KT-621, Oral STAT6 Degrader, Phase 1b Results 1 Agenda Introduction Justine Koenigsberg Vice President, Investor Relations Revolutionizing Immunology with Oral Medicines Nello Mainolfi, PhD Founder, President and Chief Executive Officer KT-621 BroADen Phase 1b Data Jared Gollob, MD Chief Medical Officer Closing Remarks Nello Mainolfi, PhD Founder, President and Chief Executive Officer Question and Answer Session 2 Forward Looking Statements This presentation contains forward-looking statements within the me ...

Core Insights - Kymera Therapeutics, Inc. is set to announce results from the BroADen Phase 1b clinical trial for KT-621, an oral STAT6 degrader for atopic dermatitis, on December 8, 2025 [1] - KT-621 has shown complete STAT6 degradation and a favorable safety profile in early studies, indicating its potential to transform treatment for over 130 million patients with Type 2 inflammatory diseases [3] - Ongoing and planned clinical trials for KT-621 aim to accelerate its development across multiple indications, including asthma and other Type 2 diseases [4] Company Overview - Kymera Therapeutics is a clinical-stage biotechnology company focused on targeted protein degradation to develop innovative therapies for significant health issues [5] - The company has advanced the first degrader into clinical evaluation for immunological diseases and aims to build a robust pipeline of oral small molecule degraders [5] - Founded in 2016, Kymera has been recognized as one of Boston's top workplaces, reflecting its commitment to innovation and employee satisfaction [5]

Summary of C4 Therapeutics FY Conference Call Company Overview - C4 Therapeutics is a targeted protein degradation company focused on developing breakthrough medicines for patients with high unmet medical needs [3][4] - The company has two active clinical programs: - Cemsidomide (IKZF1/3 degrader) with data recently presented at IMS in Toronto, expected to enter the next phase of development early next year [3][4] - CFT8919 (EGFR L858R degrader) currently in a phase one first-in-human study in collaboration with Betta Pharmaceuticals in China [3][4] Clinical Program Updates - **Cemsidomide**: - Phase 1 dose escalation study showed an overall objective response rate (ORR) of 36% across 72 patients, with higher doses (75 micrograms and 100 micrograms) achieving ORRs of 40% and 53% respectively [6][7] - Median duration of treatment was 9.3 months, with a safety profile indicating only 6% of patients had dose reductions due to safety reasons [7][8] - 100% of patients were triple-class exposed, with 75% having prior CAR T or T cell engager therapy, showing consistent response rates across these subgroups [8][14] - **Comparison with Mezigdomide**: - Cemsidomide's response rate (53%) is competitive with mezigdomide (55%), but with a significantly better safety profile, as mezigdomide had higher rates of discontinuations and dose reductions due to safety [13][14] Future Development Plans - The company plans to advance Cemsidomide to the next phase of studies, with a meeting scheduled with the FDA to align on dosing [16][18] - The expected ORR for the upcoming 4L+ study is around 40%, based on a background rate of 20% [20] Financial and Strategic Considerations - C4 Therapeutics has a cash runway through the end of 2028, which does not include potential milestone payments of up to $40 million from collaboration partners [32] - The company is focused on moving Cemsidomide to the next phase while also supporting the ongoing study with Betta Pharmaceuticals [31][32] Commercial Considerations - Pricing for Cemsidomide is still under consideration, with the goal to be competitive based on the value it brings to patients [21] - The expected duration of response in a last-line setting is anticipated to be over six months, with current data showing 9.3 months [23] Combination Therapy Insights - C4 Therapeutics is exploring the combination of Cemsidomide with bispecific T-cell engagers, with evidence suggesting potential synergistic effects [24][25] - The study design will introduce Cemsidomide only after patients reach the loaded dose of the BiTE, with careful monitoring of safety and tolerability [26][27] Key Takeaways - C4 Therapeutics is making significant progress in its clinical programs, particularly with Cemsidomide, which shows promising efficacy and safety profiles compared to competitors - The company is strategically positioned for future growth with a solid financial runway and ongoing collaborations, while also preparing for potential commercial opportunities in the near future

Core Insights - Kymera Therapeutics, Inc. (KYMR) shares reached a 52-week high of $68.8 on November 24, currently trading at $66.04, driven by investor optimism surrounding its lead pipeline candidate KT-621 [1][7] - Year-to-date, KYMR shares have surged 64.1%, significantly outperforming the industry gain of 17.7% [1][2] Pipeline and Product Development - Kymera is utilizing targeted protein degradation (TPD) to develop drugs for critical health issues, with KT-621 being the first degrader in clinical evaluation for immunological diseases [5][6] - KT-621 is a first-in-class, once-daily oral degrader of STAT6, showing complete STAT6 degradation and reductions in type 2 inflammation biomarkers in a Phase I study [6][8] - The company has initiated a Phase IIb study, BROADEN2, for KT-621 in patients with moderate to severe atopic dermatitis, with data expected by mid-2027 [7][8] - Parallel Phase IIb studies for KT-621 in asthma are set to begin in Q1 2026, aiming to expedite its development [8][9] Strategic Partnerships - In June 2025, Kymera entered an exclusive agreement with Gilead Sciences to develop a novel molecular glue degrader targeting CDK2 for oncology applications [10][12] - Kymera also collaborates with Sanofi, which has selected KT-485 for clinical studies targeting IRAK4 for immuno-inflammatory diseases, while discontinuing KT-474 [13][15] Valuation and Financial Estimates - KYMR shares are currently overvalued with a price/book ratio of 4.99X, compared to the industry average of 3.49X [16] - The Zacks Consensus Estimate for 2025 loss per share has widened, while the estimate for 2026 loss has narrowed to $3.74 [17][19] Future Outlook - Positive data from the upcoming KT-621 study is anticipated to significantly boost the stock [20] - Existing investors are advised to hold, while prospective investors should seek a better entry point due to the long development timeline ahead [20][21]

Core Insights - Kymera Therapeutics has initiated dosing in the BROADEN2 Phase 2b clinical trial for KT-621, targeting moderate to severe atopic dermatitis (AD), with data expected by mid-2027 [1][2] - The company is also set to launch the BREADTH Phase 2b trial for asthma in Q1 2026, indicating a strategic focus on multiple Type 2 diseases [3][2] - KT-621 is a first-in-class oral degrader of STAT6, which plays a crucial role in Type 2 inflammation, and has shown promising results in early studies [4][2] Company Developments - The BROADEN2 trial is a randomized, double-blind, placebo-controlled study involving approximately 200 patients over 16 weeks, with primary and secondary endpoints focused on efficacy and safety measures [2][1] - The completion of dosing in the KT-621 BroADen Phase 1b trial is anticipated to yield data in December 2025, further supporting the development timeline for KT-621 [1][2] - The parallel development of KT-621 for both AD and asthma is expected to enhance the drug's market potential and facilitate dose selection for future Phase 3 studies [3][2] Product Information - KT-621 is designed to degrade STAT6, a transcription factor involved in IL-4/IL-13 signaling, which is central to Type 2 inflammatory diseases [4][2] - The investigational drug has demonstrated complete STAT6 degradation in early trials, along with a favorable safety profile compared to placebo [4][2] - The potential market for KT-621 includes over 130 million patients globally suffering from various Type 2 diseases, highlighting significant unmet medical needs [4][2] Industry Context - Atopic dermatitis is a prevalent chronic inflammatory condition that significantly impacts patients' quality of life, with existing treatments showing limitations [5][2] - The ongoing development of innovative therapies like KT-621 reflects the industry's shift towards targeted treatments for chronic immunological diseases [6][2]

Core Insights - Kymera Therapeutics has made significant progress in its clinical trials, particularly with KT-621, which is the first STAT6-directed agent for atopic dermatitis (AD) patients, with data expected in December 2025 [1][2][3] - The company is well-capitalized with $979 million in cash as of September 30, 2025, providing a runway into the second half of 2028 [1][14] - Upcoming milestones include the initiation of the KT-621 BROADEN2 Phase 2b trial in AD and the BREADTH Phase 2b trial in asthma, both expected to accelerate development across multiple indications [2][9] Clinical Development Updates - Enrollment and dosing have been completed in the KT-621 BroADen Phase 1b trial for moderate to severe AD, with results anticipated in December 2025 [1][3] - The KT-621 BROADEN2 Phase 2b trial has been initiated, evaluating three doses in approximately 200 patients over 16 weeks, with data expected by mid-2027 [3][4] - KT-579, an oral degrader of IRF5, has completed IND-enabling studies, with a Phase 1 clinical trial expected to start in early 2026 [1][10] Financial Performance - Collaboration revenues for Q3 2025 were $2.8 million, down from $3.7 million in Q3 2024, primarily from the collaboration with Gilead Sciences [11] - Research and development expenses increased to $74.1 million in Q3 2025 from $60.4 million in Q3 2024, driven by investments in the STAT6 program [12] - The net loss for Q3 2025 was $82.2 million, compared to $62.5 million in Q3 2024, with cash and cash equivalents totaling $978.7 million as of September 30, 2025 [14][22]

Core Insights - Kymera Therapeutics announced promising preclinical data for KT-579, an oral degrader of IRF5, showing its potential to modify diseases like lupus and rheumatoid arthritis (RA) [2][3] - The company plans to initiate Phase 1 testing for KT-579 in early 2026 [4] Preclinical Data - KT-579 demonstrated broad activity in preclinical models, with effects comparable or superior to existing therapies for lupus and RA [1][3] - The data presented at the American College of Rheumatology (ACR) Convergence Annual Meeting highlighted KT-579's ability to reduce autoimmune symptoms and disease progression [3][4] Mechanism of Action - KT-579 selectively targets and degrades IRF5, a key regulator of immune responses, thereby suppressing multiple pro-inflammatory pathways [2][3] - In lupus mouse models, KT-579 significantly impacted Type I IFN signaling and pathogenic B cell subsets, leading to reductions in blood interferon-stimulated genes and serum autoantibodies [3][4] Efficacy in Disease Models - In RA rodent models, KT-579 achieved a dose-dependent reduction in joint swelling and inhibited pro-inflammatory cytokines [3][4] - In vitro studies confirmed KT-579's ability to block Th1-skewing cytokines, preventing pathogenic T cell differentiation [3] Future Developments - The company is focused on advancing KT-579 through clinical trials, aiming to provide a new oral treatment option for patients with complex rheumatic and autoimmune diseases [4][6]

Core Insights - Kymera Therapeutics (KYMR) is focused on targeted protein degradation (TPD) to develop drugs for immunological diseases, with significant partnerships with Sanofi and Gilead Sciences to enhance its pipeline [1] Partnership with Sanofi - Sanofi has selected KT-485/SAR447971, an oral candidate targeting IRAK4 for immuno-inflammatory diseases, to advance into clinical studies, following extensive preclinical work [2][3] - Sanofi will discontinue the development of KT-474, which was under evaluation for hidradenitis suppurativa and atopic dermatitis, and will exercise its participation election right for the IRAK4 target [4] - Kymera received a $20 million milestone payment in Q2 2025 related to KT-485, and is eligible for up to $975 million in potential milestones associated with this candidate [4][5] Collaboration with Gilead - Kymera entered an exclusive option and license agreement with Gilead to develop a novel molecular glue degrader (MGD) program targeting CDK2, with potential applications in breast cancer and other solid tumors [6] - The agreement includes an upfront payment of $85 million and potential total payments up to $750 million, along with tiered royalties on net product sales [7][8] Progress with Other Candidates - Kymera's KT-621 has shown strong phase I results in atopic dermatitis, with phase 2b trials planned for 2025-26 [10][11] - The data from KT-621 surpassed expectations, showing comparable efficacy to Dupixent, with ongoing studies expected to report results in Q4 2025 [12] - Kymera is advancing a follow-on oral STAT6 degrader to KT-621 and plans to initiate phase I testing for KT-579 in early 2026 [13] Overall Assessment - The oncology deal with Gilead is promising, providing a significant cash influx, but the delay in milestone payments due to Sanofi's decision to prioritize KT-485 over KT-474 presents challenges [14]

Kymera Therapeutics (KYMR) Conference Summary Company Overview - **Company**: Kymera Therapeutics - **Focus**: Development of targeted protein degradation therapies, particularly in immunology - **Key Products**: KT621 (STAT6 degrader), IRAK4, IRAK5 Core Industry Insights - **Industry**: Biopharmaceuticals, specifically focused on immunology and targeted protein degradation - **Market Need**: There is a significant unmet need for effective oral drugs in immunology, as traditional small molecule inhibitors struggle to block pathways as effectively as biologics [7][8][49] Key Points and Arguments 1. **Platform Evolution**: Kymera has evolved its platform over the past nine years, focusing on developing small molecules that can bind to untracked proteins and create orally available degraders [6][10] 2. **Target Selection**: The company prioritizes targets that have not been drugged before and focuses on pathways with validated efficacy [7][12] 3. **Pipeline Highlights**: The pipeline includes promising programs like STAT6 and IRAK5, which are seen as innovative approaches to treating Th2 inflammation [9][14] 4. **Clinical Development**: The company is transitioning from Phase I to Phase II studies for its STAT6 degrader, with a focus on demonstrating efficacy in atopic dermatitis and asthma [13][18] 5. **Dosing Strategy**: The Phase II studies will explore various dosing levels to determine the optimal degradation of STAT6 and its correlation with clinical efficacy [18][20] 6. **Biomarker Utilization**: The company plans to use established biomarkers for patient selection and efficacy measurement in clinical trials [36][41] 7. **Market Opportunity**: There are approximately 100 million patients with Th2 diseases globally, with a significant portion in the U.S. lacking access to effective treatments [48][49] 8. **Competitive Advantage**: Kymera claims to have a first-mover advantage in the STAT6 space, with data already shared from healthy volunteer studies, positioning it ahead of competitors [51][53] Additional Important Insights - **Machine Learning Integration**: The company is leveraging machine learning to identify new druggable targets and optimize small molecule design [11][12] - **Regulatory Advocacy**: Kymera is actively engaging with regulatory bodies to address disparities in treatment timelines between small molecules and biologics [68][69] - **Future Directions**: The company is focused on advancing its second-generation degraders and ensuring robust manufacturing capabilities as it scales up for Phase III trials [64][65] Conclusion Kymera Therapeutics is positioned as a leader in the biopharmaceutical industry, particularly in the development of innovative oral therapies for immunological conditions. The company's strategic focus on targeted protein degradation, robust clinical pipeline, and commitment to addressing unmet medical needs highlight its potential for significant impact in the market.

Company Overview - Kymera Therapeutics, Inc. is a clinical-stage biopharmaceutical company focused on developing oral small molecule degrader medicines for immunological diseases [1][3] - The company aims to transform care for patients with immuno-inflammatory diseases through a portfolio of first-in-class oral medicines [2][3] Leadership Change - Brian Adams has been appointed as Chief Legal Officer and Corporate Secretary, succeeding Ellen Chiniara, who is retiring [1][2] - Mr. Adams brings nearly two decades of experience in the life sciences sector, having held senior legal roles at various biopharmaceutical companies [2] Strategic Focus - Kymera is pioneering the field of targeted protein degradation (TPD) to develop innovative therapies that address health problems not accessible with conventional treatments [3] - The company has advanced its first degrader into clinical trials for immunological diseases and is building a pipeline of oral small molecule degraders [3]