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]

Vopimetostat (TNG462) Overview - Vopimetostat is an oral, once-a-day, MTAP-selective PRMT5 inhibitor with a potential best-in-class safety profile[7] - Key indications for development include pancreatic cancer (~20,000 patients/yr), lung cancer (~22,000 patients/yr), and histology agnostic cancers (~20,000 patients/yr) in the US[7] - A pivotal study in second-line (2L) pancreatic cancer is planned to initiate in 2026, with the potential to be first-to-market in 2L MTAP-del pancreatic cancer[7] Clinical Trial Data and Efficacy - Vopimetostat demonstrated an overall response rate (ORR) of 27% across cancer types, suggesting it could be best-in-class[13,16,18] - In 2L MTAP-del pancreatic cancer, the median progression-free survival (mPFS) was 7.2 months, with an ORR of 25%, supporting the planned pivotal study start in 2026[13,34] - The histology agnostic cohort (excluding sarcoma, pancreatic, and lung cancer) showed a 49% ORR and an mPFS of 9.1 months[13,51,53] Safety and Tolerability - Vopimetostat has a potential best-in-class safety and tolerability profile, with approximately 8% dose reduction and no drug-related dose discontinuations[13,25] Combination Studies and Future Plans - Ongoing combination study of vopimetostat + RAS(ON) inhibitors in 2L+ MTAP-del pancreatic and lung cancer patients, with expansion to first line (1L) cohort planned[13,43,45] - Lung cancer cohort is fully enrolled (n=41), with an update planned for 2026[13,48]

Summary of Tango Therapeutics Conference Call Company Overview - **Company**: Tango Therapeutics - **Industry**: Biotechnology, specifically focused on oncology and synthetic lethality Core Insights and Arguments - **Synthetic Lethality Platform**: Tango's discovery platform is based on synthetic lethality, which targets tumor suppressor gene loss that cannot be directly targeted due to their inactivation. This approach supplements existing therapies that focus on activated oncogenes [2][3] - **Pipeline Development**: Tango is advancing its lead asset, TNG-462, a PRMT5 inhibitor, which is synthetic lethal with MTAP deletions, common in lung and pancreatic cancers. The company is nearing the end of a Phase III study for this asset [8][9] - **Durability of Treatment**: The efficacy of TNG-462 is highlighted by its durability in patients, with some remaining on treatment for over a year, which is notable compared to standard chemotherapy options [10][11] - **Tolerability Profile**: TNG-462 is reported to have a best-in-class tolerability profile, making it suitable for patients with difficult-to-treat cancers [12] Pipeline Details - **TNG-462**: Focused on pancreatic and lung cancers, with plans to present data from over 20 patients in each category later this year [10] - **TNG-456**: A next-generation brain-penetrant asset aimed at glioblastoma, which has a high prevalence of MTAP deletions. This asset is expected to deliver more drug into the brain due to increased selectivity [13][15] - **TNG-260**: A coREST inhibitor targeting STK11 mutation patients, which represents a significant opportunity in non-small cell lung cancer. The program is currently in dose expansion [30][31] Competitive Landscape - **Key Competitors**: The primary competitors identified are Bristol Myers Squibb (BMS) and Amgen, with Tango believing it has a competitive edge in terms of pharmacokinetics (PK) and tolerability [21][22] - **Market Positioning**: Tango positions itself as a leader in the PRMT5 space, with a significant lead over other companies like AstraZeneca and BeiGene [22] Combination Strategies - **Combination with RAS Mutations**: Tango is initiating a study combining TNG-462 with RAS mutation-targeted therapies, which is expected to be transformative for pancreatic and lung cancer patients [27] - **Focus on Tolerability**: The company is monitoring overlapping toxicities in combination therapies but expects good tolerability based on existing safety profiles [29] Financial and Strategic Focus - **Capital Allocation**: Tango's capital allocation strategy is heavily focused on advancing the development of TNG-462 for pancreatic cancer, with plans to start a pivotal study next year [38] - **Investor Perception**: There is a belief that investors have underestimated the importance of PRMT5 as a target and Tango's position in the market. The company asserts it is well-resourced to compete effectively [36][37] Additional Insights - **Innovative Approach**: Tango's approach to synthetic lethality and its focus on specific genetic mutations (like STK11 and MTAP) are seen as innovative and potentially game-changing in oncology [30][31] - **Clinical Proof of Concept**: The company has demonstrated that its findings in animal models translate to human patients, reinforcing the validity of its therapeutic strategies [32][34]