Relay Therapeutics Presents Data on RLY-2608
Taking a Look at Relay Therapeutics (RLAY).
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Promising Data for RLY-2608 in Breast Cancer Readout
Relay Therapeutics (RLAY) has announced updated interim clinical data for RLY-2608, a first-in-class allosteric, pan-mutant, and isoform-selective PI3Kα inhibitor, in combination with fulvestrant for patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer. The data, presented at the San Antonio Breast Cancer Symposium (SABCS) 2024, really emphasizes the potential of RLY-2608 to redefine the standard of care in second-line (2L) settings.
Key Efficacy Findings
Median Progression-Free Survival (PFS):
In the 2L setting, RLY-2608 + fulvestrant demonstrated a median PFS of 11.4 months, which is more than double that of the current standards of care.
For all patients receiving the recommended Phase 2 dose (RP2D) of 600 mg BID, the median PFS was 9.2 months.
Objective Response Rate (ORR):
The confirmed ORR was 39% across all patients.
Among patients with kinase mutations, the ORR reached an impressive 67%.
Clinical Benefit Rate (CBR):
The clinical benefit rate was 67% for evaluable patients (defined as patients with a complete response, partial response, or stable disease for at least 24 weeks).
Progression-Free Survival is the length of time during and after treatment in which a patient lives with a disease (such as cancer) but the disease does not get worse. Essentially, it's the duration during which the patient's condition remains stable, without measurable tumor growth or spread.
Objective Response Rate is the proportion of patients in a clinical trial who experience a measurable reduction in tumor size over a defined period.
Clinical Benefit Rate is a measure used in clinical trials to evaluate the percentage of patients who experience a significant benefit from a treatment. It is broader than the ORR because it includes stable disease for a defined period in addition to partial and complete responses.
Patient Population & Trial Details
The data were derived from the ongoing ReDiscover trial, which includes heavily pre-treated patients:
41% of patients had received two or more prior lines of therapy.
52% had prior exposure to a selective estrogen-receptor degrader (SERD).
59% of patients presented with visceral metastases.
The trial's patient cohort included a total of 118 patients, with 64 patients receiving RLY-2608 at the RP2D of 600 mg BID.
Tolerability & Safety Profile
This was generally well tolerated:
Low rate of Grade 3 treatment-related adverse events (TRAEs), with only 31% of patients experiencing such events.
Minimal impact on glucose homeostasis, with only 3% of patients experiencing Grade 3 hyperglycemia.
High dose intensity was maintained at 94%, with only 3.1% of patients discontinuing due to TRAEs.
The emphasis on the 3% Grade 3 hyperglycemia on the call, is because hyperglycemia is a known issue with PI3Kα inhibitors and managing it effectively can be a key differentiator for new therapies. These numbers are very solid so far.
Next Steps & Pivotal Trial Plans
RLAY is planning to initiate a pivotal 2L study for RLY-2608 + fulvestrant in 2025. This study will further validate the efficacy and tolerability of RLY-2608 compared to capivasertib + fulvestrant, a current standard of care. Additionally, the company has initiated investigations into triplet therapies combining RLY-2608 with CDK4 inhibitors such as ribociclib and atirmociclib.
My Take
These recent results were excellent and have further increased RLAY’s probability of success. As a pre-revenue biotech, the company’s valuation hinges on the strength of its pipeline, the quality of its data, and the health of its balance sheet. The breast cancer data RLAY presented is nearly groundbreaking—very strong. They’re advancing into pivotal stages and will soon provide an update on their triplet data as well. Management’s comments on the call suggested the triplet data might not be as strong or conclusive as the doublet results. With that in mind, I’m taking a neutral stance and keeping my expectations low for this readout, just in case it doesn’t measure up to what we’ve seen before. But, with $840M in cash, they’re well-positioned to fund operations until 2027/28. By then, if RLY-2608 proves successful, they’ll likely be commercializing it and probably generating meaningful revenue. Even if they do run low on cash, securing additionally funding will not be an issue if this is the case.
Despite all this, the company remains significantly undervalued and largely overlooked. Excluding the hidden gem of Dynamo, RLAY’s current market cap is roughly on par with its cash balance, suggesting the market is applying almost no premium for their assets. Comparable biotech companies usually trade at about 4x-8x their projected annual revenue. In contrast, RLY-2608 alone will generate at least $1B in annual sales, making it a potential blockbuster. Yet RLAY is trading below a single year’s revenue projection, with an $800M market cap. That doesn’t even factor in the rest of their pipeline, the Dynamo program, or their substantial cash reserves.
In my view, RLAY is executing effectively but remains neglected—much like Coherus BioSciences pre Udenyca sale. I added to my position before the latest release, and after receiving a business update from Coherus in January, I plan to allocate a significant portion of those proceeds into RLAY.