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Protein degradation / PROTAC · Industry updates

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Amphista Therapeutics / Business Wire

Amphista previews BRD9 degradation findings and BRAMLIE trial design at ASH

Amphista announced an ASH oral presentation on AMX-883-mediated BRD9 degradation, describing disruption of hematopoietic transcriptional programs, myeloid differentiation, and reduced leukemic stem-cell frequency in experimental work. A separate abstract outlines the ongoing Phase 1 BRAMLIE study in AML and high-risk myelodysplastic syndrome. The announcement does not establish clinical efficacy for AMX-883.

Proceedings of the National Academy of Sciences / PubMed

Bispecific protein drives dual receptor degradation in mouse eye-disease models

A PNAS study reports RHV, a tetravalent bispecific protein designed to internalize and lysosomally degrade VCAM-1 and VEGFR on pathological vessels. The original abstract describes activity in mouse choroidal neovascularization models, including efficacy comparable to aflibercept at one-quarter of the molar dose. This is preclinical extracellular receptor degradation, distinct from an intracellular small-molecule PROTAC.

C4 Therapeutics

C4 Therapeutics expands target-first DEL capabilities for molecular glue discovery

C4 Therapeutics described a DNA-encoded library that incorporates its cereblon-binding ligand collection for target-first molecular glue discovery. The company reported known and novel VAV1 degrader hits as platform validation, while stating that it would not advance VAV1 without a partner. This is a discovery-platform update, not the clinical entry of a new drug candidate.

Monte Rosa Therapeutics

Novartis starts a second Phase 2 trial of VAV1 degrader MRT-6160

Monte Rosa announced that Novartis initiated a second Phase 2 study of the VAV1 molecular glue degrader MRT-6160, also called DDY391, in active moderate to severe psoriatic arthritis. The randomized, double-blind, placebo-controlled trial will assess efficacy, safety, tolerability, and dose response. The first patient visit triggers a $37.5 million milestone payment.

npj Drug Discovery

MAGEA11 recruitment enables selective BET degradation in cancer cell models

Researchers developed BET-targeting PROTACs that recruit the tissue-restricted scaffolding protein MAGEA11 rather than relying on widely expressed ligases. Lead compound 105B degraded BET proteins in two cancer cell lines but not in HEK293T cells. Mechanistic experiments implicated MAGEA11 and HUWE1. The authors emphasized that further optimization is needed to produce selective cytotoxicity.

Insilico Medicine

Insilico nominates peripheral VAV1 molecular glue degrader ISM9546

Insilico Medicine nominated ISM9546 as a preclinical candidate for autoimmune diseases, including inflammatory bowel disease and rheumatoid arthritis. The company described an orally available, peripherally restricted VAV1 molecular glue degrader, reporting cellular degradation activity and anti-inflammatory effects in disease models. Its limited brain exposure is a design feature; human safety and efficacy have not been established.

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