Debio 0432 is a small molecule deubiquitinating enzyme (DUB) designed to target several types of tumours by targeting USP1. Credit: Alexander Raths via Shutterstock.

Ubiquigent and Debiopharm have teamed up to support the development of Debiopharm’s ubiquitin-specific protease 1 (USP1) inhibitor programme, Debio 0432. 

Currently in late-stage preclinical development, Debio 0432 is a small molecule deubiquitinating enzyme (DUB) designed to target several types of tumours by targeting USP1, an important player in DNA damage repair. Through its potent and selective inhibition of USP, Debio 0432 is believed to cause synthetic lethality in tumours with faulty DNA repair genes such as BCRA1. 

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Debiopharm obtained global rights to the USP1 inhibitor from Novo Nordisk in March 2023. Debio 0432 was originally developed by Forma Therapeutics, which was acquired by Novo Nordisk in 2022. 

Under the agreement, Ubiquigent will deploy its DUB-focused platform and knowledge of the DUB field to develop target engagement assays, supporting Debio 0432’s journey to the clinic. 

DUBs are proteins that regulate the degradation of other proteins in cells by removing ubiquitin molecules. In cancer, DUBs often become dysregulated, leading to abnormal levels of key proteins involved in cell growth, proliferation, and survival. This dysregulation can promote tumour development and progression by affecting DNA repair, cell cycle regulation, and apoptosis. 

Debiopharm isn’t the only company developing DUB inhibitors. Earlier this year, Tango Therapeutics dosed the first patient in the Phase I/II clinical trial investigating its USP1 inhibitor TNG348. The study (NCT06065059) will evaluate the safety, tolerability, and preliminary antitumour activity of TNG348 alone, and in combination with AstraZeneca’s PARP inhibitor Lynparza (olaparib) in 140 patients with BRCA1/2 mutant or homologous recombination deficiency (HRD)+ solid tumours. 

In December 2023, the US Food and Drug Administration (FDA) cleared UK-based Mission Therapeutics’s investigational new drug (IND) application for its DUB inhibitor, MTX652, to treat acute kidney injury (AKI). In 2018, the company collaborated with pharma giant AbbVie for the research and preclinical development of DUB therapies to treat Alzheimer’s and Parkinson’s disease. 

In the announcement accompanying the agreement, Debiopharm’s CEO Bertrand Ducrey said: “Ubiquigent’s specialised drug discovery platform is uniquely positioned to support our USP1 inhibitor programme as it approaches the clinic, enabling the development of novel target engagement assays.  

“Selective inhibition of USP1 to interrupt DNA damage repair pathway is an exciting approach to cancer treatment.”