On June 26, 2025 Aldeyra Therapeutics, Inc. (Nasdaq: ALDX) (Aldeyra) reported receipt of a Special Protocol Assessment Agreement Letter from 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 (PVRL), a rare and potentially fatal cancer currently lacking FDA-approved therapy (Press release, Aldeyra Therapeutics, JUN 26, 2025, View Source [SID1234654131]).

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"Primary vitreoretinal lymphoma is treated today off label with intravitreal injections of compounded methotrexate," stated Todd C. Brady, M.D., Ph.D., President and Chief Executive Officer of Aldeyra. "ADX-2191, a novel, vitreous-compatible formulation of methotrexate that is specifically designed for intraocular injection, potentially allows for a reduced injection volume relative to compounding."

Based on a pre-New Drug Application (NDA) meeting with the FDA in December 2022, Aldeyra submitted a literature-based NDA of ADX-2191 for the treatment of PVRL, which was accepted for Priority Review in March 2023. In June 2023, Aldeyra received a Complete Response Letter that stated that the available literature was not sufficient to demonstrate efficacy and that adequate and well-controlled trials were required for approval. The FDA subsequently agreed that a single clinical trial in addition to literature references will be sufficient to support NDA resubmission.

The clinical trial proposed in the Special Protocol Assessment will compare cancer cell clearance after 30 days of therapy in up to 20 patients following 1:1 randomization to receive either a single intraocular injection or eight intraocular injections of ADX-2191. The frequency of methotrexate injections has been linked to cancer cell clearance in patients with PVRL,[1] and approximately five injections are required on average to achieve cancer cell clearance.[2] The clinical trial is expected to begin in the second half of 2025 and conclude in 2026.

About ADX-2191

ADX-2191 (methotrexate injection, USP) is a sterile, non-compounded intravitreal formulation of methotrexate for the potential treatment of specific rare retinal diseases, including primary vitreoretinal lymphoma 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 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 less than five years. No approved treatments are currently available, though intravitreal injection of compounded methotrexate represents the current standard of care.

On June 25, 2025 Vor Bio, Inc. (Nasdaq: VOR) and RemeGen Co., Ltd. (HKEX: 9995, SHA: 688331) reported entry into an exclusive license agreement granting Vor Bio global rights (excluding China, Hong Kong, Macau and Taiwan) to develop and commercialize telitacicept, a novel dual-target fusion protein approved in China for generalized myasthenia gravis (gMG), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA) (Press release, Vor BioPharma, JUN 25, 2025, View Source [SID1234654139]). Under the terms of the agreement, Vor Bio will pay RemeGen an initial payment of $125 million consisting of an upfront payment of $45 million as well as $80 million of warrants to purchase common stock with an exercise price of $0.0001 per share. The agreement also provides for potential regulatory and commercial milestones exceeding $4 billion, in addition to tiered royalties.

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Telitacicept is a novel, investigational fusion protein that targets key immune pathways involved in autoimmune disease. By selectively inhibiting BlyS (also known as BAFF) and APRIL—cytokines critical to B cell survival—telitacicept reduces autoreactive B cells and autoantibody production. RemeGen is conducting a global Phase 3 clinical trial which is now enrolling in the United States, Europe, and South America, with initial results expected in the first half of 2027.

Vor Bio also announced that its Board of Directors (the "Board") has appointed Jean-Paul Kress, M.D., as Chief Executive Officer and Chairman of the Board, effective today. This follows Dr. Robert Ang’s resignation from the positions of Chief Executive Officer and director earlier today. Dr. Ang will continue with Vor Bio as a strategic advisor to assist in the transition through October 2025. Dr. Kress’s strategic vision and track record of transformative leadership position him to guide the company into its next phase of growth.

"I am absolutely thrilled to be leading Vor Bio as we transform the company to become a major player in autoimmune disease treatment," said Dr. Kress, Chairman and Chief Executive Officer, Vor Bio. "Targeting BAFF/APRIL signaling with telitacicept represents a significant advancement in addressing autoantibody driven diseases, which is highly differentiated from other modalities in this space. With a clinically advanced asset, we are uniquely positioned to develop this innovative therapy, with the goal of making a meaningful impact for patients living with autoimmune diseases around the world."

Dr. Kress brings decades of executive leadership experience in the pharmaceutical and biotech industries. He most recently served as Chief Executive Officer of MorphoSys, where he led the development, approval and commercialization of Monjuvi (tafasitamab), and advanced the company’s pipeline through the landmark acquisition of Constellation Pharmaceuticals in 2021, strengthening MorphoSys’ position in oncology innovation and ultimately leading to its subsequent acquisition by Novartis in 2024. Prior to that, he was CEO of Syntimmune, guiding its lead immunology program through to acquisition by Alexion Pharmaceuticals. He currently serves on the Board of Sanofi S.A. and has held senior roles across leading biopharma companies.

"Today marks a transformative milestone for RemeGen and the global development of telitacicept," said Dr. Jianmin Fang, CEO of RemeGen. "The strategic out-licensing of telitacicept’s ex-China rights accelerates our mission to deliver this innovative therapy to patients worldwide and will help maximize telitacicept’s clinical and commercial potential on the global scale."

About Telitacicept

Telitacicept is a novel, investigational recombinant fusion protein designed to treat autoimmune diseases by selectively inhibiting BLyS (BAFF) and APRIL—two cytokines essential to B cell and plasma cell survival. This dual-target mechanism reduces autoreactive B cells and autoantibody production, key drivers of autoimmune pathology. In a Phase 3 clinical trial in generalized myasthenia gravis in China, telitacicept demonstrated a 4.8-point improvement in MG-ADL (Myasthenia Gravis Activities of Daily Living scale) vs. placebo at 24 weeks, the primary endpoint of the trial.

Telitacicept is approved in China for systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and generalized myasthenia gravis (gMG). A global Phase 3 clinical trial in gMG is currently underway across the United States, Europe, and South America to support potential approval in the United States and Europe.

On June 25, 2025 enGene Holdings Inc. (Nasdaq: ENGN, or "enGene" or the "Company"), a clinical-stage, non-viral gene-based immunotherapy company, reported that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to detalimogene voraplasmid (also known as detalimogene, and previously EG-70), the Company’s lead investigational therapy for the treatment of high-risk, Bacillus Calmette-Guérin (BCG)-unresponsive, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) (Press release, enGene, JUN 25, 2025, View Source [SID1234654126]).

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The RMAT program is intended to expedite the development and review of regenerative medicine therapies for serious or life-threatening conditions, where preliminary clinical evidence suggests potential to address unmet medical needs. This designation provides enGene with several regulatory advantages, including early and frequent engagement with the FDA, potential for rolling review and priority review, and other benefits like Fast Track and Breakthrough Therapy designations.

"Receiving the RMAT designation highlights the promising profile of detalimogene and its potential to address the high unmet need in NMIBC," stated Ron Cooper, Chief Executive Officer of enGene. "Bladder cancer patients with limited options cannot wait, and we are enthusiastic about potentially expediting the regulatory process to bring a first-in-class treatment to patients."

The designation was based on previously disclosed preliminary results from the ongoing pivotal LEGEND study, which demonstrated compelling clinical activity and a generally favorable tolerability profile in patients with BCG-unresponsive NMIBC with CIS.

Detalimogene is designed for streamlined administration in urology clinics — including community practices, where approximately 70% of urologists provide care. The therapy is being evaluated for its ability to treat NMIBC though the non-viral stimulation of a local immune response in the bladder, presenting a potentially transformative option for patients who otherwise face limited choices beyond radical cystectomy.

About Non-Muscle Invasive Bladder Cancer (NMIBC)
Non-muscle invasive bladder cancer (NMIBC) is a disease that poses a significant burden on both patients and clinics and has a massive economic impact on our healthcare system. NMIBC occurs when cancer cells grow in the tissues that line the interior of the bladder, but the cancer has not yet penetrated the muscle of the bladder wall. NMIBC can take the form of papillary outgrowths from the bladder wall, which are typically resected, or carcinoma in situ (CIS), flat, multifocal lesions that are unable to be resected, and the two can co-occur. About 75-80% of new bladder cancer diagnoses are NMIBC. Patients suffering from high-risk NMIBC who are unresponsive to the standard of care, Bacillus Calmette-Guérin (BCG), face high rates of disease recurrence (50-70%) and are subject to full removal of the bladder (cystectomy) as a curative but life-altering next step.

About Detalimogene
Detalimogene is a novel, investigational, non-viral gene-based immunotherapy for patients with high-risk NMIBC, including Bacillus Calmette-Guérin (BCG)-unresponsive disease. It is designed to be instilled in the bladder and elicit a powerful yet localized anti-tumor immune response.

Detalimogene was developed using the Company’s Dually Derivatized Oligochitosan (DDX) platform, a technology designed to transform how gene therapies are accessed by patients and utilized by clinicians. Medicines developed with the DDX platform can potentially overcome the limitations of viral-based gene therapies, simplify safe handling and cold storage complexities, and streamline both manufacturing processes and administration paradigms.

Detalimogene has received Fast Track designation from the U.S. Food and Drug Administration (FDA) based on its potential to address the high unmet medical need for patients with BCG-unresponsive CIS NMIBC, with or without resected papillary tumors, who are unable to undergo cystectomy. Fast Track designation is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.

About the Pivotal LEGEND Trial
Detalimogene is being evaluated in the ongoing, open-label, multi-cohort, Phase 2 LEGEND trial to establish its safety and efficacy in high-risk NMIBC. LEGEND’s pivotal cohort (Cohort 1) consists of approximately 100 patients with high-risk, BCG-unresponsive NMIBC with CIS (with or without papillary disease) and is designed to serve as the basis of the Company’s planned Biologics License Application (BLA) filing. In addition to this pivotal cohort, LEGEND includes three additional cohorts, including NMIBC patients with CIS who are naïve to treatment with BCG (Cohort 2a); NMIBC patients with CIS who have been exposed to BCG but have not received adequate BCG treatment (Cohort 2b); and BCG-unresponsive high-risk NMIBC patients with papillary-only disease (Cohort 3). The LEGEND trial is actively enrolling patients with sites participating in the USA, Canada, Europe, and the Asia-Pacific region.

On June 25, 2025 BeOne Medicines Ltd. (NASDAQ: ONC; HKEX: 06160; SSE: 688235), a global oncology company, reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency issued a positive opinion recommending approval of a new film-coated tablet formulation of BRUKINSA (zanubrutinib) for all approved indications (Press release, BeOne Medicines, JUN 25, 2025, View Source [SID1234654125]). The CHMP positive opinion will now be reviewed by the European Commission, which will grant the marketing authorization for the tablet formulation in the European Union and in the European Economic Area countries Norway and Iceland.

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"The CHMP’s positive opinion of our new tablet formulation of BRUKINSA is an important step toward bringing this thoughtful, patient-centered innovation to people facing certain B-cell cancers across Europe," said Giancarlo Benelli, Senior Vice President and Head of Europe, BeOne. "We look forward to a potential approval later this year and remain committed to delivering our impactful medicines to more patients in the region."

The BRUKINSA tablets have been shown to be bioequivalent to the BRUKINSA capsules based on the results of two single-dose, open-label, randomized Phase 1 crossover studies in healthy subjects. The recommended dose of BRUKINSA remains – 320 mg daily. The BRUKINSA tablets are 160 mg each, allowing patients to halve their daily pill intake and take two tablets daily. The new tablet formulation maintains BRUKINSA’s dosing flexibility by providing patients and prescribers with the option of once- or twice-daily dosing and is designed to simplify management of dose reductions as per label recommendation. Additionally, the BRUKINSA tablets are smaller than the capsules and have a film coat, which makes them easier to swallow.

BeOne Medicines will begin to convert BRUKINSA from capsules to tablets in regions outside China in 2025 as part of our commitment to sustainable business practices, including reducing our impact on the environment. This adjustment will decrease the bottle size by ~70% while also enabling the shipment of this medication with reduced temperature controls, which we expect to reduce energy needs, greenhouse gas emissions, and global transport costs.

Today’s announcement follows the U.S. Food and Drug Administration (FDA) approval of the new tablet formulation of BRUKINSA for all five approved indications earlier this month. In the U.S., BRUKINSA is the leader in new patient starts for chronic lymphocytic leukemia (CLL) across all lines of therapy, and for the first time, has become the overall BTK inhibitor market share leader.1

Important Safety Information
The current European Summary of Product Characteristics (SmPC) of BRUKINSA is available from the website of the European Medicines Agency.

This information is intended for a global audience. Product indications vary by region.

On June 25, 2025 Gilead Sciences, Inc. (NASDAQ: GILD) and Kymera Therapeutics, Inc. (NASDAQ: KYMR), reported that they have entered into an exclusive option and license agreement to accelerate the development and commercialization of a novel molecular glue degrader (MGD) program targeting cyclin-dependent kinase 2 (CDK2) with broad oncology treatment potential including in breast cancer and other solid tumors (Press release, Gilead Sciences, JUN 25, 2025, View Source [SID1234654124]).

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CDK2-directed MGDs are a new type of drug designed to remove CDK2 – a key contributor in tumor growth – rather than just inhibiting its function. Traditional inhibitors of CDK2 prevent it from working but often interfere with similar proteins, which can cause undesired side effects. MGDs have the potential to provide more precise, safe and effective treatments for cancers that rely on CDK2 activity by selectively removing this protein from cells.

"MGDs are opening exciting new possibilities in cancer research by offering a way to eliminate disease-driving proteins rather than just blocking them. This mechanism aligns within our oncology scientific framework where we evaluate therapeutic agents that selectively target and kill cancer cells with minimal impact on healthy tissue," said Flavius Martin, MD, Executive Vice President, Research, Gilead Sciences. "We are delighted to partner with Kymera to advance this novel oral program with the potential to drive meaningful improvements in the standard of care for patients living with breast cancer and other cancers that are inadequately served with existing therapies."

"We are excited to announce this strategic collaboration with Gilead Sciences, highlighting our dedication to innovation in the field with our first disclosed molecular glue program. We are committed to developing highly selective, potent, oral degrader medicines that address key disease-causing proteins and pathways that are undrugged or inadequately drugged by existing technologies," said Nello Mainolfi, PhD, Founder, President and CEO, Kymera Therapeutics. "Our highly specific, orally active, CDK2 molecular glue degraders have demonstrated a compelling preclinical profile and have the potential to transform the therapeutic landscape for breast cancer patients and other tumor types with high unmet medical need. We are excited to work with the talented Gilead team to accelerate the development and commercialization of this important program."

Terms of the Agreement

Under the terms of the agreement, Kymera is eligible to receive up to $750 million in total payments, including up to $85 million in upfront and potential option exercise payments. In addition, Kymera may also receive tiered royalties ranging from high single-digit to mid-teens on net product sales under the collaboration. Kymera will lead all research activities for the CDK2 program. If Gilead exercises its option to exclusively license the program, Gilead will have global rights to develop, manufacture and commercialize all products resulting from the collaboration.

Gilead does not exclude acquired IPR&D expenses from its non-GAAP financial measures. This transaction with Kymera is expected to reduce Gilead’s GAAP and non-GAAP 2025 EPS by approximately $0.02 – $0.03.