subjects included in the safety, PK, pharmacodynamic, and anti-tumor 
activity analyses will be summarized, along with the reason for exclusion from one or 
more analysis populations. Subjects discontinuing from study drug and the primary 

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reason for discontinuation will be summarized. Subjects withdrawing from study and 
the primary reason for withdrawal will be summarized in a similar manner. 
 
8.4.2 Demographics and Baseline Characteristics 
 
Descriptive summaries of demographic and baseline characteristics for all enrolled 
subjects will be tabulated by study phase – overall and by dose for Phase 1a (dose 
escalation/dose finding stage) and overall and by disease cohort for the additional 
subjects. Each cohort to be presented will be defined in the SAP to provide guidance 
for the tabulation summaries. 
 
This format of presentation will be used for the safety, efficacy, PK, immune response 
and biomarker presentations. 
 
8.4.3 Extent of Exposure 
 
The overall duration of study drug administration in weeks will be tabulated for each 
subject and summarized by study phase. For each subject, the average dose (in mg) of 
TTI-621 administered and cumulative dose (in mg) administered will be calculated. 
These data will be further summarized for each cohort by calculating the mean, 
standard deviation, median, and range of these values. The number and proportion of 
subjects with one or more dose modifications (i.e., reduction or delay) will be tabulated 
along with the reason for modification. 
 
8.4.4 Safety Analyses 
 
The SRC, as outlined in Section 3.4, will oversee all safety aspects of the study and 
make recommendations to the Sponsor. 
 
Safety will be assessed by clinical review of all relevant parameters including AEs, 
serious adverse events (SAEs), laboratory values, vital signs, ADA, and ECG results. 
Unless specified otherwise, safety will be analyzed using the Safety Analysis Set 
defined in Section 8.2. The results of these analyses will be presented by study phase. 
Some safety analyses, such as ADA, may be performed based on the dose escalation 
and expansion phases combined. 
 
Summary tables and listings will be provided for all reported treatment-emergent AEs 
(TEAEs), defined as AEs that start on or after the first administration of study drug. 
The reported AE term will be assigned a standardized preferred term using the current 
version of the Medical Dictionary for Regulatory Activities (MedDRA). 

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TEAEs will be summarized based on the number and percentage of subjects 
experiencing the event by MedDRA System Organ Class and preferred term. As 
outlined in Section 9.2, the causal relationship between the occurrence of an AE and 
study drug will be judged by the Investigator. In the event a subject experiences repeat 
episodes of the same AE, then the event with the highest severity grade and strongest 
causal relationship to study drug will be used for purposes of incidence tabulations. 
Tabular summaries will be provided for: 
• all TEAEs 
• TEAEs by study drug relationship (related, not related) and maximum severity 
grade 
• TEAEs with action of study drug delayed/interrupted or treatment reduced 
• TEAEs with action of study drug discontinued 
• SAEs 
 
For the escalation phase, the observed DLT rate in each cohort will be calculated by 
the crude proportion of subjects who experience DLT. Multiple concurrent AEs 
leading to DLT will be considered a single DLT. The estimate of the DLT rate will be 
accompanied by a 95% exact binomial confidence interval (CI). 
 
All deaths that occur on study (defined as during treatment or within 30 days of 
treatment discontinuation) will be reported in a subject listing, which will include the 
primary cause of death and the number of days between the date of the last dose of 
study drug and death. 
 
Hematology and serum chemistries will be summarized in a descriptive manner by 
calculating the mean, standard deviation, median, and range for baseline, minimum 
postbaseline value, maximum postbaseline value, average postbaseline value, and last 
postbaseline value. Laboratory values will be assigned toxicity grades when available 
using the NCI CTCAE scale and will be included as AEs if applicable. Directional 
shifts in laboratory toxicity grades (comparing baseline grade with worst postbaseline 
grade) will be analyzed using standard shift tables, presenting number and proportion 
of subjects and their maximum grade shift. Laboratory values taken during the PK 
sampling may be presented separately if appropriate; the final decision will be 
recorded in the SAP. 
 
Vital signs will be summarized in a descriptive manner by calculating the mean, 
standard deviation, median, and range in the same manner described for laboratory 

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values. The results of the 12-lead ECG assessments will be summarized in the same 
manner as described for laboratories and vital signs. 
 
The incidence, onset time, and titer of ADA will be summarized by descriptive 
statistics. The possible effects of ADA on PK (such as TTI-621 exposure as measured 
by Cmax and AUC after seroconversion), efficacy, and safety of TTI-621 will be 
explored. Details will be provided in the SAP. 
 
Prior and concomitant medications will be coded to the generic term using the current 
version of the World Health Organization Drug Dictionary and will be tabulated by 
cohort and listed by subject. 
 
8.4.5 PK Analyses 
 
The PK of TTI-621 will be estimated from concentration-time data using 
noncompartmental methods. The reporting of PK parameters will be determined based 
on the final parameter analysis on the available data. Parameters to be assessed may 
include, as appropriate, AUC0–τ, AUC0–∞, Tmax, Cmax, t1/2, clearance, and volume of 
distribution. CCI 
 
All final PK analyses will be 
defined in the final PK analysis plan and/or final SAP as appropriate. 
 
8.4.6 Efficacy Analyses 
 
Efficacy analyses will be conducted using the Full Analysis Set and, where 
appropriate, the Per-protocol Set; in addition, the overall response rate will also be 
presented for the Response-Evaluable Set. 
 
The overall response rate will be estimated for each cohort using disease-specific 
response criteria (see Section 7.14.1). The duration of response (DOR) will be 
calculated for a subject who achieves a response, and is defined as the number of 
weeks from the start date of the response (and subsequently confirmed) to the first date 
recurrent or progressive disease is documented. If a subject dies, irrespective of cause, 
without documentation of recurrent or progressive disease beforehand, then the date 
of death will be used to denote the response end date. 
 
Progression-free survival (PFS) is defined as the number of weeks from the date of the 
first dose of study drug to the earliest of documented recurrent or progressive disease 
or death due to any cause without prior progression. Leukemia-free survival (LFS) 
will be calculated in the same manner, as appropriate. 

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DOR and PFS will be summarized descriptively using the Kaplan-Meier method with 
95% CI calculated using Greenwood’s formula. Median follow-up for each endpoint 
will be estimated according to the Kaplan-Meier estimate of potential follow-up. The 
PFS rate at selected landmarks (e.g., 6 months) and corresponding 95% CIs will be 
estimated using the Kaplan-Meier method. Greenwood’s formula will be used to 
calculate the standard errors of the Kaplan-Meier estimate and upper and lower limits 
of the 95% CI. 
 
For DOR and PFS, subjects who meet one or more of the following conditions will be 
right-censored as follows: 
• subjects with no baseline or postbaseline disease assessments unless death 
occurred prior to the first planned assessment (in which case the death will be 
considered a PFS event) 
• subjects who initiate subsequent anticancer therapy in the absence of 
documented progression 
• subjects who die or have disease progression after missing 2 or more 
consecutively scheduled disease assessment visits 
• subjects who are last known to be alive and progression-free on or before the 
data cut-off date 
 
For such subjects, the progression or censoring date will be determined based on 
described conventions (Food and Drug Adminstration, 2007), as outlined in the SAP. 
 
8.4.7 
CTCL and PTCL Cohorts 
 
Phase 1b Part 3: CTCL and PTCL Cohorts 
 
Radiographic disease assessments for CTCL and PTCL will be centrally reviewed. 
Each of the 2 cohorts (CTCL and PTCL) will be evaluated separately for the potential 
for further study using the Simon 2-stage design. For the first stage, a total of 18 
response-evaluable subjects will be reviewed in each cohort; if 2 or fewer responders 
are observed per cohort, enrollment in that cohort will be terminated. Otherwise, 
enrollment will proceed to the second stage and an additional 17 response- 
evaluable subjects will be enrolled per cohort for a total of 35 response- 
evaluable subjects per cohort. At the end of the second stage, if 6 or fewer responders 
are observed per cohort, the drug will be rejected for further testing in this indication. 
If more than the required number of response-evaluable patients are available (i.e., 
>18 or >35), the first 18 or 35, respectively, would be used. 

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Phase 1b Part 4: CTCL Cohorts 
 
The subjects enrolled to phase 1b Part 4 will not require submission of scans for central 
review in real time, but might be requested by sponsor retrospectively. 
 
CCI  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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9 
ADVERSE EVENTS AND SAFETY REPORTING 
 
An AE is any unfavorable medical occurrence in a subject administered investigational 
product, whether or not thought to have a causal relationship with the treatment. An AE 
can therefore be any unfavorable and unintended sign, symptom, or disease temporally 
associated with the use of the investigational product. For the purposes of this study, events 
which are unequivocally due to disease progression should not be reported as AEs. 
Symptoms of the disease under study/lack of efficacy should not be classified as AEs as 
long as they are within normal day-to-day fluctuations or expected progression of the 
disease. 
 
The development of a new cancer should be regarded as an AE and will generally meet at 
least one of the serious AE criteria. New cancers are those that are not the primary reason 
for administration of study treatment and have been identified after the subject’s inclusion 
in this study. They do not include metastases of the original cancer. 
 
All AEs, complaints, or symptoms that occur from the start of the first dose of study 
treatment are to be recorded on the appropriate case report form (events ongoing prior to 
consent are considered medical history unless they worsen during study). Documentation 
must be supported by an entry in the subject’s source medical records. Laboratory 
abnormalities requiring treatment or considered by the Investigator to be clinically relevant 
should be reported in the case report form as an AE. Each AE is to be evaluated for 
duration, severity, and causal relationship with the investigational product. 
 
9.1 Grading and Severity of Adverse Events 
 
The Investigator will grade the severity of each AE using, when applicable, the current 
version of the CTCAE. In the event of an AE for which no grading scale exists, the 
Investigator will classify the AE as mild, moderate, severe, life-threatening/debilitating, or 
fatal, as defined below. 
 
• Mild – An event that is usually transient in nature and generally not 
interfering with normal activities 
• Moderate – An event that is sufficiently discomforting to interfere with 
normal activities 
• Severe – An event that is incapacitating with inability to work or do usual 
activity, or inability to work or perform normal daily activity 
• Life-threatening/debilitating – An event that puts the subject at immediate or 
potential risk of death, requires hospitalization, or which drastically impacts a 
subject’s well-being 

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• Fatal 
 
9.2 Adverse Event Attribution 
 
In early human trials, the relationship of an adverse event to the drug is not fully known. 
Therefore, all AEs should be considered relevant to determining DLT and to reporting 
unless the event can clearly be determined to be unrelated to the drug. The Investigator will 
determine whether each AE is considered related to investigational product or not using 
these categories: 
• Related – the time course between administration of investigational product and the 
occurrence or worsening of the AE is consistent with a possible, likely, or definite 
causal relationship and no other cause (concomitant drugs or therapies, complications, 
the primary disease, comorbidities, etc.) can be confirmed 
• Unrelated – the time course between the administration of investigational product and 
the occurrence or worsening of the AE rules out a causal relationship and another 
cause (concomitant drugs or therapies, complications, the primary disease, 
comorbidities, etc.) is confirmed 
 
The following factors should also be considered in the determination of attribution: 
preclinical pharmacology, PK, and toxicology of the investigational product, whether a 
particular response is a class effect, concomitant medications, and the primary disease as 
well as underlying intercurrent conditions. 
 
9.3 Serious Adverse Event Reporting 
 
An SAE is any untoward medical occurrence that, at any dose: 
• results in death 
• is life-threatening 
• requires hospitalization or prolongation of existing hospitalization. Note that 
some hospitalization scenarios should not be classified as SAEs, including (1) 
those that are related to performance of an efficacy measurement for the 
study, (2) diagnostic or elective surgical procedures for a pre-existing medical 
condition that has not changed and (3) scheduled therapy for the target disease 
under evaluation 
• results in disability/incapacity 
• is a congenital anomaly/birth defect 
• is an important medical event in the view of the Investigator 

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Medical or scientific judgment should be exercised in deciding whether reporting is 
appropriate in other situations, such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
subject or may require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These should also be considered serious. 
 
All SAEs must be reported to the Sponsor’s representative within 24 hours of knowledge: 
Tel: 
(615) 329-7358 
Fax: 
(866) 807-4325 
Email: 
CANN.SAE@scri-innovations.com 
 
To report the SAE, the completed report form will be sent to the Sponsor’s clinical safety 
representative within 24 hours of awareness. Incoming reports are reviewed during normal 
business hours. Additional reporting instructions and the Serious AE Report Form may be 
found in the Study Manual. 
 
The Investigator will be requested to supply detailed information regarding the event. 
SAEs must also be reported to the Institutional Review Board (IRB) or Ethics Committee 
(EC) and a copy of that report must be retained at the investigative site and filed in the 
Investigator Site File in accordance with the requirements of that institution. 
 
If a subject becomes pregnant while enrolled in the study or within 60 days after last dose, 
a Pregnancy Form should be completed and submitted to the Sponsor within 24 hours of 
the information being available, irrespective of whether or not it meets the criteria for 
expedited reporting. The Sponsor must be notified of any subject’s partner who becomes 
pregnant during the study or within 60 days after last dose. To capture information about 
a pregnancy from the partner of a male subject, the consent of the male subject’s partner 
must be obtained to collect information related to the pregnancy and outcome; the male 
subject should not be asked to provide this information. A consent form specific to this 
situation must be used. The outcome of any conception occurring should be followed and 
documented. If the pregnancy continues to term, details regarding the birth and health of 
the baby will be documented. 
 
9.4 Reporting Periods for Adverse Events and Serious Adverse Events 
 
All AEs regardless of seriousness or relationship to TTI-621 treatment that occur from the 
start of the first dose of study treatment until the safety follow-up visit (i.e., 30 days after 
the last study treatment) are to be recorded on the corresponding case report form (CRF). 
All AEs resulting in discontinuation from the study should be followed until resolution or 
stabilization. All AEs that occur during the reporting period must be recorded and followed 
until resolution unless, in the opinion of the investigator, the AE or laboratory 

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abnormality/ies are not likely to improve because of the underlying disease. In this case, 
the investigators must record his or her reasoning for this decision in the subject’s medical 
record and as a comment on the CRF. After 30 days following the last dose of study 
treatment, only AEs assessed by the investigator as treatment related or AEs of special 
interest are to be reported for a period of 1 year following the safety follow-up visit. Any 
SAE that is considered to be related to study treatment should be reported to the Sponsor 
at any time regardless of last treatment dose. If the study is closed at the time of the SAE, 
the SAE should be reported to drugsafety@trilliumtherapeutics.com. 
 
9.5 Adverse Events of Special Interest 
 
In the escalation phase of the study, Investigators should report to the Medical Monitor 
within 24 hours all clinically significant incidences of the AEs of special interest listed 
below, which are based on preclinical toxicology findings, theoretical mechanistic 
considerations, or clinical experience with TTI-621 to-date. Additional details are 
provided in the Investigator’s Brochure. 
 
Thrombocytopenia 
Thrombocytopenia is an important, identified risk for TTI-621. Transient decreases in 
platelets without clinical sequelae occurred in the 24 hours following infusion in the 
majority of subjects exposed to IV administered TTI-621. Overall 47/179 subjects (26%) 
who received IV TTI-621 in Study TTI-621-01 had AEs of thrombocytopenia/platelet 
count decreased. These findings were consistent with augmented systemic phagocytic 
clearance of platelets. Platelet counts returned to baseline levels within 1 week, enabling 
continued weekly dosing. No increased risk of bleeding was observed. Subjects 
participating in the clinical trials have frequent hematology assessments to monitor for 
potential thrombocytopenia. In addition, study protocols require dose delays or reductions 
in the event of Grade 3 or higher thrombocytopenia and allow use of megakaryopoiesis- 
stimulating agents and blood products to treat thrombocytopenia as needed. 
 
Hemorrhage 
Hemorrhage is considered a potential important risk for TTI-621. A total of 24/179 subjects 
(13%) in Study TTI-621-01 experienced 1 or more hemorrhage/bleeding events. Overall, 
20/179 subjects (11%) experienced Grade 1 or 2 events and 4 subjects (2%) had Grade 3 
events. Grade 3 hemorrhage events were considered treatment-related for 3 subjects (2%). 
No Grade 4 hemorrhage events were reported. One subject had 2 SAEs of gastrointestinal 
hemorrhage; the subject had a history of prior hemorrhage from a disease site. Subjects 
participating in the clinical trials will continue to be closely monitored for hemorrhage, 
changes in platelet counts and coagulation factors. 

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Other Cytopenias 
Other cytopenias are considered potential risks for TTI-621 and are not considered to be 
important risks. The incidence of treatment-emergent cytopenias (monocytes, neutrophils, 
and lymphocytes) was relatively low and consistent with that reported for patients with the 
diseases under study, including advanced hematologic malignancies. 
 
Infusion-Related Reactions 
Infusion- and injection site-related reactions are important, identified risk for TTI-621. The 
majority of subjects exposed to TTI-621 experienced mild-to-moderate infusion- or 
injection site-related reactions. Symptoms of infusion-related reactions include chills, 
fever, rash, urticaria, dyspnea, hypotension, and/or nausea/vomiting. Symptoms of 
injection site-related reactions, include injection site pain, bruising, erythema, and pruritus. 
The study protocols mandate that all subjects must be premedicated with an antihistamine 
and acetaminophen prior to TTI-621 administration. In addition, subjects will continue to 
be followed closely for the development of ADA in accordance with the schedule of 
assessments in the study protocols, as well as for infusion- and injection site-related 
reactions. 
 
Anemia 
Anemia is considered a potential risk for TTI-621 and is not considered to be an important 
risk. Treatment-related, Grade 3 anemia was reported in subjects receiving IV TTI-621. 
The overall incidence was consistent with that reported for patients with advanced 
hematologic malignancies and transfusion-dependence. In addition, events most frequently 
occurred in subjects with primary hematologic malignancies in which anemia is frequently 
caused by the malignancy itself (AML, MDS, MM, and advanced HL). No serious events 
of anemia were reported and anemia did not appear to be associated with increased 
destruction of erythrocytes. Anemia was not observed in subjects receiving intratumoral 
TTI-621. 
 
ALT/AST Elevations 
ALT/AST elevations are considered potential risks for TTI-621 and are not considered to 
be important risks. Increased ALT and AST were observed in toxicology study in 
cynomolgus monkeys, in association with increased total and direct bilirubin. 
Transaminase increases have been infrequently reported as TEAEs on Study TTI-621-01; 
5/179 subjects (3%) had ALT and AST elevations, and 1 additional subject (1%) was 
reported with an AST increase. The maximum severity ALT/AST increase was Grade 1–2 
for 3 subjects, and Grade 3–4 for 3 subjects; none of these events were reported as SAEs. 
Liver enzymes of subjects participating in the clinical trials should continue to be 
monitored closely during treatment. 

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Other 
Although the individual components of the TTI-621 fusion protein are human, the juncture 
between the components may be sensed as foreign by the immune system. Therefore, as 
with other biological therapeutics, the potential exists for the emergence of ADA. Although 
the Investigators cannot assess the development of ADA directly, serial samples will be 
taken throughout the exposure period to measure ADA. 

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10 ETHICAL AND ADMINISTRATIVE CONSIDERATIONS 
 
10.1 Regulatory Authority Approval 
 
This study will be conducted in accordance with applicable national and local regulations 
and guidelines, Good Clinical Practice (GCP)-International Conference on Harmonisation 
(ICH) guidelines (Integrated Addendum To ICH E6(R1): Guideline For Good Clinical 
Practice, E6(R2), Current Step 4 version (2016), the National Statement on Ethical Conduct 
in Human Research 2007, and The Declaration of Helsinki (Brazil, 2013). 
 
10.2 Ethics Approval 
 
Prior to initiation of the study, the Investigator will submit the study protocol, Informed 
Consent, and any other document that may be requested by the designated IRB/EC for 
review and approval. The Investigator will request that the IRB/EC provide written 
approval of the study and will keep on file records of approval of all documents pertaining 
to this study. 
 
The IRB/EC will be notified of any amendments to the protocol. With the exception of any 
amendment that is imperative to the protection of subject safety, protocol amendments 
require approval by the IRB/EC prior to being implemented by the site. 
 
10.3 Informed Consent and Protected Health Information 
 
Written informed consent and authorization of use and disclosure of protected health 
information must be obtained from each subject (or the subject’s legal representative) prior 
to performing any study evaluation. The authorization for use and disclosure of protected 
health information must contain the elements required by 45 CFR 164.508(b) for valid 
authorizations. The proposed informed consent form, which must be in compliance with 
regulatory regulations, must have been reviewed and approved by the Sponsor and the 
study IRB/EC prior to initiation of the study. The proposed informed consent form should 
contain the 20 elements of the informed consent described in ICH E6 4.8. These 
requirements are in accordance the Code of Federal Regulations (21 CFR 50.25) and the 
Declaration of Helsinki. 
 
Each subject will be given a copy of the signed Informed Consent Form. The source 
documents for each subject shall document that the Informed Consent was obtained prior 
to participation. The subjects will also be instructed that they are free to withdraw their 
consent and discontinue their participation in the study at any time without prejudice. Prior 

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to the start of the study, the Principal Investigator will provide the Sponsor with an actual 
Informed Consent Form approved by the IRB/EC for use during the study. 
 
Any amendments to the Informed Consent Form must be approved by the Sponsor and the 
IRB/EC. Consent will be verified and countersigned by the Principal Investigator or 
designee. The sample Informed Consent prepared by the Sponsor may be found in the 
Study Manual. 
 
10.4 Clinical Supplies 
 
The Principal Investigator will be responsible for the dispensing, inventory, and 
accountability of all clinical supplies, ensuring that accepted medical and pharmaceutical 
practices are followed. An accurate and timely accountability record of the disposition of 
all clinical supplies must be maintained. The supplies and inventory record must be made 
available for inspection by the Sponsor or the designated Sponsor’s representative upon 
request. Under no circumstances will the Principal Investigator allow the investigational 
product to be used other than as directed by this protocol. 
 
Additional accountability procedures are fully outlined in the Study Manual. 
 
10.5 Data Management and Study Monitoring 
 
Data will be recorded at the site on source documents and reviewed by the Sponsor’s 
monitor during periodic visits, who will verify data recorded in the case report forms with 
source documents. Additional instructions may be found in the Study Manual. 
 
The Sponsor or its representatives will periodically visit the clinical site during the conduct 
of the study in accordance with applicable regulations and GCP. These activities will be 
done in order to verify that the data are authentic, accurate, and complete; that the safety 
and rights of the subject are being protected; and that the study is conducted in accordance 
with the currently approved protocol, GCP, and all applicable regulatory requirements. 
Additional instructions are outlined in the Study Manual. 
 
10.6 Records Retention 
 
The Principal Investigator will retain copies of the approved protocol, completed case 
report forms, informed consent documents, relevant source documents, and all other 
supporting documentation related to the project for a period of at least 2 years after the last 
approval of a marketing application for TTI-621 in an ICH region or at least 2 years after 
the formal discontinuation of the clinical development of the investigational product. 
However, for some regulatory agencies, documentation may be required to be maintained 

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for up to 25 years. In order to ensure that regulatory requirements are met, the Principal 
Investigator agrees that copies of study records will be retained until the Sponsor’s written 
agreement for disposal has been obtained. 

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12 APPENDICES 

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Appendix A. Definitions of Indolent vs Aggressive B-cell Lymphomas and T cell 
lymphomas* 
 
Indolent B-cell lymphoma (IBCL) 
 
• Follicular lymphoma (follicular small-cleaved cell [grade 1], follicular mixed small- 
cleaved and large cell [grade 2], and diffuse small-cleaved cell) 
• Extranodal marginal zone B-cell lymphoma (MALT lymphoma) 
• Nodal marginal zone B-cell lymphoma (monocytoid B-cell lymphoma) 
• Splenic marginal zone lymphoma (splenic lymphoma with villous lymphocytes) 
• Cutaneous B-cell lymphoma 
 
Aggressive B-cell lymphoma (ABCL) 
 
• Diffuse large cell lymphoma (includes diffuse mixed-cell, diffuse large cell, 
immunoblastic, and T-cell rich large B-cell lymphoma) 
• Precursor B-cell lymphoblastic lymphoma 
• Mantle cell lymphoma 
• True histiocytic lymphoma 
• Primary effusion lymphoma 
• Burkitt lymphoma 
• Transformed lymphoma 
• Primary mediastinal B-cell lymphoma (PMBL) 
 
Cutaneous T-cell lymphoma 
• Mycosis fungoides with and without transformation 
• Sézary syndrome 
 
Peripheral T-cell lymphoma 
• Adult T-cell leukemia/lymphoma 
• Extranodal NK-/T-cell lymphoma, nasal type 
• Enteropathy-associated T-cell lymphoma 
• Monomorphic epitheliotropic intestinal T-cell lymphoma 
• Hepatosplenic T-cell lymphoma 

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• Subcutaneous panniculitis-like T-cell lymphoma 
• Primary cutaneous anaplastic large cell lymphoma 
• Primary cutaneous gamma delta+ T-cell lymphoma 
• Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma 
• Primary cutaneous acral CD8+ T-cell lymphoma 
• Peripheral T-cell lymphoma, NOS 
• Angioimmunoblastic T-cell lymphoma 
• Follicular T-cell lymphoma 
• Nodal peripheral T-cell lymphoma with TFH phenotype 
• Anaplastic large-cell lymphoma, ALK+ 
• Anaplastic large-cell lymphoma, ALK- 
• Breast implant–associated anaplastic large-cell lymphoma 
 
* This list is representative and is not intended to be exhaustive/include all types of 
indolent or aggressive B-cell or T-cell lymphomas that may be enrolled on study 

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Fully active, able to carry on all predisease performance without restriction 
Restricted in physically strenuous activity, but ambulatory and able to carry out work of a 
light or sedentary nature, e.g., light house work, office work 
Ambulatory and capable of all self-care, but unable to carry out any work activities, up and 
about more than 50% of waking hours 
Capable of only limited self-care, confined to bed or chair more than 50% of waking 
hours 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair 
Dead 
 
 
 
 
 
 
 
 
 
Description 
Grade 
Appendix B. Eastern Cooperative Oncology Group Performance Scale 
 
Source: (Oken et al., 1982) 

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Appendix C. Grading Scale for Skin Symptoms of Graft-vs-host Disease 
 
0 
1 
2 
3 
4 
Acute 
No rash due to 
Maculopapular 
Maculopapular 
Maculopapular 
Generalized 
GVHD 
rash < 25% of 
rash 25–50% of 
rash > 50% of 
erythroderma 
body surface 
body surface 
body surface 
with bullous 
formation 
Chronic a 
No symptoms 
< 18% BSA 
19–50% BSA or 
> 50% BSA or 
- 
with disease 
involvement with 
deep sclerotic 
signs but no 
superficial sclerotic 
features (unable to 
sclerotic 
features (able to 
pinch) or impaired 
features 
pinch) 
mobility, 
ulceration, or 
severe pruritus 
a Clinical features may include maculopapular rash, lichen planus-like features, papulosquamous lesion or ichthyosis, 
hyper- or hypopigmentation, keratosis pilaris, erythema, erythroderma, poikiloderma, sclerotic features, pruritus, hair 
involvement, nail involvement 
BSA = body surface area; GVHD = graft-vs-host-disease 

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Appendix D. Summary of Tests and Observations 
Appendix D. Table 1. 
Phase 1b - Part 2 and 3: Schedule of Assessments (additional assessments as clinically indicated) 
 
Assessments 
≤ 
-D14 
W1 
D1 
Prea 
W1 
D1 
Post 
W2 
D1 
W3 
D1 
W4 
D1 
W5 
D1 
W6 
D1 
W7 
D1 
W8 
D1 
Pre 
W8 
D1 
Post 
W9 + D1 
Intra 
Sub 
Doseg 
Intens 
EOT 
SFUe 
LTFU 
Except where otherwise noted these visit pre-dose assessments can be performed up to 24 hours pre-infusion (see also Section 7). 
All scheduled treatment days have a window of ± 2 days 
≤1 
Wkj 
±2D 
Q4 
(±1 wk) 
Informed consent 
(within 30 days) 
X 
Medical, malignancy 
history 
X 
Physical examb, 
ECOG 
X 
preb 
preb 
preb 
preb 
preb 
preb Wk 12 then Q4 wks 
X 
Xb 
Body weight 
X 
pre 
pre 
pre 
pre 
pre 
pre 
pre 
pre 
pre Wk 10 + Q2 wks q 
X 
X 
Vital signsc 
* Combo arms – 
done for both 
infusions if >1 hr 
apart 
X 
*pre 
(*1 hr 
[EOI]), 
2 hr, 
4 hr 
* pre, 
1hr 
(EOI) 
* pre, 
1 hr 
(EOI) 
* pre, 
1 hr 
(EOI) 
pre 
pre 
pre 
pre 
pre 
pre 
X 
X 
Disease assessment 
(incl. photographs)d 
Xk 
post 
post Wk16, 24 
+Q12 wkso 
Xi 
12-lead ECG 
X 
pre 
post m 
pre 
pre on Wk16 & 24 
X 
QOL by FACT-G (all 
subjects), SKINDX29 
(CTCL only) 
X 
post 
post Wk16, 24 
+ Q12 wks 
X 
TTI-621 infusions 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X (TEAE) 
Prior/concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Survival Status 
X 
Subsequent anticancer 
therapies 
X 
D = Day; Post = after start of TTI-621 infusion, EOT = end of treatment visit; SFU = safety follow-up visit; LTFU = long term safety follow-up visit; EOI = end of infusion (1 hr) 

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Assessments 
≤ 
-D14 
W1 
D1 
Prea 
W1 
D1 
Post 
W2 
D1 
W3 
D1 
W4 
D1 
W5 
D1 
W6 
D1 
W7 
D1 
W8 
D1 
Pre 
W8 
D1 
Post 
W9 + 
D1 
Intra 
Sub 
Doseg Intens 
EOT 
SFUe 
LTFU 
Dose Intensification Weeks for phase 1b Part 3 (see Section 
6.5.4) 
Except where otherwise noted the visit pre-dose assessments can be performed up to 24 hours pre-infusion 
(see also Section 7). All scheduled treatment days have a window of ± 2 days 
≤1 
Wkj 
± 2D 
Q4 
(±1 wk) 
Local Laboratory Assessments 
Hepatitis B/C panel 
X 
Pregnancy test 
(women of 
childbearing 
potential) 
X 
(serum) 
pre 
(serum or 
urine) 
pre 
(serum or 
urine) 
pre Wk 12 
then Q4 wks 
(serum or urine) 
Hematology 
X 
pre 
1 hr, 
(EOI) 
2 hr, 
4 hr 
pre 
pre 
pre 
pre 
pre 
pre 
pre 
pre 
4 hr 
X 
X 
WBC with automated 5-part differential, hemoglobin, RBC, absolute reticulocytes, platelets 
Serum chemistries 
X 
pre 
pre 
pre 
pre 
pre 
pre Wk 12 
then Q4 wks 
4 hr 
X 
X 
Alkaline phosphatase, albumin, ALT, AST, bilirubin (direct, indirect, and total), BUN, creatinine, glucose, LDH, total protein, uric acid, and electrolytes (sodium, 
potassium, calcium, chloride, bicarbonate, phosphorus) 
TSH (for 
Nivolumab 
combination only) 
X 
pre Wk12 + 
Q12 wks 
X 
X 
Coagulation panel 
X 
X 
Prothrombin time, partial thromboplastin time, INR, fibrinogen 
Urinalysis 
pre 
pre 
X 
Including color, appearance, specific gravity, pH, glucose, bilirubin, ketones, occult blood, and protein 
D = Day; Post = after start of TTI-621 infusion; EOT = end of treatment visit; SFU = safety follow-up visit; LTFU = long term safety follow-up visit; EOI = end of infusion (1 hr) 

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Assessments 
≤ 
-D14 
W1 
D 1 
Prea 
W1 
D1 
Post 
W2 
D1 
W3 
D1 
W4 
D1 
W5 
D1 
W6 
D1 
W7 
D1 
W8 
D1 
Pre 
W8 
D1 
Post 
W9 + 
D1 
Intra 
Sub 
Doseg Intens 
EOT 
SFUe 
LTFU 
Dose Intensification Weeks for phase 1b Part 3 (see Section 6.5.4) 
Except where otherwise noted pre-dose assessments can be performed up to 24 hours pre-infusion 
(see also Section 7). All scheduled treatment days have a window of ±2 days. 
≤1 
Wkj 
± 2D 
Q4 
(±1 wk) 
Central Laboratory Assessments 
PK 
pre 
1 hr 
(EOI) 
2hr, 
4hr, 
D2 
pre 
pre 
pre 
pre 
pre 
pre 
pre 
1 hr 
(EOI) 
2 hr, 
4 hr 
D2, 
D4 
pre Wk 9, 10, 
11, 12, 13, 
14, 15 & 16 
1 hr (EOI), 
4 hr 
X 
Cyto/Chemokine 
pre 
1 hr 
(EOI) 
4 hr 
pre 
pre 
1 hr 
(EOI), 
4 hr, 
D2 
pre Wk 9 
X 
ADA 
pre 
pre 
pre 
pre Wk 12 
then Q4 wks 
X 
X 
Xf 
TCR Vβp 
pre 
pre 
pre Wk 16 
Anti-Tumor 
Antibodies 
pre 
pre Wk 16 
Peripheral Receptor 
Occupancy (blood)l 
pre 
1 hr 
(EOI) 
pre 
pre 
1 hr 
(EOI) 
pre Wk 9 
pre, 
1 hr (EOI) 
Receptor Occupancy 
(bone marrow)p 
pren 
pren 
Innate and Adaptive 
Response Assay 
pre 
pre 
X 
Tissue for 
biomarkersp 
Xh 
prep 
CTCL 
O: all 
other 
diagnoses 
prep Wk 16 
(CTCL) 
Tissue for central 
pathology 
Xr 
D = Day; Post = after start of TTI-621 infusion; EOT = end of treatment visit; SFU = safety follow-up visit; LTFU = long term safety follow-up visit; 
O = optional, EOI = end of infusion (1 hr) 

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Footnotes 
a 
Screening laboratories may be used as pre-dose baseline if within 3 days of Day 1 
b 
Review of systems and physical exam: breast/chest, extremities, head/ears/eyes/nose/throat, lymph nodes, musculoskeletal, pulmonary, skin, height. Symptom driven on all 
treatment weeks and SFU. Full exam at screening and EOT. 
c 
Including heart rate, respiratory rate, body temperature. 
d  See Appendix D. Table 3 and Section 7.14.1 for further details, including disease assessment scales. For CTCL and PTCL subjects, central submission of radiographic disease 
assessment is required. Also for CTCL subjects only: mSWAT, CAILS (if applicable) and photographs. All response assessments should be performed at the end of the indicated 
weeks and the time points have a window of ±1 week. 
e 
If treatment-emergent abnormalities are present at end of treatment, repeat pertinent labs or studies 
f 
Subjects who are seropositive at end of safety follow-up should be monitored at least quarterly for 1 year post study to assess persistence of antibodies. 
g 
If not already included in the regular scheduled visit assessment, these are to be performed for dose-intensified subjects in addition to the regularly scheduled visit assessments. 
Dose intensification to occur from Week 3 to Week 8. After Week 9, additional dose intensification is not permitted. 
h 
For subjects with SS, peripheral blood is acceptable, if a biopsy is not possible. For all other subjects fresh tumor biopsy required if feasible. Archival tissue at screening 
acceptable, if biopsy not feasible. 
i 
If not done in prior 8 weeks 
j 
Within 1 week following the final dose of TTI-621 (or at the time of premature discontinuation of treatment) 
k 
Within 28 days of planned start of treatment 
l 
Blood for peripheral receptor occupancy to be drawn pre-infusion and 1 hr post-infusion (EOI) at each dose-intensification and at Week 8 
m 
12-lead ECG within approximately 30 minutes of completion of infusion (i.e., 60–90 minutes after Time 0) 
n 
For subjects with marrow based disease only, at time of disease assessments 
o 
Or at the time of observed or suspected clinical progression 
p 
±1 week to align with response assessments 
q 
After Week 8, the weight taken at the prior visit may be used to calculate dose (e.g. weight at Week 8 used for Week 9 dosing) 
r  Tumor tissue will be submitted for central review for subjects with CTCL (not including Sezary Syndrome) and PTCL. For Sezary Syndrome patients, peripheral blood and 
blood smears are required at screening, all response assessment time points and at end of treatment (See Appendix D. Table 3). Central disease confirmation not required for 
enrollment. 
s  For patients who have been given weekly infusion of TTI-621 for more than a year and are receiving clinical benefit (objective response or clinically meaningful long-term 
stable disease), investigators may exercise their discretion to reduce the dosing frequency from weekly to bi-weekly following the discussion and approval from the sponsor or 
designees. 

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Appendix D. Table 2. 
Phase 1b - Part 4 Dose Optimization: Schedule of Assessments 
 
Assessments 
≤ 
-D14 
W1a 
W2 
D1 
W3 
D1 
W4 
D1 
W5 
D1 
W6 
D1 
W7 
D1 
W8 
D1 
W9 + D1 
EOT 
SFUe 
LTFU 
DLT evaluation Period 
Except where otherwise noted these visit pre-dose assessments can be performed up to 24 hours pre-infusion (see also Section 7). 
All scheduled treatment days have a window of ± 2 days 
≤1 
Wk h 
±2D 
Q4 (±1 
wk) 
Informed consent 
(within 30 days) 
X 
Medical, 
malignancy history 
X 
Physical examb, 
ECOG 
X 
prem 
prem 
prem 
prem 
prem 
prem 
prem 
prem 
prem 
X 
Xm 
Body weight 
X 
pre 
pre 
pre 
pre 
pre 
pre 
pre 
pre 
pre Wk 10 + Q2 wksl 
X 
X 
 
Vital signsc 
X 
pre, 
(1 
hr 
[EOI]), 
2 hr, 
4 hr 
pre 
pre 
pre 
pre 
pre 
pre 
pre 
pre 
X 
X 
Disease assessment 
(incl. photographs)d 
Xi 
post 
post Wk16, 24 
+Q12 wks k 
Xg 
12-lead ECG 
X 
pre and 
postj 
pre 
pre 
pre Wk12 + Q4 weeks 
X 
QOL by FACT-G, 
SKINDX29 
X 
post 
post Wk16, 24 
+Q12 wks k 
X 
TTI-621 infusions 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AEs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
(TEAE) 
Prior/concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Survival Status 
X 
Subsequent 
anticancer therapies 
X 
D = Day; Post = after start of TTI-621 infusion, EOT = end of treatment visit; SFU = safety follow-up visit; LTFU = long term safety follow-up visit; EOI = end of infusion (1 hr) 

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Assessments 
≤ 
-D14 
W1a 
W2 
D1 
W3 
D1 
W4 
D1 
W5 
D1 
W6 
D1 
W7 
D1 
W8 
D1 
W9 + D1 
EOT 
SFUe 
LTFU 
DLT Evaluation Period 
Except where otherwise noted the visit pre-dose assessments can be performed up to 24 hours pre-infusion 
(see also Section 7). All scheduled treatment days have a window of ± 2 days 
≤1 
Wk h 
± 2D 
Q4 (±1 
wk) 
Local Laboratory Assessments 
Hepatitis B/C panel 
X 
Pregnancy test 
(women of 
childbearing 
potential) 
X 
(serum) 
pre 
(serum or 
urine) 
pre 
(serum or 
urine) 
pre Wk 12 then Q4 wks 
(serum or urine) 
 
 
Hematology n 
X 
pre, 
1 hr, (EOI), 
2 hr, 
4 hr 
D2, D4 
pre, 
4 hr, 
(D2n* 
if clinically 
indicated) 
pre, 
4 hr, 
(D2n* 
if clinically 
indicated) 
pre 
pre 
pre 
pre 
pre 
pre 
X 
X 
WBC with automated 5-part differential, hemoglobin, RBC, absolute reticulocytes, platelets 
Serum chemistries 
X 
pre 
pre 
pre 
pre 
pre 
pre Wk 12 then Q4 wks 
X 
X 
Alkaline phosphatase, albumin, ALT, AST, bilirubin (direct, indirect, and total), BUN, creatinine, glucose, LDH, total protein, uric acid, and elec trolytes (sodium, potassium, 
calcium, chloride, bicarbonate, phosphorus) 
Coagulation panel 
X 
pre 
pre 
pre 
pre 
pre 
pre Wk 12, W16 then Q4 wks P 
X 
Prothrombin time, partial thromboplastin time, INR, fibrinogen 
Urinalysis 
pre 
X 
Including color, appearance, specific gravity, pH, glucose, bilirubin, ketones, occult blood, and protein 
D = Day; Post = after start of TTI-621 infusion; EOT = end of treatment visit; SFU = safety follow-up visit; LTFU = long term safety follow-up visit; EOI = end of infusion (1 hr) 

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Assessments 
≤ 
-D14 
W1a 
W2 D1 
W3 D1 
W4 D1 
W5 D1 
W6 
W7 D1 
W8 D1 
W9 + D1 
EOT 
SFUe 
LTFU 
DLT Evaluation Period 
Except where otherwise noted pre-dose assessments can be performed up to 24 hours pre-infusion (see also Section 7). All scheduled treatment days 
have a window of ±2 days. 
≤1 
Wk h 
± 2D 
Q4 
(±1 wk) 
Central Laboratory Assessments 
 
PKo 
pre 
1 hr (EOI) 
2hr, 
4hr, 
D2, D4 
pre 
pre 
pre 
pre 
pre, 
1 hr (EOI) 
2 hr, 
4 hr 
D2,D4 
pre 
pre 
pre Wk 9, 10, 11, 12, 13, 14, 15 & 16 
X 
ADA 
pre 
pre 
pre 
pre Wk 12 then Q4 wks 
X 
X 
Xf 
Peripheral Receptor 
Occupancy (blood) 
q 
pre, 
1 hr (EOI) 
pre 
pre, 
1 hr (EOI) 
pre 
pre Wk 12 and 16 
Tissue for 
biomarkers r 
X 
pre 
pre Wk 16 
D = Day; Post = after start of TTI-621 infusion; EOT = end of treatment visit; SFU = safety follow-up visit; LTFU = long term safety follow-up visit; O = optional, EOI = end of infusion (1 hr) 
Footnotes 
a 
Screening laboratories may be used as pre-dose baseline if within 3 days of Day 1 
b 
Review of systems and physical exam: breast/chest, extremities, head/ears/eyes/nose/throat, lymph nodes, musculoskeletal, pulmonary, skin, height. Symptom driven on all 
treatment weeks and SFU. Full exam at screening and EOT. 
c 
Including heart rate, respiratory rate, body temperature. 
d  See Appendix D. Table 3 and Section 7.14.1 for further details, including disease assessment scales. mSWAT, CAILS (if applicable) and photographs are required. All response 
assessments should be performed at the end of the indicated weeks and the time points have a window of ±1 week. The subjects enrolled to phase 1b Part 4 cohorts will not 
require submission of scans for central review in real time but retrospective submissions might be requested by sponsor. 
e  If treatment-emergent abnormalities are present at end of treatment, repeat pertinent labs or studies 
f 
Subjects who are seropositive at end of safety follow-up should be monitored at least quarterly for 1 year post study to assess persistence of antibodies. 
g 
If not done in prior 8 weeks 
h 
Within 1 week following the final dose of TTI-621 (or at the time of premature discontinuation of treatment) 
i 
Within 28 days of planned start of treatment 
j 
12-lead ECG within approximately 30 minutes of completion of infusion (i.e., 60–90 minutes after Time 0) 
k 
Or at the time of observed or suspected clinical progression 
l 
After Week 8, the weight taken at the prior visit may be used to calculate dose (e.g. weight at Week 8 used for Week 9 dosing) 
m 
Symptom driven physical examination 
n 
Hematology: *The week 2 and week 3 day 2 assessments are only required if clinically indicated in the event that ≥ Grade 4 thrombocytopenia is observed on day 1 or there 
are any other clinical conditions indicated for a follow-up lab assessment at the investigator discretion. If a priming regimen is required, refer to Appendix F. 
o 
PK: if a priming regimen is required, refer to Appendix F 
p 
Symptom driven coagulation panel from week 16 onward 

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q  Peripheral Receptor Occupancy (blood): if a priming regimen is required, refer to Appendix F 
r  Fresh tumor biopsy required if feasible. Peripheral blood is acceptable for subjects with SS. Archival tissue at screening acceptable, if biopsy not feasible. 
s  For patients who have been given weekly infusion of TTI-621 for more than a year and are receiving clinical benefit (objective response or clinically meaningful long-term 
stable disease), investigators may exercise their discretion to reduce the dosing frequency from weekly to bi-weekly following the discussion and approval from the sponsor or 
designees. 

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Appendix D. Table 3. 
Response Assessments by Malignancy Type 
Radiographic disease assessments for CTCL and PTCL will be submitted for central review for those subjects enrolled to phase 1b Part 
3. The subjects enrolled to phase 1b Part 4 cohorts will not require submission of scans for central review in real time but retrospective 
submissions might be requested by sponsor. 
 
Central photography will be utilized for CTCL patients for both phase 1b Part 3 and Part 4. 
 
Disease and Assessments 
Screening 
Wk 8 l 
Wk 12 l 
Wk 16 l + 
EOT 
Lymphoma (including PTCL) 
PET/CT scan (PTCL: local and central review for phase 1b 
Part 3 only) 
X 
X 
Weeks 16, 24, and every 12 weeks thereafter 
X 
Spleen assessment 
X 
X 
Weeks 16, 24, and every 12 weeks thereafter 
X 
Bone marrow biopsy a 
X 
X 
Weeks 16, 24, and every 12 weeks thereafter 
X 
Cutaneous T-Cell Lymphoma 
Skin assessment (mSWAT and CAILS) 
X 
X 
Weeks 16, 24, and every 12 weeks thereafter 
X 
Radiographic imaging (central for CTCL for phase 1b Part 3 
only)b 
X 
X 
Weeks 16, 24, and every 12 weeks thereafter 
X 
Photography of disease (central for CTCL for phase 1b Part 
3 and Part 4 )k 
X 
X 
Weeks 16, 24, and every 12 weeks thereafter 
X 
Blood assessment (pathology and flow cytometry): local and 
central (CTCL) for phase 1b Part 3 only c 
X 
X 
Weeks 16, 24, and every 12 weeks thereafter 
X 
Spleen and liver assessment 
X 
X 
Weeks 16, 24, and every 12 weeks thereafter 
X 
Acute Leukemia (AML and ALL) 
Bone marrow aspirate or biopsy d 
X 
X 
Weeks 16, 24, and every 12 weeks thereafter 
X 
Cytogenetic evaluation e 
X 
X 
Weeks 16, 24, and every 12 weeks thereafter 
X 
Molecular and/or flow cytometric evaluation f 
X 
X 
Weeks 16, 24, and every 12 weeks thereafter 
X 
Myelodysplastic Syndrome g 
Bone marrow biopsy 
X 
X 
Week 16, 24, and every 12 weeks thereafter 
X 
Peripheral blood (including blasts) 
X 
X 
Week 16, 24, and every 12 weeks thereafter 
X 
Cytogenetic evaluation h 
X 
X 
Week 16, 24, and every 12 weeks thereafter 
X 
MDS/MPN Overlap (including CMML) 

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Disease and Assessments 
Screening 
Wk 8 l 
Wk 12 l 
Wk 16 l + 
EOT 
Bone marrow biopsy 
X 
X 
Week 16, 24, and every 12 weeks thereafter 
X 
Peripheral blood (including blasts and neutrophil precursors) 
X 
X 
Week 16, 24, and every 12 weeks thereafter 
X 
Spleen and liver assessment 
X 
X 
Week 16, 24, and every 12 weeks thereafter 
X 
Cytogenetic evaluation h 
X 
X 
Week 16, 24, and every 12 weeks thereafter 
X 
Myelofibrosis i 
Bone marrow biopsy 
X 
X 
Week 24 and every 12 weeks thereafter 
X 
Peripheral blood (including immature myeloid cells) 
X 
X 
Week 24 and every 12 weeks thereafter 
X 
Spleen and liver assessment 
X 
X 
Week 24 and every 12 weeks thereafter 
X 
Essential Thrombocythemia and Polycythemia Vera (ET, 
PV) i 
Bone marrow biopsy 
X 
X 
Week 24 and every 12 weeks thereafter 
X 
Spleen and liver assessment 
X 
X 
Week 24 and every 12 weeks thereafter 
X 
Small Cell Lung Cancer 
Radiographic imaging j 
X 
X 
Week 16 and every 8 weeks thereafter 
X 
a A bone marrow biopsy for lymphomas should be completed if clinically indicated. 
b Radiographic imaging should only be performed if visceral lesions were identified at screening and to confirm a response after screening and submitted for central review. 
c The blood assessment includes Sézary cell counts and/or flow cytometry for CD4/CD8, CD4+ CD7-, or CD4+ CD26- cells. Blood and pathology submitted for central review 
dA bone marrow aspirate or biopsy is required to establish CR, CRi, PR or relapse per IWG Criteria (Cheson et al, 2003). A bone marrow evaluation is also required when the 
peripheral blood has < 10% peripheral leukemic blasts. 
e In order to document a cytogenetic complete remission (CRc), reversion to a normal karyotype must occur; cytogenetics not necessary if normal karyotype. 
f In the event of a CR, real-time quantitative PCR (RT-PCR) and flow cytometry should be performed to monitor minimal residual disease (MRD) and to document molecular 
complete remission (CRm); for subjects in CR, consult with Medical Monitor to review specific tests indicated. 
g All criteria must be met and documented for a minimum of 4 weeks to define a complete remission, partial remission, or marrow CR. 
h At least 20 analyzable metaphases are required to diagnose or exclude the presence of a cytogenetic abnormality; for subjects in CR, consult with Medical Monitor to review 
specific tests indicated. 
i To confirm a response, all criteria must be met and documented for a minimum of 12 weeks; for subjects in CR, consult with Medical Monitor to review specific tests indicated. 
j CT scans of the chest, abdomen, and pelvis should be conducted every 8 weeks. CT/MRI of the brain should be performed if abnormal at baseline 
k Canfield photography of target lesions should be conducted and submitted for central storage 
l All time points are relative to the end of the respective weeks (ie. end of week 8) 

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Appendix E. Cockcroft-Gault Equation for Calculating Estimated Creatinine  Clearance 
 
Serum creatinine units 
Gender 
Estimated Creatinine Clearance (mL/min) 
mg/dL 
Male 
(140 − subject age [years]) × subject weight (kg) 
 
72 × subject serum creatinine (mg⁄dL) 
Female 
(140 − subject age [years]) × subject weight (kg) × 0.85 
 
72 × subject serum creatinine (mg⁄dL) 
µM/dL 
Male 
(140 − subject age [years]) × subject weight (kg) × 1.23 
 
Subject serum creatinine (µM⁄dL) 
Female 
(140 − subject age [years]) × subject weight (kg) × 1.04 
 
Subject serum creatinine (µM⁄dL) 

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Appendix F. Expansion Phase 1b Part 4 Dose Regimen Scenarios for Hematology, PK and 
Receptor Occupancy (blood) 
 
Sample Collection at Weeks 1 – 7 for Cohorts With Priming Regimens 
 
Example: Sample Collections for Cohorts With Priming (first highest stable dose at week 
2, priming for 1 week) 
 
Assessment 
Week 1 
Week 2 
Week 3 
Week 4 
Week 5 
Week 6 
Week 7 
Dose 
Priming Dose* 
Highest Stable Dose 
Hematology 
Pre, 4 hr 
Pre, 1 hr 
(EOI), 2hr, 
4hr, D2, D4 
Pre, 
4 hr, 
***D2 
Pre 
Pre 
Pre 
Pre 
PK 
Pre, 1 hr (EOI) 
Pre, 1 hr 
(EOI), 2hr, 
4hr, D2, D4 
Pre 
Pre 
Pre 
**Pre, 1 
hr (EOI), 
2hr, 
4hr, D2, 
D4 
Pre 
Receptor 
Occupancy 
(blood) 
Pre, 1 hr (EOI) 
Pre, 1 hr (EOI) 
Pre 
**Pre, 1 
hr (EOI) 
Pre 
* Priming regimens with more than 1 priming week will follow the same pattern as included for Week 1, whereby 
additional priming dose weeks will be added with the same sampling timepoints for hematology, PK and receptor 
occupancy (blood) as at week 1. 
** The PK and receptor occupancy serial samples will remain at week 6 irrespective of the number of priming 
weeks 
*** The day 2 assessments are only required if clinically indicated in the event that ≥ Grade 4 thrombocytopenia 
is observed on day 1 or there are any other clinical conditions indicated for a follow-up lab at the investigator 
discretion 

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CCI 
 

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CCI 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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CCI 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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CCI 
 

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CCI 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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CCI 
 
 
 
 
 
 
 
 
 
 

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CCI 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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CCI 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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CCI 
 
 
 
 

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CCI 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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CCI 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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CCI 
 
 
 
 
 
 
 
 

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