Summary of Revolution Medicines Conference Call - September 10, 2025 Company Overview - **Company**: Revolution Medicines (NasdaqGS: RVMD) - **Focus**: Development of innovative targeted medicines for RAS addicted cancers, particularly pancreatic cancer, lung cancer, and colorectal cancer [4][5][46]. Key Points Industry Context - **Pancreatic Cancer**: - Third leading cause of cancer death in the U.S. with over 56,000 new cases annually [6][7]. - Over 90% of pancreatic adenocarcinoma (PDAC) tumors harbor a RAS driver mutation [6]. - Current five-year survival rate is only 3% despite existing therapies [7]. - Standard treatment involves cytotoxic chemotherapy, which has significant limitations [8][12]. Clinical Development - **Investigational Drugs**: - **Doraxonerasib**: The most advanced investigational RasOn inhibitor targeting RAS mutations [5][13]. - **Combination Therapy**: Evaluating doraxonerasib in combination with standard chemotherapy (GMP) for first-line treatment of metastatic PDAC [14][39]. Clinical Trial Insights - **Current Trials**: - **RAASILUTE-303**: A planned Phase III trial comparing doraxonerasib monotherapy and its combination with GMP against standard chemotherapy [40][49]. - **RAASILUTE-302**: Ongoing trial for second-line PDAC, expected to complete enrollment in 2025 [48][49]. Efficacy and Safety Data - **Monotherapy Results**: - In second-line PDAC, doraxonerasib showed a median overall survival (OS) of 13.1 months for RAS G12X and 15.6 months for all RAS mutants [20]. - Objective response rate (ORR) of 35% in RAS G12X and 29% in broader RAS mutant populations [17][18]. - **First-Line Treatment**: - In first-line PDAC, doraxonerasib monotherapy achieved an ORR of 47% and a disease control rate (DCR) of 89% [26][39]. - Combination with GMP showed an ORR of 55% and a DCR of 90% [39]. Safety Profile - **Adverse Events**: - Grade 3 or higher treatment-related adverse events (TRAEs) were reported at approximately 60% for the combination therapy [36]. - Common TRAEs included diarrhea, anemia, and liver enzyme elevations, with manageable rates [36][37][22]. Strategic Insights - **Market Positioning**: - Revolution Medicines aims to establish doraxonerasib as a new global standard of care for PDAC, addressing significant unmet medical needs [46][49]. - The company is focused on educating physicians about RAS inhibition to enhance uptake in community settings [104][106]. Future Directions - **Trial Design**: - The upcoming trials will evaluate the efficacy of doraxonerasib both as monotherapy and in combination with GMP, with a focus on overall survival as the primary endpoint [40][42]. - The company plans to reserve combination studies with FOLFIRINOX for mutant selective inhibitors due to the higher toxicity profile of FOLFIRINOX compared to GMP [44][45]. Conclusion - Revolution Medicines is making significant strides in the development of targeted therapies for RAS addicted cancers, particularly pancreatic cancer, with promising clinical data supporting the efficacy and safety of doraxonerasib. The company is poised to change the treatment landscape for PDAC through innovative trial designs and strategic market positioning [46][49].

Core Insights - Daraxonrasib shows promising clinical activity and durability in treating metastatic pancreatic ductal adenocarcinoma (PDAC) [1][2] - The company plans to initiate a three-arm Phase 3 trial in Q4 2025 to further evaluate daraxonrasib's efficacy [1][8] Clinical Data Summary - Long-term follow-up data for daraxonrasib monotherapy in second-line metastatic PDAC indicates a confirmed objective response rate (ORR) of 35% for RAS G12X mutation and 29% for any RAS mutation, with a disease control rate (DCR) of 92% and 95% respectively [5] - Median progression-free survival (PFS) was reported at 8.5 months and 8.1 months, while median overall survival (OS) was 13.1 months and 15.6 months [5] - In first-line treatment, daraxonrasib monotherapy showed an ORR of 47% and a DCR of 89% with a median follow-up of 9.3 months [5] Safety Profile - Daraxonrasib was generally well tolerated in both second-line and first-line settings, with no new safety signals identified [5][14] - The mean dose intensity for daraxonrasib was 85% in second-line and 81% in combination with chemotherapy [5][14] Combination Therapy Insights - The combination of daraxonrasib with Gemcitabine nab-Paclitaxel (GnP) demonstrated an ORR of 55% and a DCR of 90% with a median follow-up of 6.9 months [14] - The company aims to leverage the antitumor contribution of chemotherapy while maintaining sufficient dose intensity for daraxonrasib [6][14] Future Development Plans - The ongoing Phase 3 registrational trial, RASolute 302, is expected to complete global enrollment this year, with data readout anticipated in 2026 [5] - The planned RASolute 303 trial will evaluate daraxonrasib monotherapy and its combination with GnP against a control arm [8]

Financial Data and Key Metrics Changes - The company ended Q2 2025 with $2.1 billion in cash and investments, including $250 million from the Royalty Pharma partnership [22] - R&D expenses for 2025 were $224.1 million, up from $134.9 million in 2024, primarily due to clinical trial and manufacturing expenses [23] - G&A expenses increased to $40.6 million in 2025 from $21.7 million in 2024, driven by personnel-related expenses and stock-based compensation [24] - The net loss for 2025 was $247.8 million, compared to $133.2 million in 2024, mainly due to higher operating expenses [24] - The projected full-year 2025 GAAP net loss is estimated to be between $1.03 billion and $1.09 billion [25] Business Line Data and Key Metrics Changes - The company has three clinical stage RasOn inhibitors: TiraxonRasib, Oleeronrasib, and Zoldonrasib, with ongoing trials and promising data [8][10] - Diraxonrasib received breakthrough therapy designation for previously treated metastatic pancreatic cancer with KRAS G12 mutations, indicating significant unmet medical needs [9] - The ongoing global Phase 3 trial RESLU-302 for diraxonrasib is progressing well, with expectations to complete enrollment this year [9][10] Market Data and Key Metrics Changes - The company is focusing on pancreatic cancer and non-small cell lung cancer (NSCLC) as key markets, with multiple ongoing trials in these areas [10][12] - The company is expanding its clinical trials to include international sites, particularly in Europe and Japan, for NSCLC [11] Company Strategy and Development Direction - The company aims to establish a leading global RAS-targeted franchise, focusing on innovative targeted therapies for RAS addicted cancers [19][26] - A significant partnership with Royalty Pharma provides $2 billion in committed capital, enhancing the company's financial strength and strategic agility [19][20] - The company is investing in next-generation assets and collaborations to enhance its drug discovery capabilities [18][19] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the progress of clinical trials and the potential of their pipeline to transform treatment for patients with RAS-driven cancers [8][19] - The company is committed to independent global development and commercialization strategies for its RAS-targeted portfolio [19][25] Other Important Information - The company is preparing to enter clinical development for RMC-5127, a RasOn G12V selective inhibitor, expected to initiate a Phase 1 trial in 2026 [17] - The collaboration with Summit Therapeutics aims to evaluate combinations of their PD-1 VEGF bispecific antibody with the company's RasOn inhibitors [16][18] Q&A Session Summary Question: Enrollment progress for RESLU-302 and chemotherapy combinations - Management confirmed good progress in enrollment for RESLU-302 and emphasized the importance of safety and tolerability in chemotherapy combinations [30][32][35] Question: Chemotherapy regimens and data readout timelines - Management indicated that the chemotherapy regimens are within standard practice and that the first analysis of data is expected in 2026, but specifics on interim analyses were not provided [39][42][44] Question: Data updates for doraxonerasib and considerations for frontline studies - Management stated that sufficient data will guide decisions for moving forward with studies and emphasized the importance of safety and dose intensity [48][51][52] Question: RAF upregulation and combination therapies - Management acknowledged RAS amplification as a challenge but expressed confidence in their inhibitors' effectiveness and the potential benefits of combination therapies [59][62] Question: Commercialization readiness and market engagement - The commercialization team is actively engaged in market shaping activities and building operational capabilities for future product launches [73][74] Question: Summit partnership and prioritization of combinations - Management noted that while they cannot provide specific prioritization details, they are excited about the collaboration and its potential across various solid tumors [78][80]

Financial Data and Key Metrics Changes - The company ended Q2 2025 with $2.1 billion in cash and investments, including $250 million from the Royalty Pharma partnership [19] - R&D expenses increased to $224.1 million in 2025 from $134.9 million in 2024, primarily due to clinical trial and manufacturing expenses [20] - G&A expenses rose to $40.6 million in 2025 from $21.7 million in 2024, driven by personnel-related expenses and stock-based compensation [21] - The net loss for 2025 was $247.8 million, compared to $133.2 million in 2024, attributed to higher operating expenses [22] - The projected full-year 2025 GAAP net loss is estimated to be between $1.03 billion and $1.09 billion [23] Business Line Data and Key Metrics Changes - The company has three clinical-stage RasOn inhibitors: TiraxonRasib, Oleuronrasib, and Zoldonrasib, with ongoing trials in pancreatic cancer and non-small cell lung cancer [6][10] - Diraxonrasib received breakthrough therapy designation from the FDA for previously treated metastatic pancreatic cancer with KRAS G12 mutations [7] - Oleuronrasib was granted breakthrough therapy designation for locally advanced or metastatic KRAS G12C non-small cell lung cancer [12] Market Data and Key Metrics Changes - Enrollment for the RESLU-302 Phase 3 trial in pancreatic cancer is progressing well, with expectations to complete enrollment this year [8] - The company is also initiating a first-line metastatic pancreatic cancer registrational trial, with plans to share trial design later this year [9] Company Strategy and Development Direction - The company aims to establish a leading global RAS-targeted franchise for treating RAS addicted cancers, focusing on innovative targeted therapies [17] - A partnership with Royalty Pharma provides $2 billion in committed capital to support clinical development and commercialization plans [18] - The company is preparing to enter clinical development for RMC-5127, a RasOn G12V selective inhibitor, expected to initiate a Phase 1 trial in 2026 [15] Management's Comments on Operating Environment and Future Outlook - Management emphasized the urgency of advancing development for patients with pancreatic cancer due to significant unmet medical needs [7] - The company is confident in its ability to establish new global standards of care for patients with RAS addicted cancers [24] - Management highlighted the importance of safety and tolerability in ongoing assessments to inform study designs for future trials [32] Other Important Information - The company is collaborating with Summit Therapeutics to evaluate combinations of their bispecific antibody with RasOn inhibitors [14] - The collaboration with Iambic aims to enhance drug discovery through AI capabilities, potentially improving lead discovery and optimization processes [16] Q&A Session Summary Question: Enrollment progress for RESLU-302 and chemotherapy combinations - Management indicated that enrollment is progressing well, with a solid position to share data in 2026. Efficacy assessments will inform study design, but safety and tolerability remain primary concerns [29][32] Question: Chemotherapy regimens and data readout in 2026 - Management confirmed that the chemotherapy regimens are within standard practice and that the 2026 data readout refers to the first analysis, which may be interim or final [40][42] Question: Data update for frontline pancreatic cancer trial - Management stated that they are building a sufficient data set to guide decision-making and will share more information as it becomes available [46] Question: RAF upregulation and combination therapies - Management acknowledged RAS amplification as a challenge but emphasized that therapeutic strategies are in place to address it. They also noted that there is no evidence that degraders are superior to inhibitors [60][62] Question: Commercialization readiness and field team build-out - Management confirmed that the US field team is being built out, with a focus on market shaping activities and engagement with oncologists [70][71]

Pipeline and Clinical Development - Daraxonrasib, a multi-selective RAS(ON) inhibitor, is being evaluated in a Phase 3 trial for 2L metastatic PDAC and has planned Phase 3 initiations for 1L metastatic and adjuvant resectable PDAC [15] - Elironrasib, a G12C-selective inhibitor, shows promising antitumor activity in previously treated RAS G12C NSCLC, with an objective response rate (ORR) of 56% (20 out of 36 patients) and a disease control rate (DCR) of 94% (34 out of 36 patients) at 200 mg BID [40] - Zoldonrasib, a G12D-selective inhibitor, demonstrates initial activity in previously treated KRAS G12D NSCLC, with an ORR of 61% (11 out of 18 patients) and a DCR of 89% (16 out of 18 patients) at 1200 mg QD [72] Daraxonrasib Clinical Data - In 2L PDAC patients treated with daraxonrasib at 300 mg daily, the median PFS was 85 months in RAS mutant patients, and the OS rate at 6 months was 97% [24] - In 2L/3L RAS G12X NSCLC patients treated with daraxonrasib at 120-220 mg daily, the median PFS was 98 months and the median OS was 177 months [28] - Daraxonrasib combined with pembrolizumab +/- chemotherapy in 1L RAS mutant NSCLC showed an ORR of 60% and a DCR of 90% in patients with TPS < 50%, and an ORR of 86% and a DCR of 100% in patients with TPS ≥ 50% [32] Financial Position - The company has a strong financial position with $21 billion in cash, cash equivalents, and marketable securities as of June 30, 2025 [119] - The company anticipates a 2025 GAAP Net Loss of $103 - $109 Billion [119]

[Special Note Regarding Forward-Looking Statements](index=4&type=section&id=Special%20Note%20Regarding%20Forward-Looking%20Statements) This section cautions investors about forward-looking statements, which are subject to risks and uncertainties that may cause actual results to differ materially - This report contains forward-looking statements concerning the company's business, operations, and financial performance, which are subject to known and unknown risks and uncertainties that may cause actual results to differ materially[9](index=9&type=chunk) - These statements cover various aspects including product candidate development, regulatory approvals, market size, collaborations, commercialization, intellectual property, financial estimates, and the competitive landscape[10](index=10&type=chunk) - Investors are cautioned not to unduly rely on these forward-looking statements as predictions of future events, and the company does not plan to publicly update or revise them unless required by applicable law[11](index=11&type=chunk) [PART I. FINANCIAL INFORMATION](index=6&type=section&id=PART%20I.%20FINANCIAL%20INFORMATION) This part presents the company's unaudited condensed consolidated financial statements and management's discussion and analysis of financial condition and results of operations [Item 1. Financial Statements (unaudited)](index=6&type=section&id=Item%201.%20Financial%20Statements%20(unaudited)) This item presents the unaudited condensed consolidated financial statements for Revolution Medicines, Inc., prepared in conformity with GAAP and SEC rules for interim financial reporting [Condensed Consolidated Balance Sheets](index=6&type=section&id=Condensed%20Consolidated%20Balance%20Sheets) This section provides a snapshot of the company's financial position, detailing assets, liabilities, and stockholders' equity at specific dates | Metric (in thousands) | June 30, 2025 | December 31, 2024 | | :-------------------- | :------------ | :---------------- | | Cash and cash equivalents | $402,438 | $543,064 | | Marketable securities | $1,734,733 | $1,746,235 | | Total current assets | $2,176,439 | $2,327,632 | | Total assets | $2,429,568 | $2,558,301 | | Total current liabilities | $184,534 | $163,914 | | Liability related to the sale of future royalties | $245,081 | $— | | Total liabilities | $564,199 | $293,097 | | Total stockholders' equity | $1,865,369 | $2,265,204 | - Total assets decreased by **$128,733 thousand** from December 31, 2024, to June 30, 2025, primarily due to decreases in cash and cash equivalents and marketable securities[17](index=17&type=chunk) - Total liabilities significantly increased by **$271,102 thousand**, mainly driven by the new **$245,081 thousand** liability related to the sale of future royalties[17](index=17&type=chunk) [Condensed Consolidated Statements of Operations and Comprehensive Loss](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations%20and%20Comprehensive%20Loss) This statement outlines the company's revenues, expenses, and net loss over specific reporting periods, reflecting operational performance | Metric (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Research and development | $224,134 | $134,932 | $429,883 | $252,953 | | General and administrative | $40,580 | $21,711 | $75,591 | $44,549 | | Total operating expenses | $264,714 | $156,643 | $505,474 | $297,502 | | Loss from operations | $(264,714) | $(156,643) | $(505,474) | $(297,502) | | Net loss | $(247,787) | $(133,233) | $(461,203) | $(249,236) | | Net loss per share (basic and diluted) | $(1.31) | $(0.81) | $(2.45) | $(1.51) | - Net loss increased by **$114,554 thousand (86%)** for the three months ended June 30, 2025, and by **$211,967 thousand (85%)** for the six months ended June 30, 2025, compared to the prior year periods[20](index=20&type=chunk)[147](index=147&type=chunk) - Total operating expenses increased by **$108,071 thousand (69%)** for the three months and **$207,972 thousand (70%)** for the six months ended June 30, 2025, primarily due to higher research and development expenses[20](index=20&type=chunk)[147](index=147&type=chunk) [Condensed Consolidated Statements of Stockholders' Equity](index=8&type=section&id=Condensed%20Consolidated%20Statements%20of%20Stockholders'%20Equity) This statement details changes in the company's equity accounts, including common stock, additional paid-in capital, and accumulated deficit | Metric (in thousands) | December 31, 2024 | June 30, 2025 | | :-------------------- | :---------------- | :------------ | | Common Stock | $18 | $18 | | Additional Paid-in Capital | $4,001,666 | $4,063,053 | | Accumulated Other Comprehensive Income | $1,321 | $1,302 | | Accumulated Deficit | $(1,737,801) | $(2,199,004) | | Total Stockholders' Equity | $2,265,204 | $1,865,369 | - Total stockholders' equity decreased by **$399,835 thousand** from December 31, 2024, to June 30, 2025, primarily due to the increase in accumulated deficit from net losses[23](index=23&type=chunk) - Additional paid-in capital increased by **$61,387 thousand**, driven by stock-based compensation expense, stock option exercises, and employee stock purchase plan proceeds[23](index=23&type=chunk)[28](index=28&type=chunk)[171](index=171&type=chunk) [Condensed Consolidated Statements of Cash Flows](index=10&type=section&id=Condensed%20Consolidated%20Statements%20of%20Cash%20Flows) This statement summarizes the cash inflows and outflows from operating, investing, and financing activities over specific periods | Metric (in thousands) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------- | :------------------------------- | :------------------------------- | | Net cash used in operating activities | $(416,192) | $(288,727) | | Net cash provided by (used in) investing activities | $18,327 | $(140,022) | | Net cash provided by financing activities | $257,457 | $8,314 | | Net decrease in cash, cash equivalents and restricted cash | $(140,408) | $(420,435) | | Cash, cash equivalents and restricted cash - end of period | $406,354 | $278,744 | - Net cash used in operating activities increased by **$127,465 thousand**, from **$(288,727) thousand** in 2024 to **$(416,192) thousand** in 2025[28](index=28&type=chunk)[166](index=166&type=chunk) - Net cash provided by investing activities significantly improved, shifting from a net outflow of **$(140,022) thousand** in 2024 to a net inflow of **$18,327 thousand** in 2025[28](index=28&type=chunk)[166](index=166&type=chunk) - Net cash provided by financing activities increased substantially from **$8,314 thousand** in 2024 to **$257,457 thousand** in 2025, primarily due to proceeds from the sale of future royalties[28](index=28&type=chunk)[166](index=166&type=chunk)[171](index=171&type=chunk) [Notes to Condensed Consolidated Financial Statements](index=11&type=section&id=Notes%20to%20Condensed%20Consolidated%20Financial%20Statements) These notes provide additional information and explanations essential for understanding the condensed consolidated financial statements [1. Organization](index=11&type=section&id=1.%20Organization) This note describes the company's business, its focus on oncology, and its financial condition regarding operating losses and funding - Revolution Medicines, Inc. is a clinical-stage precision oncology company founded in October 2014, focused on developing novel targeted therapies for RAS-addicted cancers[31](index=31&type=chunk) - The company has incurred net operating losses since inception, with an accumulated deficit of **$2.2 billion** as of June 30, 2025[32](index=32&type=chunk) - Management believes that existing cash, cash equivalents, and marketable securities will enable the company to fund planned operations for at least **12 months** from the issuance date of these financial statements[32](index=32&type=chunk) [2. Summary of significant accounting policies](index=11&type=section&id=2.%20Summary%20of%20significant%20accounting%20policies) This note outlines the key accounting principles and methods used in preparing the financial statements, including estimates and revenue recognition - The unaudited condensed consolidated financial statements are prepared in conformity with GAAP and SEC rules for interim financial reporting, including all normal and recurring adjustments[33](index=33&type=chunk) - Management's estimates, such as fair value, revenue recognition, clinical accruals, and valuation of assets and liabilities, are inherently uncertain and subject to change, with actual results potentially differing materially[34](index=34&type=chunk) - The company accounts for the revenue participation right purchase and sale agreement as a debt financing, amortized over the estimated life of the royalty term arrangement using the effective interest method[36](index=36&type=chunk)[37](index=37&type=chunk) Research and Development Expense Components (in thousands) | Research and Development Expense Components (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :------------------------------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Third-party R&D expenses | $144,138 | $81,657 | $276,881 | $150,926 | | Salaries and other employee-related expenses | $41,170 | $26,328 | $78,364 | $51,490 | | Stock-based compensation expense | $19,126 | $12,775 | $35,505 | $23,020 | | Amortization of intangible assets | $267 | $267 | $534 | $534 | | Other R&D costs | $19,433 | $13,905 | $38,599 | $26,983 | | **Total research and development expense** | **$224,134** | **$134,932** | **$429,883** | **$252,953** | [3. Fair value measurements](index=15&type=section&id=3.%20Fair%20value%20measurements) This note details the categorization and valuation of financial instruments recorded at fair value using a three-tier hierarchy - Financial instruments recorded at fair value are categorized into a three-tier hierarchy (Level 1, 2, or 3) based on the observability of inputs used in their valuation[47](index=47&type=chunk) Financial Assets and Warrant Liabilities (in thousands) | Financial Assets (in thousands) | Total (June 30, 2025) | Level 1 | Level 2 | Level 3 | Total (December 31, 2024) | Level 1 | Level 2 | Level 3 | | :---------------------------- | :-------------------- | :------ | :------ | :------ | :------------------------ | :------ | :------ | :------ | | Money market funds | $350,642 | $350,642 | $— | $— | $409,233 | $409,233 | $— | $— | | Commercial paper | $159,293 | $— | $159,293 | $— | $245,658 | $— | $245,658 | $— | | Certificates of deposit | $3,833 | $— | $3,833 | $— | $9,048 | $— | $9,048 | $— | | U.S. government and agency securities | $867,787 | $— | $867,787 | $— | $1,051,754 | $— | $1,051,754 | $— | | Corporate bonds | $754,880 | $— | $754,880 | $— | $571,654 | $— | $571,654 | $— | | **Total Assets** | **$2,136,435** | **$350,642** | **$1,785,793** | **$—** | **$2,287,347** | **$409,233** | **$1,878,114** | **$—** | | **Warrant liabilities** | **$5,328** | **$2,981** | **$2,347** | **$—** | **$3,189** | **$1,784** | **$1,405** | **$—** | - The fair value of public warrants is categorized as **Level 1**, while private warrants are **Level 2** due to not being actively traded, despite having substantially similar terms[50](index=50&type=chunk) [4. Available-for-sale securities](index=17&type=section&id=4.%20Available-for-sale%20securities) This note provides details on the company's available-for-sale securities, including their amortized cost, fair value, and unrealized gains/losses Available-for-sale securities (in thousands) | Available-for-sale securities (in thousands) | Amortized cost (June 30, 2025) | Estimated fair value (June 30, 2025) | Gross unrealized gain (June 30, 2025) | Gross unrealized loss (June 30, 2025) | | :----------------------------------------- | :------------------------------- | :----------------------------------- | :------------------------------------ | :------------------------------------ | | Marketable securities | $1,733,423 | $1,734,733 | $1,595 | $(285) | | Cash equivalents | $401,710 | $401,702 | $(1) | $(7) | | **Total** | **$2,135,133** | **$2,136,435** | **$1,594** | **$(292)** | Contractual Maturity of Available-for-sale securities (in thousands) | Contractual Maturity (in thousands) | Amortized cost (June 30, 2025) | Estimated fair value (June 30, 2025) | | :-------------------------------- | :------------------------------- | :----------------------------------- | | Mature in one year or less | $1,694,180 | $1,694,788 | | Mature after one year through two years | $440,953 | $441,647 | | **Total** | **$2,135,133** | **$2,136,435** | - As of June 30, 2025, the total estimated fair value of available-for-sale securities was **$2,136,435 thousand**, with a net unrealized gain of **$1,302 thousand**[51](index=51&type=chunk) [5. Balance sheet components](index=18&type=section&id=5.%20Balance%20sheet%20components) This note breaks down specific balance sheet items, including property and equipment, and accrued expenses and other current liabilities Property and equipment, net (in thousands) | Property and equipment, net (in thousands) | June 30, 2025 | December 31, 2024 | | :--------------------------------------- | :------------ | :---------------- | | Laboratory equipment | $28,045 | $25,192 | | Leasehold improvements | $21,341 | $14,280 | | Computer equipment and software | $6,536 | $5,046 | | Furniture and fixtures | $1,655 | $1,200 | | Construction in progress | $500 | $394 | | Less: accumulated depreciation and amortization | $(25,028) | $(21,823) | | **Total property and equipment, net** | **$33,049** | **$24,289** | Accrued expenses and other current liabilities (in thousands) | Accrued expenses and other current liabilities (in thousands) | June 30, 2025 | December 31, 2024 | | :-------------------------------------------------------- | :------------ | :---------------- | | Accrued compensation | $21,726 | $30,774 | | Accrued research and development | $89,583 | $63,635 | | Accrued professional services | $2,914 | $1,623 | | Other | $462 | $583 | | **Total accrued expenses and other current liabilities** | **$114,685** | **$96,615** | - Property and equipment, net, increased by **$8,760 thousand**, primarily due to increases in laboratory equipment and leasehold improvements[53](index=53&type=chunk) - Accrued expenses and other current liabilities increased by **$18,070 thousand**, mainly driven by higher accrued research and development expenses[54](index=54&type=chunk) [6. Intangible assets and goodwill](index=18&type=section&id=6.%20Intangible%20assets%20and%20goodwill) This note provides details on the company's intangible assets, including in-process research and development, and goodwill Intangible assets, net (in thousands) | Intangible assets, net (in thousands) | Gross value (June 30, 2025) | Accumulated amortization (June 30, 2025) | Net book value (June 30, 2025) | Remaining useful life (in years) | | :------------------------------------ | :-------------------------- | :--------------------------------------- | :----------------------------- | :------------------------------- | | In-process research and development — RAS Programs | $55,800 | $— | $55,800 | n/a | | Developed technology — tri-complex platform | $7,480 | $(7,144) | $336 | 0.4 | | **Total** | **$63,280** | **$(7,144)** | **$56,136** | | - Intangible assets, net, totaled **$56,136 thousand** as of June 30, 2025, primarily comprising in-process research and development for RAS Programs[55](index=55&type=chunk) - Goodwill remained constant at **$14,608 thousand** as of June 30, 2025, with no impairment recognized[57](index=57&type=chunk) [7. Commitments and contingencies](index=19&type=section&id=7.%20Commitments%20and%20contingencies) This note outlines the company's contractual obligations, such as operating leases, and discusses legal proceedings - The company has expanded its operating lease for office, laboratory, and R&D space in Redwood City, California, to include multiple buildings, with the lease term extended through **December 31, 2035**[58](index=58&type=chunk) Operating Lease Liabilities (in thousands) | Operating Lease Liabilities (in thousands) | June 30, 2025 | December 31, 2024 | | :--------------------------------------- | :------------ | :---------------- | | Operating lease liability – current | $13,088 | $12,872 | | Operating lease liability – noncurrent | $119,699 | $122,971 | | **Total operating lease liabilities** | **$132,787** | **$135,843** | - Total operating lease cost, net of sublease income, was **$3,652 thousand** for the three months ended June 30, 2025, and **$7,207 thousand** for the six months ended June 30, 2025[64](index=64&type=chunk) - The company is involved in a legal proceeding (Nemeth v. Casdin, et al.) but does not believe it will have a material adverse impact on its operations or financial position[68](index=68&type=chunk)[69](index=69&type=chunk) [8. Liability related to the sale of future royalties](index=21&type=section&id=8.%20Liability%20related%20to%20the%20sale%20of%20future%20royalties) This note details the agreement for the sale of future royalties, including proceeds received and the accounting treatment as a debt financing - In June 2025, the company entered into a Royalty Purchase Agreement with Royalty Pharma, receiving an upfront payment of **$250.0 million** for tiered royalty payments on future worldwide net product sales of RMC-6236 and RMC-9805 products[72](index=72&type=chunk) - The agreement includes potential for up to an additional **$1.0 billion** in funding across four tranches, contingent on specific clinical and commercial milestones[73](index=73&type=chunk)[74](index=74&type=chunk) - The agreement is accounted for as a debt financing, with a liability of **$245,081 thousand** recorded as of June 30, 2025, and non-cash interest expense recognized using the effective interest method[78](index=78&type=chunk)[79](index=79&type=chunk)[82](index=82&type=chunk) Liability related to the sale of future royalties (in thousands) | Liability related to the sale of future royalties (in thousands) | Amount | | :------------------------------------------------------- | :----- | | Liability related to the sale of future royalties - beginning balance | $— | | Proceeds from the sale of future royalties | $250,000 | | Issuance costs | $(5,785) | | Non-cash interest expense associated with the sale of future royalties | $846 | | Amortization of issuance costs | $20 | | **Liability related to the sale of future royalties - ending balance** | **$245,081** | [9. Term loan facility](index=24&type=section&id=9.%20Term%20loan%20facility) This note describes the senior secured term loan agreement, outlining potential tranches, interest rates, and collateral - In June 2025, the company entered into a senior secured term loan agreement providing for up to **$750.0 million** in term loans across three tranches[83](index=83&type=chunk) - The first tranche is required to be drawn upon FDA marketing approval for daraxonrasib for metastatic PDAC by **January 1, 2028**, with optional tranches upon commercial milestones[83](index=83&type=chunk) - The term loans bear interest at a floating rate (three-month term SOFR + **5.75%**) and are secured by substantially all of the company's assets[84](index=84&type=chunk)[88](index=88&type=chunk) - As of June 30, 2025, no amounts had been drawn under the Loan Agreement, and no liability was recorded[88](index=88&type=chunk) [10. Common stock](index=24&type=section&id=10.%20Common%20stock) This note provides information on the company's authorized and outstanding common stock, and shares reserved for future issuance - As of June 30, 2025, the company had **186,901,268 shares** of common stock issued and outstanding, with **300,000,000 shares** authorized[17](index=17&type=chunk)[90](index=90&type=chunk) - The company has reserved **32,905,133 shares** of common stock for future issuance, including for outstanding options, unvested restricted stock units, and the employee stock purchase plan[90](index=90&type=chunk) - No dividends have been declared on common stock to date[89](index=89&type=chunk) [11. Stock-based compensation](index=25&type=section&id=11.%20Stock-based%20compensation) This note details the company's stock-based compensation plans, including expense recognition and unrecognized compensation costs - The 2020 Incentive Award Plan and 2020 Employee Stock Purchase Plan are the primary stock-based compensation plans, with options and RSUs typically vesting over **four years**[91](index=91&type=chunk)[93](index=93&type=chunk) Stock-based compensation expense (in thousands) | Stock-based compensation expense (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Research and development | $19,126 | $12,775 | $35,505 | $23,020 | | General and administrative | $9,704 | $7,000 | $18,409 | $12,963 | | **Total** | **$28,830** | **$19,775** | **$53,914** | **$35,983** | - Total stock-based compensation expense increased by **$9,055 thousand (46%)** for the three months and **$17,931 thousand (50%)** for the six months ended June 30, 2025, compared to the prior year periods[98](index=98&type=chunk) - As of June 30, 2025, unrecognized compensation cost for unvested stock options was **$178.5 million** and for RSUs was **$127.0 million**, expected to be recognized over weighted-average periods of **2.85** and **2.96 years**, respectively[96](index=96&type=chunk)[97](index=97&type=chunk) [12. Net loss per share attributable to common stockholders](index=26&type=section&id=12.%20Net%20loss%20per%20share%20attributable%20to%20common%20stockholders) This note presents the calculation of basic and diluted net loss per share, including the impact of potentially dilutive shares Net loss per share attributable to common stockholders | Metric | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------------------------------------------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Net loss attributable to common stockholders (in thousands) | $(247,787) | $(133,233) | $(461,203) | $(249,236) | | Weighted-average common shares (basic and diluted) | 188,583,288 | 165,141,936 | 188,365,805 | 164,935,542 | | **Net loss per share (basic and diluted)** | **$(1.31)** | **$(0.81)** | **$(2.45)** | **$(1.51)** | - Net loss per share (basic and diluted) increased from **$(0.81)** to **$(1.31)** for the three months and from **$(1.51)** to **$(2.45)** for the six months ended June 30, 2025[99](index=99&type=chunk) - Potentially dilutive shares, totaling **23,970,215** as of June 30, 2025, were excluded from diluted EPS calculations due to their anti-dilutive effect resulting from the company's net loss[100](index=100&type=chunk) [13. Subsequent events](index=27&type=section&id=13.%20Subsequent%20events) This note discloses significant events occurring after the balance sheet date, such as new legislation and lease amendments - On **July 4, 2025**, the 'One Big Beautiful Bill Act' (OBBBA) was enacted, modifying corporate income tax code, with its potential impact on the company's financial statements currently being assessed[101](index=101&type=chunk) - In July 2025, the company amended its Redwood City lease to add approximately **60,841 square feet** at 400 Saginaw Drive, with an initial annual base rent of **$3.9 million** and a **$4.1 million** tenant improvement allowance[102](index=102&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=28&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) This section provides management's perspective on the company's financial condition and results of operations, emphasizing its status as a clinical-stage precision oncology company focused on RAS-addicted cancers [Overview](index=28&type=section&id=Overview) This overview introduces Revolution Medicines as a clinical-stage precision oncology company, detailing its pipeline and recent clinical developments - Revolution Medicines is a clinical-stage precision oncology company developing novel targeted therapies for RAS-addicted cancers, leveraging sophisticated structure-based drug discovery capabilities[105](index=105&type=chunk) - The pipeline includes RAS(ON) inhibitors (e.g., daraxonrasib, elironrasib, zoldonrasib) and RAS companion inhibitors, designed to be used as monotherapy or in combination regimens[106](index=106&type=chunk)[109](index=109&type=chunk) - Daraxonrasib (RMC-6236) received **Breakthrough Therapy Designation** for previously treated metastatic pancreatic ductal adenocarcinoma (PDAC) in patients with KRAS G12 mutations, with global Phase 3 trials ongoing[110](index=110&type=chunk)[111](index=111&type=chunk) - Elironrasib (RMC-6291) received **Breakthrough Therapy Designation** for KRAS G12C-mutated NSCLC, and zoldonrasib (RMC-9805) showed encouraging initial antitumor activity in PDAC and NSCLC[121](index=121&type=chunk)[127](index=127&type=chunk) - The company has established collaborations with Tango Therapeutics, Summit Therapeutics, Aethon Therapeutics, Break Through Cancer, and Iambic Therapeutics to advance its pipeline and research efforts[136](index=136&type=chunk)[137](index=137&type=chunk)[138](index=138&type=chunk)[139](index=139&type=chunk)[140](index=140&type=chunk) [Financial Operations Overview](index=34&type=section&id=Financial%20Operations%20Overview) This section outlines the key components of the company's financial operations, including research and development, general and administrative expenses, and interest income - Research and development expenses, which are expensed as incurred, consist primarily of external costs for preclinical studies, clinical trials, manufacturing, and discovery programs[141](index=141&type=chunk)[142](index=142&type=chunk) - R&D expenses are expected to increase for the foreseeable future as product candidates advance into later stages of development and larger clinical trials[143](index=143&type=chunk) - General and administrative expenses, comprising personnel, professional services, and commercial preparation activities, are also expected to increase due to anticipated growth[144](index=144&type=chunk) - Interest income is primarily from cash equivalents and marketable securities, while other income (expense) includes non-cash interest expense from the sale of future royalties and foreign currency exchange differences[145](index=145&type=chunk)[146](index=146&type=chunk) [Results of operations](index=36&type=section&id=Results%20of%20operations) This section analyzes the company's financial performance, focusing on changes in operating expenses and interest income over the reporting periods [Research and development expenses](index=37&type=section&id=Research%20and%20development%20expenses) This section details the components and changes in research and development expenses, highlighting key drivers for increases R&D Expense Components (in thousands) | R&D Expense Components (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Increase/ (decrease) | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | Increase/ (decrease) | | :------------------------------------ | :------------------------------- | :------------------------------- | :------------------- | :----------------------------- | :----------------------------- | :------------------- | | Daraxonrasib (RMC-6236) | $76,907 | $30,220 | $46,687 | $144,382 | $57,218 | $87,164 | | Zoldonrasib (RMC-9805) | $23,515 | $14,715 | $8,800 | $47,983 | $26,675 | $21,308 | | Elironrasib (RMC-6291) | $18,192 | $15,754 | $2,438 | $37,208 | $25,684 | $11,524 | | Preclinical programs | $25,457 | $19,367 | $6,090 | $46,810 | $37,439 | $9,371 | | Salaries and other employee-related expenses | $41,170 | $26,328 | $14,842 | $78,364 | $51,490 | $26,874 | | Stock-based compensation expense | $19,126 | $12,775 | $6,351 | $35,505 | $23,020 | $12,485 | | Other research and development costs | $19,433 | $13,905 | $5,528 | $38,599 | $26,983 | $11,616 | | **Total research and development expense** | **$224,134** | **$134,932** | **$89,202** | **$429,883** | **$252,953** | **$176,930** | - Research and development expenses increased by **$89.2 million (66%)** for the three months and **$176.9 million (70%)** for the six months ended June 30, 2025, compared to the prior year[148](index=148&type=chunk)[149](index=149&type=chunk) - The increase was primarily driven by higher clinical trial and manufacturing expenses for daraxonrasib (**$46.7 million** QoQ, **$87.2 million** YoY) and increased salaries and employee-related expenses due to headcount growth (**$14.8 million** QoQ, **$26.9 million** YoY)[148](index=148&type=chunk)[149](index=149&type=chunk) [General and administrative expenses](index=37&type=section&id=General%20and%20administrative%20expenses) This section analyzes the changes in general and administrative expenses, identifying the primary factors contributing to their increase - General and administrative expenses increased by **$18.9 million (87%)** for the three months and **$31.0 million (70%)** for the six months ended June 30, 2025, compared to the prior year[150](index=150&type=chunk)[151](index=151&type=chunk) - Key drivers for the increase include higher salaries and employee-related expenses (**$6.5 million** QoQ, **$10.2 million** YoY), commercial preparation expenses (**$5.3 million** QoQ, **$8.9 million** YoY), and stock-based compensation expense (**$2.7 million** QoQ, **$5.4 million** YoY)[150](index=150&type=chunk)[151](index=151&type=chunk) [Interest income](index=39&type=section&id=Interest%20income) This section discusses the company's interest income, explaining the factors influencing its changes over the reporting periods Interest income (in thousands) | Metric (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Interest income | $22,404 | $21,487 | $47,319 | $45,247 | - Interest income increased by **$0.9 million** for the three months and **$2.1 million** for the six months ended June 30, 2025, compared to the same periods in 2024, due to a larger cash, cash equivalents, and marketable securities balance[152](index=152&type=chunk) [Liquidity and Capital Resources](index=39&type=section&id=Liquidity%20and%20Capital%20Resources) This section assesses the company's ability to meet its financial obligations, detailing its cash position and future funding requirements - As of June 30, 2025, the company had **$2.1 billion** in cash, cash equivalents, and marketable securities, which management believes is sufficient to fund planned operations for at least **12 months**[162](index=162&type=chunk)[164](index=164&type=chunk) - The company's operations have been financed primarily by public offerings of common stock, the EQRx Acquisition, and the Royalty Purchase Agreement[154](index=154&type=chunk)[155](index=155&type=chunk)[156](index=156&type=chunk)[162](index=162&type=chunk) - Substantial additional funds will be required for future development and commercialization efforts, which may be sought through equity offerings, debt financings, collaborations, or licensing arrangements, with potential risks of dilution or restrictive covenants[164](index=164&type=chunk) [Cash Flows](index=42&type=section&id=Cash%20Flows) This section provides a detailed analysis of the company's cash inflows and outflows from operating, investing, and financing activities [Cash used in operating activities](index=42&type=section&id=Cash%20used%20in%20operating%20activities) This section explains the primary drivers of cash used in operating activities, including net loss and non-cash charges - Cash used in operating activities was **$416.2 million** for the six months ended June 30, 2025, primarily driven by a net loss of **$461.2 million**[167](index=167&type=chunk) - Non-cash charges, including stock-based compensation (**$53.9 million**) and depreciation and amortization (**$4.0 million**), partially offset the net loss[167](index=167&type=chunk) - Changes in operating assets and liabilities included a **$12.4 million** increase in accrued expenses and other current liabilities and a **$16.5 million** increase in other noncurrent assets[167](index=167&type=chunk) [Cash provided by (used in) investing activities](index=42&type=section&id=Cash%20provided%20by%20(used%20in)%20investing%20activities) This section details the cash flows from investing activities, highlighting the shift from net outflow to net inflow - Investing activities provided **$18.3 million** in cash for the six months ended June 30, 2025, a significant improvement from a **$140.0 million** outflow in the prior year[169](index=169&type=chunk)[170](index=170&type=chunk) - This shift was mainly due to **$1.1 billion** in maturities of marketable securities and **$6.4 million** from sales of marketable securities, partially offset by **$1.0 billion** in purchases of marketable securities and **$10.7 million** in property and equipment purchases[169](index=169&type=chunk) [Cash provided by financing activities](index=42&type=section&id=Cash%20provided%20by%20financing%20activities) This section analyzes the significant increase in cash provided by financing activities, primarily due to the sale of future royalties - Financing activities provided **$257.5 million** in cash for the six months ended June 30, 2025, a substantial increase from **$8.3 million** in the prior year[171](index=171&type=chunk)[172](index=172&type=chunk) - The primary driver was **$250.0 million** in proceeds from the sale of future royalties[171](index=171&type=chunk) - Additional proceeds came from common stock issuance under equity incentive plans (**$2.8 million**) and the employee stock purchase plan (**$4.6 million**)[171](index=171&type=chunk) [Contractual Obligations and Commitments](index=43&type=section&id=Contractual%20Obligations%20and%20Commitments) This section outlines the company's significant contractual obligations, including operating leases and royalty payment agreements - The company's contractual obligations include operating lease liabilities for its Redwood City facilities[173](index=173&type=chunk) - The Royalty Purchase Agreement creates an obligation for tiered royalty payments on future worldwide net product sales of daraxonrasib and zoldonrasib[175](index=175&type=chunk) - The company also enters into generally cancelable agreements with contract research organizations and contract manufacturing organizations for clinical trials and materials[174](index=174&type=chunk) [Indemnification Agreements](index=43&type=section&id=Indemnification%20Agreements) This section describes the company's standard indemnification arrangements and their potential financial implications - The company enters into standard indemnification arrangements in the ordinary course of business, agreeing to reimburse indemnified parties for losses related to intellectual property infringement claims[176](index=176&type=chunk) - The maximum potential amount of future payments under these perpetual agreements is not determinable, but the company believes their fair value is minimal as no related costs have been incurred to date[176](index=176&type=chunk) [Critical Accounting Policies, Significant Judgments and Use of Estimates](index=43&type=section&id=Critical%20Accounting%20Policies,%20Significant%20Judgments%20and%20Use%20of%20Estimates) This section highlights the critical accounting policies and the inherent uncertainties in management's estimates and assumptions - The company's financial statements are based on U.S. GAAP, requiring management to make significant estimates and assumptions that affect reported amounts and disclosures[177](index=177&type=chunk) - These estimates, particularly for future royalties, are inherently uncertain and subject to change, with actual results potentially differing materially from the company's estimates[178](index=178&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=44&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) This item discusses the company's exposure to market risks, primarily interest rate and foreign currency risks, and how they are managed - The company is exposed to market risks primarily related to interest rate sensitivities and foreign currency fluctuations[181](index=181&type=chunk) - Interest rate risk is managed by maintaining a portfolio of high-credit quality, short-term investments, including cash, cash equivalents, and marketable securities totaling **$2.1 billion** as of June 30, 2025[182](index=182&type=chunk) - Foreign currency risk is not material, as expenses are generally denominated in U.S. dollars, and a **10%** change in current exchange rates would not have a material effect on financial results[183](index=183&type=chunk) [Item 4. Controls and Procedures](index=44&type=section&id=Item%204.%20Controls%20and%20Procedures) This item reports on the effectiveness of the company's disclosure controls and procedures and internal control over financial reporting - Management concluded that the company's disclosure controls and procedures were effective as of **June 30, 2025**, at a reasonable assurance level[184](index=184&type=chunk) - No material changes in internal control over financial reporting were identified during the three and six months ended **June 30, 2025**[185](index=185&type=chunk) - The effectiveness of any internal control system is subject to inherent limitations, providing reasonable, not absolute, assurances[186](index=186&type=chunk) [PART II. OTHER INFORMATION](index=45&type=section&id=PART%20II.%20OTHER%20INFORMATION) This part includes additional information such as legal proceedings, risk factors, sales of equity securities, defaults, mine safety, and exhibits [Item 1. Legal Proceedings](index=45&type=section&id=Item%201.%20Legal%20Proceedings) This item addresses the company's involvement in legal proceedings and their potential impact on the business - The company is not currently a party to any litigation or legal proceedings that management believes are likely to have a material adverse effect on its business[189](index=189&type=chunk) - Regardless of outcome, litigation can adversely impact the business due to defense and settlement costs, diversion of management resources, and other factors[189](index=189&type=chunk) [Item 1A. Risk Factors](index=45&type=section&id=Item%201A.%20Risk%20Factors) This extensive section details the principal risks and uncertainties affecting the company's business, covering financial, operational, regulatory, and intellectual property aspects - The company is a clinical-stage precision oncology company with a limited operating history, no products approved for commercial sale, and a history of significant losses, making future profitability uncertain[195](index=195&type=chunk)[197](index=197&type=chunk) - Substantial additional financing will be required to achieve the company's goals, which may not be available on acceptable terms and could force delays or termination of product development or commercialization efforts[200](index=200&type=chunk)[201](index=201&type=chunk) - The business is dependent on the successful development, regulatory approval, and ultimate commercialization of its current and future product candidates, which is a lengthy, costly, and inherently unpredictable process[215](index=215&type=chunk)[216](index=216&type=chunk)[217](index=217&type=chunk) - The company faces significant competition from major multinational pharmaceutical and biotechnology companies with greater financial, manufacturing, marketing, and development resources[237](index=237&type=chunk) - Obtaining and maintaining sufficient patent and other intellectual property protection for product candidates and technology is critical, but involves complex legal issues, high costs, and uncertainties regarding validity and enforceability[379](index=379&type=chunk)[380](index=380&type=chunk)[385](index=385&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=137&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) This item reports on any unregistered sales of equity securities or use of proceeds from registered securities during the period - No unregistered sales of equity securities were reported for the period[478](index=478&type=chunk) - No use of proceeds from the sale of registered securities was reported for the period[479](index=479&type=chunk) [Item 3. Defaults Upon Senior Securities](index=137&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) This item reports on any defaults upon senior securities during the period - No defaults upon senior securities were reported for the period[481](index=481&type=chunk) [Item 4. Mine Safety Disclosures](index=137&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item reports on any mine safety disclosures during the period - No mine safety disclosures were reported for the period[482](index=482&type=chunk) [Item 5. Other Information](index=139&type=section&id=Item%205.%20Other%20Information) This item indicates that there is no other information to report - No other information was reported for the period[483](index=483&type=chunk) [Item 6. Exhibits](index=140&type=section&id=Item%206.%20Exhibits) This item lists the exhibits filed as part of the Form 10-Q, including the Revenue Participation Right Purchase and Sale Agreement, Loan Agreement, certifications of principal executive and financial officers, and Inline XBRL documents - Key exhibits filed include the Revenue Participation Right Purchase and Sale Agreement and the Loan Agreement, both dated **June 23, 2025**[484](index=484&type=chunk) - Certifications of the Principal Executive Officer and Principal Financial Officer are furnished as **Exhibits 31.1, 31.2, 32.1, and 32.2**[484](index=484&type=chunk) - Portions of certain exhibits have been omitted pursuant to Regulation S-K, as the information is not material and is treated as private or confidential[485](index=485&type=chunk)[486](index=486&type=chunk) [Signatures](index=141&type=section&id=Signatures) This section contains the required signatures of the company's principal executive and financial officers for the Form 10-Q filing - The Quarterly Report on Form 10-Q is signed by Mark A. Goldsmith, M.D., Ph.D., Chief Executive Officer, and Jack Anders, Chief Financial Officer, on **August 6, 2025**[491](index=491&type=chunk)[492](index=492&type=chunk)

[Executive Summary](index=1&type=section&id=Executive%20Summary) Revolution Medicines reported strong Q2 2025 results, advancing pivotal trials, securing BTDs, and obtaining $2 billion in funding. [Recent Achievements and Strategic Priorities](index=1&type=section&id=Recent%20Achievements%20and%20Strategic%20Priorities) Revolution Medicines reported strong Q2 2025 results, highlighting pivotal trial execution for daraxonrasib, FDA Breakthrough Therapy Designations, and a $2 billion funding agreement. - **Strong execution of two ongoing Phase 3 trials of daraxonrasib**; RASolute 302 enrollment winding down in U.S., **expected to complete this year**[4](index=4&type=chunk) - **FDA Breakthrough Therapy Designations granted for daraxonrasib and elironrasib**, two RAS(ON) inhibitors[4](index=4&type=chunk) - Company entered into a **$2 billion flexible funding agreement with Royalty Pharma** to support global development and commercialization[4](index=4&type=chunk) - Daraxonrasib received **Breakthrough Therapy Designation from the U.S. FDA** for previously treated metastatic PDAC in patients with KRAS G12 mutations[3](index=3&type=chunk) [Corporate Progress and Pipeline Update](index=1&type=section&id=Corporate%20Progress%20and%20Pipeline%20Update) Revolution Medicines is advancing its clinical pipeline, including daraxonrasib, mutant-selective inhibitors, and earlier-stage programs. [Daraxonrasib Clinical Development](index=1&type=section&id=Daraxonrasib%20Clinical%20Development) Revolution Medicines is advancing daraxonrasib through late-stage clinical development, with ongoing Phase 3 and planned earlier line registrational trials. [Pivotal Trials (RASolute 302, RASolve 301)](index=1&type=section&id=Pivotal%20Trials%20(RASolute%20302%2C%20RASolve%20301)) Revolution Medicines is actively enrolling patients in global Phase 3 trials for daraxonrasib in PDAC and NSCLC. - **RASolute 302**, a global Phase 3 trial for daraxonrasib in previously treated PDAC, continues strong enrollment, with completion expected this year for a **2026 data readout**[2](index=2&type=chunk) - **RASolve 301**, a global Phase 3 trial for daraxonrasib in previously treated NSCLC, continues U.S. enrollment and is activating sites in Europe and Japan[5](index=5&type=chunk) [Earlier Line Registrational Trials](index=2&type=section&id=Earlier%20Line%20Registrational%20Trials) The company plans to initiate registrational trials for daraxonrasib in first-line metastatic PDAC, adjuvant PDAC, and first-line RAS mutant NSCLC. - The company is on track to initiate a registrational trial this year for **daraxonrasib as first-line treatment for metastatic PDAC**, planned as a three-arm trial[6](index=6&type=chunk) - The company is also on track to initiate a registrational trial this year for **daraxonrasib as adjuvant treatment for resectable PDAC**[7](index=7&type=chunk) - Based on new clinical data, a **Phase 3 registrational trial for daraxonrasib combined with pembrolizumab** in first-line RAS mutant NSCLC is expected in **2026**[8](index=8&type=chunk) [Mutant-Selective Inhibitors (Elironrasib, Zoldonrasib)](index=2&type=section&id=Mutant-Selective%20Inhibitors%20(Elironrasib%2C%20Zoldonrasib)) Revolution Medicines advances mutant-selective inhibitors elironrasib (BTD) and zoldonrasib, with pivotal combination trials anticipated in 2026. - **Elironrasib monotherapy** in previously treated KRAS G12C NSCLC demonstrated a **highly competitive profile** with differentiated safety and compelling efficacy[10](index=10&type=chunk) - **Elironrasib received FDA Breakthrough Therapy Designation** for KRAS G12C-mutated locally advanced or metastatic NSCLC in previously treated patients[11](index=11&type=chunk) - **Zoldonrasib** clinical data showed **acceptable tolerability and encouraging antitumor activity** in previously treated KRAS G12D NSCLC and PDAC[12](index=12&type=chunk) - The company expects to initiate **one or more pivotal combination trials in 2026** incorporating zoldonrasib or elironrasib[12](index=12&type=chunk) [Earlier Stage Pipeline and Discovery](index=3&type=section&id=Earlier%20Stage%20Pipeline%20and%20Discovery) The company's earlier stage pipeline includes RMC-5127 (Phase 1 in 2026) and AI-driven discovery collaborations. - Clinical development of **RMC-5127**, a RAS(ON) G12V-selective inhibitor, is on track for **Phase 1 initiation in 2026**[13](index=13&type=chunk) - The company invests in discovery collaborations, including with **Iambic Therapeutics**, leveraging AI for lead discovery and optimization[14](index=14&type=chunk) [Commercialization and Funding](index=3&type=section&id=Commercialization%20and%20Funding) Revolution Medicines is expanding global commercialization and operational capabilities, supported by a $2 billion flexible funding agreement with Royalty Pharma. - A partnership with **Royalty Pharma provides $2 billion in committed capital** upon milestone achievement through flexible synthetic royalty and debt instruments[15](index=15&type=chunk) - The company continues to **grow commercial and operational capabilities** in support of a potential launch[16](index=16&type=chunk) [Strategic Collaborations](index=4&type=section&id=Strategic%20Collaborations) Revolution Medicines entered a clinical collaboration with Summit Therapeutics to evaluate RAS(ON) inhibitors combined with ivonescimab (PD-1 / VEGF bispecific antibody) in solid tumors. - The company entered a **clinical collaboration with Summit Therapeutics** to evaluate RAS(ON) inhibitors combined with ivonescimab (PD-1 / VEGF bispecific antibody) in solid tumors[18](index=18&type=chunk) [Financial Results and Outlook](index=4&type=section&id=Financial%20Results%20and%20Outlook) Revolution Medicines reported Q2 2025 financial results, showing increased expenses and net loss, and provided full-year 2025 GAAP net loss guidance. [Second Quarter 2025 Financial Highlights](index=4&type=section&id=Second%20Quarter%202025%20Financial%20Highlights) For Q2 2025, Revolution Medicines reported $2.1 billion in cash, increased R&D and G&A expenses, and a net loss of $247.8 million. | Metric | Q2 2025 (in thousands) | Q2 2024 (in thousands) | Change (YoY) | | :-------------------------------- | :--------------------- | :--------------------- | :----------- | | Cash, cash equivalents and marketable securities (as of June 30) | $2,137,171 | N/A | N/A | | R&D Expenses | $224,134 | $134,932 | +66.1% | | G&A Expenses | $40,580 | $21,711 | +86.9% | | Net Loss | $(247,787) | $(133,233) | +86.0% | | Net Loss per Share (basic & diluted) | $(1.31) | $(0.81) | +61.7% | | Weighted-average common shares | 188,583,288 | 165,141,936 | +14.2% | - **Cash, cash equivalents, and marketable securities totaled $2.1 billion** as of June 30, 2025, including **$250 million from Royalty Pharma**[19](index=19&type=chunk) - **R&D expenses increased** primarily due to higher clinical trial and manufacturing expenses for daraxonrasib, zoldonrasib, and elironrasib, plus personnel costs[20](index=20&type=chunk) - **G&A expenses increased** mainly due to higher personnel-related expenses, stock-based compensation, and commercial preparation activities[21](index=21&type=chunk) [Financial Guidance](index=5&type=section&id=Financial%20Guidance) Revolution Medicines projects full-year 2025 GAAP net loss guidance of $1.03 billion to $1.09 billion, including estimated non-cash stock-based compensation. - Revolution Medicines projects **full-year 2025 GAAP net loss guidance between $1.03 billion and $1.09 billion**[23](index=23&type=chunk) - The guidance includes estimated **non-cash stock-based compensation expense of $115 million to $130 million**[23](index=23&type=chunk) [Company Overview](index=5&type=section&id=Company%20Overview) Revolution Medicines is a late-stage clinical oncology company developing targeted therapies for RAS-addicted cancers. [About Revolution Medicines](index=5&type=section&id=About%20Revolution%20Medicines) Revolution Medicines is a late-stage clinical oncology company developing targeted therapies for RAS-addicted cancers, with a pipeline of RAS(ON) inhibitors. - Revolution Medicines is a **late-stage clinical oncology company** developing targeted therapies for RAS-addicted cancers[24](index=24&type=chunk) - The company's R&D pipeline includes **RAS(ON) inhibitors** designed to suppress diverse oncogenic RAS variants[24](index=24&type=chunk) - Key clinical-stage RAS(ON) inhibitors include **daraxonrasib, elironrasib (G12C-selective), and zoldonrasib (G12D-selective)**[24](index=24&type=chunk) - **RMC-5127**, a RAS(ON) G12V-selective inhibitor, is anticipated to be the next to enter clinical development[24](index=24&type=chunk) [Additional Information](index=5&type=section&id=Additional%20Information) This section provides important disclaimers regarding forward-looking statements and contact information. [Forward-Looking Statements](index=5&type=section&id=Forward-Looking%20Statements) This section contains forward-looking statements regarding financial projections, development plans, and clinical timelines, subject to inherent risks and uncertainties. - This press release contains **forward-looking statements** regarding financial projections, development plans, clinical timelines, and capital sources[25](index=25&type=chunk)[26](index=26&type=chunk) - Forward-looking statements are subject to **substantial risks and uncertainties** inherent in drug development, regulatory approval, intellectual property, and competitive changes[27](index=27&type=chunk) [Contact Information](index=6&type=section&id=Contact%20Information) Provides contact details for media and investor inquiries. - Media Contact: **media@revmed.com**[28](index=28&type=chunk) - Investor Contact: **investors@revmed.com**[28](index=28&type=chunk) [Financial Statements](index=7&type=section&id=Financial%20Statements) This section presents the unaudited condensed consolidated statements of operations and balance sheets. [Condensed Consolidated Statements of Operations](index=7&type=section&id=Condensed%20Consolidated%20Statements%20of%20Operations) Presents unaudited condensed consolidated statements of operations for the three and six months ended June 30, 2025 and 2024, detailing operating expenses and net loss. | Operating Expenses (in thousands) | Three Months Ended June 30, 2025 | Three Months Ended June 30, 2024 | Six Months Ended June 30, 2025 | Six Months Ended June 30, 2024 | | :-------------------------------- | :------------------------------- | :------------------------------- | :----------------------------- | :----------------------------- | | Research and development | $224,134 | $134,932 | $429,883 | $252,953 | | General and administrative | $40,580 | $21,711 | $75,591 | $44,549 | | Total operating expenses | $264,714 | $156,643 | $505,474 | $297,502 | | Loss from operations | $(264,714) | $(156,643) | $(505,474) | $(297,502) | | Net loss | $(247,787) | $(133,233) | $(461,203) | $(249,236) | | Net loss per share, basic and diluted | $(1.31) | $(0.81) | $(2.45) | $(1.51) | [Selected Condensed Consolidated Balance Sheets](index=8&type=section&id=Selected%20Condensed%20Consolidated%20Balance%20Sheets) Provides selected unaudited condensed consolidated balance sheet data as of June 30, 2025, and December 31, 2024, including cash, working capital, and total assets. | Balance Sheet Item (in thousands) | June 30, 2025 | December 31, 2024 | | :-------------------------------- | :------------ | :---------------- | | Cash, cash equivalents and marketable securities | $2,137,171 | $2,289,299 | | Working capital (1) | $1,991,905 | $2,163,718 | | Total assets | $2,429,568 | $2,558,301 | | Total liabilities | $564,199 | $293,097 | | Total stockholders' equity | $1,865,369 | $2,265,204 |

Core Insights - Revolution Medicines, Inc. reported significant advancements in its clinical trials for targeted therapies aimed at RAS-addicted cancers, particularly focusing on daraxonrasib for metastatic pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC) [1][2][3] Clinical Development Progress - The company is executing pivotal trials with daraxonrasib, with the RASolute 302 trial for PDAC nearing completion of U.S. enrollment and continuing globally, expecting data readout in 2026 [1][2] - Daraxonrasib has received Breakthrough Therapy Designation from the FDA for previously treated metastatic PDAC with KRAS G12 mutations [2][8] - A registrational trial for daraxonrasib as a first-line treatment for metastatic PDAC is set to initiate this year, comparing it against chemotherapy [3][4] - The company plans to initiate a Phase 3 trial in 2026 for daraxonrasib combined with pembrolizumab for RAS mutant NSCLC [5][7] Financial Highlights - As of June 30, 2025, the company reported cash, cash equivalents, and marketable securities totaling $2.1 billion, including a $250 million tranche from Royalty Pharma [16] - Research and development expenses increased to $224.1 million for Q2 2025, up from $134.9 million in Q2 2024, primarily due to clinical trial and manufacturing costs [17] - General and administrative expenses rose to $40.6 million in Q2 2025 from $21.7 million in Q2 2024, driven by personnel-related costs and commercial preparation activities [18] - The net loss for Q2 2025 was $247.8 million, compared to a net loss of $133.2 million in Q2 2024 [19] Strategic Partnerships and Funding - The company entered a $2 billion flexible funding agreement with Royalty Pharma to support its global development and commercialization efforts [8][13] - A collaboration with Iambic Therapeutics aims to enhance drug discovery through AI capabilities [12][15] Pipeline and Future Directions - The company is advancing its pipeline with mutant-selective inhibitors elironrasib and zoldonrasib, with plans for pivotal trials in 2026 [6][10] - RMC-5127, a RAS(ON) G12V-selective inhibitor, is on track for clinical readiness in 2025 [11][22]

Pipeline and Focus - Revolution Medicines' pipeline is led by three clinical-stage RAS(ON) inhibitors: Daraxonrasib (MULTI), Elironrasib (G12C), and Zoldonrasib (G12D)[6, 15] - The company's strategy is to maximize the impact of its RAS(ON) inhibitor portfolio by commercializing daraxonrasib initially in late-stage disease and developing RAS(ON) inhibitors in earlier lines of therapy[18, 19] - Revolution Medicines is also innovating for patients by producing new, differentiated drug candidates, including RMC-5127 (G12V-selective inhibitor) and next-generation programs[19, 15] Daraxonrasib (MULTI) - In 2L patients with KRAS G12X PDAC treated with daraxonrasib at 300 mg daily, the median PFS was 8.8 months, and the OS rate at 6 months was 100%[24] - In 2L/3L patients with RAS G12X NSCLC treated with daraxonrasib at 120-220 mg daily, the median PFS was 9.8 months, and the median OS was 17.7 months[28] - In 1L RAS mutant NSCLC patients treated with Daraxonrasib 100-200 mg + Pembrolizumab + Chemotherapy, the ORR was 60% and the DCR was 90% in the TPS < 50% subgroup[32] - In 1L RAS mutant NSCLC patients treated with Daraxonrasib 200 mg + Pembrolizumab, the ORR was 86% and the DCR was 100% in the TPS ≥ 50% subgroup[32] Elironrasib (G12C) - In previously treated RAS G12C NSCLC patients, Elironrasib (200 mg BID) showed an ORR of 56% and a DCR of 94%[40] - In previously treated RAS G12C NSCLC patients, Elironrasib (200 mg BID) showed a median PFS of 9.9 months[40] - In 1L RAS G12C NSCLC patients with TPS ≥ 50%, Elironrasib 200 mg BID + Pembrolizumab showed an ORR of 100% and a DCR of 100%[45] - In CRC patients previously treated with KRAS(OFF) G12C inhibitor, Elironrasib + Daraxonrasib doublet showed an ORR of 25% and a DCR of 92%[51] - In 2L+ NSCLC patients following G12C(OFF) inhibitor, Elironrasib showed an ORR of 42% and a DCR of 79%[55] - In 2L+ NSCLC patients following G12C(OFF) inhibitor, Elironrasib + Daraxonrasib showed an ORR of 62% and a DCR of 92%[56] Zoldonrasib (G12D) - In previously treated patients with KRAS G12D PDAC treated with 1200 mg daily dose, the ORR was 30% and the DCR was 80%[67] - In previously treated patients with KRAS G12D NSCLC treated with 1200 mg QD, the ORR was 61% and the DCR was 89%[72] Financials - Revolution Medicines has $2.1 billion in cash, cash equivalents, and marketable securities as of June 30, 2025[119] - The company anticipates a 2025 GAAP Net Loss of $1.03 – $1.09 billion, including $115 million to $130 million in non-cash stock-based compensation expense[119] - Royalty Pharma partnership bolsters financial position by providing $2 billion in flexible committed capital[116]

Core Insights - Revolution Medicines, Inc. is a late-stage clinical oncology company focused on developing targeted therapies for RAS-addicted cancers [3] - The company will report its financial results for Q2 2025 on August 6, 2025, after market close, followed by a webcast to discuss these results and corporate progress [1] Company Overview - Revolution Medicines is developing RAS(ON) inhibitors aimed at suppressing various oncogenic variants of RAS proteins [3] - The current R&D pipeline includes daraxonrasib (RMC-6236), elironrasib (RMC-6291), and zoldonrasib (RMC-9805), which are in clinical development [3] - The company plans to advance RMC-5127, a RAS(ON) G12V-selective inhibitor, into clinical development next [3] - Additional pipeline opportunities focus on RAS(ON) mutant-selective inhibitors, including RMC-0708 (Q61H) and RMC-8839 (G13C) [3]