On February 14, 2025 Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company that achieved regulatory approval in the European Union (EU) and the United Kingdom (UK) for the first authorized use of an ophthalmic formulation of bevacizumab for the treatment of wet age-related macular degeneration (wet AMD), reported financial results for the first quarter of fiscal year 2025 and provided a corporate update (Press release, Outlook Therapeutics, FEB 14, 2025, View Source [SID1234650286]).
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"With all of the recent progress made at Outlook Therapeutics and the upcoming milestones over the next few months, we expect to be a very different company by the end of 2025," commented Lawrence Kenyon, Chief Financial Officer and Interim Chief Executive Officer of Outlook Therapeutics. "In 2025, we plan to start realizing our goal of providing patients, physicians and payers with an approved ophthalmic formulation of bevacizumab. This year, we anticipate beginning to generate the first revenue for Outlook Therapeutics with the launch of LYTENAVA in Germany and the UK and our BLA is on track for resubmission this quarter."
Upcoming Anticipated Milestones
Resubmission of the ONS-5010 BLA targeted for Q1 CY2025;
Initial commercial launches in Germany and the UK planned to commence in Q2 CY2025; and
Potential for US FDA approval of ONS-5010 in Q3 CY2025.
LYTENAVA (bevacizumab gamma) European Commercial Update
In May 2024, the European Commission granted Marketing Authorization for LYTENAVA (bevacizumab gamma) for the treatment of wet AMD in the EU. Additionally, in July 2024, the UK Medicines and Healthcare products Regulatory Agency (MHRA) granted Marketing Authorization for LYTENAVA (bevacizumab gamma) for the same indication in the UK. In December 2024, the National Institute for Health and Care Excellence (NICE) recommended LYTENAVA (bevacizumab gamma) as an option for the treatment of wet AMD. Plans for a potential 2025 launch in Germany and the UK are ongoing. Outlook Therapeutics remains confident that ONS-5010 / LYTENAVA is an important therapy for the treatment of wet AMD in place of off-label repackaged bevacizumab that has not received regulatory approval for use in retina diseases such as wet AMD. Outlook Therapeutics intends to launch LYTENAVA (bevacizumab gamma) in Germany and the UK in the second quarter of calendar year 2025.
LYTENAVA (bevacizumab gamma) is the first and only authorized ophthalmic formulation of bevacizumab for use in treating wet AMD in adults in the EU and UK. Currently, over 2.5 million injections of off-label, repackaged bevacizumab are administered to patients across Europe each year, with about one third of these injections in Germany alone. In Germany, there are an estimated 1.6 million anti-VEGF retina injections each year, with over half of those injections representing use of off-label, repackaged bevacizumab. For Germany, LYTENAVA (bevacizumab gamma) represents an opportunity for patients there to receive an approved, cGMP produced bevacizumab for the first time. The UK market represents approximately 1.3 million anti-VEGF retina injections each year, but use of repackaged bevacizumab is not authorized. In the UK, LYTENAVA (bevacizumab gamma) represents the first time that most patients will have access to the therapy.
Authorization may also be sought in other European countries, Japan, and elsewhere. Outlook Therapeutics has entered into a strategic collaboration with Cencora (formerly AmerisourceBergen) to support the commercial launch of LYTENAVA globally following regulatory approvals. The collaborative and integrated approach is designed to support market access and efficient distribution of LYTENAVA to benefit all stakeholders, including retina specialists, providers and patients.
ONS-5010 / LYTENAVA (bevacizumab-vikg) Clinical and Regulatory Update
Outlook Therapeutics believes that the complete data set for NORSE EIGHT, combined with the data from the other NORSE clinical trials, provides the required clinical evidence to support approval of the ONS-5010 BLA in the US. Outlook Therapeutics plans to resubmit the BLA for ONS-5010 in the first quarter of calendar 2025. If approved by the U.S. Food and Drug Administration (FDA), Outlook Therapeutics plans to commercialize ONS-5010 / LYTENAVA (bevacizumab-vikg) directly in the US.
In November 2024, Outlook Therapeutics reported that in the NORSE EIGHT clinical trial, the second of two adequate and well controlled clinical trials evaluating ONS-5010 in wet AMD patients, ONS-5010 did not meet the pre-specified non-inferiority endpoint at week 8 set forth in the special protocol assessment (SPA) with the FDA. NORSE EIGHT is a randomized, controlled, parallel-group, masked, non-inferiority study of approximately 400 newly diagnosed, wet AMD subjects randomized in a 1:1 ratio to receive 1.25 mg ONS-5010 / LYTENAVA or 0.5 mg ranibizumab intravitreal injections. Subjects received injections at Day 0 (randomization), Week 4, and Week 8 visits. The primary endpoint is the mean change in best corrected visual acuity (BCVA) from baseline to week 8.
In January 2025, Outlook Therapeutics announced results from the completed analysis of the 12-week safety and efficacy results for NORSE EIGHT, which indicated that ONS-5010 demonstrated clinically meaningful anatomic and functional improvements at each study timepoint. Results from the 12-week analysis demonstrated the difference in the mean between ONS-5010 and ranibizumab was -1.009 best corrected visual acuity (BCVA) letters with a 95% confidence interval of (-2.865, 0.848) in the NORSE EIGHT trial. Applying the statistical parameters from the week 8 primary endpoint with the lower bound of the non-inferiority margin at -3.5 with a 95% confidence interval, the noninferiority margin was met at week 12, indicating that the two study arms are not different at this timepoint. In the intent-to-treat (ITT) population, NORSE EIGHT demonstrated a mean 5.5 letter improvement in BCVA in the ONS-5010 arm and 6.5 letter improvement in BCVA in the ranibizumab arm. BCVA data across all study timepoints demonstrated an improvement in vision, increasing over time, and the presence of biologic activity. Overall, in NORSE EIGHT, ONS-5010 demonstrated mean visual acuity improvements of +3.3 letters at week 4, +4.2 letters at week 8, and +5.5 letters at week 12. Additionally, the complete NORSE EIGHT data set showed that anatomical response was similar between treatments, with a reduction in central retinal thickness of -123.9 microns for ONS-5010 treated eyes and -127.3 microns for the ranibizumab group, virtually no difference between the arms. Central retinal thickness is a key indicator of effectiveness used by retina specialists in the treatment of wet AMD.
Financial Highlights for the Fiscal First Quarter Ended December 31, 2024
For the fiscal first quarter ended December 31, 2024, Outlook Therapeutics reported net income attributable to common stockholders of $17.4 million, or $0.72 per basic and diluted share, compared to a net loss attributable to common stockholders of $11.2 million, or $0.86 per basic and diluted share, for the same period last year. For the fiscal first quarter ended December 31, 2024, Outlook Therapeutics also reported an adjusted net loss attributable to common stockholders1 of $21.6 million, or $0.89 per basic and diluted share, as compared to an adjusted net loss attributable to common stockholders of $10.1 million, or $0.78 per basic and diluted share, for fiscal first quarter of 2024.
Adjusted net loss attributable to common stockholders for the fiscal first quarter ended December 31, 2024 includes $1.3 million of loss from change in fair value of warrant liability and $40.3 million of gain from change in fair value of convertible promissory notes. Adjusted net loss attributable to common stockholders includes $1.0 million of loss from change in fair value of warrant liability and $0.1 million of loss from change in fair value of convertible promissory notes for the fiscal first quarter ended December 31, 2023.
1 Adjusted net loss attributable to common stockholders and adjusted net loss attributable to common stockholders per share of common stock – basic and diluted are non-U.S. GAAP financial measures. See "Non-GAAP Financial Measures" below.
In January 2025, Outlook Therapeutics received $17.8 million in gross proceeds from its previously announced warrant exercise inducement with certain holders of existing warrants to purchase the Company’s common stock. As of December 31, 2024, Outlook Therapeutics had cash and cash equivalents of $5.7 million, excluding the proceeds received from the warrant exercise inducement in January 2025.
About ONS-5010 / LYTENAVA (bevacizumab-vikg, bevacizumab gamma)
ONS-5010 / LYTENAVA is an ophthalmic formulation of bevacizumab for the treatment of wet AMD. LYTENAVA (bevacizumab gamma) is the subject of a centralized Marketing Authorization granted by the European Commission in the European Union (EU) and Marketing Authorization granted by the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom (UK) for the treatment of wet AMD.
In the United States, ONS-5010 / LYTENAVA (bevacizumab-vikg) is investigational.
Bevacizumab-vikg (bevacizumab gamma in the EU and UK) is a recombinant humanized monoclonal antibody (mAb) that selectively binds with high affinity to all isoforms of human vascular endothelial growth factor (VEGF) and neutralizes VEGF’s biologic activity through a steric blocking of the binding of VEGF to its receptors Flt-1 (VEGFR-1) and KDR (VEGFR-2) on the surface of endothelial cells. Following intravitreal injection, the binding of bevacizumab to VEGF prevents the interaction of VEGF with its receptors on the surface of endothelial cells, reducing endothelial cell proliferation, vascular leakage, and new blood vessel formation in the retina.