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 FY Conference Call Company Overview - **Company**: Tango Therapeutics (NasdaqGM:TNGX) - **Focus**: Small molecule precision oncology targeting novel cancer pathways - **Key Programs**: Three clinical programs including bopametastat (TNG462), TNG456, and TNG260 [5][8] Key Clinical Programs Bopametastat (TNG462) - **Type**: MTA cooperative PRMT5 inhibitor - **Clinical Data**: - Overall response rate of 27% in over 150 patients, compared to 23% for BMS504 [5][6] - Median progression-free survival (PFS) of 6.4 months [5] - In second-line pancreatic cancer, overall response rate of 25% with median PFS of 7.2 months, significantly better than standard chemotherapy (2-3.5 months) [6][14] - In a selective cohort (excluding certain cancers), overall response rate was 49% with median PFS exceeding 9 months [7] - **Market Potential**: Approximately 60,000 MTAP-deleted cancer patients in the US annually, including 20,000 pancreatic cancer patients [8] TNG456 - **Description**: Brain-penetrant version of TNG462, targeting glioblastoma (GBM) [7] - **Patient Population**: 40% of GBM patients are MTAP-deleted, with about 8,000 new cases annually in the US [7] TNG260 - **Status**: Early proof of concept in non-small cell lung cancer (NSCLC) patients with specific mutations [8] Competitive Landscape - **Main Competitor**: BMS504, with ongoing studies exploring various dose levels [11] - **Differentiators**: Bopametastat shows superior safety profile (less GI toxicity, less rash) and has a defined dose for pivotal studies [11][13] - **Strategic Positioning**: Tango is the first PRMT5 inhibitor to combine with KRAS inhibitors, enhancing its competitive edge [13] Clinical Trial Design and Strategy - **Upcoming Pivotal Study**: - Focused on second-line pancreatic cancer, comparing bopametastat to standard chemotherapy [27] - Approximately 300 patients, utilizing a hierarchical design for statistical efficiency [27][28] - **FDA Alignment**: Successfully completed end-of-phase meeting with FDA, confirming trial design [29] Market Dynamics - **Emerging Treatments**: KRAS inhibitors like Diraxonracib expected to gain approval, with Tango positioning itself for second-line treatment [24] - **Combination Strategies**: Plans to explore combinations of bopametastat with Diraxonracib in both pancreatic and NSCLC [34] Financial Outlook - **Cash Runway**: Sufficient funds to support operations through 2028, covering pivotal studies and ongoing clinical trials [47] Key Takeaways - **Focus for 2026**: Execution of pivotal studies and advancing combination therapies with Revolution Medicines [47] - **Long-term Vision**: Aim to establish a strong position in both second-line and frontline treatment settings for pancreatic cancer and other malignancies [25][47]

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]