Positive Breast Cancer Data from Relay Therapeutics

Taking a Look at Relay Therapeutics' Positive Readout for RLY-4008 (lirafugratinib), Weekly Activity, & Portfolio Update

Last week, Relay Therapeutics shared results about their experimental drug, RLY-4008, designed to treat a specific type of breast cancer. The drug is being tested in a two-step study named the "ReFocus trial." They've completed the first step, and now they're in the second step, figuring out the right dosage.

For this test, they're focusing on patients with three different cancer-related changes: FGFR2 fusions, FGFR2 amplifications, and FGFR2 mutations. By August 23, 2023, they had enrolled 84 patients. Most of these patients had tried other treatments in the past, with almost all (94%) having taken a common cancer treatment and nearly half (45%) having tried other specialized treatments. Now, let's examine the outcomes they observed…

FGFR2 stands for Fibroblast Growth Factor Receptor 2. It's a type of protein found on the surface of some cells in our body. This protein is important because it's involved in various cellular functions, including helping cells grow and divide. In the context of cancer, changes (or mutations) in the genes that produce FGFR2 can lead to the development of certain types of tumors. When this happens, the FGFR2 protein might be produced in larger amounts or might act abnormally, contributing to cancerous growth. That's why drugs targeting FGFR2 (like RLY-4008 from Relay Therapeutics) are being developed. By targeting this specific protein, these drugs aim to treat the cancers that have abnormalities in FGFR2. I would reference back to my original article introducing RLAY.

Optimistic Results

Relay has been researching the effects of their drug on tumors with specific genetic alterations, particularly those related to FGFR2. The results, thus far, have shown promising potential in various areas.

In patients with FGFR2 fusions, which represent certain genetic changes in tumors, the drug demonstrated a positive response. Out of 26 patients tested, 9 experienced a partial shrinkage of their tumors, accounting for a 35% response rate. Impressively, nearly two-thirds of these patients maintained this positive response for a minimum duration of six months. The variety of cancers among these patients was diverse, spanning types such as pancreatic, ovarian, gastric, lung (specifically NSCLC), and breast.

A spotlight on breast cancer patients revealed noteworthy findings. Among 14 patients studied, 10 were diagnosed with a specific subtype of breast cancer, labeled as HR+/HER2-. Remarkably, 40% of these patients, which equates to 4 patients, observed their tumors undergoing partial shrinkage (wow!). As of the data's last update, three out of these four patients continued to benefit from the treatment, with the most prolonged response surpassing a year and a half. It's vital to note the resilience of these breast cancer patients. On average, each had endured six varying treatments in the past. Every one of them had undergone targeted therapies, almost all had experienced chemotherapy, and a vast majority had received endocrine and CDK4/6 treatments.

Lastly, patients with FGFR2-amplified tumors, another type of genetic tumor alteration, also exhibited favorable results. From a group of 34 patients, 8 (or 24%) experienced a partial reduction in their tumors. The cancers manifesting these positive outcomes ranged from gastric and breast to colorectal and esophageal. Encouragingly, six patients continue with the treatment, with four persistently observing tumor reduction.

Relay presents, in the image above, an analysis of the Overall Response Rate (ORR) and Disease Control Rate (DCR) for FGFR2 fusions and amplifications across several key tumor types. A total of 60 tumors were evaluated. Gastric tumors showed an 18% ORR and 64% DCR, while breast tumors exhibited a notably higher 43% ORR and 71% DCR. Pancreatic tumors had a 33% ORR and 67% DCR, and both NSCLC and ovarian tumors displayed a 50% ORR and 75% DCR. CRC and CUP both indicated a 33% ORR, with CRC having a 67% DCR and CUP a 67% DCR. Other tumors had a 9% ORR with a 45% DCR. The chart underscores that positive responses were observed in eight specific tumor types, which are listed below the graph.

The findings from Relay’s drug trials highlight its potential as a promising treatment alternative for patients with specific genetic tumor alterations, notably FGFR2 fusions and FGFR2 amplifications. Given the broad range of cancers and the backgrounds of the patients involved, the drug might offer a beacon of hope, especially for those who have tried multiple treatments in the past without sufficient success.

Relay’s Refined Roadmap

Aside from the data presented, Relay has made strategic changes to its pipeline. A notable decision concerns the RLY-4008 drug. Originally set for a commercial launch for CCA/liver cancer in 2025, the company now plans to delay this. Instead, they aim to amass more data from all tumor types, potentially postponing the launch to between 2025 and 2026 (this is not a bad thing at all). However, there's optimism, as the incoming data might prompt the FDA to bestow RLY-4008 with the Breakthrough Therapy designation. This could mean the launch would adhere closely to its original timeline. This strategic recalibration is fueled by fresh data. Each year, 6,000 individuals globally are diagnosed with FGFR2-altered CCA/liver cancers. In contrast, 85,000 diagnoses span all other tumor types, including 28,000 cases of HR+ breast cancers. This insight has led Relay Therapeutics to intensify its focus on its broader pipeline, which has a significant emphasis on breast cancers.

Several modifications have been made to other drugs in development. The advancement of RLY-2139, the CDK2 inhibitor, has been halted. Meanwhile, there's a plan to kickstart a triple-combo trial for RLY-2608 (PI3K-alpha) by the close of 2023. This trial will combine it with conventional chemotherapy and CDK4/6 inhibitors. The fate of this drug, be it prioritization or discontinuation, hinges on the trial's results. Furthermore, Relay Therapeutics has suspended the progress of its ER-alpha protein degrader. Their portfolio of genetic disease assets has been trimmed down to two. Interestingly, the clinical trials for RLY-5836, another PI3K-alpha inhibitor, will now mirror those of the top-tier asset.

In related industry news, Roche/Genentech has progressed the SHP2 inhibitor, GDC-1971, into a trio of combination studies. As Relay Therapeutics looks to the future, they've earmarked 2024 for the announcement of new programs. These will span two solid tumors and two genetic diseases.

A significant repercussion of these changes is financially. The modifications have granted Relay Therapeutics an additional year of financial runway. Originally estimated to last until the second half of 2025, their funds are now projected to sustain them until the latter half of 2026 (excellent).

My Take

I believe the results presented by Relay are beyond expectations. For cancers altered by FGFR2 outside of CCA/liver, there are no current treatments. This is where RLY-4008 comes in, which has set a commendably high standard, outclassing any current or upcoming solutions. It is showing great results especially in breast cancer, the primary group for FGFR2 alterations. It showcased a 43% ORR, mirroring the peak ORR of 42% seen in the best treatment for CCA/liver. This is excellent. However, RLY-4008 didn't fare as well in gastric cancers, showing a mere 18% ORR. This might hint at other mutations influencing these cancers despite the presence of FGFR2 alterations. An intriguing observation: a third of the study participants had gastric cancer. If we exclude them and the CCA/liver group, the ORR spikes to 34% for other tumors, which is great.

While the market may be shying away from smaller companies during this biotech downturn, Relay Therapeutics stands out. They're revolutionizing drug design and development. If Relay continues to execute, eventually getting to commercialization, you are looking at a $10B+ company. More than likely surpassing that mark with ease. Investors should be extremely optimistic with Relay’s execution/results, and the current levels the business is trading at presents a phenomenal opportunity to accumulate more. My personal conviction is very high right now, up there with my Coherus BioSciences position. If Relay continues its downward trend, I will have to consolidate my position further.

Weekly Activity (October 9th-13th)

No buys this week.

Portfolio Update

This week, WM outperformed VOO (S&P 500) to claim the top spot. I'd also like to mention that I've been considering selling RBOT for tax harvesting purposes. Categorized similarly to small-cap biotech, RBOT has taken a significant hit. Following its price offering announcement, many shareholders and potential buyers have been heading for the exits. However, since it constitutes only a small fraction of my portfolio, its continued decline won't significantly impact me, whether I choose to hold or sell. This situation underscores the importance of capital allocation and balancing your portfolio according to your risk/reward threshold.