Boundless Bio raises $100m for circular DNA cancer therapy

Zachary Hornby of Boundless Bio
Boundless Bio

Zachary Hornby, Boundless Bio's CEO

Boundless Bio’s plans to develop a new class of cancer therapies targeting DNA found outside the nucleus of malignant cells have been boosted by a $100 million fundraising round, co-led by the venture capital arm of Bayer and RA Capital Management.

Extrachromosomal circular DNA (ecDNA) occurs frequently across many cancer types, and while they have been known about for decades, Boundless Bio claims it is the first company to bring a therapy specifically targeting ecDNA into clinical testing.

The San Diego biotech will use the cash injection to finance its ongoing phase 1/2 trial of lead candidate BBI-335 and bring forward other small-molecule therapies targeting ecDNA.

The loops of DNA are formed when pieces of DNA break off from chromosomes, and are normally absent from healthy cells. Some are highly associated with cancer and are known as oncogenic elements – in other words they activate cancer cells – and are associated with shorter survival for patients. Studies also suggest that they promote variation in tumour cells that could protect the cancer from the effects of treatment.

Boundless Bio recently started dosing with BBI-335 in its first clinical trial, called POTENTIATE, which is recruiting patients with a range of oncogene-amplified cancers, including liposarcomas as well as lung, oesophageal, gastric, breast, bladder, ovarian, and endometrial tumours.

One common feature of oncogene-amplified tumours is that their cells tend to be under high levels of DNA replication stress, making them genomically unstable, but also less likely to die off as a result of their mutations. ecDNAs are thought to be involved in maintaining the ‘fitness’ of cancer cells.

BBI-335 inhibits checkpoint kinase 1 (CHK1), an enzyme that Boundless Bio thinks is pivotal in allowing the cells to survive in the face of replication stress. Other checkpoint kinases that could also be targeted in this way include ATR, WEE1, and MYT1, some of which already have inhibitors in clinical development.

The first of a target 47 patients in POTENTIATE started taking BBI-335 earlier this month, with a main readout expected at the start of 2025.

Juergen Eckhardt, head of the Leaps by Bayer VC unit, said the decision to back Boundless Bio came from its desire to support “fundamental breakthroughs in healthcare.”

“The ability to address oncogene amplified cancers has remained one of the industry’s greatest challenges in the treatment of cancer,” he added.

Boundless Bio estimates that around 25% of all cancers have oncogene amplifications, which translates to more than 400,000 newly-diagnosed cancers each year in the US alone.

The Series C funding brings the total raised by Boundless Bio to $250 million since it was founded in 2018. Fabio Pucci of Leaps by Bayer is joining its board of directors following the round.