Summary of Outlook Therapeutics FY Conference Call Company Overview - **Company**: Outlook Therapeutics (NasdaqCM:OTLK) - **Product**: Ophthalmic form of bevacizumab for the treatment of wet age-related macular degeneration (AMD) Key Points Regulatory Updates - Received a Complete Response Letter (CRL) from the FDA in late August 2025 due to the NORSE 1 trial missing its primary endpoint [2] - The NORSE 1 trial's eight-week endpoint was agreed upon under a Special Protocol Assessment (SPA) but was deemed not clinically relevant compared to the 12-week endpoint [3][5] - The NORSE 2 trial demonstrated non-inferiority and superiority against ranibizumab, providing confirmatory evidence for approval [7] - The FDA did not raise any manufacturing or chemistry, manufacturing, and controls (CMC) issues in the CRL [2][15] - A Type A meeting with the FDA was held to discuss the CRL, leading to a rapid resubmission and a Class 1 review with a PDUFA date before the end of the year [12][14] Clinical Trial Insights - NORSE 1 trial missed the eight-week endpoint but provided supportive data from the 12-week and retinal thickness measurements [4][10] - Visual acuity scores and retinal thickness changes were similar between the ophthalmic bevacizumab and ranibizumab arms, indicating a class effect [9][10] - Safety and tolerability across the NORSE program were reported as very good and consistent, addressing concerns with compounded bevacizumab [11] Market Landscape - Approximately 3 million injections of compounded anti-VEGF treatments are administered annually, with nearly 50% of patients receiving compounded bevacizumab as a first-line option [18] - Bevacizumab accounts for around 44% of all anti-VEGF injection claims, while ranibizumab has historically held a lower market share [23] - The company aims to position its FDA-approved product as the first and only approved bevacizumab for wet AMD, differentiating from compounded versions [19] Competitive Dynamics - New entrants like Eylea HD and Vabysmo are expected to increase competition, but compounded bevacizumab is likely to remain a frontline option due to affordability and access considerations [25] - Pricing strategy will be informed by experiences in Germany and the U.K., with expectations to align with biosimilar pricing [29][31] Commercial Strategy - The company plans to build a commercial infrastructure with a team of 30 to 50 personnel, focusing on market access and reimbursement management [34] - The transition from compounded forms to the approved product will depend on establishing confidence in coding, billing, and reimbursement processes [36] European Market Progress - The product was approved in the U.K. and Germany, with 77% market access achieved in Germany [39] - The company is activating hospitals and negotiating pricing, with a slower rollout in Germany due to inherent market challenges [40][42] - Future launches are planned for Austria, the Netherlands, and Scotland [44] Additional Insights - The company emphasizes the importance of a high-quality product that meets FDA standards, differentiating it from compounded alternatives [22] - The historical reliance on compounded bevacizumab raises questions about the transition to an FDA-approved product, with potential institutional risks influencing physician choices [37]

Core Insights - Outlook Therapeutics, Inc. is participating in a fireside chat at the Piper Sandler 37th Annual Healthcare Conference on December 2, 2025 [1] - The company focuses on enhancing the standard of care for bevacizumab in treating retina diseases [3] Company Overview - Outlook Therapeutics is a biopharmaceutical company developing ONS-5010/LYTENAVA™ (bevacizumab-vikg) to improve the treatment of retina diseases [3] - LYTENAVA™ is the first ophthalmic formulation of bevacizumab to receive marketing authorization from the European Commission and MHRA for wet AMD [3] - The commercial launch of LYTENAVA™ has commenced in Germany and the UK for wet AMD treatment [3] Investigational Status - In the United States, ONS-5010/LYTENAVA™ is currently investigational [4] - If approved, it would be the first ophthalmic formulation of bevacizumab for retinal indications, including wet AMD [4]

Core Insights - The FDA has accepted the resubmission of the Biologics License Application (BLA) for ONS-5010 (bevacizumab-vikg), with a Prescription Drug User Fee Act (PDUFA) goal date set for December 31, 2025, marking a significant milestone for Outlook Therapeutics in bringing the first FDA-approved ophthalmic formulation of bevacizumab for wet age-related macular degeneration (wet AMD) to the U.S. market [1][2][7] Company Overview - Outlook Therapeutics is a biopharmaceutical company focused on developing and commercializing ONS-5010/LYTENAVA™ (bevacizumab-vikg) to enhance the standard of care for retinal diseases, particularly wet AMD [6] - The company has commenced the commercial launch of LYTENAVA™ in Germany and the UK, where it has received Marketing Authorization from the European Commission and the Medicines and Healthcare products Regulatory Agency (MHRA) [6] Product Details - ONS-5010/LYTENAVA™ is an investigational ophthalmic formulation of bevacizumab produced in the U.S. for treating wet AMD, which is currently under review in the U.S. [3][4][7] - Bevacizumab-vikg is a recombinant humanized monoclonal antibody that binds to all isoforms of human vascular endothelial growth factor (VEGF), neutralizing its activity and reducing endothelial cell proliferation and vascular leakage in the retina [5]

Core Viewpoint - Outlook Therapeutics has re-submitted its Biologics License Application (BLA) for ONS-5010 to the FDA, aiming for approval of its ophthalmic formulation of bevacizumab for treating wet age-related macular degeneration (wet AMD) [1][2] Company Overview - Outlook Therapeutics is a biopharmaceutical company focused on developing and commercializing ONS-5010/LYTENAVA™ (bevacizumab-vikg) to optimize the standard of care for retinal diseases [6] - The company has commenced the commercial launch of LYTENAVA™ in Germany and the UK for wet AMD treatment [6] Product Details - ONS-5010/LYTENAVA™ is an investigational ophthalmic formulation of bevacizumab produced in the U.S. for wet AMD [3][7] - If approved in the U.S., it would be the first approved ophthalmic formulation of bevacizumab for retinal indications, including wet AMD [7] - LYTENAVA™ has received centralized Marketing Authorization from the European Commission and the MHRA in the UK for wet AMD treatment [3][4] Regulatory Progress - The resubmission of the BLA is seen as a significant step in addressing issues raised in the Complete Response Letter (CRL) received in August 2025 [2] - The company is accelerating its commercial efforts in Europe while preparing for potential near-term U.S. approval [2]

Core Viewpoint - Outlook Therapeutics, Inc. has completed a Type A Meeting with the FDA regarding the complete response letter for its biologics license application for ONS-5010, an investigational treatment for wet AMD, and plans to resubmit the application by the end of 2025 [1][2] Company Overview - Outlook Therapeutics is focused on developing and commercializing ONS-5010/LYTENAVA™ (bevacizumab-vikg) to optimize the standard of care for retinal diseases [6] - The company has commenced the commercial launch of LYTENAVA™ in Germany and the UK for the treatment of wet AMD [6] Product Information - ONS-5010/LYTENAVA™ is an ophthalmic formulation of bevacizumab aimed at treating wet AMD and has received centralized Marketing Authorization in the EU and the UK [3][4] - If approved in the U.S., ONS-5010/LYTENAVA™ would be the first ophthalmic formulation of bevacizumab for retinal indications, including wet AMD [7] Regulatory Discussion - The FDA meeting was described as productive, and the company is awaiting written minutes to finalize its plans for resubmission of the BLA [2] - The company remains committed to providing a safe and effective treatment for patients, physicians, and payors in the U.S. [2]

Core Insights - Outlook Therapeutics, Inc. is focused on optimizing the standard of care for bevacizumab in treating retinal diseases [1][2] - The company will present at the EURETINA Congress on September 3, 2025, discussing advancements in retinal disease treatment [1] - ONS-5010/LYTENAVA™ is the first ophthalmic formulation of bevacizumab to receive marketing authorization in Europe for wet AMD [2] Company Overview - Outlook Therapeutics is a biopharmaceutical company dedicated to the development and commercialization of ONS-5010/LYTENAVA™ (bevacizumab-vikg) [2] - The commercial launch of LYTENAVA™ has commenced in Germany and the UK for the treatment of wet AMD [2] - In the United States, ONS-5010/LYTENAVA™ is currently investigational and would be the first approved ophthalmic formulation of bevacizumab for retinal indications if approved [3]

Core Viewpoint - Outlook Therapeutics has submitted a Type A Meeting request to the FDA to discuss the complete response letter (CRL) regarding the biologics license application (BLA) resubmission for ONS-5010, an investigational treatment for wet AMD [1][2]. Company Overview - Outlook Therapeutics is focused on developing and commercializing ONS-5010/LYTENAVA™ (bevacizumab-vikg), an ophthalmic formulation of bevacizumab aimed at optimizing the standard of care for retinal diseases [7]. - The company has commenced the commercial launch of LYTENAVA™ in Germany and the UK for the treatment of wet AMD [7]. Product Details - ONS-5010/LYTENAVA™ is an investigational product in the U.S. and has received centralized Marketing Authorization in the EU and the UK for treating wet AMD [4][5]. - Bevacizumab-vikg is a recombinant humanized monoclonal antibody that targets human vascular endothelial growth factor (VEGF) to reduce endothelial cell proliferation and vascular leakage in the retina [6]. Regulatory Context - The FDA's CRL acknowledged that the NORSE TWO pivotal trial met safety and efficacy endpoints but requested additional confirmatory evidence of efficacy for ONS-5010 [2]. - The Type A meeting aims to clarify the specific confirmatory evidence required by the FDA to address the deficiencies noted in the CRL [2][3].

Core Insights - Shares of Outlook Therapeutics (OTLK) fell by 54.1% following the FDA's issuance of a second complete response letter (CRL) rejecting the biologics license application (BLA) resubmission for ONS-5010 in the treatment of wet age-related macular degeneration (wet AMD) [1][7]. Regulatory Developments - The CRL highlighted a single deficiency: insufficient evidence of efficacy, as ONS-5010 did not meet the primary efficacy endpoint in the NORSE EIGHT study, necessitating additional confirmatory data for approval [2][7]. - The FDA's first CRL in 2023 raised concerns regarding chemistry, manufacturing, and controls, which were later addressed by the company [3]. - The NORSE EIGHT study, which was a follow-up to the initial BLA based on the NORSE TWO study, failed to meet the pre-specified non-inferiority endpoint at week 8 [9]. Company Performance - Year-to-date, OTLK shares have decreased by 42.3%, contrasting with a 3.3% growth in the industry [4]. - Following the second regulatory setback, the company plans to meet with the FDA to clarify the requirements for potential approval of ONS-5010 as the first on-label bevacizumab product for intravitreal use in the U.S. [10]. Market Expansion - ONS-5010 received regulatory approval in the EU and the UK in 2024, marketed under the brand name Lytenava for treating wet AMD [12]. - The company launched Lytenava in the UK and Germany in June 2025, positioning it as the first authorized ophthalmic formulation of bevacizumab for wet AMD treatment in these regions [13]. - Outlook Therapeutics aims to provide a regulated alternative to off-label repackaged Avastin (bevacizumab), which is not approved for ophthalmic use [11][13].

Core Viewpoint - Outlook Therapeutics' stock experienced a significant decline following the FDA's issuance of a complete response letter (CRL) regarding its biologics license application (BLA) for ONS-5010, a treatment for wet age-related macular degeneration (wet AMD) [1][2][9] FDA Update - The FDA's CRL indicated that the application could not be approved in its current form due to a lack of substantial evidence of effectiveness [2][8] - The FDA noted that ONS-5010 did not meet the primary efficacy endpoint in the NORSE EIGHT trial, necessitating additional confirmatory evidence to support the application [3][8] Next Steps for the Company - The CEO of Outlook Therapeutics expressed disappointment but stated intentions to meet with the FDA for further clarification on approval requirements for ONS-5010 [5] - The company plans to continue expanding into European markets, having already received approval for Lytenava (bevacizumab gamma) for wet AMD in the EU and the U.K. [6][7] Clinical Trial Insights - The FDA acknowledged that the NORSE TWO trial met its safety and efficacy endpoints, but cited several issues including CMC concerns and open observations from pre-approval inspections as reasons for not approving the application [4][8] - The FDA has indicated that a second adequate and well-controlled clinical trial is required, suggesting a non-inferiority study comparing ONS-5010 to ranibizumab [9]

Summary of Outlook Therapeutics Conference Call Company Overview - **Company**: Outlook Therapeutics (OTLK) - **Product**: LYTENAVA, an ophthalmic formulation of bevacizumab for the treatment of wet AMD (Age-related Macular Degeneration) Key Points FDA Response and Regulatory Status - Outlook Therapeutics received a Complete Response Letter (CRL) from the FDA regarding the BLA resubmission for LYTENAVA, indicating a deficiency related to evidence of efficacy [3][4] - The pivotal NORSE TWO study met its primary endpoint, demonstrating efficacy, but the confirmatory NORSE ONE trial did not meet its primary efficacy endpoint [3][4] - The FDA did not require another study but indicated that there was insufficient confirmatory evidence for approval [4] - Outlook Therapeutics plans to engage with the FDA through a Type A meeting to clarify expectations and determine the best path forward [4][8] Market Context and Product Differentiation - Compounded bevacizumab has been used off-label for wet AMD, representing about 55% of the anti-VEGF market in the U.S. [5] - LYTENAVA is designed to provide a safer, consistent, and regulated alternative to compounded bevacizumab, ensuring quality and dosing reliability [5] - The company has received marketing authorization in Europe and the UK, with LYTENAVA now commercially available in Germany and the UK [6] Financial Outlook and Cash Management - Outlook Therapeutics estimates having sufficient cash for at least the next quarter, focusing on cash conservation while launching in Europe [7][48] - The European market is projected to be around $600 million, with Germany identified as a key market due to its large bevacizumab usage [16][35] - The company aims to achieve break-even in the European business by early 2026, depending on investment and market expansion [31] Commercial Strategy and Expansion Plans - The company is expanding its commercial footprint in Europe, particularly in Germany, the UK, Scotland, and Ireland [13][35] - Plans to assess opportunities in other countries like Austria and the Netherlands are underway [14] - The focus remains on maximizing revenue growth in approved markets while maintaining operational discipline [8][14] Future Considerations - The company is evaluating existing data from the NORSE program to determine what additional confirmatory evidence may be acceptable to the FDA [20][28] - Real-world evidence from Europe may be leveraged to address FDA data requirements, although specifics are yet to be determined [44] - Outlook Therapeutics is committed to pursuing LYTENAVA as a safe and consistent alternative for patients in the U.S. [8][9] Debt Management - The company has approximately $30 million in convertible notes, with no immediate pressure from debt service [40][41] - The maturity date for the debt is July 1, 2026, allowing time to strategize for repayment [41] Conclusion - Despite the setback with the FDA, Outlook Therapeutics remains committed to its mission and is actively pursuing opportunities in the European market while preparing for further discussions with the FDA to clarify the path forward for LYTENAVA in the U.S. [8][9]