Relay breast cancer drug shows potential in early trial

Dive Brief:

• An experimental drug regimen for breast cancer being developed by Relay Therapeutics delayed tumor growth by a median of about nine months in a small clinical trial, results that were promising enough to propel the biotechnology company’s shares higher by more than 50% Monday.
• When added to an older hormonal therapy, Relay’s drug shrank tumors by some degree in nearly three-quarters of the 30 study participants who were given the target dose and had measurable disease, the company said. The effect was large enough in 10 participants to meet the criteria for a partial tumor response.
• According to Relay, the results support advancing the two-drug combination into a pivotal trial next year to assess whether the regimen may be effective enough to supplant existing options for people with metastatic breast cancer driven to growth by mutations in a gene called PI3Ka.

Dive Insight:

The PI3Ka gene encodes for an important regulatory protein, mutations in which are often implicated in the development of solid tumors. As such, it’s long been the target of drugmakers. Several PI3Ka inhibitors are approved, including Novartis’ Piqray and AstraZeneca’s Truqap.

Relay, an eight-year-old biotech that’s made research into how proteins move its calling card, has taken a different approach. Rather than target what’s known as the “active” site on the PI3Ka protein, Relay is going after a different foothold with its drug, dubbed RLY-2608. And by using protein modeling and molecular dynamic simulations, Relay says it’s found differences in the shapes of the mutated and “wild-type” versions of PI3Ka.

The result, Relay claims, is a drug that might be able to avoid the toxicity associated with existing PI3Ka inhibitors, which can cause diarrhea, rash and potentially dangerous high blood sugar levels.

The data released by Relay Monday offer a look at its drug’s potential. According to the company, the median 9.2 months of progression-free survival that investigators reported for the target dose is greater than the roughly 5.5 months associated with approved Piqray- and Truqap-based regimens.

Most notably for Relay’s research hypothesis, treatment with RLY-2608 led to fewer cases of side effects that were judged to be Grade 3 or higher. Only two of the 64 patients given the target dose of Relay’s drug discontinued treatment.

“These interim data suggest that by selectively targeting mutant PI3Ka, RLY-2608 has the potential to offer a level of benefit to patients that has not previously been possible with existing non-selective medicines, while also having significantly less toxicity,” Don Bergstrom, Relay’s head of R&D, said in a statement.

As of Aug. 12, Relay’s study enrolled 118 patients with locally advanced or metastatic breast cancer that tested positive for PI3Ka mutations. Patients’ cancer also had be both positive for a protein called “HR” and negative for another protein known as “HER2,” a classification that made them ineligible to take drugs like Roche’s Herceptin. All were previously treated, some with two or more prior drug regimens.

Participants were given a range of RLY-2608 doses, together with another drug called fulvestrant. Sixty-four received the “recommended Phase 2 dose.” Of those 64, 12 had additional mutations in either the PTEN of AKT genes that are thought to make PI3Ka inhibitors less effective and were excluded from Relay’s efficacy analyses.

Pending discussions with regulators, Relay expects to begin a study testing RLY-2608 plus fulvestrant against Truqap and fulvestrant. The company is also studying triplet combinations that it hopes could be used in previously untreated patients. More data on that approach is expected later this year, but pivotal testing likely wouldn’t begin until 2026.

Relay’s stock jump Monday puts its market value back above $1 billion.

In addition to the RLY-2608 data, Relay also disclosed plans to seek a commercialization partner for its most advanced drug, a treatment for a type of cancer that affects bile ducts.

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