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Bristol Myers Squibb Announces Phase 3 EXCALIBER-RRMM Study Evaluating Iberdomide in Combination with Standard Therapies Demonstrated a Significant Improvement in Minimal Residual Disease Negativity Rates in Relapsed or Refractory Multiple Myeloma

On September 23, 2025 Bristol Myers Squibb (NYSE: BMY) reported that the Phase 3 EXCALIBER-RRMM study evaluating iberdomide, an investigational cereblon E3 ligase modulator (CELMoD), combined with standard therapies (daratumumab + dexamethasone) in patients with relapsed or refractory multiple myeloma (RRMM) demonstrated a statistically significant improvement in minimal residual disease (MRD) negativity rates, compared with the control arm, in a planned interim analysis of the MRD endpoint (Press release, Bristol-Myers Squibb, SEP 23, 2025, View Source [SID1234656170]). In accordance with the trial design and based on the recommendation from the Data Monitoring Committee, the trial will continue without changes to evaluate the other dual-primary endpoint of progression-free survival (PFS), and the key secondary endpoint of overall survival and safety. The safety profile of iberdomide in combination with daratumumab and dexamethasone in this study is generally consistent with previous studies.

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"This result builds on our significant experience in both targeted protein degradation and developing new treatment options for patients living with multiple myeloma," said Anne Kerber, Senior Vice President, Head of Development, Hematology, Oncology and Cell Therapy. "Iberdomide represents the first of a novel class of medicines, called CELMoDs, which has the potential to create a new foundation for multiple myeloma treatment that may be combined with other therapies."

The company plans to discuss these results with health authorities.

About EXCALIBER-RRMM
EXCALIBER-RRMM (NCT04975997) is a Phase 3, multicenter, two-stage, randomized, open-label study evaluating the efficacy and safety of iberdomide in combination with daratumumab and dexamethasone (IberDd) versus daratumumab, bortezomib, and dexamethasone (DVd) in patients with relapsed or refractory multiple myeloma (RRMM). The study is designed to assess dual-primary endpoints of minimal residual disease (MRD) negativity and progression-free survival (PFS), with additional secondary endpoints including overall survival (OS), overall response rate (ORR), duration of response (DoR), time to progression (TTP), time to next treatment (TTNT), and health-related quality of life (HR-QoL). Stage 1 of the study identified 1.0 mg iberdomide as the optimal dose based on safety, pharmacokinetics, and efficacy data. In Stage 2, approximately 664 patients were randomized to receive either IberDd or DVd.

About Minimal Residual Disease (MRD)
Minimal residual disease (MRD) refers to the small number of cancer cells that may remain in a patient’s body after treatment and are undetectable using conventional diagnostic methods. In multiple myeloma, MRD assessment has emerged as a highly sensitive and clinically meaningful tool for evaluating treatment response. MRD negativity does not necessarily mean all cancer cells are gone, but it may predict improved clinical outcomes, including longer remission and survival.

Modern MRD detection methods, such as next-generation sequencing (NGS) and next-generation flow cytometry (NGF), can identify one malignant cell among 100,000 (threshold for MRD) to 1,000,000 normal cells, offering unprecedented precision in measuring disease burden. MRD is increasingly being used in clinical trials as a surrogate endpoint for progression-free survival (PFS) and is gaining recognition from regulatory authorities for its role in accelerating therapeutic development.

About Targeted Protein Degradation and Novel CELMoD Agents
Targeted protein degradation (TPD) is a differentiated research platform at Bristol Myers Squibb built on more than two decades of scientific expertise, providing new avenues to degrade therapeutically relevant proteins that were previously considered "undruggable." We are the only company that has successfully developed and commercialized protein degrader agents – immunomodulatory drugs (IMiD) which helped establish the current standard of care in the treatment of multiple myeloma. We are building on this foundation with several investigational protein degraders in clinical trials, leveraging three different modalities including CELMoD agents, ligand-directed degraders (LDDs), and degrader antibody conjugates (DACs). This three-pronged approach allows us to match the right therapeutic modality to a molecular mechanism of action to modulate targets most effectively and ultimately provides more opportunities for potential breakthroughs that may offer meaningful new options for patients across a broad range of diseases, in and beyond hematology and oncology. Learn more about the science behind TPD at Bristol Myers Squibb.

BioNTech to Host Second AI Day as an Edition of Its Innovation Series on October 1, 2025

On September 23, 2025 BioNTech SE (Nasdaq: BNTX, "BioNTech"), alongside its artificial intelligence ("AI") company InstaDeep Ltd. ("InstaDeep"), reported it will host its second AI Day, an edition of BioNTech’s "Innovation Series", at 09:00 a.m. EDT (3:00 p.m. CEST) on Wednesday, October 1, 2025, in London, United Kingdom (Press release, BioNTech, SEP 23, 2025, View Source [SID1234656169]). The event will provide an overview of BioNTech’s AI strategy and capabilities, and the application of AI in BioNTech’s pipeline and internal processes.

The live webcast of the event will be available via this link.

Participants may also access the slides and a recording of the event via the "Events & Presentations" page in the Investor Relations section of BioNTech’s website at www.BioNTech.com. The recording will be available shortly after the event’s conclusion and archived on BioNTech’s website for one year thereafter.

SEED Therapeutics Completes $30 Million Series A-3 Financing

On September 23, 2025 SEED Therapeutics, Inc. ("SEED"), a clinical-stage biotechnology company pioneering rational molecular glue degraders for historically undruggable disease drivers, reported the successful completion of its $30 million Series A-3 financing, alongside U.S. Food and Drug Administration (FDA) clearance of its Investigational New Drug (IND) application for its lead program targeting RBM39 (Press release, Seed Therapeutics, SEP 23, 2025, View Source [SID1234656168]). The company anticipates entering first-in-human clinical trials of ST-01156 in Q1 2026.

The $30 million Series A-3 financing consists of a $24 million first close completed in August 2024 and a $6 million second close completed in August 2025. In addition, SEED has received close to $60 million in equity, as well as collaboration upfront and milestone payments combined, from its partnerships with Eli Lilly and Eisai reflecting strong partner validation of its scientific platform.

Lan Huang, Ph.D., SEED Co-Founder, Chairman, and Chief Executive Officer, said:
"FDA clearance of our IND is a defining milestone for SEED, marking our transition into a clinical-stage company. ST-01156 represents the first of a new generation of rationally designed molecular glue degraders. We continue to translate innovation into meaningful therapies for patients."

Bill Desmarais, SEED Chief Financial Officer and Chief Business Officer, added:
"Our equity financing, together with collaboration payments from Eli Lilly and Eisai, supplement our resources to move confidently into the clinic and to continue building a broad pipeline. We have the partners, capital, and momentum to deliver on SEED’s strategy."

SEED Therapeutics is a TPD 2.0 company that integrates structure-based drug design, computational chemistry, and chemical biology to discover molecular glues that reprogram the ubiquitin-proteasome system to degrade disease-causing proteins. Its proprietary RITE3 platform has generated a growing pipeline of nine programs spanning oncology, neurodegeneration, immunology, and virology.

Amphista Therapeutics discloses first details of its TEAD Targeted Glue™ program and unveils new mechanism of action for TEAD degradation via FBXO22

On September 23, 2025 Amphista Therapeutics ("the Company" or "Amphista"), a leader in the discovery of next generation targeted protein degradation (TPD) medicines, reported first data on its TEAD oncology therapeutic program including unveiling a new mechanism of action for the degradation of TEAD that is differentiated from cereblon- or VHL-based PROTACs (Press release, Amphista Therapeutics, SEP 23, 2025, View Source [SID1234656167]). Amphista’s novel TEAD Targeted Glues, which are inherently smaller and more drug like molecules than conventional PROTAC binders, have demonstrated:

Novel mechanism of degradation: Amphista’s pan-TEAD Targeted Glue series induces degradation via functional recruitment of the E3 ligase FBXO22 (F-Box Protein 22), a mechanism of degradation that has not previously been described for TEAD.
Highly specific degradation of TEAD:Global proteomics demonstrates complete, and statistically significant, selective, degradation of TEAD vs >7000 other proteins.
Deep target degradation via oral dosing: Leveraging high-resolution cryo-EM, Amphista has designed sub-nM degraders of TEAD which induce >95% degradation of TEAD in vivo after a single oral dose.
Exceptional degradation dynamics: Amphista’s Targeted Glues achieve >90% TEAD degradation within 2 hours (the first time point measured) of single dosing, sustained at >70% through to at least 72 hours,
Louise Modis, Chief Scientific Officer of Amphista Therapeutics, said: "Soon after disclosing initial details of our SMARCA2 oncology program, the first unveiling of a completely novel mechanism of action for the degradation of TEAD, represents another significant milestone for Amphista, as well as the wider targeted protein degradation field. The development of potent, rapid, orally bioavailable Targeted Glue degraders of TEAD that work via FBXO22 is testament to the power of our Eclipsys platform and our brilliant multidisciplinary team. What is particularly exciting are the structural insights that we are gaining from our technology as we build our cryo-EM datasets. Not only are these helping Amphista generate differentiated, higher quality molecules with the properties that will enable them to become medicines, but they are also unlocking mechanistic insights into the development and optimisation of Amphista’s Targeted Glues which operate through diverse ligases. The progress we have made across our portfolio this year, which includes the disclosure of two completely novel mechanisms for the degradation of therapeutically relevant targets is exceptional. I am looking forward to sharing further data and updates as we look to select our clinical candidates for TEAD and SMARCA next year."

Amphista plans to present data from its TEAD Targeted Glue program at a key forthcoming TPD scientific conference.

This news on Amphista’s TEAD Targeted Glue program follows an announcement by the Company on 17 September 2025, which disclosed first data on its SMARCA2 program including demonstrating exquisite selectivity of its sequentially bifunctional Targeted Glues for SMARCA2 over the closely related homolog, SMARCA4.

U.S. Food and Drug Administration Authorizes CytoCell KMT2A Breakapart FISH Probe Kit PDx as a New Companion Diagnostic for KMT2A rearranged Acute Leukaemia

On September 22, 2025 OGT, a leading global provider of genomic diagnostic and research solutions, reported that the U.S. Food and Drug Administration (FDA) has granted their De Novo Classification Request for the CytoCell KMT2A Breakapart FISH Probe Kit PDx as a companion diagnostic (CDx) for Syndax’s first-in-class menin inhibitor, REVUFORJ (revumenib) (Press release, Sysmex, SEP 22, 2025, View Source [SID1234656163]). Revuforj is FDA approved for the treatment of relapsed or refractory (R/R) acute leukaemia with a lysine methyltransferase 2A gene (KMT2A) translocation in adult and paediatric patients one year and older.

OGT’s CytoCell KMT2A Breakapart FISH Probe Kit PDx detects clinically relevant rearrangements that occur in patients with acute leukaemia, providing a robust, accessible, rapid turnaround test for KMT2Ar detection that will maximize the ability for clinicians to quickly identify patients who may be eligible for treatment with Revuforj. It is estimated that more than 95% of patients with KMT2Ar acute leukaemia have a KMT2A translocation, a type of rearrangement that occurs when part of one chromosome breaks and fuses to a different chromosome.

"We are delighted that our CytoCell KMT2A Breakapart FISH Probe Kit PDx has received marketing authorization as a CDx for Revuforj." said Dr. Leila Luheshi, VP of Pharma Partnering at OGT. "The development and subsequent authorization of this new CDx is an important demonstration of the skill and commitment of our clinical scientists and regulatory specialists to deliver safe and effective diagnostics for patients with one of the most devastating forms of leukaemia."

Steve Chatters, OGT’s EVP of Regulatory and Medical Affairs noted "Our strong foundation in haematology diagnostics has been a key factor in our success bringing the KMT2Ar CDx to market as a Class II device, as opposed to the more common Class III classification for companion diagnostics. We have decades of experience developing regulated FISH products, gained from our prior development of IVDR-certified and FDA-cleared FISH probes. Combined with our extensive customer partnerships in haematology labs in the USA, we have refined insights into the application of these products and are able to access a wealth of real-world data across a multitude of clinical and analytical factors, which is invaluable for product development. This is a core pillar of our success."

The emergence of precision therapies, such as the menin inhibitor Revuforj (an oral inhibitor of the menin–KMT2A interaction), offers new avenues for potentially improving outcomes for patients with these challenging acute leukaemia cases.

"Accurately identifying acute leukaemia patients with KMT2Ar is a key factor in selecting appropriate therapeutic options for a group of patients who have traditionally had a very poor prognosis" said Adrian Smith, CEO of OGT. "We are optimistic that the authorization of OGT’s CDx will help this underserved patient group benefit from developments in precision oncology."