The biotech company Relay has developed an experimental drug for people with vascular malformations. This medication targets people with a PIK3CA mutation (PIK3CA-driven malformation). The company now plans to test it in clinical trials worldwide.
Relay is a small biotech company (Cambridge, Massachusetts, USA) that focuses primarily on developing therapies for rare diseases and cancer.
Their clinical trials are taking place worldwide. Currently, three clinical trials are underway: two in breast cancer and one in vascular malformation.
The drug they now plan to test in clinical trials for vascular malformations is called Zovegalisib (RLY2608), or simply “Zovega.” The clinical trial for Zovega began last year (2025) in the US and they are now expanding it globally.
Relay wants to conduct clinical trials on people with PROS (PIK3ca Related Overgrowth Spectrum) and lymphatic malformations (LM). These two categories of conditions most often exhibit PIK3CA mutations (PROS: 100% and LM: approximately 80%).
These conditions belong to the so-called “mosaic” disorders; some parts of the body are affected and others are not. This means that you have both mutant protein (in affected parts of the body) and non-mutant/normal protein in unaffected parts of your body.
Researchers have been developing PIK3CA inhibitors for a long time (over 40 years). PIK3CA is part of the so-called P13K/AKT/mTOR pathway. This pathway is important for growth and metabolism. Mutations in the proteins of this pathway can lead to disrupted growth (overgrowth). Several inhibitors have already been developed (see image at https://www.cmtc.nl/en/pedia/diagnosis/the-genetic-cause-of-vascular-malformations-an-update/) against various proteins in the P13K/AKT/mTOR pathway. However, so far, the inhibitors have targeted both the mutant and the normal protein. For example, Alpelisib targets PIK3CA. Malformations can be reduced by inhibiting the mutant protein. This results in less overgrowth. At the same time, inhibiting the normal protein also causes many side effects. Side effects include increased blood glucose, diarrhea, rash, and mouth ulcers.
Zovega is one of the first-generation drugs of its kind that primarily binds to the mutant protein. The mutant protein has a pocket that Zovega fits into well, which is not present in the normal protein. This means that Zovega disrupts the function of the normal protein less, resulting in fewer side effects. Zovega has been tested in breast cancer patients, and it was well tolerated (few side effects) and effective (tumor shrinkage). Zovega has also been tested in a mouse model (mice with vascular malformations), which also yielded good results with few side effects.
A trial will now be conducted in patients with PIK3CA-driven vascular malformations (LM and PROS-specific conditions and other subtypes). This trial will include approximately 280 patients from Europe: the UK, Belgium, Spain, Italy, Germany, Ireland, Norway, and possibly more countries (application has been made for France). It is already underway in the USA, Australia, and Canada.
Zovega is an oral medication.
Start date: October 24, 2025. End date (EU): July 1, 2031. End date (global): October 1, 2031.
More information:
CTIS.eu, enter number 2024-518895-30-00
CT.gov, enter number NCT06789913
Or scan the QR codes:
The information presented in this article is based on a webinar held on January 7, 2026, organized by HEVAS in collaboration with Relay Therapeutics.”