Financial Data and Key Metrics Changes - The company ended Q3 2023 with $813.2 million in cash, cash equivalents, and investments, excluding anticipated proceeds from the acquisition of EQRx, which is expected to add approximately $1.1 billion in net cash [18] - GAAP net loss for Q3 2023 was $108.4 million, or $0.99 per share, with full-year 2023 GAAP net loss expected to be between $385 million and $415 million [58] Business Line Data and Key Metrics Changes - RMC-6236 has shown objective anti-tumor activity against three oncogenic RAS gene types, with a blended objective response rate in pancreatic ductal adenocarcinoma at 20%, which is higher than the 7% to 11% range for cytotoxic chemotherapy [5][8] - The objective response rate in non-small cell lung cancer is reported at 38%, with expectations to settle between 40% to 50% at the recommended Phase 2 dose [6][7] Market Data and Key Metrics Changes - The disease control rate for RMC-6236 was reported at 87%, significantly higher than most reports for salvage chemotherapy in pancreatic cancer [11] - The company is evaluating the potential for RMC-6291 in KRAS G12C cancers, with an objective response rate of 50% in lung cancer patients who had progressed on prior treatment with a G12C inhibitor [50] Company Strategy and Development Direction - The company plans to initiate a pivotal Phase 3 trial for RMC-6236 in pancreatic cancer and a Phase 3 trial for non-small cell lung cancer in 2024, focusing on achieving full regulatory approval [12][13] - The acquisition of EQRx is expected to enhance the company's ability to develop its pipeline and support late-stage development for RAS(ON) inhibitors [20][54] Management's Comments on Operating Environment and Future Outlook - Management emphasized the importance of durability of clinical benefit as indicated by progression-free survival and overall survival, rather than solely relying on objective response rates [10] - The company is committed to evaluating several combination options for RMC-6236 and RMC-6291, with ongoing discussions with regulators and investigators [17][20] Other Important Information - Total operating expenses for Q3 2023 were $123.2 million, primarily due to clinical trial and manufacturing expenses for RMC-6236 and RMC-6291 [57] - The company reiterated its cash runway guidance into 2025 based on current plans, excluding the impact of the proposed EQRx transaction [58] Q&A Session Summary Question: Why pursue a monotherapy trial against docetaxel instead of a combination? - Management expressed a desire to eliminate chemotherapy from treatment options and aims to demonstrate superiority over docetaxel as a standalone treatment [64] Question: What is the strategy for prioritizing cohorts in the trials? - The company is expanding its protocol to include various histologies, including colorectal cancer, while focusing on dose selection for non-small cell lung cancer and pancreatic cancer [29] Question: What are the benchmarks for disease control and PFS in previously treated pancreatic ductal adenocarcinoma? - Management indicated that median progression-free survival for standard treatments is approximately three months, and they are working to establish benchmarks for RMC-6236 [49][73] Question: What is the anticipated expense ramp for supporting multiple studies? - The company plans to increase spending to support mid and late-stage studies while ensuring judicious use of capital, especially following the EQRx acquisition [100][101]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2023 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ___ to ___ Commission File Number: 001-39219 Revolution Medicines, Inc. (Exact Name of Registrant as Specified in its Charter) Delaware 47-2029180 (State or ...

Financial Data and Key Metrics Changes - The company ended Q2 2023 with $909.5 million in cash, cash equivalents, and investments [8] - Total revenue for Q2 2023 was $3.8 million, primarily from a terminated collaboration agreement with Sanofi [8] - Total operating expenses for Q2 2023 were $112.6 million, driven by clinical trial and manufacturing expenses for RMC-6236 and RMC-6291 [17] - The net loss for Q2 2023 was $98.3 million, or $0.92 per share, with a full-year GAAP net loss guidance of $360 million to $400 million [18][19] Business Line Data and Key Metrics Changes - The company is focusing on the development of RAS(ON) inhibitors, specifically RMC-6236 and RMC-6291, with significant updates expected in the fall [21][72] - The acquisition of EQRx aims to strengthen the company's cash position and support the development of its RAS(ON) inhibitor pipeline [4][5] Market Data and Key Metrics Changes - The company is preparing for clinical updates on RMC-6236 and RMC-6291, with presentations scheduled for the ESMO Congress and the Triple Meeting in October [71][72] - The company is evaluating the potential of RMC-5552 as a RAS Companion Inhibitor in combination with RAS(ON) inhibitors [3][72] Company Strategy and Development Direction - The company is committed to a parallel development approach for its RAS(ON) inhibitor pipeline, aiming to maximize patient benefits quickly [57] - The acquisition of EQRx is intended to provide the financial depth necessary for pursuing multiple late-stage development paths [57] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the upcoming clinical updates and the potential for significant advancements in the second half of the year [6][21] - The company is focused on providing hope to patients with RAS-addicted cancers through its innovative drug development efforts [22] Other Important Information - The company plans to initiate pivotal clinical trials for RMC-6236 potentially in 2024, based on encouraging data trends [71][72] - The company is also advancing its oral mutant selective KRAS G12D inhibitor, RMC-9805, with site activation underway [73] Q&A Session Summary Question: Financial guidance and R&D expenses trajectory - The CFO indicated that the second half of the year will see a step-up in R&D expenses compared to the first half, with no guidance provided for 2024 yet [26][27] Question: Single agent path forward for RMC-6236 - Management stated that clinical updates will be provided in the fall, with more visibility expected based on actual data [29] Question: Dose selection for RMC-6236 - The selection of the optimal dose is ongoing, with management committed to ensuring efficacy and tolerability [33][39] Question: Current standard of care for lung and pancreatic cancer - Management discussed the complexities of current treatment options and the need for RMC-6236 to outperform existing therapies [48][50] Question: Pivotal studies for RMC-6236 - Management confirmed a commitment to a parallel approach for late-stage development, depending on data outcomes [57] Question: Update on RMC-5552 - The focus remains on dose optimization for RMC-5552 as a potential RAS Companion Inhibitor, with no immediate plans for single-agent development [60] Question: Plans for assessing different dosing schedules - Management clarified that daily dosing is currently effective, with no immediate plans to explore alternative schedules [62]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended June 30, 2023 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ___ to ___ Commission File Number: 001-39219 Revolution Medicines, Inc. (Exact Name of Registrant as Specified in its Charter) Delaware 47-2029180 (State or othe ...

Financial Data and Key Metrics Changes - The company reported a net loss of $68.1 million for Q1 2023, equating to $0.72 per share, with an updated full-year GAAP net loss guidance of $360 million to $400 million, reflecting increased investments in clinical advancements [38][22][23] - Revenue from collaboration with Sanofi was $7.0 million in Q1 2023, while total operating expenses increased by 25% year-over-year to $82.2 million, primarily due to R&D expenses [23][22] Business Line Data and Key Metrics Changes - The company is advancing its first-in-class RASMULTI(ON) inhibitor, RMC-6236, with ongoing dose escalation studies showing encouraging antitumor activity and tolerability [5][8] - RMC-9805, a mutant selective oral and covalent KRAS G12D(ON) inhibitor, is on track for clinical evaluation in mid-2023, completing the first wave of RAS(ON) inhibitors under clinical evaluation [9] Market Data and Key Metrics Changes - The company raised $345 million in a public equity offering in March 2023, enhancing its financial position to support clinical development and organizational growth [7][22] - The estimated annual incidence of KRAS G12D cancers in the U.S. is around 55,000 cases, indicating a substantial patient population for ongoing studies [55] Company Strategy and Development Direction - The company aims to expand its clinical development capabilities and is focused on combination studies for RMC-6291, indicating a strategic shift towards combination therapies rather than monotherapy [49][34] - The management emphasized the importance of addressing unmet medical needs, particularly in brain metastases, as part of their long-term strategy [18] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the clinical progress and pipeline, with plans for multiple updates throughout the year, particularly in Q3 [17][24] - The management acknowledged the competitive landscape, noting that standard of care remains the primary competition for many indications, while also recognizing emerging compounds in the clinic [99] Other Important Information - The company has made significant leadership additions, including a new Chief Medical Officer, to enhance its R&D capabilities [21] - The company plans to provide further updates on its clinical programs and organizational progress in the second half of the year [24][17] Q&A Session All Questions and Answers Question: Context for patient numbers and mutation focus - The company is currently focused on KRAS G12D patients due to epidemiology but is seeing additional genotypes and histologies in the study [41] Question: Growth in expenses and priority trials - The management indicated that the increase in expenses is linked to priority trials, including monotherapy expansion and combination studies [42] Question: Tolerability at 160 mg and dose escalation - The management confirmed that the tolerability profile of RMC-6236 remains favorable, allowing for continued dose escalation [44] Question: CNS activity and translatability to human subjects - The management noted that the impact of CNS metastases will depend on the patient population and the ability to control visceral disease effectively [51] Question: Combination partners for RMC-6236 - The management stated that all potential combination partners are currently open, with a focus on those that do not overlap in mechanism [52] Question: Feedback from physicians following AACR - The management reported positive feedback from investigators, highlighting the well-tolerated and active nature of RMC-6236 [90]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2023 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ___ to ___ Commission File Number: 001-39219 Revolution Medicines, Inc. (Exact Name of Registrant as Specified in its Charter) Delaware 47-2029180 (State or oth ...

Revolution Medicines, Inc. (NASDAQ:RVMD) Q4 2022 Earnings Conference Call February 27, 2023 4:30 PM ET Company Participants Margaret Horn - Chief Operating Officer Mark Goldsmith - Chairman, President and Chief Executive Officer Steve Kelsey - President of Research and Development Jack Anders - Chief Financial Officer Conference Call Participants Faisal Khurshid - SVB Securities Michael Schmidt - Guggenheim Partners Marc Frahm - Cowen and Company, LLC Eric Joseph - JPMorgan Chase & Co. Benjamin Burnett - St ...

Financial Performance - The company has incurred significant net losses of $248.7 million, $187.1 million, and $108.2 million for the years ended December 31, 2022, 2021, and 2020, respectively, with an accumulated deficit of $701.3 million as of December 31, 2022[197]. - The company has never generated revenue from product sales and does not anticipate doing so for the next several years, if ever[198]. - As of December 31, 2022, the company had cash, cash equivalents, and marketable securities totaling $644.9 million, with substantial funds required for ongoing preclinical and clinical development[202]. - The company raised $250.7 million in February 2020, $167.8 million in July 2020, $281.1 million in February 2021, and $248.1 million in July 2022 through public offerings[202]. - The company expects to continue incurring significant expenses and operating losses for the foreseeable future due to the nature of biopharmaceutical product development[197]. - The company may require additional financing to achieve its goals, which may not be available on acceptable terms[201]. Regulatory and Clinical Development Challenges - The collaboration agreement with Sanofi has been terminated effective June 2023, ending reimbursement obligations for research and development costs[197]. - The company plans to seek regulatory approval for its product candidates in the United States and select foreign countries, which will require compliance with varying regulatory requirements[213]. - The success of the company's product candidates depends on successful completion of clinical trials, obtaining marketing approvals, and establishing agreements with third-party manufacturers[214]. - The company has not yet demonstrated the ability to successfully complete clinical trials or obtain marketing approvals for any product candidates[197]. - Preclinical development is uncertain, with potential delays affecting the ability to obtain regulatory approvals or commercialize product candidates[216]. - Conducting preclinical testing is lengthy and expensive, often taking several years per program, which may lead to increased operating expenses[217]. - Clinical trials may not demonstrate sufficient safety or efficacy, impacting the ability to obtain regulatory approvals for product candidates[218]. - The regulatory approval processes are lengthy and unpredictable, with no current product candidates having received regulatory approval[226]. - Delays in clinical trials can harm commercial prospects and increase costs, jeopardizing the ability to generate product revenues[233]. - Clinical trial sites may be affected by the COVID-19 pandemic, leading to delays in patient enrollment and data collection[234]. - The company has not previously submitted an NDA to the FDA or a Marketing Authorization Application to the EMA, raising uncertainty about future approvals[229]. - Development of BRo5 compounds may face challenges such as solubility, potency, and bioavailability, increasing the risk of delays and costs[223]. - Regulatory authorities may impose suspensions or terminations of clinical trials due to various factors, impacting the approval process[232]. - The company faces potential delays in clinical trials due to COVID-19 impacts on third-party manufacturers and clinical trial sites[236]. - There is a high failure rate for drugs in clinical trials, and the company cannot guarantee the success of its current or future clinical trials[240]. - Interim data from clinical trials may differ significantly from final results, highlighting the uncertainty in early-stage clinical data[241]. - Patient enrollment challenges may arise due to competition with approved therapies and other clinical trials, potentially delaying development timelines[245]. - The ongoing conflict between Russia and Ukraine may adversely affect European clinical sites involved in the company's studies[247]. - The company has not yet demonstrated the safety of its product candidates in humans, and unforeseen side effects could arise during clinical development[251]. - Regulatory approval processes are expensive and time-consuming, with no guarantee of success for any product candidate[254]. - Marketing approval in one jurisdiction does not ensure approval in others, and varying requirements may complicate the process[258]. - The company may face increased costs and delays in clinical trials due to difficulties in patient enrollment[248]. - The results of preclinical studies may not predict the outcomes of later-stage clinical trials, leading to potential setbacks in product development[239]. - The company may face significant delays and costs in obtaining foreign marketing approvals due to compliance with international regulatory requirements[259]. - Public perception of targeted cancer therapies could negatively impact the commercial success of the company's products, especially if adverse events occur in clinical trials[260]. - Increased governmental regulation and stricter labeling requirements may arise from future adverse events in oncology, potentially delaying marketing approvals[261]. - Ongoing regulatory obligations and potential penalties could result in significant additional expenses even after receiving marketing approval for product candidates[262]. Competition and Market Dynamics - The market acceptance of any approved product candidate will depend on factors such as efficacy, pricing, and the willingness of physicians and patients to adopt new therapies[267]. - The addressable patient population for the company's therapies may be limited, impacting the potential for commercial success[268]. - The company faces significant competition from major pharmaceutical and biotechnology firms, which may have greater resources and established products[273]. - Competitors may obtain marketing approvals more rapidly, potentially establishing a strong market position before the company can enter the market[277]. - Pricing regulations and reimbursement policies in various countries could hinder the company's ability to recoup investments in product candidates[279]. - Coverage and reimbursement availability from government authorities and private insurers will significantly influence the commercialization success of the company's product candidates[280]. - The company faces significant delays in obtaining coverage and reimbursement for newly approved drugs, which can be time-consuming and costly[282]. - Reimbursement rates for drugs may vary significantly among third-party payors, impacting the commercial viability of product candidates[284]. Product Development and Liability Risks - The company has selected three RAS(ON) inhibitors, RMC-6236, RMC-6291, and RMC-9805, for clinical evaluation, but may face challenges in advancing these candidates due to limited resources[285]. - The company may not successfully identify or discover other product candidates, which could hinder its ability to capitalize on greater commercial opportunities[286]. - The company may seek orphan drug designation for its product candidates, which could provide financial incentives, but there is no guarantee of obtaining or maintaining such designation[298]. - The company may incur substantial liabilities from product liability lawsuits, which could limit the commercialization of approved products[302]. - The company may face challenges in obtaining sufficient product liability insurance, which could inhibit its ability to commercialize products[305]. Intellectual Property and Patent Challenges - The company's success significantly depends on obtaining and maintaining sufficient patent protection for its product candidates; failure to do so may impair its competitive position[367]. - The process of obtaining and maintaining pharmaceutical patents is costly and complex, and the company may not be able to secure necessary patent protections in a timely manner[368]. - The company has entered into licensing agreements, and any failure to comply with these agreements could harm its competitive position and financial condition[374]. - The termination of the Sanofi Agreement in June 2023 has resulted in the company regaining decision-making rights over its SHP2 inhibitor program, which may impact its patent management[376]. - The company may face challenges in enforcing its intellectual property rights, which could limit its ability to stop competitors from commercializing similar products[372]. - The government may have certain rights to the company's patent rights developed with federal funding, which could affect its competitive position[379]. - The company may struggle to obtain licenses from third parties on commercially reasonable terms, which could hinder its ability to commercialize products[382]. - The patent position of the company is uncertain, and its pending patent applications may not result in issued patents that provide meaningful protection[371]. - The company may need to rely on third parties for the preparation and maintenance of patent applications, which could jeopardize its intellectual property rights[375]. - The company may face infringement claims if it fails to identify and correctly interpret relevant patents, which could divert substantial financial and management resources[384]. - Patents have a limited lifespan of generally 20 years from the earliest U.S. non-provisional filing date, which may not provide sufficient protection against competition from generic medications[385]. - The company may be eligible for a patent term extension of up to five years under the Hatch-Waxman Amendments, but failure to meet specific requirements could shorten the enforcement period of patent rights[387]. - The company may struggle to protect its intellectual property rights globally due to high costs and varying enforcement practices in different jurisdictions[389]. - Compulsory licensing laws in many foreign countries could compel the company to grant licenses to third parties, potentially diminishing the value of its patents[391]. - Changes in patent law could weaken the company's ability to obtain new patents or enforce existing ones, leading to increased uncertainty regarding patent value[392]. - The company may not be able to list patents in the FDA's Orange Book, which could allow generic manufacturers to bypass advance notice requirements for abbreviated new drug applications[388]. - The company may face significant costs and risks in enforcing its intellectual property rights in foreign jurisdictions, which could divert attention from other business aspects[390]. - The company’s owned and licensed patent portfolio may not provide adequate rights to exclude competitors from commercializing similar products[385]. - The company may incorrectly determine the relevance or scope of third-party patents, negatively impacting its ability to market product candidates[383]. Operational and Compliance Risks - The company faces significant risks related to reliance on third parties for clinical trials, which could affect the ability to obtain marketing approval for product candidates[343]. - Cybersecurity risks are increasing due to reliance on third-party vendors and remote work, which could lead to potential data breaches and operational disruptions[329]. - The company has not experienced significant system failures or security breaches to date, but any future incidents could materially disrupt operations and research programs[330]. - The company may incur substantial costs related to compliance with U.S. and international data protection laws, which could adversely affect business practices[326]. - The company is dependent on third-party vendors for data collection and processing, and any failure to comply with data protection laws could result in enforcement actions and reputational harm[327]. - The complexity of transitioning rights and obligations from Sanofi to the company may adversely impact the development efforts for RMC-4630[333]. - The company may face challenges in establishing new collaborations on commercially reasonable terms, which could hinder the development of product candidates[337]. - The company relies heavily on collaborations for the commercialization of product candidates, and any disputes with collaborators could delay or terminate development efforts[342]. - The company relies on third parties for conducting clinical trials, which may lead to less direct control over data management and potential delays in marketing approval[347]. - The company does not own manufacturing facilities and relies on third-party manufacturers for preclinical and clinical drug supplies, increasing the risk of supply shortages[351]. - There is a risk that third-party manufacturers may not be able to scale up production in a timely or cost-effective manner, potentially delaying clinical trials and regulatory approvals[352]. - The company has no long-term agreements with third-party manufacturers for commercial supply, which may hinder its ability to secure necessary product quantities[356]. - The company must comply with various healthcare laws and regulations, which could expose it to legal and financial risks[362]. - Increased scrutiny of healthcare interactions may lead to investigations and settlements, diverting management's attention from core business activities[365]. - The company may face penalties, including civil and criminal penalties, if found in violation of applicable laws, which could harm its operations and financial results[366]. Geopolitical and Economic Factors - The ongoing conflict between Russia and Ukraine may lead to significant market disruptions, including volatility in commodity prices and supply chain interruptions[306]. - The U.S. and allied countries have imposed substantial sanctions against Russia, affecting major financial institutions and trade relationships[307]. - Russian authorities have implemented strict currency controls and economic restrictions, which could adversely impact global financial markets and the company's operations[308]. - The conflict may limit the company's ability to conduct clinical trials in Europe, potentially delaying or suspending operations[309]. - Legislative reforms in the U.S., such as the Inflation Reduction Act of 2022, may impose price negotiations and rebates that could affect the pharmaceutical industry[314]. - The Affordable Care Act has increased Medicaid rebates and established new coverage gap discount programs, impacting the company's financials[312]. - The company faces compliance challenges with evolving data protection laws, including the GDPR, which could result in significant penalties for non-compliance[325]. - The California Consumer Privacy Act (CCPA) and the California Privacy Rights Act (CPRA) impose additional data protection obligations that may increase operational costs[322]. - The company may incur liabilities and operational losses due to compliance with stringent privacy laws in various jurisdictions[324]. - Disruptions at the FDA and other regulatory agencies could delay the approval of new products, negatively impacting the company's business[318]. - The termination of the collaboration agreement with Sanofi effective June 2023 may require the company to seek additional funding to avoid delays or reductions in research and development programs[332]. - Following the termination of the Sanofi Agreement, the company will no longer receive research and development funding, milestone payments, or other benefits, which could impact its financial stability[334].

Financial Data and Key Metrics Changes - The company raised gross proceeds of $265 million through a follow-on equity financing, strengthening its balance sheet [11][17] - Revenue from collaboration with Sanofi was $3.4 million in Q3 2022, up from $1.1 million in the prior year [17] - Total operating expenses for Q3 2022 were $79.9 million, a 47% increase from the previous year, primarily due to clinical trial costs and personnel-related expenses [18] - The net loss for Q3 2022 was $73.3 million, or $0.87 per share, with a full-year GAAP net loss expected between $260 million and $280 million [19] Business Line Data and Key Metrics Changes - The company advanced two RAS(ON) inhibitor candidates into Phase I/Ib trials, with four compounds now in human studies [6][12] - RMC-6236, an oral RAS multi-on inhibitor, is in a Phase IIb trial targeting tumors with common KRAS G12 mutations [7] - RMC-6291, an oral KRAS G12C inhibitor, is in a Phase I/Ib trial, with promising preclinical data reported [8][10] Market Data and Key Metrics Changes - The company is focusing on RAS-addicted cancers, which represent 30% of all human cancers, indicating a significant market opportunity [6] - The collaboration with Amgen is showing promising preliminary evidence for the combination of RMC-4630 with Amgen's KRAS G12C inhibitor, sotorasib [10] Company Strategy and Development Direction - The company aims to deliver on important clinical milestones in 2023, focusing on the development of RAS(ON) inhibitors and companion inhibitors [11][12] - A second wave of RAS(ON) inhibitors is planned, including a KRAS G13C inhibitor, ARMC-8839, anticipated to enter development after 2023 [13] - The strategy includes evaluating RAS companion inhibitors in combination with RAS(ON) inhibitors in the future [10][16] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's position to fulfill its mission of treating RAS-addicted cancers, highlighting recent scientific and business progress [21] - The company is committed to a science-driven approach and is optimistic about the potential of its RAS(ON) inhibitor pipeline [15][16] Other Important Information - The company recorded a non-cash GAAP accounting adjustment that reduced collaboration revenue by $4.6 million due to changes in estimates [18] - The company expects to nominate its next RAS(ON) inhibitor development candidate by the end of the year [13] Q&A Session Summary Question: How does the company view the parallel development of RMC-6236 and mutant selective inhibitors? - Management indicated that it is too early to determine which indications will benefit most from the multi-RAS inhibitor versus mutant selective inhibitors, and that clinical data will guide this [24][25] Question: What are the initial focuses for RMC-5552 in combination studies? - The focus will be on co-mutations affecting the mTOR signaling pathway, with preclinical data supporting its efficacy in combination with RAS(ON) inhibitors [26][27] Question: How is the enrollment pace for multi-RAS versus specific programs like G12C? - Both programs are on track with expectations, with high demand for RMC-6236 due to the lack of approved therapies in those indications [29][30] Question: What qualifies as superior activity for RMC-6291? - Initial data will focus on safety, tolerability, and objective responses, with combination therapy expected to be crucial for patient impact [34][35] Question: What is the therapeutic window for RMC-9805? - RMC-9805 is highly mutant selective and is expected to have a favorable therapeutic window based on preclinical results [36][37] Question: How does the company plan to pursue specific tumor histologies for RMC-6236? - The company plans to develop RMC-6236 as a single agent and in combination with other therapies, focusing on G12 mutant tumors [52]

Drug Development - The company is advancing three development-stage candidates as the first wave of RAS(ON) Inhibitors, including RMC-6236, RMC-6291, and RMC-9805, with expectations to provide evidence of first-in-class activity for these compounds in 2023[106][107][109] - RMC-6236 is designed to inhibit multiple RAS(ON) variants and is currently undergoing a monotherapy dose-escalation study[106] - RMC-6291 targets KRAS G12C(ON) with subnanomolar potency and has begun patient dosing in a monotherapy dose-escalation study, with preliminary evidence of superior activity expected in 2023[107] - RMC-9805 is designed to covalently inactivate KRAS G12D(ON) and is expected to announce dosing of the first patient in mid-2023[109] - The company is collaborating with Sanofi on RMC-4630, a SHP2 inhibitor, with multiple active clinical studies evaluating its combination with RAS inhibitors[111][113] - RMC-4630-03, a Phase 2 study of RMC-4630 in combination with sotorasib, is planned to release topline data in the second half of 2023[113] - The company is pursuing pipeline expansion programs targeting additional KRAS mutations, including KRAS G12R, G12V, G13D, and Q61X[110] - RMC-5552, another RAS Companion Inhibitor, is being evaluated as a monotherapy in a Phase 1 study, with additional evidence of single-agent activity expected in 2023[116][117] - RMC-5845, targeting SOS1, is ready for IND preparation and is under evaluation for advancement into clinical development[118] Financial Performance - Collaboration revenue for the three months ended September 30, 2022, was $3.356 million, a 205% increase from $1.101 million in the same period of 2021[138] - Total revenue for the nine months ended September 30, 2022, was $20.050 million, reflecting a $0.120 million increase from $19.930 million in the same period of 2021[138] - Research and development expenses increased by $23.0 million, or 49%, during the three months ended September 30, 2022, compared to the same period in 2021[142] - General and administrative expenses rose by $2.6 million, or 34%, during the three months ended September 30, 2022, compared to the same period in 2021[145] - Interest income increased by $2.7 million during the three months ended September 30, 2022, compared to the same period in 2021, due to a larger cash and marketable securities balance[147] - The net loss for the three months ended September 30, 2022, was $73.329 million, compared to a net loss of $52.940 million in the same period of 2021[138] - Research and development expenses for the nine months ended September 30, 2022, totaled $186.946 million, a $53.679 million increase from $133.267 million in the same period of 2021[143] - General and administrative expenses for the nine months ended September 30, 2022, were $29.676 million, reflecting a $7.918 million increase from $21.758 million in the same period of 2021[146] - The company expects research and development expenses to increase in the foreseeable future as it continues to invest in product candidates[134] - The company received an aggregate of $172.0 million from Sanofi through September 30, 2022, including the upfront payment and research and development expense reimbursements[128] - As of September 30, 2022, the company had $655.0 million in cash, cash equivalents, and marketable securities[154] - The accumulated deficit as of September 30, 2022, was $644.8 million, with cash used in operating activities amounting to $162.6 million for the nine months ended September 30, 2022[155][160] - Cash provided by financing activities for the nine months ended September 30, 2022, was $250.1 million, primarily from a follow-on offering[164] - The company expects to need substantial additional funding for research and development activities and ongoing operations[157] - Cash used in investing activities for the nine months ended September 30, 2022, was $17.0 million, with significant purchases of marketable securities[162] - The company anticipates that existing cash and marketable securities will fund planned operations for at least 12 months following the report date[156] - The net cash change for the nine months ended September 30, 2022, was an increase of $70.4 million[159] - The company incurred a net loss of $192.2 million during the nine months ended September 30, 2022[160] Contractual Obligations - The company has contractual obligations related to office and laboratory space leases in California and Massachusetts[166] - The company has not entered into any off-balance sheet arrangements as defined in Item 303 of Regulation S-K[168]