Core Insights - Summit Therapeutics Inc. reported progress on its lead drug candidate, ivonescimab, and its third-quarter financial results, with stock trading lower [1][7] Clinical Trial Results - The Phase 3 HARMONi-6 trial demonstrated that ivonescimab combined with chemotherapy reduced the risk of progression or death by 40% compared to BeOne Medicines' Tevimbra and chemotherapy for advanced squamous non-small cell lung cancer (NSCLC) [2] - The ivonescimab regimen extended the median time without tumor progression to 11.1 months, an increase of 4.2 months over the Tevimbra-based therapy [2] - The overall response rate (ORR) for ivonescimab plus chemotherapy was 75.9%, compared to 66.5% for tislelizumab plus chemotherapy, with a duration of response (DoR) of 11.20 months versus 8.38 months [3] Future Plans - Based on the HARMONi-6 results, the company plans to submit a Biologics License Application (BLA) for ivonescimab plus chemotherapy in Q4 2025 [4] - Summit is currently enrolling patients in the HARMONi-3 Phase 3 study to compare ivonescimab with Merck's Keytruda for first-line metastatic NSCLC, with expected completion of enrollment in the squamous cohort by H1 2026 [5] - A new Phase 3 HARMONi-GI3 study has been initiated for first-line unresectable metastatic colorectal cancer (CRC), with plans for further expansion of the ivonescimab clinical development program [6] Financial Position - As of September 30, 2025, the company reported cash and cash equivalents of $238.6 million [6]

Financial Data and Key Metrics Changes - The company ended Q3 2025 with a cash position of approximately $238.56 million [36] - Total GAAP operating expenses for Q3 2025 were $234.2 million, a decrease from $568.4 million in Q2 2025, primarily due to a higher stock-based compensation expense recorded in the previous quarter [36][37] - Non-GAAP operating expenses for Q3 2025 were $103.4 million, an increase from $89.6 million in the previous quarter, mainly due to increased R&D expenses related to ongoing trials [37] Business Line Data and Key Metrics Changes - The Harmony Three study is enrolling ahead of goals, with over 80% of the planned 600 squamous patients cohort expected to complete enrollment in Q1 2026 [35] - The Harmony GI3 study, evaluating ivonescimab in colorectal cancer, is set to begin activating clinical trial sites in the U.S. by the end of 2025, with an expected enrollment of 600 patients [30][22] Market Data and Key Metrics Changes - The Harmony Six study demonstrated a median progression-free survival (PFS) of 11.14 months for ivonescimab plus chemotherapy compared to 6.90 months for the control group, indicating a significant clinical benefit [10][17] - The study showed consistent benefits across various PD-L1 expression levels, with hazard ratios of 0.55 for negative, 0.63 for low, and 0.71 for high PD-L1 expression [11][17] Company Strategy and Development Direction - The company plans to submit a Biologics License Application (BLA) for ivonescimab based on the Harmony study results, aiming to establish it as a new standard of care for advanced squamous non-small cell lung cancer [24][19] - The clinical development program has expanded to include multiple phase three trials across various solid tumors, indicating a strategic focus on broadening the application of ivonescimab [22][30] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism regarding the results from Harmony Six and its implications for future studies, emphasizing the potential of ivonescimab to improve outcomes for patients with limited treatment options [21][19] - The company is actively engaging with the FDA and is confident in the safety and efficacy data supporting the BLA submission [52][51] Other Important Information - The Harmony Six study was conducted in China and sponsored by Akeso Inc., with all relevant data managed and analyzed by them [2][6] - The company highlighted the importance of the safety profile of ivonescimab, noting low rates of adverse events leading to discontinuation [12][17] Q&A Session Summary Question: When could the first overall survival (OS) cut from Harmony Six be expected? - Management indicated that a review in 2026 is likely, but specific timelines are difficult to disclose [41][43] Question: What options are being evaluated to extend the runway for funding? - The company has an ATM with approximately $350 million and has received inbound interest for additional capital [47][48] Question: Can you provide insights on the BLA submission and interactions with the FDA? - Continuous interactions with the FDA have been positive, and the company is preparing to submit the BLA based on the Harmony data [51][52] Question: What prompted the protocol amendments to Harmony Three? - The amendments were made to accelerate the front-line lung cancer opportunity and reduce regulatory risks by separating analyses for squamous and non-squamous histologies [70][71]

Core Insights - The Phase III HARMONi trial data for ivonescimab plus chemotherapy shows an improving overall survival (OS) trend with a nominal p-value of 0.0332 compared to chemotherapy alone, particularly in North American patients with an OS hazard ratio (HR) of 0.70 [1][4][6] Group 1: Trial Overview - HARMONi trial evaluated ivonescimab plus platinum-doublet chemotherapy against placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who progressed after third-generation EGFR TKI treatment [2][18] - The trial's primary endpoints were progression-free survival (PFS) and overall survival (OS), with previous PD-1 monoclonal antibodies failing to show benefits in similar settings [2] Group 2: Efficacy Results - In the primary analysis, ivonescimab plus chemotherapy showed a median OS of 16.8 months versus 14.0 months for placebo plus chemotherapy, with a hazard ratio of 0.79 (95% CI: 0.62 – 1.01; p=0.057) [4][6] - Longer-term follow-up analysis indicated a median OS of 17.0 months for ivonescimab compared to 14.0 months for placebo in Western patients, with an improved hazard ratio of 0.84 [6][7] - The overall response rate was higher in the ivonescimab arm at 45% compared to 34% in the placebo arm, with a median duration of response of 7.6 months versus 4.2 months [10] Group 3: Safety Profile - Ivonescimab plus chemotherapy demonstrated a manageable safety profile, with 7.3% of patients discontinuing due to treatment-related adverse events (TRAEs) compared to 5.0% in the placebo group [12][13] - The most common TRAEs included anemia and decreases in white blood cell counts, with less than 1% experiencing Grade 3 or higher hemorrhage events [12][13] Group 4: Future Developments - Summit Therapeutics plans to host a conference call on September 8, 2025, to discuss the ivonescimab data presented at the WCLC 2025 [14][30] - The company is engaged in multiple Phase III clinical trials for ivonescimab, including HARMONi-2 and HARMONi-6, which are expected to further evaluate its efficacy [19][20]

Summit Therapeutics Q1 2025 Earnings Call May 1, 2025 4:30pm ET Forward Looking Statement Any statements in this presentation about the Company's future expectations, plans and prospects, including but not limited to, statements about the clinical and preclinical development of the Company's product candidates, entry into and actions related to the Company's partnership with Akeso Inc., the Company's anticipated spending and cash runway, the therapeutic potential of the Company's product candidates, the pot ...

Core Viewpoint - Summit Therapeutics' stock is experiencing a decline following the FDA approval of Akeso Inc.'s PD-1 monoclonal antibody, penpulimab-kcqx, for treating non-keratinizing nasopharyngeal carcinoma (NPC) [1][8]. Group 1: FDA Approval and Drug Development - Akeso Inc. received FDA approval for penpulimab-kcqx in combination with cisplatin or carboplatin and gemcitabine for first-line treatment of adult recurrent or metastatic NPC [1]. - The FDA also approved penpulimab-kcqx as a single agent for adults with metastatic NPC who have disease progression after platinum-based chemotherapy and at least one other prior line of therapy [2]. - Penpulimab-kcqx is Akeso's first internally developed biologic to receive FDA approval, marking the company's entry into the U.S. regulatory system [4]. Group 2: Clinical Trials and Efficacy - The FDA approval was based on the international Phase 3 trial AK105-304 and pivotal AK105-202 study, which demonstrated the drug's clinical benefits and favorable safety profile for metastatic NPC [5]. - The Phase 3 HARMONi-6/K112-306 trial evaluated Summit Therapeutics' ivonescimab in combination with platinum-based chemotherapy, meeting its primary endpoint of progression-free survival (PFS) [6]. - Ivonescimab monotherapy showed a statistically significant improvement in PFS compared to Merck's Keytruda, achieving a hazard ratio of 0.51 in the Phase 3 HARMONi-2 trial [7]. Group 3: Market Impact and Stock Performance - Following the FDA approval, Summit Therapeutics' stock price fell by 36.8%, trading at $23.21 [8]. - The National Medical Products Administration in China approved ivonescimab for use as a monotherapy for first-line treatment of PD-L1-positive non-small cell lung cancer (NSCLC) [8].