Outlook Therapeutics, a biopharmaceutical company, has embarked on an ambitious journey to reshape the landscape of ophthalmic care. With a laser-sharp focus on developing and commercializing the first-ever approved ophthalmic formulation of bevacizumab, the company is poised to make a significant impact in the treatment of retinal diseases, particularly wet age-related macular degeneration (wet AMD).

Company Background

Outlook Therapeutics, Inc. was incorporated in New Jersey on January 5, 2010, and began operations in July 2011. The company underwent a significant transformation in October 2015 when it reincorporated in Delaware by merging with and into a Delaware corporation. In November 2018, the company changed its name to Outlook Therapeutics, Inc., solidifying its identity and mission in the biopharmaceutical industry. Since its inception, Outlook Therapeutics has maintained a steadfast focus on developing and commercializing an ophthalmic formulation of bevacizumab for use in retinal indications.

Regulatory Milestones

In May 2024, the European Commission granted marketing authorization for LYTENAVA™ (bevacizumab gamma) for the treatment of wet AMD in the European Union (EU). This historic approval marked a significant achievement, as LYTENAVA™ became the first and only authorized ophthalmic formulation of bevacizumab for this indication in the EU. Just two months later, in July 2024, the company received similar marketing authorization from the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) for the use of LYTENAVA™ in the treatment of wet AMD.

These regulatory approvals paved the way for Outlook Therapeutics to initiate its commercial launch plans in the EU and UK. The company is currently engaged in crucial market access work, inventory planning, and ongoing discussions with potential partners to ensure a successful rollout of LYTENAVA™ in these key markets, with the first commercial launches anticipated in the first half of calendar year 2025.

US Pipeline Progress

The company's pipeline extends beyond the EU and UK, as Outlook Therapeutics continues to make progress in the United States. In the U.S., the company is diligently working to resubmit its Biologics License Application (BLA) for ONS-5010/LYTENAVA™ to the Food and Drug Administration (FDA) for the treatment of wet AMD. The NORSE EIGHT clinical trial, a critical component of this effort, is currently underway, with Outlook Therapeutics expecting to report top-line results in the fourth quarter of 2024 and resubmit the BLA in the first quarter of 2025.

Clinical Trials and Results

The NORSE EIGHT study is the second of two adequate and well-controlled clinical trials evaluating ONS-5010/LYTENAVA™ for the treatment of wet AMD. In November 2024, the company reported that the candidate did not meet the pre-specified non-inferiority endpoint at week 8 set forth in the Special Protocol Assessment (SPA) with the FDA. However, the preliminary data demonstrated an improvement in vision and the presence of biological activity, as well as a continued favorable safety profile for ONS-5010/LYTENAVA™.

Subsequent analysis of the complete 12-week data set from the NORSE EIGHT trial has now been completed, and the results have been presented at the Hawaiian Eye and Retina 2025 Meeting. These data confirmed that intravitreal ONS-5010/LYTENAVA™ provided early and sustained anatomic improvements, with steady gains in best-corrected visual acuity (BCVA) and a reliable, consistent safety profile. Importantly, ONS-5010/LYTENAVA™ was demonstrated to be non-inferior to Lucentis (ranibizumab) at 12 weeks. Armed with these positive findings, Outlook Therapeutics remains on track to resubmit the BLA for ONS-5010/LYTENAVA™ in the first quarter of 2025.

Financials

Financially, Outlook Therapeutics has been actively managing its resources to support its commercial launch plans and ongoing clinical development efforts. As of September 30, 2024, the company reported $14.93 million in cash and cash equivalents. This cash position, combined with the expected $107 million in proceeds from the full exercise of warrants to purchase shares of common stock, subject to meeting certain requirements, is expected to be sufficient to support the company's operations through calendar year 2025.

For the fiscal year 2024, Outlook Therapeutics reported no revenue, with an annual net loss of $75.37 million and an annual operating cash flow of -$68.79 million. The company's free cash flow for the year was also -$68.79 million. In the first quarter of fiscal year 2025, the company again reported no revenue, but saw a net income of $17.38 million, primarily due to a $40.27 million gain from the change in fair value of the warrant liability.

As of December 31, 2024, Outlook Therapeutics had cash and cash equivalents of $5.7 million. The company's debt-to-equity ratio stood at -6.17E-07, with a current ratio of 0.32 and a quick ratio of 0.26. These figures highlight the company's ongoing need for additional financing to support its operations and development initiatives.

Liquidity

To further strengthen its financial position, Outlook Therapeutics recently entered into a warrant inducement transaction that generated net proceeds of $15.7 million. Additionally, the company has secured a $33.1 million unsecured convertible promissory note from Avondale Capital, LLC, which will be used to repay the remaining $30.74 million outstanding under the existing December 2022 convertible note.

The company estimates the total cost to complete the NORSE EIGHT trial at $30 million, with most of these expenses expected to be incurred during the first three calendar quarters of 2024. As of June 30, 2024, Outlook Therapeutics reported a cash position of $32 million, which, when combined with the expected $107 million of proceeds from the full exercise of warrants, should be sufficient to support operations through calendar 2025.

Future Outlook

Despite the challenges faced, Outlook Therapeutics has demonstrated its resilience and unwavering commitment to its mission. The company's achievements, including the regulatory approvals in the EU and UK, the positive NORSE EIGHT results, and the ongoing efforts to secure financing, position Outlook Therapeutics as a formidable player in the ophthalmic care landscape.

As Outlook Therapeutics prepares for the commercial launch of LYTENAVA™ in Europe and the potential approval and launch of ONS-5010/LYTENAVA™ in the United States, the company's focus remains laser-sharp on delivering innovative solutions and improving the quality of life for patients suffering from retinal diseases. The company is continuing market access work and inventory planning for Germany and the UK, with expected product availability in those markets in the first half of calendar 2025.

For the NORSE EIGHT clinical trial in the U.S., Outlook Therapeutics currently has 359 of the planned 400 subjects enrolled and expects to complete enrollment before the end of the third quarter of 2024. The company anticipates reporting top-line results from the NORSE EIGHT trial in the fourth quarter of 2024. If the trial yields positive results, Outlook Therapeutics plans to resubmit its BLA with the FDA in the first calendar quarter of 2025.

In December 2024, the company underwent a leadership change, with CEO Russell Trenary stepping down and CFO Lawrence Kenyon being appointed as Interim CEO. This transition comes at a crucial time as the company navigates the final stages of its clinical trials and prepares for potential market entry.

With a strong pipeline, a seasoned management team, and a steadfast determination to transform the treatment paradigm, Outlook Therapeutics is well-poised to make a lasting impact on the industry and the lives of those it serves. If approved, ONS-5010/LYTENAVA™ could become the first and only approved ophthalmic bevacizumab for the treatment of wet AMD in the United States, potentially revolutionizing the standard of care for patients suffering from this debilitating condition.