Outlook Therapeutics, a biopharmaceutical company, has been on a mission to achieve the first-ever approval for an ophthalmic formulation of bevacizumab for the treatment of retinal diseases. After years of dedicated research and development, the company has made significant strides, recently securing marketing authorizations in the European Union (EU) and the United Kingdom (UK) for its lead product candidate, LYTENAVA™ (bevacizumab gamma).

Business Overview Outlook Therapeutics was incorporated in New Jersey on January 5, 2010, and started operations in July 2011. The company later reincorporated in Delaware by merging with and into a Delaware corporation in October 2015 and changed its name to Outlook Therapeutics, Inc. in November 2018. The company’s primary focus has been the development and commercialization of ONS-5010, an ophthalmic formulation of bevacizumab, for the treatment of wet age-related macular degeneration (wet AMD) and other retinal diseases.

In May 2024, the European Commission granted marketing authorization for LYTENAVA™ (bevacizumab gamma) for the treatment of wet AMD in the EU. This followed a positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use in March 2024. Additionally, in July 2024, the United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA) granted marketing authorization for LYTENAVA™ for the same indication. These approvals mark a significant milestone for the company, as LYTENAVA™ is the first and only authorized ophthalmic formulation of bevacizumab for the treatment of wet AMD in these key markets. The EU Marketing Authorization grants Outlook Therapeutics an initial ten years of market exclusivity in the EU for LYTENAVA™ bevacizumab gamma.

Outlook Therapeutics’ development efforts for ONS-5010 in the United States have faced some challenges. In March 2022, the company submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for ONS-5010. However, in August 2023, Outlook Therapeutics received a Complete Response Letter (CRL) from the FDA, citing several chemistry, manufacturing and control (CMC) issues, open observations from pre-approval manufacturing inspections, and a lack of substantial evidence.

In response, Outlook Therapeutics agreed to conduct an additional adequate and well-controlled clinical trial, NORSE EIGHT, to support the planned resubmission of the ONS-5010 BLA. The NORSE EIGHT study is a randomized, controlled, parallel-group, masked, non-inferiority trial evaluating ONS-5010 in approximately 400 newly diagnosed wet AMD patients. The company recently announced the completion of enrollment for the NORSE EIGHT trial and expects to report topline results in the fourth quarter of 2024. If successful, the NORSE EIGHT trial, along with the resolution of the CMC comments, is expected to provide the necessary data for the company to resubmit the ONS-5010 BLA in the first quarter of 2025.

Financials and Liquidity Outlook Therapeutics has not generated any revenue from product sales to date, as the company’s lead candidate, LYTENAVA™, is still in the commercialization phase. The company has funded its operations primarily through the sale and issuance of equity and debt securities, as well as collaborations and licensing agreements.

For the fiscal year ended September 30, 2023, the company reported no revenue, a net loss of $58,982,668, and negative operating cash flow and free cash flow of $42,973,398. In the most recent quarter ended June 30, 2024, Outlook Therapeutics reported no revenue, but saw a significant improvement in net income, reporting $44,409,187. This increase was primarily due to a gain recorded on the change in fair value of the warrant liability. However, operating cash flow and free cash flow remained negative at -$19,512,357 due to ongoing R&D and operating expenses.

As of June 30, 2024, the company reported cash and cash equivalents of $32.0 million. When combined with the expected $107 million in proceeds from the full exercise of warrants to purchase shares of common stock, subject to meeting the requirements for calling such warrants, Outlook Therapeutics believes the existing cash and cash equivalents would be sufficient to support its operations through calendar year 2025.

It’s worth noting that the company has also received approximately $29 million in cumulative funding from its collaboration and licensing agreements related to its inactive biosimilar development programs.

The company’s debt-to-equity ratio as of June 30, 2024, was -0.3876, with $32.43 million in unsecured convertible promissory notes classified as current liabilities. The current ratio and quick ratio both stood at 1.07 as of the same date.

Outlook and Risks The recent marketing authorizations in the EU and UK for LYTENAVA™ represent a significant achievement for Outlook Therapeutics. The company is now focused on launching the product in these key markets, with initial commercial launches anticipated in the first calendar quarter of 2025. The company is actively engaged in market access initiatives, product inventory planning, and evaluating potential partnership opportunities to support the commercialization efforts.

In the United States, the successful completion of the NORSE EIGHT trial and the resolution of the CMC comments from the FDA are crucial for the company’s resubmission of the ONS-5010 BLA, expected in the first quarter of 2025. The outcome of the NORSE EIGHT trial and the FDA’s review of the resubmitted BLA will be critical for the company’s path to approval and commercialization of ONS-5010 in the US market.

Outlook Therapeutics expects to complete enrollment in the NORSE EIGHT clinical trial before the end of the third calendar quarter of 2024, with 359 of the planned 400 subjects already enrolled at the time of their recent conference call. The company estimates the total cost to complete the NORSE EIGHT trial to be $30 million, with most of these expenses incurred during the first three calendar quarters of 2024.

Risks facing Outlook Therapeutics include the potential for further delays or setbacks in the regulatory approval process, challenges in securing favorable pricing and reimbursement for LYTENAVA™ in the EU and UK, and the ability to successfully launch and commercialize the product in these markets. Additionally, the company’s reliance on the successful completion of the NORSE EIGHT trial and the resolution of the CMC comments poses a significant risk, as any unfavorable outcomes could further delay the US approval and commercialization of ONS-5010.

Conclusion Outlook Therapeutics has made impressive strides in its mission to bring the first-ever ophthalmic formulation of bevacizumab to the market for the treatment of wet AMD and other retinal diseases. The company’s recent marketing authorizations in the EU and UK for LYTENAVA™ are a testament to its dedication and the quality of its work. As the company now pivots towards the commercialization of LYTENAVA™ in these key markets and the regulatory path forward in the United States, investors will be closely watching the execution of the company’s strategy and the outcomes of the NORSE EIGHT trial and the FDA’s review of the resubmitted ONS-5010 BLA. With a clear focus on addressing unmet needs in the retinal disease treatment landscape, Outlook Therapeutics remains poised to make a significant impact in the years to come.

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