Susannah Rodgers

The UK startup Duke Street Bio has exited stealth mode with funding to develop PARP enzyme inhibitors that treat cancer by blocking the repair of DNA in tumor cells. London-based Duke Street Bio said Tuesday that it has a portfolio of PARP1 and PARP7 enzyme inhibitors and has raised enough cash to fund its pipeline into clinical studies. The company aims to deliver next-generation cancer therapies based on DNA damage repair (DDR) and immuno-oncology and claims to have made rapid development progress. It has several drug discovery programs targeting the key enzymes that control DDR and immune system activation. Poly (ADP-ribose) polymerases, or PARPs, are a type of enzyme that helps repair DNA damage in cells. PARP inhibitors work by preventing cancer cells from carrying out vital DNA repairs inside the cell. Duke Street Bio was founded in 2020 by the management team behind the Scottish firm IOmet Pharma. IOmet Pharma, which developed medicines for cancer with a focus on immunotherapy and metabolism, went on to be bought by US-based MSD in 2016. “We focused on immuno-oncology at IOmet and it made sense to continue that with Duke Street,” Alan Wise, Duke Street Bio chief executive and co-founder, told us. “And then we’ve got involved in the DNA damage repair space as well. There’s a lot of connectivity between DDR and immuno-oncology. There’s a lot of emerging evidence to show that deficiencies or genetic vulnerabilities in DDR can impact very positively on orchestrating an immune response.” While marketed DDR and immuno-oncology therapies only work in limited patient populations, the molecules Duke Street Bio is developing could significantly expand the number of patients that could benefit from these types of treatment approaches, he said. The startup’s DDR program targets PARP1, an enzyme that’s essential for initiating various forms for DNA repair and which has been clinically verified. The company says its second-generation approach means it can deliver safer therapeutics that can be used in combination with chemotherapies and targeted agents. The immuno-oncology program targets PARP7, an enzyme that has recently emerged as a key regulator of the immune system in the tumor microenvironment. Inhibitors of PARP7 can create a hostile immune environment to the cancer that enables tumor targeting and elimination. Duke Street Bio’s goal is to reprogram the cancer cell and tumor microenvironment biology to harness the natural power of the body’s immune system to fight cancer. “There is significant therapeutic opportunity in further exploration of the cellular signaling pathways controlled by the PARP family of enzymes,” said Elliott Sigal, advisor to Duke Street Bio and former chief scientific officer and president of research and development at Bristol Myers Squibb. Additional programs focused on related enzymes are at the validation phase, the company said. The startup has a similar hybrid business model to that of IOmet Pharma, with a small internal team and the outsourcing of experimental work to contract research organizations around the world, some of which the team has worked with for over a decade. “We’ve got the track record so fundraising has been relatively straightforward,” Peter Trill, chairman and co-founder of Duke Street Bio, told us. Other companies researching cancer therapies based on DNA repair include Artios, which is developing DNA damage response inhibitors and raised €129M in a Series C funding round last year. Breakpoint Therapeutics, a spinoff from German biotech Evotec, aims to develop drugs that kill cancer cells by sabotaging their DNA repair machinery. Meanwhile, Paris-based Onxeo is trialing a cancer treatment that interferes with DNA repair mechanisms.

Susannah Rodgers

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