On February 9, 2024 Outlook Therapeutics, Inc. (Nasdaq: OTLK), a biopharmaceutical company working to achieve U.S. Food and Drug Administration (FDA) approval for the first ophthalmic formulation of bevacizumab for the treatment of retinal diseases, reported recent corporate highlights and financial results for its fiscal year ended September 30, 2023 (Press release, Outlook Therapeutics, FEB 9, 2024, View Source [SID1234639957]).

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"We remain committed to working with the FDA to design and undertake the additional clinical study for ONS-5010 that, if successful, will satisfy the FDA’s requirements for approval," commented Russell Trenary, President and Chief Executive Officer of Outlook Therapeutics. "The patient need for an ophthalmic approved bevacizumab remains and we are steadfast in our mission to meet this need."

Upcoming Anticipated Milestones

· FDA response on NORSE EIGHT Special Protocol Assessment (SPA) in early February 2024;
· Commencement of NORSE EIGHT expected in first calendar quarter of 2024;
· MAA decision date in the EU for ONS-5010 expected targeted for first half of 2024;
· Completion of NORSE EIGHT in the U.S. anticipated in 2024; and
· Resubmission of the ONS-5010 BLA expected by the end of calendar year 2024.

ONS-5010 / LYTENAVA (bevacizumab-vikg) Regulatory Update

As previously announced, following a Type A meeting with the FDA held in October 2023, the FDA informed Outlook Therapeutics that it can conduct a non-inferiority study evaluating ONS-5010 versus ranibizumab in a 3-month study of treatment naïve patients with a primary efficacy endpoint at 2 months. Subsequently, as discussed with and recommended by the FDA, Outlook Therapeutics submitted a clinical trial protocol and requested a Type A meeting with the FDA for feedback. The FDA has already provided written feedback on the protocol, which Outlook Therapeutics has incorporated. The revised protocol is the subject of the SPA request, in which Outlook Therapeutics is seeking further confirmation from the FDA that NORSE EIGHT, if successful, addresses the FDA’s requirement for a second adequate and well-controlled clinical trial to support the resubmission of the ONS-5010 BLA for wet AMD. The FDA is expected to provide a response to the SPA by early February 2024.

NORSE EIGHT will be a randomized, controlled, parallel-group, masked study of neovascular age-related macular degeneration subjects randomized in a 1:1 ratio to receive 1.25 mg ONS-5010 or 0.5 mg ranibizumab intravitreal injections. Subjects will receive injections at Day 0 (randomization), Week 4, and Week 8 visits. Approximately 400 patients are expected to be enrolled in the study.

Additionally, the Company previously announced that it submitted an MAA in Europe, which was validated for review in December 2022. The formal review process of the MAA by the European Medicines Agency (EMA) 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 Cencora (formerly AmerisourceBergen) to support the launch of ONS-5010 in international markets.

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

Financial Highlights for the 2023 Fiscal Year Ended September 30, 2023

For the fiscal year ended September 30, 2023, Outlook Therapeutics reported a net loss attributable to common stockholders of $59.0 million, or $0.24 per basic and diluted share, compared to a net loss attributable to common stockholders of $66.1 million, or $0.31 per basic and diluted share, for the prior fiscal year.

As of September 30, 2023, Outlook Therapeutics had cash and cash equivalents of $23.4 million. On December 21, 2023, Outlook Therapeutics reached an agreement with the holder of its outstanding convertible promissory note to extend the maturity until April 1, 2024.

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 FDA-approved ophthalmic formulations of bevacizumab are available currently, 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 would provide an FDA-approved option for physicians that currently prescribe 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.

On February 9, 2024 Lineage Cell Therapeutics, Inc. (NYSE American and TASE: LCTX), a clinical-stage biotechnology company developing allogeneic cell therapies for unmet medical needs, reported the closing of its previously announced registered direct offering for the purchase and sale of 13,461,540 of the company’s common shares at an offering price of $1.04 per common share (Press release, Lineage Cell Therapeutics, FEB 9, 2024, View Source [SID1234639956]). The price per share was the closing price of the company’s common shares on NYSE American on February 5, 2024. Broadwood Partners, L.P., which is affiliated with Neal Bradsher, a member of the Company’s board of directors, has purchased 6,730,770 common shares in the offering, and Don M. Bailey, a member of the Company’s board of directors, has purchased approximately 100,000 common shares in the offering.

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"This offering strategically strengthens our balance sheet, which can aid us in reaching important milestones in the months ahead," stated Brian M. Culley, Lineage CEO. "This deal was priced at-market, without a discount or dilutive structural elements like warrants. It featured significant insider and pre-existing shareholder participation and was executed without an investment bank. We appreciate the contributions of all parties involved in this transaction and look forward to advancing our product candidates this year."

The aggregate gross proceeds to Lineage from the offering at the closing were $14.0 million before deducting estimated offering expenses payable by Lineage. Lineage intends to use the proceeds from the offering for general corporate purposes, which may include clinical trials, research and development activities, general and administrative costs, and to meet working capital needs.

The securities described above were offered and sold by Lineage pursuant to a "shelf" registration statement on Form S-3 (File No. 333-254167), including a base prospectus, previously filed with the Securities and Exchange Commission, or the SEC, on March 11, 2021, and declared effective by the SEC on March 19, 2021. Such securities were offered only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement. A final prospectus supplement and an accompanying base prospectus relating to the securities was filed with the SEC. Electronic copies of the prospectus supplement and the accompanying base prospectus may be obtained by visiting the SEC’s website at View Source

This press release does not constitute an offer to sell or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or other jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or other jurisdiction.

On February 9, 2024 Adagene Inc. ("Adagene") (Nasdaq: ADAG), a company transforming the discovery and development of novel antibody-based therapies, reported progress and expansion of the clinical collaboration development program for its masked, anti-CTLA-4 SAFEbody, ADG126 in combination with Merck & Co., Inc., Rahway, NJ, USA’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in patients with metastatic microsatellite-stable (MSS) colorectal cancer (CRC) (Press release, Adagene, FEB 9, 2024, View Source [SID1234639955]).

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"Following completion of enrollment of 12 additional patients at the end of last year, together with our ongoing expansion plans, we are on track to deliver data in 2024 that support the findings released at the recent ASCO (Free ASCO Whitepaper)-GI Symposium demonstrating the safety and efficacy profile of ADG126 in combination with pembrolizumab in MSS CRC," said Peter Luo, Ph.D., Chairman, CEO and President of R&D at Adagene.

He continued, "To address the requirements for Project Optimus by FDA, we have initiated evaluation of ADG126 20 mg/kg loading doses in combination with pembrolizumab, which we believe can unlock even greater efficacy for MSS CRC in planned cohort expansion, while still maintaining a robust safety profile. Additionally, we are now cleared to evaluate ADG126 in combination with pembrolizumab in China, strengthening our efficacy evaluation with additional patients enrolled at unprecedented dosing regimens for anti-CTLA-4 therapy."

The updates, which increase the ongoing phase 2 dose expansion in MSS CRC to over 50 patients, include the following:

· The company announced it completed enrollment of 12 additional patients in the fourth quarter of 2023 in the ongoing phase 2 dose expansion cohort evaluating ADG126 10 mg/kg Q3W in combination with pembrolizumab in MSS CRC. These Part 2 results are expected to support data from Part 1 of the dose expansion in MSS CRC that was recently presented at the 2024 ASCO (Free ASCO Whitepaper)-GI Symposium.

· Given the safety profile of ADG126, Adagene has also initiated evaluation of 20 mg/kg loading doses in combination with pembrolizumab in patients with advanced/metastatic cancer. Following the ongoing safety evaluation, the company plans to study efficacy of the loading doses followed by a maintenance regimen of ADG126 10 mg/kg Q3W in combination with pembrolizumab. The company plans dose expansion with this regimen in patients with MSS CRC in the US and Asia Pacific.

· Adagene has also received clearance from the CDE in China to initiate clinical evaluation of ADG126 in combination with pembrolizumab. This enables the company to broaden its dose expansion cohorts for MSS CRC at selected dosing regimens, and potentially in other tumor types.

2024 Milestones

Data from the ongoing phase 1b/2 clinical trial of ADG126 in combination with pembrolizumab, including dose expansion cohorts, are anticipated throughout 2024:

· Follow up of Part 1 evaluable patients at 10 mg/kg Q3W (n=12) and 10 mg/kg Q6W (n=10)
· Data from Part 2 patients at 10 mg/kg Q3W (n=12)
· Evaluation of 20 mg/kg loading doses for Project Optimus requirements:
o Safety data with repeat doses
o Dose expansion in MSS CRC (n~10)
· Additional patients in China (n≥10)

On February 9, 2024 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that anti-CD20/CD3 bispecific antibody mosunetuzumab achieved the primary endpoint of complete response rate (CRR) in an expansion cohort of the Japanese Phase I study evaluating the efficacy and safety in patients with relapsed or refractory (R/R) follicular lymphoma (FL) who have received two or more prior systemic therapies (Press release, Chugai, FEB 9, 2024, View Source;category= [SID1234639948]). The safety profile was consistent with previous overseas studies.

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"R/R FL is a disease that repeatedly recurs and is difficult to cure, and new treatment strategies are required. We are very pleased that bispecific antibody mosunetuzumab achieved CRR and showed promising results for remission. We will continue efforts to apply for the approval of mosunetuzumab in Japan to deliver this drug as a new treatment option for patients as quickly as possible," said Dr. Osamu Okuda, Chugai’s President and CEO.

Chugai will file a new drug application in Japan based on these study results and the overseas Phase I/II clinical studies conducted by Roche in the same patient population.

About Japanese Phase I study for mosunetuzumab
This study is a Japanese phase I clinical study to evaluate the efficacy and safety of mosunetuzumab in a dose-escalation cohort and in an expansion cohort for patients with R/R FL who have previously received two or more systemic therapies. 19 patients were enrolled in the expansion cohort. The primary endpoint was CRR. Key secondary endpoints included overall response rate, progression-free survival, and duration of response.

About mosunetuzumab
Mosunetuzumab is a CD20xCD3 T cell-engaging bispecific antibody designed to target CD20 on B cells and CD3 on T cells. Mosunetuzumab is expected to activate the immune system through cytotoxic T cells and have antitumor effects on CD20 expressed tumor cells. Mosunetuzumab is currently being developed with intravenous and subcutaneous formulations for the treatment of R/R FL and R/R aggressive B-cell non-Hodgkin lymphoma.

About follicular lymphoma
FL is a type of lymphoma that occurs when B lymphocytes, a type of white blood cell, become cancerous. At diagnosis, 70-85% of patients reach an advanced stage1. Generally, the progression is slow, and chemotherapy is initially effective, but recurrences occur repeatedly in many cases. Repeated recurrences can make it difficult for existing treatments to be effective, and new highly effective treatments are expected. In Japan, approximately 5,000 people reportedly become afflicted with FL each year.

On February 8, 2024 Attovia Therapeutics, a biotech company pioneering spatially optimized biparatopic biologics, reported the closing of the $30 million second tranche of its previously reported $60 million Series A financing (Press release, Attovia Therapeutics, FEB 8, 2024, View Source [SID1234647442]). Attovia also announced the nomination of the first development candidate generated from its Attobody biologics platform, ATTO-1310, a potential first-in-class, long half-life anti-IL31 Attobody. Proceeds from the second tranche will be used to advance ATTO-1310 through early clinical trials, move the Company’s second program, ATTO-002, a bispecific IL31 x IL13 ligand trap, toward IND-enabling studies, and to further develop the Attobody platform and early discovery pipeline.

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"The novel advantages of the biparatopic binding mode of the Attobody technology include potential for higher efficacy and the ability to expand the universe of druggable epitopes," said Tao Fu, CEO of Attovia. "Our first set of programs validate the Attobody platform and illustrate Attovia’s core capabilities to discover and develop small format biologics with first- or best-in-class potential at industry-leading speed. In just eight months, the Attovia team has successfully closed both tranches of the $60 million Series A financing, built a pipeline of five novel programs, and rapidly advanced our lead programs towards the clinic. I am thrilled to partner with our investors, executive team, and advisors to develop our highly innovative product portfolio."

Pipeline Update

Attovia’s lead programs focus on immune-mediated disease. The Company’s first program, ATTO-1310, is currently in IND enabling studies and is intended for the treatment of atopic dermatitis and other pruritic diseases. Through biparatopic binding and ligand- rather than receptor-targeting, ATTO-1310 has the potential to achieve faster and deeper responses than other IL31-pathway targeting molecules. ATTO-1310 utilizes clinically validated half-life extension technology designed to lengthen its dosing interval to potentially once every three months, compared to bi-weekly or monthly dosing with marketed biologics for these indications. ATTO-1310 is currently on track to enter the clinic around year-end 2024.

The Company’s second program, ATTO-002, is a small format, bispecific ligand trap targeting IL31 and IL13. ATTO-002 seeks to establish a new standard of care in the treatment of atopic dermatitis by simultaneously inhibiting two non-overlapping pathways involved in disease pathology with potentially best-in-class potency, and by avoiding receptor-mediated drug removal. Attovia expects to nominate a development candidate and advance the candidate to IND enabling studies in the second half of 2024. Given the modularity of the platform, the existing IL13 binder from ATTO-002 can be combined with new additional arms such as anti-TSLP, -OX40L, -IL33, and others, to build Attobody-based bispecifics targeting respiratory and fibrotic diseases such as asthma, idiopathic pulmonary fibrosis (IPF), or chronic obstructive pulmonary disease (COPD).

Attovia has initiated three additional discovery programs in immune mediated disease and oncology:

ATTO-004, targeting a novel G-protein-coupled receptor (GPCR);
ATTO-005, targeting a first-in-class bispecific combination in inflammatory bowel disease (IBD);
ATTO-003, an anti-B7H4 drug conjugate program exploring the possibility of using Attobody as the ideal binder for payload delivery to improve therapeutic index in select solid tumors.