On December 21, 2022 Alentis Therapeutics ("Alentis" or "the Company"), the biotechnology company developing breakthrough treatments for organ fibrosis and fibrotic-associated cancers, reported that Scientific Founder Professor Thomas Baumert’s team has published an article in the peer-reviewed journal Science Translational Medicine providing preclinical proof-of-concept for Claudin-1-specific monoclonal antibodies for the treatment of fibrosis and cancer prevention across organs (Press release, Alentis Therapeutics, DEC 21, 2022, View Source [SID1234625481]).

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Severe tissue fibrosis is a key driver of end-stage organ failure and cancer, overall accounting for up to 45% of deaths in developed countries, and there is currently a large unmet need for effective antifibrotic therapies1.

In this study, highly specific monoclonal antibodies targeting a conformation-dependent epitope of exposed non-junctional Claudin-1 were tested in patient-derived liver 3D fibrosis and human liver chimeric mouse models, and showed that Claudin-1 is a previously unknown mediator and target for liver fibrosis. Targeting Claudin-1 reverted inflammation-induced hepatocyte pro-fibrogenic signaling and suppressed the myofibroblast differentiation of hepatic stellate cells. Safety studies did not reveal any significant adverse events even at high steady-state concentrations.

In addition, the use of Claudin-1-specific monoclonal antibodies in lung and kidney fibrosis models demonstrated clear antifibrotic effects, further indicating a role of Claudin-1 as a therapeutic target for tissue fibrosis across organs.

Separately, in a further demonstration of the role of CLDN1 as a therapeutic target, an article was published recently in the Journal of Hepatology which provided preclinical proof-of-concept for Claudin-1-specific monoclonal antibodies as potential first-in-class therapies for hepatocellular carcinoma (View Source).

Professor Thomas Baumert commented: "Fibrosis causes organ tissue scarring and thickening over time, which can lead to organ malfunction and cancer. This study provides valuable new evidence of the role of non-junctional Claudin-1 in the progression of fibrosis and proof-of-concept to treat fibrotic diseases with Claudin-1 specific monoclonal antibodies discovered by our research unit. Moreover, our study paves the way for further exploration of Claudin-1-targeting therapies for fibrotic diseases in patients."

Roberto Iacone, CEO at Alentis Therapeutics, added: "Since anti-Claudin-1 monoclonal antibodies target exposed non-junctional Claudin-1 they exhibit an excellent safety profile. Using this innovative approach which now has entered clinical development, Alentis Therapeutics aims to reverse the course of fibrosis and sensitize solid tumors to immuno-oncologic and chemotherapeutic medication. The important data published in Science Translational Medicine provide further validation for our approach and we look forward to progressing our candidates in clinical development."

This study was led by Professor Thomas Baumert at Inserm and the University of Strasbourg and conducted as a collaboration between Inserm, University of Strasbourg, Alentis Therapeutics, Novo Nordisk, German Cancer Research Center, IRB Bellizona, University of Texas Southwestern Medical Center Dallas, the Universities of Aalborg, Geneva, Leuven and Copenhagen, Massachusetts General Hospital Cancer Center and Harvard Medical School.

The full paper can be accessed here: View Source

References

Wynn TA. Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat Rev Immunol. 2004; 4(8):583–594. doi: 10.1038/nri1412.
Roehlen N et al. Treatment of HCC with Claudin-1 specific antibodies suppresses carcinogenic signaling and reprograms the tumor microenvironment. Journal of Hepatology 2022; View Source
View Source

On December 21, 2022 Aldeyra Therapeutics, Inc. (Nasdaq: ALDX) (Aldeyra) reported the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for ADX‑2191 (methotrexate injection, USP), an investigational drug candidate, for the treatment of primary vitreoretinal lymphoma, a rare but potentially fatal cancer with no FDA-approved therapy (Press release, Aldeyra Therapeutics, DEC 21, 2022, View Source [SID1234625480]).

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The NDA submission is supported by a combination of published literature on the safety and efficacy of methotrexate for the treatment of primary vitreoretinal lymphoma and safety data from the recently completed Phase 3 GUARD Trial of ADX‑2191 for the prevention of proliferative vitreoretinopathy. During the Phase 3 GUARD Trial, no safety signals were observed, and ADX-2191 was well tolerated; there were no observed treatment-emergent serious adverse events. The most common adverse event associated with ADX-2191 treatment was punctate keratitis, a frequently observed side effect of intravitreal methotrexate, that was most commonly mild in severity. In the Phase 3 GUARD Trial, the incidence of punctate keratitis with ADX-2191 administration was observed to be less than that previously reported with intravitreal injection of compounded methotrexate.1

"Compounding methotrexate for intravitreal injection, the current standard of care for primary vitreoretinal lymphoma, poses several challenges for physicians and patients, including risk of infection and increased injection volume, potentially leading to ocular hypertension and corneal inflammation," stated Todd C. Brady, M.D., Ph.D., Aldeyra’s President and Chief Executive Officer. "ADX-2191 is a novel formulation of methotrexate that is designed to be vitreous-compatible and has the potential to be the first marketed drug for patients suffering from primary vitreoretinal lymphoma."

ADX-2191 has received FDA Orphan Drug Designation for the treatment of primary vitreoretinal lymphoma. In addition, as part of the NDA submission, Aldeyra requested Priority Review Designation, which reduces the review period during which the FDA aims to take action on an NDA to within 6 months, compared to 10 months under standard review.

A Type C meeting with the FDA to discuss the completion of clinical development of ADX-2191 for the prevention of proliferative vitreoretinopathy is planned for the first half of 2023, and results from the Phase 2 clinical trial of ADX-2191 in retinitis pigmentosa are expected in the first half of 2023.

About ADX-2191

ADX-2191 (methotrexate injection, USP) is a sterile, non-compounded intravitreal formulation of methotrexate for the potential prevention or treatment of specific rare retinal diseases, including primary vitreoretinal lymphoma, proliferative vitreoretinopathy, and retinitis pigmentosa. The ADX-2191 intravitreal formulation is preservative-free, is designed to be vitreous-compatible, and is optimized for excipient composition, viscosity, density, tonicity, pH, concentration, and volume of administration. ADX-2191 has received FDA Orphan Drug Designation for the prevention of proliferative vitreoretinopathy, and for the treatment of primary vitreoretinal lymphoma and retinitis pigmentosa.

About Primary Vitreoretinal Lymphoma

Primary vitreoretinal lymphoma is a rare, aggressive, and potentially fatal retinal cancer that is diagnosed in approximately 300 to 600 patients in the United States per year. The median survival for newly diagnosed patients is 4.83 years. The most common ocular complaints reported by patients include blurred vision, painless loss of vision, floaters, red eye, and photophobia. No approved treatments are currently available, though intravitreal injection of compounded methotrexate represents the current standard of care.

On December 21, 2022 Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in the field of cellular metabolism pioneering therapies for rare diseases, reported that the company is scheduled to present at the 41st Annual J.P. Morgan Healthcare Conference on Wednesday, January 11, 2023, at 7:30 a.m. PT (Press release, Agios Pharmaceuticals, DEC 21, 2022, View Source [SID1234625479]).

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A live webcast of the presentation can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com. A replay of the webcast will be archived on the Agios website for at least two weeks following the presentation.

On December 21, 2022 Biomica Ltd., a clinical-stage biopharmaceutical company developing innovative microbiome-based therapeutics and a subsidiary of Evogene Ltd. (Nasdaq: EVGN, TASE: EVGN), reported the signing of a definitive agreement for a $20 million financing round, to be led by Shanghai Healthcare Capital (SHC) (Press release, Biomica, DEC 21, 2022, View Source [SID1234625471]). The financing is subject to customary closing conditions, including clearance by Chinese regulatory authorities.

Shanghai Healthcare Capital is a leading Chinese private equity fund, based in Shanghai and focused on biotech and healthcare investments globally. The fund’s goal is investment in early stage and best-in-class innovators with a pipeline of therapies for improving the lives and long-term outcome of patients. The fund is managed by SIIC Capital, with Shanghai Pharma as one of the founding and strategic Limited Partners.

The financing round will enable Biomica to forge ahead, developing its pipeline of microbiome-based therapeutics. Biomica plans to use the proceeds to complete its current BMC128 phase 1 immuno-oncology study and advance to phase 2 clinical trial; scale up and complete GMP production of BMC333 in preparation for a phase 1 clinical trial for the treatment of inflammatory bowel disease (IBD); as well as advance additional programs.

Biomica’s drug candidates are based on a rationally designed consortia of microbes, selected through high-resolution functional microbiome analysis using PRISM, a computational platform powered by Evogene’s ‘MicroBoost AI’ tech engine.

"We are delighted to welcome SHC to Biomica as a strong value-adding shareholder and we are grateful to our existing shareholders and partners for their continued support," commented Dr. Elran Haber, Chief Executive Officer of Biomica. "Biomica has made tremendous progress in the past year. This includes the initiation of the first in-human phase 1 immune-oncology clinical trial of BMC128 as well as advancing our infectious and gastrointestinal-related disease programs. We look forward to working closely with our shareholders, as we continue our advancements and meet our milestones in the coming years."

Dr. Jing Bao, Senior Advisor of Shanghai HealthCare Capital with a PhD from the Weizmann Institute of Science, commented: "Microbiome research is an attractive field for SHC. It could potentially benefit a very large Chinese population. We see that the FDA just approved the first microbiome product, and we believe there is more to come. Specifically, Shanghai Pharma plays a strong role in China’s Live Biotherapeutic Product industry. Biomica, together with Evogene, has deep knowledge in the field and is pushing its first asset into the clinical stage. By leading the investment, we look forward to a meaningful and fruitful collaboration in the years to come."

Added Ofer Haviv, Chairman of Biomica and President & CEO of Evogene, "We are pleased to bring this new strategic partner, Shanghai Healthcare Capital, to join us. This external and independent endorsement validates our belief in the long-term potential of Biomica. It shows that all our hard work in building and investing in Biomica’s development, whose underpinning technology leverages our AI tech engine, MicroBoost AI, is a successful strategy and continues to bear fruit."

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On December 21, 2022 Celyad Oncology (Euronext & Nasdaq: CYAD) (the "Company"), a biotechnology company focused on the discovery and development of innovative technologies for chimeric antigen receptor (CAR) T-cell therapies, reported an update on its Celyad 2.0 business strategy which has been adopted and implemented over the last few months (Press release, Celyad, DEC 21, 2022, View Source [SID1234625470]).

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In keeping with this strategy, the Company intends to focus on maximizing its valuable intellectual property (IP) estate, and strengthening its research focus.

The Company has compiled a foundational and broad IP estate that controls key aspects of developing therapies in the allogeneic cell therapy space. The patents around allogeneic CAR T-cell therapies and NKG2D-based therapies provide an avenue to develop intellectual property programs and to partner with outside parties around the licensing of these patents.

In addition to IP partnering transactions, Celyad 2.0 will prioritize discovery research in areas of expertise where it can leverage the differentiated nature of its platforms. The Company is implementing a differentiated and innovative strategy, tackling the major current limitations of CAR T-cell therapies. This strategy includes:
Multiplexing approach of the short hairpin RNA (shRNA) platform, allowing multiple genes, including essential and functional genes, to be modulated simultaneously;

Dual CAR development of a next-generation NKG2D-based CAR which may help to overcome resistance and immune escape often observed with traditional single targeting approaches; and
Development of B7-H6-targeting immunotherapies as the Company believes that B7-H6 is an underappreciated target that could change the paradigm of cell therapy due to its broad expression in a large variety of cancers.
Celyad Oncology is of the opinion that it will potentially create more shareholder value by licensing its patent estate and further strengthening its research efforts to improve the differentiated nature of its platforms.

Based on a strategic and financial review, the Company has decided to discontinue the development of its remaining clinical program CYAD-211 (the allogeneic shRNA-based, anti-BCMA CAR T candidate for relapsed or refractory multiple myeloma (r/r MM)). There were no safety concerns leading to this decision and all patients previously treated with CYAD-211 will continue to receive their protocol-defined follow-up.

The key data points of the program are as follows:

19 r/r MM patients have been treated with CYAD-211 in the IMMUNICY-1 trial which was developed to validate shRNA technology in the clinic;
The observed safety profile, including the lack of observed Graft-versus-Host disease, provides proof-of-concept for the use of shRNA technology for allogeneic CAR Ts;
Out of 17 evaluable patients, a partial response was achieved in five patients. One patient was recently re-treated with a second dose of CYAD-211 after having reached stable disease post first infusion; and
Enhanced lymphodepletion did not seem to improve clinical activity nor persistence of the cells post-infusion.
Anticipated milestones for 2023

The Company will take part in several conferences including The World Oncology Cell Therapy Congress in April and the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 38th Annual Meeting in November; and
The Company will provide updates on the potential proof-of-concept of the dual CAR and multiplexing research programs and on business development in the second quarter of 2023.