Boehringer Ingelheim has slipped another piece of its oncology R&D strategy into place, partnering with Tessellate Bio on a synthetic lethal program in a deal worth more than 500 million euros ($570 million) in biobucks.
European biotech Tessellate exited stealth in 2023 with a focus on novel synthetic lethality approaches. PARP inhibitors have shown the potential to shrink tumors by targeting pairs of genes that are essential for the survival of cancer cells. Companies including AstraZeneca and Merck KGaA are studying forms of synthetic lethality beyond the homologous recombination deficiency pathway targeted by PARP drugs.
Tessellate has found a largely unclaimed piece of territory, namely tumors that depend on alternative lengthening of telomeres (ALT) for their growth. About 10% to 15% of cancers rely on ALT, according to the biotech. ALT-positive tumors are associated with poor prognosis and a lack of targeted therapies.
Boehringer is paying an upfront fee, of publicly undisclosed size, for global rights to the ALT program. Once milestones and other fees are factored in, the value of the agreement could swell to more than 500 million euros.
Telomeres, the caps at the ends of chromosomes, shorten with each cell division and limit the life span of cells. Some cancers, including many sarcomas, gliomas and neuroepithelial tumors, use ALT to maintain telomere length. Tumors’ reliance on ALT creates opportunities to selectively kill cancer cells by targeting the mechanism.
Tessellate said it has developed inhibitors of an undisclosed target that helps enable uncontrolled growth of ALT-positive cancer cells. Blocking the target drives DNA damage, replication stress and cell death, the biotech said. When it exited stealth, Tessellate said its lead ALT program targeted the FANCM protein complex. Studies have shown FANCM suppresses DNA replication stress at ALT telomeres.
Artios Pharma, another European biotech, has a discovery-stage ALT program, but the industry’s efforts to expand synthetic lethality have largely focused on other pathways to date. AstraZeneca, which helped put PARP inhibitors on the map, is running trials of drug candidates that hit targets including ATR. Other targets include WEE1, USP1 and POLθ.