ONS-5010 / LYTENAVA™ (bevacizumab-vikg), an Investigational Ophthalmic Formulation of Bevacizumab: Potential First Approved Bevacizumab for Ophthalmic Indications

Despite clinicians’ widespread use of unapproved repackaged intravenous (IV) bevacizumab from compounding pharmacies to treat ophthalmic diseases such as wet AMD, DME and BRVO, no other manufacturer has previously sought approval from the FDA for use of bevacizumab in these diseases.

Outlook Therapeutics is developing ONS-5010 / LYTENAVA™ as an investigational ophthalmic formulation of bevacizumab for a new BLA filing under the PHSA 351(a) regulatory pathway.

If approved, ONS-5010 will be the first and only FDA-approved, on-label bevacizumab approved initially for the treatment of wet-AMD and potentially for other ophthalmic indications (DME and BRVO).

Outlook Therapeutics plans to submit its Biologics License Application (BLA) to the FDA for ONS-5010, based on its completed registration clinical program for treatment of wet AMD. The Company’s clinical registration program design for ONS-5010 was reviewed and agreed upon by the FDA in an end-of-Phase 2 (EOP2) meeting in April 2018.

NORSE ONE is a clinical experience trial that evaluated ONS-5010 vs an alternate dosing regimen of ranibizumab (LUCENTIS®); it demonstrated proof-of-concept for using ONS-5010 as a treatment for wet AMD and validated the clinical trial protocol for NORSE TWO.

NORSE TWO, the second of two registration clinical trials, is our pivotal trial. We reported strongly positive efficacy and safety topline data in August 2021. In the trial, ONS-5010 achieved highly statistically significant and clinically relevant primary data (p = 0.0052) and key secondary efficacy endpoints (p = 0.0043), with 41.7% of subjects gaining at least 15 letters of BCVA. It was designed as a superiority trial comparing ONS-5010 with LUCENTIS®, which was dosed as one of the regimens listed in the LUCENTIS® label (i.e., patients are treated monthly for the first 3 months followed by less frequent dosing; the PIER regimen).

NORSE THREE is an open-label safety study that was conducted to ensure that an adequate number of safety exposures to ONS-5010 are available for the initial BLA regulatory filing. We reported a positive safety profile from this trial in March 2021.

With the wet AMD clinical program complete, Outlook Therapeutics originally submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for ONS-5010 to treat wet AMD on March 30, 2022. After conversations with the FDA about the filing, the Company has voluntarily withdrawn the BLA as it works to provide supplemental information that the FDA has requested. Outlook Therapeutics remains in active discussions with the FDA and expects to resubmit the BLA by September 2022.

The Company also intends to initiate registration studies for ONS-5010 for approvals in diabetic macular edema (DME) and branch retinal vein occlusion (BRVO).

Outlook Therapeutics expects to establish responsible pricing for ONS-5010, if approved. If approved for marketing, ONS-5010 has the potential to help lower the aggregate costs of treating retinal diseases for the overall healthcare system.

About Bevacizumab

Bevacizumab-vikg 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-vikg 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.

Since the advent of anti-VEGF therapy, it has become the standard-of-care treatment option within the retina community globally (National Eye Institute).