San Diego-based biotech KymaThera has banked $80m in a Series B funding round to bring a breast cancer drug to clinic that it claims may overcome the challenges linked to current PI3Kα-targeting therapies such as Roche’s Itovebi (inavolisib).
Through this financing, which was led by Alta Partners and contributed to by Foresite Capital, Venrock, J. Wood Capital and other investors, KymaThera will bring its oral, selective pan-mutant PI3Kα inhibitor, K-1728, into Phase I trials in HR-positive, HER2-negative breast cancer and PI3Kα-driven vascular malformations. This financing follows a $20m Series A raise.
During this early-stage study, KymaThera will assess the potential of K-1728 as both a monotherapy and in combination with other agents in breast cancer, while evaluating the drug’s standalone promise in PI3Kα-driven vascular malformations.
With cash in hand, KymaThera plans to set the wheels in motion for its Phase I trial, with the company planning to begin dosing patients in the final quarter of 2026.
KymaThera progresses K-1728 with the hope that it can overcome the traditional challenges linked to successfully drugging PI3Kα – a well-validated, but complex oncology target. With this goal in mind, the biotech designed K-1728 to be selective to all mutant forms of PI3Kα, which the company says could result in the drug being both less toxic and more able to target all PI3Kα mutations that drive tumour growth.
According to KymaThera, K-1728 has already shown promise in achieving these outcomes in both preclinical and IND-enabling studies. When testing the drug in models with relevant kinase and helical domain PI3Kα, the biotech found that a once-daily dose of the drug was able to potently inhibit both types of mutation. On top of this, K-1728 also showed early signs of maintaining a wide preclinical therapeutic window.
By employing a pan-mutant mechanism, KymaThera is hoping to progress a therapy with differential potential to currently approved PI3Kα inhibitors on the breast cancer market, such as Novartis’ Piqray (alpelisib) and Roche’s Itovebi.
Currently, analysts at GlobalData, parent company of Pharmaceutical Technology, forecast that Itovebi sales will eclipse Piqray in 2026, with the former expected to become a blockbuster seller in 2029. Meanwhile, Piqray’s sales are forecast to drop by more than half between 2026 and 2032.
The debut of new therapies for HR-positive, HER2-negative breast cancer would be welcome news for patients, who continue to face significant unmet needs due to resistance to endocrine therapies. Currently, researchers estimate that this breast cancer subtype is the most common, with statistics from the National Cancer Institute estimating that the age-adjusted rate of HR-positive HER2-negative is an age-adjusted rate of cases between 2019 and 2023 was 92.9 new cases per 100,000 women.
