To Determine Safe and Effective Dose of ACE-011 for the Treatment of Chemotherapy Induced Anemia in Patients With Advanced Non-small Cell Lung Cancer

The ACE-011-NSCL-001 Phase 2a study was an open-label, randomized, dose-ranging study
designed to assess the efficacy, safety, tolerability, pharmacokinetic and quality of life of
sotatercept (ACE-011) for treatment of CIA in participants with advanced or metastatic solid
tumors treated with platinum-based chemotherapeutic regimens. Other objectives included the
effect of sotatercept treatment on bone metabolism, the evaluation of the expression of
Activin A and other proteins/biomarkers (including myostatin and follistatin) and the
assessment of renal function biomarkers. The study consisted of a Screening Period, a
Treatment Period of approximately 6 months (up to 4 doses of sotatercept at either 15 mg or
30 mg administered subcutaneously every 42 days) and a Post-treatment Follow-up Period or End
of Treatment (42 days after the last dose of sotatercept). The study was terminated early due
to a slower than expected rate of enrollment as a result of substantial changes in the
standard of care for cancer participants with anemia which resulted in challenges to timely
accrual and completion of the study. Therefore, 26 participants were randomized into the
study and the planned Part 2 of the study consisting of a double-blind, randomized,
placebo-controlled Phase 2b/3 study conducted at the optimal dose of sotatercept (ACE-011) in
up to 750 subjects with metastatic NSCLC was not performed. Due to the small sample size and
variability of the data, changes were made to modify the study endpoints and revise them to
be exploratory only.

Inclusion Criteria:

1. Men and women > 18 years of age

2. Part 1: Histologically confirmed (cytology or biopsy) solid tumor malignancy,
excluding those solid tumors treated with curative intent.

Part 2: Histologically confirmed non-small cell lung cancer

3. Documented metastatic disease

4. Measurable or non-measurable disease evaluable by Response Evaluation Criteria in
Solid Tumors (RECIST) Version 1.1

5. All of the following laboratory values:

- Hemoglobin ≥ 6.5 to < 11.0 g/dL (≥ 65 to < 110 g/L), due to chemotherapy-induced
anemia

- Absolute neutrophil count ≥ 500/mm^3

- Platelet count ≥ 75,000/mm^3 (> 72 hours since prior platelet transfusion

- Adequate renal function

- creatinine clearance ≥ 40mL/min or ≥ 50 mL/min if cisplatin is concomitantly
administered and

- urine protein / creatinine ratio ≤ 1.0; or ≤ 2.0 if bevacizumab (Avastin®)
is concomitantly administered

- Hepatic function (bilirubin < 1.5 x upper limits of normal (ULN); AST and ALT <
3.0 x ULN and ≤ 5.0 ULN for subjects with liver metastases)

6. Subjects must have received:

- at least one cycle and up to 4 cycles (q3w schedule) of platinum-based
chemotherapy and be randomized prior to receiving Cycle 5 OR

- at least one cycle and up to 3 months (depending upon regimen) of platinum-based
chemotherapy

7. >28 days since previous treatment with ESA

8. >14 days since last red blood cell transfusions

9. Eastern Oncology Cooperative Group (ECOG) Performance status 0-2

10. For females of childbearing potential, highly effective method of birth control for at
least 28 days before starting study, during participation and at least 112 days
following last dose of ACE-011

11. Males must use latex condom or non-latex condom not made of (animal) membrane during
any sexual contact with female of childbearing potential

12. Life expectancy of >3 months

13. Willing to adhere to study visit schedule

14. Understand and voluntarily sign informed consent

Exclusion Criteria:

Part 2 only, history of prior regimen(s)of platinum-based chemotherapy for metastatic NSCLC
and/or history of adjuvant platinum-based chemotherapy with last dose received less than
six months prior to the start of current first-line platinum-based chemotherapy for
metastatic NSCLC.

1. National Cancer Institute Common Terminology for Adverse Events Grade >3 toxicity

2. Prior radiation to >20% of whole skeleton

3. Prior regimen(s) of platinum based chemotherapy for metastatic disease and/or history
of adjuvant platinum-based chemotherapy with the last dose received less than six
months prior to the start of current first-line platinum-based chemotherapy for
metastatic disease

4. Central nervous system metastases

5. Clinically significant pulmonary, endocrine, neurologic, gastrointestinal, hepatic, or
genitourinary disease unrelated to underlying malignancy

6. Classification of 3 or higher heart failure (as classified by New York Heart
Association)

7. History of thrombosis, deep vein thrombosis, pulmonary emboli, or embolic stroke, if
not stable on anticoagulants and/or one of these events occurring in past 6 months

8. Diagnosis of a myeloid malignancy or known history of myelodysplasia

9. Recent history (within 14 days of Day 1) of IV/oral antibiotics due to post septic
episode

10. Uncontrolled hypertension. Controlled hypertension is considered clinically stable,
and systolic blood pressure (SBP) must be < 150 mmHg and diastolic blood pressure
(DBP) must be < 100 mmHg.

11. Known human immunodeficiency virus (HIV)

12. Known active hepatitis B or C antibody

13. Iron deficiency

14. History of anemia as a result of inherited hemoglobinopathy

15. History of anemia due to autoimmune or hereditary hemolysis or gastrointestinal
bleeding

16. Received treatment with another investigational drug or device within 28 days prior to
Day 1, or if the half life of the previous product is known, within 5 times the half
life prior to dosing, whichever may be longer.

17. Any prior use of Sotatercept (ACE-011).

18. Pregnant or lactating females or females planning to become pregnant

19. History of severe allergic or anaphylactic reactions or hypersensitivity to
recombinant proteins or excipients in the investigational product (Refer to the
Investigator's Brochure for further information).

20. Major surgery within 30 days prior to Day 1 (subjects must have completely recovered
from any previous surgery prior to Day 1).