Q1 2026 Summit Therapeutics Inc Business Update Call

June 1, 2026

Operator: Welcome everyone to the Summit Therapeutics ASCO 2026 update call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, press star one again. Thank you.Thank you. I would now like to turn the call over to Dave Gancarz, Chief Business & Strategy Officer. Please go ahead.

Operator: Welcome everyone to the Summit Therapeutics ASCO 2026 Update Call. All lines have been placed on mute to prevent any background noise. After the speaker's remarks, there will be a question and answer session. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question, press star one again. Thank you. I would now like to turn the call over to Dave Gancarz, Chief Business and Strategy Officer. Please go ahead.

Speaker #1: Everyone to the Summit Therapeutics ESCO 2026 update call. All lines have been placed on mute to prevent any background noise. After the speakers' remarks, there will be a question-and-answer session.

Speaker #1: If you would like to ask a question during this time, simply press start, followed by the number 1 on your telephone keypad. If you would like to reject your question, press star 1 again.

Speaker #1: Thank you. I would now like to turn the call over to Dave Gancarz, Chief Business and Strategy Officer. Please go ahead.

Speaker #2: Good morning, and thank you for joining us. Team Summit is pleased to be hosting this call from Chicago, where the oncology community has gathered for what has already been an exciting ESCO 2026 congress.

Dave Gancarz: Good morning, and thank you for joining us. Team Summit is pleased to be hosting this call from Chicago, where the oncology community has gathered for what has already been an exciting ASCO 2026 progress. This meeting continues to showcase the rapid pace of innovation across cancer research and treatment, and we're energized to be a part of this important scientific and clinical discussion, directing the next wave of medicines for patients with cancer. We issued two press releases over the weekend relating to encouraging phase II data in metastatic colorectal cancer, and of course, the historic results of the phase III HARMONi-6 trial featuring ivonesimab, presented as part of yesterday's plenary session at ASCO. The phase II CRC data is a global data set, including patients enrolled in the United States and China. The HARMONi-6 study was conducted exclusively in China, sponsored by our partners at Akeso.

Speaker #2: This meeting continues to showcase the rapid pace of innovation across cancer research and treatment, and we're energized to be a part of this important scientific and clinical discussion directing the next wave of medicines for patients with cancer.

Speaker #2: We issued two press releases over the weekend relating to encouraging phase two data in metastatic colorectal cancer and, of course, the historic results of the phase three Harmony 6 trial featuring Ivanesimab presented as part of yesterday's plenary session at ESCO.

Speaker #2: The phase two CRC data is a global data set including patients enrolled in the United States and China, and the Harmony 6 study was conducted exclusively in China, sponsored by our partners at Accesso.

Dave Gancarz: The phase II CRC data is a global data set, including patients enrolled in the United States and China. The HARMONi-6 study was conducted exclusively in China, sponsored by our partners at Akeso. All data in the HARMONi-6 study was exclusively generated, managed, and analyzed by Akeso. The press releases are available on our website, www.summittherapeutics.com. Today's call is being simultaneously webcast, and an archived replay will also be made available later today on our website.

Speaker #2: All data in the Harmony 6 study was exclusively generated, managed, and analyzed by Accesso. The press releases are available on our website, www.smnttx.com. Today's call is being simultaneously webcast, and an archived replay will also be made available later today on our website.

Dave Gancarz: All data in the HARMONi-6 study was exclusively generated, managed, and analyzed by Akeso. The press releases are available on our website, www.summittherapeutics.com. Today's call is being simultaneously webcast, and an archived replay will also be made available later today on our website. Joining me on the call today is Bob Duggan, our Chairman of the Board and Co-Chief Executive Officer, Dr. Maky Zanganeh, our President and Co-Chief Executive Officer, Manmeet Soni, our Chief Operating Officer and Chief Financial Officer, Dr. Bilal Safradi, our Chief Medical Officer, Dr. Allen Yang, our Chief R&D Strategy Officer, and Dr. H. Jack West, our VP of Global Medical Affairs. I am Dave Gancarz, our Chief Business and Strategy Officer.

Speaker #2: Joining me on the call today is Bob Duggan, our Chairman of the Board and Co-Chief Executive Officer. Dr. Maky Zanganeh, our President and Co-Chief Executive Officer.

Dave Gancarz: Joining me on the call today is Bob Duggan, our Chairman of the Board and Co-Chief Executive Officer, Dr. Maky Zanganeh, our President and Co-Chief Executive Officer, Manmeet Soni, our Chief Operating Officer and Chief Financial Officer, Dr. Bilal Safradi, our Chief Medical Officer, Dr. Allen Yang, our Chief R&D Strategy Officer, and Dr. H. Jack West, our VP of Global Medical Affairs. I am Dave Gancarz, our Chief Business and Strategy Officer.

Speaker #2: Manmeet Soni, our Chief Operating Officer and Chief Financial Officer. Dr. Bilal Papardi, our Chief Medical Officer. Dr. Allen Yang, our Chief R&D Strategy Officer.

Speaker #2: And Dr. Howard Jack West, our VP of Global Medical Affairs. I am Dave Gancarz, our Chief Business and Strategy Officer. Before we get started with the call, I would like to note that some statements made by our management team and some responses to questions that we make today may be considered forward-looking statements based on our current expectations.

Dave Gancarz: Before we get started with the call, I would like to note that some statements made by our management team and some responses to questions that we make today may be considered forward-looking statements based on our current expectations. Summit cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Please refer to our SEC filings for information about these risks and uncertainties. Summit undertakes no obligation to update these forward-looking statements except as required by law. One item of note, this presentation is being webcast with slides, so we'll be referring to slides being displayed on the webcast link. I'd encourage you to use the webcast link to see the slides being presented this morning that will accompany our comments. Following comments from our team, we will take questions.

Speaker #2: Summit cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements.

Speaker #2: Please refer to our FCC filings for information about these risks and uncertainties. Summit undertakes no obligation to update these forward-looking statements except as required by law.

Speaker #2: One item of note, this presentation is being webcast with slides, so we'll be referring to slides being displayed on the webcast link. I'd encourage you to use the webcast link to see the slides being presented this morning that will accompany our comments.

Dave Gancarz: I'd encourage you to use the webcast link to see the slides being presented this morning that will accompany our comments. Following comments from our team, we will take questions. With that, I would like to hand it over to Dr. Jack West to walk through the beginning of the presentation.

Speaker #2: Following comments from our team, we will take questions. And with that, I would like to hand it over to Dr. Jack West to walk through the beginning of the presentation.

Dave Gancarz: With that, I would like to hand it over to Dr. Jack West to walk through the beginning of the presentation.

Speaker #3: Thank you, Dave. Yesterday, as you are aware, Ivanesimab data were featured in a presentation as part of the plenary session of ESCO, the presentation titled "Ivanesimab + Chemotherapy vs. Physalisimab + Chemotherapy: In Previously Untreated Advanced Squamous Non-Small Cell Lung Cancer," overall survival results of the phase three Harmony 6 trial was delivered by Dr. Sean Liu, MD, PhD, Principal Investigator of Harmony 6, Director of the Lung Cancer Center at Shanghai Chest Hospital, and tenured professor.

H. Jack West: Thank you, Dave. Yesterday, as you are aware, ivonescimab data were featured in a presentation as part of the plenary session of ASCO. The presentation, titled "Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in previously untreated advanced squamous non-small cell lung cancer: Overall survival results of the phase III HARMONi-6 trial" was delivered by Dr. Shun Lu, MD, PhD, Principal Investigator of HARMONi-6, Director of the Lung Cancer Center at Shanghai Chest Hospital, and tenured professor. Prior to discussing the results of the study, we will reinforce the study design and baseline characteristics that were discussed at ESMO last fall, as well as published simultaneously in the first paper for the study in The Lancet. The study was highly significant in its primary endpoint of progression-free survival. Of course, the focus of the data release was the overall survival data from this study.

Howard Jack West: Thank you, Dave. Yesterday, as you are aware, ivonescimab data were featured in a presentation as part of the plenary session of ASCO. The presentation, titled "Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in previously untreated advanced squamous non-small cell lung cancer: Overall survival results of the phase III HARMONi-6 trial" was delivered by Dr. Shun Lu, MD, PhD, Principal Investigator of HARMONi-6, Director of the Lung Cancer Center at Shanghai Chest Hospital, and tenured professor. Prior to discussing the results of the study, we will reinforce the study design and baseline characteristics that were discussed at ESMO last fall, as well as published simultaneously in the first paper for the study in The Lancet. The study was highly significant in its primary endpoint of progression-free survival.

Speaker #3: Prior to discussing the results of the study, we will reinforce the study design, baseline characteristics that were discussed at ESMO last fall. As well as published simultaneously in the first paper for the study in The Lancet.

Speaker #3: The study was highly significant in its primary endpoint of progression-free survival. And of course, the focus of the data release was the overall survival data from this study.

Howard Jack West: Of course, the focus of the data release was the overall survival data from this study. Revisiting the schema for the HARMONi-6 trial, this study evaluated ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, a PD-1 inhibitor, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous non-small cell lung cancer, irrespective of PD-L1 expression. HARMONi-6 is a single-region, multicenter, phase III study conducted in China and sponsored by Akeso, with all relevant data exclusively generated, managed, and analyzed by Akeso. Key eligibility criteria are shown here. Patients were randomized one-to-one and stratified by stage of cancer and PD-L1 tumor expression at baseline.

Speaker #3: Revisiting the schema for the Harmony 6 trial, this study evaluated Ivanesimab in combination with platinum-based chemotherapy compared with Physalisimab, a PD-1 inhibitor in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous non-small cell lung cancer irrespective of PD-L1 expression.

H. Jack West: Revisiting the schema for the HARMONi-6 trial, this study evaluated ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, a PD-1 inhibitor, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous non-small cell lung cancer, irrespective of PD-L1 expression. HARMONi-6 is a single-region, multicenter, phase III study conducted in China and sponsored by Akeso, with all relevant data exclusively generated, managed, and analyzed by Akeso. Key eligibility criteria are shown here. Patients were randomized one-to-one and stratified by stage of cancer and PD-L1 tumor expression at baseline. Patients received either ivonescimab at 20 milligrams per kilogram plus carboplatin paclitaxel or tislelizumab plus carboplatin paclitaxel for up to 4 cycles, then received either ivonescimab or tislelizumab as maintenance therapy for up to 24 months. Treatment was to be discontinued for intolerability, progressive disease, or initiation of new antitumor therapy.

Speaker #3: Harmony 6 is a single region multicenter phase three study conducted in China and sponsored by Accesso, with all relevant data exclusively generated, managed, and analyzed by Accesso.

Speaker #3: Key eligibility criteria are shown here. Patients were randomized one to one, and stratified by stage of cancer. And PD-L1 tumor expression is baseline. Patients received either Ivanesimab at 20 milligrams per kilogram plus carboplatin paclitaxel or Physalisimab plus carboplatin paclitaxel for up to four cycles, then received either Ivanesimab or Physalisimab as maintenance therapy for up to 24 months.

Howard Jack West: Patients received either ivonescimab at 20 milligrams per kilogram plus carboplatin paclitaxel or tislelizumab plus carboplatin paclitaxel for up to 4 cycles, then received either ivonescimab or tislelizumab as maintenance therapy for up to 24 months. Treatment was to be discontinued for intolerability, progressive disease, or initiation of new antitumor therapy. The study's single primary endpoint was progression-free survival by independent radiologic review committee. The focus of today's progression will be overall survival.

Speaker #3: Treatment was to be discontinued for intolerability progressive disease or initiation of new anti-tumor therapy. The study's single primary endpoint was progression-free survival by independent radiologic review committee.

H. Jack West: The study's single primary endpoint was progression-free survival by independent radiologic review committee. The focus of today's progression will be overall survival. The trial included a total of 532 patients. Baseline characteristics show that this was a predominantly male population, nearly all with Stage 4 disease. It's important to underscore that these patients with advanced squamous non-small cell lung cancer included patients with characteristics that have traditionally been considered as potentially associated with bleeding on anti-angiogenic therapy. Specifically, approximately two-thirds had a central tumor, 17% had encasement of major blood vessels in the chest, 9% had tumor cavitation, and nearly one in three had a history of some hemostasis.

Speaker #3: The focus of today's progression will be overall survival. The trial included a total of 532 patients. Baseline characteristics showed that this was a predominantly male population, nearly all with stage four disease, and it's important to underscore that these patients with advanced squamous non-small cell lung cancer included patients with characteristics that have traditionally been considered as potentially associated with bleeding on anti-angiogenic therapy.

Howard Jack West: The trial included a total of 532 patients. Baseline characteristics show that this was a predominantly male population, nearly all with Stage 4 disease. It's important to underscore that these patients with advanced squamous non-small cell lung cancer included patients with characteristics that have traditionally been considered as potentially associated with bleeding on anti-angiogenic therapy. Specifically, approximately two-thirds had a central tumor, 17% had encasement of major blood vessels in the chest, 9% had tumor cavitation, and nearly one in three had a history of some hemostasis.

Speaker #3: Specifically, approximately two-thirds had a central tumor, 17% had encasement of major blood vessels in the chest, 9% had tumor cavitation, and nearly one in three had a history of some hemoptysis.

Speaker #3: The breakdown of PD-L1 expression showed approximately 40% had a PD-L1 negative cancer, with the remaining 60% of PD-L1 positive cancers showing 40% in the low range of one to 49% and about 20% with high PD-L1 expression of 50% or greater.

H. Jack West: The breakdown of PD-L1 expression showed approximately 40% had a PD-L1 negative cancer, with the remaining 60% of PD-L1 positive cancers showing 40% in the low range of 1% to 49%, and about 20% with high PD-L1 expression of 50% or greater. The median follow-up time of this current data cut is 21.4 months. At the planned interim analysis of the study, the trial was positive for overall survival, with a hazard ratio of 0.66 and a corresponding p-value of 0.0017, and representing at least a four-month difference in median survival, though this remains early at this time. The curves separate early at approximately six months after treatment begins and continue to expand with additional time. Landmark two-year overall survival rates were 64.7% for those patients receiving ivonescimab compared to 48.6% for those receiving anti-PD-L1 therapy with tislelizumab.

Howard Jack West: The breakdown of PD-L1 expression showed approximately 40% had a PD-L1 negative cancer, with the remaining 60% of PD-L1 positive cancers showing 40% in the low range of 1% to 49%, and about 20% with high PD-L1 expression of 50% or greater. The median follow-up time of this current data cut is 21.4 months. At the planned interim analysis of the study, the trial was positive for overall survival, with a hazard ratio of 0.66 and a corresponding p-value of 0.0017, and representing at least a four-month difference in median survival, though this remains early at this time. The curves separate early at approximately six months after treatment begins and continue to expand with additional time.

Speaker #3: The median follow-up time of this current data cut is 21.4 months. At the planned interim analysis of the study, the trial was positive for overall survival, with a hazard ratio of 0.66 and a corresponding p-value of 0.0017 and representing at least a four-month difference in median survival though this remains early at this time.

Speaker #3: The curve separates early at approximately six months. After treatment begins, and continues to expand with additional time. Landmark two-year overall survival rates were 64.7% for those patients receiving Ivanesimab compared to 48.6% for those receiving anti-PD-1 therapy with Physalisimab.

Howard Jack West: Landmark two-year overall survival rates were 64.7% for those patients receiving ivonescimab compared to 48.6% for those receiving anti-PD-L1 therapy with tislelizumab. This represents the first randomized phase III study conducted in driver mutation negative frontline non-small cell lung cancer against another PD-L1 therapy in combination with chemotherapy to achieve a statistically significant benefit in overall survival. When we look at various subgroups, it's important to highlight that the size of the subgroups is smaller by definition and not designed to show statistical significance on their own. The subgroup analyses for overall survival confirms the benefit in pre-planned subsets, as indicated by point estimates for each subgroup landing on the left side of the dividing line favoring ivonescimab, overall showing that the study results were observed broadly and not driven by a specific subset or subsets of patients.

Speaker #3: This represents the first randomized phase three study conducted in driver mutation negative frontline non-small cell lung cancer against another PD-1 therapy in combination with chemotherapy to achieve a statistically significant benefit in overall survival.

H. Jack West: This represents the first randomized phase III study conducted in driver mutation negative frontline non-small cell lung cancer against another PD-L1 therapy in combination with chemotherapy to achieve a statistically significant benefit in overall survival. When we look at various subgroups, it's important to highlight that the size of the subgroups is smaller by definition and not designed to show statistical significance on their own. The subgroup analyses for overall survival confirms the benefit in pre-planned subsets, as indicated by point estimates for each subgroup landing on the left side of the dividing line favoring ivonescimab, overall showing that the study results were observed broadly and not driven by a specific subset or subsets of patients. These overall survival curves show benefit in patients with negative, low, and high PD-L1 expression, representing PD-L1 TPS scores less than 1%, 1% to 49%, and 50% or more respectively at baseline.

Speaker #3: When we look at various subgroups, it's important to highlight that the size of the subgroups is smaller by definition and not designed to show statistical significance on their own.

Speaker #1: National time. Landmark two-year overall survival rates were 64.7% for those patients receiving ivonesimab compared to 48.6% for those receiving anti-PD-1 therapy with tislelizumab. This represents the first randomized phase 3 study conducted in driver mutation–negative frontline non-small cell lung cancer against another PD-1 therapy, in combination with chemotherapy, to achieve a statistically significant benefit in overall survival.

Speaker #3: The subgroup analyses for overall survival confirms the benefit in preplanned subsets, as indicated by point estimates for each subgroup landing on the left side of the dividing line favoring Ivanesimab.

Speaker #3: Overall, showing that the study results reserve broadly and not driven by a specific subset or subsets of patients. These overall survival curves show benefit in patients with negative low and high PD-L1 expression.

Howard Jack West: These overall survival curves show benefit in patients with negative, low, and high PD-L1 expression, representing PD-L1 TPS scores less than 1%, 1% to 49%, and 50% or more respectively at baseline. Patients with negative PD-L1 tumor expression had a hazard ratio of 0.64. Those with low PD-L1 tumor expression had a hazard ratio of 0.67, and those with high PD-L1 tumor expression had a hazard ratio of 0.64. In other words, ivonescimab with chemotherapy demonstrated benefit compared to tislelizumab with chemotherapy across the entire spectrum of tumor PD-L1 expression. Ivonescimab continued to demonstrate an acceptable and manageable safety profile in the HARMONi-6 study consistent with previous phase III studies of ivonescimab plus chemotherapy. No additional safety signals were noted in the HARMONi-6 study.

Speaker #3: Representing PD-L1 TPS scores less than 1%, one to 49%, and 50% or more respectively at baseline. Patients with negative PD-L1 tumor expression had a hazard ratio of 0.64.

Speaker #1: When we look at various subgroups, it's important to highlight that the size of the subgroups is smaller by definition and not designed to show statistical significance on their own.

H. Jack West: Patients with negative PD-L1 tumor expression had a hazard ratio of 0.64. Those with low PD-L1 tumor expression had a hazard ratio of 0.67, and those with high PD-L1 tumor expression had a hazard ratio of 0.64. In other words, ivonescimab with chemotherapy demonstrated benefit compared to tislelizumab with chemotherapy across the entire spectrum of tumor PD-L1 expression. Ivonescimab continued to demonstrate an acceptable and manageable safety profile in the HARMONi-6 study consistent with previous phase III studies of ivonescimab plus chemotherapy. No additional safety signals were noted in the HARMONi-6 study. Treatment-related serious adverse events occurred in 41.4% of patients receiving ivonescimab plus chemotherapy and 34.3% of patients receiving tislelizumab plus chemotherapy. Treatment-related adverse events leading to discontinuation in the study occurred in 5.3% of patients receiving ivonescimab plus chemotherapy, compared to 4.5% for those receiving tislelizumab plus chemotherapy.

Speaker #1: The subgroup analyses for overall survival confirm the benefit in preplanned subsets, as indicated by point estimates for each subgroup landing on the left side of the dividing line favoring Ivonesimab.

Speaker #3: Those with low PD-L1 tumor expression had a hazard ratio of 0.67, and those with high PD-L1 tumor expression had a hazard ratio of 0.64.

Speaker #3: In other words, Ivanesimab with chemotherapy demonstrated benefit compared to Physalisimab with chemotherapy across the entire spectrum of tumor PD-L1 expression. Ivanesimab continued to demonstrate an acceptable and manageable safety profile in the Harmony 6 study consistent with previous phase three studies of Ivanesimab plus chemotherapy.

Speaker #1: Overall, the study results were observed broadly and were not driven by a specific subset or subsets of patients. These overall survival curves show benefit in patients with negative, low, and high PD-L1 expression.

Speaker #1: Representing PD-L1 TPS scores of less than 1%, 1% to 49%, and 50% or more, respectively, at baseline. Patients with negative PD-L1 tumor expression had a hazard ratio of 0.64.

Speaker #3: No additional safety signals were noted in the Harmony 6 study. Treatment-related serious adverse events occurred in 41.4% of patients receiving Ivanesimab plus chemotherapy and 34.3% of patients receiving Physalisimab plus chemotherapy.

Howard Jack West: Treatment-related serious adverse events occurred in 41.4% of patients receiving ivonescimab plus chemotherapy and 34.3% of patients receiving tislelizumab plus chemotherapy. Treatment-related adverse events leading to discontinuation in the study occurred in 5.3% of patients receiving ivonescimab plus chemotherapy, compared to 4.5% for those receiving tislelizumab plus chemotherapy. The most common treatment-related adverse events in both arms were commonly associated with platinum doublet chemotherapy and included anemia, decreases in neutrophil counts, and white blood cell counts.

Speaker #1: Those with low PD-L1 tumor expression had a hazard ratio of 0.67, and those with high PD-L1 tumor expression had a hazard ratio of 0.64.

Speaker #3: Treatment-related adverse events leading to discontinuation in the study occurred in 5.3% of patients receiving Ivanesimab plus chemotherapy compared to 4.5% for those receiving Physalisimab plus chemotherapy.

Speaker #1: In other words, ivonesimab with chemotherapy demonstrated benefit compared to tislelizumab with chemotherapy across the entire spectrum of tumor PD-L1 expression. Ivonesimab continued to demonstrate an acceptable and manageable safety profile in the HARMONi-6 study consistent with previous phase 3 studies of ivonesimab plus chemotherapy.

Speaker #3: The most common treatment-related adverse events in both arms were commonly associated with platinum doublet chemotherapy and included anemia, decreases in neutrophil counts, and white blood cell counts.

H. Jack West: The most common treatment-related adverse events in both arms were commonly associated with platinum doublet chemotherapy and included anemia, decreases in neutrophil counts, and white blood cell counts. Most of the possibly VEGF-related adverse events occurring in the ivonescimab plus chemotherapy arm were classified as Grade 1 or 2. Grade 3 or higher hemorrhage events were observed in 2.6% of patients in the ivonescimab plus chemotherapy arm, compared to 0.8% of patients in the tislelizumab plus chemotherapy arm of the study. In summary, ivonescimab provided a statistically significant and clinically meaningful overall survival benefit for patients with advanced squamous non-small cell lung cancer as first-line treatment in the HARMONi-6 trial, with a hazard ratio of 0.66, which was consistent across all key subgroups, including those with negative, low, or high PD-L1 tumor expression. Regardless of PD-L1 tumor expression, patients received consistent benefit.

Speaker #1: No additional safety signals were noted in the HARMONY-6 study. Treatment-related serious adverse events occurred in 41.4% of patients receiving ivonesimab plus chemotherapy and 34.3% of patients receiving tislelizumab plus chemotherapy.

Speaker #3: Most of the possibly vegF-related adverse events occurring in the Ivanesimab plus chemotherapy arm were classified as grade one or two. Grade three or higher hemorrhage events were observed in 2.6% of patients in the Ivanesimab plus chemotherapy arm compared to 0.8% of patients in the Physalisimab plus chemotherapy arm of the study.

Howard Jack West: Most of the possibly VEGF-related adverse events occurring in the ivonescimab plus chemotherapy arm were classified as Grade 1 or 2. Grade 3 or higher hemorrhage events were observed in 2.6% of patients in the ivonescimab plus chemotherapy arm, compared to 0.8% of patients in the tislelizumab plus chemotherapy arm of the study. In summary, ivonescimab provided a statistically significant and clinically meaningful overall survival benefit for patients with advanced squamous non-small cell lung cancer as first-line treatment in the HARMONi-6 trial, with a hazard ratio of 0.66, which was consistent across all key subgroups, including those with negative, low, or high PD-L1 tumor expression.

Speaker #1: Treatment-related adverse events leading to discontinuation in the study occurred in 5.3% of patients receiving ivonesimab plus chemotherapy, compared to 4.5% for those receiving tislelizumab plus chemotherapy.

Speaker #3: In summary, Ivanesimab provided a statistically significant and clinically meaningful overall survival benefit for patients with advanced squamous non-small cell lung cancer as first-line treatments in the Harmony 6 trial, with a hazard ratio of 0.66, which was consistent across all key subgroups including those with negative low or high PD-L1 tumor expression.

Speaker #1: The most common treatment-related adverse events in both arms were those commonly associated with platinum doublet chemotherapy and included anemia, decreases in neutrophil counts, and white blood cell counts.

Speaker #1: Most of the possibly VEGF-related adverse events occurring in the ivonesimab plus chemotherapy arm were classified as grade 1 or 2. Grade 3 or higher hemorrhage events were observed in 2.6% of patients in the ivonesimab plus chemotherapy arm, compared to 0.8% of patients in the tislelizumab plus chemotherapy arm of the study.

Speaker #3: Regardless of PD-L1 tumor expression, patients received consistent benefits. Ivanesimab's strong performance across all levels of PD-L1 expression is important as Ivanesimab appears to provide clinically meaningful improvements to patients irrespective of PD-L1 expression.

Howard Jack West: Regardless of PD-L1 tumor expression, patients received consistent benefit. Ivonescimab's strong performance across all levels of PD-L1 expression is important as ivonescimab appears to provide clinically meaningful improvements to patients irrespective of PD-L1 expression. Ivonescimab was well-tolerated, with low rates of adverse events leading to discontinuation or death, both comparable to the tislelizumab plus chemotherapy arm. Prior to HARMONi-6, there were no known phase III clinical trials in non-small cell lung cancer that have shown a statistically significant improvement in both PFS and now OS compared to PD-1 or PD-L1 inhibitor therapy in combination with chemotherapy in a head-to-head comparison.

H. Jack West: Ivonescimab's strong performance across all levels of PD-L1 expression is important as ivonescimab appears to provide clinically meaningful improvements to patients irrespective of PD-L1 expression. Ivonescimab was well-tolerated, with low rates of adverse events leading to discontinuation or death, both comparable to the tislelizumab plus chemotherapy arm. Prior to HARMONi-6, there were no known phase III clinical trials in non-small cell lung cancer that have shown a statistically significant improvement in both PFS and now OS compared to PD-1 or PD-L1 inhibitor therapy in combination with chemotherapy in a head-to-head comparison.

Speaker #1: In summary, ivonesimab provided a statistically significant and clinically meaningful overall survival benefit for patients with advanced squamous non-small cell lung cancer as first-line treatment in the HARMONi-6 trial, with a hazard ratio of 0.66. This benefit was consistent across all key subgroups, including those with negative, low, or high PD-L1 tumor expression.

Speaker #3: Ivanesimab was well tolerated with low rates of adverse events leading to discontinuation or death. Both comparable to the Physalisimab plus chemotherapy arm. Prior to Harmony 6, there were no known phase three clinical trials in non-small cell lung cancer that have shown a statistically significant improvement in both PFS and now OS compared to PD-1 or L-1 inhibitor therapy in combination with chemotherapy in a head-to-head comparison.

Speaker #1: Regardless of PD-L1 tumor expression, patients received consistent benefits. Ivonesimab's strong performance across all levels of PD-L1 expression is important, as Ivonesimab appears to provide clinically meaningful improvements to patients irrespective of PD-L1 expression.

Speaker #3: Following the success of Acasso's Harmony 2 study in China, where the PFS benefit was observed in a monotherapy setting for patients whose squamous or non-squamous tumors were positive for PD-L1 expression, this is the second time in which Ivanesimab-based regimens have become the first known investigational therapy to demonstrate a statistically significant benefit compared to standard-of-care PD-1 or L-1 inhibitor-based therapy.

H. Jack West: Following the success of Akeso's HARMONi-2 study in China, where the PFS benefit was observed in a monotherapy setting for patients whose squamous or non-squamous tumors were positive for PD-L1 expression, this is the second time in which ivonescimab-based regimens have become the first known investigational therapy to demonstrate a statistically significant benefit compared to standard of care PD-1 or PD-L1 inhibitor-based therapy. This underscores the specific value that ivonescimab in the HARMONi-6 regimen could bring to patients in this setting, with the opportunity to include a differentiated mechanism of action for physicians and patients to choose from. We believe that ivonescimab has the potential to become a new standard of care for advanced squamous non-small cell lung cancer, and we look forward to the near-term readout for our global Phase III study, HARMONi-3, evaluating ivonescimab in frontline non-small cell lung cancer.

Howard Jack West: Following the success of Akeso's HARMONi-2 study in China, where the PFS benefit was observed in a monotherapy setting for patients whose squamous or non-squamous tumors were positive for PD-L1 expression, this is the second time in which ivonescimab-based regimens have become the first known investigational therapy to demonstrate a statistically significant benefit compared to standard of care PD-1 or PD-L1 inhibitor-based therapy. This underscores the specific value that ivonescimab in the HARMONi-6 regimen could bring to patients in this setting, with the opportunity to include a differentiated mechanism of action for physicians and patients to choose from.

Speaker #1: Ivonesimab was well tolerated, with low rates of adverse events leading to discontinuation or death—both comparable to the tislelizumab plus chemotherapy arm. Prior to HARMONi-6, there were no known phase 3 clinical trials in non-small cell lung cancer that have shown a statistically significant improvement in both PFS and now OS compared to PD-1 or L1 inhibitor therapy in combination with chemotherapy in a head-to-head comparison.

Speaker #3: This underscores the specific value that Ivanesimab in the Harmony 6 regimen could bring to patients in this setting with the opportunity to include a differentiated mechanism of action for physicians and patients to choose from.

Speaker #3: We believe that Ivanesimab has the potential to become a new standard of care for advanced squamous non-small cell lung cancer and we look forward to the near-term readouts for our global phase three study, Harmony 3, evaluating Ivanesimab in frontline non-small cell lung cancer.

Howard Jack West: We believe that ivonescimab has the potential to become a new standard of care for advanced squamous non-small cell lung cancer, and we look forward to the near-term readout for our global Phase III study, HARMONi-3, evaluating ivonescimab in frontline non-small cell lung cancer. With today's positive HARMONi-6 overall survival update, we gain even more confidence in the potential for ivonescimab to make a meaningful difference in the lives of patients with lung cancer. On that note, we want to extend a heartfelt thank you to the patients and their families, the clinical site personnel, and the Akeso team for contributing to and conducting the HARMONi-6 trial. Additionally, it is worth highlighting that "The Lancet" published a full HARMONi-6 manuscript concurrent with yesterday's plenary session.

Speaker #1: Following the success of Acceso's Harmony2 study in China, where the PFS benefit was observed in a monotherapy setting for patients whose squamous or non-squamous tumors were positive for PD-L1 expression, this is the second time in which ivonesimab-based regimens have become the first known investigational therapy to demonstrate a statistically significant benefit compared to standard-of-care PD-1 or L1 inhibitor-based therapy.

Speaker #3: With today's positive Harmony 6 overall survival update, we gain even more confidence in the potential for Ivanesimab to make a meaningful difference in the lives of patients with lung cancer.

H. Jack West: With today's positive HARMONi-6 overall survival update, we gain even more confidence in the potential for ivonescimab to make a meaningful difference in the lives of patients with lung cancer. On that note, we want to extend a heartfelt thank you to the patients and their families, the clinical site personnel, and the Akeso team for contributing to and conducting the HARMONi-6 trial. Additionally, it is worth highlighting that "The Lancet" published a full HARMONi-6 manuscript concurrent with yesterday's plenary session. With that, I'd like to turn it back to Dave.

Speaker #3: On that note, we want to extend a heartfelt thank you to the patients and their families the clinical site personnel, and the Acasso team for contributing to and conducting the Harmony 6 trial.

Speaker #1: This underscores the specific value that Ivanesimab and the Harmony6 regimen could bring to patients in this setting, with the opportunity to include a differentiated mechanism of action for physicians and patients to choose from.

Speaker #3: Additionally, it is worth highlighting that Harmony 6 manuscript concurrent with yesterday's plenary session. And with that, I'd like to turn it back to Dave.

Speaker #1: We believe that ivonesimab has the potential to become a new standard of care for advanced squamous non-small cell lung cancer, and we look forward to the near-term readouts for our global Phase 3 study, HARMONi-3, evaluating ivonesimab in frontline non-small cell lung cancer.

Howard Jack West: With that, I'd like to turn it back to Dave.

Speaker #1: Thanks, Jack. I'd like to echo Jack's comments around our gratitude for the patients who enrolled on Harmony 6, their family members, trial site personnel, investigators, and of course, the Acasso team.

Dave Gancarz: Thanks, Jack. I'd like to echo Jack's comments around our gratitude for the patients who enrolled on HARMONi-6, their family members, trial site personnel, investigators, and of course, the Akeso team. We are highly encouraged by the read-through of this study to HARMONi-3 in frontline all-comers non-small cell lung cancer, as well as HARMONi-7 in non-small cell lung cancer with high PD-L1 expression. Anti-PD-1 therapy, with or without chemotherapy, depending on PD-L1 status, is the overwhelming standard of care in frontline lung cancer without driver mutations. Ivonescimab, both as monotherapy and in combination with chemotherapy, now compares favorably in both settings in phase III studies conducted in China.

Speaker #1: With today's positive Harmony6 overall survival update, we gain even more confidence in the potential for ivanesimab to make a meaningful difference in the lives of patients with lung cancer.

Speaker #1: We are highly encouraged by the read-through of this study to Harmony 3 in frontline all-comers non-small cell lung cancer as well as Harmony 7 in non-small cell lung cancer with high PD-L1 expression.

Speaker #1: On that note, we want to extend a heartfelt thank you to the patients and their families, the clinical site personnel, and the Accessos team for contributing to and conducting the Harmony6 trial.

Speaker #1: Anti-PD-1 therapy with or without chemotherapy, depending on PD-L1 status, is the overwhelming standard of care in frontline lung cancer without driver mutations. Ivanesimab, both as monotherapy and in combination with chemotherapy, now compared favorably in both settings in phase three studies conducted in China.

Speaker #1: Additionally, it is worth highlighting that The Lancet published a full Harmony 6 manuscript concurrent with yesterday's plenary session. And with that, I'd like to turn it back to Dave.

Speaker #1: While additional Harmony 3 data will be important to see in the coming quarters, the consistent statistically significant clinically meaningful results in progression-free survival and overall survival in Harmony 6 and the PFS and OS data generated today from Harmony 2 are very encouraging, and we look to our ongoing global frontline lung cancer studies and beyond.

Dave Gancarz: While additional HARMONi-3 data will be important to see in the coming quarters, the consistent, statistically significant, clinically meaningful results in progression-free survival and overall survival in HARMONi-6 and the PFS and OS data generated to date from HARMONi-2 are very encouraging when we look to our ongoing global frontline lung cancer studies and beyond. One additional point I'd like to ensure we go over. There were some commentary with respect to the subgroup analysis hazard ratios that were disclosed in the forest plot for overall survival related to results by age groups presented yesterday. As you may recall from ESMO 2025, while patients under 65 and over 65 both showed a PFS benefit from ivonescimab plus chemotherapy as compared to tislelizumab plus chemotherapy, the effect was seen less in older patients.

Speaker #2: Thanks, Jack. I'd like to echo Jack's comments regarding our gratitude to the patients who enrolled in Harmony6, their family members, trial site personnel, investigators, and of course, the Accessos team.

Speaker #2: We are highly encouraged by the read-through of this study to Harmony3 in frontline all-comers non-small cell lung cancer, as well as Harmony7 in non-small cell lung cancer with high PD-L1 expression.

Speaker #1: One additional point I'd like to ensure we go over: there were some commentary with respect to subgroup analyses to the subgroup analysis hazard ratios that were disclosed in the fourth plot for overall survival, related to results by age groups presented yesterday.

Speaker #2: Anti-PD-1 therapy, with or without chemotherapy depending on PD-L1 status, is the overwhelming standard of care in frontline lung cancer without driver mutations. Ivanesimab, both as monotherapy and in combination with chemotherapy, has now compared favorably in both settings in phase three studies conducted in China.

Speaker #1: As you may recall from ESMO 2025, while patients under 65 and over 65 both showed a PFS benefit from Ivanesimab plus chemotherapy as compared to Physalisimab plus chemotherapy, the effects were seen less in older patients.

Speaker #2: While additional Harmony3 data will be important to see in the coming quarters, the consistent statistically significant clinically meaningful results in progression-free survival and overall survival in Harmony6 and the PFS and OS data generated today from Harmony2 are very encouraging, and we look to our ongoing global frontline lung cancer studies and beyond.

Speaker #1: An analysis was performed by Acasso to review differences in baseline characteristics between those over 65 in the IVO arm versus the TISLI arm to understand this difference.

Dave Gancarz: An analysis was performed by Akeso to review differences in baseline characteristics between those over 65 in the ivo arm versus the tisli arm to understand this difference. In doing so, multiple imbalances were noted, including target lesion size and the presence of brain metastases. This was specifically addressed previously during the ESMO 2025 presentation. Correcting for these baseline differences explained a substantive portion of the difference in hazard ratios by age for PFS, and it is important to see that written on the slide on the screen right now. If you are on the webcast, the slides from ESMO 2025 note that when adjusting for these covariates, the adjusted PFS hazard ratio for those patients greater than 65 years old was 0.69. Note that for both PFS and OS, not even considering the imbalanced baseline characteristics, the older subgroup did not show any detriment.

Speaker #1: In doing so, multiple imbalances were noticed, including target lesion size and the presence of brain metastases. This was specifically addressed previously during the ESMO 2025 presentation.

Speaker #2: One additional point I'd like to ensure we go over: there was some commentary with respect to subgroup analyses, specifically the subgroup analysis hazard ratios that were disclosed in the fourth slot, where overall survival related to results by age groups was presented yesterday.

Speaker #1: Correcting for these baseline differences, explained a substantive portion of the difference in hazard ratios by age for PFS. And it is important to see that written on the slide on the screen right now.

Speaker #2: As you may recall from ESMO 2025, while patients under 65 and over 65 both showed a PFS benefit from ivonesimab plus chemotherapy compared to tislelizumab plus chemotherapy, the effects were less pronounced in older patients.

Speaker #1: If you are on the webcast, the slides from ESMO 2025 note that when adjusting for these covariates, the adjusted PFS hazard ratio for those patients greater than 65 years old was 0.69.

Speaker #2: An analysis was performed by Accessos to review differences in baseline characteristics between those over 65 in the IVO arm versus the TIZLI arm to understand this difference.

Speaker #1: Note that for both PFS and OS, not even considering the imbalance baseline characteristics, the older subgroup did not show any detriment. Once adjusted for these baseline differences, the hazard ratio for PFS was normalized to the overall population.

Dave Gancarz: Note that for both PFS and OS, not even considering the imbalanced baseline characteristics, the older subgroup did not show any detriment. Once adjusted for these baseline differences, the hazard ratio for PFS was normalized to the overall population. Therefore, the difference noted appears to be most likely driven by the imbalanced baseline characteristics. These differences were seen in PFS and could be seen in the OS forest plots as well, and can happen in clinical trials. Each subgroup is not powered and is not necessarily balanced for baseline characteristics, and if prognostic factors are not balanced, a subgroup can be impacted, as we described previously last October.

Speaker #2: In doing so, multiple imbalances were noted, including target lesion size and the presence of brain metastases. This was specifically addressed previously during the ESMO 2025 presentation. Correcting for these baseline differences explained a substantive portion of the difference in hazard ratios by age for PFS.

Dave Gancarz: Once adjusted for these baseline differences, the hazard ratio for PFS was normalized to the overall population. Therefore, the difference noted appears to be most likely driven by the imbalanced baseline characteristics. These differences were seen in PFS and could be seen in the OS forest plots as well, and can happen in clinical trials. Each subgroup is not powered and is not necessarily balanced for baseline characteristics, and if prognostic factors are not balanced, a subgroup can be impacted, as we described previously last October. Importantly, remember that HARMONi-6 is the fourth phase III study conducted evaluating ivonescimab. In the first three studies, results for patients under and over 65 were very comparable. In the global HARMONi study, the longer-term follow-up of OS showed a numerically better hazard ratio for those patients over 65.

Speaker #1: Therefore, the difference noted appears to be more most likely driven by the imbalance baseline characteristics. These differences were seen in PFS, could be seen in could be seen in the OS fourth plot as well, and can happen in clinical trials.

Speaker #2: And it is important to see that written on the slide on the screen right now. If you are on the webcast, the slides from ESMO 2025 note that when adjusting for these covariates, the adjusted PFS hazard ratio for those patients greater than 65 years old was 0.69.

Speaker #1: Each subgroup is not powered and is not necessarily balanced for baseline characteristics and, if prognostic factors are not balanced, a subgroup can be impacted as we described previously last October.

Speaker #1: Importantly, remember that Harmony 6 is the fourth phase three study conducted evaluating Ivanesimab. In the first three studies, results for patients under and over 65 were very comparable.

Dave Gancarz: Importantly, remember that HARMONi-6 is the fourth phase III study conducted evaluating ivonescimab. In the first three studies, results for patients under and over 65 were very comparable. In the global HARMONi study, the longer-term follow-up of OS showed a numerically better hazard ratio for those patients over 65. HARMONi-6 is the only study where we see this difference in this unpowered subgroup at imbalanced baseline characteristics. Let's move on and discuss the continued deep experience we have with ivonesimab. Ivonesimab has read out four phase III clinical studies to date, all four of which had positive data, leading to two approvals in China thus far.

Speaker #2: Note that for both PFS and OS, not even considering the imbalanced baseline characteristics, the older subgroup did not show any detriment. Once adjusted for these baseline differences, the hazard ratio for PFS was normalized to the overall population.

Speaker #1: In the global Harmony study, the longer-term follow-up of OS showed a numerically better hazard ratio for those patients over 65. So Harmony 6 is the only study where we see this difference in this unpowered subgroup had imbalanced baseline characteristics.

Speaker #2: Therefore, the difference noted appears to be more most likely driven by the imbalanced baseline characteristics. These differences were seen in PFS, could be seen in could be seen in the OS fourth slot as well, and can happen in clinical trials.

Dave Gancarz: HARMONi-6 is the only study where we see this difference in this unpowered subgroup at imbalanced baseline characteristics. Let's move on and discuss the continued deep experience we have with ivonesimab. Ivonesimab has read out four phase III clinical studies to date, all four of which had positive data, leading to two approvals in China thus far. At this time, a total of 15 phase III clinical trials have either been announced, are currently ongoing, or have read out in multiple tumor types. 47 clinical trials have been initiated since 2019 between Summit and Akeso, evaluating ivonesimab in a variety of solid tumors. When considering investigator-initiated and collaborative studies, a total of 155 clinical trials are now listed on ClinicalTrials.gov.

Speaker #1: Let's move on and discuss the continued deep experience we have with Ivanesimab. Ivanesimab has read out four phase three clinical studies to date; all four of which had positive data leading to two approvals in China, thus far.

Speaker #2: Each subgroup is not powered and is not necessarily balanced for baseline characteristics, and if prognostic factors are not balanced, a subgroup can be impacted, as we described previously last October.

Dave Gancarz: At this time, a total of 15 phase III clinical trials have either been announced, are currently ongoing, or have read out in multiple tumor types. 47 clinical trials have been initiated since 2019 between Summit and Akeso, evaluating ivonesimab in a variety of solid tumors. When considering investigator-initiated and collaborative studies, a total of 155 clinical trials are now listed on ClinicalTrials.gov. The enthusiasm demonstrated by investigators around the world to generate data and seek positive signals for patients facing high unmet medical needs really speaks to the opportunity and optimism surrounding ivonescimab.

Speaker #1: At this time, a total of 15 phase three clinical trials have either been announced, are currently ongoing, or have read out in multiple tumor types.

Speaker #2: Importantly, remember that Harmony6 is the fourth phase III study conducted evaluating ivonesimab. In the first three studies, results for patients under and over 65 were very comparable.

Speaker #1: 47 clinical trials have been initiated since 2019 between Summit and Acasso, evaluating Ivanesimab in a variety of solid tumors. When considering investigator-initiated and collaborative studies, the total of 155 clinical trials are now listed on clinicaltrials.gov.

Speaker #2: In the global Harmony study, the longer-term follow-up of OS showed a numerically better hazard ratio for those patients over 65. So, Harmony-6 is the only study where we see this difference in this unpowered subgroup, which had imbalanced baseline characteristics.

Speaker #1: The enthusiasm demonstrated by investigators around the world to generate data and seek positive signals for patients facing high unmet medical needs really speaks to the opportunity and optimism surrounding Ivanesimab.

Dave Gancarz: The enthusiasm demonstrated by investigators around the world to generate data and seek positive signals for patients facing high unmet medical needs really speaks to the opportunity and optimism surrounding ivonescimab. Together with our partner, Akeso, we have enrolled over 4,000 patients in either Summit-sponsored or Akeso-sponsored clinical trials around the world. Commercially, in China, over 70,000 patients have received ivonescimab. Turning to our pipeline and our global Phase III HARMONi study. In April, we provided an update with respect to the squamous cohort of this study. We added to our protocol an interim analysis for PFS for the specific purpose of providing a potential opportunity for earlier regulatory discussions, specifically with the FDA. To achieve statistical significance at this early interim look, there was a meaningfully higher bar compared to the upcoming planned final PFS analysis based on minimal alpha spent on the interim analysis.

Speaker #2: Let's move on and discuss the continued, deep experience we have with Ivanesimab. Ivanesimab has read out four Phase 3 clinical studies to date, all four of which had positive data, leading to two approvals in China thus far.

Speaker #1: Together with our partner, Acasso, we have enrolled over 4,000 patients in either Summit-sponsored or Acasso-sponsored clinical trials around the world. Commercially, in China, over 70,000 patients have received Ivanesimab.

Dave Gancarz: Together with our partner, Akeso, we have enrolled over 4,000 patients in either Summit-sponsored or Akeso-sponsored clinical trials around the world. Commercially, in China, over 70,000 patients have received ivonescimab. Turning to our pipeline and our global Phase III HARMONi study. In April, we provided an update with respect to the squamous cohort of this study. We added to our protocol an interim analysis for PFS for the specific purpose of providing a potential opportunity for earlier regulatory discussions, specifically with the FDA. To achieve statistical significance at this early interim look, there was a meaningfully higher bar compared to the upcoming planned final PFS analysis based on minimal alpha spent on the interim analysis.

Speaker #2: At this time, a total of 15 Phase 3 clinical trials have either been announced, are currently ongoing, or have read out in multiple tumor types.

Speaker #2: Forty-seven clinical trials have been initiated since 2019 between Summit and Accessos, evaluating ivanesimab in a variety of solid tumors. When considering investigator-initiated and collaborative studies, a total of 155 clinical trials are now listed on ClinicalTrials.gov.

Speaker #1: Turning to our pipeline, in our global phase three Harmony study, in April, we provided an update with respect to the squamous cohort of this study.

Speaker #1: We added to our protocol an interim analysis for PFS for the specific purpose of providing a potential opportunity for earlier regulatory discussions specifically with the US FDA.

Speaker #2: The enthusiasm demonstrated by investigators around the world to generate data and seek positive signals for patients facing high unmet medical needs really speaks to the opportunity and optimism surrounding ivanesimab.

Speaker #1: To achieve statistical significance at this early interim look, there was a meaningfully higher bar compared to the upcoming planned final PFS analysis based on minimal alpha spent on the interim analysis.

Speaker #2: Together with our partner Accessos, we have enrolled over 4,000 patients in either Summit-sponsored or Accessos-sponsored clinical trials around the world. Commercially, in China, over 70,000 patients have received Ivanesimab.

Speaker #1: The interim PFS analysis was reviewed by an independent data monitoring committee or an IDMC, and the committee recommended the study continuous plan. Importantly, no safety concerns were noted, and the study continues to be double-blinded.

Dave Gancarz: The interim PFS analysis was reviewed by an independent data monitoring committee, or an IDMC, and the committee recommended the study continue as planned. Importantly, no safety concerns were noted, and this study continues to be double-blinded. In line with prior guidance, we expect the final progression-free survival and interim overall survival analyses for the squamous cohort in H2 of this year. For the non-squamous cohort, we expect the final progression-free survival analysis to occur in H1 of 2027. The study continues to be double-blinded, and we do not have further information regarding the results of the study. We look forward to the results of the final PFS and interim OS in H2 of this year. With respect to the non-squamous cohort of HARMONi-3, we have completed screening for patient enrollment and expect to complete enrollment of the 1,000-patient cohort this month.

Speaker #2: Turning to our pipeline, in our global Phase 3 HARMONY study, in April we provided an update with respect to the squamous cohort of this study.

Speaker #1: In line with prior guidance, we expect the final progression-free survival and interim overall survival analyses for the squamous cohort in the second half of this year.

Speaker #2: We added to our protocol an interim analysis for PFS for the specific purpose of providing a potential opportunity for earlier regulatory discussions, specifically with the US FDA.

Speaker #1: For the non-squamous cohort, we expect the final progression-free survival analysis to occur in the first half of 2027. The study continues to be double-blinded, and we do not have further information regarding the results of the study.

Speaker #2: To achieve statistical significance at this early interim look, there was a meaningfully higher bar compared to the upcoming planned final PFS analysis, based on minimal alpha spent on the interim analysis.

Speaker #1: We look forward to the results of the final PFS and interim OS in the second half of this year. With respect to the non-squamous cohort of Harmony 3, we have completed screening for patient enrollment and expect to complete enrollment of the 1,000 patient cohort this month.

Dave Gancarz: With respect to the non-squamous cohort of HARMONi-3, we have completed screening for patient enrollment and expect to complete enrollment of the 1,000-patient cohort this month. We continue to enroll in HARMONi-7 and HARMONi-GI3. Look forward to continuing our work with GORTEC in head and neck cancer, as well as Revolution Medicines with novel RAS inhibitors, kicking off the GSK collaboration testing ivonescimab with ADCs, and expanding the number of collaborations we have with other agents with novel mechanisms of action. With that, I'd like to turn it over to Allen to review the phase II CRC data in combination with FOLFOX chemotherapy, the backbone chemotherapy for our phase III HARMONi-GI3 clinical study. Allen?

Speaker #2: The interim PFS analysis was reviewed by an independent Data Monitoring Committee, or IDMC, and the committee recommended the study continue as planned. Importantly, no safety concerns were noted, and the study continues to be double-blinded.

Speaker #1: We continue to enroll in Harmony 7 and Harmony GI 3. Look forward to continuing our work with Cortex in head and neck cancer as well as RevMed with novel RAS inhibitors, kicking off the GSK collaboration testing Ivanesimab with ADCs, and expanding the number of collaborations we have with other agents with novel mechanisms of action.

Dave Gancarz: We continue to enroll in HARMONi-7 and HARMONi-GI3. Look forward to continuing our work with GORTEC in head and neck cancer, as well as Revolution Medicines with novel RAS inhibitors, kicking off the GSK collaboration testing ivonescimab with ADCs, and expanding the number of collaborations we have with other agents with novel mechanisms of action. With that, I'd like to turn it over to Allen to review the phase II CRC data in combination with FOLFOX chemotherapy, the backbone chemotherapy for our phase III HARMONi-GI3 clinical study. Allen?

Speaker #2: In line with prior guidance, we expect the final progression-free survival and interim overall survival analyses for the squamous cohort in the second half of this year.

Speaker #2: For the non-squamous cohort, we expect the final progression-free survival analysis to occur in the first half of 2027. The study continues to be double-blinded, and we do not have further information regarding the results of the study.

Speaker #1: With that, I'd like to turn it over to Alan to review the phase two CRC data in combination with FOLFOX chemotherapy for backbone chemotherapy for our phase three Harmony GI 3 clinical study.

Speaker #2: We look forward to the results of the final PFS and interim OS in the second half of this year. With respect to the non-squamous cohort at Harmony3, we have completed screening for patient enrollment and expect to complete enrollment of the 1,000-patient cohort this month.

Speaker #1: Alan?

Speaker #2: Thanks, Dave. At this year's ASCO conference, Ivanesimab data and colorectal cancer was also featured from the global phase two study, AK112206. Which evaluates two doses of Ivanesimab, 20 milligrams per kilogram and 10 milligrams per kilogram, in combination with FOLFOX chemotherapy as first-line treatment in patients with microsatellite stable metastatic colorectal cancer.

Allen Yang: Thanks, Dave. At this year's ASCO conference, ivonescimab data in colorectal cancer was also featured from the global phase II study, AK112-206, which evaluates two doses of ivonescimab, 20 mg per kilogram and 10 mg per kilogram, in combination with FOLFOX chemotherapy as first-line treatment in patients with microsatellite stable metastatic colorectal cancer. The study was conducted in China and the US. Akeso had previously disclosed encouraging phase II study data with ivonescimab in combination with different chemotherapy regimens in microsatellite stable CRC. The standard of care chemotherapy in first-line metastatic setting is most often FOLFOX, and so we expanded the phase II study to include two cohorts of ivonescimab at different doses in combination with FOLFOX. This was the basis for our phase III study, HARMONi-GI3, as Dave alluded to.

Speaker #2: We continue to enroll in Harmony 7 and Harmony GI3. We look forward to continuing our work with GORE-TEX in head and neck cancer, as well as RevMed with novel RAS inhibitors, kicking off the GSK collaboration testing ivonesimab with ADCs, and expanding the number of collaborations we have with other agents with novel mechanisms of action.

Speaker #2: The study was conducted in China, and the US. Acasso had previously disclosed encouraging phase two study data with Ivanesimab in combination with different chemotherapy regimens in microsatellite stable CRC.

Speaker #2: With that, I'd like to turn it over to Alan to review the Phase 2 CRC data in combination with FOLFOX chemotherapy, which is the backbone chemotherapy for our Phase 3 HarmonyGI3 clinical study.

Speaker #2: The standard of care chemotherapy in first-line metastatic setting is the is most often FOLFOX, and so we expanded the phase two study to include two cohorts of Ivanesimab at different doses in combination with FOLFOX.

Speaker #2: Alan?

Speaker #3: Thanks, Dave. At this year's ASCO conference, ivonesimab data in colorectal cancer was also featured from the global phase II study AK112206, which evaluates two doses of ivonesimab—20 mg per kg and 10 mg per kg—in combination with FOLFOX chemotherapy as first-line treatment in patients with microsatellite stable metastatic colorectal cancer.

Speaker #2: This was the basis for our phase three study, Harmony GI 3, as Dave alluded to. This also represents global data as a mix of patients who are enrolled from the US and China for these two arms.

Allen Yang: This was the basis for our phase III study, HARMONi-GI3, as Dave alluded to. This also represents global data as a mix of patients who are enrolled from the US and China for these two arms. In this analysis, all patients experienced a reduction in tumor burden compared to their baseline assessment. The addition of ivonesimab to FOLFOX delivered deep and durable response rates, and responses were consistent across the 2 dose levels. In the overall study population, ivonesimab plus FOLFOX chemotherapy achieved an adjusted response rate of 70.8% and a disease control rate of 100%. Treatment responses in the higher dose of ivonesimab plus FOLFOX arm were more durable than the lower dose of ivonesimab plus FOLFOX, with a duration response landmark estimate at nine months of 79.1% and 41.5%, respectively.

Allen Yang: This also represents global data as a mix of patients who are enrolled from the US and China for these two arms. In this analysis, all patients experienced a reduction in tumor burden compared to their baseline assessment. The addition of ivonesimab to FOLFOX delivered deep and durable response rates, and responses were consistent across the 2 dose levels. In the overall study population, ivonesimab plus FOLFOX chemotherapy achieved an adjusted response rate of 70.8% and a disease control rate of 100%. Treatment responses in the higher dose of ivonesimab plus FOLFOX arm were more durable than the lower dose of ivonesimab plus FOLFOX, with a duration response landmark estimate at nine months of 79.1% and 41.5%, respectively. For patients in the higher dose ivonesimab arm, the landmark PFS rate at nine months was 76.1%.

Speaker #2: In this analysis, all patients experienced a reduction in tumor burden compared to their baseline assessment. The addition of Ivanesimab to FOLFOX delivered deep and durable response rates, and responses were consistent across the two dose levels.

Speaker #3: The study was conducted in China and the US. Accessus had previously disclosed encouraging Phase 2 study data with ivanesimab in combination with different chemotherapy regimens in microsatellite stable CRC.

Speaker #2: In the overall study population, Ivanesimab plus FOLFOX chemotherapy achieved an objective response rate of 70.8%, and the disease control rate of 100%. Treatment responses in the higher dose of Ivanesimab plus FOLFOX arm were more durable than the lower dose of Ivanesimab plus FOLFOX.

Speaker #3: The standard of care chemotherapy in the first-line metastatic setting is most often FOLFOX, and so we expanded the Phase 2 study to include two cohorts of Ivonesimab at different doses in combination with FOLFOX.

Speaker #3: This was the basis for our Phase 3 study, HarmonyGI3, as Dave alluded to. This also represents global data, as it's a mix of patients who were enrolled from the US and China for these two arms.

Speaker #2: With a duration response landmark estimate at nine months of 79.1% and 41.5%, respectively, for patients in the higher dose Ivanesimab arm, the landmark PFS rate at nine months was 76.1%.

Allen Yang: For patients in the higher dose ivonesimab arm, the landmark PFS rate at nine months was 76.1%. While progression-free survival remains immature, the high proportion of patients who are progression free at 9 months is encouraging. The study demonstrated an acceptable and manageable safety profile for the ivonesimab regimen, and no new safety signals were observed. This was consistent with previous studies of ivonesimab, including phase II data in metastatic microsatellite stable CRC, and demonstrate the potential for a favorable benefit risk profile for ivonesimab plus FOLFOX in this setting. In total, including both arms, 20.4% of patients experienced serious treatment-related adverse events associated with either ivonesimab or chemotherapy. There were no ivonesimab-related deaths and 1 ivonesimab-related discontinuation, supporting the tolerability and ability to manage these adverse effects.

Speaker #3: In this analysis, all patients experienced a reduction in tumor burden compared to their baseline assessment. The addition of ivonesimab to FOLFOX delivered deep and durable response rates, and responses were consistent across the two dose levels.

Speaker #2: While progression-free survival remains immature, the high proportion of patients whose progression-free at nine months is encouraging, the study demonstrated an acceptable and manageable safety profile for the Ivanesimab regimen and no new safety signals were observed.

Allen Yang: While progression-free survival remains immature, the high proportion of patients who are progression free at 9 months is encouraging. The study demonstrated an acceptable and manageable safety profile for the ivonesimab regimen, and no new safety signals were observed. This was consistent with previous studies of ivonesimab, including phase II data in metastatic microsatellite stable CRC, and demonstrate the potential for a favorable benefit risk profile for ivonesimab plus FOLFOX in this setting. In total, including both arms, 20.4% of patients experienced serious treatment-related adverse events associated with either ivonesimab or chemotherapy. There were no ivonesimab-related deaths and 1 ivonesimab-related discontinuation, supporting the tolerability and ability to manage these adverse effects. These support continued expansion of ivonesimab clinical development in metastatic colorectal cancer. They also support the design of our global phase III HARMONi-GI3 study in microsatellite stable metastatic colorectal cancer that is currently enrolling.

Speaker #3: In the overall study population, Ivanesimab plus FOLFOX chemotherapy achieved an objective response rate of 70.8% and a disease control rate of 100%. Treatment responses in the higher dose Ivanesimab plus FOLFOX arm were more durable than in the lower dose Ivanesimab plus FOLFOX arm.

Speaker #2: This was consistent with previous studies of Ivanesimab, including phase two data in metastatic microsatellite stable CRC and demonstrate the potential for a favorable benefit-risk profile for Ivanesimab plus FOLFOX in this setting.

Speaker #3: With the duration response landmark estimate at nine months of 79.1% and 41.5%, respectively, for patients in the higher dose Ivanesimab arm, the landmark PFS rate at nine months was 76.1%.

Speaker #2: In total, including both arms, 20.4% 20.4% of patients experienced serious treatment-related adverse events associated with either Ivanesimab or chemotherapy. There were no Ivanesimab-related deaths and one Ivanesimab-related discontinuation.

Speaker #3: While progression-free survival remains immature, the high proportion of patients who were progression-free at nine months is encouraging. The study demonstrated an acceptable and manageable safety profile for the Ivonesimab regimen, and no new safety signals were observed.

Speaker #2: Supporting the tolerability and ability to manage these adverse events. These support continued expansion of Ivanesimab clinical development in metastatic colorectal cancer. They also support the design of our global phase three Harmony GI 3 study in microsatellite stable metastatic colorectal cancer that is currently enrolling.

Allen Yang: These support continued expansion of ivonesimab clinical development in metastatic colorectal cancer. They also support the design of our global phase III HARMONi-GI3 study in microsatellite stable metastatic colorectal cancer that is currently enrolling. We are pleased with these results at ASCO and are excited about the potential to help patients facing colorectal cancer. The disease has a particularly poor outcome in the metastatic disease setting, with a five-year survival rate between 13% and 18%, underscoring the urgent need for improved treatment options.

Speaker #3: This was consistent with previous studies of Ivanesimab, including phase 2 data in metastatic microsatellite stable CRC, and demonstrates the potential for a favorable benefit-risk profile for Ivanesimab plus FOLFOX in this setting.

Speaker #2: We are pleased with these results at ASCO and are excited about the potential to help patients facing colorectal cancer. The disease has a particularly poor outcome in the metastatic disease setting, with a five-year survival rate between 13 and 18%.

Allen Yang: We are pleased with these results at ASCO and are excited about the potential to help patients facing colorectal cancer. The disease has a particularly poor outcome in the metastatic disease setting, with a five-year survival rate between 13% and 18%, underscoring the urgent need for improved treatment options. Before concluding the call, I wanted to take the opportunity to remind everyone of our upcoming catalysts and recent accomplishments. As we have discussed on past calls, we will continue to provide further detail on additional new global studies throughout the year as they are ready to share. To date, we have initiated global phase III studies in non-small cell lung cancer, colorectal cancer, and head and neck cancer through our partnership with GORTEC. We look forward to continuing to grow our global pipeline and explore ivonesimab's potential to help more patients in new tumor settings.

Speaker #3: In total, including both arms, 20.4% of patients experienced serious treatment-related adverse events associated with either ivonesimab or chemotherapy. There were no ivonesimab-related deaths and one ivonesimab-related discontinuation.

Speaker #2: Underscoring the urgent need for improved treatment options. Before concluding the call, I wanted to take the opportunity to remind everyone of our upcoming catalyst and recent accomplishments.

Allen Yang: Before concluding the call, I wanted to take the opportunity to remind everyone of our upcoming catalysts and recent accomplishments. As we have discussed on past calls, we will continue to provide further detail on additional new global studies throughout the year as they are ready to share. To date, we have initiated global phase III studies in non-small cell lung cancer, colorectal cancer, and head and neck cancer through our partnership with GORTEC. We look forward to continuing to grow our global pipeline and explore ivonesimab's potential to help more patients in new tumor settings.

Speaker #3: Supporting the tolerability and ability to manage these adverse events, these support continued expansion of ivanesimab clinical development in metastatic colorectal cancer. They also support the design of our global Phase 3 HarmonyGI3 study in microsatellite stable metastatic colorectal cancer that is currently enrolling.

Speaker #2: As we have discussed on past calls, we will continue to provide further details on additional new global studies throughout the year as they are ready to share.

Speaker #2: To date, we have initiated global phase three studies in non-small cell lung cancer, colorectal cancer, and head and neck cancer through our partnership with Cortex.

Speaker #3: We are pleased with these results at ASCO and are excited about the potential to help patients facing colorectal cancer. The disease has a particularly poor outcome in the metastatic disease setting, with a five-year survival rate between 13% and 18%.

Speaker #2: We look forward to continuing to grow our global pipelines and explore Ivanesimab's potential to help more patients in new tumor settings. For Harmony 3 trial for the Harmony 3 trial evaluating Ivanesimab with chemotherapy in frontline all-comers non-small cell lung cancer, we have completed enrollment in the squamous cohort.

Allen Yang: For the HARMONi-3 trial evaluating ivonesimab with chemotherapy in frontline all-comers non-small cell lung cancer, we have completed enrollment in the squamous cohort. We are now completing enrollment for the non-squamous cohort and expect to conclude enrollment this month. As I mentioned earlier, the final PFS and interim OS analysis for the squamous cohort are expected in H2 of this year for the non-squamous cohort, and the final PFS analysis is expected in H1 of 2027. Turning to our BLA filing, based on our Phase III HARMONi study seeking approval for ivonesimab plus chemotherapy in the EGFR mutated non-small cell lung cancer setting post-TKI, the submission is currently under review with the US FDA. The agency has provided a target PDUFA date of 14 November later this year.

Speaker #3: Underscoring the urgent need for improved treatment options. Before concluding the call, I wanted to take the opportunity to remind everyone of our upcoming catalysts and recent accomplishments.

Speaker #2: We are now completing enrollment for the non-squamous cohort and expect to conclude enrollment this month. As I mentioned earlier, the final PFS and interim OS analysis for the squamous cohort are expected in the second half of this year for the non-squamous cohort and the final PFS analysis is expected in the first half of 2027.

Speaker #3: As we have discussed on past calls, we will continue to provide further details on additional new global studies throughout the year as they are ready to share.

Speaker #3: To date, we have initiated global Phase 3 studies in non-small cell lung cancer, colorectal cancer, and head and neck cancer through our partnership with GORE-TEX.

Speaker #2: Turning to our BLA filing, based on our phase three Harmony study seeking approval for Ivanesimab plus chemotherapy in the EGFR mutated non-small cell lung cancer setting, post-TKI, the submission is currently under review with the US FDA Agency has provided a target to do for date of November 14th later this year.

Speaker #3: We look forward to continuing to grow our global pipelines and explore ivanesimab's potential to help more patients in new tumor settings. For the Harmony3 trial, evaluating ivanesimab with chemotherapy in frontline...

Speaker #3: All-comers non-small cell lung cancer—we have completed enrollment in the squamous cohort. We are now completing enrollment for the non-squamous cohort, and expect to conclude enrollment this month.

Speaker #2: We continue to grow our commercial capabilities as we prepare for the anticipation of Ivanesimab's potential first US approval and potential launch later this year.

Allen Yang: We continue to grow our commercial capabilities as we prepare for the anticipation of ivonesimab's potential first US approval and potential launch later this year. Okay, I'd like to give it back to Dave Gancarz.

Speaker #3: As I mentioned earlier, the final PFS and interim OS analysis for the squamous cohort are expected in the second half of this year. For the non-squamous cohort, the final PFS analysis is expected in the first half of 2027.

Speaker #2: Okay, I'd like to give it back to Dave Gancarz.

Speaker #1: Thanks, John. On today's call, we've covered Ivanesimab's accomplishments thus far in the clinic. But this is only the beginning of a vast potential market opportunity set for Ivanesimab across solid tumors.

Dave Gancarz: Thanks, Alan. On today's call, we've covered ivonescimab's accomplishments thus far in the clinic, but this is only the beginning of a vast potential market opportunity set for ivonescimab across solid tumors. We have discussed this several times before, but with each successful data set, the reality becomes closer. Ivonescimab has the potential to be a platform blockbuster drug. Ivonescimab is well-positioned to make a significant impact across the solid tumor treatment landscape between checkpoint inhibitors and anti-VEGF therapies, with an estimated total addressable market to be in excess of $100 billion globally. Looking only at the checkpoint inhibitor market for non-small cell lung cancer, market estimates for immunotherapy are expected to exceed $20 billion per year by 2028. On the slide you see on the screen now, many solid tumor settings where anti-PD-1 and anti-VEGF therapies are highlighted: PD-1 and PD-L1 indications in green, and anti-VEGF indications in purple.

Speaker #3: Turning to our BLA filing, based on our Phase 3 HARMONY study seeking approval for ivonesimab plus chemotherapy in the EGFR-mutated non-small cell lung cancer setting, post-TKI, the submission is currently under review with the U.S. FDA. The agency has provided a target PDUFA date of November 14th later this year.

Speaker #1: We have discussed this several times before, but with each successful data set, it becomes the reality becomes closer. Ivanesimab has the potential to be a platform blockbuster drug.

Speaker #1: Ivanesimab is well positioned to make a significant impact across the solid tumor treatment landscape. Between checkpoint inhibitors and anti-VEGF therapies, with an estimated total addressable market to be in excess of 100 billion dollars globally.

Speaker #3: We continue to grow our commercial capability as we prepare for the anticipated first U.S. approval of ivonesimab and its potential launch later this year.

Speaker #1: Looking only at the checkpoint inhibitor market for non-small cell lung cancer, market estimates for immunotherapy are expected to exceed 20 billion dollars per year.

Speaker #3: Okay. I'd like to give it back to Dave Gancarz.

Speaker #2: Thanks, Alan. On today’s call, we’ve covered Ivonesimab’s accomplishments thus far in the clinic. But this is only the beginning of a vast potential market opportunity set for Ivonesimab across solid tumors.

Speaker #1: By 2028. On the slide you see on the screen now, many solid tumor settings where anti-PD-1 and anti-VEGF therapies are highlighted. PD-1 and PD-L1 indications in green and anti-VEGF indications in purple.

Dave Gancarz: On the slide you see on the screen now, many solid tumor settings where anti-PD-1 and anti-VEGF therapies are highlighted: PD-1 and PD-L1 indications in green, and anti-VEGF indications in purple. The ones highlighted in yellow represent the indications where we are currently running Phase III trials for ivonesimab globally, lung and colorectal cancers. Clearly, there are several additional opportunities for ivonesimab, including, in addition, novel settings where neither have been effective, such as EGFR mutant non-small cell lung cancer. Ivonesimab's differentiated profile, as we saw with HARMONi-6 achieving a statistically significant, highly clinically meaningful PFS and OS benefit, supports its platform potential across multiple indications, each of which could be blockbuster opportunities on their own. We have only just begun to see the potential of ivonesimab to help patients with solid tumors.

Speaker #2: We have discussed this several times before, but with each successful data set, the reality becomes closer. Ivanesimab has the potential to be a platform blockbuster drug.

Speaker #1: The ones highlighted in yellow represent the indications where we are currently running phase three trials for Ivanesimab globally. Lung and colorectal cancers. Clearly, there are several additional opportunities for Ivanesimab, including in addition novel settings where neither have been effective.

Dave Gancarz: The ones highlighted in yellow represent the indications where we are currently running Phase III trials for ivonesimab globally, lung and colorectal cancers. Clearly, there are several additional opportunities for ivonesimab, including, in addition, novel settings where neither have been effective, such as EGFR mutant non-small cell lung cancer. Ivonesimab's differentiated profile, as we saw with HARMONi-6 achieving a statistically significant, highly clinically meaningful PFS and OS benefit, supports its platform potential across multiple indications, each of which could be blockbuster opportunities on their own. We have only just begun to see the potential of ivonesimab to help patients with solid tumors. These are exciting times at Summit, and we encourage you to stay tuned to our journey as we continue to expand the ivonesimab clinical development plan in new tumor settings.

Speaker #2: Ivanesimab is well positioned to make a significant impact across the solid tumor treatment landscape. Between checkpoint inhibitors and anti-VEGF therapies, with an estimated total addressable market to be in excess of 100 billion dollars globally.

Speaker #1: Such as EGFR mutant on small cell lung cancer. Ivanesimab's differentiated profile, as we saw with Harmony 6 achieving a statistically significant highly clinically meaningful PFS and OS benefits, supports its platform potential across multiple indications.

Speaker #2: Looking only at the checkpoint inhibitor market for non-small cell lung cancer, market estimates for immunotherapy are expected to exceed $20 billion per year.

Speaker #2: By 2028. On the slide you see on the screen now, there are many solid tumor settings where anti-PD-1 and anti-VEGF therapies are highlighted. PD-1 and PD-L1 indications are in green, and anti-VEGF indications are in purple.

Speaker #1: Each of which could be blockbuster opportunities on their own. We have only just begun to see the potential of Ivanesimab to help patients with solid tumors.

Speaker #1: These are exciting times at Summit, and we encourage you to stay tuned to our journey as we continue to expand the Ivanesimab clinical development plan in new tumor settings.

Dave Gancarz: These are exciting times at Summit, and we encourage you to stay tuned to our journey as we continue to expand the ivonesimab clinical development plan in new tumor settings. We'll now turn the call back to the operator to see if there are any questions that our team can help answer. If you could please open the line for questions.

Speaker #2: The ones highlighted in yellow represent the indications where we are currently running Phase 3 trials for Ivanesimab globally: lung and colorectal cancers. Clearly, there are several additional opportunities for Ivanesimab, including novel settings where neither have been effective.

Speaker #1: We'll now turn the call back to the operator to see if there are any questions that our team can help answer. If you could please open the line for questions.

Dave Gancarz: We'll now turn the call back to the operator to see if there are any questions that our team can help answer. If you could please open the line for questions.

Speaker #3: At this time, I would like to remind everyone in order to ask a question, press star, then the number one on your telephone keypad.

Speaker #2: Such as EGFR mutant or small cell lung cancer. Ivanesimab’s differentiated profile, as we saw with Harmony 6 achieving a statistically significant and highly clinically meaningful PFS and OS benefits, supports its platform potential across multiple indications.

Speaker #3: Please limit yourself to one question and one follow-up. We will pause for just a moment to compile the Q&A roster. Your first question comes from the line of Tyler Van Buren with TD Cullen.

Operator: Your first question comes from the line of Tyler Van Buren with TD Cowen. Your line is open.

Operator: At this time, I would like to remind everyone, in order to ask a question, press star then the number one on your telephone keypad. Please limit yourself to one question and one follow-up. We will pause for just a moment to compile the Q&A roster. Your first question comes from the line of Tyler Van Buren with TD Cowen. Your line is open.

Speaker #2: Each of which could be blockbuster opportunities on their own. We have only just begun to see the potential of ivonesimab to help patients with solid tumors.

Speaker #3: Your line is open.

Speaker #4: Hey guys, congratulations on the tremendous and potentially practice-changing data presented this weekend. Just can you provide your latest thoughts on how you believe the PFS has a ratio and now the impressive OS hazard ratio for Harmony 6 will translate to the ongoing Harmony 3 trial?

Tyler Van Buren: Hey, guys. Congratulations on the tremendous and potentially practice-changing data presented this weekend. Just can you provide your latest thoughts on how you believe the PFS hazard ratio and now the impressive OS hazard ratio for HARMONi-6 will translate to the ongoing HARMONi-3 trial? As the follow-up to that, specifically what is your confidence that ivo is performing similarly to HARMONi-6 in the ongoing HARMONi-3 trial, considering the fact that it passed on the recent interim PFS analysis?

Speaker #2: These are exciting times at Summit, and we encourage you to stay tuned to our journey as we continue to expand the ivanesimab clinical development plan in new tumor settings.

Speaker #2: We'll now turn the call back to the operator to see if there are any questions that our team can help answer. If you could please open the line for questions.

Speaker #4: And is the follow-up to that, what is specifically, what is your confidence that Ivo is performing similarly to Harmony 6 in the ongoing Harmony 3 trial considering the fact that it passed on the recent interim PFS analysis?

Speaker #3: At this time, I would like to remind everyone that in order to ask a question, please press star, then the number one on your telephone keypad.

Speaker #1: Thanks, Tyler. I think with respect to the overall confidence on Harmony 3, as we mentioned on the call, as well as we've mentioned a few times historically, the purpose for that interim analysis was specifically as we look at the landscape overall competitively, there are multiple PD-1, VEGF, and class of which we are significantly in the lead.

Dave Gancarz: Thanks, Tyler. I think with respect to the overall confidence on HARMONi-3, as we mentioned on the call, as well as we've mentioned a few times historically, the purpose for that interim analysis was specifically as we look at the landscape overall competitively, there are multiple PD-1, VEGF in class of which we are significantly in the lead. We looked at an opportunity to take the final PFS timing in the second half of this year and look to accelerate the timing by which we could speak to the US health authorities, in effect, the regulators and, in that case, specifically the FDA. With the minimal out allocation, we looked to perform that interim analysis, as I mentioned on the call. As I said earlier, the IDMC recommended to continue and recommended no changes to the study.

Speaker #3: Your line is open.

Speaker #4: Hey, guys. Congratulations on the tremendous and potentially practice-changing data presented this weekend. Can you provide your latest thoughts on how you believe the PFS hazard ratio and now the impressive OS hazard ratio for Harmony6 will translate to the ongoing Harmony3 trial?

Speaker #1: And so we looked at an opportunity to take the final PFS timing in the second half of this year and with and look to accelerate the timing by which we could speak to the US health authorities and affect the regulators and in that case specifically the FDA.

Speaker #4: And is the follow-up to that, specifically, what is your confidence that Ivo is performing similarly to Harmony6 in the ongoing Harmony3 trial, considering the fact that it passed the recent interim PFS analysis?

Speaker #1: And so with the minimal alpha allocation, we looked to perform that interim analysis, as I mentioned on the call. And so we and as I said earlier, the IDMC looked recommended to continue and recommended no changes to the study.

Speaker #2: Thanks, Tyler. I think, with respect to the overall confidence on Harmony3, as we mentioned on the call, as well as we've mentioned a few times historically, the purpose for that interim analysis was specifically, as we look at the landscape overall competitively, there are multiple PD-1, VEGF, and in that class of which we are significantly in the lead.

Dave Gancarz: As I said earlier, the IDMC recommended to continue and recommended no changes to the study. With that, we have no change in terms of our overall confidence because what we did in that process was not change the final PFS threshold in effect. It was extraordinarily minimal in terms of the cost on the final. As we look now at the data from HARMONi-6, we see two things. We see a highly statistically significant PFS and a highly statistically significant OS. That, in the same setting, gives us a lot of confidence as we look to translation overall from one study to another in that same setting, that we are very well-positioned with respect to the H2 of this year.

Speaker #1: With that, we have no change in terms of our overall confidence because what we did in that process was not change the final PFS threshold in effect.

Dave Gancarz: With that, we have no change in terms of our overall confidence because what we did in that process was not change the final PFS threshold in effect. It was extraordinarily minimal in terms of the cost on the final. As we look now at the data from HARMONi-6, we see two things. We see a highly statistically significant PFS and a highly statistically significant OS. That, in the same setting, gives us a lot of confidence as we look to translation overall from one study to another in that same setting, that we are very well-positioned with respect to the H2 of this year.

Speaker #1: It was extraordinarily minimal in terms of the cost on the final. So as we look now at the data from Harmony 6, we see two things.

Speaker #2: And so, we looked at an opportunity to take the final PFS timing in the second half of this year and look to accelerate the timing by which we could speak to the US health authorities and affect the regulators, in that case specifically the FDA.

Speaker #1: We see a highly statistically significant PFS and a highly statistically significant OS. And so that in the same setting, gives us a lot of confidence as we look to translation overall from one study to another in that same setting.

Speaker #2: And so, with the minimal alpha allocation, we looked to perform that interim analysis, as I mentioned on the call. And so, as I said earlier, the IDMC looked, recommended to continue, and recommended no changes to the study.

Speaker #1: That we have are very well positioned with respect to the second half of this year. I'd also remind if we look back at the gold standard endpoint of OS, when we look at the Harmony and the Harmony A studies, we had remarkably consistent median OS from the east and the west as well as highly consistent hazard ratios.

Dave Gancarz: I'd also remind if we look back at the gold standard endpoint of OS, when we look at the HARMONi and the HARMONi-8 studies, we had remarkably consistent median OS from the East and the West as well as highly consistent hazard ratios. We've seen in the past consistency overall between data with ivonescimab in China as compared to globally. The final point I would make is overall, again, we've had four phase III readouts in total. All four have been positive. When we look at the trajectory of that data, it's all pointing in one direction at this point, and that's been positive. From that perspective, while no one has a clear crystal ball, it is very much as we look at the data, we see everything moving and aligning in the same direction from that perspective.

Speaker #2: With that, we have no change in terms of our overall confidence, because what we did in that process was not change the final PFS threshold, in effect.

Speaker #2: It was extraordinarily minimal in terms of the cost on the final. So, as we look now at the data from Harmony 6, we see two things.

Speaker #1: We've seen in the past consistency overall between data with Ivanesimab in China as compared to globally. And then the final point I would make is overall, again, we've had four phase three readouts in total, all four have been positive.

Speaker #2: We see a highly statistically significant PFS and a highly statistically significant OS, and so that in the same setting gives us a lot of confidence as we look to translation overall from one study to another in that same setting.

Speaker #1: And so when we look at the trajectory of that data, it's all pointing in one direction at this point. And that's been positive. And so from that perspective, while no one has a clear crystal ball, it is very much as we look at the data, we see everything moving in a lining in the same direction from that perspective.

Speaker #2: We are very well positioned with respect to the second half of this year. I'd also remind you, if we look back at the gold standard endpoint of OS, when we look at the Harmony and the HarmonyA studies, we had remarkably consistent median OS from the East and the West, as well as highly consistent hazard ratios.

Dave Gancarz: From that perspective, while no one has a clear crystal ball, it is very much as we look at the data, we see everything moving and aligning in the same direction from that perspective.

Speaker #5: Dave, I'd like to add, Tyler, thanks for the question. The capsule is going to terrific partner. So the Harmony 6 and Harmony 3 trials are very similar.

Allen Yang: Dave, I'd like to add. Tyler, thanks for the question. Akeso has been a terrific partner, the HARMONi-6 and HARMONi-3 trials are very similar, if not almost identical. In addition, Akeso has helped us enroll patients from China for the HARMONi-3 study. About a third of those patients will be from overlapping sites and investigators with the HARMONi-3 and HARMONi-6 study. The one thing I'd also like to point out is we took a calculated risk trying to bring this drug to patients earlier. The enrollment for the squamous cohort just recently completed, and therefore that data was immature. We understood that risk, but we took it. Obviously, we were not happy with the results, but we thought that was important for patients. As the data matures, we expect our data to strengthen, although we haven't seen it.

Speaker #5: It's not almost identical. In addition, the capsule has helped us enroll patients from China for the Harmony 3 study. So about a third of those patients will be from overlapping sites and investigators.

Speaker #2: So we've seen in the past consistency overall between data with ivonesimab in China as compared to globally. And then the final point I would make is, overall, again, we've had four Phase 3 readouts in total— all four have been positive.

Speaker #5: With the Harmony 3 and Harmony 6 study. So the one thing I'd also like to point out is we took a calculated risk trying to bring this drug to patients earlier.

Speaker #2: And so, when we look at the trajectory of that data, it's all pointing in one direction at this point, and that's been positive. And so, from that perspective, while no one has a clear crystal ball, as we look at the data, we see everything moving and aligning in the same direction from that perspective.

Speaker #5: But the enrollment for the squamous cohort just recently completed and therefore that data was immature. We understood that risk, but we took it. Obviously, we were not happy with the results, but we thought that was important for patients.

Allen Yang: Obviously, we were not happy with the results, but we thought that was important for patients. As the data matures, we expect our data to strengthen, although we haven't seen it.

Speaker #5: But as the data matures, we expect our data to strengthen although we haven't seen it.

Speaker #5: Dave, I'd like to add—Tyler, thanks for the question. The capital has been a terrific partner. The Harmony6 and Harmony3 trials are very similar, if not almost identical.

Speaker #3: Your next question comes from the line of Salveen Richter with Goldman Sachs. Your line is open.

Operator: Your next question comes from the line of Salveen Richter with Goldman Sachs. Your line is open.

Speaker #5: In addition, Acasso has helped us enroll patients from China for the Harmony3 study. So about a third of those patients will be from overlapping sites and investigators.

Speaker #6: Good morning. Thanks for taking my questions and congratulations on the data here. Two for me. One is how do you think the strong squamous results read through to the non-squamous portion of the study?

Salveen Richter: Good morning. Thanks for taking my questions and congratulations on the data here. Two from me. One is, how do you think the strong squamous results read through to the non-squamous portion of the study? Secondly, at the presentation, the presenter noted that the median OS was reached with the last patient event. Could you put that finding in context and expectations for OS upon additional maturation? Thank you.

Speaker #5: With the Harmony3 and Harmony6 study, the one thing I'd also like to point out is we took a calculated risk trying to bring this drug to patients earlier.

Speaker #6: And secondly, at the presentation, the presenter noted that the median OS was reached with the last patient event. Could you put that finding in context and expectations for OS upon additional maturation?

Speaker #5: But the enrollment for the SWINGS cohort just recently completed, and therefore, that data was immature. We understood that risk, but we took it. Obviously, we were not happy with the results, but we thought that was important for patients.

Speaker #6: Thank you.

Speaker #1: Thanks, Salveen. Why don't we start with the first question that you asked there with respect. Can you repeat the first question? I just want to make sure I've got full context on the first question.

Dave Gancarz: Thanks, Salveen. Why don't we start with the first question that you asked there. Can you repeat the first question? I just want to make sure I've got full context on the first question.

Speaker #5: But as the data matures, we expect our data to strengthen, although we haven't seen it.

Speaker #6: Sure. Just how to think of the read-through from the squamous results to the non-squamous portion of the study.

Salveen Richter: Sure. Just how to think of the read-through from the squamous results to the non-squamous portion of the study.

Speaker #3: Your next question comes from the line of Salvine Richter with Goldman Sachs. Your line is open.

Speaker #1: Very good. And so I think it's important, and I'll give a little bit of history here, Salveen, because I think this is good context overall.

Dave Gancarz: Very good. I think it's important, I'll give a little bit of history here, Salveen, because I think this is good context overall. When we look at the history of HARMONi-3, for example, we started in squamous, and that was generally because when we entered into our transaction with Akeso, the phase II data in squamous in combination with chemotherapy was very strong and was maturing. We immediately, and I think Bob's alluded to this 2 times in the past, it was very important that when we entered into the transaction with Akeso, that we started very quickly in terms of establishing a presence with the PD-1 VEGF-5 specific. The squamous data in phase II was mature. It was highly encouraging, and that's what prompted an immediate opening of that study.

Speaker #6: Good morning. Thanks for taking my questions, and congratulations on the data here. Two for me. One is: how do you think the strong squamous results read through to the non-squamous portion of the study?

Speaker #1: When we look at the history of Harmony 3, for example, we started in squamous and that was generally because when we entered into our transaction with the capsule, the phase two data in squamous in combination with chemotherapy was very strong and was maturing.

Speaker #6: And secondly, at the presentation, the presenter noted that the median OS was reached with the last patient event. Could you put that finding in context and share expectations for OS upon additional maturation?

Speaker #1: And so we immediately and I think Bob's alluded to this a few times in the past. It was very important that we when we entered into the transaction with the capsule, that we started very quickly in terms of establishing a presence with the PD-1, VEGF-5 specific.

Speaker #6: Thank you.

Speaker #2: Thanks, Alvin. Why don't we start with the first question that you asked there, with respect. Can you repeat the first question? I just want to make sure I've got full context on the first question.

Speaker #1: And so the squamous data in phase two was mature. It was highly encouraging. And that's what prompted an immediate opening of that study. As we then looked at the non-squamous portion, it was just simply less mature at that point in time.

Speaker #6: Sure. Just how to think of the read-through from the squamous result to the non-squamous portion of the study.

Dave Gancarz: We then looked at the non-squamous portion, it was just simply less mature at that point in time, and so it was in our pipeline in terms of traffic. Fast-forward now to the middle of 2024, we see the positive data from HARMONi-2 that showed monotherapy Ivo performing well in both squamous and non-squamous histologies. At that same time in 2024, the phase II non-squamous data in combination with chemotherapy was also maturing, was highly encouraging. I say all that because when we get to now HARMONi-6 and your question with respect to the read-through, that HARMONi-6 data was highly validating to the phase II data that was seen in AK112, the phase II study. We saw highly encouraging phase II data in squamous. That then translated to the HARMONi-6 success that we're seeing now.

Speaker #2: Very good. And so I think it's important, and I'll give a little bit of history here, Salvine, because I think this is good context overall.

Speaker #1: And so it was in our pipeline in terms of addressing. Fast forward now to the middle of 2024, we see the positive data from Harmony 2 that showed monotherapy, IVO, performing well in both squamous and non-squamous histologies.

Speaker #2: When we look at the history of Harmony3, for example, we started in squamous, and that was generally because, when we entered into our transaction with Akeso, the Phase 2 data in squamous in combination with chemotherapy was very strong and was maturing.

Speaker #1: At that same time in 2024, the phase two non-squamous data in combination with chemotherapy was also maturing with highly encouraging. So I say all that because when we get to now Harmony 6 and your question with respect to the read-through, that Harmony 6 data was highly validating to the phase two data that was seen in AK112201, the phase two study.

Speaker #2: And so we immediately—and I think Bob's alluded to this a few times in the past—it was very important that, when we entered into the transaction with Acasso, we started very quickly in terms of establishing a presence with the PD-1, VEGF-5 specific.

Speaker #2: And so the squamous data in Phase Two was mature. It was highly encouraging, and that's what prompted an immediate opening of that study. As we then looked at the non-squamous portion, it was just simply less mature at that point in time.

Speaker #1: And so we saw highly encouraging phase two data in squamous. That then translated to the Harmony 6 success that we've seen now. We have highly encouraging phase two data in non-squamous as well.

Speaker #2: And so it was in our pipeline in terms of addressing. Fast forward now to the middle of 2024—we see the positive data from Harmony2 that showed monotherapy IVO performing well in both squamous and non-squamous histologies.

Dave Gancarz: We have highly encouraging phase II data in non-squamous as well, that data becomes a little bit more validated as well with the phase III replicating the phase II data. When I say replicating, for example, the median PFS was nearly identical between the phase II and the phase III. What we're seeing is the data that we've relied on in terms of the encouraging opportunity in non-squamous, that phase II data that same study has been shown to replicate phase II to phase III. Obviously, it's frontline lung cancer as well, highly encouraging opportunities are present, the existing phase III data in squamous is highly encouraging. There's certainly nothing negative with respect to the non-squamous portion. I'll turn it over to Jack for the second half of that question with respect to-

Speaker #1: And so that data becomes a little bit more validated as well with the phase three replicating the phase two data. And when I say replicating, for example, the median PFS was nearly identical between the phase two and the phase three.

Speaker #2: At that same time in 2024, the phase two non-squamous data in combination with chemotherapy was also maturing and was highly encouraging. So I say all that because, when we get to now Harmony6 and your question with respect to the read-through, that Harmony6 data was highly validating to the phase two data that was seen in AK112201, the phase two study.

Speaker #1: And so what we're seeing is the data that we've relied on in terms of the encouraging opportunity in non-squamous, that phase two data, has been that same study has been shown to replicate phase two to phase three.

Speaker #1: Obviously, it's frontline lung cancer as well. And so highly encouraging opportunities are present. And the existing phase three data in squamous is highly encouraging.

Speaker #2: And so, we saw highly encouraging phase 2 data in squamous. That then translated to the Harmony 6 success that we've seen now. We have highly encouraging phase 2 data in non-squamous as well.

Speaker #1: So there's certainly nothing negative with respect to the non-squamous portion. I'll turn it over to Jack for the second half of that question with respect to.

Dave Gancarz: I'll turn it over to Jack for the second half of that question with respect to-

H. Jack West: Remind me?

Howard Jack West: Remind me?

Speaker #1: Yeah. With respect to the last patient who passed away leading to the median.

Dave Gancarz: Yeah. With respect to the last patient who passed away, leading to the median.

Speaker #2: And so that data becomes a little bit more validated as well, with the phase three replicating the phase two data. And when I say replicating, for example, the median PFS was nearly identical between the phase two and the phase three.

Speaker #5: Well, yeah. The highlight there is that at that part of the curve, it's a very small number of patients. And so a single patient death among four patients at that time led to a drop just below the median.

H. Jack West: Well, the highlight there is that at that part of the curve, it's a very small number of patients. A single patient death among four patients at that time led to a drop just below the median, but that's a very unstable finding. In fact, it is defining the lower limit of the confidence interval for that median, which means it can only improve from what that is. That's exactly what Akeso, I believe, expects will be the case as the data mature and there's a much larger population to draw from who gets out to and beyond the median data point.

Howard Jack West: Well, the highlight there is that at that part of the curve, it's a very small number of patients. A single patient death among four patients at that time led to a drop just below the median, but that's a very unstable finding. In fact, it is defining the lower limit of the confidence interval for that median, which means it can only improve from what that is. That's exactly what Akeso, I believe, expects will be the case as the data mature and there's a much larger population to draw from who gets out to and beyond the median data point.

Speaker #2: And so what we're seeing is the data that we've relied on in terms of the encouraging opportunity in non-squamous—that phase 2 data—has been that the same study has been shown to replicate from phase 2 to phase 3.

Speaker #5: But that's a very unstable finding. In fact, it is defining the lower limit of the confidence interval for that median, which means it can only improve from what that is.

Speaker #2: Obviously, it's frontline lung cancer as well, and so highly encouraging opportunities are present. And the existing phase 3 data in squamous is highly encouraging.

Speaker #5: And that's exactly what a capsule, I believe, expects will be the case. As the data mature, and there's a much larger population to draw from who gets out to and beyond the median point.

Speaker #2: So, there's nothing—there's certainly nothing negative with respect to the non-squamous portion. I'll turn it over to Jack for the second half of that question with respect to—

Speaker #2: Yeah. With respect to the last patient who passed away leading to the median.

Speaker #5: So that is the lowest number that would ever be seen. And we might anticipate based on the patterns that that isn't truly a representative number and that it's going to end up with further follow-up as a stronger difference in terms of absolute number of months between the two arms.

H. Jack West: That is the lowest number that would ever be seen and we might anticipate, based on the patterns, that that isn't truly a representative number and that it's going to end up with further follow-up as a stronger difference in terms of absolute number of months between the two arms.

Howard Jack West: That is the lowest number that would ever be seen and we might anticipate, based on the patterns, that that isn't truly a representative number and that it's going to end up with further follow-up as a stronger difference in terms of absolute number of months between the two arms.

Speaker #5: But that's a very unstable finding. In fact, it is defining the lower limit of the confidence interval for that median, which means it can only improve from what that is.

Speaker #5: And Salveen, this is Allen. I'd add to I understand the question about squamous translating over to non-squamous being non-squamous is of greater unmet need in Western markets.

Allen Yang: Salveen, this is Allen. I'd add too, I understand the question about squamous translating over to non-squamous, being non-squamous is a greater unmet need in Western markets. I want to point out the HARMONi and HARMONi-8 studies. Those were non-squamous histologies with the same chemo backbones, even though they are EGFR mutant non-small cell lung cancer. Again, all the strong ivonescimab data in complete different tumor types like CRC, PNET. The drug is active. The jump from squamous to non-squamous histology is small compared to the breadth of this molecule.

Speaker #5: And that's exactly what Acasso, I believe, expects will be the case. As the data mature, and there's a much larger population to draw from, who gets out to and beyond the median point.

Speaker #5: I want to point out the Harmony and Harmony 8 study. Those were non-squamous histologies with the same back chemo backbone, even though they are EGFR mutant non-squamous cell lung cancer.

Speaker #5: So, that is the lowest number that would ever be seen. And we might anticipate, based on the patterns, that this isn't truly a representative number and that it's going to end up, with further follow-up, as a stronger difference in terms of the absolute number of months between the two arms.

Speaker #5: And again, all the strong IV and SMAB data in complete different tumor types like CRC, TNBC. So the drug is active. So the jump from squamous to non-squamous histology is small compared to the breadth of this molecule.

Speaker #1: That's right. And I think the other piece I would add on top of Jack's nice explanation, when you look at the curve overall, what you are seeing is the curve separating at six months, but then continuing to expand.

Dave Gancarz: That's right. I think the other piece I would add on top of Jack's nice explanation, when you look at the curve overall, what you are seeing is the curve separating at 6 months, but then continuing to expand. That's really what reflects the hazard ratio of 0.66 and that 34% relative improvement in reducing the risk of death.

Speaker #5: And Salvine, this is Alan. I'd add to—I understand the question about squamous translating over to non-squamous, being non-squamous is of greater unmet need in Western markets.

Speaker #1: And that's really what reflects the hazard ratio of 0.66. And that's 34% relative improvement in reducing the risk of death.

Speaker #5: Yeah. Obviously, the median is just one point in time, but that shape of the curve has everyone highlighted it, including at the plenary session.

Speaker #5: I want to point out the HARMONY and HARMONYA studies. Those were non-squamous histologies with the same chemo backbone, even though they are EGFR-mutant non-squamous cell lung cancer.

H. Jack West: Obviously the median is just one point in time, but that shape of the curve, as everyone highlighted, including at the plenary session, it is widening as the patients continue over time and the curve moves to the right. That median kind of underrepresents the benefit that was really seen.

Howard Jack West: Obviously the median is just one point in time, but that shape of the curve, as everyone highlighted, including at the plenary session, it is widening as the patients continue over time and the curve moves to the right. That median kind of underrepresents the benefit that was really seen.

Speaker #5: It is widening as the patients continue over time and the curve moves to the right. So that median kind of underrepresents the benefit that was really seen.

Speaker #5: And again, all the strong IV and SMAB data in completely different tumor types, like CRC and TNBC, show that the drug is active. So, the jump from squamous to non-squamous histology is small compared to the breadth of this molecule.

Speaker #1: Yeah. So when you look at the baseline tizolizumab plus chemotherapy, which performed either on par with or slightly above historical results with respect to the rationale 307 study, which was the pivotal study in which tizolizumab plus chemo was approved, that relative improvement of 34% relative improvement on top of that 22, 23-month benchmark, you would certainly expect that to be a bit higher than the four months.

Dave Gancarz: Yeah. When you look at the baseline, tislelizumab plus chemotherapy, which performed either on par with or slightly above historical results with respect to the RATIONALE 307 study, which was the pivotal study in which tislelizumab plus chemo was approved. That relative improvement of 34% relative improvement on top of that 22, 23-month benchmark, you would certainly expect that to be a bit higher than the 4 months. Just the math would tell you it's closer to 7 to 8. When you look at the median follow-up time of 21 months and change, what this really represents, because those curves are widening further with more time, that hazard ratio in respect to confidence interval, and thus the P value, becomes statistically significant, showing that there's clearly the benefit already with more opportunity to continue to look at longer-term follow-ups, if you will.

Speaker #2: That's right. And I think the other piece I would add on top of Jack's nice explanation is, when you look at the curve overall, what you are seeing is the curve separating at six months, but then continuing to expand.

Speaker #2: And that's really what reflects the hazard ratio of 0.66. And that's a 34% relative improvement in reducing the risk of death.

Speaker #5: Yeah. Obviously, the median is just one point in time, but that shape of the curve has everyone highlighted, including at the plenary session. It is widening as the patients continue over time, and the curve moves to the right.

Speaker #1: Just the math would tell you it's closer to 7 to 8. And so when you look at the median follow-up time of 21 months and change, what this really represents, because those curves are widening further with more time, that hazard ratio in respect to confidence interval, and thus the p-value, becomes statistically significant showing that there's clearly the benefit already with more opportunity to continue to look at longer-term follow-ups, if you will.

Dave Gancarz: When you look at the median follow-up time of 21 months and change, what this really represents, because those curves are widening further with more time, that hazard ratio in respect to confidence interval, and thus the P value, becomes statistically significant, showing that there's clearly the benefit already with more opportunity to continue to look at longer-term follow-ups, if you will. This is the primary overall survival analysis. It is statistically significant and highly statistically significant at that. I think that 34% relative risk reduction is the important part to look at.

Speaker #5: So, that median kind of underrepresents the benefits that were really seen.

Speaker #2: Yeah. So when you look at the baseline, tislelizumab plus chemotherapy, which performed either on par with or slightly above historical results with respect to the RATIONALE 307 study—which was the pivotal study in which tislelizumab plus chemo was approved—that relative improvement of 34%, relative improvement on top of that 22-23 month benchmark, you would certainly expect that to be a bit higher than the four months.

Speaker #1: But this is the final this is the primary overall survival analysis. It is statistically significant and highly statistically significant at that. And I think that 34% relative risk reduction is the important part to look at.

Dave Gancarz: This is the primary overall survival analysis. It is statistically significant and highly statistically significant at that. I think that 34% relative risk reduction is the important part to look at.

Speaker #6: Your next question comes from the line of Yigal Nochomovitz with a city. Your line is open.

Operator: Your next question comes from the line of Yigal Nochomovitz with Citi. Your line is open.

Speaker #2: Just the math would tell you it's closer to 7 to 8. And so, when you look at the median follow-up time of 21 months and change, what this really represents—because those curves are widening further with more time—is that the hazard ratio, in respect to confidence interval and thus the p-value, becomes statistically significant, showing that there's clearly the benefit already, with more opportunity to continue to look at longer-term follow-ups, if you will.

Speaker #7: Hi. Great. Thanks. And congrats on the very, very strong result at ASCO. Thanks for also mentioning the covariate analysis that you did at ESMA with regard to the PFS.

Yigal Nochomovitz: Hi. Great. Thanks, and congrats on the very, very strong result at ASCO. Thanks for also mentioning the covariate analysis that you did at ESMO with regard to the PFS. I'm just curious, if you were to apply that same math and logic to OS, what the conclusions may be, and curious as to why the ASCO discussion didn't put forward that piece of analysis. Also, could you just clarify as to why the interim was triggered at 204, versus the planned 225 events, as defined in the protocol for the study? Thank you.

Speaker #7: I'm just curious, if you were to apply that same math and logic to OS, what the conclusions may be. And curious as to why the ASCO discussant didn't put forward that piece of analysis.

Speaker #7: And then also, could you just clarify as to why the interim was triggered at 204 versus the planned 225 events as defined in the protocol for the study?

Speaker #2: But this is the final—this is the primary overall survival analysis. It is statistically significant, and highly statistically significant at that. And I think that 34% relative risk reduction is the important part to look at.

Speaker #7: Thank you.

Speaker #1: Thanks, Yigal. And so I think the so we appreciate the comment with respect to the covariate analysis. And so importantly, there was not a separate covariate analysis run at this point with respect to overall survival.

Dave Gancarz: Thanks, Yigal. We appreciate the comment with respect to the covariate analysis. Importantly, there was not a separate covariate analysis run at this point with respect to overall survival. However, the baseline characteristics, to be very clear, don't change over the course of the study, right? These are the baseline characteristics of the patients entering in. The baseline characteristics, if the PFS analysis remain, of course, consistent with those at the overall survival analysis. That's why we thought it was important today to remind everyone of this particular topic, which was discussed back in October of 2025, where those imbalanced characteristics, baseline characteristics within the greater than 65 year-old patients between Ivo and Tisley is very relevant.

Speaker #1: Your next question comes from the line of Legal Legitimates with Citi. Your line is open.

Speaker #5: Hi. Great, thanks. And congrats on the very, very strong result at ASCO. Thanks for also mentioning the covariate analysis that you did at ESMO with regard to the PFS.

Speaker #1: However, the baseline characteristics, to be very clear, don't change over the course of the study, right? These are the baseline characteristics of the patients entering in.

Speaker #5: I'm just curious: if you were to apply that same math and logic to OS, what conclusions might you reach? And I'm also curious as to why the ASCO discussant didn't put forward that piece of analysis.

Speaker #1: And so the baseline characteristics if the PFS analysis are remain, of course, consistent with those at the overall survival analysis. And that's why we thought it was important today to remind everyone of this particular topic, which was discussed back in October of 2025, where those imbalanced characteristics, baseline characteristics within the greater than 65-year-old patients, between IVO and tizoliz, is very relevant.

Speaker #5: And then also, could you just clarify as to why the interim was triggered at 204 versus the planned 225 events, as defined in the protocol for the study?

Speaker #5: Thank you.

Speaker #2: Thank you, Gal. And so, I think—so we appreciate the comment with respect to the covariate analysis. Importantly, there was not a separate covariate analysis run at this point with respect to overall survival.

Speaker #1: So as you saw that translates from a PFS hazard ratio of about 0.88 down to about 0.69 when you took into account the fact that those in the IVO arm had higher rates of brain metastases had larger target lesions at baseline, right?

Dave Gancarz: As you saw, that translates from a PFS hazard ratio of about 0.88 down to about 0.69 when you took into account the fact that those in the Ivo arm had higher rates of brain metastases, had larger target lesions at baseline, right? Those baseline characteristics, when adjusted, normalize the difference between those under and over 65. I think it is really important also to note that this is the fourth phase III study conducted with ivonescimab. The other three did not show any detriment when looking at those over 65 as compared to those under 65. This is where it's important to remember, these are non-powered subgroups as well. You don't have necessarily balanced baseline characteristics amongst the subgroups, and you also aren't powering your study to reflect the results of those patients.

Speaker #2: However, the baseline characteristics, to be very clear, don't change over the course of the study, right? These are the baseline characteristics of the patients entering in.

Speaker #2: And so the baseline characteristics for the PFS analysis remain, of course, consistent with those at the overall survival analysis. And that's why we thought it was important today to remind everyone of this particular topic, which was discussed back in October of 2025, where those imbalanced baseline characteristics within the greater-than-65-year-old patients between IVO and Tizli is very relevant.

Speaker #1: Those baseline characteristics, when adjusted, normalize the difference between those under and over 65. I think it's also it is really important also to note that this is the fourth phase three study conducted with IV and SMF.

Speaker #1: The other three did not show any detriment when looking at those over 65 as compared to those under 65. And so this is where it's important to remember these are non-powered subgroups as well.

Speaker #1: And so you don't have necessarily balanced baseline characteristics amongst the subgroups and you also aren't powering your study to reflect the results of those patients.

Dave Gancarz: You don't have necessarily balanced baseline characteristics amongst the subgroups, and you also aren't powering your study to reflect the results of those patients. We see other studies, for example there's studies that have been run where highly statistically significant overall survival benefits. FLAURA2 is an example of this, where the results in first-line EGFR mutant non-small cell lung cancer, osimertinib plus chemo versus osimertinib monotherapy. About a third to 35% of those patients were enrolled in Asia ex China. That specific subgroup, that region, showed a hazard ratio of 1.00, representing a third of the patients or more enrolled in that study.

Speaker #2: So, as you saw, that translates from a PFS hazard ratio of about 0.88 down to about 0.69 when you took into account the fact that those in the IVO arm had higher rates of brain metastases and had larger target lesions at baseline, right?

Speaker #1: So we see other studies for example, there's studies that have been run where highly statistically significant overall survival benefits FLORA2 is an example of this where the results in first-line EGFR mutant non-small cell lung cancer osimertinib plus chemo versus osimertinib monotherapy about a third to 35% of those patients were enrolled in Asia x China.

Dave Gancarz: We see other studies, for example there's studies that have been run where highly statistically significant overall survival benefits. FLAURA2 is an example of this, where the results in first-line EGFR mutant non-small cell lung cancer, osimertinib plus chemo versus osimertinib monotherapy. About a third to 35% of those patients were enrolled in Asia ex China. That specific subgroup, that region, showed a hazard ratio of 1.00, representing a third of the patients or more enrolled in that study. However, I don't think anybody would argue that osimertinib plus chemotherapy works in China, but not in the rest of Asia from that perspective, and then also works in the US and in Europe.

Speaker #2: Those baseline characteristics, when adjusted, normalize the difference between those under and over 65. I think it's also really important to note that this is the fourth Phase 3 study conducted with IV and SMAB.

Speaker #2: The other three did not show any detriment when looking at those over 65 as compared to those under 65. And so, this is where it's important to remember these are non-powered subgroups as well.

Speaker #1: But that specific subgroup, that region, showed a hazard ratio of 1.00. Representing a third of the patients or more enrolled in that study, however, I don't think anybody would argue that osimertinib plus chemotherapy works in China, but not in the rest of Asia.

Speaker #2: And so, you don't necessarily have balanced baseline characteristics among the subgroups, and you also aren't powering your study to reflect the results of those patients.

Dave Gancarz: However, I don't think anybody would argue that osimertinib plus chemotherapy works in China, but not in the rest of Asia from that perspective, and then also works in the US and in Europe. I say all that just to provide an example of a place where when you look specifically at a subgroup and then you try to extract too much from that, it's very difficult to do because you don't balance for everything else that goes into a very well-designed and robust clinical study. As we think about that, there was no detriment to patients over 65, either from a PFS or an OS perspective. I think that's really important to point out.

Speaker #1: From that perspective. And then also Europe. So I say all that just to provide example an example of a place where when you look specifically at a subgroup and then you try to extract too much from that, it's very difficult to do because you don't balance for everything else that goes into a very well-designed and robust clinical study.

Speaker #2: So we see other studies—for example, there are studies that have been run where there are highly statistically significant overall survival benefits. FLAURA-2 is an example of this, where the results in first-line EGFR-mutant non-small cell lung cancer, osimertinib plus chemo versus osimertinib monotherapy—about a third to 35% of those patients were enrolled in Asia ex-China.

Dave Gancarz: I say all that just to provide an example of a place where when you look specifically at a subgroup and then you try to extract too much from that, it's very difficult to do because you don't balance for everything else that goes into a very well-designed and robust clinical study. As we think about that, there was no detriment to patients over 65, either from a PFS or an OS perspective. I think that's really important to point out.

Speaker #1: And so as we think about that, there was no detriment to patients over 65 either from a PFS or an OS perspective. And I think that's really important to point out.

Speaker #2: But that specific subgroup, that region, showed a hazard ratio of 1.00. Representing a third of the patients or more enrolled in that study, however, I don't think anybody would argue that osimertinib plus chemotherapy works in China but not in the rest of Asia.

Allen Yang: I'll take the next question if you can add in. You've answered the question. The other question was about why they did the OS analysis slightly early. I think it was 204 events versus 220. It's not uncommon. It's a goal and it's often hard to predict how many patients you'll have at the time of the analysis, because there's a cleaning and sort of preparation of the data and the locking of the database. As long as you're well within 10%, that's not unusual. I can't comment. That question is probably best for our Genentech partner, it's often, as part of a regulatory discussion, there may be a query from a regulatory agency. That's the reason I see that they would slightly vary from their targets.

Speaker #8: I'll take the next question then if you can add anything. So Yigal, thanks for the question. The other question was about why they did the OS analysis slightly earlier.

Speaker #8: I think it was 204 events versus 220. It's not uncommon. It's a goal and it's often hard to predict how many patients you'll have at the time of the analysis.

Speaker #2: From that perspective—and it also works in the US and Europe. I say all that just to provide an example of a place where, when you look specifically at a subgroup and then try to extract too much from that, it's very difficult to do, because you don't balance for everything else that goes into a very well-designed and robust clinical study.

Speaker #8: Because there's a cleaning and sort of preparation of the data and the locking of the database. So as long as you're within well within 10%, that's not unusual.

Speaker #8: I can't comment. That question is probably best for our ASCO partners. But it's often as part of a regulatory discussion, there may be a query from a regulatory agency.

Speaker #2: And so as we think about that, there was no detriment to patients over 65, either from a PFS or an OS perspective. And I think that's really important to point out.

Speaker #8: That's the reason I've seen that they would slightly vary from their targets.

Speaker #6: Your next question comes from the line of Brad Canino with Guggenheim Partners, your line is open.

Operator: Your next question comes from Delano Brad Canino with Guggenheim Partners. Your line is open.

Speaker #5: I'll take the next question and you can add in. So Gal, thanks for the question. The other question was about why they did the OS analysis slightly earlier.

Speaker #1: Hey, thanks for the question. And congrats to you, your team, and your partner on those data. Now, the 0.66 hazard ratio and the at least four-month benefit, can you contextualize these results within the past frontline squamous lung trials that have changed practice?

Brad Canino: Hey, thanks for the question and congrats to you, your team, and your partner on those data. Now, the 0.66 hazard ratio and the at least 4-month benefit, can you contextualize these results within the past frontline squamous lung trials that have changed practice? You always get a lot of questions on the translation of that benefit to HARMONi-3. Do you need to translate that magnitude, or is there some margin where even a lower result could be significant enough to still change practice? Thanks.

Speaker #5: I think it was 204 events versus 220. It's not uncommon. It's a goal, and it's often hard to predict how many patients you'll have at the time of the analysis.

Speaker #5: Because there's a cleaning and sort of preparation of the data and the locking of the database. So as long as you're well within 10%, that's not unusual.

Speaker #1: And then you always get a lot of questions on the translation of that benefit to Harmony 3. But do you need to translate that magnitude?

Speaker #5: I can't comment. That question is probably best for our ASCO partners. But often, as part of a regulatory discussion, there may be a query from a regulatory agency.

Speaker #1: Or is there some margin where even a lower result could be significant enough to still change practice? Thanks.

Speaker #8: Yeah. This is Jack. I will field that. I spend a lot of my time talking with my colleagues who are clinical oncologists. And I would say that a huge amount of the excitement about Harmony 2 I know I'm going back in time was just that as impressive and as integral as pembrolizumab has been, a sense that it was an impenetrable plateau.

Dave Gancarz: This is Jack. I will field that. I spend a lot of my time talking with my colleagues who are clinical oncologists. I would say that a huge amount of the excitement about HARMONi-2, I know I'm going back in time, was just that as impressive and as integral as pembrolizumab has been, a sense that it was an impenetrable plateau that we might never exceed in our careers. Just seeing the capacity to do better than that is remarkable and all of the potential opportunities to exceed that with pembro or potentially other checkpoint inhibitors. Squamous in particular is a setting that has had a dearth of developments over time, as compared to non-squamous, where there's new driver mutations and targeted therapies that chip away. Squamous has really been left without many new opportunities. That would make any development especially welcome.

Howard Jack West: This is Jack. I will field that. I spend a lot of my time talking with my colleagues who are clinical oncologists. I would say that a huge amount of the excitement about HARMONi-2, I know I'm going back in time, was just that as impressive and as integral as pembrolizumab has been, a sense that it was an impenetrable plateau that we might never exceed in our careers. Just seeing the capacity to do better than that is remarkable and all of the potential opportunities to exceed that with pembro or potentially other checkpoint inhibitors. Squamous in particular is a setting that has had a dearth of developments over time, as compared to non-squamous, where there's new driver mutations and targeted therapies that chip away. Squamous has really been left without many new opportunities.

Speaker #5: That's the reason I've seen that they would slightly vary from their targets.

Speaker #1: Your next question comes from the line of Brad Canino with Guggenheim Partners. Your line is open.

Speaker #4: Hey, thanks for the question. And congrats to you, your team, and your partner on those data. Now, the 0.66 hazard ratio and the at least four-month benefit—can you contextualize these results within the past frontline squamous lung trials that have changed practice?

Speaker #8: That we might never exceed in our careers. And just seeing the capacity to do better than that is remarkable. And all of the potential opportunities to exceed that with Pembro or potentially other checkpoints inhibitors.

Speaker #4: And then you always get a lot of questions on the translation of that benefit to Harmony 3. But do you need to translate that magnitude?

Speaker #4: Or is there some margin where even a lower result could be significant enough to still change practice? Thanks.

Speaker #5: Yeah, this is Jack. I will field that. I spend a lot of my time talking with my colleagues who are clinical oncologists, and I would say that a huge amount of the excitement about Harmony 2—I know I'm going back in time—was just that as impressive and as integral as pembrolizumab has been, there was a sense that it was an impenetrable plateau.

Speaker #8: Squamous in particular is a setting that has been has had a dearth of developments over time. As compared to non-squamous where there's new driver mutations and targeted therapies that chip away.

Speaker #8: But squamous has really been left without many new opportunities. And that would make any development especially welcome. Seeing a PFS benefit is not negligible.

Howard Jack West: That would make any development especially welcome. Seeing a PFS benefit is not negligible, and in many settings of oncology, that is eagerly accepted as enough to adopt a new therapy. I think that in lung cancer, non-small cell at least particularly, we often impose a higher bar of overall survival. That said, if it is a hazard ratio below about 0.75 or 0.8, that is enough for nearly every oncologist I speak with to consider that to be very clinically relevant, clinically meaningful, and worth adopting as a new treatment.

Dave Gancarz: Seeing a PFS benefit is not negligible, and in many settings of oncology, that is eagerly accepted as enough to adopt a new therapy. I think that in lung cancer, non-small cell at least particularly, we often impose a higher bar of overall survival. That said, if it is a hazard ratio below about 0.75 or 0.8, that is enough for nearly every oncologist I speak with to consider that to be very clinically relevant, clinically meaningful, and worth adopting as a new treatment. I would also say that when I've spoken with and seen results of survey questions from colleagues about, well, if you see a PFS benefit, but the overall survival may or may not be statistically significant, but trending in the right direction, you get a splay, a mix of different opinions about

Speaker #5: That we might never exceed in our careers. And just seeing the capacity to do better than that is remarkable. And all of the potential opportunities to exceed that with pembro or potentially other checkpoint inhibitors.

Speaker #8: And in many settings of oncology, that is eagerly accepted as enough to adopt a new therapy. I think that in lung cancer, non-small cell at least particularly, we often impose a higher bar of overall survival.

Speaker #8: That said, if it is a hazard ratio below about 0.75 or 0.8, that is enough for nearly every oncologist I speak with to consider that to be very clinically relevant, clinically meaningful, and worth adopting as a new treatment.

Speaker #5: Squamous, in particular, is a setting that has had a dearth of developments over time, as compared to non-squamous, where there are new driver mutations and targeted therapies that chip away.

Speaker #5: But squamous has really been left without many new opportunities, and that would make any development especially welcome. Seeing a PFS benefit is not negligible.

Speaker #8: I would also say that when I've spoken with and seen results of survey questions from colleagues about, well, if you see a PFS benefit but the overall survival may or may not be statistically significant, but trending in the right direction, you get a splay, a mix of different opinions about whether that is clearly enough.

Howard Jack West: I would also say that when I've spoken with and seen results of survey questions from colleagues about, well, if you see a PFS benefit, but the overall survival may or may not be statistically significant, but trending in the right direction, you get a splay, a mix of different opinions about whether that is clearly enough, about half of my colleagues really feel that PFS benefit and even a modest trend of improvement in overall survival is perfectly welcome, first to their patients, and secondly themselves, because this is not a comparison against placebo or chemotherapy alone. This is the first time we're seeing an improvement against such a high bar, and it's not accompanied by a counterbalancing major liability and toxicity.

Speaker #5: And in many settings of oncology, that is eagerly accepted as enough to adopt a new therapy. I think that in lung cancer—non-small cell, at least, particularly—we often impose a higher bar of overall survival.

H. Jack West: Whether that is clearly enough, about half of my colleagues really feel that PFS benefit and even a modest trend of improvement in overall survival is perfectly welcome, first to their patients, and secondly themselves, because this is not a comparison against placebo or chemotherapy alone. This is the first time we're seeing an improvement against such a high bar, and it's not accompanied by a counterbalancing major liability and toxicity. People are saying, if this is compared to Pembro or tislelizumab, and you clearly exceed on PFS, and it's in the right direction for OS, and not accompanied by a problematic increase in toxicity, why would my patient not want to pursue that option? Yes, there's going to be a range in what clinicians require to adopt something.

Speaker #8: But about half of my colleagues really feel that PFS benefit and even a modest trend of improvement in overall survival is perfectly welcome first to their patients and secondly themselves.

Speaker #5: That said, if it is a hazard ratio below about 0.75 or 0.8, that is enough for nearly every oncologist I speak with to consider that to be very clinically relevant, clinically meaningful, and worth adopting as a new treatment.

Speaker #8: Because this is not a comparison against placebo or chemotherapy alone. This is the first time we're seeing an improvement against such a high bar.

Speaker #5: I would also say that when I've spoken with—and seen results of—survey questions from colleagues about, well, if you see a PFS benefit, but the overall survival may or may not be statistically significant, but trending in the right direction, you get a splay—a mix of different opinions—about whether that is clearly enough.

Speaker #8: And it's not accompanied by a counterbalancing major liability and toxicity. So people are saying, if this is compared to Pembro or tizulizumab and you clearly exceed on PFS and it's in the right direction for OS, and not accompanied by a problematic increase in toxicity, why would my patient not want to pursue that option?

Howard Jack West: People are saying, if this is compared to Pembro or tislelizumab, and you clearly exceed on PFS, and it's in the right direction for OS, and not accompanied by a problematic increase in toxicity, why would my patient not want to pursue that option? Yes, there's going to be a range in what clinicians require to adopt something. I would say the results we saw yesterday would be on the very far end of that range and really not controversial, but with a lot of room to see less than that and still be enough to motivate patients and most oncologists, or many oncologists, to readily adopt an improvement in some, even if not every parameter across the board.

Speaker #5: But about half of my colleagues really feel that PFS benefit and even a modest trend of improvement in overall survival is perfectly welcome—first to their patients, and secondly, to themselves.

Speaker #8: So yes, there's going to be a range in what clinicians require to adopt something. I would say the results we saw yesterday would be on the very far end of that range and really not controversial.

H. Jack West: I would say the results we saw yesterday would be on the very far end of that range and really not controversial, but with a lot of room to see less than that and still be enough to motivate patients and most oncologists, or many oncologists, to readily adopt an improvement in some, even if not every parameter across the board.

Speaker #5: Because this is not a comparison against placebo or chemotherapy alone. This is the first time we're seeing an improvement against such a high bar.

Speaker #8: But with a lot of room to see less than that and still be enough to motivate patients and most oncologists or many oncologists to readily adopt an improvement in some, even if not every parameter across the board.

Speaker #5: And it's not accompanied by a counterbalancing major liability and toxicity. So people are saying, if this is compared to pembrolizumab or tislelizumab, and you clearly exceed on PFS and it's in the right direction for OS, and not accompanied by a problematic increase in toxicity, why would my patient not want to pursue that option?

Speaker #6: Your next question comes from the line of Mohit Bansal with Wells Fargo. Your line is open.

Operator: Your next question comes from the line of Mohit Bansal with Wells Fargo. Your line is open.

Speaker #1: Great. Thank you very much. And my congratulations as well. So would love to talk a little bit about the median follow-up at the point of interim in Harmony 3 versus Harmony 6.

Mohit Bansal: Great. Thank you very much. My congratulations as well. Would love to talk a little bit about the median follow-up at the point of interim in HARMONi-3 versus HARMONi-6. To what extent you can comment on that, was there a difference between the median follow-up in HARMONi-3 interim versus six interim that could explain why you did not hit the interim at that time point? Thank you.

Speaker #5: So yes, there's going to be a range in what clinicians require to adopt something. I would say the results we saw yesterday would be on the very far end of that range and really not controversial.

Speaker #1: To what extent you can comment on that? And was there a difference between the median follow-up in Harmony 3 interim versus 6 interim that could explain why you did not hit the interim at that time point?

Speaker #5: But with a lot of room to see less than that and still be enough to motivate patients, and most oncologists—or many oncologists—to readily adopt an improvement in some, even if not every, parameter across the board.

Speaker #1: Thank you.

Speaker #8: Yeah. This is Dave. I'll jump in and then I'll ask Bilal to provide any additional color. So what I would say overall is enrollment patterns are a little bit different.

Dave Gancarz: Yeah, this is Dave. I'll jump in and then I'll ask Bilal to provide any additional color. What I would say overall is enrollment patterns are a little bit different. As we know, in any study in China versus any study globally, the enrollment patterns are a little bit longer. What you will see in general when you look at enrollment in a global study is a little bit more back-ended enrollment, one, and two, longer period of time. I'm making very general comments with respect to enrollment in a global study as compared to China, where you tend to ramp up very quickly and enroll the duration of the study over a shorter period of time.

Speaker #1: Your next question comes from the line of Mohit Bansal with Wells Fargo. Your line is open.

Speaker #8: We know in any study in China versus any study globally, the enrollment patterns are a little bit longer. So what you will see in general when you look at enrollments in a global study is a little bit more back-ended enrollment, one.

Speaker #4: Great, thank you very much. And my congratulations as well. I would love to talk a little bit about the median follow-up at the point of interim in Harmony 3 versus Harmony 6.

Speaker #8: And two, longer period of time. I'm making very general comments with respect to enrollments in a global study as compared to China where you tend to ramp up very quickly.

Speaker #4: To what extent can you comment on that? And was there a difference between the median follow-up in Harmony 3 interim versus 6 interim that could explain why you did not hit the interim at that time point?

Speaker #8: And enroll the duration of the study over a shorter period of time. And so while Mohit, we're not going to give particular color in terms of here's median follow-ups in very specific related to Harmony 3.

Dave Gancarz: While, Mohit, we're not going to give particular color in terms of, here's median follow-ups and very specific related to HARMONi-3, as it would be incredibly unusual to provide that commentary on an interim look. What I would say is there are patterns that you can look at across global studies in general, across studies conducted in a single region, and particularly in China in general, where the distribution of events, the follow-up time, will be a little bit different just naturally, just based on the traditional patterns that you see for enrollment. Then I'll ask Bilal if there's anything else you'd like to add.

Speaker #4: Thank you.

Speaker #5: Yeah, this is Dave. I'll jump in, and then I'll ask Bilal to provide any additional color. So what I would say overall is enrollment patterns are a little bit different.

Speaker #8: It would be incredibly unusual to provide that commentary on an interim look. But what I would say is there are patterns that you can look at across global studies in general, across studies conducted in a single region and particularly in China, in general, where the distribution of events, the follow-up time, will be a little bit different just naturally, just based on the traditional patterns that you see for enrollment.

Speaker #5: We know that in any study in China versus any study globally, the enrollment patterns are a little bit longer. So, what you will see in general, when you look at enrollments in a global study, is a little bit more back-ended enrollment, one.

Speaker #5: And two, a longer period of time. I'm making very general comments with respect to enrollments in a global study as compared to China, where you tend to ramp up very quickly.

Speaker #8: And then I'll ask Bilal if there's anything else you'd like to add.

Speaker #1: Anyway, thanks for the question. I agree with Dave. I think more important rather than the median is the pattern of enrollment. And so sometimes it's a little hard to translate one to the other.

Bilal Safradi: Great. Thanks for the question. I agree with Dave. I think more important, rather than the median, is the pattern of enrollment. Sometimes it's a little hard to translate one to the other. For the last interim for HARMONi-3, we took a calculated risk because we want to get this drug through earlier to the patients. I think we're really fine now. We are very confident with how this is going towards the final analysis.

Bilal Piperdi: Great. Thanks for the question. I agree with Dave. I think more important, rather than the median, is the pattern of enrollment. Sometimes it's a little hard to translate one to the other. For the last interim for HARMONi-3, we took a calculated risk because we want to get this drug through earlier to the patients. I think we're really fine now. We are very confident with how this is going towards the final analysis.

Speaker #5: And enroll the duration of the study over a shorter period of time. And so while, Mohit, we're not going to give particular color in terms of, here's median follow-ups in very specific related to Harmony 3.

Speaker #1: For the last interim for Harmony 3, we took a calculated risk because we want to get this drug earlier to the patients. And I think we're really fine now.

Speaker #5: It would be incredibly unusual to provide that commentary on an interim look. But what I would say is, there are patterns that you can look at across global studies in general, across studies conducted in a single region, and particularly in China, in general, where the distribution of events and the follow-up time will be a little bit different just naturally, just based on the traditional patterns that you see for enrollment.

Speaker #1: We are very confident with how this is going towards the final analysis. Very helpful. Thank you.

Mohit Bansal: Very helpful. Thank you.

Speaker #6: Your next question comes from the line of Cory Kasimov with Evercore ISI. Your line is open.

Operator: Your next question comes from the line of Cory Kasimov with Evercore ISI. Your line is open.

Speaker #5: Hi. This is Josh on for Cory Kasimov. Thanks for taking our question. Given there's precedence of China-only trials, allowing for approval in the EU, such as rationale 307, wondering if there's any plans to use the Harmony 6 data set to look for approval in the EU.

Josh Schimmer: Hi, this is Josh on for Cory Kasimov. Thanks for taking our question. Given there's precedence of China-only trials allowing for approval in the EU, such as RATIONALE 307, wondering if there's any plans to use the HARMONi-6 data set to look for approval in EU, and if not, how could these results help with the HARMONi-3 application? Thank you.

[Analyst] (Evercore ISI): Hi, this is Josh on for Cory Kasimov. Thanks for taking our question. Given there's precedence of China-only trials allowing for approval in the EU, such as RATIONALE 307, wondering if there's any plans to use the HARMONi-6 data set to look for approval in EU, and if not, how could these results help with the HARMONi-3 application? Thank you.

Speaker #5: And then I'll ask Bilal if there's anything else he'd like to add.

Speaker #6: Okay. Thanks for the question. I agree with Dave. I think what's more important, rather than the median, is the pattern of enrollment. And so, sometimes it's a little hard to translate one to the other.

Speaker #5: And if not, how could these results help with the Harmony 3 application? Thank you.

Speaker #6: For the last interim for Harmony 3, we took a calculated risk because we want to get this drug to patients earlier. And I think we're really fine now.

Speaker #8: Thanks for the question, Josh. I think I'll make a couple of points here. So obviously, when we entered into the great partnership with Acacia, one of the things that we were pretty clear on with respect to the US individually was that we'd never had an intent to take a single region study conducted outside of the US.

Dave Gancarz: Thanks for the question, Josh. I think I'll make a couple of points here. When we entered into the great partnership with Akeso, one of the things that we were pretty clear on with respect to the US individually was that we never had an intent to take a single-region study conducted outside of the US and look to bring that specifically in China, and look to bring that to the FDA for approval. I think the FDA had made plenty of comments prior to that that was not what they were looking for. We, of course, opened the HARMONi-3 study. With respect to HARMONi-3, that'll be the primary study for which we would seek approval, especially in the United States. There's complementary considerations. There's another randomized phase III in the same setting, particularly in the squamous, the cohort of HARMONi-3.

Speaker #6: We are very confident in how this is progressing towards the final analysis.

Speaker #4: Very helpful. Thank you.

Speaker #1: Your next question comes from the line of Corey Gasimov with Evercore ISI. Your line is open.

Speaker #6: Hi, this is Josh on for Corey Gasimov. Thanks for taking our question. Given there's precedence of China-only trials allowing for approval in the EU, such as the Rationale 307 study, I'm wondering if there are any plans to use the HARMONY 6 data set to look for approval in the EU.

Speaker #8: And look to bring that specifically and specifically in China. And then look to bring that to the FDA for approval. I think the FDA had made plenty of comments prior to that that that was not what they were looking for.

Speaker #8: We then, of course, opened the Harmony 3 study. And with respect to Harmony 3, that'll be the primary study for which we would seek approval, especially in the United States.

Speaker #6: And if not, how could these results help with the Harmony 3 application? Thank you.

Speaker #5: Thanks for the question, Josh. I think I'll make a couple of points here. Obviously, when we entered into the great partnership with Acacia, one of the things that we were pretty clear on, with respect to the US individually, was that we'd never had an intent to take a single-region study conducted outside of the US.

Speaker #8: But there's complementary considerations. There's another state randomized phase three in the same setting, particularly in the squamous cohort of Harmony 3. So from a package perspective, Harmony 6 could be included to strengthen that overall package.

Dave Gancarz: There's complementary considerations. There's another randomized phase III in the same setting, particularly in the squamous, the cohort of HARMONi-3. From a package perspective, HARMONi-6 could be included to strengthen that overall package. The other piece is when we look at, to your point, Josh, questions and other geographic locations, those are things that we can continue to consider. Obviously we're running HARMONi-3 in Europe as well. That's part of the calculus that needs to go into this. Part of this is also we have, if you take the totality of events. We completed enrollment in the Q1 of this year for the COYAMUS cohort.

Dave Gancarz: From a package perspective, HARMONi-6 could be included to strengthen that overall package. The other piece is when we look at, to your point, Josh, questions and other geographic locations, those are things that we can continue to consider. Obviously we're running HARMONi-3 in Europe as well. That's part of the calculus that needs to go into this. Part of this is also we have, if you take the totality of events. We completed enrollment in the Q1 of this year for the COYAMUS cohort. This data, it was a late breaker at ASCO, so it's pretty fresh in terms of what we have here. Part of that, as we look at next steps, we'll consider multiple options. It's important that we have the global HARMONi-3 data reading out in the H2 of this year.

Speaker #8: And so the other piece is when we look at, to your point, Josh, questions in other geographic locations, those are things that we can continue to consider.

Speaker #5: And look to bring that specifically—and specifically in China—and then look to bring that to the FDA for approval. I think the FDA had made plenty of comments prior to that, that that was not what they were looking for.

Speaker #8: And so obviously, we're running Harmony 3 in Europe as well. So that's part of the calculus that needs to go into this. And part of this is also is we have, if you take the totality of events, we've completed enrollment in the first quarter of this year for the squamous cohort.

Speaker #5: We then, of course, opened the Harmony 3 study. With respect to Harmony 3, that will be the primary study for which we would seek approval, especially in the United States.

Speaker #8: And then also this data is it was a late breaker at ASCO. So it's pretty fresh in terms of what we have here. And so part of that is we look at next steps.

Dave Gancarz: This data, it was a late breaker at ASCO, so it's pretty fresh in terms of what we have here. Part of that, as we look at next steps, we'll consider multiple options. It's important that we have the global HARMONi-3 data reading out in the H2 of this year. We can look at combining packages in certain ways. This is also unlike the RATIONALE 307, there wasn't necessarily a study being run in those regions at the same time, which is where we were always. We've talked very consistently about our strong strategic and operational desires to bring ivonescimab around the world.

Speaker #5: But there's complementary considerations. There's another state-randomized Phase 3 in the same setting, particularly in the squamous cohort of Harmony 3. So, from a package perspective, Harmony 6 could be included to strengthen that overall package.

Speaker #8: We'll consider multiple options. But it's important that we have the global Harmony 3 data reading out. And the second half of this year. And so we can look at combining packages in certain ways.

Speaker #5: And so, the other piece is, when we look at—to your point, Josh—questions in other geographic locations, those are things that we can continue to consider.

Dave Gancarz: We can look at combining packages in certain ways. This is also unlike the RATIONALE 307, there wasn't necessarily a study being run in those regions at the same time, which is where we were always. We've talked very consistently about our strong strategic and operational desires to bring ivonescimab around the world. With that, we can look at whether it makes sense to combine those packages based on what things look like when we get to the second half of this year as well, which will make that a much more straightforward question to answer.

Speaker #8: But this is also unlike the rationale 307, there wasn't necessarily a study being run in those regions at the same time, which is where we were always we've talked very consistently about our strong strategic and operational desires to bring Ibanazimab around the world.

Speaker #5: And so, obviously, we're running Harmony 3 in Europe as well, so that's part of the calculus that needs to go into this. And part of this also is, if you take the totality of events, we've completed enrollment in the first quarter of this year for the squamous cohort.

Speaker #8: And so with that, we can look at whether it makes sense to combine those packages based on what things look like when we get to the second half of this year as well, which will make that a much more straightforward question to answer.

Dave Gancarz: With that, we can look at whether it makes sense to combine those packages based on what things look like when we get to the second half of this year as well, which will make that a much more straightforward question to answer.

Speaker #5: And then also, this data was a late breaker at ASCO, so it's pretty fresh in terms of what we have here. Part of that is, we look at next steps.

Speaker #1: Thank you.

Josh Schimmer: Thank you.

[Analyst] (Evercore ISI): Thank you.

Speaker #6: Your next question comes from the line of Ryan Benjamin with Citizens. Your line is open.

Operator: Your next question comes from the line of Reni Benjamin with Citizens. Your line is open.

Speaker #5: We'll consider multiple options, but it's important that we have the global Harmony 3 data reading out in the second half of this year, so we can look at combining packages in certain ways.

Speaker #1: Hey, good morning, guys. Thanks for taking the questions. And we had Mike congratulations as well. I guess the question I have is kind of given all that you know now for the Harmony 6 study, and the required kind of amount of follow-up, which occurred for the interim OS to hit statistical significance, can you maybe talk us through your thoughts as to why maybe you wouldn't delay the reporting of the interim OS for Harmony 3?

Reni Benjamin: Hey, good morning, guys. Thanks for taking the questions. And let me add my congratulations as well. I guess the question I have, given all that you know now for the HARMONi-6 study and the required amount of follow-up which occurred for the interim OS to hit statistical significance, can you maybe talk us through your thoughts as to why maybe you wouldn't delay the reporting of the interim OS for HARMONi-3? How do you maybe optimize so that you have the right amount of follow-up and the right amount of events that might occur so that both PFS and OS are potentially hitting in the second half of this year? Maybe as a follow-up, I think you mentioned the OS significance boundary was like 0.049 for this HARMONi-6 study.

Speaker #5: But this is also unlike the rationale 307; there wasn't necessarily a study being run in those regions at the same time, which is where we were always—we've talked very consistently about our strong strategic and operational desires to bring Ibezapolstat-Mab around the world.

Speaker #1: How do you maybe optimize so that you have the right amount of follow-up and the right amount of events that might occur so that both PFS and OS are potentially hitting in the second half of this year?

Speaker #5: And so with that, we can look at whether it makes sense to combine those packages based on what things look like when we get to the second half of this year as well, which will make that a much more straightforward question to answer.

Speaker #1: And maybe as a follow-up, I think you mentioned the OS significance boundary was like 0.049 for this Harmony 6 study. Do we is it fair to apply kind of the stats since you've never specified the stat plan that we see in Harmony 6 to Harmony 3?

Speaker #6: Thank you.

Speaker #1: Your next question comes from the line of Ryan Benjamin with Citizens. Your line is open.

Reni Benjamin: Is it fair to apply kind of the stat, since you've never specified the stat plan that we see in HARMONi-6 to HARMONi-3, and why you would choose a one-sided test over a two-sided test? Thank you.

Speaker #4: Hey. Good morning, guys. Thanks for taking the questions, and let me add my congratulations as well. I guess the question I have is, kind of given all that you know now for the Harmony 6 study and the required amount of follow-up, which occurred for the interim OS to hit statistical significance, can you maybe talk us through your thoughts as to why you wouldn't delay the reporting of the interim OS for Harmony 3?

Speaker #1: And why you would choose a one-sided test over a two-sided test? Thank you.

Speaker #8: You added a couple of questions in there. I think the.

Dave Gancarz: You added a couple of questions in there.

Speaker #1: I did. Sorry. Sorry, Dave.

Reni Benjamin: I did. Sorry, Dave

Speaker #8: Oh, good. Right. So I think one of the points with respect to the one-sided test versus the two-sided test I mean, I think that's probably a little bit I think there's a little bit of noise in one of the media coverage articles.

Dave Gancarz: All good, Reni. I think one of the points with respect to the one-sided test versus the two-sided test, I think there's a little bit of noise in one of the media coverage articles. I don't think that's a particularly relevant aspect here. The idea of both HARMONi-3 and HARMONi-6 is looking to show statistical superiority over PD-1 plus chemotherapy. We're not looking at it the other way around. There's really no functional difference between the two. It's just a different way to describe the results of the same test. With respect to the stat plan for HARMONi-3, I appreciate the question. I think as I mentioned a couple of times and as we've talked about as a group and is common across nearly all interim analyses, we don't plan to provide individual details on the individual statistical plan for the study.

Speaker #4: How do you maybe optimize so that you have the right amount of follow-up and the right amount of events that might occur so that both PFS and OS are potentially hitting in the second half of this year?

Speaker #8: I don't think that's a particularly relevant aspect here. The idea of both Harmony 3 and Harmony 6 is looking to show statistical superiority over PD1 plus chemotherapy.

Speaker #4: And maybe as a follow-up, I think you mentioned the OS significance boundary was like 0.049 for this HARMONY 6 study. Is it fair to apply kind of the stats—since you've never specified the stat plan that we see in HARMONY 6—to HARMONY 3?

Speaker #8: And so that is we're not looking at it the other way around. And so the different there's really no functional difference between the two.

Speaker #4: And why would you choose a one-sided test over a two-sided test? Thank you.

Speaker #8: They just are just it's just a different way to describe the results of the same test. With respect to the stat plan for Harmony 3, I appreciate the question.

Speaker #5: You added a couple of questions in there. I think the—

Speaker #4: I did. Sorry. Sorry, Dave.

Speaker #5: All good. Right. So I think one of the points with respect to the one-sided test versus the two-sided test—I mean, I think that's probably a little bit... I think there's a little bit of noise in one of the media coverage articles.

Speaker #8: But I think as I mentioned a couple of times and as we've talked about, is a group and is common across nearly all interim analyses.

Dave Gancarz: I think as I mentioned a couple of times and as we've talked about as a group and is common across nearly all interim analyses, we don't plan to provide individual details on the individual statistical plan for the study. That includes both the previous interim PFS look as well as the upcoming interim OS look. The third piece, which is important is your question with respect to the bar in the interim OS at the end of this year, less the bar in terms of what the thresholds are, but the ability to compare the follow-up time in HARMONi-6 or other studies in looking at the timing of HARMONi-3. HARMONi-3, as we've talked about, this is an interim OS analysis, but it's also the final PFS analysis. Those are effectively tied together.

Speaker #8: We don't plan to provide individual details on the individual statistical plan for the study. And that includes both the previous interim PFS look as well as the upcoming interim OS look.

Speaker #5: I don't think that's a particularly relevant aspect here. The idea of both Harmony 3 and Harmony 6 is to show statistical superiority over PD-1 plus chemotherapy.

Dave Gancarz: That includes both the previous interim PFS look as well as the upcoming interim OS look. The third piece, which is important is your question with respect to the bar in the interim OS at the end of this year, less the bar in terms of what the thresholds are, but the ability to compare the follow-up time in HARMONi-6 or other studies in looking at the timing of HARMONi-3. HARMONi-3, as we've talked about, this is an interim OS analysis, but it's also the final PFS analysis. Those are effectively tied together. We'll look at the final PFS analysis based on our pre-specified number of events, and that's looked at, those events look like they'll come in the H2 of this year. That's the end of the testing for PFS.

Speaker #8: I think the third piece, I think, which is important, is your question with respect to the bar in the interim OS at the end of this year.

Speaker #5: And so that is, we're not looking at it the other way around. And so, really, there's no functional difference between the two.

Speaker #8: And let's the bar in terms of what the thresholds are. But the ability to compare the follow-up time in Harmony 6 or other studies and looking at the timing of Harmony 3.

Speaker #5: They just are—it's just a different way to describe the results of the same test. With respect to the stat plan for Harmony 3, I appreciate the question.

Speaker #8: So Harmony 3, as we've talked about, this is an interim OS analysis. But it's also the final PFS analysis. And so those are effectively tied together.

Speaker #5: But I think, as I mentioned a couple of times, and as we've talked about as a group—and as is common across nearly all interim analyses—we don't plan to provide individual details on the individual statistical plan for the study.

Speaker #8: So we'll look at the final PFS analysis based on our pre-specified number of events. And that will that's looked at at the end of those events look like they'll come in the second half of this year.

Dave Gancarz: We'll look at the final PFS analysis based on our pre-specified number of events, and that's looked at, those events look like they'll come in the H2 of this year. That's the end of the testing for PFS. Traditionally, when you look at a final PFS analysis, you also at that same time, have a look at interim OS, or you have a look at OS on an interim basis. I would say we should set no expectations that the idea is an interim OS look at H2 of this year is a make or break look. I think it will be very informative in terms of what that looks like from overall survival.

Speaker #5: And that includes both the previous interim PFS look as well as the upcoming interim OS look. I think the third piece, which is important, is your question with respect to the bar in the interim OS at the end of this year.

Speaker #8: And that's the end of the testing for PFS. And traditionally, when you look at a final PFS analysis, you also at that same time have a look at interim OS.

Dave Gancarz: Traditionally, when you look at a final PFS analysis, you also at that same time, have a look at interim OS, or you have a look at OS on an interim basis. I would say we should set no expectations that the idea is an interim OS look at H2 of this year is a make or break look. I think it will be very informative in terms of what that looks like from overall survival. That will also take place at a median follow-up time that's less than what the HARMONi-6 follow-up time was. HARMONi-6, I believe, completed enrollment in January 2025. This analysis had a data cutoff that was presented yesterday of the end of February 2026. You've got last patient in plus about 13 months there.

Speaker #8: Or you have a look at OS on an interim basis. So I would say we should set no expectations that the idea is an interim OS look at the second half of this year is a make-or-break look.

Speaker #5: And let's set the bar in terms of what the thresholds are. But the ability to compare the follow-up time in Harmony 6 or other studies, and looking at the timing of Harmony 3.

Speaker #8: But I think it will be very informative in terms of what that looks like from overall survival. And that will also take place at a median follow-up time that's less than what the Harmony 6 follow-up time was.

Speaker #5: So, Harmony 3, as we've talked about, this is an interim OS analysis, but it's also the final PFS analysis. And so those are effectively tied together.

Dave Gancarz: That will also take place at a median follow-up time that's less than what the HARMONi-6 follow-up time was. HARMONi-6, I believe, completed enrollment in January 2025. This analysis had a data cutoff that was presented yesterday of the end of February 2026. You've got last patient in plus about 13 months there. We talked about the fact that we completed enrollment in Q1 of 2024. We're saying that this final PFS and interim OS will take place in H2 of 2024.

Speaker #5: So, we'll look at the final PFS analysis based on our pre-specified number of events, and that's looked at at the end of those events. It looks like they'll come in the second half of this year.

Speaker #8: And so Harmony 6, I believe, completed enrollment in January of 2025. This analysis had a data cutoff that was presented yesterday of the end of February, 2026.

Speaker #8: And so you've got less patient in plus about 13 months there. We talked about the fact that we completed enrollment in the first quarter of this year.

Speaker #5: And that's the end of the testing for PFS. Traditionally, when you look at a final PFS analysis, you also, at that same time, have a look at interim OS.

Dave Gancarz: We talked about the fact that we completed enrollment in Q1 of 2024. We're saying that this final PFS and interim OS will take place in H2 of 2024. While you don't know necessarily when in H2, it's obviously going to be less than 13 months of median follow-up time. We think that's very informative in terms of what directionally where OS looks. I certainly wouldn't go into this with the expectations that we feel that OS as an endpoint is make or break in H2 of 2024. We have a look, just like most trials do, at OS at the time of the final PFS, which is pre-specified, and that's what we're looking at H2 of 2024.

Speaker #8: And then we're saying that this final PFS and interim OS will take place in the second half of this year. So while you don't know necessarily when in the second half, it's obviously going to be less than 13 months of median follow-up time.

Speaker #5: Or you have a look at OS on an interim basis. So, I would say we should set no expectations that the idea is an interim OS look in the second half of this year is a make-or-break look.

Dave Gancarz: While you don't know necessarily when in H2, it's obviously going to be less than 13 months of median follow-up time. We think that's very informative in terms of what directionally where OS looks. I certainly wouldn't go into this with the expectations that we feel that OS as an endpoint is make or break in H2 of 2024. We have a look, just like most trials do, at OS at the time of the final PFS, which is pre-specified, and that's what we're looking at H2 of 2024. Within that interim OS gives us directional inference in terms of where we go from what that data looks like to describe the OS at this point.

Speaker #5: But I think it will be very informative in terms of what that looks like from overall survival. And that will also take place at a median follow-up time that's less than what the HARMONY-6 follow-up time was.

Speaker #8: So we think that's very informative in terms of what directionally where OS looks. But I certainly wouldn't go into this with the expectations that we feel that OS is an endpoint, is make or break in the second half of this year.

Speaker #8: We have a look just like most trials do at OS at the time of the final PFS. Which is pre-specified. And that's what we're looking at the second half of this year.

Speaker #5: And so Harmony 6, I believe, completed enrollment in January 2025. This analysis had a data cutoff that was presented yesterday of the end of February 2026.

Speaker #8: And so within that interim OS gives us directional inference in terms of where we go from what that data looks like to describe the OS at this point.

Dave Gancarz: Within that interim OS gives us directional inference in terms of where we go from what that data looks like to describe the OS at this point.

Speaker #5: And so you've got less patient input in about 13 months there. We talked about the fact that we completed enrollment in the first quarter of this year.

Speaker #5: And then we're saying that this final PFS and interim OS will take place in the second half of this year. So, while you don't know necessarily when in the second half, it's obviously going to be less than 13 months of median follow-up time.

Speaker #1: Great. Thanks for taking the questions.

Reni Benjamin: Great. Thanks for taking the questions.

Speaker #6: Your next question comes from the line of David Dai with UBS. Your line is open.

Operator: Your next question comes from the line of David Dai with UBS. Your line is open.

Speaker #1: Oh, great. Thanks for taking my question. I was also on my congratulations on the data. So Winthe mentioned Dave was that there is an imbalance between the 65 years of age and under 65 based on lesion size and BREMED.

David Dai: Great. Thanks for taking my questions. Also want to add my congratulations on the data. Lindsay mentioned, Dave, was that there's the imbalance between the 65 years of age and under 65 based on lesion size and brain mets. How do you think this might impact patient selection for HARMONi-3 trial? Do you expect to exclude some patients with these kind of covariates for HARMONi-3 trial?

Speaker #5: So we think that's very informative in terms of, directionally, where OS looks. But I certainly wouldn't go into this with the expectation that we feel that OS is an endpoint—or make-or-break—in the second half of this year.

Speaker #1: So how do you think this might impact patient selection for Harmony 3 trial? And do you expect to see some patients with these kind of covariance for Harmony 3 trial?

Speaker #5: We have a look, just like most trials do, at OS at the time of the final PFS, which is pre-specified. And that's what we're looking at in the second half of this year.

Speaker #8: Yeah. I understand your question, David. So and I appreciate what you're asking. The importantly, Harmony 3 remains completely blinded. So if we step back, what you aren't able to define within subgroups before as you look at the data is what different covariables will be unbalanced within the arm.

Dave Gancarz: Yeah, I understand your question, David, and I appreciate what you're asking. Importantly, HARMONi-3 remains completely blinded. If we step back, what you aren't able to define within subgroups as you look at the data is what different covariates will be unbalanced within the arm. I think it's a little bit of a speculative question of will different subgroups, which are not stratified in the trial, will they contain imbalanced baseline characteristics? Again, I would say, there's no way to know that before you go into trial. I would also say that's where looking at subgroups can be helpful, and I think as Jack mentioned in his comments. They're not powered for individual results, right?

Speaker #5: And so, within that interim, OS gives us directional input—an inference in terms of where we go, from what that data looks like—to describe the OS at this point.

Speaker #4: Great excitement.

Speaker #2: Thanks for taking the questions.

Speaker #1: Your next question comes from the line of David Dye with UBS. Your line is open.

Speaker #8: So I think it's a little bit of a speculative question of will different subgroups, which are not stratified in the trial, will they contain an imbalanced baseline characteristics?

Speaker #6: Oh, great. Thanks for taking my question. I also want to add my congratulations on the data. So, what Dave mentioned was that there's an imbalance between the 65 years of age and under-65, based on lesion size and BMED.

Speaker #6: So, how do you think this might impact patient selection for the Harmony 3 trial? And do you expect to see some patients with these kinds of co-variates for the Harmony 3 trial?

Speaker #8: Again, I would say so there's no way to know that before you go into trial. But I would also say that's where looking at subgroups can be helpful.

Speaker #8: And I think as Jeff mentioned in his comments, but they're not powered for individual results, right? And so what you're looking for is do you see a subgroup with a detriment, a hazard ratio, over one in particularly directionally well over one that gives you pause to say clinically, is there something here that may be more informative maybe than what we had thought hypothetically going into a study?

Speaker #5: Yeah. I understand your question, David, and I appreciate what you're asking. Importantly, Harmony 3 remains completely blanket. So if we step back, what you aren't able to define within subgroups, when before as you look at the data, is what different covariables will be unbalanced within the arm.

Dave Gancarz: What you're looking for is do you see a subgroup with a hazard ratio over one and particularly directionally well over one that gives you pause to say clinically, is there something here that may be more informative maybe than what we had thought hypothetically going into a study? I want to be very clear. All subgroups had a hazard ratio of less than one. All subgroups received benefit from ivonesimab plus chemotherapy in comparison to cemiplimab plus chemotherapy. All subgroups trended were to the left of the line on the forest plots, right? There were no subgroups that were detrimental or had a detriment from ivonesimab as compared to PD-1. That's a really important context here. Even with the imbalance of these covariates, we did not see a detriment to any of these patients, right?

Speaker #5: So I think it's a little bit of a speculative question of, will different subgroups, which are not stratified in the trial, have imbalanced baseline characteristics?

Speaker #8: I want to be very clear. All subgroups had a hazard ratio of less than one. All subgroups receive benefit from either an estimate plus chemotherapy in comparison to this list plus chemotherapy.

Speaker #5: Again, I would say, there's no way to know that before you go into trial. But I would also say that's where looking at subgroups can be helpful.

Speaker #8: All subgroups trended were to the left of the line on the forest plots, s, right? So there were no subgroups that were detrimental when received or were had a detriment from either an estimate as compared to PD1.

Speaker #5: And I think, as Jeff mentioned in his comments, they're not powered for individual results, right? And so what you're looking for is: do you see a subgroup with a detriment—a hazard ratio over one, and particularly, directionally well over one—that gives you pause to say, clinically, is there something here that may be more informative than what we had thought hypothetically going into a study?

Speaker #8: That's a really important context here. And so even with the imbalance of these covariables, we did not see a detriment to any of these patients, right?

Dave Gancarz: Even with the imbalance of these covariates, we did not see a detriment to any of these patients, right? It was a smaller improvement, but an improvement nonetheless, right. I think that's the difference here that I want to make sure we don't lose sight of. This isn't an example where we're looking at a subgroup with a 1.3 hazard ratio and saying, Hey, we really need to take a step back and understand if there's something there. There's no way to know a priori going into a study if the Western patients versus the Eastern patients or the PD-L1 high versus the PD-L1 low will ultimately have more brain metastases versus less or whatnot, because that's not really what you planned for.

Speaker #8: It was a smaller improvement, but an improvement nonetheless, right? And I think that's the difference here that I want to make sure we don't lose sight of.

Dave Gancarz: It was a smaller improvement, but an improvement nonetheless, right. I think that's the difference here that I want to make sure we don't lose sight of. This isn't an example where we're looking at a subgroup with a 1.3 hazard ratio and saying, Hey, we really need to take a step back and understand if there's something there. There's no way to know a priori going into a study if the Western patients versus the Eastern patients or the PD-L1 high versus the PD-L1 low will ultimately have more brain metastases versus less or whatnot, because that's not really what you planned for. I think that's where we'll see that data that comes through. It is very important that all subgroups were less than one, and therefore, none of these imbalances actually led to a detriment.

Speaker #5: I want to be very clear. All subgroups had a hazard ratio of less than one. All subgroups received benefit from either NSMS plus chemotherapy in comparison to zolizumab plus chemotherapy.

Speaker #8: This isn't an example where we're looking at a subgroup with a 1.3 hazard ratio and saying, "Hey, we really need to take a step back and understand if there's something there." And so there's no way to know a priori going into a study if the western patients versus the eastern patients or the PL1 high versus the PDL1 low will ultimately have more brain metastases versus less or whatnot.

Speaker #5: All subgroups trended to the left of the line on the forest plots, right? So there were no subgroups that were detrimental when received, or that had a detriment from either an SMS as compared to PD-1.

Speaker #8: Because that's not really what's planned for. But I think that's where the that's where we'll see that data as it comes through. But it is very important that all subgroups were less than one.

Speaker #5: That's a really important context here. And so, even with the imbalance of these covariables, we did not see a detriment to any of these patients, right?

Dave Gancarz: I think that's where we'll see that data that comes through. It is very important that all subgroups were less than one, and therefore, none of these imbalances actually led to a detriment.

Speaker #5: It was a smaller improvement, but an improvement nonetheless, right? And I think that's the difference here that I want to make sure we don't lose sight of.

Speaker #8: And therefore, none of these imbalances actually led to a detriment.

Speaker #1: But yeah, Dave.

H. Jack West: Yeah, Dave.

Allen Yang: Yeah, Dave.

Speaker #8: Yeah. Just to go ahead.

Dave Gancarz: Yeah.

Speaker #1: Oh. I was just going to add one thing too to reassure you. There are criteria which we believe could impact the outcome. And so things like brain metastases as well as PDL1 expression levels are stratified for in the Harmony 3 study.

Speaker #5: This isn't an example where we're looking at a subgroup with a 1.3 hazard ratio and saying, "Hey, we really need to take a step back and understand if there's something there." And so there's no way to know a priori going into a study if the Western patients versus the Eastern patients, or the PD-L1 high versus the PD-L1 low, will ultimately have more brain metastases versus less, or whatnot.

H. Jack West: I was just going to add one thing too, to reassure you. There are criteria which we believe could impact the outcome. Things like brain metastases as well as PD-L1 expression level are stratified for in the HARMONi-3 study.

Allen Yang: I was just going to add one thing too, to reassure you. There are criteria which we believe could impact the outcome. Things like brain metastases as well as PD-L1 expression level are stratified for in the HARMONi-3 study.

Speaker #8: Yeah. Just to add on it, yeah, this below here. And if you need to look at the 95% confidence interval, I think they are overlapping between the two age groups.

Bilal Safradi: Yeah, just to add on it, yeah, this is Balaji here. If you need to look at the 95% confidence interval, I think they are overlapping between the two age groups. This further strengthens that. This could be fairly random.

Bilal Piperdi: Yeah, just to add on it, yeah, this is Balaji here. If you need to look at the 95% confidence interval, I think they are overlapping between the two age groups. This further strengthens that. This could be fairly random.

Speaker #5: Because that's not really what's been planned for. But I think that's where we'll see that data as it comes through. But it is very important that all subgroups were less than one.

Speaker #8: This further strengthened that. I mean, this could be fairly random.

Speaker #6: Your next question comes from the line of Dara Azar with Stifel. Your line is open.

Operator: Your next question comes from the line of Dara Azar with Stifel. Your line is open.

Speaker #5: And therefore, none of these imbalances actually led to a detriment.

Speaker #9: Hi. Congrats on the data. Could you please characterize the growing separation of the OS curves? Do you attribute this to either an estimate or the histology more?

Speaker #6: Yeah, Dave.

Dara Azar: Hi. Congrats on the data. Could you please characterize the growing separation of the OS curves? Do you attribute this to ivonesimab or the histology more? How strong is the case to see a similar phenomenon in non-squamous, non-small cell, considering HARMONi-2 OS hazard ratio translation from PFS was a little bit different in that mixed histology study? Thanks so much.

Speaker #5: Yeah, just to go ahead.

Speaker #6: Oh, I was just going to add one thing, too, to reassure you. There are criteria which we believe could impact the outcome, and so things like brain metastases, as well as PD-L1 expression levels, are stratified for in the HARMONY-3 study.

Speaker #9: And how strong is the case to see a similar phenomenon in non-squamous, non-small cell considering Harmony 2 OS has a ratio translation from PFS was a little bit different in that mixed histology study?

Speaker #5: Yeah, just to add on to that, this blog here—and if you need to look at the 95% confidence interval, I think they are overlapping between the two age groups.

Speaker #9: Thanks so much.

Speaker #5: It's further strengthened that, I mean, this could be fairly random.

Speaker #1: I this is Jack. I think that the most noticeable thing, again, when you see the separation becomes clearer as the chemotherapy has been completed, chemotherapy is kind of a normalizing effect.

H. Jack West: This is Jack. I think that the most noticeable thing, again, when you see the separation becomes clearer as the chemotherapy has been completed. Chemotherapy is kind of a normalizing effect, and then once you're at the point where you're directly testing the ivonescimab against the other tier immunotherapy in cemiplimab, the longer you go, the more that differential becomes apparent. I think that with non-squamous, non-small cell lung cancer, it's different because there's going to be ongoing maintenance pemetrexed, and so that may still have some kind of normalizing or effect that will change it from a paradigm where there's a prolonged period of just ivonescimab as monotherapy in the maintenance setting against pembrolizumab.

Howard Jack West: This is Jack. I think that the most noticeable thing, again, when you see the separation becomes clearer as the chemotherapy has been completed. Chemotherapy is kind of a normalizing effect, and then once you're at the point where you're directly testing the ivonescimab against the other tier immunotherapy in cemiplimab, the longer you go, the more that differential becomes apparent. I think that with non-squamous, non-small cell lung cancer, it's different because there's going to be ongoing maintenance pemetrexed, and so that may still have some kind of normalizing or effect that will change it from a paradigm where there's a prolonged period of just ivonescimab as monotherapy in the maintenance setting against pembrolizumab.

Speaker #1: Your next question comes from the line of Dara Azar with Stifel. Your line is open.

Speaker #4: Hi. Congrats on the data. Could you please characterize the growing separation of the OS curves? Do you attribute this to either an SMS or the histology more?

Speaker #1: And then you once you're at the point where you're directly testing, the either an estimate against the other tier immunotherapy and to Lismap, the longer you go, the more that differential becomes apparent.

Speaker #4: And how strong is the case to see a similar phenomenon in non-squamous, non-small cell, considering Harmony 2 OS has a ratio translation from PFS was a little bit different in that mixed histology study?

Speaker #1: I think that with non-squamous, non-small cell lung cancer, it's different because there's going to be ongoing maintenance pemetrexed. And so that may still have some kind of normalizing or effect that may that will change it from a paradigm where there's a prolonged period of just either an estimate as monotherapy and the maintenance setting against pembrolizumab.

Speaker #4: Thanks so much.

Speaker #6: Hi, this is Jack. I think that the most noticeable thing, again, is when you see the separation become clearer after the chemotherapy has been completed. Chemotherapy has kind of a normalizing effect.

Speaker #6: And then, once you're at the point where you're directly testing either an SMS against the other, here immunotherapy and atezolizumab, the longer you go, the more that differential becomes apparent.

Speaker #1: So it'll be a little different. But you still see the separation occur. And I am optimistic that that's what we will see. Especially as if patients are fortunate enough to be doing well without progression, in some cases, patients will have pemetrexed discontinued due to cumulative myelosuppression issues.

H. Jack West: It'll be a little different, but you still see the separation occur, and I am optimistic that that's what we will see. Especially as patients are fortunate enough to be doing well without progression, in some cases, patients will have pemetrexed discontinued due to cumulative myelosuppression issues, renal issues, and even though pemetrexed is generally considered a very well-tolerated therapy, it has cumulative toxicities if patients are on it for enough of a period that it really becomes longitudinal. There will still be patients who are just on ongoing, essentially monotherapy of, in HARMONi-3, ivonesimab against pembrolizumab. The separation, I think will be there, but it'll be a little different question in the non-squamous population, both because of the underlying differences in biology and because there is not a maintenance chemo component in squamous.

Howard Jack West: It'll be a little different, but you still see the separation occur, and I am optimistic that that's what we will see. Especially as patients are fortunate enough to be doing well without progression, in some cases, patients will have pemetrexed discontinued due to cumulative myelosuppression issues, renal issues, and even though pemetrexed is generally considered a very well-tolerated therapy, it has cumulative toxicities if patients are on it for enough of a period that it really becomes longitudinal. There will still be patients who are just on ongoing, essentially monotherapy of, in HARMONi-3, ivonesimab against pembrolizumab. The separation, I think will be there, but it'll be a little different question in the non-squamous population, both because of the underlying differences in biology and because there is not a maintenance chemo component in squamous.

Speaker #6: I think that with non-squamous, non-small cell lung cancer, it's different because there's going to be ongoing maintenance pemetrexed, and so that may still have some kind of normalizing effect. That may change it from a paradigm where there's a prolonged period of just either an SMS as monotherapy in the maintenance setting against pembrolizumab.

Speaker #1: Renal issues and even though pemetrexed is generally considered a very well-tolerated therapy, it has cumulative toxicities if patients are on it for enough of a period that it really becomes longitudinal.

Speaker #1: So there will still be patients who are just on ongoing essentially monotherapy of in Harmony 3. Either an estimate against pembrolizumab. But the separation, I think, will be there.

Speaker #6: So it'll be a little different. But you still see the separation occur. And I am optimistic that that's what we will see, especially as, if patients are fortunate enough to be doing well without progression, in some cases, patients will have pemetrexed discontinued due to cumulative myelosuppression issues.

Speaker #1: But it'll be a little different question in the non-squamous population, both because of the underlying differences in biology and because there is not a maintenance chemo component in squamous.

Speaker #8: And again, I think the only thing I would add to that is really the again, we go back to the highly encouraging phase two data generated in this space where we saw very in some of this was disclosed as recently as ELCC 2024.

Dave Gancarz: I think the only thing I would add, Jack, is really the, again, we go back to the highly encouraging phase II data generated in the space where we saw some of this was disclosed as recently as ELCC 2024. Obviously that's highly encouraging data as well that helps provide additional comfort on that front as well in terms of the applicability of ivonesimab plus chemotherapy in the non-squamous cohort.

Speaker #6: Renal issues, and even though pemetrexed is generally considered a very well-tolerated therapy, it has cumulative toxicities if patients are on it for enough of a period that it really becomes longitudinal.

Speaker #8: And obviously, that's highly encouraging data as well that helps provide additional comfort on that front as well in terms of the applicability of either an estimate plus chemotherapy in the non-squamous cohort.

Speaker #6: So, there will still be patients who are just on ongoing, essentially monotherapy, in Harmony 3—either NSMS against pembrolizumab. But the separation, I think, will be there.

Speaker #6: I'd now like to turn the call over to Dave Gancarz for closing remarks.

Operator: I'd now like to turn the call over to Dave Gancarz for closing remarks.

Speaker #6: But it'll be a little different question in the non-squamous population, both because of the underlying differences in biology and because there is not a maintenance chemo component in squamous.

Speaker #8: I want to take the time to thank everybody for attending today's call. Obviously, the historic results of Harmony 6 is we've gone over multiple times is a day for celebration across both Summit Team and I want to once again congratulate our partners at Akeso for a wonderful result.

Dave Gancarz: I want to take the time to thank everybody for attending today's call. Obviously, the historic results of HARMONi-6, as we've gone over multiple times, is a day for celebration across both the Summit team. I want to once again congratulate our partners at Akeso for a wonderful result. A hazard ratio of 0.66 is not something to shake a stick at. Not only that, this is the first trial to go head-to-head against the PD-1 plus chemotherapy in frontline driver mutation negative non-small cell lung cancer and show a statistically significant benefit, not only in PFS, but now overall survival. That is not, as Jack was very eloquently describing earlier, not a borderline case and not anything other than something to be fully celebrated. We want to take the time to thank you for attending today's call.

Speaker #5: And again, I think the only thing I would add to that is really, again, we go back to the highly encouraging Phase 2 data generated in this space, where we saw—very, and some of this was disclosed as recently as ELCC 2024.

Speaker #8: This is a hazard ratio of 0.66 is not something to shake a sick at. But not only that, this is the first trial to go head-to-head against a PD1 plus chemotherapy and frontline driver mutation negative non-small cell lung cancer and show a statistically significant benefit not only in PFS but now overall survival.

Speaker #5: And obviously, that's highly encouraging data as well that helps provide additional comfort on that front as well, in terms of the applicability of either an SMS plus chemotherapy in the non-squamous cohort.

Speaker #1: I'd now like to turn the call over to Dave Gancarz for closing remarks.

Speaker #8: And that is not, as Jack was very eloquently describing earlier, not a borderline case. And not anything other than something to be fully celebrated.

Speaker #5: I want to take the time to thank everybody for attending today's call. Obviously, the historic results of Harmony 6, as we've gone over multiple times, is a day for celebration across both Summit team.

Speaker #8: So we want to take the time to thank you for attending today's call. And archive version of the webcast will be available on our website.

Dave Gancarz: We want to take the time to thank you for attending today's call. An archived version of the webcast will be available on our website, and enjoy the rest of your day. For those of you here in Chicago, we hope you have a wonderful rest of your ASCO.

Dave Gancarz: An archived version of the webcast will be available on our website, and enjoy the rest of your day. For those of you here in Chicago, we hope you have a wonderful rest of your ASCO.

Speaker #8: And enjoy the rest of your day. And for those of you here in Chicago, we hope you have a wonderful rest of your outcome.

Speaker #5: And I want to once again congratulate our partners at Akeso for a wonderful result. A hazard ratio of 0.66 is not something to shake a stick at.

Operator: Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.

Speaker #5: But not only that, this is the first trial to go head-to-head against a PD-1 plus chemotherapy in frontline, driver mutation-negative, non-small cell lung cancer.

Speaker #5: And so, it is a statistically significant benefit, not only in PFS but now in overall survival. And that is not, as Jack was very eloquently describing earlier.

Speaker #5: This is not a borderline case and nothing other than something to be fully celebrated. So, we want to take the time to thank you for attending today's call.

Speaker #5: An archived version of the webcast will be available on our website. Enjoy the rest of your day. And for those of you here in Chicago, we hope you have a wonderful rest of your afternoon.

Speaker #1: Ladies and gentlemen, that concludes today's call. Thank you all for joining. You may now disconnect.

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