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]