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]