Tango Therapeutics (TNGX) 2025 Conference September 03, 2025 02:45 PM ET Speaker0Okay. Good afternoon, everyone, and welcome back to the Cantor conference. We're on time here, so we're going to get started. My name is Eric Schmidt. I'm one of the analysts at the firm, and it is my pleasure to welcome Tango Therapeutics today.And Barbara Weber, the company's Chief Executive Officer, will be sharing this fireside chat with me. We also have in the audience Adam Christel, the company's President and Head of R a ...

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]

Core Insights - Tango Therapeutics has initiated the first patient dosing in a Phase 1/2 trial for TNG462 in combination with Revolution Medicines' daraxonrasib or zoldonrasib targeting MTAP-deleted and RAS mutant metastatic pancreatic or lung cancer [1][2] - The trial aims to evaluate the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of TNG462 in combination with the mentioned inhibitors [2] - TNG462 is a promising MTA-cooperative PRMT5 inhibitor, with monotherapy data expected in the second half of 2025, which may inform a registrational trial for pancreatic cancer in 2026 [3] Company Overview - Tango Therapeutics is a clinical-stage biotechnology company focused on discovering novel drug targets and developing precision cancer medicines [4] - The company employs the genetic principle of synthetic lethality to create therapies targeting critical cancer-related pathways [4]

Core Insights - Revolution Medicines has partnered with Royalty Pharma to secure $2 billion in flexible funding aimed at supporting its global development and commercialization strategy for RAS-addicted cancers [1][2][5] - The funding agreement allows Revolution Medicines to maintain full control over the development and commercialization of its RAS(ON) inhibitor portfolio, which is crucial for establishing new standards of care [1][2][3] Funding Agreement Overview - The funding consists of up to $1.25 billion in synthetic royalty monetization on sales of daraxonrasib and up to $750 million in corporate debt [3][5] - The agreement provides significant flexibility, with $1.25 billion available at the company's discretion, contingent on achieving specific milestones [3][5] Synthetic Royalty Details - Royalty Pharma will provide up to $1.25 billion in exchange for tiered royalties over 15 years on worldwide annual net sales of daraxonrasib, with decreasing royalty rates based on sales volume [6][13] - The first two tranches of $250 million each are payable before FDA approval, with the first tranche already received [6][13] Debt Facility Details - The debt facility consists of up to $750 million in senior secured term loans, with the first tranche available after FDA approval of daraxonrasib for metastatic pancreatic ductal adenocarcinoma [13] - The interest rate for the debt is based on the 3-month Standard Overnight Financing Rate (SOFR) plus 5.75%, with a SOFR floor of 3.50% [13] Cash Runway Update - Following the funding agreement, the company has removed its cash runway end date guidance, indicating improved financial stability [9] Company Background - Revolution Medicines is focused on developing targeted therapies for RAS-addicted cancers, with a pipeline that includes multiple RAS(ON) inhibitors currently in clinical development [12]

Core Insights - Tango Therapeutics is advancing its clinical-stage pipeline, particularly focusing on TNG462, a PRMT5 inhibitor, with data updates expected in the second half of 2025 [1][6][16] - The company has a strong cash position of $217 million as of March 31, 2025, which is projected to fund operations into the first quarter of 2027 [1][9] - The company is strategically reducing preclinical spending to extend its cash runway while prioritizing its PRMT5 programs [2][9] Pipeline Update - TNG462 is anticipated to show promising efficacy, safety, and tolerability data, particularly in pancreatic and lung cancer, with a registrational study planned for next year [2][6] - TNG456, a next-generation PRMT5 inhibitor, is set to begin a Phase 1/2 trial for glioblastoma in the second quarter of 2025 [4][6] - TNG260 is undergoing a Phase 1/2 trial in combination with pembrolizumab for NSCLC, with updates expected in the second half of 2025 [5][6] Financial Results - Collaboration revenue for the first quarter of 2025 was $5.4 million, down from $6.5 million in the same period of 2024 [10] - Research and development expenses decreased to $36.4 million in Q1 2025 from $38.1 million in Q1 2024, attributed to reduced spending on discontinued programs [11] - The net loss for the first quarter of 2025 was $39.9 million, or $0.36 per share, compared to a net loss of $37.9 million, or $0.35 per share, in Q1 2024 [12][20] Upcoming Milestones - Clinical data updates for TNG462 and TNG260 are expected in the second half of 2025 [16] - Enrollment for the combination trial of TNG462 with RAS(ON) inhibitors is projected to begin in the second quarter of 2025 [1][16]

Financial Data and Key Metrics Changes - The company ended Q1 2025 with $2.1 billion in cash and investments, projected to fund operations into the second half of 2027 [42] - R&D expenses for Q1 2025 were $205.7 million, up from $118 million in Q1 2024, primarily due to increased clinical trial and manufacturing expenses [42] - G&A expenses rose to $35 million in Q1 2025 from $22.8 million in Q1 2024, driven by personnel-related expenses and stock-based compensation [43] - The net loss for Q1 2025 was $213.4 million, compared to $116 million in Q1 2024, attributed to higher operating expenses [43] - The company reiterated its 2025 financial guidance, expecting a full-year GAAP net loss between $840 million and $900 million [43] Business Line Data and Key Metrics Changes - The company is advancing three clinical-stage RasOn inhibitors: doraxonrasib, elieronrasib, and zoldonrasib, focusing on RAS mutant cancers [6][10] - Doraxonrasib is currently in two Phase III trials, with significant progress in pancreatic cancer and non-small cell lung cancer [45][46] - The ongoing RESOLVE-301 study is randomizing approximately 420 patients to evaluate doraxonrasib monotherapy versus docetaxel in previously treated non-small cell lung cancer [19] Market Data and Key Metrics Changes - Approximately 30% of non-small cell lung cancer patients harbor a RAS mutation, with no full regulatory approvals for RAS inhibitors in this space [10] - The segmentation of RAS mutant non-small cell lung cancer is expected to continue as more selective inhibitors advance through clinical development [11] Company Strategy and Development Direction - The company aims to revolutionize treatment for RAS addicted cancers through innovative targeted medicines, focusing on both single-agent and combination strategies [5][6] - A key focus for 2025 is executing registrational studies for doraxonrasib in both pancreatic and non-small cell lung cancers [45] - The company plans to initiate additional Phase III studies for doraxonrasib in pancreatic cancer in the second half of 2025 [7][46] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing enrollment for the RASLUT-302 trial and the RESOLVE-301 trial, expecting substantial completion this year [45][46] - The company is also advancing its earlier-stage pipeline, including a G12V mutant selective RasOn inhibitor, with plans for a Phase I study next year [48] - The management emphasized the importance of building commercialization capabilities in the U.S. and ensuring patient access to doraxonrasib globally [49][50] Other Important Information - The company has appointed Anthony Mancini as Chief Global Commercialization Officer to oversee commercialization strategy and operations [49] - The company is focused on establishing a leading portfolio of RasOn inhibitors as therapies for RAS mutant non-small cell lung cancer across all mutations and lines of therapy [11][12] Q&A Session Summary Question: Can you comment on the confidence and tolerability of the triplet combination for first-line non-small cell lung cancer? - Management expressed optimism based on the profile seen so far, noting no new safety signals have emerged [56][57] Question: What is the average follow-up in the cohorts, and what data is needed to declare Phase III intent for combinations? - Management indicated that follow-up data is available from previous presentations, and they believe they have sufficient data to proceed with the non-G12C program [60][62] Question: What is the company's strategy for commercial opportunities outside the U.S.? - Management discussed the importance of a comprehensive commercial strategy and potential partnerships, with plans to meet with the FDA to discuss pivotal trial designs [92]

Core Insights - Revolution Medicines, Inc. reported financial results for Q1 2025, highlighting progress in clinical trials and strategic priorities for the year [1][30][31] Clinical Development - The company is executing pivotal trials for daraxonrasib in previously treated metastatic pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC), with strong enrollment in the U.S. and initiation in the EU and Japan [1][2] - Plans are underway to advance daraxonrasib into first-line metastatic and earlier-line randomized pivotal trials for PDAC, expected to start in the second half of 2025 [3] - The company anticipates initiating pivotal combination trials for elironrasib and zoldonrasib in 2026 [4] - Recent data from zoldonrasib and elironrasib monotherapy in KRAS G12D and G12C mutant NSCLC patients show promising tolerability and antitumor activity [5][16] Combination Therapies - Clinical updates indicate encouraging results for combinations of daraxonrasib with pembrolizumab and elironrasib with pembrolizumab in NSCLC [6][19] - The combination of elironrasib with daraxonrasib demonstrated preliminary antitumor activity in patients previously treated with a KRAS G12C(OFF) inhibitor, with an objective response rate (ORR) of 62% [27][29] Financial Performance - As of March 31, 2025, the company reported cash, cash equivalents, and marketable securities totaling $2.1 billion [31][42] - Research and development expenses increased to $205.7 million from $118.0 million year-over-year, primarily due to clinical trial and manufacturing costs [32] - General and administrative expenses rose to $35.0 million from $22.8 million, attributed to personnel-related costs and commercial preparation activities [33] - The net loss for Q1 2025 was $213.4 million, compared to a net loss of $116.0 million in Q1 2024 [34] Strategic Initiatives - The company is enhancing its commercialization capabilities, appointing Anthony Mancini as chief global commercialization officer to strengthen its strategy in the U.S. and evaluate options for international reach [10][11] - Revolution Medicines is focused on advancing its pipeline of RAS(ON) inhibitors, with plans for future clinical development of RMC-5127, a G12V-selective inhibitor [37]