Conditions: Lymphoma, Large B-Cell, Diffuse Lymphoma, Mantle-Cell Lymphoma, Follicular Cancer Neoplasm Tumor Lymphoma, Malignant Lymphoma, B-cell Lymphoma, Non-Hodgkin B-Cell Chronic Lymphocytic Leukemia B-Cell Leukemia, Chronic B-Lymphocytic Leukemia, Chronic Chronic Lymphocytic Leukemia Leukemia, Lymphocytic, Chronic Leukemia, Lymphocytic, Chronic, B Cell Myelofibrosis Chronic Idiopathic Myelofibrosis Idiopathic Myelofibrosis Lymphoma, T Cell, Peripheral Peripheral T-Cell Lymphoma T-Cell Lymphoma, Peripheral
Keywords: DLBCL FL MCL PTCL MF CLL
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 51
Healthy volunteers: no

Brief summary:
This study is a dose escalation, and cohort expansion study in subjects with advanced cancer for which no standard therapy exists. Subjects must have received prior treatment for cancer that has not worked, or has stopped working.

Detailed description:
The study will be conducted in two parts. Part A is a dose escalation study to determine a safe and tolerable dose of ASN002 for subjects with relapsed or refractory lymphoma, or advanced solid tumors. Part A will also characterize the pharmacokinetics and pharmacodynamics of ASN002 through blood sampling. Subjects in Part B will enroll subjects with four types of lymphoma Diffuse Large B-cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL) and Peripheral T-cell lymphoma (PTCL). Additional groups of subjects with Myelofibrosis (MF) and Chronic Lymphocytic Leukemia (CLL) will be enrolled. Subjects will be treated with the highest safe and tolerable dose determined in Part A of the study to determine preliminary efficacy. Subjects may continue to receive ASN002 for up to 1 year in the absence of severe side effects or disease progression.

Arms:
arm 1: Multiple ascending doses of ASN002 will be administered to determine the maximum tolerated dose (MTD). Arm Closed arm 2: ASN002 administered at the recommended dose

Interventions: intervention 1: ASN002 Dose Escalation intervention 2: ASN002 RD
Intervention descriptions: intervention 1: Multiple ascending doses of ASN002 assigned by cohort intervention 2: Recommended dose of ASN002 from Part A

Protocol document:
Prot_000.pdf: 
 
Asana BioSciences, LLC. 
 
ASN002 
 
ASN002-101 
 
A PHASE 1/2, OPEN-LABEL, UNCONTROLLED, MULTIPLE-DOSE ESCALATION, 
COHORT EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, 
PHARMACOKINETICS AND PRELIMINARY EFFICACY OF ASN002 IN 
RELAPSED/REFRACTORY LYMPHOMA, MYELOFIBROSIS, CHRONIC 
LYMPHOCYTIC LEUKEMIA AND ADVANCED SOLID TUMORS 
IND # 124113 
 
Date: 17 Dec 2014 
Amendment 1: 26 Jan 2015 
Amendment 2: 30 Jan 2015 
Amendment 3: 17 Mar 2015 
Amendment 4: 12 Apr 2016 
Amendment 5: 15 Aug 2016 
Amendment 6: 24 May 2017 
 
Confidentiality Statement 
This document is the property of Asana BioSciences, LLC. and may not—in full or part—be 
passed on, reproduced, published, distributed to any person, or submitted to any regulatory 
authority without the express written permission of Asana BioSciences, LLC. 
 
 
 
 


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Rationale for the Amendment 
 
1. Based on safety, tolerability, PK and PD considerations, the starting dose for Part B is 75 
mg BID. 
2. The protocol is amended to include additional dose cohorts in Part B of the study which 
include: myelofibrosis (MF) including primary MF (PMF), post-polycythemia vera (post-
PV) MF, or post-essential thrombocythemia (post-ET) MF; Peripheral T-cell lymphoma 
(PTCL) and chronic lymphocytic leukemia (CLL). A full rationale for the inclusion of 
these subjects is found in Section 6.1. 
3. The protocol is amended to in Part A of the study to evaluate the safety and tolerability of 
ASN002 when co-administered with a meal. Currently ASN002 is administered under 
fasted conditions. A single dose study in healthy subjects indicated that co-administration 
with a meal increased systemic exposure by about 80% compared to fasted conditions. 
The first dose level at which the effect of a meal on safety, tolerability and 
pharmacokinetics will be evaluated will at least one dose lower than the highest dose 
evaluated when ASN002 was administered under fasted conditions. 
4. Correction of errata from Amendment 05 
5.  Update of contact information 
 
 
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Summary of Changes 
 
Modifications 
Location 
An additional 3 disease-specific cohorts, of 14 subjects each, were added in Part B to evaluate 
preliminary efficacy in Peripheral T-Cell Lymphoma (PTCL), Myelofibrosis (MF) and Chronic 
Lymphocytic Leukemia (CLL). 
 
The medical and scientific rationale for including subjects with 
PTCL, MF and CLL was added. 
Section 6.1 
 
The study objectives were modified to allow for the additional 
cohorts 
o Additional cohorts added to the primary objective for Part B. 
o Additional exploratory biomarker objectives were added for 
pharmacodynamic biomarkers 
Synopsis, Section 7.3 
 
Additional biomarker assays were added to correlate with any 
observed clinical activity in DLBCL, MF and CLL. 
Synopsis, Section 7.3, 
Section 11.3.1, Section 14, 
and Table 9 
 
Forty-two subjects were added to Part B of the study in the additional 
cohorts of PTCL, MF, and CLL, 14 in each cohort. 
Synopsis, Section 8.2 
 
Additional efficacy/outcome measurements were added to define the 
efficacy endpoints for MF, and CLL. 
Synopsis, Section 8.6, 
Section 11.1.1.3 and Section 
11.1.1.4, Section 15.6.1, and 
Table 2 
 
Additional entry criteria were added to support enrollment of subjects 
with MF, and CLL. 
Synopsis, Section 9.1 (10f-n) 
 
Removed the restriction for subjects with extensive bone marrow 
involvement to allow for the enrollment of subjects with CLL. 
Synopsis, Section 9.1 (10a) 
 
Previous treatment with JAK inhibitors is allowed for subjects with 
MF, as this is a standard treatment. 
Synopsis, Section 9.2 (16) 
 
Modifications to the Study Procedures Section were made in 
accordance to the protocol amendment requirements. 
Section 10 
 
The study schema was updated to reflect the additional cohorts. 
Figure A 
 
 
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The Schedule of Assessment Tables were changed to accommodate changes to the study design 
 
The interval for Disease Assessments in solid tumors was 
increased to every 12 weeks after Week 24. 
Table 1 
 
An additional Schedule of Assessments Table and PK/PD Table 
for Part B were added. 
Table 2 and Table 4  
 
The pharmacokinetic (PK), Vital signs, and electrocardiogram 
(ECG) assessments timepoints were reduced in Part B. 
Table 2 and Table 4 
 
The requirement for Liver Function Testing (LFT) on Days 4 and 
11 of Cycle 1 was removed in Part B. 
Table 2 
 
Footnotes to the Schedule of Assessments and Cycle 1 Serial 
Assessments Tables were updated to reflect the changes to the 
protocol. 
Table 1 - Table 4 
Additional changes to the entry criteria 
 
The entry criterion for total bilirubin was lowered to 1.5x the 
upper limit of normal, as an additional safety measure for a Phase 
1 clinical trial. 
Synopsis, Section 9.1 (6b) 
 
The entry criterion for creatinine was expanded to allow calculated 
creatinine clearance of > 45 ml/min as qualification for the study. 
Synopsis, Section 9.1 (6c) 
 
The interval from prior chemotherapy was modified to include 
prior oral tyrosine kinase inhibitors. The interval for TKIs is 2 
weeks or 5 half-lives, whichever is longer. 
Synopsis, Section 9.2 (1) 
 
Reduced the accepted dose of corticosteroids to a level of 10 
mg/day of prednisone or equivalent. Avoids the needs for tapering 
steroids prior to start of study treatment. 
Synopsis, Section 9.2 (7) 
 
Revised the exclusion of subjects with a known bleeding diathesis, 
to clarify exclusion based on safety risks. 
Synopsis, Section 9.2 (8) 
 
 
Revised the PK parameters for Part B of the study. 
Synopsis, Section 15.7, 
Table 2, Table 4 
Additional changes to the protocol 
 
Based on the safety and tolerability data, the starting dose for 
subjects with lymphoma is 75 mg twice daily. A table for dose 
modifications was added for Part B 
Synopsis, Section 6.4.2, 
Section 8.3.2, Table 7 
 
The summary of risks and benefits was updated with the most 
recent human data. 
Section 6.3 
 
Additional cohorts to explore the pharmacokinetic profile of 
ASN002 in a fed rather than fasted state were added. 
Synopsis, Section 6.4.2, 
Section 8.3.1, Figure A, and  
Table 6 
 
 
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 
The overall survival efficacy variable was corrected to Time to 
Progression (TTP).  
Synopsis Section 15.6.3 
 
Biomarkers for C-reactive protein (CRP, beta microglobulin, and 
Interleukin-10 were removed as these cytokines are part of the 
inflammation panel.  
Synopsis, Section 7.3, 
Section 11.3, and Section 14 
 
The 
total 
number 
of 
subjects 
enrolled 
increased 
from 
approximately 100 to approximately 148, including early 
terminations. 
Synopsis, Section 8.2 
 
The requirements for dose modification in Part B were clarified to 
indicate that the observed toxicity must be considered drug-
related. 
Section 8.3.3 
 
The dosing schedule for subjects receiving once daily versus twice 
daily dosing was clarified 
Synopsis, Section 8.4,  
Table 1, and Table 2 
 
The interval for disease assessments was extended for subject with 
solid tumors to once every 12 weeks after 24 weeks of therapy for 
subject convenience and to reduce radiation exposure.   
Section 10.3.2 
 
Concomitant use of medications that affect gastric pH was 
changed to allow for the use of H2 antagonists as well as antacids 
within a 2-10-hour window after administration of ASN002 
Section 10.6.2 
 
Objective outcome measures for solid tumors and lymphoma were 
added to the efficacy section  
Section 11.1.1.1 and 11.1.1.2 
 
Assays for CD 69 and CD 86 were removed  
Synopsis, Section 11.3 
 
The table of PK variables was revised 
Table 11 
Administrative changes 
 
The contact information for the CRO was removed.  CRO contact 
information is contained in a separate study manual. 
Section 1 
 
Abbreviations were added to the List of Abbreviations to support 
changes to the protocol.  
Section 0 
 
Additional literature references were added to support the 
enrollment of subjects with PTCL, MF and CLL 
Section 25 
 
Minor corrections of errata from Amendment 05 
Throughout the protocol 
 
Headers and tables have been renumbered as appropriate to 
support the changes to the protocol. 
Throughout the protocol 
 
 
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1 
SPONSOR CONTACT INFORMATION 
Asana BioSciences, LLC 
Name 
Telephone and Email Address 
  
 
Office: 
 
E-mail: 
 
 
 
Office: 
  
E-mail: 
 
 
 
Office: 
 
E-mail: 
 
 
. 
Telephone: 
 
E-mail: 
  
 
A list of other key study personnel will be provided separately for your reference. 
 
2 
SYNOPSIS 
Name of Sponsor/Company: Asana BioSciences, LLC 
Name of Investigational Product: ASN002 
Name of Active Ingredient: ASN002 
Title of Study: A Phase 1/2, Open-Label, Uncontrolled, Multiple-Dose Escalation, Cohort Expansion 
Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of ASN002 In 
Relapsed/Refractory Lymphoma, Myelofibrosis, Chronic Lymphocytic Leukemia, And Advanced Solid 
Tumors 
Study period:  
Estimated date first subject enrolled: March 31, 2015 
Estimated date last subject completed: March 31, 2018 
Phase of development: Phase ½ 
Objectives: 
Primary: 
Part A: 
 
To evaluate the safety and tolerability of ASN002 including dose-limiting toxicities (DLTs) and to 
determine the maximum tolerated dose (MTD). 
Part B: 
 
To evaluate the safety, tolerability, and preliminary efficacy of ASN002 in subjects with 
relapsed/refractory diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) and mantle cell 
lymphoma (MCL), peripheral T-cell lymphoma (PTCL), myelofibrosis (MF), and chronic lymphocytic 
leukemia (CLL). 
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Secondary: 
Part A and B: 
 
To evaluate the pharmacokinetic (PK) profile of ASN002 after single and multiple doses. 
Exploratory: 
Parts A and B 
 
To evaluate the effects of ASN002 on Phospho-STAT3, Phospho-S6, Phospho-SYK 525/526, 
Phospho-ERK, and a panel of markers of inflammation (Appendix C) 
 
Evaluate the response to therapy based on DLBCL molecular subtype [germinal center B-cell like 
(GCB) or activated B-cell (ACB)]. 
 
To evaluate the effects of ASN002 on JAK (V617F) mutant allele burden in subjects with MF. 
 
To evaluate the effects of ASN002 on a panel of selected cytokines including inflammatory mediators 
associated with STAT. 
Number of subjects (planned): A total of 148 evaluable subjects are estimated for the study with the 
distribution as follows: 
Part A: Approximately 64 subjects (up to 6 subjects per dose level, with and without food) 
Part B: Approximately 84 subjects in 6 groups of 14 each. The groups are patients diagnosed with 
relapsed/refractory DLBCL, MCL, FL, PTCL, MF, and CLL. 
Assuming a 10% early termination rate, the total number of subjects is approximately163. 
Study center(s): Approximately 3-15 study centers located in the United States and Latin America 
Study Design: 
This study is an open-label, non-randomized uncontrolled, multicenter, dose escalation, and cohort expansion 
study in subjects with histologically or cytologically confirmed advanced malignancies (including solid tumors, 
lymphomas, MF and CLL for which no standard therapy exists. The study will be conducted in 2 parts: 
Part A: Patients with either advanced solid tumors or lymphoma for which no standard therapy exists. 
Standard 3+3 design in which subjects will be dosed for 28 days, either twice daily or once daily. 
Dose finding may include dosing with or without food Section 8.4 of the protocol provides 
detailed instructions on dosing for twice daily and once daily dosing. After assessment of safety, 
subjects will be eligible to continue study for a maximum number of 12 additional cycles of 28-
day treatment as long as they do not meet criteria for withdrawal. 
Part B: Expansion cohorts of 14 subjects each with DLBCL, FL MCL, PTCL, MF and CLL treated with 
the recommended dose of 75 mg BID. 
Parts A and B will include a screening period (up to 28 days) and a treatment period for up to 12 months.  
Following the 28-day DLT assessment period in Part A and throughout Part B, treatment can continue as long a 
subject demonstrates at least stable disease, or until a subject experiences an intolerable adverse event (AE) or 
disease progression, withdraws consent or until termination of the study by the sponsor. At the end of treatment, 
a post-treatment period of 4 weeks will commence that concludes with an end-of-study visit. 
Diagnosis and inclusion/exclusion criteria: 
Inclusion criteria: 
1. Written informed consent obtained prior to any study-related procedure being performed; 
2. Male or female subjects at least 18 years of age at the time of consent; 
3. ECOG Performance Status 0-2; 
4. Radiographically evaluable tumor by 2014 Lugano Classification recommendations (lymphomas) or 
RECIST 1.1 (advanced solid tumors); 
5. Recovered from the reversible effects of prior antineoplastic therapy (with the exception of alopecia and 
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Grade 1 neuropathy). Screening blood counts of the following: 
a. Absolute neutrophil count ≥ 1000/μL 
b. Platelets ≥ 75,000/μL 
c. Hemoglobin ≥ 8 g/dL (with transfusion support); 
6. Screening chemistry values of the following: 
a. Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3.0 × upper limit of the normal 
reference range (ULN) 
b. Total bilirubin ≤ 1.5 × ULN 
c. Creatinine ≤ 1.5 × ULN, or a calculated creatinine clearance of > 45 ml/min; 
7. At screening, life expectancy of at least 3 months; 
8. Subject is willing and able to comply with all protocol required visits and assessments; 
9. Male and female subjects of child-bearing potential must agree to use medically acceptable methods of 
birth control throughout the study and for thirty (30) days after the last dose of study medication. 
10. Subjects must have one of the following disease characteristics 
(Part A only) 
a. 
Histologically or cytologically confirmed metastatic and/or advanced solid tumors or lymphomas 
for which no standard therapy exists, or who are not eligible for standard treatment. Subjects must 
have received at least one prior therapy for their malignancy; 
Lymphoma (Part A or B) 
a. 
Histologically confirmed DLBCL/MCL/FL/PTCL on the basis of excisional lymph node or 
biopsy; 
b. Diagnosis of relapsed/refractory DLBCL/MCL/FL/PTCL defined as 1) recurrence of disease after 
a CR, or 2) PR, SD at completion of treatment regimen preceding entry into study. 
c. 
Subjects must not be candidates for standard therapy. 
d. Subjects who have not received SCT must be ineligible to receive SCT. 
Primary Myelofibrosis (Part B only) 
e. 
Confirmed diagnosis of PMF, post-PV MF, or post-ET MF according to the 2008 WHO criteria 
f. 
High risk or intermediate-2 risk or symptomatic intermediate -1 risk as defined by Dynamic 
International Prognostic Scoring System (DIPSS), See Appendix D. 
g. Palpable splenomegaly at least 5 cm below the left costal margin. 
h. Known JAK2 mutational status. 
i. 
Refractory/relapsed disease or intolerant to prior JAK2 therapy in the judgement of the 
investigator. 
Chronic Lymphocytic Leukemia (Part B only) 
j. 
Confirmed diagnosis of B-cell CLL, according to International Workshop on Chronic 
Lymphocytic Leukemia (IWCCL) 
k. Measurable disease defined as lymphocytosis> 5,000/uL, or at least one palpable or CT 
measurable lesion (> 2.0 cm), or quantifiable bone marrow involvement. 
l. 
Active disease requiring treatment as defined by IWCLL consensus criteria 
m. Relapsed/refractory disease following prior treatment with at least 2 and no more than 4 prior 
regimens, which may include chemotherapy, an approved anti-CD20 antibody with or without 
maintenance therapy, and an approved targeted agent, unless patients are ineligible to receive such 
agents. 
Exclusion criteria: 
1. Have received prior standard chemotherapy regimens within 4 weeks of Day 1, for targeted kinase 
inhibitors, an interval of 5 half-lives or at least 2 weeks whichever is longer. 
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2. Have received prior treatment with monoclonal antibodies within 6 weeks of first dose of Day 1; 
3. Have had major surgery within 30 days prior to the start of Day 1; 
4. Received any investigational treatment within 4 weeks prior to the start of study medication; 
5. Have had an infection requiring the use of parenteral antibiotics within 14 days prior to the start of  
Day 1; 
6. Have known central nervous system metastasis or CNS lymphoma; 
7. Is receiving corticosteroids (>10 mg prednisone daily or equivalent); 
8. Has known bleeding diathesis that could be considered a safety concern; 
9. Has a history of other malignancy within the 3 years prior to screening, except adequately treated basal 
cell or squamous cell carcinoma of the skin, or carcinoma in-situ; 
10. Has difficulty swallowing medications, or known history of malabsorption syndrome; 
11. Has a serious concurrent medical condition, such as: 
a. 
History of congestive heart failure New York Heart Association (NYHA) class III or IV or 
uncontrolled hypertension at screening 
b. 12-Lead electrocardiogram (ECG) abnormalities considered by the investigator to be 
clinically significant or QTcF ≥ 450 milliseconds, regardless of clinical significance, at 
screening. Abnormal ECG may be confirmed with one repeat assessment. For subjects with 
QTcF≥450 msec on initial ECG, the mean of the two QTcF assessments will determine 
eligibility; 
c. 
Myocardial infarction, angioplasty, or cardiac stent placement within the last 6 months. 
d. HIV infection 
e. 
Known Hepatitis B or C infection. Subjects at high risk for Hepatitis B or C infection should 
have serology testing to rule out infection; 
f. 
A medical condition requiring the therapeutic use of anticoagulants; 
g. Condition or situation which may put the patient at significantly increased risk, may confound 
the study results, or may interfere significantly with subject’s participation in the study; 
12. Known hypersensitivity to ASN002 or its excipients; 
13. Prior participation, i.e., receipt of study medication, in this study; 
14. Any condition that, in the opinion of the investigator, would impair the subject’s ability to comply with 
study procedures; 
15. Female subjects that are pregnant or lactating. 
16. Part B only: Prior treatment with SYK or JAK inhibitors, except for MF patients who have received 
prior JAK inhibitor. 
Investigational product, dosage and mode of administration: ASN002 administered orally. Planned doses 
are 10, 20, 30, 40, 50, 75, and 100 mg q12h. Cohorts of subjects have been added to explore q24 h dosing, at 80 
mg and 120 mg once daily. The initial qd dose will not exceed the total daily dose of the highest well tolerated 
bid dose. The initial dose taken with food will not exceed 75% of the highest tolerated dose. ASN002 is 
available in 5-mg, 20-mg, and 50-mg strength tablets. 
Duration of study: Parts A and B will include a screening period (up to 28 days) and a treatment period up to 
12 months. A subject with no DLTs may have the opportunity to continue treatment at the discretion of the 
investigator and sponsor. If the subject is not a candidate for, or chooses not to participate in additional 
treatment, an end-of-study visit will take place followed by a 4-week post-treatment period. 
Criteria for evaluation: 
Assessment of PK variables: For Parts A, the following single-dose PK parameters for ASN002 will be derived 
from the concentration-time data of ASN002 after the first dose administration in the fasted state: 
 
Cmax: peak plasma concentration 
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 
tmax: the time to reach the peak plasma concentration 
 
AUC0-∞: area under the plasma concentration-time curve from time zero to infinity 
 
AUC0-t: area under the plasma concentration-time curve from time zero to the last sample with a 
quantifiable concentration 
 
AUC0-24: area under the plasma concentration-time curve from time zero to 24 hours 
 
λz: terminal elimination rate constant 
 
t½: terminal elimination half-life 
For Part A, the following PK parameters for ASN002 will be calculated after multiple dosing on Day 15: 
 
Cmax: peak plasma concentration 
 
tmax: the time to reach the peak plasma concentration  
 
AUC0-12: area under the plasma concentration-time curve from time zero to 12 hours for bid dosing 
cohorts, 
 
AUC0-24: area under the plasma concentration-time curve from time zero to 24 hours for qd dosing 
cohorts 
 
CL/F: Total clearance following oral administration 
 
Vd/F: Volume of distribution at terminal phase following oral administration 
For Part B, PK parameters, such as CL/F and other parameters as appropriate, will be determined via population 
PK analysis 
Assessment of efficacy variables: 
 
Assessment of efficacy will be in accordance with 
- 
the 2014 Lugano Classification for lymphoma (ref JCO September 20, 2014 vol. 32 no. 27 
3059-3067), or 
- 
RECIST 1.1 for advanced solid tumors, or as applicable 
- 
The International Working Group-Myeloproliferative Neoplasms Research and Treatment 
(IWG-MRT) and European LeukemiaNet (ELN) response criteria for myelofibrosis 
- 
International Workshop on Chronic Lymphocytic Leukemia for CLL guidelines, 2008 
Assessment of safety: Safety will be assessed by AEs, vital signs, 12-lead ECG, physical examination, and 
laboratory safety assessments. 
Criteria for DLT: 
All adverse events unless they have been determined to be not related to study drug will be taken into 
consideration in determining dose limiting toxicity. During Phase 1, the MTD will be determined based on 
DLTs occurring during the first 28 days plus any rest period if applicable (i.e. Cycle 1). NCI-CTCAE version 
4.03 will be the basis for the descriptive terminology and grading of adverse events.  DLT are as follows: 
Non-hematologic DLT is defined as: 
Any Grade ≥ 3 AE, with the following exceptions 
 
Symptomatic adverse events such as nausea, vomiting and diarrhea will not be considered dose 
limiting if they can be reduced to less than grade 3 within 72 hours with standard supportive measures 
such as antiemetics and antidiarrheals. 
 
Asymptomatic Grade 3 electrolyte abnormalities which can be corrected by optimal supplementation. 
Hematologic DLT is defined as: 
 
≥Grade 4 neutropenia or thrombocytopenia that lasts more than 7 days after the last dose of study drug. 
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 
Febrile neutropenia 
 
≥Grade 3 thrombocytopenia in the presence of bleeding 
Assessment of pharmacodynamic parameters: 
 
Lymphoma 
o 
Inhibition of phosphorylation of S6, STAT3, SYKTyr525/526, ERK 
o 
DLBCL molecular subtyping. 
o 
Changes from baseline in a panel of markers of inflammation (Appendix C) 
 
MF 
o 
Changes from baseline in JAK (V617F) mutant allele burden 
o 
Changes from baseline in a panel of markers of inflammation 
 
CLL 
o 
Changes from baseline in BCL2 expression 
o 
Changes in the status of chromosome 17p 
o 
Changes from baseline in a panel of markers of inflammation 
Statistical methods: 
Analysis Populations: 
The safety population will include all subjects who take at least 1 dose of study medication. Safety analyses will 
be conducted using the safety population. The safety population will apply to Parts A and B. 
The PK population will include all subjects who receive at least 1 dose of ASN002 and have sufficient plasma 
concentration data to facilitate the calculation of PK parameters. 
The PD population will include all subjects who have a baseline and a post dose assessment of the PD 
parameters, where a change from baseline is determined. 
Efficacy Population (EP) will include all subjects who have an evaluable screening and post-dose tumor 
assessment. 
The Per Protocol (PP) population will include all EP subjects without major protocol violations. The PP 
population will be used as the primary analysis population for efficacy. 
PK Analyses: 
The PK parameters will be derived by non-compartmental analysis for Part A and by population PK analysis for 
Part B. PK variables including concentrations and parameters will be summarized using descriptive statistics. 
Efficacy Analyses: 
Evaluation of response rate and survival rate: Responses will be listed by tumor type and dose level. 
In Part B, the overall response rate (ORR), time to progression (TTP) and progression free survival (PFS) will 
be reported for each lymphoma histology, MF, and CLL. 
Evaluation of time on treatment: The time from the start of study treatment to the discontinuation or completion 
of study treatment at each dose level will be summarized descriptively. 
All efficacy summaries will be performed by dose level and Parts A and B, separately and combined, if 
appropriate. 
Safety Analyses: 
Assessment of safety will be based on the incidence of AEs, AEs resulting in discontinuation, and serious 
adverse events (SAEs) in each dose level. AEs will be graded using the NCI CTCAE v4 and coded using the 
Medical Dictionary for Regulatory Activities (MedDRA). Summaries of AEs will be provided showing the 
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number and percentage of subjects who experienced at least 1 AE. These summaries will be presented by dose 
level, system organ class, and preferred term. The occurrence of AEs will also be tabulated by severity and 
relationship to study medication. SAEs and AEs resulting in discontinuation will be summarized separately. 
Vital sign measurements, clinical laboratory results, and ECG findings will be summarized by dose level and 
time point using descriptive statistics or frequency distributions. 
Maximum Tolerated Dose: The MTD is one dose level below that at which at least two subjects in a cohort of 
up to 6 subjects experience DLTs during the first 28 days. 
All safety summaries will be performed by dose level and Parts A, and B, separately and combined, if 
appropriate. 
Sample Size Consideration: 
Part A: A traditional 3+3 design will be used to identify the MTD.  In addition to the 40 subjects enrolled in the 
previous amendments, an additional 24 subjects may be enrolled and dose in either fed or fasted states. A total 
of 64 subjects will be enrolled into the Part A dose escalation phase of the study. No randomization will be 
performed for Part A. 
Part B: A sample size of 84 subjects (14 each in DLBCL, MCL, FL, PTCL, MF, and CLL) will be enrolled. The 
null hypothesis that the true response rate is 0.05 will be tested against a one-sided alternative. A total of 14 
patients will be accrued in each cohort. The null hypothesis will be rejected if at least 3 responses are observed 
in 14 subjects. This design yields a type I error rate of 0.02 and power of 0.9 when the true response rate is 0.4. 
 
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a Subsequent cycles should begin within 3 days of either Day1, or the previous cycle. Subjects may continue to receive additional cycles of ASN002 in the absence of 
intolerable or severe toxicity or disease progression.  All safety laboratory and radiographic evaluations for continued dosing must be completed prior to evaluation by the 
investigator. 
b End of Treatment Visit should take place < 1 week from the last dose of study medication. 
c Complete physical examination will be conducted at screening and end of treatment. Other examinations may be brief, problem-focused examinations and review of 
systems. 
d Vital signs will consist of heart rate, blood pressure, and temperature. Day 3 and Day 16 apply to QD dosing cohorts only. 
e Height to be obtained at baseline only. 
f Refer to the Schedule of Assessments Table for Day 1, and Day 15. Day 3 and Day 16 apply to QD dosing cohorts only. 
g Laboratory assessments may be drawn up to 72 hours in advance of the scheduled visit for patient convenience. Refer to Table 10 for a complete list of required safety 
laboratory assessments. Labs need not be repeated on day 1 cycle 1 if baseline data were obtained within the preceding 72 hours. 
h  Subjects will be evaluated based on malignancy-specific requirements. Evaluations may be completed up to one week prior to the nominal visit. 
2014 Lugano Classification (every 12 weeks ± 1 week) or 
RECIST 1.1 for advanced solid tumors every 8 weeks for the first 24 weeks, and every 12 weeks thereafter after the initiation of treatment with ASN002. 
i In the QD dosing cohorts, the Day 2 dose should be omitted. All other assessments should be performed. 
j PK samples are to be drawn as trough samples prior to study drug administration. 
k  Cycle 2, Day 1 only, prior to dose administration. 
l 30-day follow up for Adverse Events may be conducted as a telephone contact. 
 
 
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Table 2: 
Schedule of Assessments (Part B) 
 
 
 
Study Procedure 
Screening 
D (-28 to -
1) 
Cycle 1 
Subsequent Cyclesa 
End of  
Treatmentb 
30-day  
Follow Up 
Days 
1 
2 
8 
15 
22 
1 
15 
22 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
Eligibility Screening 
X 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
Physical Examinationc 
X 
X 
 
 
 
 
X 
 
 
X 
X 
Disease History & Stage 
X 
 
 
 
 
 
 
 
 
 
 
Vital signsd 
X 
X 
 
 
X 
 
X 
 
 
X 
X 
Heighte and weight 
X 
 
 
 
 
 
X 
 
 
X 
X 
ECOG PS 
X 
X 
 
 
 
 
X 
 
 
X 
 
12-lead ECG 
X 
X 
 
 
 
 
X 
 
 
X 
 
Pregnancy test, if applicable 
X 
 
 
 
 
 
 
 
 
X 
 
Serum Chemistryg 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
Liver Function Testsg 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
CBC with Diff and Plateletsg 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
Urinalysish 
X 
 
 
 
 
 
X 
 
 
 
 
Disease Assessmenti 
X 
 
 
 
 
 
 
 
X 
 
 
MPN-SAF (MF subjects only) j 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
Medication Administration 
 
X-------------------------------------------------------X 
 
 
Pharmacokinetic Samples 
 
Xk 
Xl 
Xl 
Xl 
 
Xl 
Xl 
 
Xm 
 
Pharmacodynamic Samples 
 
X 
 
 
X 
 
X 
 
 
 
 
Adverse Events 
 
  X-------------------------------------------------------------------------------------Xn 
Concomitant Medications 
       X---------------------------------------------------------------------------------X 
 
Dispense Drug Diary 
 
X 
 
 
 
 
X 
 
 
 
 
Medication Compliance 
 
 
 
 
 
 
X 
 
 
X 
 
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a Subsequent cycles should begin within 3 days of either Day1, or the previous cycle.  Subjects may continue to receive additional cycles of ASN002 in the 
absence of intolerable or severe toxicity or disease progression. All safety laboratory and radiographic evaluations for continued dosing must be completed prior 
to evaluation by the investigator. 
b End of Treatment Visit should take place < 1 week from the last dose of study medication. 
c Complete physical examination will be conducted at screening and end of treatment. Other examinations may be brief, problem-focused examinations and 
review of systems. Physical exam includes spleen measurement for subjects with MF. 
d Vital signs will consist of heart rate, blood pressure, and temperature. 
e Height to be obtained at baseline only. 
f Refer to the Schedule of Assessments Table for Day 1, and Day 15. 
g Laboratory assessments may be drawn up to 72 hours in advance of the scheduled visit for patient convenience. Refer to Table 10 for a complete list of 
required safety laboratory assessments. Labs need not be repeated on day 1 cycle 1 if baseline data were obtained within the preceding 72 hours. Part B: Day 22 
laboratory assessments may be omitted. 
h Urinalysis is conducted on Day 1, and then as clinically indicated. 
i Subjects will be evaluated based on malignancy-specific requirements. Evaluations may be completed up to one week in advance of the nominal time to 
accommodate scheduling. 
Lymphoma: every 12 weeks by 2014 Lugano Classification. 
MF: MDS-SAF questionnaire to be done weekly, spleen measurement by PE every 4 weeks for the first 24 weeks and then every 12 weeks, spleen measurement 
by MRI/CT to be done at baseline and on week 24. 
CLL: every 8 weeks during the first 24 weeks and every 12 weeks thereafter by IWCLL criteria (and updates). A CT scan of chest/abdomen/pelvis is 
recommended if previously abnormal and otherwise in case of CR, a bone marrow aspirate/biopsy is recommended in case of CR or cytopenia of uncertain 
cause. 
j The MPN-SAF questionnaire will be completed weekly while on-study.On Day 22, and during subsequent cycles a form for completion at home should be 
given to the subject. 
k PK timepoints for Day 1 will be collected at predose, 2, 4 and 6 hours. See Table 4 for additional details. 
l Predose PK samples are to be drawn as trough samples prior to study drug administration.  A trough PK sample will be drawn on Day 1 of Cycle 3, 6, 9 and 12. 
m Two PK samples are requested at the end of treatment. The first may be drawn with other safety laboratory assessments.The second optional sample is drawn 2-
3 hours later. 
n 30-day follow up for Adverse Events may be conducted as a telephone contact. 
 
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Table 3: 
Cycle 1 Serial Assessments (Part A) 
 
Day 
Nominal 
Timea 
(hours) 
Windows 
Assessmentsb 
PK Sample 
PD Sample 
ECG 
VS 
Day 1 
Predose 
Up to -60 
minutes 
X 
X 
X 
X 
0.5 
(± 5 mins.) 
X 
 
 
 
1.0 
X 
 
X 
X 
2.0 
X 
X 
X 
X 
4.0 
(± 15 mins.) 
X 
 
X 
X 
8.0 
(± 1 hr) 
X 
 
 
 
12.0 
X 
 
X 
X 
Day 2 
24 h post-
day 1 dose 
± 1 hr from 
1st dose 
X 
 
X 
X 
Day 3c 
(QD cohorts 
only) 
48 h post-
Day 1 dose 
± 2 hr from 
1st dose 
X 
 
X 
X 
Day 8 
Predose 
N/A 
X 
X 
X 
X 
Day 15 
Predose 
Up to -60 
minutes 
X 
X 
X 
X 
Day 15 
0.5 
(± 5 mins.) 
X 
 
 
 
1.0 
X 
 
X 
X 
2.0 
X 
X 
X 
X 
4.0 
(± 15 mins.) 
X 
 
X 
X 
8.0 
(± 1 hr) 
X 
 
 
 
12.0 
X 
 
X 
X 
Day 16 
(QD cohort only) 
24 h post-
Day 15 dose 
 
X 
 
X 
X 
Day 22 
Pre-dose 
N/A 
X 
 
X 
X 
Cycle 2, Day 1 
Pre-dose 
N/A 
X 
X 
 
X 
a The actual time of all assessments will be recorded in source documents and on the eCRF 
b The priority of assessments for the procedures is (1) PK/PD, (2)ECG, (3)VS 
c Only subjects in single daily dose cohorts require PK on Day 3 and 16. 
 
 


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Table 4:  PK/PD Assessments (Part B) 
 
Day 
Nominal Timea 
(hours) 
Windows 
Assessments 
PK Sample 
PD Sampleb 
Day 1 
 
Predose 
N/A 
X 
X 
2. 0 
± 15 mins 
X 
X 
4.0 
± 15 mins 
X 
 
6.0 
± 30 mins 
X 
 
Day 2 
Predose 
N/A 
X 
 
Day 8 
Predose 
N/A 
X 
 
Day 15 
 
Predose 
N/A 
X 
X 
2.0 
± 15 mins. 
X 
X 
Cycle 2, Day 1 
 
Predose 
N/A 
X 
X 
2.0 
± 15 mins. 
X 
X 
Cycle 2, Day 15 
Predose 
N/A 
X 
 
Day 1, Cycle 3, 6, 9 and 
12 
Predose 
N/A 
X 
 
End of Treatment 
 
N/A 
N/A 
X 
 
2-3 (optional) 
± 15 mins. 
X 
 
a  The actual time of all assessments will be recorded in source documents and on the eCRF 
b In Part B of the study, only selected sites will be collecting the PD samples for phospho-proteins 
 
 


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4 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES 
TABLE OF CONTENTS 
1 
SPONSOR CONTACT INFORMATION .........................................................................6 
2 
SYNOPSIS .........................................................................................................................6 
3 
SCHEDULE OF ASSESSMENTS ..................................................................................13 
4 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ....................19 
5 
LIST OF ABBREVIATIONS ..........................................................................................25 
6 
INTRODUCTION ...........................................................................................................27 
6.1 
Background ............................................................................................................27 
6.1.1 
Peripheral T-cell Lymphomas......................................................................28 
6.1.2 
Myelofibrosis ...............................................................................................28 
6.1.3 
Chronic Lymphocytic Leukemia .................................................................29 
6.2 
Summary of Nonclinical Studies ...........................................................................29 
6.3 
Summary of Clinical Studies and Known Risks and Benefits ...............................30 
6.4 
Rationale ................................................................................................................31 
6.4.1 
Rationale for Study ......................................................................................31
6.4.2 
Rationale for Initial Dose and Schedule ......................................................32 
6.4.3 
Rationale for Recommended Part B Dose ...................................................33 
6.4.4 
Rationale for Additional Dose Finding in Advanced Solid Tumors ...........33 
6.4.5 
Rationale for the Evaluation of ASN002 with Food ....................................33 
7 
OBJECTIVES ..................................................................................................................34 
7.1 
Primary Objectives.................................................................................................34
7.2 
Secondary Objectives.............................................................................................34 
7.3 
Exploratory/Pharmacodynamic Objectives ...........................................................34 
8 
INVESTIGATIONAL PLAN ..........................................................................................34 
8.1 
Study Design ..........................................................................................................34 
8.2 
Number of Subjects................................................................................................36 
8.3 
Selection of Doses..................................................................................................36 
8.3.1 
Part A (Dose Escalation) ..............................................................................36 
8.3.2 
Part B (Cohort Expansion) ...........................................................................37 
8.3.3 
Dose Modifications ......................................................................................37 
8.4 
Study Drug Administration ....................................................................................38
8.4.1 
Missed or Vomited Doses ............................................................................39 
8.4.2 
Duration of Treatment..................................................................................39 
8.5 
Procedures and Criteria for Dose Escalation .........................................................39 
8.5.1 
Safety Review Committee ...........................................................................39 
8.5.2 
Dose Escalation Criteria ..............................................................................39 
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8.5.3 
Dose-Limiting Toxicity (DLT) Definitions .................................................40
8.6 
Definitions of Response to ASN002 ......................................................................41 
8.6.1 
Relapsed/Refractory Lymphomas ................................................................41 
8.6.2 
Solid Tumors ................................................................................................41
8.6.3 
Myelofibrosis ...............................................................................................41 
8.6.4 
Chronic Lymphocytic Leukemia .................................................................41 
8.6.5 
Clinical Disease Progression........................................................................41 
9 
SELECTION AND WITHDRAWAL OF SUBJECTS ...................................................42 
9.1 
Subject Inclusion Criteria ......................................................................................42
9.2 
Subject Exclusion Criteria .....................................................................................43 
9.3 
Subject Discontinuation Criteria ............................................................................45 
9.3.1 
Replacement Procedures ..............................................................................46 
10 VISIT PROCEDURES ....................................................................................................46 
10.1 
Screening................................................................................................................46 
10.1.1 
Subject Screening.........................................................................................46 
10.2 
Cycle 1 ...................................................................................................................46 
10.2.1 
Day 1 ............................................................................................................47 
10.2.2 
Day 2 ............................................................................................................47 
10.2.3 
Day 3 ............................................................................................................48 
10.2.4 
Day 4, and 11 (± 1 day) ...............................................................................48
10.2.5 
Day 8 (± 1 day) ............................................................................................48 
10.2.6 
Day 15 (± 1 day) ..........................................................................................49 
10.2.7 
Day 16 (± 1 day) ..........................................................................................49 
10.2.8 
Day 22 (± 1 day) ..........................................................................................50 
10.2.9 
Day 28 ..........................................................................................................51 
10.3 
Subsequent Cycles (± 3 days) ................................................................................51 
10.3.1 
Day 1 ............................................................................................................51 
10.3.2 
Day 15 (± 2 days) .........................................................................................51 
10.4 
End of Treatment ...................................................................................................52 
10.5 
30-Day Follow-up ..................................................................................................52 
10.6 
Prior and Concomitant Medications ......................................................................52 
10.6.1 
Prohibited Medications ................................................................................53 
10.6.2 
Concomitant Use of Drugs that may Affect Gastric pH ..............................53 
10.7 
Treatment Compliance ...........................................................................................54 
10.8 
Blinding and Randomization .................................................................................54 
11 ASSESSMENT OF EFFICACY .....................................................................................54 
11.1 
Primary Efficacy Variable .....................................................................................54 
11.1.1 
Disease Response .........................................................................................54 
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11.1.1.1 
DLBCL, MCL, FL, and PTC..............................................................54
11.1.1.2 
Advanced Solid Malignancies............................................................55
11.1.1.3 
Myelofibrosis......................................................................................55 
11.1.1.4 
CLL.....................................................................................................55 
11.2 
Secondary Efficacy Variables. ...............................................................................56 
11.2.1 
Eastern Cooperative Oncology Group (ECOG) Performance Status ..........56 
11.3 
Exploratory Markers ..............................................................................................56 
11.3.1 
Assessment of Biomarkers ...........................................................................56 
12 ASSESSMENT OF SAFETY ..........................................................................................57 
12.1 
Definitions..............................................................................................................57 
12.1.1 
Adverse Events ............................................................................................57 
12.1.2 
Serious Adverse Events ...............................................................................58 
12.2 
Monitoring Adverse Events ...................................................................................59 
12.3 
Relationship to Study Drug ....................................................................................59 
12.4 
Intensity Assessment ..............................................................................................59 
12.5 
Reporting Adverse Events and Serious Adverse Events .......................................60 
12.5.1 
Reporting Adverse Events ...........................................................................60 
12.5.2 
Reporting Serious Adverse Events ..............................................................60 
12.5.2.1 
Follow-up Procedures for Serious Adverse Events............................61 
12.6 
Special Reporting Situations ..................................................................................61 
12.6.1 
Overdose ......................................................................................................61 
12.6.2 
Pregnancy .....................................................................................................62 
12.7 
Clinical Laboratory Determinations ......................................................................62 
12.8 
Vital Signs ..............................................................................................................63 
12.9 
Electrocardiogram ..................................................................................................63 
12.10 Physical Examination.............................................................................................64 
13 ASSESSMENT OF PHARMACOKINETICS ................................................................64 
13.1 
PK Sample Collections ..........................................................................................64 
13.2 
Sample Storage and Shipment ...............................................................................65 
13.3 
PK Analytical Methodology ..................................................................................65 
14 ASSESSMENT OF PHARMACODYNAMICS .............................................................65 
14.1 
PD Sample Collection ............................................................................................65 
15 STATISTICAL CONSIDERATIONS AND METHODS ...............................................66 
15.1 
Determination of Sample Size ...............................................................................66 
15.2 
Subject Populations ................................................................................................66 
15.3 
Subject Disposition ................................................................................................67 
15.4 
Demographics and Other Baseline Characteristics ................................................67
15.5 
Safety Analyses ......................................................................................................67 
15.5.1 
Prior, Concomitant, and Post Medications ..................................................67 
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15.5.2 
Study Drug Exposure ...................................................................................68 
15.5.3 
Measurement of Treatment Compliance ......................................................68 
15.5.4 
Adverse Events ............................................................................................68 
15.5.5 
Vital Signs ....................................................................................................69 
15.5.6 
Clinical Laboratory Parameters ...................................................................69 
15.5.7 
Electrocardiogram ........................................................................................69 
15.5.8 
Physical Examination...................................................................................69 
15.6 
Efficacy Analyses ..................................................................................................69 
15.6.1 
Evaluation of Disease Status ........................................................................70 
15.6.1.1 
DLBCL, MCL, FL, PTCL..................................................................70
15.6.1.2 
Advanced Solid Malignancies............................................................70 
15.6.1.3 
Myelofibrosis......................................................................................70 
15.6.1.4 
CLL.....................................................................................................70
15.6.1.5 
Evaluation of Performance Status.......................................................70
15.6.2 
Evaluation of Time on Treatment ................................................................70 
15.6.3 
Evaluation of Time to Progression ..............................................................70 
15.6.4 
Evaluation of Progression Free Survival .....................................................71 
15.7 
Pharmacokinetic Analyses .....................................................................................71 
15.7.1 
Calculation of Pharmacokinetic Variables ...................................................71 
15.7.2 
Analysis of Pharmacokinetic Results...........................................................72 
15.7.3 
Handling of Missing Values ........................................................................72 
15.8 
Pharmacodynamic Analyses ..................................................................................72 
15.9 
Protocol Deviations ................................................................................................72 
15.10 Interim Analysis .....................................................................................................73 
15.11 Statistical Software ................................................................................................73 
16 STUDY DRUG MATERIALS AND MANAGEMENT ................................................73 
16.1 
Study Drug Identity................................................................................................73 
16.2 
Study Drug Packaging and Labeling .....................................................................73 
16.3 
Study Drug Storage ................................................................................................73 
16.4 
Study Drug Preparation..........................................................................................73 
16.5 
Study Drug Accountability ....................................................................................73 
16.5.1 
Study Drug Handling and Disposal .............................................................74
17 DIRECT ACCESS TO SOURCE DATE/DOCUMENTS ..............................................74 
17.1 
Source Documents .................................................................................................74 
17.2 
Study Monitoring ...................................................................................................74 
17.3 
Audits and Inspections ...........................................................................................75 
17.4 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) .............75 
17.5 
Data Recording and Documentation ......................................................................75 
18 QUALITY CONTROL AND QUALITY ASSURANCE ...............................................75 
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19 ETHICS............................................................................................................................76 
19.1 
Ethics Review ........................................................................................................76 
19.2 
Ethical Conduct of the Study .................................................................................76
19.3 
Subject Information and Consent...........................................................................77 
20 DATA COLLECTION ....................................................................................................77
21 REPORTING AND PUBLICATION ..............................................................................78 
22 INVESTIGATOR OBLIGATIONS ................................................................................78 
22.1 
Regulatory Documents...........................................................................................78 
22.2 
Delegation of Responsibilities and Adequate Resources.......................................79 
22.3 
Medical Care of Study Subjects .............................................................................79 
22.4 
Use of Investigational Materials ............................................................................79 
22.5 
Retention of Records..............................................................................................80
22.6 
Subject Confidentiality ..........................................................................................80
22.7 
Clinical Trials Registration ....................................................................................81
23 TERMINATION OF STUDY .........................................................................................81 
24 PROTOCOL SIGNATURE PAGE .................................................................................82 
24.1 
Asana BioSciences, LLC .......................................................................................82 
24.2 
Investigator Signature ............................................................................................82 
25 REFERENCES ................................................................................................................83
 
LIST OF IN-TEXT TABLES 
Table 1:  
Schedule of Assessments (Part A) ...............................................................13 
Table 2: 
Schedule of Assessments (Part B) ...............................................................15 
Table 3: 
Cycle 1 Serial Assessments (Part A) ...........................................................17
Table 4:  
PK/PD Assessments (Part B) .......................................................................18
Table 5: 
Abbreviations and Specialist Terms ............................................................25 
Table 6: 
Twice Daily and Once Daily Dosing Cohorts .............................................37 
Table 7:  
Dose Modifications for Part B .....................................................................38 
Table 8: 
 Examples of H2 antagonists, and Proton Pump Inhibitors .........................53 
Table 9:  
Pharmacodynamic Assessments ..................................................................57 
Table 10: 
Clinical Laboratory Tests .............................................................................62 
Table 11: 
Pharmacokinetic Variables for Part A .........................................................71 
LIST OF IN-TEXT FIGURES 
Figure A: Study Schema ....................................................................................................36
 
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LIST OF APPENDICES 
Appendix A 
NATIONAL CANCER INSTITUTE COMMON TERMINOLOGY 
CRITERIA FOR ADVERSE EVENTS (NCI CTCAE V4.03) ...................................86 
Appendix B 
EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) 
PERFORMANCE STATUS ........................................................................................87 
Appendix C 
PANEL OF PHARMACODYNAMIC MARKERS OF 
INFLAMMATION ......................................................................................................88 
Appendix D:  
DYNAMIC INTERNATIONAL PROGNOSTIC SCORING 
SYSTEM (DIPSS) .......................................................................................................89 
 
 
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5 
LIST OF ABBREVIATIONS 
The following abbreviations and specialist terms are used in this study protocol. 
Table 5: 
Abbreviations and Specialist Terms 
Abbreviation or specialist term 
Explanation 
ADL 
Activities of Daily Living 
ADME 
Absorption, Distribution, Metabolism, Excretion 
AE 
Adverse Event 
ALT  
Alanine aminotransferase  
AST  
Aspartate aminotransferase  
ALP 
Alkaline Phosphatase 
BCR 
B-Cell Receptor  
bid 
Twice daily 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CLL 
Chronic Lymphocytic Leukemia 
CNS 
Central Nervous System 
CR 
Complete Response 
CT 
Computed Tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CRP 
C – Reactive Protein 
CV 
Cardiovascular 
CYP 
Cytochrome P450  
DHHS 
Department of Health and Human Services 
DLBCL 
Diffuse Large B-Cell Lymphoma 
DLT 
Dose-limiting toxicity 
EC50 
One half maximal effective concentration 
ECG  
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
ELN 
European LeukemiaNet 
ET 
Essential Thrombocytopenia 
FDA 
Food and Drug Administration 
FIH 
First in Human 
FL 
Follicular Lymphoma 
GALT 
Gut-Associated Lymphoid Tissue 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practice 
hERG 
Human Ether-a-go-go Related Gene 
HEL 
Human Erythroleukemia 
HSNTD 
Highest Non-Severely Toxic Dose 
IB 
Investigator Brochure 
IC50 
Half maximal inhibitory concentration 
ICH  
International Conference on Harmonisation 
ID 
Identification 
IEC 
Independent Ethics Committee 
IND 
Investigational New Drug 
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Abbreviation or specialist term 
Explanation 
IRB 
Institutional Review Board 
IWCLL 
International Workshop on Chronic Lymphocytic Leukemia 
IWG-MRT 
International Working Group-Myeloproliferative Neoplasms 
Research and Treatment 
JAK 
Janus kinase 
MCL 
Mantle Cell Lymphoma 
MedDRA 
Medical Dictionary for Regulatory Activities 
MF 
Myelofibrosis 
MRI 
Magnetic Resonance Imaging 
MTD 
Maximum Tolerated Dose 
NCI 
National Cancer Institute 
NOAEL 
No Observed Adverse Effect Level 
PD 
Pharmacodynamics, Progressive Disease 
PET 
Positron Emission Tomography 
PK 
Pharmacokinetics 
PP 
Per Protocol 
PR 
Partial Response 
PTCL 
Peripheral T-cell Lymphoma 
PV 
Polycythemia Vera 
qd 
Once daily 
QTc 
Corrected QT interval 
QTcF 
Fridericia’s correction of QT interval 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Stable Disease 
SMP 
Safety Management Plan 
SCT 
Stem Cell Transplant 
STD10 
Severely Toxic Dose in 10% of animal species 
SYK 
Spleen tyrosine kinase 
TEAE 
Treatment-Emergent Adverse Event 
TBIL 
Total bilirubin 
TNM 
Tumor, Nodes, Metastasis 
US 
United States 
Units of Measure 
g 
Gram 
kg 
Kilogram 
mg 
Milligram 
mL 
Milliliter 
µM 
Micromole 
nM 
Nanomole 
 
 
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6 
INTRODUCTION 
6.1 
Background 
Spleen tyrosine kinase (SYK) and Janus kinase (JAK) are tyrosine kinases that play important 
roles in the pathogenesis of various types of lymphomas, myeloproliferative disorders and many 
types of solid tumors (1-3). Inhibition of these targets has been shown to suppress tumor growth 
in various preclinical and/or clinical studies. Most B-cell malignancies are driven by the B-cell 
receptor (BCR) pathway and SYK plays a critical role in this pathway by initiating and 
amplifying the signal from the receptor. A number of small molecule inhibitors of SYK or 
Bruton’s tyrosine kinase (downstream target of SYK) have been shown to suppress the growth of 
tumor cells in these malignancies (4). SYK is therefore an attractive target for the development 
of therapies for BCR-mediated lymphomas and leukemias. 
 
The JAK kinases (JAK1, JAK2, JAK3 and TYK2) are required for the physiologic signaling 
through the cytokines and growth factor receptors that intrinsically lack kinase activity (5,6). 
JAK kinases, upon stimulation with factors such as erythropoietin, granulocyte–macrophage 
colony stimulating factor, IL-3, IL-5, thrombopoietin, and growth hormone, phosphorylate signal 
transducers and activators of transcription (STAT1 -5) family proteins which are translocated to 
the nucleus and activate various downstream target genes involved in cytokine and growth factor 
response. JAK kinases play a significant role in myeloproliferative neoplasms, lymphomas, 
various solid tumors, and inflammatory conditions. The role of JAK kinases in 
myeloproliferative diseases has been well validated and ruxolitinib (Jakafi®) is the standard of 
care for primary myelofibrosis (7). Another JAK inhibitor, tofacitinib (Xeljanz®), is an approved 
drug for rheumatoid arthritis (8). JAK inhibitors are also being investigated in the clinic for their 
efficacy in various lymphomas (9, 10). 
 
ASN002 is an orally bioavailable, potent dual inhibitor of SYK and JAK kinases with 50% 
inhibitory concentrations (IC50 values) of 5-46 nM in biochemical assays. The compound 
showed antiproliferative activity in a broad panel of cell lines representing both solid and 
leukemia/lymphoma tumor types. When evaluated in an in vivo multiple myeloma xenograft 
model, ASN002 caused strong inhibition of tumor growth during the treatment period. There was 
a significant improvement in median days to incidence of hind limb paralysis in mice treated 
with ASN002 in a human Erythroleukemia (HEL) model, which is driven by JAK2V617 mutation. 
These preclinical data provide a strong rationale for the evaluation of ASN002 in patients with 
lymphomas which include mantle cell lymphoma (MCL), diffuse large B cell lymphoma 
(DLBCL) and follicular lymphoma (FL), and potentially in certain types of solid tumors. 
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6.1.1 
Peripheral T-cell Lymphomas 
Peripheral T/NK-cell Lymphomas are an uncommon and heterogeneous group of non-Hodgkin’s 
lymphomas (NHL) that originate from mature, post-thymic (peripheral) T cells or mature natural 
killer (NK) cells. They represent 10%-15% of all NHL. They are characterized by an aggressive 
clinical course with inferior outcomes to those of aggressive B-cell lymphomas and the overall 5-
year disease-free survival usually is less than 30% (11, 12). 
The standard first-line therapy still consists of cyclophosphamide, doxorubicin, vincristine, and 
prednisone (CHOP) or a CHOP-like regimen. Response to first-line regimes is usually poor. 
After 1st-line failure, treatment options are limited and guidelines suggest enrolling patients in 
clinical trials. 
Four agents received accelerated approval in the US for the treatment of relapsed/refractory 
peripheral T-cell Lymphomas (PTCL). Two HDAC inhibitors: Istodax® (romidepsin) and 
Beleodaq® (belinostat), the folate analogue pralatrexate (Folotyn®) and the CD30-directed 
antibody-drug conjugate brentuximab vedotin (Adcetris®), approved for ALCL only. However, 
clinical benefit based on patient reported outcome or survival is yet to be demonstrated and there 
is no consensus on standard treatment for PTCL. 
Signaling pathways of therapeutic interest in PTCL include SYK and JAK. Mutations in JAK3 
have been seen in natural killer (NK)-cell/T-cell lymphomas, and activation of the JAK/STAT 
signaling pathway has been described in PTCL (13,14). SYK expression was assessed in 
specimens from 141 patients with PTCL diagnosed by WHO criteria (15). This study 
demonstrated that SYK is overexpressed in the majority of PTCLs. suggesting that SYK merits 
further evaluation as a candidate target for pharmacologic inhibition in patients with PTCL. 
Together, this data provides a strong rationale for the treatment of PTCL with an inhibitor of 
SYK and JAK. 
 
6.1.2 
Myelofibrosis 
Primary myelofibrosis, essential thrombocythemia and polycythemia vera are clonal 
hematopoietic stem cell disorders, in which the JAK2 V617F mutation is detected in more than 
95% of PV patients and in approximately 50% of patients with ET and MF. The JAK-STAT 
pathway dysregulation, regardless of JAK2 mutational status, is a key pathologic feature of 
myeloproliferative disorders (MPD) (16, 17). The role of JAK kinases in MPD has been well 
validated and ruxolitinib (Jakafi®) is the standard of care for primary myelofibrosis (18, 19). 
However, not all patients respond to ruxolitinib, others experience progression of disease while 
on treatment, and some have to discontinue treatment due to toxicities (20). Treatment options 
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for MF patients remain very limited. Novel JAK inhibitors are under clinical investigation in this 
disease. 
 
ASN002 produces a dose-dependent inhibition of phospho-STAT5, the downstream target of 
JAK1 and JAK3, as demonstrated in a PK-PD study in rats. The compound was also tested in a 
human Erythroleukemia (HEL) model, which is driven by JAK2V617 mutation, showing a 
significant improvement in median days to incidence of hind limb paralysis in treated mice. 
There is therefore a strong rationale for the evaluation of ASN002 in myelofibrosis. 
 
6.1.3 
Chronic Lymphocytic Leukemia 
Chronic Lymphocytic Leukemia (CLL), as most B-cell malignancies, is driven by the B-cell 
receptor (BCR) pathway, and spleen tyrosine kinase (SYK), a non-receptor protein tyrosine 
kinase, plays a critical role in this pathway by initiating and amplifying the signal from the 
receptor (21). The SYK pathway has been clinically validated as a target for CLL therapy 
through the BTK inhibitor, ibrutinib (Imbruvica®) (22, 23). However, ibrutinib, despite 
remarkable responses in CLL, does not eradicate the malignant clone and patients who do not 
respond or become resistant have a dismal prognosis. 
Other pathways are being recognized as relevant in CLL biology, including STAT5A/B and 
STAT3, thus making JAK inhibition a potentially valid target (24, 25). ASN002, a potent dual 
SYK and JAK inhibitor with potent anti-proliferative activity in B-cell lymphoma models, has 
demonstrated anti-proliferative activity in ibrutinib and idelalisib resistant cells lines. There is 
therefore a strong rationale for testing ASN002 in patients with CLL. 
 
6.2 
Summary of Nonclinical Studies 
Nonclinical studies necessary to support clinical studies have been performed and are 
summarized below. Further information can be obtained from the Investigator Brochure (IB). 
 
ASN002 showed potent inhibition of SYK and JAK kinases in biochemical assays with an IC50 
range of 5-46 nM. In mechanistic cell-based studies involving IL-6 and IgE stimulation, ASN002 
strongly blocks the SYK and JAK family kinase signaling pathways. The compound inhibited 
the proliferation of a broad range of lymphoma and solid tumor cell lines including H929, 
Pfeiffer, SUDHL6 and OCI-Ly10. In a multiple myeloma model (H929), ASN002 exhibited 
significant efficacy in inhibiting tumor growth (>95% at 90 mg/kg dose). It also delayed the 
onset of hind limb paralysis in the human erythroleukemia (HEL) model by nearly 33%, 
compared to vehicle. 
 
ASN002 exhibits a medium to rapid rate of oral absorption, moderate to good oral bioavailability 
and short T1/2 in pre-clinical species. It exhibits good permeability characteristics and does not 
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appear to be a Pgp substrate in vitro. It is moderately bound to plasma protein and exhibits good 
metabolic stability in vitro. Limited metabolism may occur via 2C8, 2D6 and 3A4 pathways. 
Glucuronidation does not appear to be a pathway for metabolism of ASN002. ASN002 does not 
appear to have significant inhibitory activity on any of the CYP450 isozymes evaluated, which 
suggest a low potential for drug-drug interactions. Adequate systemic exposure was observed at 
the NOAEL in the 28-day GLP toxicology studies in both rat and dog. 
The results of the mutagenicity studies suggest the genotoxic potential of ASN002 would be low. 
Safety pharmacology studies suggest no adverse effects on the cardiovascular (CV), CNS or 
respiratory systems. Decreased systolic, mean, and pulse blood pressure were observed in the 
dog, but the effects were reversible and can be easily monitored in the clinic. 
 
In both the rat and dog 28-day toxicity studies, NOAELs were demonstrated. The primary 
toxicities in bone marrow and lymphoid tissue and were reversible. In dogs, the bile duct and gall 
bladder were additional target organs. One would expect hematologic changes before significant 
toxicity in the bile duct or gall bladder. 
 
6.3 
Summary of Clinical Studies and Known Risks and Benefits  
This is the first study in humans. There are no known clinical benefits associated with ASN002. 
As of 09 February 2017, a total of 27 patients had been treated in Part A of this study at doses of 
10 – 75 mg twice daily (22 patients), and 80 mg once daily (5 patients). Nineteen patients have 
solid tumors and 8 have non-Hodgkins’ lymphomas of various histologies. Accrual and clinical 
evaluation of ASN002 is ongoing. 
 
At the cut-off date, 21 patients discontinued treatment, mostly (13/21) due to disease 
progression. 
Overall 24 patients (89%) experienced at least one treatment-emergent adverse event (TEAE), 
and drug-related TEAEs occurred in 44% of patients. Considering TEAE of all causality, the 
most commonly involved system organ classes, were gastrointestinal disorders (52% of patients), 
general disorders and administrative site conditions (44%), nervous system disorders (37%), 
infections and infestations (30%), and investigations, psychiatric and skin disorders (22% each) 
Infections and infestations, including events of any severity and causality, appear more common 
at higher doses, with 1/10 patients (10%) at doses ≤60 mg daily compared with 7/17 (41%) of 
patients at doses ≥80 mg daily experiencing infectious events. This finding is not unexpected 
based on experience with other JAK inhibitors. 
 
Individual TEAE occurring in > 10% of subjects, regardless of causality, were chills (5 patients, 
19%); anemia, headache, pyrexia, and vomiting (4 patients each, 15%); abdominal pain, 
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constipation, diarrhea, nausea, small intestine obstruction, fatigue, dehydration, dizziness, 
anxiety and alopecia, (3 patients each, 11%). 
Eleven patients (41%) developed serious adverse events (SAE) and 5 died on study, none of 
these events were considered to be related to study medication. 
 
No clinically significant abnormalities were noted on ECGs during the study, as of the data 
cutoff. Hematologic changes, expected based on the preclinical toxicology studies, have usually 
been mild to moderate at the dose levels tested, but severe anemia, neutropenia, lymphopenia 
and thrombocytopenia has been observed.  Post-treatment white blood cell counts tended to 
return towards baseline, indicating reversibility of myelosuppression. 
 
Of note, a patient diagnosed with mantle cell lymphoma experienced elevation of the 
lymphocytosis within a week of initiation of ASN002, per investigator suggestive of lymphocyte 
‘redistribution’. 
 
Mild abnormalities were noted on liver and renal function tests; however, no systematic shifts 
suggesting a clear treatment effect were noted. Acute kidney injury has been reported in patients 
with extensive retroperitoneal lymph node or kidney involvement by lymphoma. None were 
considered related to study drug. 
Evidence of clinical activity was reported in a patient diagnosed with peripheral T-cell 
lymphoma who experienced reduction of pruritus within a week after initiation of ASN002 80mg 
QD and for a patient diagnosed with follicular lymphoma (75 mg BID) who experienced 
reduction in measurements of lymphadenopathy of 43%. 
In summary, ASN002 has been relatively well tolerated at the doses up to 75 mg BID (150 mg 
daily) and the safety profile is in line with that expected based on preclinical data. 
Patients developed adverse events, including serious adverse events, which were generally 
expected given their underlying advanced cancers and lymphomas. 
Detailed information on ASN002 clinical data, a description of the nonclinical safety risks and 
guidance to the Investigators are provided in the Investigator Brochure. 
 
6.4 
Rationale  
6.4.1 
Rationale for Study 
The primary objectives of this first-in-human study are to evaluate the safety and tolerability of 
escalating doses of ASN002 including dose-limiting toxicities (DLTs) and the maximum 
tolerated dose (MTD), if possible, in subjects with relapsed/refractory lymphoma, and advanced 
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solid tumors (see 8.5.3 for the definitions of MTD). Preliminary antitumor activity will be 
evaluated based on the radiographic assessments of response. 
 
Rule-based design (3+3) will be used in the dose escalation component (Part A). This method is 
commonly used in Phase 1 oncology clinical trials for cytotoxic agents and molecularly targeted 
agents (26). The starting dose will be 10 mg administered every 12 hours. The subsequent 
cohorts will be treated on increasing dose levels that have been predetermined in the study 
protocol. 
 
The pharmacokinetic (PK) properties of ASN002 will be evaluated after single and multiple dose 
administrations at different dose levels. Every 12-hour administration was chosen based on the 
data from the nonclinical studies. 
 
 In Part B, 6 additional cohorts with approximately 14 subjects each will be assigned in disease-
specific cohorts (DLBCL, MCL, FL, PTCL, MF, and CLL) to obtain further safety and efficacy 
data for subsequent development decisions on ASN002. Cohort expansion after determination of 
the MTD is commonly used in Phase 1 oncology study designs. 
 
Subject with a response to treatment of complete response (CR), partial response (PR) or stable 
disease (SD) may continue ASN002 treatment until progression of disease (PD) or an intolerable 
adverse event (AE), withdraw of consent, or until termination of the study by the sponsor. 
 
6.4.2 
Rationale for Initial Dose and Schedule 
Based on the ICH S9 Guidance (27), an acceptable clinical starting dose for an oncology drug is 
1/10 the severely toxic dose in 10% of the animals (STD10) in rats, or 1/6 the highest nonseverely 
toxic dose (HNSTD) in dogs. The NOAEL and HNSTD are considered approximate in these 
studies. 
 
The non-clinical pharmacology, ADME, safety pharmacology and toxicology of ASN002 have 
been comprehensively evaluated. For systemic toxicity of ASN002, the NOAEL in the 28-day 
rat and dog toxicity studies were determined to be 20 mg/kg/day and 15 mg/kg/day, respectively. 
Based on the recommended body surface area conversion method, the rat and dog NOAEL 
equate to human equivalent doses of 3 mg/kg and 8 mg/kg, respectively. The proposed starting 
dose of 20 mg per day (dosed as 10 mg bid) is approximately 1/10 of the human equivalent dose 
(3 mg/kg) based on the NOAEL in the most sensitive species, i.e., rat, and lower than ICH S9 
recommended 1/6 of the highest non-severely toxic dose. Asana BioSciences believes that, 
considering the intended patient population, the 10-mg bid dose represents a safe starting dose 
for human exposure. 
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Preliminary pharmacokinetic analysis of data from cohorts 1-6, and 4a- suggest a half-life at 
least 12-14 hours. Therefore, once daily dosing of ASN002 are being evaluated in parallel 
cohorts.  Since no DLTs have been identified at the 75 mg BID cohort (150 mg total daily dose) 
and escalation has continued at 100 mg BID, the first QD regimen was 80 mg QD. Additional 
doses that are being evaluated include 120 mg QD. Patients will be accrued into these cohorts 
after safety assessment of the previous cohort during the DLT phase is completed, similar to that 
for the BID regimen. Since co-administration with a low-fat meal increased ASN002 AUC by 
about 80% compared to administration under fasted conditions, future cohorts may evaluate 
safety and tolerability of ASN002 when administered immediately after a light meal.  The first 
dose level at which this evaluation will occur will not be greater than 75% of the highest dose 
administered under fasted conditions. 
 
6.4.3 
Rationale for Recommended Part B Dose 
The safety review committee met on May 18, 2017 to review and discuss clinical experience and 
key safety data. It was agreed that the recommended dose for Part B of the study will be 75 mg 
BID in patients with hematologic malignancies and that enrollment in Part B can proceed. The 
selection of the recommended dose was supported by the observation of SAE / DLT 
(Pneumonia) of a NHL patient at a dose of 100 mg BID, the observed cumulative hematologic 
toxicity in patients enrolled at a dose of 120mg QD and the SAE (Pneumonitis) observed in a 
NHL patient at Cycle 2 considered possibly related to ASN002. 
At the recommended dose of 75 mg BID good systemic exposure and inhibition of serum 
biomarkers of inflammation can be observed. In NHL patients, treatment duration for more than 
6 months without dose limiting toxicities and evidence of clinical activity is observed. 
6.4.4 
Rationale for Additional Dose Finding in Advanced Solid Tumors 
The SRC also noted that the dose limiting toxicity (Pneumonia) at 100 mg BID and the Cycle 2 
SAE (Pneumonitis) at 120 mg QD were reported only in NHL patients, while patients with solid 
malignancies enrolled at 120mg QD were dosed up to 4 cycles without need for dose reduction. 
The SRC agreed to continue dose finding for patients with solid malignancies to further 
characterize safety, PK and PD in this study population. 
 
6.4.5 
Rationale for the Evaluation of ASN002 with Food 
Co-administration of ASN002 with a standardized low fat meal increased systemic exposure by 
about 80% in healthy subjects in a previous study. Future cohorts may evaluate safety and 
tolerability when ASN002 is administered immediately after a meal. The starting dose level at 
which the effect of a meal on safety, tolerability and pharmacokinetics will be evaluated will be 
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at least one dose lower than the highest dose evaluated when ASN002 was administered under 
fasted conditions 
 
7 
OBJECTIVES 
7.1 
Primary Objectives 
Part A: 
 To evaluate the safety and tolerability of ASN002 including dose-limiting toxicities (DLTs) 
and to determine the maximum tolerated dose (MTD). 
 
Part B: 
 To evaluate the safety, tolerability, and preliminary efficacy of ASN002 in subjects with 
relapsed/refractory diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), 
mantle cell lymphoma (MCL), peripheral T-cell lymphoma (PTCL), myelofibrosis (MF), 
and chronic lymphocytic leukemia (CLL). 
 
7.2 
Secondary Objectives 
Part A and B:  
 To evaluate the pharmacokinetic (PK) profile of ASN002 after single and multiple doses. 
 
7.3 
Exploratory/Pharmacodynamic Objectives 
Parts A and B: 
 To evaluate the effects of ASN002 on Phospho-STAT3, Phospho-S6, Phospho-SYK 
525/526, Phospho-ERK, and a panel of markers of inflammation (Appendix C)  
 Evaluate the response to therapy based on DLBCL molecular subtype [germinal center B-
cell like (GCB) or activated B-cell (ACB)]. 
 To evaluate the effects of ASN002 on JAK (V617F) mutant allele burden in subjects with 
MF. 
 To evaluate the effects of ASN002 on BCL2, and chromosome 17p. 
 
8 
INVESTIGATIONAL PLAN 
8.1 
Study Design 
This study will be performed at approximately 3 to 15 study centers located in the United States 
and Latin America. 
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The study is an open-label, non-randomized, uncontrolled, multicenter, dose escalation, cohort 
expansion and extension study with single and multiple-dose PK in subjects with 
relapsed/refractory lymphomas, MF, CLL. and advanced/metastatic solid tumors for which no 
standard therapy exists. The study will be conducted in 2 parts: 
 
Part A: Evaluation of the safety and tolerability of escalating multiple doses of ASN002; 
Part B: Cohort expansion of 6 identified disease-specific cohorts (DLBCL, MCL, FL, PTCL, 
MF and CLL) from Part A to further evaluate the safety, tolerability and antitumor 
activity of multiple doses of ASN002. 
 
Parts A will be a “3+3” dose escalation scheme beginning with dose level 1 at a dose of 10 mg 
every 12 hours. Subjects will receive a single dose of ASN002 on Day 1, followed by every 12 
or 24 hours, as assigned, dosing beginning on Day 3. The dose of ASN002 will be escalated to 
identify DLTs, and the MTD. If an MTD is not identified by the last scheduled cohort, dose 
escalation will continue in less than or equal to 50% increments until the MTD is identified. If 
supported by the PK profile, transition to once daily dosing may be considered. The starting dose 
of the once daily (qd) dosing cohorts will not exceed the total daily dose of the highest twice 
daily dose that is considered safe and well tolerated. Daily dosing cohorts may include doses 
beginning at 60 mg QD. Additional dose escalation may be performed for the qd dose cohorts, if 
the MTD is not identified by the 100 mg qd dose. 
 
The study design includes a screening period (up to 28 days), and a DLT observation period of 
28 days (Cycle 1). A subject with no DLTs during Cycle 1 will have the opportunity to continue 
to receive ASN002, at the discretion of the investigator. Subjects that are not able to complete 
Cycle 1 for reasons other than DLT will be replaced. Subjects participating in Parts B who 
discontinue from the study due to non-compliance or protocol violations may be replaced at the 
discretion of the Sponsor. Subjects may receive treatment with ASN002 in the absence of 
intolerable toxicity or disease progression for up to 12 months. If the subject is not a candidate 
for or chooses not to participate in additional treatment cycles, an end of treatment visit will be 
performed. A follow-up visit will be performed at least 30 days after the last dose of study 
medication. 
 
In Part A of the study, after the Safety Review Committee (SRC) has met and agreed to dose 
escalation, up to 3 additional subjects may be allowed in a lower cohort to gather additional PK, 
PD and safety data. The inclusion of these subjects will be based on agreement with members of 
the SRC and the Sponsor.
 
Part B will be an expansion of the MTD cohort into 6 disease-specific groups to evaluate 
preliminary clinical anti-tumor activity. Each cohort will contain up to 14 subjects with DLBCL, 
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MCL, FL, PTCL, MF, and CLL. Subjects may receive treatment with ASN002 in the absence of 
intolerable toxicity or disease progression for up to 12 months. 
 
The study design is illustrated in Figure A. The Schedule of Assessments for all parts of the 
study is located in Table 1 and Table 2. 
 
 
Figure A: Study Schema 
8.2 
Number of Subjects 
Approximately 148 evaluable subjects will be enrolled in the study 
Part A: Approximately 64 subjects which includes 40 subjects currently enrolled and an 
additional 24 subjects in cohorts dosed in fasted or fed states. 
Part B: Eighty-four subjects in 6 groups of 14 each.  The 6 groups are patients diagnosed 
with relapsed/refractory DLBCL, MCL, FL, PTCL, MF, and CLL. 
Assuming a 10% early termination rate, the total number of subjects is approximately 163. 
 
8.3 
Selection of Doses 
8.3.1 
Part A (Dose Escalation) 
Dose escalation will commence with dose level 1 (10 mg every 12 hours). Subsequent planned 
dose levels in Part A include: 20, 30, 40, 50, 75 and 100 mg administered every 12 hours or, 80, 
120, and 150 mg every 24 hours. These planned dose levels may be modified based on data 
obtained throughout the course of study conduct. If an MTD is not identified after completion of 
the highest scheduled dosing cohort (either bid or qd) dose escalation may continue in 
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increments of ≤ 50% until the MTD is identified. The doses for twice daily and the single daily 
doses are found in Table 6. 
The PK of ASN002 may be evaluated when administered with food. Up to 6 subjects per dose 
cohort may receive ASN002 after consuming a light meal. Subjects receiving ASN002 with food 
will receive no more than 75% of the highest dose that is deemed safe and well tolerated. 
Table 6: 
Twice Daily and Once Daily Dosing Cohorts  
 
Twice Daily Dose Cohorts 
Single Daily Dose Cohorts 
1 
10 mg 
N/A 
2 
20 mg 
N/A 
3 
30 mg 
 N/A 
4 
40 mg 
4aa 
80 mg 
5a 
50 mg 
5aa 
120 mg 
6a 
75 mg 
6aa 
150 mg 
7a 
100 mg 
 
a Cohorts may be administered ASN002 with and/or without food. 
Dose escalation may continue in increments of ≤ 50% until the MTD is identified 
 
8.3.2 
Part B (Cohort Expansion) 
Based on the safety and tolerability data from Part A, the initial dose for Part B is 75 mg BID for 
subjects with hematologic malignancies, including lymphoma, CLL and MF. Dose adjustments 
for individual subjects may be made based on observed toxicity per Section 8.3.3. 
 
8.3.3 
Dose Modifications 
Part A 
No dose reductions are permitted in Part A. If a subject experiences a DLT during Cycle 1, the 
subject should be discontinued from the study. 
At the end of Part A, if the subject is receiving a sub-MTD dose, the dose may be escalated to the 
MTD in consultation with the Medical Monitor and Sponsor. 
 
If a subject experiences an AE meeting DLT criteria after Cycle 1, dosing with ASN002 will be 
interrupted. If the AE resolves within 7 days to CTCAE grade ≤ 1, the subject may resume dose 
administration at the same dose or at a lower dose level as agreed between the sponsor and 
investigator. If the AE does not resolve to CTCAE grade ≤ 1 within 7 days or if the DLT 
reoccurs, the subject must be discontinued from the study. 
 
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Part B 
During Part B of the study, dose interruption (of up to 7 days) and modification for an AE 
meeting the criteria for DLT is allowed. For a drug-related toxicity, the dose should be 
immediately interrupted and supportive care provided until the AE resolves to ≤ Grade 1. After 
the AE resolves to ≤ Grade 1, retreatment at a lower dose may be considered upon agreement 
between the investigator and Sponsor medical monitor. If the toxicity recurs after re-challenge at 
a lower dose, study treatment should be discontinued. In the absence of > Grade 1 drug-related 
toxicity after at least 4 weeks of study treatment, subjects may be considered for intra-patient 
escalation to a higher dose that has been declared safe, in agreement with the investigators and 
Sponsor. The decision on possible escalation to a higher dose will be made on a case by case 
basis. 
Guidelines for dose modification for patients starting at 75 mg BID are listed in Table 7. 
Table 7:  Dose Modifications for Part B 
Dose Level 
mg (BID) 
-1 
50 
Recommended dose 
75 
+1 
100 
 
8.4 
Study Drug Administration 
ASN002 will be provided as 5-mg, 20-mg, and 50-mg tablets for oral administration. All study 
medication supplies will be provided by Asana BioSciences, LLC. The subject should be 
instructed to take the study drug at the same time, either once or twice daily. 
 
All study drugs will be administered orally every 12 or 24 hours, as assigned, on an empty 
stomach (either 1 hour before or 2 hours after a meal or snack) with approximately 240 mL of 
water (unless the patient is participating in a cohort in which co-administration with food is 
required). On study days in which there is a single PK sample, the subject should fast for at least 
2 hours prior to collection of the PK sample. On study days with multiple PK samples, the 
subject should fast overnight (at least 8 hours prior to study drug administration) and remain 
fasting for 2 hours after study drug administration. The date and time of the dose(s) taken prior to 
or on PK sampling days will be collected by the study site or via a diary card provided to the 
subject. 
 
Subjects receiving the twice daily dosing schedule will receive a single dose on Day 1 and skip 
the evening dose. On Day 2, twice daily dosing cohorts will begin twice daily dosing. Subjects 
assigned to the once daily dosing schedule will have a single dose on Day 1 and will skip the 
Day 2 dose. All other Day 2 study procedures should be completed per protocol except study 
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drug dosing. On Day 3, subjects assigned to once daily dosing will begin continuous once daily 
dosing. The effect of co-administration of ASN002 with a meal may be evaluated. Patients 
enrolling in this cohort will take their medication immediately after a meal 
 
8.4.1 
Missed or Vomited Doses 
Should the subject forget to take the study drug, s/he should take the study drug as soon as s/he 
remembers up to 2 hours after the planned dosing time. Thereafter, the forgotten dose should not 
be taken. Vomited doses should not be retaken. 
 
8.4.2 
Duration of Treatment 
The subject may continue to receive treatment with ASN002 in the absence of progressive 
disease or intolerable toxicity for up to 12 months. 
 
Further details regarding the study drug can be found in Section 16 
 
8.5 
Procedures and Criteria for Dose Escalation 
8.5.1 
Safety Review Committee 
The safety review committee will decide whether the dose escalation will continue to the next 
planned (or intermediate) dose level, if additional subjects will be added to the current dose level 
or if the dose escalation will be stopped. The safety review committee can also terminate the 
study due to safety concerns. Each review will be conducted with the latest available data. 
 
The overall safety will be evaluated after each cohort based on the safety data from the first 
28 days of treatment. The safety data will include medical history, all AEs, concomitant 
medications, vital signs, electrocardiogram (ECG) findings, and laboratory data. 
 
The safety review committee will be comprised of the following members: sponsor 
representatives including the clinical pharmacologist, medical adviser, chief medical officer, 
clinical manager; site investigators from active sites; CRO representatives including the medical 
monitor, pharmacovigilance medical monitor. Other representatives may be included as needed. 
 
8.5.2 
Dose Escalation Criteria 
Dose escalation will continue until the MTD, a plateau of ASN002 plasma concentration has 
been identified, or until the planned highest dose level is reached (refer to section 8.3.1). 
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Initially, 3 subjects will be treated at the same dose level. There will be at least a 24-hour interval 
between the administrations of the first dose of the study drug for each subject. 
 
After a minimum of 3 subjects in each cohort have completed cycle 1 of treatment and the safety 
review has been performed, 3 new subjects can be enrolled at the next higher dose level, in the 
absence of DLT. No intra-subject dose escalation is permitted during the dose escalation phase. 
 
If 1 of the first 3 subjects experiences a DLT, an additional 3 subjects will be enrolled at the 
same dose level. The dose escalation will be stopped if 2 or more subjects among a cohort of 3 or 
6 subjects experience a DLT. Three additional subjects will be entered to the previous lower dose 
level cohort, if only 3 subjects were treated in that cohort. 
 
The MTD is defined as a dose level immediately below that at which ≥ 2 of 6 subjects 
experience a DLT. Subjects considered to be evaluable for the MTD determination are the 
subjects who have received the study drug for 28 days or who have discontinued the study drug 
earlier than 28 days because of a DLT. 
 
Dose escalation can also be stopped based on the PK data if a plateau in ASN002 plasma 
concentration versus the dose curve is observed prior to reaching the MTD. Subsequent 
development decisions regarding the therapeutic doses of ASN002 for future studies will be 
considered in the evaluation of PK data. 
 
8.5.3 
Dose-Limiting Toxicity (DLT) Definitions 
During Phase 1, the MTD will be determined based on DLT occurring during the first 28 days 
plus any rest period if applicable (i.e. Cycle 1). All adverse events unless they have been 
determined to be not related to study drug will be taken into consideration in determining DLT. 
NCI-CTCAE version 4.03 will be the basis for the descriptive terminology and grading of 
adverse events. DLT are defined as follows: 
 
Non-hematologic DLT is defined as: 
Any Grade ≥ 3 AE, with the following exceptions 
 Symptomatic adverse events such as nausea, vomiting and diarrhea will not be 
considered dose limiting if they can be reduced to less than grade 3 within 72 hours with 
standard supportive measures such as antiemetics and antidiarrheals. 
 Asymptomatic Grade 3 electrolyte abnormalities which can be corrected by optimal 
supplementation. 
 
 
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Hematologic DLT is defined as: 
≥ Grade 4 neutropenia or thrombocytopenia that lasts more than 7 days after the last dose of 
study drug; 
 
Febrile neutropenia; 
≥ Grade 3 thrombocytopenia in the presence of bleeding; 
See section 12.4 for assessments of intensity criteria. 
 
8.6 
Definitions of Response to ASN002 
8.6.1 
Relapsed/Refractory Lymphomas 
The 2014 Lugano Classification will be used to document disease response or progression in 
subjects with DLBCL, MCL, FL, or PTCL (28). 
 
8.6.2 
Solid Tumors  
The RECIST 1.1 criteria will be used to document disease response or progression in subjects 
with advanced/metastatic solid tumors (29). 
 
8.6.3 
Myelofibrosis 
The International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-
MRT) criteria will be used to document disease response or progression in subjects with 
myelofibrosis (30) 
 
8.6.4 
Chronic Lymphocytic Leukemia 
The International Workshop on Chronic Lymphocytic Leukemia (31) will be used to document 
disease response or progressions in subjects with CLL. For patients with persistent 
lymphocytosis, a partial response in all other measures will be defined as a partial response with 
lymphocytosis (33). 
 
8.6.5 
Clinical Disease Progression 
Clinical disease progression can be characterized by loss of appetite, weight loss, change in bone 
pain/worsening bone pain, increased use of analgesics, cachexia/decrease in performance scale 
(e.g., an increase in the subject’s ECOG score) and other symptoms of progressive neoplastic 
disease. 
 
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The investigator will evaluate the integrated results of all these parameters and based on this 
evaluation will decide if a subject has clinical progression. 
 
9 
SELECTION AND WITHDRAWAL OF SUBJECTS 
9.1 
Subject Inclusion Criteria 
In order to be eligible to participate in the study, subjects must meet the following criteria: 
1.  Written informed consent obtained prior to any study-related procedure being performed; 
2.  Male or female subjects at least 18 years of age at the time of consent; 
3.  ECOG Performance Status 0-2; 
4.  Radiographically evaluable tumor by 2014 Lugano Classification recommendations 
(lymphomas) or RECIST 1.1 (advanced solid tumors); 
5.  Recovered from the reversible effects of prior antineoplastic therapy (with the exception of 
alopecia and Grade 1 neuropathy). Screening blood counts of the following: 
a. Absolute neutrophil count ≥ 1000/μL, 
b. Platelets ≥ 75,000/μL, 
c. Hemoglobin ≥ 8 g/dL (with transfusion support); 
6.  Screening chemistry values of the following: 
a. Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3.0 × upper 
limit of the normal reference range (ULN), 
b. Total bilirubin ≤ 1.5 × ULN, 
c. Creatinine ≤ 1.5 × ULN; 
7. At screening, life expectancy of at least 3 months; 
8. Subject is willing and able to comply with all protocol required visits and assessments; 
9. Male and female subjects of child-bearing potential must agree to use medically acceptable 
methods of birth control throughout the study and for thirty (30) days after the last dose of 
study medication. 
10. Subjects must have one of the following disease characteristics 
 
(Part A only)  
a. Histologically or cytologically confirmed metastatic and/or advanced solid 
tumors or lymphomas for which no standard therapy exists, or who are not 
eligible for standard treatment. Subjects must have received at least one prior 
therapy for their malignancy; 
(Part A or B only)  
Lymphomas 
b. Histologically confirmed DLBCL/MCL/FCL/PTCL on the basis of excisional 
lymph node or extranodal tissue biopsy; 
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c. Diagnosis of relapsed/refractory DLBCL/MCL/FL/PTCL defined as 1) 
recurrence of disease after a CR, or 2) PR, SD at completion of treatment 
regimen preceding entry into study.  Subjects must have received at least one 
regimen of treatment for lymphoma. 
d. Subjects must not be candidates for standard therapy. 
e. Subjects who have not received SCT must be ineligible to receive SCT. 
 
 
 
(Part B only) 
Primary Myelofibrosis 
f. Confirmed diagnosis of PMF, post-PV MF, or post-ET MF according to the 
2008 WHO criteria (30), 
g. High risk or intermediate-2 risk or symptomatic intermediate-1 risk as defined 
by Dynamic International Prognostic Scoring System (DIPSS), see Appendix 
D 
h. Palpable splenomegaly at least 5 cm below the left costal margin, 
i. Known JAK2 mutational status, 
j. Refractory/relapsed, or intolerant to prior JAK2 therapy in the judgement of 
the investigator. 
Chronic Lymphocytic Leukemia 
k. Confirmed diagnosis of B-cell CLL, according to the International Workshop 
on Chronic Lymphocytic Leukemia (IWCCL) (31) 
l. Measurable disease defined as lymphocytosis> 5,000/uL, or at least one 
palpable or CT measurable lesion (> 2.0 cm), or quantifiable bone marrow 
involvement. 
m. Active disease requiring treatment as defined by IWCLL consensus criteria 
n. Relapsed or refractory disease or intolerant to a maximum of 2 prior systemic 
therapies. One of the prior regimens must have included a purine analog 
and/or an alkylating agent. 
9.2 
Subject Exclusion Criteria 
Subjects who meet any of the following criteria will not be eligible to participate or continue 
further in the study: 
 
1. Have received prior standard therapy regimens within 4 weeks of Day 1; 
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2. Have received prior treatment with monoclonal antibodies within 6 weeks of first dose of 
Day 1; 
3. Have had major surgery within 30 days prior to the start of Day 1; 
4. Received any investigational treatment within 4 weeks prior to the start of study 
medication; 
5. Have had an infection requiring the use of parenteral antibiotics within 14 days prior to the 
start of Day 1; 
6. Have known central nervous system metastasis or CNS lymphoma; 
7. Is receiving corticosteroids (>10 mg prednisone daily or equivalent);  
8. Has known bleeding diathesis that could be considered a safety concern; 
9. Has a history of other malignancy within the 3 years prior to screening, except adequately 
treated basal cell or squamous cell carcinoma of the skin, or carcinoma in situ; 
10. Has difficulty swallowing medications, or known history of malabsorption syndrome; 
11. Has a serious concurrent medical condition, such as: 
a. History of congestive heart failure New York Heart Association (NYHA) class III 
or IV, 
b. 12-Lead ECG abnormalities considered by the investigator to be clinically 
significant or QTcF ≥ 450 milliseconds at screening.  Abnormal values may be 
confirmed from one additional assessment. For subjects with QTcF ≥ 450 on initial 
screening ECG, the mean of the two QTcF assessments will be used to determine 
eligibility; 
c. Myocardial infarction, angioplasty, or cardiac stent placement within the last 6 
months, 
d. HIV infection, 
e. Known Hepatitis B or C infection. Subjects at high risk for Hepatitis B or C 
infection should have serology testing to rule out infection; 
f. A medical condition requiring the therapeutic use of anticoagulants 
g. Condition or situation which may put the subject at significantly increased risk, 
may confound the study results, or may interfere significantly with the subject’s 
participation in the study 
12. Known hypersensitivity to ASN002 or its excipients; 
13. Prior participation, i.e., receipt of study medication, in this study; 
14. Any condition that, in the opinion of the investigator, would impair the subject’s ability 
to comply with study procedures; 
15. Subjects that are pregnant of lactating; 
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16. Part B only:Prior treatment with SYK or JAK inhibitors, except for subjects with 
myelofibrosis treated with a JAK inhibitor. 
 
9.3 
Subject Discontinuation Criteria 
Study discontinuation will occur when a subject who signed informed consent ceases 
participation in the study. Subjects can be discontinued from the study for one of the following 
reasons: 
 An adverse event; 
 Progression of disease; 
 Death; 
 A protocol violation (reason must be specified, for example: lack of compliance, use of a 
prohibited concomitant medication, failure to meet inclusion/exclusion criteria after 
study entry, etc.); 
 Withdrawal of consent by the subject (reason must be specified); 
 The subject was “lost to follow-up”; 
 Other reasons (reason must be specified, for example: the subject moved, investigator 
decision, sponsor decision to terminate study, etc.). 
A subject is free to withdraw his consent and discontinue participation in the study at any time. 
The investigator must withdraw any subject from the study if the subject requests to be 
withdrawn.  Any subject who withdraws consent as a result of an adverse event, regardless of 
intensity or investigator’s opinion, must be reported as a discontinuation due to adverse event. 
If a subject discontinues from the study, all end of treatment procedures should be conducted as 
detailed in Table 1 or Table 2. The date a subject discontinues ASN002, and the reason for 
discontinuation will be recorded in the source documentation and electronic Case Report Form 
(eCRF). If a subject has an ongoing adverse event, the event will be followed until resolution or 
stabilization for at least 30 days after the last dose of ASN002. If a subject refuse to complete 
any of the specified End of Treatment procedures, this information will be recorded in the source 
documentation. A subject who discontinues from the study will not be allowed to re-enter the 
study.  
 
When a subject is “lost to follow-up” (i.e., fails to return for study visits), a reasonable effort will 
be made to contact the subject: 
1. to determine the reason for the failure to return and these contacts will be recorded in the 
source documents; 
2. to follow up on any ongoing AEs from the previous visits; 
3. to recover any unused ASN002. 
 
The subject should be identified as “lost to follow up” in the eCRF, as appropriate. 
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9.3.1 
Replacement Procedures 
During Part A, a subject who prematurely discontinues from the study before completing 28 days 
of the dose escalation component for reasons other than DLT, or has demonstrated significant 
non-compliance with ASN002 dosing, may be replaced at the discretion of the sponsor. Subjects 
participating in Parts B who discontinue from the study due to non-compliance or protocol 
violations may be replaced at the discretion of the Sponsor. 
 
10  VISIT PROCEDURES 
10.1 Screening 
The Schedule of Assessments to be performed during the study are detailed in Table 1 - Table 4 
10.1.1 
Subject Screening  
Investigators will maintain a screening log of all potential study subjects. This log will include 
limited information about the potential subject (screening identification (ID), date of consent, 
initials, date of birth, sex, race and ethnicity), the outcome of the screening process, and the date 
of the outcome. Investigators will provide information about the study to subjects who appear to 
meet the criteria for participation in the study.  
 
After obtaining informed consent, the full assessment of eligibility will be conducted according 
to the Schedule of Assessments in Table 1 or Table 2. Results of tests performed that would 
ordinarily be performed according to the standard of medical care, may be used for screening 
purposes if obtained within the screening period. Once the subject has fulfilled all entry criteria, 
a subject ID will be assigned. 
 
Subjects who do not meet eligibility criteria may be re-screened at the discretion of the sponsor. 
Any subject who is re-screened will be assigned a new screening ID number and will be required 
to repeat all screening procedures unless approved in advance by the sponsor. 
 
For those subjects who are screened for the study but are considered ineligible or are never 
entered into the study (i.e., do not receive study medication), the following eCRF data will be 
collected: date of informed consent, demographic information, AEs, and reason for non-
participation (e.g., inclusion and/or exclusion criteria not met, withdrawal of consent, etc.). 
 
10.2 Cycle 1 
All study assessments will be conducted in accordance with the Schedule of Assessments in 
Table 1 - Table 4, as applicable to the study part assignment. During visits when multiple PK 
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samples are collected, the following “priority order” will be in effect when more than 1 
assessment is required at a particular time point: 

PK blood sampling will take priority over all study procedures except ASN002 dose
administration. Pre-dose samples should be obtained immediately (within 1 hour) prior to
dose administration.

Safety assessments (e.g., vital signs, 12-lead ECG, AE questioning) may be performed
within 15 minutes of the protocol specified time point.
10.2.1 
Day 1 
The subject should arrive at the investigational site after an overnight fast of at least 8 hours. The 
investigator will confirm the subject’s eligibility for the study and ensure the subject’s condition 
has not changed since the screening assessments. The subject will have the following procedures 
performed on Day 1: 

Obtain hematology, serum chemistry, liver function tests, urinalysis, and pregnancy test
(if applicable) if not done within 72 hours prior to Day 1  (Table 10);

Perform physical examination within 72 hours of Day 1 (Section 12.10), including ECOG
PS and measurement of the spleen by manual palpation in subjects with MF;

Review study entry criteria to confirm eligibility (Section 9);

Obtain baseline MPN-SAF form completed for MF subjects only;

Obtain pre-dose PK/PD samples (Section 13.1), ECG tracing (Section 12.9), and vital 
signs including weight (Section 12.8) according to the schedule in Table 3 or Table 4, as 
applicable;

If dosing is to occur in the presence of food, a light meal will be administered prior to
dosing. ASN002 should be administered within 15 minutes of consumption of the light
meal.

Administer assigned dose of ASN002 with approximately 240 mL of water;

Obtain post-dose PK/PD samples, ECG tracings, and vital signs according to the schedule
in Table 3 or Table 4, as applicable;

Observe for adverse events;

Record any changes in concomitant medications since the last visit
10.2.2 
Day 2 

Obtain a l PK sample (Section 13.1), ECG tracing (Section 12.9), and vital signs (Section 
12.8) according to the schedule in Table 3 or Table 4 (as applicable).

Assess for AEs and changes to concomitant medications.

If dosing is to occur in the presence of food, a light meal will be administered prior to
dosing. ASN002 should be administered within 15 minutes of consumption of the light
meal.

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• Hold dosing if the subject is participating in a QD cohort. 
• Provide Diary card to the subject, and provide instructions for completion 
 
10.2.3 
Day 3  
For subjects in the QD dosing cohorts only  
The subject will arrive at the study site in the morning in a fasted state prior to taking the study 
drug.  
• Obtain a pre-dose PK sample (Section 13.1), ECG tracing (Section 12.9), and vital signs 
(Section 12.8) according to the schedule in Table 3; prior to study drug administration; 
• If dosing is to occur in the presence of food, a light meal will be administered prior to 
dosing.  ASN002 should be administered within 15 minutes of consumption of the light 
meal.  
• Administer assigned dose of ASN002 with approximately 240 mL of water after PK 
sample is collected; 
• Dispense ASN002 for dosing at home; 
• Fast may be broken approximately 2 hours after dosing; 
• Assess for AEs and changes to concomitant medications. 
 
10.2.4 
Day 4, and 11 (± 1 day) 
Part A only 
• Obtain blood sample for liver function tests (Table 10); 
• Assess for AEs and changes to concomitant medications. 
 
10.2.5 
Day 8 (± 1 day) 
The subject will arrive at the study site in the morning in a fasted state prior to taking the study 
drug.  
Part A 
• Obtain a trough level PK sample and PD sample prior to study drug administration 
(Table 3 or Table 4, as applicable); 
• Obtain clinical laboratory assessments as described in Table 1, or Table 2 (as applicable) 
and Table 10; Perform ECG; Obtain vital signs (Section 12.8); 
• Assess ASN002 treatment compliance (Section 10.7); 
 
 


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 Observe for adverse events, and record any changes in concomitant medications since the 
last visit; 
 If dosing is to occur in the presence of food, a light meal will be administered prior to 
dosing.  ASN002 should be administered within 15 minutes of consumption of the light 
meal.  
 Administer ASN002 with approximately 240 mL of water; 
 Dispense ASN002 for dosing at home, if indicated; 
 Fast may be broken approximately 2 hours after dosing for subjects who remain fasted. 
 
Part B assessments 
 Obtain MPN-SAF form completed for MF subjects only; 
 Vital signs and ECG are not required on Day 8, 15 and 22 in Part B 
 Treatment compliance occurs at the end of Cycle 1 
 
10.2.6 
Day 15 (± 1 day) 
Subjects will arrive at the study site in the morning of Day 15 after an overnight fast of at least 8 
hours. The following procedures will be performed. 
 Obtain PK/PD samples according to Section 13.1 and Table 3 or Table 4, as applicable; 
 Perform physical examination (Section 12.10); 
 Obtain clinical laboratory assessments as described in Table 1, Table 2, and Table 10  
 Obtain vital signs according to Table 3;  
 Obtain ECG tracing according to Table 3;  
 Assess ASN002 treatment compliance; 
 Observe for adverse events, and record any changes in concomitant medications since the 
last visit; 
 If dosing is to occur in the presence of food, a light meal will be administered prior to 
dosing. ASN002 should be administered within 15 minutes of consumption of the light 
meal.  
 Administer ASN002 with approximately 240 mL of water; 
 Dispense ASN002 for dosing at home, if indicated; 
 Fast may be broken approximately 2 hours after dosing. 
 
Part B assessments 
 Obtain MPN-SAF form completed for MF subjects only  
 
10.2.7 
Day 16 (± 1 day) 
For subjects in the QD dosing cohorts only 
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 Obtain a trough level PK sample (Section 13.1), ECG tracing (Section 12.9), and vital 
signs (Section 12.8) according to the schedule in Table 3; 
 If dosing is to occur in the presence of food, a light meal will be administered prior to 
dosing. ASN002 should be administered within 15 minutes of consumption of the light 
meal.  
 Administer assigned dose of ASN002 with approximately 240 mL of water; 
 Fast may be broken approximately 2 hours after dosing; 
 Assess for AEs and changes to concomitant medications. 
 
10.2.8 
Day 22 (± 1 day) 
The subject should arrive at the study site in the morning of Day 22 in a fasted state of at least 2 
hours. The following procedures will be performed.  
 Obtain a trough level PK sample prior to study drug administration;  
 Obtain clinical laboratory assessments as described in Table 1 or Table 2 (as applicable) 
and Table 10; 
 Obtain vital signs (Section 12.8); 
 Perform ECG  
 Assess ASN002 treatment compliance (Section 10.7); 
 Observe for adverse events, and record any changes in concomitant medications since the 
last visit; 
 If dosing is to occur in the presence of food, a light meal will be administered prior to 
dosing. ASN002 should be administered within 15 minutes of consumption of the light 
meal.  
 Administer ASN002 with approximately 240 mL of water; 
 Dispense ASN002 for dosing at home; 
 Fast may be broken approximately 2 hours after dosing. 
 
Part B assessments 
 The MPN-SAF form (completed for MF subjects only) may be completed at home if the 
Day 22 laboratory assessments are not performed. Day 22 laboratory assessments may be 
omitted. 
 
10.2.9 
Day 28 
Day 28 is considered the end of Cycle 1 and the DLT assessment period. No site procedures are 
scheduled for Day 28. The subject should return to the study site the following day for the 
beginning of the next cycle. All scheduled follow up assessments must be completed prior to the 
initiation of subsequent ASN002 dosing. 
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10.3 Subsequent Cycles (± 3 days) 
10.3.1 
Day 1 
• Perform clinical laboratory assessments according to Table 1 or Table 2 (as applicable) 
and Table 10, if not performed within 3 days of Day 1; 
• Review disease status, if an assessment was performed (Section 11.1.1); 
• Perform physical examination (Section 12.10) including vital signs, weight, ECOG PS.  
Determine if the subject should continue ASN002;  
• Obtain pre-dose PK/PD sample (Section 14.1) and Table 3 or Table 4, as applicable); 
• Assess ASN002 treatment compliance (Section 10.7); 
• Observe for adverse events, and record any changes in concomitant medications since the 
last visit; 
• Dispense additional ASN002 and subject diary. 
 
Part B assessments 
• Obtain MPN-SAF form completed weekly for MF subjects only  
• Spleen length should be assessed by manual palpation every 4 weeks for the first 24 weeks 
and every 12 weeks thereafter of the study (MF subjects only); 
 
10.3.2 
 Day 15 (± 2 days) 
• Obtain clinical laboratory assessments as described in Table 1 and Tabel 10 
• Obtain vital signs (Section 12.8); 
• Obtain PK sample as specified in Table 4 
• Observe for adverse events, and record any changes in concomitant medications since the 
last visit; 
• Schedule radiographic evaluation of the subject’s disease status to be conducted and 
evaluated prior to the end of the cycle, if appropriate; 
o For DLBCL, MCL, FL, and PTCL schedule every 12 weeks (end of Cycle 3, 6, 9, etc.). 
o For advanced solid malignancies schedule every 8 weeks (end of Cycle 2, 4, 6, etc.) for 
the first 24 weeks, and then every 12 weeks thereafter. 
o For MF schedule MRI (preferred) or CT of abdomen on week 24 
o For CLL schedule every 8 weeks for the initial 24 weeks and every 12 weeks thereafter 
(CT scan for chest/abdomen/pelvis recommended if previously abnormal and otherwise 
with a CR). 
• Schedule a bone marrow aspirate and biopsy for CLL subjects in case of CR or cytopenias 
of uncertain origin. 
• Obtain MPN-SAF form completed weekly for MF subjects only 


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10.4 End of Treatment 
The following assessments should be performed within 1 week of last dose of ASN002. 
• Perform physical examination (Section 12.10); 
• Obtain vital signs, including weight (Section 12.8); 
• Obtain ECOG performance status (Appendix B); 
• Obtain ECG (Section 12.9);Perform clinical laboratory tests Table 1 or Table 2  
(As applicable) and Table 10, including pregnancy test if applicable; 
• Observe for adverse events, and record any changes in concomitant medications since the 
last visit; 
• Perform disease assessment (Section 11.1.1); 
• Assess medication compliance (Section 10.7); 
• Obtain all unused medication for reconciliation and destruction. 
• Obtain MPN-SAF form completed weekly for MF subjects only 
• Obtain PK samples (Part B only, Table 2) 
 
10.5 30-Day Follow-up 
The following assessments should be performed at the follow-up visit. 
• Perform physical examination (Section 12.10); 
• Obtain vital signs, including weight (Section 12.8); 
• Perform clinical laboratory tests (Table 10); 
• Follow up on all AEs ongoing at the End of Treatment visit. 
 
10.6 Prior and Concomitant Medications 
Any concomitant therapy with the exceptions noted in Section 10.6.1 that are considered 
necessary for the subject’s welfare may be given at the discretion of the investigator. The 
investigator will authorize the therapy after consideration of the clinical situation, the potential 
for masking symptoms of a more significant underlying event, and whether the use of the therapy 
will compromise the outcome or validity of the study. 
 
Any concomitant therapy used while the subject is in the study must be recorded in the source 
documents and eCRF. The medication name, dosage, date, and indication for use must be 
recorded. The Medical Monitor should be notified in advance of (or as soon as possible after) 
any instances in which prohibited therapies are or need to be administered.  
 
 


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Any changes to ongoing concomitant medications or the addition of new medications must be 
recorded in the source documents and eCRF. 
 
Upon entering the study, each subject will be instructed to report the use of any medication to the 
investigator. Subjects will also be instructed about the importance of not taking any medication 
(including over-the-counter medications) without consulting the investigator. 
 
10.6.1 
Prohibited Medications  
The following medications will be prohibited during the study: 
 
• Chemotherapy, radiotherapy, immunotherapy, or investigational treatments are not 
allowed with concomitant use of ASN002; 
• Use of localized palliative radiation for pre-existing lesions for pain control may be 
approved after discussion with the sponsor. The radiation field must not include any 
target or non-target lesions, and progressive disease must be ruled out as the underlying 
requirement for palliative radiotherapy. 
• Therapeutic doses of anticoagulants.  
 
10.6.2 
Concomitant Use of Drugs that may Affect Gastric pH 
The use of antacids and H2 antagonists should be considered in place of proton pump inhibitors 
in patients receiving ASN002. Aluminum, magnesium, or calcium-based antacids and H2-
antagonists should be taken in a window of 2-10 hours after administration of the actual dose of 
ASN002. Refer to Table 8 for examples of concomitant medication that may affect gastric pH. 
 
Table 8:  
Examples of H2 antagonists, and Proton Pump Inhibitors 
 
H2 antagonists 
Proton Pump Inhibitors 
Antacids 
cimetidine 
esomeprazole 
Aluminum-based antacids 
omeprazole 
lansoprazole 
Magnesium-based antacids 
nizatidine 
pantoprazole 
Calcium-based antacids 
ranitidine 
rabeprazole 
 
The examples provided are not an exhaustive list of possible drugs that may affect gastric pH.  
The investigator is responsible for assessing all concomitant medications that may have effects on gastric pH. 
  


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10.7 Treatment Compliance 
Study drug compliance will be calculated weekly during Cycle 1. In subsequent cycles, 
compliance will be calculated on Day 1 prior to receiving additional ASN002. Subjects taking 
too much or too little study drug should be re-educated on the proper use of study drug. Repeated 
non-compliance (less than 80% or greater than 100%) should be evaluated by the investigator for 
the need to withdraw the subject. 
 
Compliance can be assessed using the following formula:  
 
(Number of tablets taken/number of tablets required per protocol) * 100 = % compliance  
Accidental or intentional overdoses should be reported to the sponsor/designee promptly (refer to 
Section 12.6.1). 
 
10.8 Blinding and Randomization 
The study is an open-label, non-randomized study. 
 
11 ASSESSMENT OF EFFICACY 
11.1 Primary Efficacy Variable 
11.1.1 
Disease Response 
It is expected that the investigator will choose the most appropriate method for radiographic 
assessment of the individual subject’s disease status. Subjects with a diagnosis of lymphoma are 
expected to undergo CT (for non-FDG-avid lymphoma), or PET-CT (for FDG-avid lymphoma) 
for their efficacy evaluation. Subjects with advanced or metastatic solid tumors are expected to 
undergo CT with contrast (unless medically contraindicated) or MRI for their efficacy 
evaluation. 
For patients with MF spleen measurement will be performed by palpation and by MRI 
(preferred) or CT scan. 
For patients with CLL a baseline CT scan of chest/abdomen/pelvis and a bone marrow aspirate 
and biopsy are desirable. 
11.1.1.1 
DLBCL, MCL, FL, and PTCL 
The International Conference on Malignant Lymphoma (ICML) Recommendations for Initial 
Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma (2014 
Lugano Classification) will be used to determine the stage of subjects with lymphoma, and the 
response to treatment. 
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The following endpoints will be used to determine the response to treatment with ASN002 in 
subjects with solid tumors: 
• Objective Response Rate 
• Duration of Response 
• Time to Tumor Progression (TTP) 
• Progression-free Survival (PFS) 
• PFS rate at week 24 
11.1.1.2 
Advanced Solid Malignancies 
The Tumor, Nodes, Metastasis (TNM) staging system developed by the American Joint 
Committee on Cancer (AJCC) will be used to record the subject’s clinical stage. Disease 
response will be assessed using the RECIST 1.1 criteria.  
The following endpoints will be used to determine the response to treatment with ASN002 in 
subjects with solid tumors: 
• Objective Response Rate 
• Duration of Response 
• TTP 
• PFS 
• PFS rate at week 24 
 
11.1.1.3 
Myelofibrosis 
The International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-
MRT) and European LeukemiaNet (ELN) response criteria will be used to evaluate the response 
to treatment with ASN002 (31). 
The following endpoints will be used to determine the response to treatment with ASN002 in 
subjects with MF:  
• Splenic response rate at week 24 
• Clinical improvement rate at week 24 
• Symptom response evaluated using the Myeloproliferative Neoplasm Symptom 
Assessment Form (MPN-SAF) tool  
• rate of RBC transfusion through week 24  
 
11.1.1.4 
CLL 
The response in patients with CLL will be evaluated according to the criteria of the International 
Workshop on Chronic Lymphocytic Leukemia (32); with the exception that lymphocytosis will 
not be the sole criterion for disease progression. For patients with persistent lymphocytosis, 


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A partial response in all other measures will be defined as a partial response with lymphocytosis 
(33). 
The following endpoints will be used to determine the response to treatment with ASN002 in 
subjects with CLL: 
• Objective Response rate 
• Duration of response 
• TTP 
• PFS 
• PFS rate at week 24 
 
11.2 Secondary Efficacy Variables. 
11.2.1 
Eastern Cooperative Oncology Group (ECOG) Performance Status 
ECOG performance status will be assessed according to the schedule of assessments in Table 1 
or Table 2. Changes from baseline will be evaluated. Refer to Appendix B for further 
information. 
 
11.3 Exploratory Markers 
11.3.1 
Assessment of Biomarkers 
A panel of biological markers will be assessed to determine the effect of ASN002 on both SYK 
and JAK/STAT pathways in the disease process. Biomarkers for this study are shown in Table 9. 
Some of these markers include the following:  
 
Lymphomas and solid tumors, changes from baseline in the following biomarkers 
• Phopsho-STAT3, Phospho-S6, Phospho-SYK 525/526, Phospho-ERK 
• DLBCL molecular subtype (GCB, ACB) (baseline only) 
• Inflammation panel (Appendix C). 
 
Myelofibrosis 
• Changes in JAK (V617F) mutant allele burden.  
• Inflammation panel (Appendix C).  
CLL 
• Changes in BCL2 expression  
• Changes in the status of chromosome 17p.  
• Inflammation panel (Appendix C). 


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Table 9:  Pharmacodynamic Assessments 
 
Solid Tumors, and 
Lymphoma 
MF 
CLL 
Phospho-STAT 3 
X 
X 
X 
Phospho-S6 
X 
X 
X 
Phospho-SYK 525/526 
X 
X 
X 
Phospho-ERK 
X 
X 
X 
Inflammation panel 
X 
X 
X 
JAK (V617F) allele 
 
X 
 
BCL2 expression 
 
 
X 
Chromosome 17p del. 
 
 
X 
Molecular subtyping 
DLBCL only 
 
 
 
Additional details regarding specimen ascertainment may be found in the Laboratory Manual. 
 
12 ASSESSMENT OF SAFETY 
12.1 Definitions 
12.1.1 
Adverse Events 
An adverse event (AE) is any unfavorable or unintended change in body structure (signs), body 
function (symptoms), laboratory result (e.g., chemistry, ECG, X-ray, etc.), or worsening of a 
preexisting condition associated temporally with the use of the study medication whether or not 
considered related to the study medication. AE will be captured once a subject has signed the 
informed consent. AEs include: 
 
• Changes in the general condition of the subject; 
• Subjective symptoms offered by or elicited from the subject; 
• Objective signs observed by the investigator or other study personnel; 
 
 


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 All concurrent diseases that occur after the start of the study, including any change in 
severity or frequency of pre-existing disease; 
 All clinically relevant laboratory abnormalities or physical findings that occur during the 
study. 
 
A treatment-emergent adverse event (TEAE) is any condition that was not present prior to 
treatment with study medication but appeared following treatment, was present at treatment 
initiation but worsened during treatment, or was present at treatment initiation but resolved and 
then reappeared while the individual was on treatment (regardless of the intensity of the AE 
when the treatment was initiated). 
 
All AEs, including any observed or volunteered problems, complaints, signs or symptoms must 
be recorded on the AE page of the eCRF, regardless of whether the AE is considered related to 
ASN002. This would include AEs resulting from concurrent illness, reactions to concurrent 
medication use, or progression of disease states (excluding the disease under study). A condition 
present at baseline that worsens after initiation of study treatment will be captured as an AE; the 
onset date will be the date the event worsened. The AE should be recorded in standard medical 
terminology when possible. The reporting of AEs should include a definitive diagnosis. 
Reporting of a list of signs or symptoms should only occur when no definitive diagnosis can be 
made. 
 
12.1.2 
Serious Adverse Events 
A serious adverse event (SAE) is defined as an AE that: 
 Results in death; 
 Is immediately life-threatening (there is an immediate risk of death from the AE as it 
occurred; this does not include an AE that had it occurred in a more serious form may 
have caused death); 
 Results in or prolongs an inpatient hospitalization (Note: a hospitalization for elective or 
pre-planned surgery, procedure, or drug therapy does not constitute an SAE); 
 Results in permanent or substantial disability (permanent or substantial disruption of 
one’s ability to conduct normal life functions); 
 Is a congenital anomaly/birth defect (in offspring of a subject using the study medication 
regardless of time to diagnosis); 
 Is considered an important medical event. 
 
Important medical events are defined as events that, based upon appropriate medical judgment, 
may jeopardize the subject and may require medical or surgical intervention to prevent one of the 
other serious outcomes. Examples of important medical events include allergic bronchospasm 
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requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions 
that do not result in inpatient hospitalization. 
 
12.2 Monitoring Adverse Events 
At each visit, subjects will be queried regarding any AEs that have occurred since the last visit. 
Subjects will be asked to volunteer information concerning AEs with a non-leading question 
such as, “How do you feel?” Study site personnel will then record all pertinent information in the 
source documents and the eCRF. The study drug compliance record should also be reviewed to 
detect non-compliance. 
 
Any AEs identified on the subject’s diary will be reported in the appropriate eCRF module.  
 
12.3 Relationship to Study Drug 
The degree of “relatedness” of the AE to the study medication must be described using the 
following scale:  
 
 Not related indicates that the AE is definitely not related to the study medication; 
 Possibly related indicates that a direct cause and effect relationship between study 
medication and the AE has not been demonstrated, but there is evidence to suggest there 
is a reasonable possibility that the event was caused by the study medication; 
 Probably related indicates that there is evidence suggesting a direct cause and effect 
relationship between the AE and the study medication. 
 
12.4 Intensity Assessment 
An assessment of intensity grade will be made using the NCI CTCAE version 4.03 (refer to 
Appendix A), which includes the following descriptors: 
 
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated; 
 
Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental activities of daily living (ADL); 
 
Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self-care ADL; 
 
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Grade 4: Life-threatening consequences; urgent intervention indicated; 
 
Grade 5: Death related to the AE. 
 
For those AEs not directly referenced in CTCAE, the investigator should use clinical judgment 
in assessing the intensity of such events using the above categories as a guide. For a continuous 
episode of an AE with variable intensity, the greatest intensity should be recorded for the AE. 
 
12.5 Reporting Adverse Events and Serious Adverse Events 
12.5.1 
Reporting Adverse Events 
Throughout the study, AEs will be documented on the source document and on the appropriate 
page of the eCRF whether or not considered treatment-related. This includes any new signs, 
symptoms, injury or illness, including increased severity of previously existing signs, symptoms, 
injury, or illness. Conditions existing prior to screening will be recorded as part of the subject’s 
medical history. The investigator is responsible for assessing the relationship of AEs to the study 
medication; relationship will be classified as not related, possibly related, or probably related.  
 
All AEs will be collected by the investigator from the time of signing the informed consent 
through 30 days after the last dose of ASN002; this includes any AEs that are ongoing at the time 
of completion/termination of the study. All ongoing AEs must be followed until resolution or for 
30 days after the subject’s last study visit, whichever comes first. 
 
12.5.2 
Reporting Serious Adverse Events 
Any SAE, including death resulting from any cause, which occurs to any subject participating in 
this study, must be reported according to the Safety Management Plan within 24 hours of first 
becoming aware of the SAE. SAEs will be collected by the investigator from the time of signing 
the informed consent through 30 days after the last dose of study medication. SAEs that occur 
within 30 days, following cessation of the study treatment, or within 30 days, following 
premature discontinuation from the study for any reason, must also be reported within the same 
timeframe. Any SAE that is felt by the investigator to be related to the study medication must be 
reported regardless of the amount of time since the last dose received. Follow-up information 
collected for any initial report of an SAE must also be reported to the sponsor within 24 hours of 
receipt by the investigator. 
 
All SAEs will be followed until resolution, stabilization of condition, or until follow-up is no 
longer possible. 
 
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In the event discussion is necessary regarding treatment of a subject, call the Medical 
Monitor  
 
All SAEs should be entered into the eCRF within 24 hours of knowledge of the event. If the 
eCRF is not available, report the SAE via telephone, fax or e-mail using the information 
from the Study Reference Manual or Section 1 
The sponsor will determine the reporting time frame to regulatory authorities in compliance with 
local and regional law. If so, the sponsor (or the sponsor’s representative) will report the event to 
the appropriate regulatory authorities. The investigator will report SAEs to the institutional 
review board (IRB) per their IRB policy. 
 
12.5.2.1 
Follow-up Procedures for Serious Adverse Events 
To fully understand the nature of any SAE, obtaining follow-up information is important. 
Whenever possible, relevant medical records such as discharge summaries, medical 
consultations, reports of radiographic studies, and clinical laboratory reports should be obtained. 
In the event of death, regardless of cause, all attempts should be made to obtain the death 
certificate and any autopsy report, if performed. These records should be reviewed in detail, and 
the investigator should comment on any event, lab abnormality, or any other finding, noting 
whether it should be considered a serious or non-serious AE, or whether it should be considered 
as part of the subject’s history. In addition, all events or other findings determined to be SAEs 
should be identified on the follow-up SAE form and the investigator should consider whether the 
event is related or not related to study drug. All events determined to be non-serious should be 
reported on the eCRF. 
 
12.6 Special Reporting Situations 
12.6.1 
Overdose 
Study drug overdose is any accidental or intentional use of study drug in an amount higher than 
the dose indicated per protocol for a given subject. Study drug compliance (see section 10.7) 
should be reviewed to detect potential instances of overdose (intentional or accidental). 
 
Any study drug overdose during the study should be noted on the study medication eCRF.  
 
All AEs associated with an overdose should both be entered on the Adverse Event eCRF and 
reported using the procedures detailed in section 12.5.2, Reporting of Serious Adverse Events, 
even if the events do not meet seriousness criteria. If the AE associated with an overdose does 
not meet seriousness criteria, it must still be reported using the SAEs reporting procedures and in 
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an expedited manner, but should be noted as non-serious on the form and the Adverse Event 
eCRF.  
 
12.6.2 
Pregnancy  
All pregnancies in subjects receiving ASN002 or in the sexual partners of subjects receiving 
ASN002 must be reported within 24 hours of knowledge of the event according to SAE reporting 
procedures. 
 
Pregnancy itself is not regarded as an AE unless there is suspicion that the investigational 
product under study may have interfered with the effectiveness of a contraceptive medication. 
Likewise, elective abortions without complications are not considered AEs. Any SAEs 
associated with pregnancy (e.g., congenital abnormalities/birth defects/spontaneous miscarriages 
or any other serious events) must additionally be reported as such using the SAE report form. 
Spontaneous miscarriages should also be reported and handled as SAEs.  
 
Subjects should be instructed to immediately notify the investigator of any pregnancies.  
 
12.7 Clinical Laboratory Determinations 
The investigator will review all abnormal lab results for clinical significance. Any abnormal 
clinical laboratory test result meeting the investigator’s criteria for clinical significance will be 
recorded as an AE or SAE as appropriate (see section 12.1.1, Adverse Events, and section 12.1.2, 
Serious Adverse Events). 
 
Clinical laboratory parameters that will be measured in this study are listed in Table 10. 
 
Table 10: Clinical Laboratory Tests 
Hematology 
Comprehensive Metabolic 
Panel 
Urinalysis 
Hemoglobin 
Glucose 
Specific gravity 
Hematocrit 
Sodium 
pH 
Red blood cell 
Potassium 
Glucose 
White blood cell (WBC) 
Calcium 
Protein 
Platelets 
Chloride 
Ketones 
WBC Differential 
Carbon dioxide 
Bilirubin 
Reticulocyte count 
Phosphorus 
Urobilinogen 
 
Blood urea nitrogen 
Nitrite 
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Hematology 
Comprehensive Metabolic 
Panel 
Urinalysis 
Lipid Panel 
Creatinine 
Blood* 
Total cholesterol 
Uric acid 
Leukocytes* 
Triglycerides 
Lactate dehydrogenase (LDH) 
Reflex microscopic 
evaluation, if abnormal or 
clinically indicated. 
Liver Function Tests 
Albumin 
 
ALP 
Total protein 
 
AST 
 
 
ALT 
Pregnancy test 
 
Gamma-glutamyl transferase 
(GGT) 
Serum or urine pregnancy testing is required at screening and 
within 72 hours of Day 1 of every cycle for females of 
childbearing potential. 
TBIL (direct bilirubin reflex if 
elevated) 
 
 
* Microscopic examination will be performed if blood or leukocytes are detected by dipstick 
 
12.8 Vital Signs 
Vital sign measurements will be recorded in source documents and conducted at the times 
indicated in Table 1 - Table 4, as appropriate. These parameters include systolic and diastolic 
blood pressure, and pulse rate. Blood pressure and pulse readings will be taken after the subject 
has been seated or recumbent for 5 minutes. Oral body temperature will be collected at Visit 1 
only, unless clinically indicated. 
 
The investigator will review all vital sign values for clinical significance. Additional vital signs 
will be obtained when clinically indicated. Any additional relevant data obtained by the 
investigator during the course of the study will be supplied to the sponsor. 
12.9 Electrocardiogram 
A 12-lead ECG recording will be conducted at the times indicated in Table 1 - Table 4. The 
subject should rest in a semi-recumbent position for at least 5 minutes before the recording is 
conducted. Lead position will be that of a standard 12-lead ECG; no additional or special lead 
placements will be necessary. The ECG record should include 10 seconds of 12-lead data. A 
copy of the tracing and report must be filed in the subject’s records.  
 
The investigator will review all ECG results for clinical significance. 
 
Refer to the site operations manual for further information. 
 
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12.10 Physical Examination 
A complete physical examination will be performed at the Screening and End of Treatment 
visits. The examination will include an assessment of the following: general appearance, skin, 
head and neck (including eyes, ears and throat), thorax, lymph nodes, thyroid, 
musculoskeletal/extremities (including spine), cardiovascular, lungs, abdomen and neurological 
systems. Subjects with MF will have splenic measurements by palpation. The screening physical 
examination will also include a measurement of body height and weight. 
 
Follow up physical examinations may be brief problem-focused examinations and review of 
systems. Additional weight measurements will be performed as indicated. Any abnormal 
clinically significant findings on follow up examination will be recorded as AEs on the eCRF. 
 
All examinations will be performed by a physician or health professional listed on the Form 
FDA 1572 and licensed to perform physical examinations. The investigator will review all 
physical examination findings for clinical significance. 
 
13 ASSESSMENT OF PHARMACOKINETICS 
13.1 PK Sample Collections 
PK assessments for the ASN002 parent compound will be performed for all subjects 
participating in Parts A and B of the study. Samples of venous blood will be obtained according 
to the study site procedures and collected at the times indicated in Table 1 - Table 4, as 
appropriate. Samples collected within the specified windows will not be considered protocol 
deviations; however, every attempt will be made by the study site personnel to collect samples at 
the specified times. The exact sample collection times will be recorded in the eCRF to the 
nearest minute. 
 
Individual venipunctures for each time point may be performed or an indwelling catheter may be 
used. If an indwelling catheter is used, the catheter should be kept patent according to 
institutional standards. If using an indwelling catheter for PK/PD samples, care should be taken 
to waste an appropriate amount of blood to avoid contaminating the PK/PD sample with 
anticoagulant or saline. Procedures for processing the blood samples will be provided in the site 
Laboratory Manual. 
 
All sample collection and freezing tubes will be clearly labeled in a manner that identifies the 
study, the subject or accession number, and the collection nominal time. Labels will be fixed to 
freezing tubes in a manner that will prevent the label from becoming detached after freezing. 
 
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13.2 Sample Storage and Shipment 
All PK plasma samples will be stored frozen until they are shipped to the central laboratory. 
Prior to shipping, the samples will be packed into thermal insulated containers and packed in 
sufficient dry ice to assure they remain frozen, and are protected from breakage during shipment. 
Samples will be shipped by courier with appropriate documentation to identify the samples.  The 
samples will be divided into 2 shipments, each containing 1 aliquot of plasma for each time 
point. After receipt of verification that the first shipment was received by the central laboratory, 
the second shipment will be processed. 
 
Refer to the site Laboratory Manual for further information regarding sample storage and 
shipment requirements. 
 
13.3 PK Analytical Methodology  
A validated liquid chromatography-tandem mass spectrophotometry (LC-MS/MS) method will 
be used for the determination of concentration of the ASN002 from the plasma samples. Details 
of the method validation and sample analysis will be included in the final analytical report. 
 
14 ASSESSMENT OF PHARMACODYNAMICS 
14.1 PD Sample Collection 
Blood samples will be collected according to the schedule in Table 1- Table 4, and analyzed to 
assess 
 Inhibition of phosphorylation of S6, STAT3, SYKTyr525/526; and ERK; 
 DLBCL molecular subtyping may be conducted on archived tumor if the subtyping has 
not been done as standard of care. 
 Change from baseline in a panel of markers of inflammation (see Appendix C) 
 Change from baseline in JAK (V617F) mutant allele burden in subjects with MF 
 Change from baseline in BCL2 and chromosome 17p in subjects with CLL.  
 
Due to specimen shipping considerations, only U.S. sites will collect PD samples to determine 
the inhibition of phospho-proteins.   
 
Refer to the Study Laboratory Manual for further information regarding sample collection and 
shipments. 
 
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15 STATISTICAL CONSIDERATIONS AND METHODS 
This section outlines the statistical methodology and principles which will be used for data 
analysis in this study. A separate statistical analysis plan (SAP) will further describe the details 
regarding statistical methods and will govern the analysis. Where differences occur between the 
protocol and the SAP, the SAP will take priority. 
 
15.1 Determination of Sample Size 
Part A: A traditional 3+3 design will be used. Including the 40 subjects currently enrolled in dose 
cohorts ranging from 10 – 100 mg BID and 80 and 120 mg QD, up to an additional 4 cohorts 
will be tested under fed conditions.  It is anticipated that a total of 64 subjects may be enrolled in 
Part A.  No randomization will be performed for Part A. 
 
Part B: 
A sample size of 84 subjects (14 each in DLBCL, MCL, FL, PTCL, MF and CLL) will be 
enrolled. The null hypothesis that the true response rate is 0.05 will be tested against a one-sided 
alternative. A total of 14 patients will be accrued in each cohort. The null hypothesis will be 
rejected if at least 3 responses are observed in 14 subjects. This design yields a type I error rate 
of 0.02 and power of 0.9 when the true response rate is 0.4. 
 
15.2 Subject Populations 
The following populations will be considered in the statistical analysis of the study: 
 
Safety population: The safety population will include all subjects who take at least 1 dose of 
study medication. Safety analyses will be conducted using the safety population. The safety 
population will apply to Parts A, B and C. 
PK population: The PK population will include all subjects who receive at least 1 dose of 
ASN002 and have sufficient plasma concentration data to facilitate the calculation of PK 
parameters as determined by the pharmacokineticist.  
 
Efficacy Population (EP) will include all subjects who have an evaluable screening and post-
dose tumor assessment. 
 
The Per Protocol (PP) population will include all EP subjects without major protocol violations. 
The PP population will be used as the primary analysis population for efficacy. 
 
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15.3 Subject Disposition 
The number and percentage of subjects included in each study population will be summarized by 
dose level and overall. Subjects excluded from the safety and efficacy (EP or PP) populations or 
PK populations will be listed by dose level. 
 
The number and percentage of subjects completed and discontinued during the treatment periods 
will be presented for each dose level and overall. Reasons for discontinuation from the treatment 
period as recorded on the eCRF will be summarized (number and percentage) by dose level and 
overall for all treated subjects. 
 
15.4 Demographics and Other Baseline Characteristics 
Demographic and baseline characteristics, including sex, age, age group, race, height, and 
weight, and baseline values (e.g., clinical stage, ECOG performance status), will be summarized 
by dose level and overall, for all populations, using descriptive statistics. All baseline 
characteristics and medical information will also be summarized by dose level using descriptive 
statistics. The descriptive summaries will include frequency tables for all categorical response 
variables and number, mean, standard deviation, minimum, and maximum for all continuous 
variables. 
 
15.5 Safety Analyses 
Safety variables include AEs, concomitant medications, laboratory parameters, vital signs, ECG 
parameters, and physical examinations. For each safety parameter, the last assessment made 
prior to the first dose of study drug will be used as the baseline. 
All safety summaries will be performed by dose level and Part A and B, separately and 
combined, if appropriate. 
15.5.1 
Prior, Concomitant, and Post Medications 
The current version of WHO Drug at the initiation of protocol conduct will be used to classify 
prior and concomitant medications by therapeutic class. Prior medication will be defined as any 
medication taken prior to the first dose of study drug. Concomitant medication is defined as any 
medication taken between the date of first dose of study drug and the date of last dose of study 
drug. Any medications taken after the last dose of study drug will be considered as post 
medications. 
 
Prior, concomitant, and post medication use will be summarized descriptively by the number and 
percentage of subjects in each dose level receiving each medication within each therapeutic 
class. Multiple use of the same medication by a subject will be counted only once. 
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15.5.2 
Study Drug Exposure 
Exposure to study drug for the Safety Population will be summarized in terms of treatment 
duration, which will be calculated as the number of days from the date of first study drug taken 
to the date of last dose taken, inclusively. Descriptive statistics (n, mean, standard deviation, 
median, minimum, and maximum) for treatment duration will be presented for each dose level. 
 
15.5.3 
Measurement of Treatment Compliance 
Descriptive statistics for study drug compliance will be presented by dose level for each period, 
as well as for the whole treatment period of the study. 
 
15.5.4 
Adverse Events  
The Medical Dictionary for Regulatory Activities (MedDRA, version 17.0 or higher) will be 
used to code AEs. 
 
An AE (classified by preferred term) that started during the treatment period will be considered a 
TEAE if it was not present prior to the first dose of study drug, or was present prior to the first 
dose of study drug but increased in intensity during the treatment period. If more than 1 AE is 
reported prior to the first dose of study drug and coded to the same preferred term, then the AE 
with the least intensity will be used as the benchmark for comparison to the AEs occurring 
during the treatment period which were also coded to that preferred term. Any AE present prior 
to the first dose of study drug that increases in intensity during the treatment period will be re-
entered with a new start date of the date of increased intensity. An AE that occurs more than 30 
days after the last dose of study drug will not be counted as a TEAE. 
 
Descriptive statistics (the number and percentage) for subjects reporting TEAEs will be tabulated 
by system organ class, preferred term, and dose level. If more than 1 AE is coded to the same 
preferred term for the same subject, the subject will be counted only once for that preferred term.  
 
The incidence of TEAEs by severity and relationship to study drug will be summarized by 
system organ class, preferred term, and dose level. If more than 1 AE is coded to the same 
preferred term for the same subject, the subject will be counted only once for that preferred term 
using the most severe and most related occurrence for the summarization by severity and by 
relationship to the study drug respectively. The incidence of TEAEs will also be summarized by 
preferred term and dose level and sorted by decreasing frequency. SAEs and AEs leading to 
premature discontinuation of study drug will be summarized by preferred term and dose level, 
and sorted by decreasing frequency for dose level. 
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Descriptive statistics (the number and percentage) for subjects reporting TEAEs will be tabulated 
by system organ class, preferred term, and dose level. If more than 1 AE is coded to the same 
preferred term for the same subject, the subject will be counted only once for that preferred term.  
 
The incidence of TEAEs by severity and relationship to study drug will be summarized by 
system organ class, preferred term, and dose level. If more than 1 AE is coded to the same 
preferred term for the same subject, the subject will be counted only once for that preferred term 
using the most severe and most related occurrence for the summarization by severity and by 
relationship to the study drug respectively. The incidence of TEAEs will also be summarized by 
preferred term and dose level and sorted by decreasing frequency. SAEs and AEs leading to 
premature discontinuation of study drug will be summarized by preferred term and dose level, 
and sorted by decreasing frequency for dose level. 
Listings will be presented for subjects with AEs, subjects with SAEs, subjects with AEs leading 
to discontinuation, and death. All safety summaries will be performed by dose level and Parts A, 
and B, separately and combined, if appropriate. 
 
15.5.5 
Vital Signs 
Descriptive statistics for vital signs (e.g., systolic and diastolic blood pressure, pulse rate, 
temperature, and body weight) and their changes from baseline at each visit and at the end of 
study will be presented by dose level.  
 
15.5.6 
Clinical Laboratory Parameters 
Descriptive statistics for clinical laboratory values in International System of Units (SI units) and 
changes from baseline at each assessment time point will be presented by dose level for each 
clinical laboratory parameter. 
 
15.5.7 
Electrocardiogram 
Descriptive statistics for ECG parameters (e.g., heart rate, PR interval, QRS interval, QT 
interval, and QTc interval) at baseline and changes from baseline at each assessment time point 
will be presented by dose level. QTc interval will be calculated using both Bazett [QTcB = 
QT/(RR)½] and Fridericia [QTcF = QT/(RR)⅓] corrections; and if RR is not available, it will be 
replaced with 60/HR in the correction formula. 
 
15.5.8 
Physical Examination 
Clinically significant changes from the screening and/or Day 1 physical examinations will be 
captured as AEs, and analyzed according to the criteria in Section 15.5.4. 


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15.6.1 
Evaluation of Disease Status 
15.6.1.1 
DLBCL, MCL, FL, PTCL 
The frequency of responders according to the 2014 Lugano Classification for subjects with 
lymphoma will be evaluated at each dose level and for each lymphoma subgroup in Part B.  
Differences in response to therapy based on the molecular subtypes of DLBCL will be explored. 
 
15.6.1.2 
Advanced Solid Malignancies 
The frequency of responders according to modified RECIST 1.1 criteria for subjects with 
advanced solid malignancies will be evaluated at each dose level.  The changes from baseline in 
overall assessment of CR, PR, SD and PD will be reported. 
 
15.6.1.3 
Myelofibrosis 
The frequency of response and type of response according to IWG-MRT response criteria for 
subjects with MF will be evaluated.  
15.6.1.4 
CLL 
The frequency of response, and type of response according to the criteria of the International 
Workshop on Chronic Lymphocytic Leukemia (32), will be evaluated. For patients with 
persistent lymphocytosis, a partial response in all other measures will be defined as a partial 
response with lymphocytosis (33). Duration of response and the PFS rate at week 24 will also be 
evaluated. 
15.6.1.5 
Evaluation of Performance Status 
The ECOG performance status and the changes from baseline will be presented with frequency 
tables at each dose level. 
 
15.6.2 
Evaluation of Time on Treatment 
The time from the start of study treatment to the discontinuation or completion of study 
treatment at each dose level will be summarized descriptively. 
 
15.6.3 
Evaluation of Time to Progression 
The time to disease progression (radiographic or clinical) will be calculated as the number of 
days from the date of the first dose of study medication to the date the progression is observed or 
death due to tumor progression in the absence of previous documented PD. For subjects who 
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have not progressed at the end of the study, the time to progression will be censored at the last 
assessment, unless the subject dies due to disease progression. The time to progression will be 
analyzed using the Kaplan-Meier method. The number and percent of subjects progressed, 
number and percent of subjects censored, and median time to progression along with its 95% 
confidence interval will be presented by dose level and combined.  
 
15.6.4 
Evaluation of Progression Free Survival 
PFS will be calculated as the number of days from the date of the first dose of study medication 
to the date progression is observed, or death from any cause. PFS will be analyzed using the 
Kaplan-Meier method. The number and percent of subjects progressed, number and percent of 
subjects censored, and median time to progression along with its 95% confidence interval will be 
presented by dose level and combined. The Kaplan-Meier survival curves will be presented by 
dose level and combined. 
 
15.7 Pharmacokinetic Analyses 
15.7.1 
Calculation of Pharmacokinetic Variables 
For Part A, PK variables for the ASN002 parent compound will be estimated from the plasma 
concentration data using standard non-compartmental methods. Actual sample times (hours, 
relative to the corresponding administration time) rounded to 2 decimal digits and negative pre-
dose times set to zero, will be used in the computation of the PK variables, rather than scheduled 
times. Refer to Section 15.7.3 for the handling of missing values. 
 
For Part B, PK analysis for the parent compound will be performed using a population PK 
method. The population PK analysis plan will be described separately and the results will be 
reported separately. 
 
The definition for each PK variable is summarized in Table 11 
 
Table 11: Pharmacokinetic Variables for Part A 
 
Variable 
Definition 
AUC0-∞ 
Area under the plasma concentration versus time curve from time 0 to 
infinity after first dose only 
AUC0-t  
Area under the plasma concentration versus time curve from time 0 to the 
time of last measured concentration (Ct) 
AUC0-24 
Area under the plasma concentration versus time curve from time 0 to 24 
hours 
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Variable 
Definition 
AUC0-∞ 
Area under the plasma concentration versus time curve from time 0 to 
infinity after first dose only 
AUC0-t  
Area under the plasma concentration versus time curve from time 0 to the 
time of last measured concentration (Ct) 
AUC0-24 
Area under the plasma concentration versus time curve from time 0 to 24 
hours 
AUC0-12 
Area under the plasma concentration versus time curve from time 0 to 12 
hours 
Cmax  
Observed maximum plasma concentration; the highest concentration 
observed after a dose  
tmax 
The time to reach the peak plasma concentration  
CL/F 
Total clearance following oral administration 
Vd/F 
Volume of distribution at terminal phase following oral administration 
λz 
Terminal elimination rate constant, calculated as the negative slope of the ln-
linear portion of the terminal plasma concentration-time curve  
t½ 
Terminal half-life, calculated as ln(2)/λz  
 
15.7.2 
Analysis of Pharmacokinetic Results 
The PK variables will be summarized using descriptive statistics by dose level. Mean, median, 
standard deviation, coefficient of variance, and range will be reported for each variable. 
 
Part A and Part B data may be combined for PK/pharmacodynamic (PD) analysis. This will be 
described in a separate PK/PD analysis plan. 
 
15.7.3 
Handling of Missing Values 
For PK analyses, plasma concentrations below the limit of quantification (BLQ) will be set to 
zero in the computation of mean concentration values; however, BLQ concentrations between 2 
non-BLQ concentrations will be set to missing. For the computation of PK variables, the BLQ 
concentrations prior to the first measurable concentration will be set to zero and other BLQ 
concentrations will be set to missing. 
 
15.8 Pharmacodynamic Analyses 
The actual values and the changes from baseline for the PD variables will be summarized using 
descriptive statistics by dose level. mean, median, standard deviation, coefficient of variance, 
and range will be reported for each PD variable. 
 


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15.9 Protocol Deviations 
A list of subjects with protocol deviations will be compiled based on entry criteria deviations as 
well as deviations from study conduct and assessments. Prior to database lock, an evaluation of 
subjects with protocol deviations will be performed to assess the appropriateness of their 
inclusion into the various analyses. 
 
15.10 Interim Analysis 
An interim analysis is not applicable to this study. As this is an open-label study, appropriate 
analyses will be conducted on an ongoing basis. 
 
15.11 Statistical Software 
Statistical analyses will be performed using version 9.2 (or higher) of SAS® (SAS Institute, 
Cary, NC). 
 
16 STUDY DRUG MATERIALS AND MANAGEMENT 
16.1 Study Drug Identity 
ASN002 5-mg, 20-mg, and 50 mg oral tablets will be manufactured and supplied by Kashiv 
Pharma, LLC, for Asana BioSciences, LLC.  
 
16.2 Study Drug Packaging and Labeling 
ASN002 5-mg, 20-mg, and 50 mg tablets will be supplied in high density polyethylene bottles. 
The bottles will have a foil induction seal and child-resistant screw cap. Each bottle will be 
minimally labeled with a single-panel label containing the protocol number, name of the product 
and dosage form/strength, contents, lot number, dosing directions, storage directions, appropriate 
cautionary statements, and sponsor name and address.   
 
16.3 Study Drug Storage 
All study drugs will be provided by Asana BioSciences, LLC. Study drug must be stored in an 
appropriate, secure area (e.g., a locked cabinet in a locked room) at room temperature 
[25°C (77°F)], with excursions permitted to 15°C-30°C (59°F-86°F). 
 
16.4 Study Drug Preparation 
Not applicable 


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16.5 Study Drug Accountability 
The principal investigator is responsible for ensuring that all study drug received at the site is 
inventoried and accounted for and that dispensed study drug is recorded in the drug 
accountability source records. Drug accountability will be verified by the monitor during site 
visits. 
The principal investigator will not supply the study drug to any person except those named as 
sub-investigators on Form FDA 1572, designated staff reflected on the Delegation of Authority 
Log, and consented subjects in this study. Study drug may not be relabeled or reassigned for use 
by other subjects. 
 
16.5.1 
Study Drug Handling and Disposal 
All unused study drug that was dispensed to the subject will be returned to the site for 
reconciliation and assessment of compliance. The site must account for all study drug received, 
dispensed, and returned including study drug that was accidentally or deliberately destroyed.  
Any discrepancies between the actual and expected returned study drug counts should be 
documented.  The site will destroy all study medication returned by the subject after it has been 
verified by the clinical monitor. At the end of the study, all unused drug supplies will be 
destroyed according to local standards. A copy of the Standard Operating Procedure or 
documented process for drug destruction will be filed in the Investigational Site File. 
 
17 DIRECT ACCESS TO SOURCE DATE/DOCUMENTS 
17.1 Source Documents 
Source documents include but are not limited to original documents, data and records such as 
hospital/medical records (including electronic health records), clinic charts, lab results, subject 
diaries, data recorded in automated instruments, microfilm or magnetic media, and pharmacy 
records, etc. At a minimum, all data required to be collected by the protocol should have 
supporting source documentation for entries in the eCRF, unless the protocol specifies that data 
can be recorded directly on/in the eCRF or other device. 
 
17.2 Study Monitoring 
A representative of Asana BioSciences, LLC will meet with the investigator and his/her staff 
prior to the entrance of the first subject to review study procedures and methods of recording 
study data.  
 


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After enrollment of the first subject, an Asana BioSciences, LLC representative will be assigned 
to periodically monitor each investigator site for study progress and to verify that standards of 
Good Clinical Practice (GCP) and/or ICH guidelines were followed. The investigator is expected 
to prepare for the monitor visit, ensuring that all source documents, completed eCRFs, signed 
consent forms and other study related documents are readily available for review. 
17.3 Audits and Inspections 
The investigator shall permit audits and inspections by the sponsor, its representatives and 
members of regulatory agencies. The investigator should immediately notify the sponsor of an 
upcoming Food and Drug Administration (FDA) or other regulatory agency inspection. 
 
17.4 Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
The investigator shall permit members of the IRB/IEC to have direct access to source 
documents. 
 
17.5 Data Recording and Documentation 
All data recordings and source documentation (including electronic health records) must be made 
available to the sponsor (or designee), FDA, and any other regulatory agencies that request 
access to study records, including source documents, for inspection and copying, in keeping with 
federal and local regulations. 
 
18 QUALITY CONTROL AND QUALITY ASSURANCE 
Steps to assure the accuracy and reliability of data include the selection of qualified principal 
investigators and appropriate study centers, review of protocol procedures with the principal 
investigators and associated personnel prior to start of the study, and periodic monitoring visits 
conducted by the sponsor or sponsor representative. Significant and/or repeated non-compliance 
will be investigated and remedial action instituted when appropriate. Failure to comply with 
remedial actions may result in investigator site termination and regulatory authority notification. 
The sponsor or its designee will utilize qualified monitors to review and evaluate activities 
conducted at investigator sites. 
 
The data will be entered into the clinical study database and verified for accuracy, following 
procedures defined by the sponsor (or designee). Data will be processed and analyzed following 
procedures defined by the sponsor (or designee). 
 
The study will be monitored and/or audited at intervals to ensure that the clinical study is 
conducted and data are generated, documented (recorded), and reported in compliance with the 


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19 ETHICS 
19.1 Ethics Review 
Approval by the IRB/IEC prior to the start of the study will be the responsibility of the 
investigator. A copy of approval documentation will be supplied to Asana BioSciences, LLC 
along with a roster of IRB members that demonstrates appropriate composition (a Department of 
Health and Human Services [DHHS] Assurance Number will satisfy this requirement).  
 
The study protocol, the informed consent form, advertisements, materials being provided to 
subjects and amendments (if any) will be approved to IRB/IECs at each study center in 
conformance with ICH E6, the Code of Federal Regulations (CFR), Title 21, Part 56 and any 
other applicable local laws. The investigator is responsible for supplying the IRB/IEC with a 
copy of the current IB, as well as any updates issued during the study. During the course of the 
study, the investigator will provide timely and accurate reports to the IRB/IEC on the progress of 
the study, at intervals not exceeding 1 year (or as appropriate), and will notify the IRB/IEC of 
SAEs or other significant safety findings, per the policy of the IRB/IEC. At the conclusion of the 
study, the investigator will submit a final report or close out report to the IRB/IEC and provide a 
copy to Asana BioSciences, LLC. 
 
Any amendment to this protocol will be provided to the investigator in writing by Asana 
BioSciences, LLC. No protocol amendment may be implemented (with the exceptions noted 
below) before it has been approved by the IRB/IEC and the signature page, signed by the 
investigator, has been received by Asana BioSciences, LLC. Where the protocol is amended to 
eliminate or reduce the immediate risk to the subject, the amendment may be implemented 
before IRB/IEC review and approval. However, the IRB/IEC must be informed in writing of 
such an amendment and approval obtained within reasonable time limits. Deviating from the 
protocol is permitted only if absolutely necessary for the safety or clinical management of the 
subject, and must be immediately reported to Asana BioSciences, LLC.  
 
The investigator will be responsible for supplying updated safety and/or study information to 
study subjects as it becomes available. 
 
19.2 Ethical Conduct of the Study 
The study will be conducted in accordance with ICH-GCP and all applicable regulations 
including, where applicable, the Declaration of Helsinki. The study will also be carried out in 
keeping with applicable local laws and regulations. This may include an inspection by the 
sponsor representative and/or regulatory authority representatives at any time. In accordance 
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with any applicable local regulations, the sponsor or designee will obtain approval from the 
appropriate regulatory agency prior to a site initiation of the study in the country or jurisdiction. 
 
19.3 Subject Information and Consent 
The principal investigator will ensure that each subject is given full and adequate oral and 
written information about the nature, purpose, possible risk and benefit of the study. A subject 
must also be notified that he is free to discontinue from the study at any time. The subject should 
be given the opportunity to ask questions and allowed time to consider the information provided. 
 
Each subject must voluntarily sign and date the informed consent form (and other locally 
required documents) prior to the performance of any study-related activity. The consent form 
must be approved by both the reviewing IRB/IEC and by the sponsor prior to use. 
 
The consent form will incorporate (or, in some cases, be accompanied by a separate document 
incorporating) wording that complies with relevant data protection and privacy legislation. 
Pursuant to this wording, subjects will authorize the collection, use and disclosure of their study 
data by the investigator and by those persons who need that information for the purposes of the 
study. 
 
The consent form will explain that study data will be stored in a computer database, maintaining 
confidentiality in accordance with national data legislation. For data verification purposes, 
authorized representatives of the sponsor, a regulatory authority or an IRB/IEC may require 
direct access to source data relevant to the study, including the subjects’ medical history. 
 
The consent process shall be recorded in source documents. Signed copies of the informed 
consent will be given to the subject and originals will be placed in the investigator study files. 
For Latin America sites, per local regulations, an original signed copy of the informed consent 
form will be given to the subjects. 
 
20 DATA COLLECTION 
Data that is not captured directly via an electronic device or instrument will be collected from 
source documents and entered into an eCRF within an electronic data capture (EDC) system. 
EDC security features will include the requirement for a unique user ID and password for each 
individual who make entries, reviews or makes changes to the data. 
 
The investigator will be responsible for ensuring data is electronically captured or that it is 
entered into the eCRF in a timely manner relative to the subject visit. The investigator will 
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ensure the accuracy and completeness of all subject data specified in the protocol. Upon study 
completion, the data collected in the eCRF will be provided to each study site in portable 
document format (PDF). 
 
21 REPORTING AND PUBLICATION 
All data generated in this study are the property of Asana BioSciences, LLC. An integrated 
clinical and statistical report will be prepared at the completion of the study. Publication of the 
results by the investigator will be subject to mutual agreement between the investigator and 
Asana BioSciences, LLC. 
 
22 INVESTIGATOR OBLIGATIONS 
22.1 Regulatory Documents 
The investigator is responsible for creating and/or maintaining all study documentation required 
by 21 CFR 50, 54, 56 and 312, ICH E6 section 8, as well as any other documentation defined in 
the protocol or the Investigator Agreement. The investigator must maintain the documentation 
relating to this study and permit Asana BioSciences, LLC or a member of a regulatory agency 
access to such records. 
The investigator must provide the following key documents to Asana BioSciences, LLC prior to 
the start of the study: 
 A completed and signed Form FDA 1572. If during the course of the study any 
information reported on the Form FDA 1572 changes, a revised Form FDA 1572 must be 
completed and returned to Asana BioSciences, LLC for submission to the FDA. For 
studies executed outside the United States, documentation required by the governing 
regulatory authority may be substituted for the Form FDA 1572; 
 A fully executed contract; 
 The Investigator’s Statement page in this protocol signed and dated by the investigator 
and any subsequent amendment signature pages; 
 The IB acknowledgment of receipt page; 
 Curricula vitae for the principal investigator and all sub-investigators listed on Form FDA 
1572, including a copy of each physician’s license (if applicable); 
 A copy of the original IRB/IEC approval for conducting the study. If the study is 
ongoing, renewals must be submitted at yearly intervals or shorter intervals defined by 
the IRB/IEC. All subsequent modifications must be submitted and approved by the IRB, 
as described in section 19.1; 
 A copy of the IRB/IEC-approved informed consent form; 
 A list of IRB/IEC members or DHHS Assurance Number; 
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 Laboratory certifications and normal ranges (if local labs are required by the protocol); 
 Financial Disclosure Forms will be completed and signed by the investigator and all sub-
investigators listed on Form FDA 1572. Investigator site staff that submitted an initial 
financial disclosure are also responsible for informing Asana BioSciences, LLC of any 
changes to their initial financial disclosure form throughout the duration of the study, and 
for up to1 year after the completion of the study. 
 
A complete list of required regulatory documents will be supplied by Asana BioSciences, LLC 
or its representative. 
 
22.2 Delegation of Responsibilities and Adequate Resources 
The investigator should have adequate time to conduct the study properly and should have an 
adequate number of qualified staff to assist with the conduct of the study. The investigator shall 
delegate tasks only to individuals qualified by education, training and experience to perform the 
delegated tasks. The investigator or sub-investigator shall have direct oversight of or be easily 
accessible to all personnel with delegated activities. A log documenting delegation of 
responsibilities will be maintained throughout the study. The investigator is responsible for 
ensuring all delegated staff have been properly trained on the protocol and their assigned study 
responsibilities. 
 
22.3 Medical Care of Study Subjects 
The investigator and/or a qualified sub-investigator shall be responsible for the subjects’ medical 
care. Any unrelated medical condition discovered during the course of the study should be 
communicated to the subject so that they may seek appropriate medical care. The investigator 
will report all AEs as required by the protocol (section 12.5). The investigator will inform study 
subjects of new information regarding the study drug as it becomes available. 
 
22.4 Use of Investigational Materials 
The investigator will acknowledge that the study drug supplies are investigational and as such 
must be used strictly in accordance with the protocol and only under the supervision of the 
principal investigator or sub-investigators listed on Form FDA 1572 (or other regulatory 
document, depending on region). Study drug must be stored in a safe and secure location. At 
study initiation, a representative from Asana BioSciences, LLC or designee will inventory the 
study drug at the site. The investigator must maintain adequate records documenting the receipt 
and disposition of all study supplies. The investigator is responsible for monitoring subject’s use 
of the study drug to ensure compliance with the protocol. All unused ASN002 will be destroyed 
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at the investigational site, according to institutional standards after reconciliation by the clinical 
monitor. It is the investigator’s responsibility to ensure that subjects return their medication. 
 
22.5 Retention of Records 
Federal and local regulations require that the investigator retain a copy of all regulatory 
documents and records that support the data for this study (e.g., informed consents, laboratory 
reports, source documents, study drug dispensing records) for whichever of the following is the 
longest period of time: 
 A period of 2 years following the final date of approval by the FDA or other regulatory 
agency of the study drug for the purposes that were the subject of the investigation; or 
 A period of 5 years following the date on which the results of the investigation were 
submitted to the FDA or other regulatory agency in support of, or as part of, an 
application for a research or marketing permit for the study drug for the purposes that 
were the subject of the investigation. 
 Longer retention times may be required by individual local, or national regulatory 
authorities. The investigator is responsible to understanding and complying with all 
retention requirements. 
 
Asana BioSciences, LLC will notify investigators once one of the above 3 timeframes has been 
satisfied. 
 
If the investigation does not result in the submission of the data in support of, or as part of, an 
application for a research or marketing permit, records must be retained according to applicable 
local and national governmental authority regulation. 
 
If the investigator retires, relocates, or for other reasons withdraws from the responsibility of 
keeping the study records, custody must be transferred to a person who will accept the 
responsibility. Asana BioSciences, LLC must be notified in writing of the name and address of 
the new custodian. Study records should not be destroyed without consultation with Asana 
BioSciences, LLC. 
 
22.6 Subject Confidentiality 
All subject records submitted to Asana BioSciences, LLC or its designee will be identified only 
by initials and code number. Subjects’ names are not to be transmitted to Asana BioSciences, 
LLC. The investigator will keep a Master Subject List on which the ID number and the full 
name, address, and telephone number of each subject are listed. It is the investigators’ 
responsibility to inform study subjects that representatives of the sponsor, FDA, or other 
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regulatory agencies may review all records that support their participation in the study. The 
investigator will adhere to all privacy laws to which he/she is subject.  
 
22.7 Clinical Trials Registration 
The Sponsor will be responsible for entering information on the www.ClinicalTrials.gov website. 
Information on investigator name and site information may be disclosed as part of this posting.  
 
23 TERMINATION OF STUDY 
The sponsor has the right to suspend or terminate the study at any time. The study may be 
suspended or terminated for any reason. 
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guidelines. Blood 2008; 111:5446-5456 [Erratum, Blood 2008; 112:5259]. 
33. Hallek M, Cheson BD, Catovsky D, et al. Response assessment in chronic lymphocytic 
leukemia treated with novel agents causing an increase of peripheral blood lymphocytes. 
Blood 2012 June 4 (http:// www. bloodjournal .org/ content/ 111/ 12/ 5446. e-letters 
 
 
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ASN002-101 Protocol Amendment 06 
 
 
24 May 2017 
Asana BioSciences, LLC 
 
 
Confidential 
Appendix A 
NATIONAL CANCER INSTITUTE COMMON TERMINOLOGY 
CRITERIA FOR ADVERSE EVENTS (NCI CTCAE V4.03) 
A printed copy of the National Cancer Institute (NCI) Common Terminology Criteria for 
Adverse Events (CTCAE) version 4.03 (publication date: June 14, 2010) will be provided in the 
site operations manual. This document is also available on the NCI website: 
http://evs.nci.nih.gov/ftp1/CTCAE/About.html. 
 
 
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ASN002-101 Protocol Amendment 06 
 
 
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Asana BioSciences, LLC 
 
 
Confidential 
Appendix B 
EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) 
PERFORMANCE STATUS  
Grade 
ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
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 
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities. Up 
and about more than 50% of waking hours 
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of waking 
hours 
4 
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair 
5 
Dead 
As published in Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the 
Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982; 5(6):649-655. 
 
 
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ASN002-101 Protocol Amendment 06 
 
 
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Asana BioSciences, LLC 
 
 
Confidential 
Appendix C 
PANEL OF PHARMACODYNAMIC MARKERS OF 
INFLAMMATION 
 
Human Inflammation MAP® v. 1.0  
# 
Analyte 
Short 
Name 
 # 
Analyte 
Short 
Name 
1 
Beta-2-Microglobulin 
B2M 
25 
Tumor Necrosis Factor beta 
TNF-beta 
2 
C-Reactive Protein 
CRP 
26 
Brain-Derived Neurotrophic 
Factor 
BDNF 
3 
Von Willebrand Factor 
vWF 
27 
Eotaxin-1 
  
4 
Alpha-2-Macroglobulin 
A2Macro 
28 
Factor VII 
  
5 
Ferritin 
FRTN 
29 
Intercellular Adhesion 
Molecule 1 
ICAM-1 
6 
T-Cell-Specific Protein 
RANTES 
RANTES 
30 
Interleukin-1 alpha 
IL-1 alpha 
7 
Tissue Inhibitor of 
Metalloproteinases 1 
TIMP-1 
31 
Interleukin-1 beta 
IL-1 beta 
8 
Tumor necrosis factor 
receptor 2 
TNFR2 
32 
Interleukin-1 receptor 
antagonist 
IL-1ra 
9 
Vascular Cell Adhesion 
Molecule-1 
VCAM-1 
33 
Interleukin-12 Subunit p40 
IL-12p40 
10 
Granulocyte-Macrophage 
Colony-Stimulating Factor 
GM-CSF 
34 
Interleukin-12 Subunit p70 
IL-12p70 
11 
Interferon gamma 
IFN-
gamma 
35 
Interleukin-15 
IL-15 
12 
Interleukin-10 
IL-10 
36 
Interleukin-17 
IL-17 
13 
Interleukin-18 
IL-18 
37 
Interleukin-23 
IL-23 
14 
Interleukin-2 
IL-2 
38 
Matrix Metalloproteinase-3 
MMP-3 
15 
Interleukin-3 
IL-3 
39 
Matrix Metalloproteinase-9 
MMP-9 
16 
Interleukin-4 
IL-4 
40 
Stem Cell Factor 
SCF 
17 
Interleukin-5 
IL-5 
41 
Vascular Endothelial 
Growth Factor 
VEGF 
18 
Interleukin-6 
IL-6 
42 
Alpha-1-Antitrypsin 
AAT 
19 
Interleukin-7 
IL-7 
43 
Fibrinogen 
  
20 
Interleukin-8 
IL-8 
44 
Haptoglobin 
  
21 
Macrophage Inflammatory 
Protein-1 alpha 
MIP-1 
alpha 
45 
Vitamin D-Binding Protein 
VDBP 
22 
Macrophage Inflammatory 
Protein-1 beta 
MIP-1 
beta 
 
 
 
23 
Monocyte Chemotactic 
Protein 1 
MCP-1 
 
 
 
24 
Tumor Necrosis Factor 
alpha 
TNF-
alpha 
 
 
 
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SAP_001.pdf: 




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Page 3 of 29 
 
ABBREVIATIONS ..................................................................................................................................... 6 
DEFINITIONS OF TERMS ...................................................................................................................... 7 
1 
INTRODUCTION ......................................................................................................................... 8 
2 
STUDY OBJECTIVE(S), TREATMENTS, AND ENDPOINT(S) ............................................ 8 
2.1 
Study Objectives ............................................................................................................................ 8 
2.1.1 
Primary Objectives ........................................................................................................................ 8 
2.1.2 
Secondary Objectives ..................................................................................................................... 8 
2.1.3 
Exploratory/Pharmacodynamic Objectives ................................................................................ 8 
2.2 
Treatment Comparisons ................................................................................................................ 8 
2.3 
Study Endpoints and Evaluations ................................................................................................ 9 
2.3.1 
Efficacy ........................................................................................................................................... 9 
2.3.1.1  Primary Efficacy Variable ............................................................................................................ 9 
2.3.1.2  Secondary Efficacy Variables ..................................................................................................... 11 
2.3.1.3  Exploratory Efficacy Variables .................................................................................................. 11 
2.3.2 
Safety Evaluations ........................................................................................................................ 11 
3 
STUDY DESIGN .......................................................................................................................... 12 
3.1 
Overall Study Design and Treatment Groups ........................................................................... 12 
3.2 
Summary of Scheduled Events ................................................................................................... 14 
4 
SAMPLE SIZE CONSIDERATIONS ....................................................................................... 20 
5 
ANALYSIS POPULATIONS ..................................................................................................... 20 
5.1 
Safety Population ......................................................................................................................... 20 
5.2 
Efficacy Population (EP) ............................................................................................................. 20 
5.3 
Per-Protocol (PP) Population ...................................................................................................... 20 
6 
CONSIDERATIONS FOR DATA ANALYSIS ........................................................................ 20 
6.1 
Programming Environment ........................................................................................................ 20 


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6.2 
Strata and Covariates .................................................................................................................. 20 
6.3 
Subgroups ..................................................................................................................................... 20 
6.4 
Multiple Comparisons and Multiplicity ..................................................................................... 20 
6.5 
Significance Level ........................................................................................................................ 21 
6.6 
Statistical Notation and Methodology ........................................................................................ 21 
7 
DATA HANDLING METHODS ................................................................................................ 21 
7.1 
Missing Data ................................................................................................................................. 21 
7.1.1 
Date Values ................................................................................................................................... 21 
7.1.2 
Non-Date Values .......................................................................................................................... 21 
7.2 
Visit Windows .............................................................................................................................. 21 
7.3 
Data Derivations .......................................................................................................................... 21 
8 
STUDY POPULATION .............................................................................................................. 22 
8.1 
Subject Enrollment ...................................................................................................................... 22 
8.2 
Subject Disposition ...................................................................................................................... 22 
8.3 
Protocol Deviations ...................................................................................................................... 23 
8.4 
Inclusion/Exclusion Criteria ....................................................................................................... 23 
8.5 
Demographic Characteristics ..................................................................................................... 23 
8.6 
Clinical Stage ................................................................................................................................ 23 
8.7 
Prior Antineoplastic Therapy ..................................................................................................... 24 
8.8 
Medical History ............................................................................................................................ 24 
9 
EFFICACY ANALYSIS .............................................................................................................. 24 
9.1 
Evaluation of Disease Status ....................................................................................................... 24 
9.1.1 
DLBCL, MCL, FL, PTCL ........................................................................................................... 24 
9.1.2 
Advanced Solid Malignancies ..................................................................................................... 25 
9.1.3 
Myelofibrosis ................................................................................................................................ 25 


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9.1.4 
Chronic Lymphocytic Leukemia ................................................................................................ 25 
9.1.5 
Evaluation of Performance Status .............................................................................................. 25 
9.2 
Evaluation of Time to Treatment ............................................................................................... 25 
9.3 
Evaluation of Time to Progression ............................................................................................. 25 
9.4 
Evaluation of Progression-free Survival .................................................................................... 26 
9.5 
Exploratory Efficacy Variables .................................................................................................. 26 
9.5.1 
Panel of Biomarkers .................................................................................................................... 26 
10 
SAFETY ANALYSIS .................................................................................................................. 26 
10.1 
Adverse Events ............................................................................................................................. 26 
10.2 
Treatment Exposure .................................................................................................................... 27 
10.3 
Prior, Concomitant, and Post-Treatment Medications ............................................................ 27 
10.4 
Laboratory Evaluations ............................................................................................................... 27 
10.5 
Vital Signs ..................................................................................................................................... 28 
10.6 
Pregnancy Test ............................................................................................................................. 28 
10.7 
Electrocardiograms ...................................................................................................................... 28 
10.8 
Physical Examinations ................................................................................................................. 28 
11 
OTHER ANALYSES ................................................................................................................... 28 
11.1 
Dose Escalation Safety Analyses ................................................................................................. 28 
11.2 
Pharmacokinetic and Pharmacodynamic Analysis .................................................................. 29 
12 
INTERIM ANALYSIS ................................................................................................................ 29 
13 
END-OF-STUDY-ANALYSIS .................................................................................................... 29 
14 
SUMMARY OF CHANGES FROM THE PROTOCOL......................................................... 29 
15 
REFERENCES ............................................................................................................................. 29 


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ABBREVIATIONS 
α 
 
Significance level 
AE  
 
Adverse event 
CR 
 
Complete response 
CRF 
 
Case Report Form 
CTCAE  
Common Toxicity Criteria for Adverse Events 
DLT 
 
Dose-limiting toxicity 
DOR 
 
Duration of Response 
ECG 
 
Electrocardiogram 
ECOG 
 
Eastern Cooperative Oncology Group 
EP 
 
Efficacy population 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
 
Magnetic resonance imaging 
MTD 
 
Maximum tolerated dose 
NE 
 
Non-evaluable 
NR 
 
No response 
PD 
 
Progressive disease or Pharmacodynamics 
PFS 
 
Progression-free Survival 
PK 
 
Pharmacokinetics 
PP 
 
Per-protocol 
PR 
 
Partial response or interval between the P wave and the QRS complex 
q12H 
 
Every 12 hours 
QRS 
 
Quasi-random signal 
QT 
 
QT interval 
QTcB 
 
QT interval, Bazett’s formula 
QTcF 
 
QT interval, Frederica’s formula 
RECIST  
Response Evaluation Criteria in Solid Tumors  
RR 
 
Interval between heart beats 
SAE 
 
Serious adverse event 
SAF 
 
Safety 
SD 
 
Stable Disease or Standard Deviation 
SOC 
 
System Organ Class 
TEAE 
 
Treatment-emergent adverse event 
TTP 
 
Time to Tumor Progression 
WHO 
 
World Health Organization 
 
 
 
 
 
 
 
 
 
 
 


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DEFINITIONS OF TERMS 
Part A 
Part A, the dose escalation component of this study, will evaluate the 
safety and tolerability of ASN002 (study drug) including dose-limiting 
toxicities (DLT) and to determine the maximum tolerated dose (MTD). 
Part B 
Part B, the cohort expansion component of this study, will evaluate the 
safety, tolerability, and preliminary efficacy of ASN002 in subjects with 
relapsed/refractory diffuse large B-cell lymphoma (DLBCL), follicular 
lymphoma (FL), mantle cell lymphoma (MCL), peripheral T-cell 
lymphoma (PTCL), myelofibrosis (MF), and chronic lymphocytic 
leukemia (CLL). 
Safety population 
The safety population will include all subjects who take at least 1 dose of 
study medication.  Safety analyses will be conducted using the safety 
population.  The safety population will apply to Parts A and B. 
Efficacy population 
The efficacy population (EP) will include all subjects who have an 
evaluable screening and post-dose tumor assessment.  The EP will be used 
as the supportive analysis population for efficacy endpoints. 
PP population 
The Per Protocol (PP) population will include all EP subjects without 
major protocol violations.  The PP population will be used as the primary 
analysis population for efficacy. 
Treatment Cohort 
There are nine treatment cohorts planned for Part A of this study: 
   Treatment Cohort 1 – 10 mg ASN002 q12H 
   Treatment Cohort 2 – 20 mg ASN002 q12H 
   Treatment Cohort 3 – 30 mg ASN002 q12H 
   Treatment Cohort 4 – 40 mg ASN002 q12H 
   Treatment Cohort 5 – 50 mg ASN002 q12H 
   Treatment Cohort 6 – 75 mg ASN002 q12H 
   Treatment Cohort 7 – 100 mg ASN002 q12H 
   Treatment Cohort 4a – 80 mg q24H 
   Treatment Cohort 5a –120 mg q24H 
 
Treatment-emergent 
Symptoms or conditions with onset after the first administration of 
ASN002. 


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1 
INTRODUCTION 
This document describes the statistical methods and data presentations to be used in summarizing and 
analyzing the safety, tolerability, and efficacy data from Protocol ASN002-101.  Background information 
is provided for the overall study design and objectives.  The reader is referred to the study protocol and 
case report forms (CRFs) for details of study conduct and data collection. 
Pharmacokinetic analyses and reporting are not included in this analysis plan. 
2 
STUDY OBJECTIVE(S), TREATMENTS, AND ENDPOINT(S) 
2.1 
Study Objectives 
2.1.1 
Primary Objectives 
The primary objectives of this study are: 
Part A: 
 
To evaluate the safety and tolerability of ASN002 including dose-limiting toxicities (DLTs) and to 
determine the maximum tolerated dose (MTD). 
Part B: 
 
To evaluate the safety, tolerability, and preliminary efficacy of ASN002 in subjects with 
relapsed/refractory diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell 
lymphoma (MCL), peripheral T-cell lymphoma (PTCL), myelofibrosis (MF), and chronic 
lymphocytic leukemia (CLL). 
2.1.2 
Secondary Objectives 
Part A and B: 
 
To evaluate the pharmacokinetic (PK) profile of ASN002 after single and multiple doses. 
2.1.3 
Exploratory/Pharmacodynamic Objectives 
Parts A and B: 
 
To evaluate the effects of ASN002 on Phospho-STAT3, Phospho-S6, Phospho-SYK 525/526, 
Phospho-ERK, and a panel of markers of inflammation (Appendix C of Protocol Amend 6). 
 
Evaluate the response to therapy based on DLBCL molecular subtype [germinal center B-cell like 
(GCB) or activated B-cell (ACB)]. 
 
To evaluate the effects of ASN002 on JAK (V617F) mutant allele burden in subjects with MF. 
 
To evaluate the effects of ASN002 on BCL2, and chromosome 17p. 
2.2 
Treatment Comparisons 
The dose escalation component (Part A) of this study will identify – based on safety and tolerability – a 
dose of ASN002 to be evaluated within the cohort expansion component of the study (Part B).  In Part B, 
eligible subjects will enroll into one of the six disease-specific cohorts (DLBCL, FL, MCL, PTCL, MF 
and CLL) and receive the dose of ASN002 identified in Part A.   


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2.3 
Study Endpoints and Evaluations 
2.3.1 
Efficacy 
2.3.1.1 Primary Efficacy Variable 
The primary efficacy variable for this study is disease response to ASN002.  It is expected that the 
investigator will choose the most appropriate method for radiographic assessment of the individual 
subject’s disease status. Subjects with a diagnosis of lymphoma are expected to undergo CT (for non-
FDG-avid lymphoma), or PET-CT (for FDG-avid lymphoma) for their efficacy evaluation. Subjects with 
advanced or metastatic solid tumors are expected to undergo CT with contrast (unless medically 
contraindicated) or MRI for their efficacy evaluation.  
For patients with MF spleen measurement will be performed by palpation and by MRI (preferred) or CT 
scan.  
For patients with CLL a baseline CT scan of chest/abdomen/pelvis and a bone marrow aspirate and 
biopsy are desirable. 
If Part B is not completed, only listings will be generated for descriptive summary of efficacy. 
DLBCL, MCL, FL, and PTCL 
The International Conference on Malignant Lymphoma (ICML) Recommendations for Initial Evaluation, 
Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma (2014 Lugano 
Classification) will be used to determine the stage of subjects with lymphoma, and the response to 
treatment.  
For cohorts that have at least 5 subjects at the recommended Part B dose of 75 mg BID, the following 
endpoints will be used to determine the response to treatment with ASN002 in subjects with lymphomas: 
 
Objective Response Rate 
 
Duration of Response 
 
Time to Tumor Progression (TTP) 
 
Progression-free Survival (PFS) 
 
PFS rate at week 24 
For cohorts with less than 5 subjects at the recommended Part B dose of 75 mg BID, efficacy will be 
summarized in a descriptive manner for those subjects who have at least stable disease per protocol 
criteria. 
Advanced Solid Malignancies 
The Tumor, Nodes, Metastasis (TNM) staging system developed by the American Joint Committee on 
Cancer (AJCC) will be used to record the subject’s clinical stage. Disease response will be assessed using 
the RECIST 1.1 criteria.  
For cohorts that have at least 5 subjects at the recommended Part B dose of 75 mg BID, the following 
endpoints will be used to determine the response to treatment with ASN002 in subjects with solid tumors: 
 
Objective Response Rate 
 
Duration of Response 


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 
TTP 
 
PFS 
 
PFS rate at week 24 
For cohorts with less than 5 subjects at the recommended Part B dose of 75 mg BID, efficacy will be 
summarized in a descriptive manner for those subjects who have at least stable disease per protocol 
criteria.  
 
Myelofibrosis 
The International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) 
and European LeukemiaNet (ELN) response criteria will be used to evaluate the response to treatment 
with ASN002.  If  less than 5 subjects were enrolled at the recommended Part B dose of 75 mg BID, 
efficacy will be summarized in a descriptive manner for those subjects who have at least stable disease 
per protocol criteria. 
 
The following endpoints will be used to determine the response to treatment with ASN002 in subjects 
with MF:  
 
Splenic response rate at week 24 
 
Clinical improvement rate at week 24 
 
Symptom response evaluated using the Myeloproliferative Neoplasm Symptom Assessment Form 
(MPN-SAF) tool  
 
rate of RBC transfusion through week 24 
CLL 
The response in patients with CLL will be evaluated according to the criteria of the International 
Workshop on Chronic Lymphocytic Leukemia with the exception that lymphocytosis will not be the sole 
criterion for disease progression. For patients with persistent lymphocytosis, a partial response in all other 
measures will be defined as a partial response with lymphocytosis. 
If  less than 5 subjects were enrolled at the recommended Part B dose of 75 mg BID, efficacy will be 
summarized in a descriptive manner for those subjects who have at least stable disease per protocol 
criteria. 
The following endpoints will be used to determine the response to treatment with ASN002 in subjects 
with CLL: 
 
Objective Response Rate 
 
Duration of Response 
 
TTP 
 
PFS 
 
PFS rate at week 24 


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2.3.1.2 Secondary Efficacy Variables  
 
Eastern Cooperative Oncology Group (ECOG) performance status – ECOG performance status will 
be assessed in accordance with the schedule of assessments (Section 3.2).  Change from baseline in 
ECOG performance status will be evaluated for each post-baseline assessment. 
2.3.1.3 Exploratory Efficacy Variables 
The exploratory pharmacodynamics variables for efficacy are: 
 
Inhibition of phosphorylation of S6, STAT3, SYK 525/526, and ERK. 
 
Inhibition of the basal B-cell surface activation markers, CD69 and CD88. 
 
Change from baseline in JAK (V617F) in ML patients. 
 
Change from baseline in BCL and chromosome 17p in CLL patients. 
 
Reduction of CRP, β2-microglobulin, and IL-10. 
 
Change from baseline in a panel of markers of inflammation (see Appendix C of the Study Protocol 
for the panel of markers).  
2.3.2 
Safety Evaluations 
The primary objective of part A of the study is to evaluate the safety and tolerability of ASN002 including 
DLTs and to determine the MTD.  This will be accomplished by evaluation of the safety and occurrence 
of DLTs at each dose level.   
All adverse events (AEs), unless they have been determined to be not related to study drug, will be taken 
into consideration in determining a DLT.  NCI CTCAE version 4.03 will be used to grade AEs. A DLT is 
defined as follows: 
Non-hematologic DLT 
Any grade ≥ 3 AE, with the following exceptions: symptomatic adverse events such as nausea, vomiting 
and diarrhea will not be considered dose limiting if they can be reduced to less than grade 3 within 72 
hours with standard supportive measures such as antiemetics and antidiarrheals.  
Hematologic DLT 
 
A grade ≥ 4 neutropenia or thrombocytopenia that lasts more than 7 days after the last dose of study 
drug; 
 
Febrile neutropenia; 
 
A grade ≥ 3 thrombocytopenia in the presence of bleeding. 
If one of the first 3 patients treated at a given dose level develops a DLT, up to 3 additional patients are to 
be treated at that dose level.  If at least 2 patients treated at a given dose level develop DLT, dose 
escalation is to be stopped, and the penultimate dose level will be considered the MTD.   
The MTD is defined as a dose level immediately below that at which ≥ 2 of 6 subjects experience a DLT.  
Subjects considered to be evaluable for the MTD determination are the subjects who have received the 
study drug for 28 days or who have discontinued the study drug earlier than 28 days because of a DLT. 


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The safety evaluations used to define tolerability and determine DLTs will include the following: 
 
Adverse events (AEs), monitored from the time the subject signs the consent form until 30 days after 
the last dose of ASN002; 
 
Prior, concomitant, and post medication use; 
 
Extent of exposure to study drug; 
 
Study drug compliance; 
 
Clinical laboratory tests (hematology, lipid panel, liver function, comprehensive metabolic panel, 
urinalysis, pregnancy [if applicable]); 
 
Vital signs; 
 
12-lead Electrocardiogram (ECG); 
 
Physical examination. 
3 
STUDY DESIGN 
3.1 
Overall Study Design and Treatment Groups 
This study will be performed at approximately 3 to 15 study centers located in the United States and Latin 
America. 
The study is an open-label, non-randomized, uncontrolled, multicenter, dose escalation, cohort expansion 
and extension study with single and multiple-dose PK in subjects with relapsed/refractory lymphomas, 
MF, CLL. and advanced/metastatic solid tumors for which no standard therapy exists. The study will be 
conducted in 2 parts: 
Part A: 
Evaluation of the safety and tolerability of escalating multiple doses of ASN002; 
Part B: 
Cohort expansion of 6 identified disease-specific cohorts (DLBCL, MCL, FL, PTCL, MF and 
CLL) from Part A to further evaluate the safety, tolerability and antitumor activity of multiple doses of 
ASN002. 
Parts A will be a “3+3” dose escalation scheme beginning with dose level 1 at a dose of 10 mg every 12 
hours. Subjects will receive a single dose of ASN002 on Day 1, followed by every 12 or 24 hours, as 
assigned, dosing beginning on Day 3. The dose of ASN002 will be escalated to identify DLTs, and the 
MTD. If an MTD is not identified by the last scheduled cohort, dose escalation will continue in less than 
or equal to 50% increments until the MTD is identified. If supported by the PK profile, transition to once 
daily dosing may be considered. The starting dose of the once daily (qd) dosing cohorts will not exceed 
the total daily dose of the highest twice daily dose that is considered safe and well tolerated. Daily dosing 
cohorts may include doses beginning at 60 mg QD.  Additional dose escalation may be performed for the 
qd dose cohorts, if the MTD is not identified by the 100 mg qd dose. 
The study design includes a screening period (up to 28 days), and a DLT observation period of 28 days 
(Cycle 1). A subject with no DLTs during Cycle 1 will have the opportunity to continue to receive 
ASN002, at the discretion of the investigator. Subjects that are not able to complete Cycle 1 for reasons 
other than DLT will be replaced. Subjects participating in Parts B who discontinue from the study due to 
non-compliance or protocol violations may be replaced at the discretion of the Sponsor. Subjects may 


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receive treatment with ASN002 in the absence of intolerable toxicity or disease progression for up to 12 
months. If the subject is not a candidate for or chooses not to participate in additional treatment cycles, an 
end of treatment visit will be performed. A follow-up visit will be performed at least 30 days after the last 
dose of study medication. 
In Part A of the study, after the Safety Review Committee (SRC) has met and agreed to dose escalation, 
up to 3 additional subjects may be allowed in a lower cohort to gather additional PK, PD and safety data. 
The inclusion of these subjects will be based on agreement with members of the SRC and the Sponsor 
Part B will be an expansion of the MTD cohort into 6 disease-specific groups to evaluate preliminary 
clinical anti-tumor activity. Each cohort will contain up to 14 subjects with DLBCL, MCL, FL, PTCL, 
MF, and CLL. Subjects may receive treatment with ASN002 in the absence of intolerable toxicity or 
disease progression for up to 12 months. 




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Protocol ASN002-101 
 
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a Subsequent cycles should begin within 3 days of either Day1, or the previous cycle. Subjects may continue to receive 
additional cycles of ASN002 in the absence of intolerable or severe toxicity or disease progression.  All safety laboratory 
and radiographic evaluations for continued dosing must be completed prior to evaluation by the investigator. 
b End of Treatment Visit should take place < 1 week from the last dose of study medication. 
c Complete physical examination will be conducted at screening and end of treatment. Other examinations may be brief, 
problem-focused examinations and review of systems. 
d Vital signs will consist of heart rate, blood pressure, and temperature. Day 3 and Day 16 apply to QD dosing cohorts only. 
e Height to be obtained at baseline only. 
f Refer to the Schedule of Assessments Table for Day 1, and Day 15. Day 3 and Day 16 apply to QD dosing cohorts only. 
g Laboratory assessments may be drawn up to 72 hours in advance of the scheduled visit for patient convenience. Refer to 
Error! Reference source not found. for a complete list of required safety laboratory assessments. Labs need not be repeated 
on day 1 cycle 1 if baseline data were obtained within the preceding 72 hours. 
h  Subjects will be evaluated based on malignancy-specific requirements. Evaluations may be completed up to one week 
prior to the nominal visit. 
2014 Lugano Classification (every 12 weeks ± 1 week) or 
RECIST 1.1 for advanced solid tumors every 8 weeks for the first 24 weeks, and every 12 weeks thereafter after the 
initiation of treatment with ASN002. 
i In the QD dosing cohorts, the Day 2 dose should be omitted. All other assessments should be performed. 
j PK samples are to be drawn as trough samples prior to study drug administration. 
k  Cycle 2, Day 1 only, prior to dose administration. 
l 30-day follow up for Adverse Events may be conducted as a telephone contact. 
 
 
 
 
 
 
 
 
 


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Table 2: Schedule of Assessments (Part B) 
 
 
 
 
Study Procedure 
Screening 
D (-28 to 
-1) 
Cycle 1 
Subsequent 
Cyclesa 
End of  
Treatmentb 
30-day  
Follow 
Up 
Days 
1 
2 
8 
15
22
1 
15
22 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
Eligibility Screening 
X 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
Physical Examinationc 
X 
X 
 
 
 
 
X 
 
 
X 
X 
Disease History & Stage 
X 
 
 
 
 
 
 
 
 
 
 
Vital signsd 
X 
X 
 
 
X 
 
X 
 
 
X 
X 
Heighte and weight 
X 
 
 
 
 
 
X 
 
 
X 
X 
ECOG PS 
X 
X 
 
 
 
 
X 
 
 
X 
 
12-lead ECG 
X 
X 
 
 
 
 
X 
 
 
X 
 
Pregnancy test, if 
applicable 
X 
 
 
 
 
 
 
 
 
X 
 
Serum Chemistryg 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
Liver Function Testsg 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
CBC with Diff and 
Plateletsg 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
Urinalysish 
X 
 
 
 
 
 
X 
 
 
 
 
Disease Assessmenti 
X 
 
 
 
 
 
 
 
X 
 
 
MPN-SAF (MF subjects 
only) j 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
Medication 
Administration 
 
X--------------------------------------------
-----------X 
 
 
Pharmacokinetic 
Samples 
 
Xk
Xl
Xl
Xl
Xl
Xl 
 
Xm 
 
Pharmacodynamic 
Samples 
 
X 
 
 
X 
 
X 
 
 
 
 
Adverse Events 
 
  X---------------------------------------------------------------------------
----------Xn 
Concomitant 
Medications 
       X-----------------------------------------------------------------------
----------X 
 
Dispense Drug Diary 
 
X 
 
 
 
 
X 
 
 
 
 
Medication Compliance 
 
 
 
 
 
 
X 
 
 
X 
 


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a Subsequent cycles should begin within 3 days of either Day1, or the previous cycle.  Subjects may continue to 
receive additional cycles of ASN002 in the absence of intolerable or severe toxicity or disease progression. All 
safety laboratory and radiographic evaluations for continued dosing must be completed prior to evaluation by the 
investigator. 
b End of Treatment Visit should take place < 1 week from the last dose of study medication. 
c Complete physical examination will be conducted at screening and end of treatment. Other examinations may be 
brief, problem-focused examinations and review of systems. Physical exam includes spleen measurement for 
subjects with MF. 
d Vital signs will consist of heart rate, blood pressure, and temperature. 
e Height to be obtained at baseline only. 
f Refer to the Schedule of Assessments Table for Day 1, and Day 15. 
g Laboratory assessments may be drawn up to 72 hours in advance of the scheduled visit for patient convenience. 
Refer to Error! Reference source not found. for a complete list of required safety laboratory assessments. Labs need 
not be repeated on day 1 cycle 1 if baseline data were obtained within the preceding 72 hours. Part B: Day 22 
laboratory assessments may be omitted. 
h Urinalysis is conducted on Day 1, and then as clinically indicated. 
i Subjects will be evaluated based on malignancy-specific requirements. Evaluations may be completed up to one 
week in advance of the nominal time to accommodate scheduling. 
Lymphoma: every 12 weeks by 2014 Lugano Classification. 
MF: MDS-SAF questionnaire to be done weekly, spleen measurement by PE every 4 weeks for the first 24 weeks 
and then every 12 weeks, spleen measurement by MRI/CT to be done at baseline and on week 24. 
CLL: every 8 weeks during the first 24 weeks and every 12 weeks thereafter by IWCLL criteria (and updates). A CT 
scan of chest/abdomen/pelvis is recommended if previously abnormal and otherwise in case of CR, a bone marrow 
aspirate/biopsy is recommended in case of CR or cytopenia of uncertain cause. 
j The MPN-SAF questionnaire will be completed weekly while on-study.On Day 22, and during subsequent cycles a 
form for completion at home should be given to the subject. 
k PK timepoints for Day 1 will be collected at predose, 2, 4 and 6 hours.   
l Predose PK samples are to be drawn as trough samples prior to study drug administration.  A trough PK sample 
will be drawn on Day 1 of Cycle 3, 6, 9 and 12. 
m Two PK samples are requested at the end of treatment. The first may be drawn with other safety laboratory 
assessments.The second optional sample is drawn 2-3 hours later. 
n 30-day follow up for Adverse Events may be conducted as a telephone contact. 
 


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Table 3: 
Cycle 1 Serial Assessments (Part A) 
Day 
Nominal 
Timea 
(hours) 
Windows 
Assessmentsb 
PK Sample
PD Sample 
ECG 
VS 
Day 1 
Predose 
Up to -60 
minutes 
X 
X 
X 
X 
0.5  
(± 5 mins.) 
X 
 
 
 
1.0  
X 
 
X 
X 
2.0 
X 
X 
X 
X 
4.0 
(± 15 mins.) 
X 
 
X 
X 
8.0 
(± 1 hr) 
X 
 
 
 
12.0 
X 
 
X 
X 
Day 2 
24 h post-
day 1 dose 
± 1 hr from 
1st dose 
X 
 
X 
X 
Day 3c 
(QD cohorts 
only) 
48 h post-
Day 1 dose 
± 2 hr from 
1st dose 
X 
 
X 
X 
Day 8 
Predose 
N/A 
X 
X 
X 
X 
Day 15 
Predose 
Up to -60 
minutes 
X 
X 
X 
X 
Day 15 
0.5  
(± 5 mins.) 
X 
 
 
 
1.0  
X 
 
X 
X 
2.0 
X 
X 
X 
X 
4.0 
(± 15 mins.) 
X 
 
X 
X 
8.0 
(± 1 hr) 
X 
 
 
 
12.0 
X 
 
X 
X 
Day 16 
(QD cohort only) 
24 h post-
Day 15 dose 
 
X 
 
X 
X 
Day 22 
Pre-dose 
N/A 
X 
 
X 
X 
Cycle 2, Day 1 
Pre-dose 
N/A 
X 
X 
 
X 
a The actual time of all assessments will be recorded in source documents and on the eCRF 
b The priority of assessments for the procedures is (1) PK/PD, (2)ECG, (3)VS 
c Only subjects in single daily dose cohorts require PK on Day 3 and 16. 
 
 
 


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Table 14:  
PK/PD Assessments (Part B) 
Day 
Nominal Timea 
(hours) 
Windows 
Assessments 
PK Sample 
PD Sampleb 
Day 1 
 
Predose 
N/A 
X 
X 
2. 0 
± 15 mins 
X 
X 
4.0 
± 15 mins 
X 
 
6.0 
± 30 mins 
X 
 
Day 2 
Predose 
N/A 
X 
 
Day 8 
Predose 
N/A 
X 
 
Day 15 
 
Predose 
N/A 
X 
X 
2.0 
± 15 mins. 
X 
X 
Cycle 2, Day 1 
 
Predose 
N/A 
X 
X 
2.0 
± 15 mins. 
X 
X 
Cycle 2, Day 15 
Predose 
N/A 
X 
 
Day 1, Cycle 3, 6, 9 and 
12 
Predose 
N/A 
X 
 
End of Treatment 
 
N/A 
N/A 
X 
 
2-3 (optional) 
± 15 mins. 
X 
 
a  The actual time of all assessments will be recorded in source documents and on the eCRF 
b In Part B of the study, only selected sites will be collecting the PD samples for phospho-proteins 
 
 


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4 
SAMPLE SIZE CONSIDERATIONS 
Part A:   
A traditional 3+3 design will be used to identify the MTD. In addition to the 40 subjects enrolled in the 
previous amendments, an additional 24 subjects may be enrolled and dose in either fed or fasted states. A 
total of 64 subjects will be enrolled into the Part A dose escalation phase of the study. No randomization 
will be performed for Part A. 
Part B:  A sample size of 84 subjects (14 each in DLBCL, MCL, FL, PTCL, MF, and CLL) will be 
enrolled. The null hypothesis that the true response rate is 0.05 will be tested against a one-sided 
alternative. A total of 14 patients will be accrued in each cohort. The null hypothesis will be rejected if at 
least 3 responses are observed in 14 subjects. This design yields a type I error rate of 0.02 and power of 
0.9 when the true response rate is 0.4.  
5 
ANALYSIS POPULATIONS 
5.1 
Safety Population 
The safety population includes all subjects who receive at least 1 dose of study medication.  Safety 
analyses will be conducted against the safety population. The safety population will apply to Parts A and 
B. 
5.2 
Efficacy Population (EP) 
The efficacy population (EP) will include all subjects who have an evaluable screening and post-dose 
tumor assessment.  The EP will be used as the supportive analysis population for summaries and analyses 
of the efficacy endpoints. No EP will be reflected if Part B is not completed for at least one indication. 
5.3 
Per-Protocol (PP) Population 
The PP population includes all EP subjects without major protocol deviations.  The PP population will be 
used as the primary analysis population for efficacy summaries and analyses.   No PP will be reflected if 
Part B is not completed for at least one indication. 
6 
CONSIDERATIONS FOR DATA ANALYSIS 
6.1 
Programming Environment 
All analyses will be conducted using SAS version 9.3. 
6.2 
Strata and Covariates 
There are no other planned strata or covariates for the analysis of this study. 
6.3 
Subgroups  
There are no planned subgroup analyses. 
6.4 
Multiple Comparisons and Multiplicity 
There are no planned adjustments for multiple hypothesis testing. 


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6.5 
Significance Level 
Unless otherwise specified, all statistical analyses will be conducted using a one-sided significance level 
(α) of 0.05 and one-sided hypothesis testing. 
6.6 
Statistical Notation and Methodology 
Unless stated otherwise, the term “descriptive statistics” refers to the number of subjects (n), mean, 
median, standard deviation, minimum, and maximum for continuous data and frequencies (counts and 
percentages) for categorical data.  Unless otherwise noted, all data collected during the study will be 
included in subject data listings and will be sorted by study component (i.e., Part A, and Part B), dosing 
cohort, subject number, and date/time within each subject.  
7 
DATA HANDLING METHODS 
7.1 
Missing Data 
7.1.1 
Date Values 
The missing component(s) of incomplete dates (e.g. start and/or stop dates of AE, concomitant 
medication, medical history) will be assumed as the most conservative value possible.  For example, if the 
start date has a missing day value, the first day of the month will be imputed for study day computations, 
etc.  If day is missing for an end date, the last day of the month will be imputed.  Similar logic will be 
assumed for missing month and year components.  For determination of treatment-emergent status, the 
start date will be imputed as the date of the first dose of study drug. 
Date imputation will only be used for computational purposes such as treatment-emergent status, etc.  
Actual data values, as they appear in the original CRFs, will be presented in the subject data listings. 
7.1.2 
Non-Date Values 
Every effort will be made to obtain required data at each scheduled evaluation from all subjects who have 
been enrolled.  There will be no imputation for missing data. 
7.2 
Visit Windows 
The screening assessments and the treatment/post-treatment assessments will be partitioned into the 
following two visit windows: 
 
A screening window, beginning on Day -28 and ending on Day -1. 
 
A treatment window, beginning on Day 1 of Cycle 1 and ending on the Study Day (see Section 7.3) 
corresponding with the End of Treatment visit. 
Subject visits for all parts of the study (i.e., Part A, and Part B) will be presented according to the nominal 
visit as obtained upon the CRF.  All values will be included in the subject data listings. 
7.3 
Data Derivations  
Day 1 will be the date corresponding to the first administration of study drug. 
Baseline values will be considered as the last non-missing assessment prior to the first administration of 
study drug (ASN002).  Pre-dose assessments of ECG, vital signs, and the samples for pharmacokinetics 
(PK) and pharmacodynamics (PD) on Day 1 of Cycle 1 will be considered the baseline assessment for 


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each of these respective study procedures.  Assessments performed on Day 1 of Cycle 1 for all other 
study procedures will be assumed to have been performed prior to administration of ASN002.  Unless 
otherwise specified, change from baseline calculations for a treatment window assessment will be the 
applicable treatment window assessment minus the baseline assessment. 
For a given date within the treatment window, Study Day will be computed as the given date minus Day 1 
of Cycle 1 plus 1 day (i.e., Study Day = Date – Day 1 of Cycle 1 + 1).  For a given date within the 
screening window, Study Day will be computed as the given date minus Day 1 of Cycle 1 (i.e., Study Day 
= Date – Day 1 of Cycle 1). 
For a given entry upon the Drug Log Form of the eCRF, total dose of ASN002 administered for the entry 
will be calculated as: 
   Total dose of ASN002 for entry (mg) = Total Daily Dose (mg/day) * (Stop Date – Start Date + 1). 
Furthermore, for a given date which lies between (non-inclusive) the Start Date and Stop Date, partial 
total dose of ASN002 for the entry can be calculated by substituting the given date for either the Stop 
Date or Start Date within the above formula. 
  
For each visit over the treatment window and overall, total dose of ASN002 will be calculated as the 
cumulative sum of the total dose and partial total dose of ASN002 administered over the entries to the 
Drug Log Form pertaining to the visit (or, overall).  An entry to the Drug Log Form will pertain to a given 
visit, if: (1) the Start Date of the entry is earlier than the date corresponding to the visit; and, (2) the Stop 
Date of the entry falls after the date corresponding to the immediately preceding visit. 
Expected total dose of ASN002 to be administered – for, a Drug Log Form entry, a visit, or overall – will 
be calculated similarly, with the daily dose corresponding to the assigned treatment cohort substituted in 
lieu of Total Daily Dose within the above formula. 
8 
STUDY POPULATION 
Unless otherwise stated, all study population analyses will be performed against the Safety Population. 
8.1 
Subject Enrollment 
Subject enrollment will be summarized as the number and percentage for each analysis population (EP, 
PP, and Safety) by treatment cohort and overall (all treatment cohorts combined).  The denominators for 
calculating percentages will be based on the number of subjects in each analysis population by treatment 
cohort and overall. 
Enrollment information will be provided in a data listing by subject.   
8.2 
Subject Disposition 
Subject disposition will be summarized by treatment cohort and overall.  The number and percentage of 
subjects who are still on treatment on this study or who have rolled over to the extension study, and the 
number and percentage of subjects discontinued from the study will be presented by reason for 
discontinuation.  The denominators for calculating the percentages will be based on the number of 
subjects in the analysis population by treatment cohort and overall. 
Discontinued subjects will be provided in a data listing by subject. 


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8.3 
Protocol Deviations 
Major protocol deviations are defined to be those deviations that could potentially bias either efficacy or 
safety summaries of the study.  Subjects associated with major protocol deviations will be identified prior 
to database lock. 
Major deviations from the clinical protocol may include, but are not limited to: 
 
Subjects that were administered at least one dose of ASN002 and who did not satisfy the 
inclusion/exclusion criteria. 
 
Subjects meeting conditions for withdrawal that were not withdrawn. 
 
Subjects that received a prohibited concomitant medication. 
 
Repeated non-compliance in administration of study drug, as monitored by the study site at the 
assessment timepoints shown within Table 1 of Section 3.2, where non-compliance is less than 80% 
or greater than 105% of expected administration of study drug. 
The number and percentage of subjects with major deviations and the number of deviations will be 
summarized by type of violation and overall.  Summaries will be provided by treatment cohort and 
overall.  The denominators for calculating percentages will be based on the number of subjects in the 
analysis population for each treatment cohort and overall. 
Major protocol deviations will be provided in a data listing by subject.  
8.4 
Inclusion/Exclusion Criteria 
Inclusion and exclusion criteria deviations will be provided in a data listing by subject. 
8.5 
Demographic Characteristics 
Subject demographics at screening: gender; age; ethnicity; height; weight; and, race, will be summarized 
by treatment cohort and overall.  
Gender, ethnicity, and race will be summarized as the number and percentage (n, %) of subjects within 
each category by treatment cohort and overall.  Denominators used in the calculation of percentages will 
be based on the number of subjects in the analysis population for each treatment cohort and overall. 
Age, weight, and height will be summarized as a continuous variable using descriptive statistics (n, mean, 
standard deviation, median, minimum, and maximum) by treatment cohort and overall. 
Demographic characteristics will be provided in a data listing by subject. 
8.6 
Clinical Stage  
Subject clinical stage at study entry will be summarized by diagnosis type (Lymphoma or Solid Tumor).  
For subjects with Lymphoma diagnosis, the summary of clinical stage will include stratification on the 
following factors:  FDG avidity status; Lymphoma type; and, Lugano Stage at study entry.  For subjects 
with Solid Tumor diagnosis, clinical stage will be summarized by TNM Stage at study entry.  Summaries 
will present the number and percentage of subjects by treatment cohort and overall.  Denominators used 
in the calculation of percentages will be based on the number of subjects in the analysis population for 
each treatment cohort and overall. 


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Clinical stage will be presented in a data listing by subject. 
8.7 
Prior Antineoplastic Therapy 
Prior antineoplastic cancer therapy will be reported in a data listing by subject. 
8.8 
Medical History 
Medical history (excluding prior antineoplastic cancer therapy) will be provided in a data listing by 
subject. 
9 
EFFICACY ANALYSIS  
 
 
 
The PP population and EP will be used for summaries and analyses of the efficacy variables described 
below. 
All efficacy results for each lymphoma type will be calculated and presented separately.  Efficacy results 
for solid tumor patients will be shown in listings, and parameters will be shown in text and text tables by 
range only.  
If Part B is not completed for at least one indication, efficacy parameters will only be reported as 
individual patient listings for summary descriptive reporting in the CSR. 
9.1 
Evaluation of Disease Status 
9.1.1 
DLBCL, MCL, FL, PTCL   
For cohorts that have at least 5 subjects at the recommended Part B dose of 75 mg BID, the frequency of 
responders according to the 2014 Lugano Classification for subjects with lymphoma will be evaluated at 
each dose level and for each lymphoma subgroup in Part B.  Differences in response to therapy based on 
the molecular subtypes of DLBCL will be explored.  
Assessments will be made after every two 28-day cycles of therapy, i.e., starting just before Day 1 of 
cycle 3 and then just before each odd-numbered cycle, for solid tumor patients and after every 3 cycles, 
i.e., just before Day 1 of cycle 4 and then just before cycles 7, 10, and 13, etc, for lymphoma patients.   
In Part B, response to treatment will be analyzed using the binomial test for each of the disease-specific 
cohorts (DLBCL, MCL, FL, PTCL, MF and CLL).  The dichotomous classifications to be assessed in 
each binomial test are disease responders versus non-responders.  Responders will be considered as 
subjects with 2014 Lugano Classifications given by Complete Response (CR) or Partial Response (PR), 
and non-responders as subjects with 2014 Lugano Classifications given by No Response (NR) or Stable 
Disease (SD), or Progressive Disease (PD).  For each binomial test, the null hypothesis is that the rate of 
disease responders is 5% and the one-sided alternative hypothesis is that the rate of disease responders is 
greater than 5%.  The null hypothesis will be rejected if the p-value is less than 0.05 (i.e., using a one-
sided significance level of 0.05).  
Summaries for best disease response will be provided by treatment cohort for subjects diagnosed with 
lymphoma using frequencies (counts and percentages).  For Part B, the estimated rate of disease 
responder and the p-value from the binomial test will be provided by disease-specific cohort (DLBCL, 
MCL, FL, PTCL, MF and CLL). 
Response to treatment will be provided in a data listing by subject. 


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9.1.2 
Advanced Solid Malignancies   
For cohorts that have at least 5 subjects at the recommended Part B dose of 75 mg BID, the frequency of 
responders according to modified RECIST 1.1 criteria for subjects with advanced solid malignancies will 
be evaluated at each dose level.  The changes from baseline in overall assessment of CR, PR, SD and PD 
will be reported. The frequency of disease assessment to treatment will be provided in a data listing by 
subject. 
9.1.3 
Myelofibrosis 
For cohorts that have at least 5 subjects at the recommended Part B dose of 75 mg BID, the frequency of 
response and type of response according to IWG-MRT response criteria for subjects with MF will be 
evaluated. The frequency of disease assessment to treatment and type of response (e.g. every 2 months, 
and spleen volume) will be provided in a data listing by subject. 
9.1.4 
Chronic Lymphocytic Leukemia 
For cohorts that have at least 5 subjects at the recommended Part B dose of 75 mg BID, the frequency of 
response, and type of response according to the criteria of the International Workshop on Chronic 
Lymphocytic Leukemia, will be evaluated. For patients with persistent lymphocytosis, a partial response 
in all other measures will be defined as a partial response with lymphocytosis. Duration of response and 
the PFS rate at week 24 will also be evaluated. 
9.1.5 
Evaluation of Performance Status 
For cohorts that have at least 5 subjects at the recommended Part B dose of 75 mg BID, the ECOG 
performance status and the changes from baseline will be presented with frequency tables at each dose 
level. 
The ECOG performance status will be assessed according to the Schedule of Assessments (see Section 
3.2).  ECOG scores – numeric scale, range from 0 to 5, inclusive – will correspond to the ECOG 
responses, as shown within Appendix B of the Study Protocol.  For a given treatment window ECOG 
assessment, change from baseline (CFB) in ECOG will be calculated as the difference between the 
treatment window ECOG assessment and baseline ECOG (i.e., CFB in ECOG = treatment window 
ECOG – baseline ECOG). 
Summaries for absolute and CFB in ECOG will be provided by visit and treatment cohort using 
frequencies (counts and percentages) for each study component separately and combined. 
Absolute and CFB in ECOG will be provided in a data listing by subject. 
9.2 
Evaluation of Time to Treatment 
The time (days) on treatment, beginning with the date of first administration of study drug and ending 
with the date of discontinuation or completion of study treatment, will be provided by treatment cohort 
using descriptive statistics (n, mean, standard deviation, median, minimum, and maximum. 
Time on treatment will be provided in a data listing by subject. 
9.3 
Evaluation of Time to Progression 
For cohorts that have at least 5 subjects at the recommended Part B dose of 75 mg BID, the time to 
disease progression (radiographic or clinical) will be calculated as the number of days from the date of the 


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first dose of study medication to the date the progression is observed or death due to tumor progression in 
the absence of previous documented PD. For subjects who have not progressed at the end of the study, the 
time to progression will be censored at the last assessment, unless the subject dies due to disease 
progression.  
9.4 
Evaluation of Progression-free Survival 
For cohorts that have at least 5 subjects at the recommended Part B dose of 75 mg BID, PFS will 
be calculated as the number of days from the date of the first dose of study medication to the date 
progression is observed, or death from any cause. PFS will be analyzed using the Kaplan-Meier method.  
9.5 
Exploratory Efficacy Variables 
9.5.1 
Panel of Biomarkers 
Serum concentrations of the biomarkers Phospho-S6, Phospho-STAT3, Phospho-SYK 525/526, Phospho 
-ERK, basal B-cell surface activation markers, CD69, CD88, and the panel of markers of inflammation 
(see Appendix C of the Study Protocol), including CRP, β2-microglobulin, and IL-10, will be collected 
pre-dose on Day 1 of Cycle 1 (baseline assessment) and at the visits/timepoints indicated within the 
within the Schedule of Assessments (see Section 3.2).  For each biomarker and post-baseline assessment, 
change from baseline (CFB) in the biomarker will be calculated as the difference between the post-dose 
assessment and the baseline value (i.e., CFB in biomarker = post-dose biomarker value – baseline 
biomarker value). 
Summaries for absolute and CFB for each biomarker will be provided by visit/timepoint and treatment 
cohort using descriptive statistics (n, mean, standard deviation, median, coefficient of variance, minimum, 
and maximum). 
Absolute and CFB for each biomarker will be provided in a data listing by subject. 
10 
SAFETY ANALYSIS 
Unless stated otherwise, all safety analyses will be performed on the Safety Population.   
10.1 
Adverse Events 
Treatment emergent adverse events (TEAE) will be classified into a standardized terminology using the 
Medical Dictionary for Regulatory Activities (MedDRA, version 17.0 or higher) system organ 
classifications and preferred terms.  All summaries of the incidence of treatment-emergent adverse events 
will be provided using the Safety Population by treatment cohort and overall.  Although a preferred term 
or system organ class may be reported more than once for a subject, each subject will only be counted 
once in the incidence count for that preferred term or system organ class.  Summaries of the following 
types will be provided: 
 
Summary of treatment-emergent adverse events; 
 
Summary of treatment-emergent adverse events by MedDRA system organ class and MedDRA 
preferred term; 
 
Summary of treatment-emergent adverse events by MedDRA system organ class, MedDRA preferred 
term, relationship to study drug, and intensity; 


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 
Summary of serious treatment-emergent adverse events leading to discontinuation from the study by 
MedDRA preferred term, sorted alphabetically by system organ class and preferred term; 
 
Summary of treatment-emergent adverse events leading to discontinuation from the study by 
MedDRA preferred term, sorted alphabetically by system organ class and preferred term. 
These summaries will present the number and percentage of subjects reporting an adverse event for each 
classification level.  The denominators for calculating the percentages will be based on the number of 
exposed subjects in the Safety population (i.e., study drug was administered) in the treatment cohort 
summarized. 
Listing of subject dropouts due to AEs prior to post-dose tumor assessment will be generated. All adverse 
events, serious adverse events and deaths, and adverse events leading to discontinuation from the study 
will also be provided in data listings by subject. 
10.2 
Treatment Exposure 
The duration of exposure (days) to study drug, total dose of ASN002, and average dose of ASN002 will 
be summarized using descriptive statistics (n, mean, standard deviation, median, minimum, and 
maximum) by treatment cohort.  Duration of exposure will be calculated as the difference between the 
date of last administration of study drug and the date of first administration of study drug plus 1 day. 
Exposure data including study drug bottle assignment, date and time of study drug administration at study 
site visits, diary dispense/return dates, and study drug log data will be provided in separate data listings by 
subject. 
10.3 
Prior, Concomitant, and Post-Treatment Medications 
Medication usage will be coded using the World Health Organization (WHO) Drug Dictionary.  
Medication use will be presented for the Safety population by WHO Drug 
Anatomical/Therapeutic/Chemical (ATC) category and WHO Drug preferred name.  Medication use 
summaries will be presented for prior medication use (prior to first administration of study drug), 
concomitant medication use (between the date of first administration of study drug, but not beyond the 
date of the last administration of study drug), and post medication use (superseding the date of last 
administration of study drug).  Summaries will be provided by treatment cohort and overall.  Medications 
with partial start and/or stop dates, which cannot be definitely categorized as prior, concomitant, or post-
treatment medications will be considered concomitant. 
All summaries will present the number and percentages of subjects using each medication by treatment 
cohort.  The denominators for percentages will be the number of subjects in the analysis population for 
the treatment cohort summarized. 
Prior, concomitant, and post medications will be provided in separate data listings by subject. 
10.4 
Laboratory Evaluations 
Absolute and change from baseline values for continuous hematology panel, lipid panel, comprehensive 
metabolic panel, and urinalysis parameters will be summarized by analyte, assessment (see Section 3.2), 
and treatment cohort using descriptive statistics (mean, median, SD, minimum, maximum, and number of 
subjects).  Categorical laboratory evaluations will also be summarized by analyte as the number and 
percentage of subjects at each possible analyte level.  The denominators for percentages will be the 
number of subjects in the analysis population for the treatment cohort summarized.  The following 
analytes will be considered for all summary tables described within this section: hemoglobin, total white 


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blood cell (WBC), WBC differential, platelets, alkaline phosphatase (ALP), ALT, AST, bilirubin, 
creatinine, total cholesterol, and triglycerides.   
Shifts relative to baseline will be evaluated based on the Common Terminology Criteria for Adverse 
Events (CTCAE) v4.0 criteria and presented by analyte, assessment, and treatment cohort.  Summaries 
will contain the numbers and percentages of subjects with sufficient data to evaluate new Grade 1 
abnormalities (i.e., normal at baseline) and shifts of one Grade higher relative to baseline. 
Data listings for laboratory parameters and shifts will be presented by subject.    
10.5 
Vital Signs 
Vital sign measurements (blood pressure, heart rate, temperature [Visit 1 only]), height (Screening Visit 
only), and weight will be provided in a data listing by subject.  
10.6 
Pregnancy Test 
Serum or urine pregnancy testing is required at screening and within 72 hours of Day 1 of every Cycle for 
females of childbearing potential.  Results of pregnancy tests will be provided in a data listing by subject.  
10.7 
Electrocardiograms 
For QTcF intervals, the proportion of QTcF above the upper limit of normal – both ≥ 450 msec and ≥ 481 
msec will be considered as upper limits of normal QTcF – and change from baseline > 30 msec and > 60 
msec will be presented.  Denominators for percentages will be the number of subjects in the analysis 
population for the treatment cohort summarized. 
ECG data will be displayed in a data listing by subject. 
10.8 
Physical Examinations 
A complete physical examination (PE) will be performed at the Screening and End of Treatment visits.  
The examination will include an assessment of the following: general appearance, skin, head and neck 
(including eyes, ears and throat), thorax, lymph nodes, thyroid, musculoskeletal/extremities (including 
spine), cardiovascular, lungs, abdomen and neurological systems.  The screening exam will also include a 
measurement of body height and weight.  The investigator will review all PE findings for clinical 
significance.  Findings from the screening PE will be recorded as Medical History.  Except for the 
screening PE, only changes from the previous PE will be recorded.  Clinically significant changes from 
the screening PE will be captured as AEs, and analyzed according to the criteria in Section 10.1. 
 
A data listing, comprised of status of whether or not each assessment was conducted and date of each 
assessment, for physical examinations will be presented by subject.  
11 
OTHER ANALYSES 
11.1 
Dose Escalation Safety Analyses 
The study will include multiple safety analyses for the dose escalation component (Part A).  Each 
treatment cohort is viewed as a separate safety analysis, insofar as the safety review committee will 
decide whether the dose escalation will continue to the next planned (or intermediate) dose level, if 
additional subjects will be added to the current dose level, or if the dose escalation will be stopped.  The 
safety review committee can also terminate the study due to safety concerns.  Each review will be 
conducted with the latest available data. 


Statistical Analysis Plan 
 
Asana BioSciences, LLC 
Protocol ASN002-101 
      
  
 
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A data listing of dose-limiting toxicities (DLTs) for Part A will be presented by subject. 
11.2 
Pharmacokinetic and Pharmacodynamic Analysis 
Pharmacokinetic (PK) analysis will be included in a separate analysis plan. 
Part A and Part B may be combined for population PK/PD analysis.  This analysis will be included in a 
separate population PK/PD analysis plan. 
12 
INTERIM ANALYSIS 
An interim analysis is not applicable to this study.  As this is an open-label study, appropriate analyses 
will be conducted on an ongoing basis. 
13 
END-OF-STUDY-ANALYSIS 
A final analysis will be conducted after the last patient completes or discontinues the study and the 
resulting clinical database has been cleaned, quality checked, and locked.   
14 
SUMMARY OF CHANGES FROM THE PROTOCOL 
No changes from the protocol were made in this analysis plan. 
15 
REFERENCES 
[1]  Cheson BD, Fisher RI, Barrington SF, et al.  Recommendations for initial evaluation, staging, and 
response assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification.  J Clin 
Oncol.  2014; 32(27): 3059-3068. 
[2]  Eisenhauer EA, Therasse P, Bogaerts J, et al.  New response evaluation criteria in solid tumours: 
revised RECIST guideline (version 1.1).  Eur J Cancer.  2009; 45(2): 228-247.