On August 14, 2023 Vaccinex, Inc. (Nasdaq: VCNX), a clinical-stage biotechnology company pioneering a differentiated approach to treating neurodegenerative disease and cancer through the inhibition of SEMA4D, reported financial results for the second quarter ended June 30, 2023 and provided a corporate update on progress in key programs (Press release, Vaccinex, AUG 14, 2023, View Source [SID1234634387]). .

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Over the last few months, Vaccinex achieved several important clinical milestones for pepinemab in both Alzheimer’s disease and Head and Neck Cancer.

Alzheimer’s Disease (AD):

Completed enrollment in the randomized, double-blind, Phase 1b/2 SIGNAL-AD trial of pepinemab in patients with mild Alzheimer’s disease (NCT04381468), funded in part by the Alzheimer’s Drug Discovery Foundation and by a grant from the Alzheimer’s Association.
Anticipate completing 12-months treatment in June, 2024 at which time we will evaluate the impact of treatment on brain metabolic activity, a key biomarker of clinical progression in AD, as well as treatment effects on cognition employing several validated, clinically meaningful Alzheimer’s cognitive scales.
An improving AD-drug development environment, based on FDA’s recent full approval of LEQEMBI, enables the pathway to reimbursement and supports further investment in Alzheimer’s Disease drug development.
As previously reported, pepinemab has a differentiated mechanism of action, blocking SEMA4D, which is upregulated in neurons during stress of Alzheimer’s and Huntington’s disease and triggers the transformation of astrocytes and microglia from normal homeostatic functions to neuroinflammatory activity. Blockade of SEMA4D restores healthy astrocyte and neuronal functions while reducing neuroinflammation (Nature Medicine 2022).
Head and Neck Cancer:

Analyzed interim data from the first 36 patients in the single-arm, Phase 2 KEYNOTE B-84 study (NCT04815720) evaluating pepinemab in combination with KEYTRUDA in immunotherapy naïve patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).
The combination of pepinemab and KEYTRUDA resulted in an approximately 2X increase in objective responses (ORR) and progression free survival (PFS) in patients with hard-to-treat PD-L1-low tumors compared to historical response rates for checkpoint monotherapy in this population.
Biomarker data suggest that treatment induced the formation of highly organized lymphoid aggregates in tumor that correlate with disease control and have previously been shown to be important for response to checkpoint inhibitors.
Vaccinex and Merck are currently in the design stages for an expansion of the KEYNOTE-B84 study that may extend benefits to more patients.
Investors and stakeholders will recall that the design and motivation for this study grew out of very encouraging data from our completed phase 2 SIGNAL study of pepinemab in Huntington’s disease (Nature Medicine 2022) that demonstrated treatment-induced increase in brain metabolic activity and improved cognition in patients with early manifest HD. The known parallels in pathology between Huntington’s and Alzheimer’s disease and the successful outcomes already observed for pepinemab in HD suggest that these may be predictive of similar outcomes in AD. It is noteworthy that pepinemab has a very different mechanism of action in AD than do antibodies to Aβ amyloid and that, to date, pepinemab has shown no evidence of ARIA, which is associated with amyloid-targeted therapies (e,g., Leqembi or donanemab). Pepinemab could be developed as an alternative treatment for AD, or, potentially, in combination with an anti-Aβ for greater efficacy.

In cancer, pepinemab is best employed in combination with an immune checkpoint inhibitor (ICI) such as KEYTRUDA. We are, therefore, pleased to have initiated two additional clinical studies with pepinemab in combination with another ICI in metastatic pancreatic cancer (PDAC) at the University of Rochester and in combination with a cell-based immunotherapy for breast cancer (MBC) at the Moffitt Cancer Center. Continuing progress and expanding interest in these studies affirms our view that pepinemab has the potential to improve outcomes for patients with different serious diseases and highlights the growing compendium of promising clinical data for pepinemab.

Recent Milestones and News

ASCO Presentations: Vaccinex and its collaborators presented two posters in the "Trial in Progress" sessions at the American Society for Clinical Oncology in June 2023 (ASCO23):
Phase 1b/2 PDAC Study: The team from University of Rochester Cancer Center and Wilmot Cancer Institute presented the plan for the single-arm, open-label study to evaluate pepinemab in combination with BAVENCIO (avelumab) as second line combination immunotherapy for patients with metastatic pancreatic ductal adenocarcinoma (PDAC, TPS4195, NCT05102721). The Vaccinex-sponsored study will employ a Bayesian Optimal Interval (BOIN) Design in the Phase 1b segment and a Simon two stage assessment in the Phase 2 segment and is expected to enroll 40 subjects. The trial rationale builds on safety and efficacy of the CLASSICAL-Lung study of pepinemab and avelumab in lung cancer and the observation that pepinemab appears to modulate the TME by increasing effector cell infiltration and reducing immune suppression in the TME, rendering "cold" tumors such as PDAC to become "hot". The study is being conducted with grant support from the Gateway Discovery Award.
Phase 1 Metastatic Breast Cancer Study: The team from the Moffitt Cancer Center presented the plan for an open-label, Phase I study to evaluate up to 28 patients with HER2+ metastatic breast cancer (MBC, TPS1113, NCT05378464). Patients will receive a combination of dendritic cell vaccines (DC1) plus trastuzumab (an anti-HER-2 antibody) and pepinemab, together with adoptive CD4+ T cell therapy. . The study rationale is supported by preclinical and clinical studies suggesting that pepinemab enhances the activity of dendritic cells to organize B cells and CD4+ T cells into productive lymphoid aggregates and boost anti-tumor immunity in cancers like MBC that are resistant to ICI therapies.
Huntington’s Disease:

Following an in-depth analysis of the Phase 2 SIGNAL-HD trial, Vaccinex is evaluating its HD development strategy, including further clinical studies and potential partnering discussions. The Company has an ongoing discussion with the FDA regarding the design of a potential Phase 3 trial. Further updates to be provided as we receive clarification from FDA.
ActivMAb Platform Technology:

The first clinical candidate selected through use of this technology (SRF114, a fully human monoclonal antibody targeting CCR8 for the potential treatment of solid tumors), is in a Phase 1/2 study sponsored by our licensee, Surface Oncology, recently acquired by Coherus Biosciences, Inc. (transaction announced June 16, 2023 and expected to close in Q3 2023). The technology and its potential applications for drug discovery against complex membrane protein targets including the "hard to drug" class of membrane-associated G protein-coupled receptors (GPCRs) and ion channels have been described in several publications and has also been utilized in multiple antibody discovery collaborations with leading biopharmaceutical companies.
Financial Results for the Three Months Ended June 30, 2023:
Cash and Cash Equivalents and Marketable Securities. Cash and cash equivalents and marketable securities on June 30, 2023 were $1.9 million, as compared to $6.4 million as of December 31, 2022.

Financing activities in Q2 2023 included financing of $5.46 million as part of the May 2023 Private Placement, based on a purchase price of $0.37/share. The financing, which included no warrants, derivatives or financial covenants, was completed in two segments. In the first segment, completed on May 12, 2023, Vaccinex sold approximately 7.9 million shares of common stock for aggregate proceeds of $2.96 million. The investors in the March 2023 Private Placement include FCMI, which is controlled by Albert D. Friedberg, the chairman of the Company’s board of directors, and Vaccinex (Rochester) L.L.C., which is majority owned and controlled by Dr. Maurice Zauderer, the Company’s President, Chief Executive Officer, and a member of its board of directors. In the second segment, FCMI purchased approximately 6.7 million shares of common stock for gross proceeds of $2.51 million.

In addition, on May 16, 2023, in connection with the second installment of the Alzheimer’s Drug Discovery Foundation (ADDF) Award, Vaccinex sold approximately 2.5 million shares at a purchase price of $0.39/share for aggregate gross proceeds of $0.99 million. This represents a milestone payment achieved upon completion of enrollment in the SIGNAL-AD study.

Research and Development Expenses. Research and development expenses for the quarter ended June 30, 2023 were $5.1 million as compared to $3.8 million for the comparable period in 2022.

The increase in research and development expenses is primarily attributable to increased patient enrollment in the SIGNAL-AD study and the Phase 1b/2 KEYNOTE B84 study in HNSCC.

General and Administrative Expenses. General and administrative expenses for the quarter ended June 30, 2023 were $2.0 million as compared to $1.6 million for the comparable period in 2022.

The nominal increase in general and administrative expenses reflects careful cost control measures.

Comprehensive loss/Net loss per share. The Comprehensive Loss and Net loss per share for the quarter ended June 30, 2023 was $7.1 million and $(0.12) compared to $5.4 million and $(0.13) for the comparable period in 2022.

Full financial tables are included below. For further details on Vaccinex’s financials, refer to its Form 10Q filed August 14, 2023 with the S.E.C.

Vaccinex has global commercial and development rights to pepinemab and is the sponsor of the KEYNOTE-B84 study which is being performed in collaboration with Merck Sharp & Dohme Corp, a subsidiary of Merck and Co, Inc. Kenilworth, NJ, USA. Additional information about the study is available at: clinicaltrials.gov.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA.

BAVENCIO/avelumab is co-developed and co-commercialized by Merck KGaA, Darmstadt, Germany and Pfizer Inc.

About Pepinemab
Pepinemab is a humanized IgG4 monoclonal antibody. It inhibits SEMA4D which regulates the actin cytoskeleton of cells and plays an important role in tumor immune evasion as well as in inflammatory reactions in the brain. Preclinical and clinical data show that pepinemab promotes infiltration and activation of dendritic cells and CD8+ T cells and reverses immunosuppression within the tumor microenvironment. Separately, studies in neurodegenerative disease show that by preventing deleterious inflammatory gliosis during disease progression, pepinemab preserves normal function of astrocytes and microglia, two types of glial cells that play a crucial role in the function and health of neurons in the brain. Pepinemab is being evaluated in several studies in neurodegenerative disease and cancer. Pepinemab has been administered to more than 400 patients and appears to have a favorable safety and tolerability profile.

On August 14, 2023 Enveric Biosciences, Inc. (NASDAQ: ENVB) ("Enveric" or the "Company"), a biotechnology company dedicated to the development of novel neuroplastogenic small-molecule therapeutics for the treatment of anxiety, depression, and addiction disorders, reported a corporate update and provided financial results for the second quarter of 2023 ended June 30, 2023 (Press release, Enveric Biosciences, AUG 14, 2023, View Source [SID1234634386]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The second quarter of 2023 was an exciting and productive period for Enveric as we made significant steps to advance a pipeline of differentiated neuroplastogenic small-molecule therapeutics that, we believe, have the potential to transform the treatment of mental health disorders," said Joseph Tucker, Ph.D., Director and CEO of Enveric. "Our efforts during the quarter focused on two important elements in realizing this goal – enhancing the intellectual property ("IP") portfolio covering EB-373 and our EVM201 and EVM301 Series and advancing preclinical and manufacturing processes for EB-373 in preparation for an anticipated first-in-human clinical trial."

Dr. Tucker continued: "Securing strong IP coverage is critical to the value potential of our technologies, and we were pleased to have been awarded multiple Notices of Allowance from the USPTO for composition of matter claims involving EB-373 and our EVM201 and EVM301 Series. We are continuing to pursue numerous additional patent filings, which are collectively designed to protect our technological advances as we seek to create a portfolio of novel small-molecule therapeutics for the treatment of mental health disorders."

Dr. Tucker continued: "During the quarter we also completed multiple preclinical studies involving our lead candidate, EB-373, that demonstrated oral bioavailability, and rapid oral absorption and systemic clearance. Additionally, we enhanced our manufacturing capabilities for EB-373, improving yield, purity and production efficiency as we finalize the formulation in preparation for entry into the clinic."

Dr. Tucker concluded: "We are on track to identify a lead candidate from the EVM301 Series by year-end, which will enable us to begin preclinical development in 2024 in preparation for an Investigational New Drug application. We believe that our EVM301 Series of compounds are distinctive as demonstrated by the patentability of our candidate molecules which engage the serotonin 5HT2a receptor and other neurotransmitter receptors in the effort to promote neuroplasticity and, consequently, therapeutic benefit while avoiding inducing the hallmark hallucinations associated with most psychedelic and psychedelic-inspired molecules. We believe that this innovative therapeutic approach could be game-changing in the treatment of depression and anxiety disorders by offering the opportunity to administer medications without requiring a healthcare professional to be present during treatment."

SECOND QUARTER AND RECENT PROGRAM UPDATES

Reported initial results from animal studies of EB-373 demonstrating oral bioavailability and rapid absorption and systemic clearance, improving on PK characteristics of psilocybin
Completed in-vitro absorption, distribution, metabolism, and excretion and toxicology assays demonstrated rapid conversion of EB-373 to the active metabolite psilocin
Announced the development of EB-373 drug substance and initiation of scaled up manufacturing
Expanded existing manufacturing agreement with CDMO partner for enhanced supply of non-GMP and GMP EB-373 drug substance
Received multiple notices of allowance from the USPTO protecting composition of matter claims governing lead clinical candidate, EB-373 and EVM301 Series
Compelling research presented at Canadian Chemistry Conference and Exhibition in June 2023
Announced cost reduction plan designed to extend financial runway into the first quarter of 2024
SECOND QUARTER 2023 FINANCIAL RESULTS

Net loss attributable to shareholders was $6.40 million for the second quarter ended June 30, 2023, including $1.64 million in net non-cash expenses, with a basic and diluted loss per share of $3.04, as compared to a net loss of $2.87 million and non-cash income of $1.04 million, with primary and diluted loss per share of $2.73 per share for the quarter ended June 30, 2022.

Net cash used in operations for the quarter ended June 30, 2023, was $4.47 million consisting of a $6.37 million net loss, adjusted by a net of $1.59 million in non-cash expenses and changes in asset and liability balances of $0.30 million. Included in the net cash used in operations were one-time charges totaling $2.76 million for prepayment of preclinical costs, restructuring costs, and redemption of Akos Series A preferred stock.

As of June 30, 2023, the Company had cash and cash equivalents of $7.08 million.

On August 14, 2023 Enveric Biosciences, Inc. (NASDAQ: ENVB) ("Enveric" or the "Company"), a biotechnology company dedicated to the development of novel neuroplastogenic small-molecule therapeutics for the treatment of anxiety, depression, and addiction disorders, reported a corporate update and provided financial results for the second quarter of 2023 ended June 30, 2023 (Press release, Enveric Biosciences, AUG 14, 2023, View Source [SID1234634386]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The second quarter of 2023 was an exciting and productive period for Enveric as we made significant steps to advance a pipeline of differentiated neuroplastogenic small-molecule therapeutics that, we believe, have the potential to transform the treatment of mental health disorders," said Joseph Tucker, Ph.D., Director and CEO of Enveric. "Our efforts during the quarter focused on two important elements in realizing this goal – enhancing the intellectual property ("IP") portfolio covering EB-373 and our EVM201 and EVM301 Series and advancing preclinical and manufacturing processes for EB-373 in preparation for an anticipated first-in-human clinical trial."

Dr. Tucker continued: "Securing strong IP coverage is critical to the value potential of our technologies, and we were pleased to have been awarded multiple Notices of Allowance from the USPTO for composition of matter claims involving EB-373 and our EVM201 and EVM301 Series. We are continuing to pursue numerous additional patent filings, which are collectively designed to protect our technological advances as we seek to create a portfolio of novel small-molecule therapeutics for the treatment of mental health disorders."

Dr. Tucker continued: "During the quarter we also completed multiple preclinical studies involving our lead candidate, EB-373, that demonstrated oral bioavailability, and rapid oral absorption and systemic clearance. Additionally, we enhanced our manufacturing capabilities for EB-373, improving yield, purity and production efficiency as we finalize the formulation in preparation for entry into the clinic."

Dr. Tucker concluded: "We are on track to identify a lead candidate from the EVM301 Series by year-end, which will enable us to begin preclinical development in 2024 in preparation for an Investigational New Drug application. We believe that our EVM301 Series of compounds are distinctive as demonstrated by the patentability of our candidate molecules which engage the serotonin 5HT2a receptor and other neurotransmitter receptors in the effort to promote neuroplasticity and, consequently, therapeutic benefit while avoiding inducing the hallmark hallucinations associated with most psychedelic and psychedelic-inspired molecules. We believe that this innovative therapeutic approach could be game-changing in the treatment of depression and anxiety disorders by offering the opportunity to administer medications without requiring a healthcare professional to be present during treatment."

SECOND QUARTER AND RECENT PROGRAM UPDATES

Reported initial results from animal studies of EB-373 demonstrating oral bioavailability and rapid absorption and systemic clearance, improving on PK characteristics of psilocybin
Completed in-vitro absorption, distribution, metabolism, and excretion and toxicology assays demonstrated rapid conversion of EB-373 to the active metabolite psilocin
Announced the development of EB-373 drug substance and initiation of scaled up manufacturing
Expanded existing manufacturing agreement with CDMO partner for enhanced supply of non-GMP and GMP EB-373 drug substance
Received multiple notices of allowance from the USPTO protecting composition of matter claims governing lead clinical candidate, EB-373 and EVM301 Series
Compelling research presented at Canadian Chemistry Conference and Exhibition in June 2023
Announced cost reduction plan designed to extend financial runway into the first quarter of 2024
SECOND QUARTER 2023 FINANCIAL RESULTS

Net loss attributable to shareholders was $6.40 million for the second quarter ended June 30, 2023, including $1.64 million in net non-cash expenses, with a basic and diluted loss per share of $3.04, as compared to a net loss of $2.87 million and non-cash income of $1.04 million, with primary and diluted loss per share of $2.73 per share for the quarter ended June 30, 2022.

Net cash used in operations for the quarter ended June 30, 2023, was $4.47 million consisting of a $6.37 million net loss, adjusted by a net of $1.59 million in non-cash expenses and changes in asset and liability balances of $0.30 million. Included in the net cash used in operations were one-time charges totaling $2.76 million for prepayment of preclinical costs, restructuring costs, and redemption of Akos Series A preferred stock.

As of June 30, 2023, the Company had cash and cash equivalents of $7.08 million.

On August 14, 2023 Enveric Biosciences, Inc. (NASDAQ: ENVB) ("Enveric" or the "Company"), a biotechnology company dedicated to the development of novel neuroplastogenic small-molecule therapeutics for the treatment of anxiety, depression, and addiction disorders, reported a corporate update and provided financial results for the second quarter of 2023 ended June 30, 2023 (Press release, Enveric Biosciences, AUG 14, 2023, View Source [SID1234634386]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The second quarter of 2023 was an exciting and productive period for Enveric as we made significant steps to advance a pipeline of differentiated neuroplastogenic small-molecule therapeutics that, we believe, have the potential to transform the treatment of mental health disorders," said Joseph Tucker, Ph.D., Director and CEO of Enveric. "Our efforts during the quarter focused on two important elements in realizing this goal – enhancing the intellectual property ("IP") portfolio covering EB-373 and our EVM201 and EVM301 Series and advancing preclinical and manufacturing processes for EB-373 in preparation for an anticipated first-in-human clinical trial."

Dr. Tucker continued: "Securing strong IP coverage is critical to the value potential of our technologies, and we were pleased to have been awarded multiple Notices of Allowance from the USPTO for composition of matter claims involving EB-373 and our EVM201 and EVM301 Series. We are continuing to pursue numerous additional patent filings, which are collectively designed to protect our technological advances as we seek to create a portfolio of novel small-molecule therapeutics for the treatment of mental health disorders."

Dr. Tucker continued: "During the quarter we also completed multiple preclinical studies involving our lead candidate, EB-373, that demonstrated oral bioavailability, and rapid oral absorption and systemic clearance. Additionally, we enhanced our manufacturing capabilities for EB-373, improving yield, purity and production efficiency as we finalize the formulation in preparation for entry into the clinic."

Dr. Tucker concluded: "We are on track to identify a lead candidate from the EVM301 Series by year-end, which will enable us to begin preclinical development in 2024 in preparation for an Investigational New Drug application. We believe that our EVM301 Series of compounds are distinctive as demonstrated by the patentability of our candidate molecules which engage the serotonin 5HT2a receptor and other neurotransmitter receptors in the effort to promote neuroplasticity and, consequently, therapeutic benefit while avoiding inducing the hallmark hallucinations associated with most psychedelic and psychedelic-inspired molecules. We believe that this innovative therapeutic approach could be game-changing in the treatment of depression and anxiety disorders by offering the opportunity to administer medications without requiring a healthcare professional to be present during treatment."

SECOND QUARTER AND RECENT PROGRAM UPDATES

Reported initial results from animal studies of EB-373 demonstrating oral bioavailability and rapid absorption and systemic clearance, improving on PK characteristics of psilocybin
Completed in-vitro absorption, distribution, metabolism, and excretion and toxicology assays demonstrated rapid conversion of EB-373 to the active metabolite psilocin
Announced the development of EB-373 drug substance and initiation of scaled up manufacturing
Expanded existing manufacturing agreement with CDMO partner for enhanced supply of non-GMP and GMP EB-373 drug substance
Received multiple notices of allowance from the USPTO protecting composition of matter claims governing lead clinical candidate, EB-373 and EVM301 Series
Compelling research presented at Canadian Chemistry Conference and Exhibition in June 2023
Announced cost reduction plan designed to extend financial runway into the first quarter of 2024
SECOND QUARTER 2023 FINANCIAL RESULTS

Net loss attributable to shareholders was $6.40 million for the second quarter ended June 30, 2023, including $1.64 million in net non-cash expenses, with a basic and diluted loss per share of $3.04, as compared to a net loss of $2.87 million and non-cash income of $1.04 million, with primary and diluted loss per share of $2.73 per share for the quarter ended June 30, 2022.

Net cash used in operations for the quarter ended June 30, 2023, was $4.47 million consisting of a $6.37 million net loss, adjusted by a net of $1.59 million in non-cash expenses and changes in asset and liability balances of $0.30 million. Included in the net cash used in operations were one-time charges totaling $2.76 million for prepayment of preclinical costs, restructuring costs, and redemption of Akos Series A preferred stock.

As of June 30, 2023, the Company had cash and cash equivalents of $7.08 million.

On August 14, 2023 Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company working to achieve FDA approval for the first ophthalmic formulation of bevacizumab for the treatment of wet AMD, reported recent corporate highlights and financial results for its fiscal third quarter ended June 30, 2023 (Press release, Outlook Therapeutics, AUG 14, 2023, View Source [SID1234634385]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Russell Trenary, President and Chief Executive Officer of Outlook Therapeutics, commented, "We continue to be focused on our pre-launch activities and positioning for Outlook Therapeutics as an innovative leader in the anti-VEGF space. By meeting strict FDA requirements for an ophthalmic approved formulation of bevacizumab, we believe we can enhance the standard of care. If we achieve FDA approval, it will be the catalyst to transform Outlook Therapeutics into a commercial-stage company."

Upcoming Anticipated Milestones

PDUFA goal date of August 29, 2023;
Evaluation of ONS-5010 in a pre-filled syringe in the NORSE SEVEN clinical trial expected to be complete in 2024; and
MAA decision date from the EMA’s CHMP in the EU for ONS-5010 expected in first half of 2024.
Commercial Planning Underway to Support Potential Approval of the First Ophthalmic Formulation of Bevacizumab for Use in Retinal Indications

According to GlobalData, the use of unapproved repackaged IV bevacizumab from compounding pharmacies is estimated to account for approximately 50% of all wet AMD injections in the United States each year. This represents approximately 3.5 million injections of off-label, repackaged bevacizumab each year in the United States alone. Globally, the nine major markets account for an estimated $13.1 billion market for anti-VEGF drugs to treat retina diseases.

Because patients, physicians and payors rely heavily on bevacizumab as an important option for treating wet AMD, ONS-5010 has been developed to address the concerns for not meeting standards required for ophthalmic approval, including potential potency and safety issues that have been reported to be associated with using off-label, repackaged bevacizumab from compounding pharmacies, such as:

Study reports published in JAMA indicating 81% of all tested syringes of repackaged bevacizumab received from 11 different compounding pharmacies contained less drug protein concentration than the control arm, which could result in lower clinical efficacy.
Non-standard materials used to transfer and hold repackaged bevacizumab which can potentially add particulates to non-ophthalmic approved bevacizumab, which in turn may fail to meet the standards FDA requires for ophthalmic approval.
In August 2022, Outlook Therapeutics submitted a PHSA 351(a) BLA for ONS-5010 as an original biologic application. ONS-5010, if approved, is not a biosimilar because the PHSA requires a biosimilar to have the same "conditions of use" (e.g., indications) as a reference product. AVASTIN, the currently marketed non-ophthalmic formulation of bevacizumab, is not approved by FDA for the treatment of wet AMD or other retinal diseases.

In the NORSE TWO Phase 3 clinical trial, which compared ONS-5010 (dosed monthly) with LUCENTIS (using the PIER dosing regimen of 3 consecutive months of loading doses followed by 2 more doses separated by 3 months each), ONS-5010 consistently improved BCVA by ≥ 15 letters from baseline to 11 months (41.7% compared to 23.1% in LUCENTIS group, p = 0.0052). Patients receiving ONS-5010 also demonstrated statistically significant mean change in BCVA of 11.2 letters compared to 5.8 letters in the control arm (p = 0.0043). Additionally, the majority of ONS-5010 subjects maintained or gained BCVA during the study (defined as change from baseline in BCVA ≥ 0), with at least 80% of ONS-5010 subjects gaining or maintaining BCVA each month. Safety evaluations revealed similar safety profiles of ONS-5010 and the comparator LUCENTIS. In fact, only one serious ocular adverse event occurred in the ONS-5010 arm (increase in intraocular pressure that was treated and resolved) in 1100 injections.

If approved, ONS-5010 / LYTENAVA (bevacizumab-vikg) will be the first ophthalmic formulation of bevacizumab.

ONS-5010 / LYTENAVA (bevacizumab-vikg) Pre-Launch Preparations Proceeding as Planned

In anticipation of potential FDA marketing approval in 2023, Outlook Therapeutics has begun commercial inventory production, with best-in-class partnerships with FUJIFILM Diosynth Biotechnologies for drug substance, and with drug product manufacturer Aji Bio-pharma Services for the finished drug product.

Outlook Therapeutics is actively building out its own sales and commercial team, and additionally entered into a strategic distribution partnership with AmerisourceBergen in September 2022, in preparation for the anticipated commercial launch in the United States of ONS-5010. As Outlook Therapeutics moves toward a potential launch in the United States, AmerisourceBergen’s commercialization support has expanded to include additional services. Through the agreement with AmerisourceBergen, Outlook Therapeutics expects to significantly increase market access and efficient distribution of ONS-5010, if approved by the FDA. Moreover, working with AmerisourceBergen will help to provide Outlook Therapeutics with an accelerated pathway to deliver a high-quality customer experience to retina specialists. Outlook Therapeutics has also been in collaborative discussions with payors and the retina community to bring ONS-5010 to market benefiting all stakeholders – patients, clinicians, and payors.

Outlook Therapeutics also submitted a Marketing Authorization Application (MAA) in Europe, which was validated for review in December 2022. The formal review process of the MAA by the EMA’s Committee for Medicinal Products for Human Use (CHMP) is underway with an estimated decision date expected in the first half of 2024. In addition to pursuing potential strategic partnering opportunities in the EU and other regions, such as the current partnership with Syntone Biopharma JV in China, Outlook Therapeutics is also exploring potential expanded relationships with AmerisourceBergen to support the launch of ONS-5010 in international markets. AmerisourceBergen increased its global capabilities in 2021 with the acquisition of PharmaLex and Alliance Healthcare, leading wholesalers and specialized service providers of healthcare products in Europe.

In addition to the clinical development program evaluating ONS-5010 for wet AMD, Outlook Therapeutics has received agreements from the FDA on three Special Protocol Assessments (SPAs) for three additional registration clinical trials. These SPAs cover the protocols for a planned registration clinical trial evaluating ONS-5010 to treat branch retinal vein occlusion (BRVO), NORSE FOUR, and two planned registration clinical trials evaluating the drug candidate for the treatment of diabetic macular edema (DME), NORSE FIVE and NORSE SIX.

Financial Highlights for the Fiscal Third Quarter Ended June 30, 2023

For the fiscal third quarter ended June 30, 2023, Outlook Therapeutics reported a net loss attributable to common stockholders of $20.7 million, or $0.08 per basic and diluted share, compared to a net loss attributable to common stockholders of $17.5 million, or $0.08 per basic and diluted share, for the same period last year.

As of June 30, 2023, Outlook Therapeutics had cash and cash equivalents of $33.7 million, which is expected to be sufficient to fund its operations through the anticipated approval of the BLA for ONS-5010 in the third calendar quarter of 2023, and potentially through the fourth calendar quarter of 2023.

About ONS-5010 / LYTENAVA (bevacizumab-vikg)

ONS-5010 is an investigational ophthalmic formulation of bevacizumab under development as an intravitreal injection for the treatment of wet AMD and other retinal diseases. Because no currently approved ophthalmic formulations of bevacizumab are available, clinicians wishing to treat retinal patients with bevacizumab have had to use unapproved repackaged IV bevacizumab provided by compounding pharmacies, products that have known risks of contamination and inconsistent potency and availability. If approved, ONS-5010 can replace the need to use unapproved repackaged oncologic IV bevacizumab from compounding pharmacies for the treatment of wet AMD.

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.