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.

Summary of Tango Therapeutics Conference Call Company Overview - **Company**: Tango Therapeutics (TNGX) - **Lead Program**: TNG462, an MTA cooperative PRMT5 inhibitor, targeting cancer across multiple histologies [3][4] Industry Insights - **Target**: PRMT5, a methylase essential for regulating various proteins, with differential activity in tumor cells versus normal cells due to MTAP deletion [4] - **MTAP Deletions**: Occur in 15-20% of all solid tumors, most prevalent in lung cancer, pancreatic cancer, and glioblastoma [5] - **Screening**: MTAP deletion screening is not routine, but included in major commercial and academic panels [6][7] Competitive Landscape - **Key Competitors**: Bristol Myers Squibb (BMS) and Amgen are the main competitors, with BMS being the most significant due to their promising data [18][19] - **TNG462 Advantages**: Expected to have better MTAP selectivity and tolerability compared to BMS's molecule, allowing for higher dosing and potentially better efficacy [20][21][23] Clinical Data and Efficacy - **Clinical Experience**: TNG462 showed a median progression-free survival (PFS) of 24 weeks in a dose escalation cohort for late-line difficult-to-treat cancers [26] - **Cholangiocarcinoma Results**: TNG462 demonstrated an overall response rate (ORR) nearly double that of BMS and Amgen, indicating strong activity [26] - **Durability of Response**: Both TNG462 and BMS's PRMT5 inhibitors show a gradual onset of action, with sustained tumor shrinkage over time [10][28] Future Plans - **Upcoming Data**: Full trial data expected in the second half of the year, focusing on pancreatic cancer [31][38] - **Registration Strategy**: Plans for a registration trial in pancreatic cancer as a second-line monotherapy and potential first-line combination with RAS inhibitors [46][63] - **Combination Studies**: Ongoing studies with RAS inhibitors, with plans for a dose expansion cohort after initial results [54][56] Additional Programs - **TNG456**: A brain-penetrant PRMT5 inhibitor targeting glioblastoma, with enrollment ongoing [86][90] - **CoREST Program**: Aiming to reverse resistance to checkpoint inhibitors in lung cancer patients with STK11 mutations, with data expected by year-end [92][94] Key Takeaways - **Market Position**: Tango Therapeutics is positioned to potentially lead in the PRMT5 inhibitor space, with TNG462 showing promising early data and a clear strategy for future development [42][46] - **Focus on Durability**: Emphasis on the durability of response as a critical metric for evaluating PRMT5 inhibitors, which may change treatment paradigms in oncology [28][30]