Breakpoint Therapeutics

Breakpoint Therapeutics GmbH operates as a preclinical-stage biotechnology company focused on developing oncology drugs that target the DNA Damage Response (DDR) in cancer cells. The company was established in July 2019 as a spin-off from the German contract research organization Evotec SE. This strategic formation was designed to accelerate the development of Evotec's promising DDR portfolio. The company launched with a significant Series A financing of €30 million ($33.6 million) from a consortium of investors including Evotec, the life sciences investment firm Medicxi, and Taiho Ventures, the corporate venture capital arm of Taiho Pharmaceutical.

The company was co-founded by Dr. Daniel Speidel and Dr. Jon Hollick, who both serve as Managing Directors. Dr. Speidel contributes over two decades of experience in molecular oncology research with a specialization in DNA damage responses and previously led the initiative at Evotec to spin off the DDR projects into an independent entity. Dr. Hollick brings more than 20 years of experience in oncology research and drug discovery, having previously managed many of Evotec's oncology drug discovery partnerships and established the DDR project portfolio. His doctoral work at Newcastle University, in collaboration with KuDOS Pharmaceuticals (now part of AstraZeneca), focused on the discovery of DNA repair enzyme inhibitors.

Breakpoint Therapeutics' business model is centered on the discovery and preclinical development of first-in-class drugs that interfere with DNA repair and replication stress pathways. The company operates in a highly virtual setup, leveraging Evotec's established and industrialized research and development platforms to maintain capital efficiency and flexibility. Its primary objective is to develop therapies for cancer patients who are resistant to existing treatments. By modulating DDR pathways, the company aims to create drugs that selectively kill cancer cells while minimizing harm to healthy tissue, thus addressing a significant unmet medical need.

The company's therapeutic pipeline is focused on developing inhibitors for two key oncology targets: DNA Polymerase theta (Polθ or POLQ) and Werner Syndrome Helicase (WRN). These targets are critical for the survival of certain cancer cells, particularly those with existing defects in primary DNA repair pathways. For instance, Polθ is overexpressed in many cancers and is a crucial component of a repair pathway used by cancer cells when primary repair mechanisms fail. WRN helicase is essential for the survival of cancer cells exhibiting microsatellite instability (MSI-high), a characteristic found in several hard-to-treat cancers like colorectal cancer. In March 2024, Breakpoint announced the nomination of its first preclinical development candidate, BTX-011, a potent and selective oral inhibitor of Polθ, for which IND-enabling studies have commenced. This candidate has shown significant efficacy in preclinical models, especially when combined with standard-of-care PARP inhibitors.

Keywords: DNA Damage Response, DDR inhibitors, oncology therapeutics, cancer treatment, precision oncology, PolQ inhibitors, WRN helicase inhibitors, preclinical stage, Evotec spin-off, DNA repair pathways, targeted therapy, therapy-resistant cancers, synthetic lethality, molecular oncology, drug discovery, biotechnology, pharmaceutical development, cancer research, solid tumors, small molecule drugs