Scorpion unveils early data on breast cancer drug challenging Novartis, Roche

In an initial assessment of Scorpion Therapeutics' experimental treatment for breast cancer and other solid tumors, a small group of patients experienced tumor shrinkage without severe toxicities typically associated with earlier drugs of this kind. This trial marks a promising development for the Boston-based biotech firm, which recently secured $150 million in a Series C funding round.

Scorpion Therapeutics is developing an inhibitor targeting PI3Kɑ, a prevalent cancer driver found in various tumors. This initiative places the company in competition with established biopharma giants like Novartis and Roche, both of which have developed drugs for breast cancer with PIK3CA mutations. The PIK3CA gene produces a component of the PI3Ka kinase, crucial in cancer progression.

During the European Society for Medical Oncology annual meeting in Barcelona, Scorpion disclosed preliminary data from its trial. Out of 43 patients with specific PIK3CA mutations, nine saw their tumors shrink by at least 30% after being treated with STX-478. Initially, five of these responses were unconfirmed at the data cutoff in June but were later confirmed.

Adam Friedman, CEO of Scorpion Therapeutics, remarked on the positive trend in the monotherapy data, suggesting that stronger and longer targeting of the cancer driver could lead to better patient outcomes. Investors in the recent Series C funding round had access to early trial results.

The trial data also revealed that five out of 22 patients with HR+/HER2- breast cancer responded to the therapy. Nearly all these patients had previously been treated with a CDK inhibitor. Additionally, four of nine patients with gynecologic cancers showed positive responses. Currently, no PI3Kɑ-targeted drugs are approved for cancers other than breast cancer.

However, the trial also recorded elevated liver enzyme levels in eight patients, with five experiencing grade 3 and one experiencing grade 4 levels. These instances were described as asymptomatic, temporary, and reversible. One case each of grade 3 and 4 levels occurred at a 160 mg dose, higher than the future maximum tolerated dose of 100 mg. Importantly, there were no grade 3 or higher toxicities related to wild-type PI3Kɑ, such as hyperglycemia, diarrhea, and rash. No patients discontinued the study due to adverse events.

Scorpion Therapeutics is part of a competitive field aiming to develop next-generation PI3Kɑ inhibitors. Alexander Drilon of Memorial Sloan Kettering Cancer Center categorized these inhibitors based on their selectiveness. Novartis' Piqray and Roche's inavolisib are 'PI3Kɑ selective,' while Scorpion's STX-478 and Relay Therapeutics' candidates are 'PI3Kɑ mutant-selective,' sparing the wild type protein. Lilly's LOXO-783 is the most selective, targeting a specific PI3Kɑ mutant known as H1047R.

Drilon highlighted that mutant-selective PI3Kɑ inhibitors could potentially expand therapeutic options. Novartis' Piqray, approved in 2019 for certain breast cancer patients, has significant side effects like high blood sugar and rash, leading to a quarter of patients discontinuing the trial due to adverse events. Roche is awaiting potential approval for inavolisib in combination with other breast cancer treatments, and Relay Therapeutics plans to initiate a pivotal trial next year.

Friedman emphasized that Scorpion's study included pre-diabetic and diabetic patients, who are typically excluded from PI3K inhibitor trials due to known side effects. The study aimed to test the real-world applicability of their selective inhibitor, particularly for pre-diabetic and diabetic patients at risk for severe hypoglycemia.

Looking ahead, Scorpion plans to study STX-478 in combination with CDK4/6 inhibitors and fulvestrant for first- and second-line HR+/HER2- breast cancer with PIK3CA mutations. The company is also exploring its options in other cancer types where the PI3Kɑ mutation plays a significant role but lacks approved inhibitors, with further details to be disclosed soon.