Outlook Therapeutics Inc (OTLK)

[thermo]

Outlook Therapeutics – new position for me today.

Overview
1. Clinical-stage biopharmaceutical company seeking Bevacizumab-vikg (ONS-5010) approval in Neovascular Age-related Macular Degeneration (Wet AMD).
a. Become first-line “step-edit” drug of choice
b. Product is biosimilar to Bevacizumab. Bevacizumab first approved in the United States in February 2004 for metastatic colorectal cancer. Used in other cancers. Well understood.
c. ONS-5010 meets ophthalmic criteria. E.g. USP 789 for particulates (General Chapters: <789> PARTICULATE MATTER IN OPHTHALMIC SOLUTIONS (uspbpep.com)).

2. File as new BLA with FDA – 12-year exclusivity.
a. End of phase 2 meeting with FDA.
a. Confirmed availability of BLA pathway.
b. Same study design used for Wet-AMD, Branch Retinal Vein Occlusion (DME) and Branch Retinal Vein Occlusion (BRVO)
c. FDA granted Special Protocol Assessment for DME and BRVO. See: Outlook Therapeutics Receives FDA Agreement for Three Special Protocol Assessments for Additional Planned Clinical Trials of ONS-5010 - Outlook Therapeutics, Inc.
d. Since study designs of nAMD same as DME, believe design will be acceptable to FDA.
e. OTLK submitted SPA for wAMD. Received comments and incorporated into study. Didn’t want to wait for final SPA, since first to file provided exclusivity.

b. Expect data release July/August 2021.
c. File BLA with FDA by year end 2021, EU 1H’2021.
d. In discussion with European regulators for filing using same data.
a. FDA / EU requires 9 / 12 mos of stability data on GMP batch. So FDA will file with FDA first.
b. Have 9 months of data November 2021
e. Approval: 2022 USA, 2023 EU

3. Solving public health concerns of using off-label Bevacizumab (Avastin).
a. Current off label use of compounded Bevacizumab raises issues with correct potency, infection.
i. Intravitreal preparations of bevacizumab acquired from compounding pharmacies => 81% had lower protein concentrations (mean [SD], 22.2 [4.9] mg/mL; range, 19.2-24.5 mg/mL) compared with bevacizumab acquired directly from Genentech. See: https://pubmed.ncbi.nlm.nih.gov/25233052/
b. Pre-filled syringe would be best solution. A syringe pre-filled with ONS-5010 likely to follow 1 – 1.5 years after approval of vial form.

4. Commercialization
a. Off label Bevacizumab used in 50% of Wet-AMD cases (USA) and 30% of cases (Europe)
b. Payor discussion on pricing. Expect strong support for product.
c. if they get ¼ - ½ of off label beva to switch to approved version => peak revenue of $500M - $1B.