DCAF16

-PLX-61639, a selective, oral SMARCA2 degrader, demonstrated sustained PD response and single-agent efficacy in SMARCA4 mutant tumors; program is advancing through IND-enabling studies- -PLX-4545, a selective IKZF2 molecular glue degrader, completely degraded IKZF2 across a range of well-tolerated doses in Phase 1, resulting in a shift from Treg to an effector-like T cell phenotype- -Preclinical data was presented on its CDK2 selective molecular glue degrader, which exhibited superior selectivity over inhibitor-based approaches; program is targeting CCNE1 amplified cancers- SAN DIEGO, April 28, 2025 /PRNewswire/ -- Plexium, Inc. (Plexium), a leading next-generation targeted protein degradation company, announced today multiple presentations with the Company's selective monovalent degrader programs for SMARCA2, IKZF2 and CDK2 at the 2025 American Association for Cancer Research (AACR) Annual Meeting, taking place April 25-30, 2025, in Chicago, IL. "These data highlight the clinical and preclinical progress we've made across our portfolio, including the use of a novel E3 ligase DCAF16, in our SMARCA2 program—an industry first that reinforces the differentiated potential of our monovalent degrader platform," said Jorge F. DiMartino, MD, PhD, Chief Medical Officer at Plexium. "We are also excited to share initial clinical data from PLX-4545, which demonstrated clinical proof of mechanism and intended pharmacological immunophenotypic effects." Oral Presentation Details: Title: "Discovery and characterization of novel, potent and selective CDK2 molecular glue degrader against CCNE1-amplified tumors" Session: MS.ET09.01 – Degraders and Glues Abstract Number: 6375 Date and Time: April 29, 2:55 PM – 3:10 PM Presenting Author: Leenus Martin, PhD Title: "PLX-4545, a selective IKZF2 degrader, reprograms suppressive Tregs leading to tumor growth inhibition and combination benefit with immune checkpoint therapy" Session: MS.ET09.01 – Degraders and Glues Abstract Number: 6380 Date and Time: April 29, 4:10 PM – 4:25 PM Presenting Author: Peggy Thompson, PhD Poster Presentation Highlights: Title: "Mechanistic characterization of selective monovalent direct degraders of SMARCA2″ Session: PO.ET09.04 – Degraders and Glues 1 Abstract Number: 404 Section: 18 Date and Time: April 27, 2025, 2:00 PM – 5:00 PM Presenting Author: Julia Toth, PhD Plexium's SMARCA2 degraders function by bromodomain binding and covalent modification A CRISPR knockout screen identified DCAF16 as being required for PLX-61639 mediated SMARCA2 degradation MOA studies demonstrate PLX-61639-mediated SMARCA2:DCAF16 protein interactions and the requirement of covalent binding to a specific DCAF16 cysteine to support a stable ternary complex and subsequent SMARCA2 degradation Title: "Preclinical characterization of PLX-61639, a potent and orally bioavailable SMARCA2-selective monovalent direct degrader" Session: PO.ET09.10 – Degraders and Glues 2 Abstract Number: 1653 Section: 18 Date and Time: April 28, 2025, 9:00 AM – 12:00 PM Presenting Author: Gregory Parker, PhD Plexium has designed PLX-61639, a potent and selective direct degrader of SMARCA2, and nominated it as a development candidate Daily oral dosing of PLX-61639 results in deep and sustained SMARCA2 degradation, eliciting robust tumor growth inhibition and regression in SM4mut CDX and PDX models, no tumor growth inhibition is observed in a control SM4wt CDX model PLX-61639 is currently advancing through IND-enabling studies Title: "A first in human trial of PLX-4545, a molecular glue degrader of IKZF2, in healthy volunteers, shows pharmacologic modulation of Tregs at well-tolerated doses" Session Title: PO.CT01.02. First-in-Human Phase I Clinical Trials 2 Abstract Number: CT150 Section: 48 Date and Time: April 29, 2025, 9:00 AM – 12 PM Presenting Author: Jorge DiMartino, MD, PhD PLX-4545 an oral, CRBN molecular glue degrader of IKZF2, a lineage-defining transcription factor for Tregs was tested in healthy adult volunteers With repeated daily dosing for 14 days, all dose levels achieved complete degradation of IKZF2 in PBMCs by Day 2 leading to conversion of Tregs into effector-like T cells and an increase in activated T effector cells TEAEs were mostly Grade 1 or 2 (mild or moderate) in severity and no Dose Limiting Toxicities were encountered. All AEs were reversible with discontinuation of dosing The AACR 2025 posters will be made available on the Plexium website. About Plexium Inc. Plexium is the premier, next-generation Targeted Protein Degradation (TPD) company seeking to discover a wide range of monovalent degraders that address the limitations of first-generation heterobifunctional degraders. The company is powered by its proprietary AI-integrated ultra-high-throughput phenotypic drug discovery platform technologies that have enabled the identification of novel small molecules that induce E3 ligase mediated selective degradation of target proteins. From molecular glues to direct degraders, Plexium is advancing a pipeline of novel monovalent targeted protein degraders for the treatment of cancer, neurodegeneration, and other diseases. For more information, visit and engage with us on LinkedIn. Plexium Investor and Media Contact: Amy Conrad Juniper Point [email protected] 858-366-3243 SOURCE Plexium WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

PRESS RELEASE Amphista Therapeutics unveils new differentiated mechanism of action for BRD9 degradation at 2024 Protein Degradation in Focus Symposium First presentation of a novel mechanism of action for the degradation of BRD9 – completely differentiated from cereblon- or VHL-based PROTACs Amphista’s bifunctional BRD9 degraders selectively induce BRD9 to DCAF16 proximity and serve as molecular glues, leading to strong and rapid degradation of BRD9 Discovery further underscores Amphista’s proprietary chemistry and high-quality science which is being applied to the discovery and development of additional targeted glues beyond BRD9 Cambridge, UK, May 23, 2024 – Amphista Therapeutics (“Amphista”), a leader in next generation targeted protein degradation (TPD) approaches, today announces the unveiling of a new mechanism of action for the degradation of BRD9, an emerging target in oncology, that is differentiated from cereblon- or VHL-based PROTACs, during an oral presentation at the 2024 Protein Degradation in Focus Symposium held in Dundee, UK. This significant news for the TPD field builds upon an earlier announcement by Amphista of two compelling data sets demonstrating in vivo efficacy and central nervous system (CNS) activity of its mechanistically differentiated protein degraders. At today’s presentation titled “Degradation of BRD9 by a novel targeted glue”, Dr Andrea Testa, Scientific Co-Founder and Senior Director, Discovery Chemistry showed data from proteomic and genetic validation studies which demonstrate that Amphista’s bifunctional degraders induced degradation of BRD9 by target-assisted E3 ligase recruitment. This novel mechanism selectively induces the proximity of BRD9 to DCAF16 and serves as a molecular glue. DCAF16 is a cullin-RING E3 ligase which can facilitate degradation of proteins of interest via ternary complex formation. Induction of this complex leads to deep and rapid degradation of BRD9 in vivo. Louise Modis, Chief Scientific Officer of Amphista Therapeutics, said: “The discovery of a novel mechanism for BRD9 degradation, differentiated from cereblon- or VHL-based PROTACs, is a testament to Amphista’s proprietary chemistry and know-how. Our ability to translate this novel approach into high-quality, drug-like compounds with oral bioavailability and activity in vivo is truly exciting. As we continue to spearhead our efforts to advance new TPD approaches, our goal remains clear – to expand the offering of TPD medicines beyond CRBN and VHL-based agents and bring effective treatments to patients in areas of high unmet need.” In the results presented, Amphista’s sub-nanomolar BRD9 degraders showed activity in both solid and liquid cancer cell lines and demonstrated a high degree of selectivity over 8,000 proteins quantified by proteomics, including the closely related proteins BRD7 and BRD4. Notably, these compounds induced BRD9 degradation in a mouse xenograft model illustrating Amphista’s BRD9 degraders are orally bioavailable and active in vivo. This is the first-time in vivo degradation of BRD9 has been demonstrated via DCAF16, underscoring the potential therapeutic application of Amphista’s bifunctional degraders. Building on this knowledge, Amphista is applying its proprietary scientific know-how and expertise to the development of targeted glues which induce degradation of different targets, expanding the opportunity beyond BRD9. Future announcements will provide details of additional pipeline targets as part of Amphista’s ambitions to develop a first- and/or best-in-class portfolio of degraders with leading physicochemical properties. About Amphista Therapeutics Amphista Therapeutics is focused on transforming the lives of patients with severe diseases, including cancer and neurodegenerative disease, through the advancement of next generation targeted protein degradation (TPD) medicines. Amphista is applying its proprietary warhead chemistry and mechanistic know-how to generate bifunctional targeted glues with a differentiated mechanism and leading physicochemical properties. Its portfolio offers the potential for first- and/or best-in-class assets and expanding the offering of TPD medicines beyond CRBN and VHL-based agents. Founded by Advent Life Sciences, Amphista is a spin-out of TPD expert Professor Alessio Ciulli’s laboratories at the University of Dundee. Amphista is funded by leading life science investors including Forbion, Gilde Healthcare, Novartis Venture Fund, Advent Life Sciences, Eli Lilly & Company and The Dementia Discovery Fund, and also has strategic collaborations with Bristol Myers Squibb and Merck. For more information, please visit: Amphista and the Amphista logo are all trademarks or registered trademarks of Amphista Therapeutics Limited. For more information please contact: ICR Consilium Amber Fennell, Namrata Taak Email: Amphista@consilium-comms.com Tel: +44 (0)20 3709 5813