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]

Financial Data and Key Metrics Changes - In Q2 2022, the company reported a net loss of $61.2 million, or $0.82 per share, compared to a loss of $X million in the prior year period [29] - Revenue from the collaboration agreement with Sanofi was $9.1 million in Q2 2022, up from $8.7 million in the prior year [28] - Total operating expenses for Q2 2022 were $71.2 million, an increase of 34% over the prior year [28] - The company updated its 2022 GAAP net loss guidance to between $260 million and $280 million, lowering the top end by $10 million [27] Business Line Data and Key Metrics Changes - The company advanced two drug candidates from its RAS(ON) Inhibitor portfolio into clinical development, with RMC-6236 now dosing patients and RMC-6291 preparing to begin dosing [22][12] - RMC-6236 is designed to inhibit a wide range of RAS proteins and is the first development candidate from the RAS(ON) Inhibitor portfolio to enter clinical development [9] - RMC-6291 is a selective covalent inhibitor targeting the KRASG12C variant, with extensive preclinical data supporting its antitumor profile [11] Market Data and Key Metrics Changes - The company is focusing on RAS-addicted cancers, which represent 30% of all human cancers, and aims to address the unmet needs of patients with these types of cancers [6] - The company is also evaluating RAS companion inhibitors, RMC-4630 and RMC-5552, which have shown clinical evidence of antitumor activity [13] Company Strategy and Development Direction - The company completed an equity financing raising gross proceeds of $265 million to strengthen its balance sheet and support ongoing development [16] - The focus for 2022 and 2023 will be on advancing the three most advanced RAS(ON) Inhibitors and two clinical-stage RAS companion inhibitors [17] - The company plans to nominate its next RAS(ON) Inhibitor development candidate in the second half of 2022 [18] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the company's position to fulfill its mission for cancer patients, emphasizing a science-driven approach to treating RAS-addicted cancers [32] - The company expects to deliver on important milestones in the coming period, including evidence of first-in-class activity for RMC-6236 and dosing of the first patient in studies for RMC-6291 and RMC-9805 [20][21] Other Important Information - The company maintains a strong commitment to research activities that provide critical scientific insights to support ongoing development [18] - The upcoming milestones for the RAS(ON) Inhibitor portfolio include providing evidence of single-agent activity for RMC-6236 in 2023 and dosing the first patient in monotherapy studies for RMC-6291 and RMC-9805 [20] Q&A Session Summary Question: How does the company weigh the pros and cons of using limited resources for expanding positive signals with combinations versus proof-of-concept for the platform? - Management indicated that the priority is to move additional RAS(ON) inhibitors into the clinic while also considering specialized inhibitors targeting specific mutants [36] Question: What are the gating factors for expanding into combinations with RMC-4630 and RMC-5552? - Management stated that they need sufficient information to believe they have an active drug and a good sense of the dosing schedule before starting combination programs [42] Question: Can the company provide details on the dose of RMC-4630 being taken forward in the context of the combination study? - Management confirmed that the plan is to dose escalate to 200 mg and continue expanding at that level until a clear RAS signal is observed [49] Question: How will the company prioritize which RAS(ON) inhibitors to advance? - Management explained that they will create a basket of additional development candidates and prioritize based on learnings from the initial three RAS(ON) inhibitors [56] Question: Can the company provide updates on the Phase 2 RMC-4630-03 study? - Management clarified that they will provide top-line data rather than interim updates, focusing on overall response rate and durability of response [63][66] Question: What are the enrollment criteria for the Phase 1 RMC-6291 study? - Management indicated that the eligibility criteria are similar to the CodeBreaK 101 study, allowing for both previously treated and KRAS inhibitor naive patients [72] Question: Is the observed tolerability profile of combining KRAS inhibitors and PD-1s a class effect or specific to individual molecules? - Management noted that while it is hard to tell, there may be a class effect due to shared chemical features among first-generation G12C inhibitors [80]

A u g u s t 9 , 2022 On Target to Outsmart Cancer TM © 2022 Revolution Medicines Legal Disclaimer This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, business strategy, prospective products, availability of funding, ability to maintain existing collaborations, incl ...

RAS Inhibitors Development - The company is focused on developing RAS(ON) inhibitors and RAS companion inhibitors to target RAS-addicted cancers, leveraging proprietary technologies and a deep understanding of cancer biology [103]. - The RAS(ON) inhibitors portfolio includes four compounds: RMC-6236, RMC-6291, RMC-9805, and RMC-8839, with RMC-6236 expected to show first-in-class single agent activity in 2023 [106][110]. - RMC-6291 is designed to be a potent, selective inhibitor of KRAS G12C(ON) with subnanomolar potency, with first patient dosing expected in the second half of 2022 [107]. - RMC-9805 targets KRAS G12D(ON) and is planned for first patient dosing in mid-2023, while RMC-8839's dosing timeline is yet to be determined [109][110]. - RMC-4630, a RAS companion inhibitor, is being evaluated in multiple clinical studies, including a Phase 1b study in combination with Amgen's sotorasib, with topline data expected in 2023 [111][113]. - The company plans to focus development resources on RAS(ON) inhibitors and RAS companion inhibitors through 2023 [110]. - The company is pursuing pipeline expansion programs targeting additional KRAS variants and other relevant pathways [110]. - RMC-5552 is being evaluated as a monotherapy in a Phase 1 study, with additional evidence of single agent activity expected in 2023 [115][116]. Financial Performance - Collaboration revenue for Q2 2022 was $9.1 million, a 5% increase from $8.7 million in Q2 2021, but a decrease of $2.1 million, or 11%, for the first half of 2022 compared to the same period in 2021 [138]. - Research and development expenses increased by $15.1 million, or 33%, in Q2 2022 compared to Q2 2021, primarily due to higher third-party costs and increased employee-related expenses [139]. - Total operating expenses for Q2 2022 were $71.2 million, an increase of $17.9 million, or 34%, from $53.2 million in Q2 2021 [137]. - The net loss for Q2 2022 was $61.2 million, compared to a net loss of $44.3 million in Q2 2021, reflecting an increase of $16.9 million [137]. - As of June 30, 2022, the company had $461.4 million in cash, cash equivalents, and marketable securities [150]. - The accumulated deficit as of June 30, 2022, was $571.5 million, with ongoing expenses expected to increase due to continued product development [151]. - The company received a total of $166.4 million from Sanofi through upfront payments and research and development reimbursements as of June 30, 2022 [127]. - General and administrative expenses increased by $2.9 million, or 40%, in Q2 2022 compared to Q2 2021, driven by higher stock-based compensation and legal fees [141]. - Interest income increased by $0.6 million in Q2 2022 compared to Q2 2021, attributed to higher interest rates [143]. - The company expects research and development expenses to continue to rise as it advances product candidates into later stages of development [133]. - Cash used in operating activities for the six months ended June 30, 2022, was $110.9 million, compared to $71.3 million for the same period in 2021, reflecting a net loss of $118.9 million [156]. - Cash provided by investing activities for the six months ended June 30, 2022, was $106.4 million, primarily from maturities of marketable securities totaling $350.3 million [159]. - Cash provided by financing activities for the six months ended June 30, 2022, was $1.7 million, significantly lower than $283.1 million in the same period of 2021 [161]. - The company expects to require substantial additional funding for research and development activities and ongoing operations, with potential dilution of existing stockholders' interests if additional capital is raised through equity offerings [154]. - As of June 30, 2022, the company held cash, cash equivalents, and marketable securities totaling $461.4 million, down from $577.1 million as of December 31, 2021 [172]. - The company incurred non-cash charges of $20.0 million during the six months ended June 30, 2022, primarily due to stock-based compensation expenses of $14.7 million [156]. Risk Factors - The company is subject to interest rate risk, but historical fluctuations in interest income have not been significant, with an immediate one percent change in interest rates not materially affecting the fair value of cash equivalents and marketable securities [172]. - The company has contractual obligations related to office and laboratory space leases in Redwood City, California, and Cambridge, Massachusetts [163]. - The company has not entered into any off-balance sheet arrangements as defined in Item 303 of Regulation S-K [165]. - The company is exposed to foreign currency risk due to limited contracts with vendors for research and development services denominated in foreign currencies, but such risks have not been material to financial results [173]. Collaboration with Sanofi - The company has a collaboration agreement with Sanofi, which includes an upfront payment of $50 million and potential milestone payments up to $520 million [124]. - Sanofi is responsible for the commercialization of SHP2 inhibitors globally, with the company retaining co-promotion rights in the U.S. [122].

Revolution Medicines, Inc. (NASDAQ:RVMD) Q1 2022 Earnings Conference Call May 9, 2022 4:30 PM ET Company Participants David Errington - Senior Vice President of Investor Relations & Corporate Affairs Mark Goldsmith - Chairman & Chief Executive Officer Jack Anders - Senior Vice President of Finance Conference Call Participants Marc Frahm - Cowen & Company Michael Smith - Guggenheim Christopher Zap - Goldman Sachs Jonathan Chang - SVB Leerink Operator Good day. My name is Katherine, and I'll be your conferenc ...