A Phase 1/2 Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of AO-176

This is a first-in-human, Phase 1/2 multi-center, open-label, dose escalation and expansion
study of AO-176 which will evaluate the safety, tolerability, pharmacokinetics (PK),
pharmacodynamics, and clinical effects of AO-176 in patients with advanced solid tumors.

Key Inclusion Criteria

1. Select advanced solid tumor for which standard therapy proven to provide clinical
benefit does not exist, or is no longer effective

Part A:

- Epithelial ovarian carcinoma (EOC)

- Endometrial carcinoma

- Castration resistant prostate cancer

- Non-small cell lung adenocarcinoma

- Papillary thyroid carcinoma

- Malignant mesothelioma (pleural or peritoneal)

- Gastroesophageal adenocarcinoma

- Squamous cell carcinoma of the head and neck

Part B and Part C:

- Platinum-resistant EOC (including fallopian tube or primary peritoneal cancer)

- Endometrial carcinoma

- Gastric adenocarcinoma/gastroesophageal adenocarcinoma

2. Measurable disease

3. ECOG status 0-1

4. Resolution of prior-therapy-related adverse effects

5. Minimum of 4 weeks or 5 half-lives since last dose of cancer therapy

Key Exclusion Criteria:

1. Previous hypersensitivity reaction to treatment with another monoclonal antibody

2. Unresolved hypersensitivity to paclitaxel or any of its excipients (Part B only).
Patients who have been desensitized may participate.

3. Part C Only

1. History of interstitial lung disease or a history of (non-infectious) pneumonitis
that required steroids or has current pneumonitis.

2. History of immune mediated colitis, hepatitis, endocrinopathies, nephritis or
significant immune mediated skin reactions such as toxic epidermal necrolitis or
Stevens -Johnson Syndrome

3. History of any autoimmune disease which required systemic therapy* in the past 2
years (i.e., with use of disease modifying agents, corticosteroids or
immunosuppressive drugs) including but not limited to: i. Inflammatory bowel
disease (including ulcerative colitis and Crohn's Disease) ii. Rheumatoid
arthritis iii. Systemic progressive sclerosis (scleroderma) iv. Systemic lupus
erythematosus v. Autoimmune vasculitis (e.g. Wegener's granulomatosis)
*Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a
form of systemic treatment and is allowed)

4. Prior treatment with a checkpoint inhibitor (anti-PD-1, PD-L1, CTLA-4 etc.) within 4
weeks prior to the start of study drug

5. Prior treatment with a CD47-targeted therapy

6. Prior organ or stem cell transplant