Our science is transforming the development of TPD therapeutics
Targeted Protein Degradation
Unlike traditional therapies that transiently inhibit a single function of a protein associated with disease onset or progression, targeted protein degradation (TPD) medicines are designed to use the cell’s natural waste disposal system to selectively target and remove pathogenic proteins completely from the body.
Targeted Glues®– Next Generation TPD Technology
Based on the ground-breaking science of TPD leader Alessio Ciulli of Dundee University, Amphista is pioneering the next generation of TPD technology, which works through a completely novel mechanism and doesn’t rely on cereblon or VHL, which were commonly used in first generation approaches. We have developed a curated set of unique, patented AMPX TPD warheads which work as Targeted Glues®.
Amphista’s Targeted Glues® are rationally designed through a chemistry-first approach. They offer significant advantages over first generation approaches including class-leading physiochemical properties, which enable broader cell and tissue reach coupled with excellent drug-like and in vivo properties. Oral bioavailability is routinely achieved, and our warheads are inherently brain penetrant, which means we can degrade proteins deep within the CNS in vivo.
Our Team, Capabilities and Approach
We have brought together an multidisciplinary team of experts who have built deep scientific know-how and a broad suite of capabilities to guide the discovery and development of our novel protein degraders. We are structurally enabled and use cutting-edge high-content, multiplexed assay technologies to rapidly advance our programs. We leverage advanced data analytics, including AI-ML, and computational modelling to aid our understanding. Our Bioinformatics, Computational Chemists and Cheminformatics teams work closely to unlock unique insights from across internal and external datasets, enabling us to target the right structurally optimized molecules to the right patient populations.
Our projects
We are developing category-leading degrader therapeutics against important disease targets which have clear genetic or clinical relevance in patient populations of high unmet need.
Name
Indication:
Acute Myeloid Leukaemia (AML)
Target rationale:
BRD9, as part of the ncBAF chromatin remodelling complex, plays a crucial role in halting the normal differentiation of myeloid precursor cells into healthy blood cells, the accumulation of undifferentiated leukemic blasts and the maintenance of Acute Myeloid Leukemia. We believe that selective degradation of BRD9 will lead to a significant reduction in leukemic burden and promote recovery of normal blood cell counts in AML patients. We are developing an oral, highly selective degrader of BRD9.
Indication:
Non-Small Cell Lung Cancer (NSCLC) with the potential to treat CNS metastasis
Target rationale:
Selective degradation of SMARCA2 (BRM), a component of the BAF chromatin remodelling complex, will lead to cell death in tumors carrying deleterious mutations in SMARCA4 (BRG1). This will lead to disease regression and clinical benefit for patients whose tumors carry these mutations. SMARCA4 deleterious mutations are found in about 5% of solid tumors generally and up to 10% of Non-Small Cell Lung Cancer. We are developing an oral, SMARCA2 selective degrader, with the potential for CNS penetration.
Indication:
Solid Tumours
Target rationale:
We are developing oral, selective Targeted Glues® against high value targets.
Indication:
Solid Tumours
Target rationale:
We are developing oral, selective Targeted Glues® against high value targets.
Indication:
Neurodegeneration
Target rationale:
We are developing oral, CNS penetrant, Targeted Glues against targets with a high degree of genetic validation in Neurodegeneration.