Summary of Tango Therapeutics FY Conference Call Company Overview - **Company**: Tango Therapeutics (NasdaqGM:TNGX) - **Date of Conference**: January 14, 2026 - **New CEO**: Malte Peters, who succeeded Barbara Weber as CEO Key Points and Arguments Leadership Transition - Barbara Weber, the founding CEO, transitioned leadership to Malte Peters, emphasizing the need for a focus on late-phase drug development and regulatory discussions [2][3][29] - Peters has a background in R&D and has been involved with Tango since 2018, ensuring a smooth transition [2][30] Pipeline and Drug Development - Tango is moving from clinical validation to late-phase drug development, focusing on drugs targeting MTAP deletions in cancer [4][6] - **Pipeline Highlights**: - **TNG462**: In dose expansion studies, targeting approximately 60,000 patients annually in the U.S. with MTAP deletions [5][9] - **TNG456**: A blood-brain barrier penetrant molecule entering phase one clinical trials [5][9] - **TNG961**: An HBS1L degrader ready for clinical trials, targeting FOCAT deletion in MTAP-deleted cancers [19] Clinical Milestones for 2026 - Launch a pivotal trial in second-line pancreatic cancer [6][20] - Complete TNG462 RAS inhibitor combination studies [6][20] - Expand knowledge base in lung cancer and other indications [6][20] - Evaluate TNG456 efficacy in glioblastoma [6][20] Competitive Advantages - Received FDA support for pivotal trial protocol and statistical analysis plan [12][8] - Best-in-class potential for TNG462 based on selectivity, potency, and safety profile [8][9] - First company to combine a PRMT5 inhibitor with RAS inhibitors in clinical trials [9] Clinical Data Insights - TNG462 shows a 27% response rate and a median progression-free survival (PFS) of 6.4 months across multiple tumor histologies [10] - Comparison with standard care indicates a potential doubling of median PFS for patients with MTAP deletions [11][12] - A 49% response rate observed in a histology-selective cohort with a median PFS of 9.1 months [17] Strategic Focus - Emphasis on addressing high unmet medical needs in difficult-to-treat cancers [6] - Potential for a chemo-free treatment regimen for pancreatic cancer patients [15] - Commitment to robust data before public disclosure, independent of medical meetings [27] Other Important Content - Discussion on the mechanism of PRMT5 inhibitors and their reliance on MTAP deletion for therapeutic efficacy [22] - Peters' priorities include rapid advancement into late-phase drug development and regulatory readiness [23] - Barbara Weber highlighted the successful transition from a genomic target discovery platform to readiness for pivotal studies [28] This summary encapsulates the critical aspects of Tango Therapeutics' conference call, focusing on leadership changes, pipeline developments, clinical milestones, competitive advantages, and strategic focus.

Pipeline and Clinical Development - Vopimetostat, a PRMT5 inhibitor, is in dose expansion for MTAP-del cancers and dose escalation for RAS-mut pancreatic and lung cancer, including combinations with RAS inhibitors[13] - TNG456, a brain-penetrant PRMT5 inhibitor, is in dose escalation for MTAP-del glioblastoma[13] - TNG961, an HBS1L degrader, has Phase 1 enabled for MTAP/FOCAD-del solid tumors[13] - A pivotal study for vopimetostat monotherapy in 2L MTAP-del pancreatic cancer is planned to start in 2026[23, 37] - Early data from the vopimetostat + RAS(ON) inhibitor clinical study is encouraging, with 30 patients dosed and both combinations well-tolerated[45, 48] Vopimetostat Clinical Data - Vopimetostat monotherapy demonstrated an Overall Response Rate (ORR) of 27% across 16 different histologies and a Disease Control Rate (DCR) of 78%[30] - In 2L pancreatic cancer, vopimetostat showed a median Progression-Free Survival (mPFS) of 7.2 months, more than twice historical Standard of Care (SOC) trials[32, 35] - In a histology-selective cohort, vopimetostat achieved an ORR of 49%, a DCR of 89%, and an mPFS of 9.1 months[50, 53] Financial Status - The company reported a cash balance of $343 million as of December 31, 2025, providing a cash runway into 2028[19, 81] Glioblastoma Focus - TNG456 is being developed for MTAP-del glioblastoma, which represents 45% of GBM cases, or approximately 7,000 patients per year in the US[23]

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]