On August 12, 2021 Relay Therapeutics, Inc. (Nasdaq: RLAY), a clinical-stage precision medicine company transforming the drug discovery process by combining leading edge computational and experimental technologies, reported second quarter 2021 financial results and announced a collaboration with EQRx (Press release, Relay Therapeutics, AUG 12, 2021, View Source [SID1234586444]).

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"PI3Kα mutations have been a known oncogene for the past 20 years but this has been a very difficult drug discovery challenge to solve using conventional approaches. Leveraging our Dynamo platform, the Relay Therapeutics team has been able to create what we believe to be the first ever mutant selective inhibitor of PI3Kα, which offers the potential to address a significant unmet medical need," said Sanjiv Patel, M.D., president and chief executive officer. "Other programs in our pipeline continue to progress as anticipated, with RLY-4008, our FGFR2 inhibitor on track for an initial data disclosure later this year. We hope to demonstrate that our platform has achieved another breakthrough by potentially creating the first ever selective small molecule inhibitor of FGFR2. Finally, our new collaboration with EQRx announced today opens yet another avenue for our Dynamo platform to potentially impact the lives of more patients and generate value for our shareholders. This partnership allows us to utilize the scale and efficiencies of our machine learning and artificial intelligence capabilities against an expanded target landscape. We look forward to a productive remainder of 2021."

PI3Kα Mutant Selective Program Update

Phosphoinositide 3-kinase alpha (PI3Kα) is the most frequently mutated kinase in solid tumors. Approximately 60%-70% of the mutations in PI3Kα cluster at three amino acids (H1047, E542, and E545). Traditionally, the development of PI3Kα inhibitors has focused on the active, or orthosteric site. The therapeutic index of orthosteric inhibitors is limited by the lack of clinically meaningful selectivity for mutant versus wild-type PI3Kα and off-isoform activity. Toxicity related to inhibition of wild-type PI3Kα and other PI3K isoforms results in sub-optimal inhibition of mutant PI3Kα with reductions in dose intensity and frequent discontinuation. RLY-2608, the first allosteric, pan-mutant (H1047X, E542X and E545X), and isoform-selective PI3Kα inhibitor was designed to overcome these limitations.

Relay Therapeutics solved the full-length cryo-EM structure of PI3Kα, performed computational long time-scale molecular dynamic simulations to elucidate conformational differences between wild-type and mutant PI3Kα, and leveraged these insights to enable the design of RLY-2608. In biochemical assays, RLY-2608 inhibits H1047R, E542K, and E545K mutant PI3Kα activity with <10nM potency and 8-12x selectivity relative to wild-type PI3Kα. RLY-2608 is > 1000-fold selective over the β, δ, and γ PI3K isoforms in biochemical assays and demonstrates exquisite selectivity across a panel of 322 kinases.

This progress puts RLY-2608 on path to initiate a first-in-human clinical study in the first half of 2022. RLY-2608 is the lead program of multiple preclinical efforts to discover and develop mutant selective inhibitors of PI3Kα.

Strategic Collaboration with EQRx

Relay Therapeutics and EQRx entered a worldwide strategic collaboration to discover, develop, and commercialize novel medicines against validated oncology targets. Under the terms of the agreement, Relay Therapeutics will be responsible for the discovery phase through to Investigational New Drug application filing, while EQRx will be responsible for clinical development, regulatory and commercialization efforts of the product candidates developed pursuant to the collaboration. Relay Therapeutics and EQRx will equally share in the discovery, development and commercialization costs and the net profits from sales of any collaboration medicines, if approved. The collaboration will start with one program, but the companies can mutually agree to add additional programs to the collaboration in the future. Relay Therapeutics retains the right to develop any collaboration medicines in combination with its wholly-owned pipeline.

Other Recent Corporate Highlights

RLY-4008, a potent, selective and oral small molecule inhibitor of FGFR2, remains on track to report initial safety, tolerability and pharmacokinetics data across multiple dose levels before the end of 2021. Most patients to be reported on will be FGFR2 altered cholangiocarcinoma (CCA) patients with prior exposure to pan-FGFR inhibitor therapies. The disclosure will also include preliminary efficacy data focusing on FGFR2 fusion CCA pan-FGFR treatment naïve patients.

In July 2021, Genentech initiated the cohort of RLY-1971/GDC-1971, an inhibitor of SHP2, in combination with GDC-6036, an inhibitor of KRAS G12C, in a Phase 1b trial.
Second Quarter 2021 Financial Results

Cash, Cash Equivalents and Investments: As of June 30, 2021, cash, cash equivalents and investments totaled approximately $671.2 million, compared to $678.1 million as of December 31, 2020. The change in cash reflects the receipt of Genentech’s $75 million upfront payment in the first quarter, partially offset by $25.1 million in net cash paid for the acquisition of ZebiAI and cash used to fund our operations. The Company expects its current cash and cash equivalents will be sufficient to fund its current operating plan into 2024.

R&D Expenses: Research and development expenses were $180.0 million for the second quarter of 2021, as compared to $21.7 million for the second quarter of 2020. $134.9 million was due to the acquisition of ZebiAI in April 2021. The additional increase of $23.5 million was primarily due to $12.3 million of additional employee related costs, including an increase in stock-based compensation of $8.2 million, $7.3 million related to our pre-clinical candidates and $2.5 million related to increased clinical trial expenses associated with RLY-1971 and RLY-4008.

G&A Expenses: General and administrative expenses were $14.4 million for the second quarter of 2021, as compared to $6.1 million for the second quarter of 2020. The increase of $8.4 million was primarily due to $5.8 million of increased personnel costs, including increased stock-based compensation of $3.9 million, to support our infrastructure and $2.6 million related to increases in other general and administrative expenses primarily attributed to an increase in insurance expense.

Net Loss: Net loss was $193.4 million for the second quarter of 2021, or a net loss per share of $2.10, as compared to a net loss of $26.7 million for the second quarter of 2020, or a net loss per share of $6.06.