Financial Data and Key Metrics Changes - In Q4 2025, total revenue was approximately $12.5 billion, flat year-over-year, while the growth portfolio revenue increased by 15% to $7.4 billion, representing nearly 60% of total revenue [14][15] - For the full year, the growth portfolio grew 17%, offsetting a decline of roughly $4 billion in revenue from the legacy portfolio [6][7] - Adjusted diluted earnings per share for Q4 were $1.26, and for the full year, it was $6.15, both including a net charge related to in-process R&D and licensing income [20] Business Line Data and Key Metrics Changes - Opdivo revenue grew 7% to nearly $2.7 billion in Q4, driven by new indications and share growth in first-line non-small cell lung cancer [15] - Reblozyl achieved 21% growth, reflecting solid uptake across MDS-associated anemia patients [16] - Breyanzi's revenue increased by 47% in Q4, driven by strong demand across its approved indications [16] - Eliquis revenue was nearly $3.5 billion in Q4, up 6%, supported by demand growth and market share gains [16] Market Data and Key Metrics Changes - The U.S. market for Eliquis saw a 4% revenue increase, contributing to its overall growth [16] - Camzyos revenue grew 57% to $353 million in Q4, benefiting from global demand growth [17] - Sotyktu's global revenue grew 3%, with upcoming PDUFA dates for psoriatic arthritis and phase III readouts for lupus and Sjögren's disease [17] Company Strategy and Development Direction - The company aims to deliver industry-leading sustainable growth into the 2030s, focusing on executing its growth strategy and advancing its pipeline [11][23] - A multi-year plan is in place to rewire the company for long-term growth, with expectations to introduce over 10 new medicines and 30 meaningful launch opportunities by 2030 [9][10] - The company is expanding the use of AI to enhance operational efficiency and reinvest strategically in growth [11] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the growth portfolio's ability to drive revenue despite anticipated declines in the legacy portfolio due to ongoing LOE impacts [12] - The company expects 2026 revenue in the range of $46-$47.5 billion, with a projected decline of 12%-16% in the legacy portfolio [12][21] - Management highlighted the importance of maintaining a strong say-to-do ratio and delivering on commitments as part of the company culture [11] Other Important Information - The company completed a targeted $10 billion debt paydown ahead of schedule and generated strong cash flow from operations of approximately $2 billion in Q4 [20] - The effective tax rate for Q4 was 22.1%, reflecting a one-time non-tax deductible in-process R&D charge related to the Orbital acquisition [19] Q&A Session Summary Question: Insights on pivotal catalysts for 2026 - Management highlighted the potential for over 10 phase III data readouts this year, with a focus on products like Milvexian and Admilparant [25][28] Question: Eliquis dynamics for 2026 - Eliquis is expected to grow 10%-15% in 2026, driven by market share gains and pricing strategy adjustments [39] Question: Business development priorities - The company is focused on deepening its presence in existing therapeutic areas while remaining opportunistic for new opportunities [37] Question: Milvexian AFib study updates - The study is progressing well, with a focus on demonstrating non-inferiority to Eliquis and potential benefits in bleeding risks [46] Question: Admilparant's hypotension risk - Management indicated that the hypotension risk is being well managed in the phase three studies, with a focus on higher dosing [89]

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]