A pipeline of Targeted Glue^™ 
degrader medicines to benefit patients

AMX-883 is a potent, selective, orally bioavailable Targeted Glue™ degrader of BRD9 designed to benefit patients with Acute Myeloid Leukemia (AML).

AML is characterized by the clonal expansion of myeloid progenitors blocked at various stages of their differentiation process. Targeted therapies able to induce differentiation have shown clinical efficacy in limited AML subtypes. Degradation of BRD9 by AMX-883 releases differentiation block in a broad AML population.

AMX-883 has demonstrated robust in vivo efficacy as a monotherapy in a diverse panel of AML models and shows synergistic efficacy in combination with venetoclax. AMX-883 regulates known markers of venetoclax resistance and prevents emergence of resistance to venetoclax in long term culture models indicating potential for durable clinical responses. AMX-883 has received FDA clearance of IND application for its clinical evaluation as the first BRD9 targeted therapy for AML.

Amphista is developing an orally bioavailable, selective SMARCA2 Targeted Glue™ degrader, targeting tumors with loss-of-function SMARCA4 mutations, including Non-Small Cell Lung Cancer (NSCLC).

SMARCA2 and SMARCA4 are functionally redundant catalytic subunits of the BAF chromatin remodelling complex. In tumors harbouring SMARCA4 loss-of-function mutations, cells become dependent on SMARCA2 for BAF complex function and survival. SMARCA4 mutations occur in approximately 5% of solid tumors and up to 10% of NSCLC, creating a vulnerability that selective SMARCA2 degradation can exploit through synthetic lethality, with a favourable therapeutic index over SMARCA4-expressing normal tissue.

Amphista’s SMARCA2 degraders act through a novel DCAF16-mediated mechanism, and deliver class leading selectivity over SMARCA4. Our degraders have demonstrated deep in vivo SMARCA2 degradation following oral dosing.

Amphista is developing an orally bioavailable pan-TEAD Targeted Glue™ degrader, targeting Hippo pathway-driven cancers including mesothelioma and combination strategies for Non Small Cell Lung Cancer (NSCLC).

TEAD transcription factors are critical effectors of the Hippo signalling pathway, regulating gene transcription when bound to coactivators YAP and TAZ. Hippo pathway dysregulation leads to increased TEAD target gene transcription, driving tumorigenesis in solid tumors such as mesothelioma, and underpinning resistance mechanisms in NSCLC.

Amphista’s TEAD degraders act through a novel FBXO22-mediated mechanism, delivering best-in-class pharmacology with deep and rapid target degradation and robust in vivo oral efficacy in a mesothelioma xenograft model. The degradation-based modality, combined with TEAD’s long half-life, results in extended pharmacodynamic effects enabling an efficacious once-every-three-day in vivo dosing schedule.

Read more about the rational and systematic optimization of our early TEAD Targeted Glues here: https://www.biorxiv.org/content/10.64898/2026.04.21.719895v1.full

Amphista is developing orally bioavailable KRAS G12D selective and pan KRAS Targeted Glue™ degraders to treat KRAS mutant cancers including Pancreatic cancer (PDAC) and Non Small Cell Lung Cancer (NSCLC).

Amphista is developing orally bioavailable, selective HDAC6 Targeted Glue™ degraders for use in multiple indications.