Revolution Medicines(RVMD) - 2021 Q4 - Earnings Call Transcript

Financial Data and Key Metrics Changes - The company ended 2021 with $577 million in cash and investments, with revenue from collaboration agreements totaling $9.5 million for Q4 2021 and $29.4 million for the full year [42] - Total operating expenses for Q4 2021 increased to $62 million, primarily driven by R&D expenses of $54 million, while total operating expenses for the full year rose to $217 million, with R&D expenses increasing to $187 million [44] - The net loss for Q4 2021 was $53 million or $0.71 per share, and for the full year, the net loss was $187 million or $2.57 per share [45] - For 2022, the company expects a GAAP net loss between $260 million and $290 million, including estimated non-cash stock-based compensation of $35 million to $40 million [46] Business Line Data and Key Metrics Changes - The company is advancing its RAS (ON) inhibitor portfolio, which includes several drug candidates targeting RAS-addicted cancers, particularly focusing on KRAS mutations [5][10] - RMC-6236, the first RAS (ON) inhibitor, is in late stages of IND preparation, with plans to submit an IND in the coming months [11] - RMC-6291, a selective inhibitor for KRAS G12C, is also expected to submit an IND in the first half of 2022 [14] Market Data and Key Metrics Changes - The company targets over 130,000 new pancreatic, colorectal, and lung cancer patients in the US each year with tumors bearing various KRAS mutations [9] - RMC-6291 is aimed at approximately 29,000 new US patients per year, primarily with lung or colorectal cancers [13] Company Strategy and Development Direction - The company aims to combine RAS (ON) inhibitors with companion inhibitors to enhance clinical outcomes for patients with RAS-addicted cancers [21] - The strategy includes developing specific KRAS companion inhibitors to suppress cooperating targets and pathways that sustain RAS-addicted cancers [21] - The company is focused on expanding its pipeline with distinctive new assets derived from its RAS cancer innovation engine [40] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's position to aggressively pursue its mission for cancer patients, supported by a strong balance sheet and a compelling strategy [48] - The management highlighted the importance of addressing resistance mechanisms in RAS-mutant cancers and the potential for combination therapies to improve patient outcomes [28][30] Other Important Information - The company has initiated a global Phase 2 study of RMC-4630 in combination with sotorasib for KRAS G12C lung cancer patients [25] - RMC-5552, an innovative mTORC1 inhibitor, is in the dose escalation phase of its initial clinical trial, showing promising anti-tumor activity [36] Q&A Session Summary Question: How many addressable second line non-small cell lung cancer KRAS G12C patients are there in the US? - The company acknowledged the complexity of the question and suggested discussing it offline [52] Question: How does targeting just mTORC1 compare to targeting both mTORC1 and mTORC2? - The company explained that RMC-5552 selectively inhibits mTORC1 without the toxicity associated with mTORC2, allowing for higher dosing and better therapeutic effects [56] Question: How different are the pharmacokinetics of the KRAS inhibitors? - The company noted that pharmacokinetics vary among their RAS (ON) inhibitors, influenced by factors such as affinity for cyclophilin A and whether the warhead is covalent or non-covalent [64] Question: What are the expectations for the preliminary data readout from RMC-4630? - The company plans to treat up to 46 patients in the RMC-4630-03 study, with a focus on overall response rate as the primary outcome measure [69] Question: Will there be an accelerated pathway for RMC-4630? - The company indicated that options for accelerated approval are being explored, particularly for RAS inhibitors outside of the G12C space, which may have more straightforward pathways due to the lack of existing therapies [91] Question: Can you discuss the bioavailability and dosing for RMC-9805? - The company reported good pharmacodynamic effects in preclinical models, with expectations for once-daily dosing in humans, though actual dosing will depend on clinical pharmacokinetics [97]