Breakpoint Therapeutics sabotages DNA repair in cancer cells

November 2, 2022 - 4 minutes

The Hamburg-based Evotec spinout Breakpoint Therapeutics is working on cancer treatments that block the ability of tumor cells to repair their own DNA.

In the last decade, a new class of drugs known as DNA damage response (DDR) inhibitors has risen to prominence in the oncology space. These drugs are able to break down the way cells repair their own DNA. 

In the case of tumor cells that are already impaired with mutations in their DNA repair machinery, this strategy can quickly kill the tumor. However, current DDR drugs can only affect a limited range of cancer cells with the relevant mutation.

“The promise of DDR inhibition is that you exploit a specific type of defect in cancer cells,” said Daniel Speidel, co-managing director of the German firm Breakpoint Therapeutics. “It’s really precision oncology.”

Since the approval of the first-in-class drug Lynparza for the treatment of types of breast and ovarian cancer in 2014, the field has become hot. Many firms are hunting for new DDR targets that can widen the range of cancers that can be treated with DDR blockers.

Breakpoint Therapeutics originated as a project at the German contract research giant Evotec, and was spun out in 2019 to allow its team to focus more on DDR drug discovery. Speidel originated from an academic background and joined up to co-lead the company’s efforts.

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“We ended up finding good investors and forming an independent company,” recalled Speidel. Though Evotec is a parent company of Breakpoint, there are no option rights or other strings attached to Breakpoint’s business model.

At present, Breakpoint is focusing its drug discovery efforts on DDR targets called polymerase theta (Pol theta) and Werner helicase, which are present in a wide range of mutated cancer cells. For example, targeting Werner helicase could allow the firm to place its crosshairs on colorectal cancer, which is a big challenge for cancer therapies.

“There are very many people suffering from colorectal cancer,” said Speidel. “Treatment options are there, especially checkpoint inhibitors, but around 50% [of patients] don’t respond. And we don’t really know why.”

Both Pol theta and Werner helicase are hot DDR targets. For example, the U.K. firm Artios Pharma is taking a Pol theta blocker into clinical trials. However, Breakpoint aims to produce best-in-class candidates, not necessarily the first.

According to Speidel, the targets the company selected are a major challenge to work with. Research into Werner helicase, for example, can require a lot of patience and experience when screening to minimize errors that can impact drug development at a later stage.

“If you’re too low in budget and you’re anxious at the beginning, you end up in trouble later on,” added Speidel. Therefore, the backing of Evotec allows the company to explore these DDR targets more thoroughly than many competitors.

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Another obstacle in DDR drug discovery is teasing out the intricate DNA repair mechanisms at play in cancer cells, which can be very adaptable to resist treatments.

To fund its drug development, Breakpoint raised €30 million ($33 million) when it launched in 2019. The firm doesn’t need to hunt for funding at the moment and is keeping its secrets regarding when it aims to progress to clinical trials. 

“DDR companies have suffered by giving out timelines and not holding to them,” said Speidel. “So I will not try to do that.”

Now that the maturing DDR space has its success stories in the form of drugs like Lynparza, the field is attracting attention from big pharma companies and investors. Speidel sees a DDR target called ATR as one of the next success stories in the field.

“It’s very satisfying to us that this turned out to be not a crazy idea of some science nerds,” concluded Speidel. “It’s really working for patients in the clinic.”

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