Q1 2025 Summit Therapeutics Inc Earnings Call

[music].

Okay.

Unknown Executive: Thank you for standing by.

Thank you for standing by.

Unknown Executive: Hello and welcome to the Summit Therapeutics Q1 2025 earnings conference call.

Hello, and welcome to the Summit Therapeutics Q1, 2025 earnings Conference call.

Dave Gancarz: I would now like to turn the call over to our Chief Business and Strategy Officer, Dave Gancarz. Please go ahead. Good afternoon, and thank you for joining. The press release was issued earlier this afternoon and is available on the homepage of our website. Our Form 10-Q was also filed. Available on. Today's call is being simultaneously webcast.

Speaker Change: I'd now like to turn the call over to our Chief business and strategy Officer, Dave cars. Please go ahead Sir.

Speaker Change: Good afternoon, and thank you for joining US a press release was issued earlier this afternoon and is available on the homepage of our website.

Speaker Change: Our Form 10-Q was also filed and is available on our website.

Speaker Change: <unk> call is being simultaneously webcast.

Unknown Executive: Archived Replay will also be made available later today on our website www.smmtx.gov.

Speaker Change: Archived replay will also be made available later today on our website www Dot S. M M T T X dot com.

Dave Gancarz: Joining me on the call today is Bob Duggan, our Chairman of the Board and Co-Chief Executive Officer. Dr. Mahkam Zanganeh, our Co-Chief Executive Officer and President. Manmeet Soni, our Chief Operating Officer and Chief Financial Officer. Dr. Allen Yang, our Chief Medical Officer. and Dr. Jack West, Vice President and our Thoracic Oncology TA.

Speaker Change: Joining me on the call today is Bob Duggan, our chairman of the Board and co Chief Executive Officer, Dr. <unk> <unk>, our co Chief Executive Officer and President.

Speaker Change: <unk> Soni, our Chief operating officer, and Chief Financial Officer Dr.

Speaker Change: Dr. Allen Yang, our Chief Medical Officer, and Dr. Jack West Vice President and our thoracic oncology T I had.

Speaker Change: Yeah.

Dave Gancarz: Before we get started with the rest of the call, I would like to note that some of the statements made by our management... Some responses to questions that we make today may be considered forward-looking. Summit cautions that these forward-looking statements are subject to risks and uncertainties. may cause actual results to different materials.

Speaker Change: Before we get started with the rest of the call.

Speaker Change: We'd like to note that some of the 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.

Speaker Change: Stomach 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.

Unknown Executive: co-organizer, Good. Please refer to our SEC filings for information about these risk. undertakes no obligation to update these forward.

Speaker Change: These refer to our SEC filings for information about these risks and uncertainties.

Speaker Change: Summit undertakes no obligation to update these forward looking statements, except as required by law.

Unknown Executive: Gould, Allen Yang, Bradley Canino, cities, etc.

Unknown Executive: Following comments from Bob, Mekhi, and We will take questions.

Bob Mackie: Following comments from Bob Mackie and <unk>.

Bob Mackie: We will take questions with that I would like to turn the call over to Bob. Thank.

Robert Duggan: With that, I would like to turn the call over to Bob. Thank you, Dave. Good afternoon, everyone, and thank you for joining us today. You can imagine, I'm very proud of, as well as encouraged by, the ongoing accomplishments of Team Summit and the continuing positive information Enthusiasm surrounding Ivanistamab our lead medicinal investigational We have begun 2025 with excellent progress and continue to take meaningful steps in the development of an We continue to advance our mission of building a viable organization, making a significant positive difference in serious unmet medical needs. Specifically, last week, our partner, Acaso, made two important, as well as material, announcements.

Speaker Change: Thank you Jay and good afternoon, everyone and thank you for joining US today as you can imagine I'm very proud of as well as encouraged by the ongoing accomplishments of team summit and the continuing positive information and then Susie azzam surrounding I've initiatives, our lead medicinal investigational assets we have.

Speaker Change: 2025, with excellent progress and continue to take meaningful steps in the development of evidence of that we continue to advance our mission of building a viable organization, making a significant positive difference in serious unmet medical needs specifically last week, our partner a Castro made two important <unk>.

Speaker Change: It was a material announcements first I mean, there's some I have received approval from an MTA the health authority in China as frontline monotherapy treatment for patients with an S. TLC, whose tumors have positive PDL. One expression. This marks an important regulatory milestone for our partners out of Casto and.

Robert Duggan: First, Ivanissima have received approval from NMPA, the health authority in China, as frontline monotherapy treatment for patients with NSTLC whose tumors have positive PD-L1 expression. This marks an important regulatory milestone for our partners at Acaso and adds to the growing evidence of Ivanissima's differentiated profile and its potential to make a significant difference in the lives of patients dealing with hard-to-treat cancer. On behalf of the Summit team, we want to extend our congratulations to our partners at KESO for this achievement and our gratitude for our strong, ongoing partnership. This approval was based on positive PFS results from Akeso's Harmony 2 trial, which was disclosed at last year's World Conference on Lung Cancer.

Speaker Change: Adds to the growing evidence of <unk> differentiated profile and has potential to make a significant difference in the lives of patients dealing with it's hard to treat cancers on behalf of the summit team, we want to extend our congratulations to our partners. So.

Speaker Change: So for this achievement and our gratitude for our strong ongoing partnership. This approval was based on positive PFS results from Mckesson as harmony, two trial, which was disclosed at last year's World Conference on lung cancer. Additionally to supplement this groundbreaking PFS data that represented the first drug to achieve.

Robert Duggan: Additionally, to supplement this groundbreaking PFS data that represented the first drug to achieve a statistically significant benefit over Pembrolizumab in a Phase 3 clinical trial, the NMPA requested that Akeso perform an interim analysis of overall survival. Last week, Akeso reported on the Health Authority-requested early interim analysis. The analysis showed a clinically meaningful and strongly positive trend favoring Ivanissimab at 39% data maturity with a hazard ratio of 0.777, implying a potential 22% reduction in the risk of death compared to Pembroke. To be clear, at Summit, we are pleased and excited about this remarkable outcome. McKee will discuss this a little further in a few moments.

Speaker Change: Statistically significant benefit over <unk> and a phase III clinical trial, the NFPA requested that a cursor perform an interim analysis of overall survival.

Speaker Change: Last week, the Castro reported on the Health Authority requested early interim analysis. The analysis showed a clinically meaningful and strongly positive trend favoring <unk> at 39% data maturity with a hazard ratio of 0.7 hundred 77, implying.

Speaker Change: A potential 22% reduction in the risk of death compared <unk> to be clear at summit. We are pleased and excited about this remarkable outcome Micky will discuss this a little bit further in a few moments. Additionally cast those harmony six phase III clinical trial met its primary endpoint of progression.

Robert Duggan: Additionally, Kessil's Harmony 6 Phase 3 clinical trial met its primary endpoint of progression pre-survival at a pre-specified interim analysis conducted by an independent data monitoring committee. This trial evaluated Ivanizumab in combination with chemotherapy against Tizolizumab, a PD-1 inhibitor in combination with chemotherapy in patients with advanced squamous non-small cell lung cancer, regardless of PD-L1 attrition. Conducted in China by our partners at Kessil, the trial showed statistically significant and clinically meaningful improvement in progression-free survival for Ivanizumab plus chemotherapy. Kessil noted that no new safety signals were identified. This marks the first known Phase 3 trial in NSCLC to show significant improvement over a PD-1 or PD-L1 inhibitor combined with chemotherapy in a head-to-head situation.

Speaker Change: And free survival at a pre specified interim analysis conducted by an independent data monitoring committee. This trial evaluated <unk> in combination with chemotherapy I guess, just really this map a PD one inhibitor in combination with chemotherapy in patients with advanced squamous non small.

Speaker Change: Cell lung cancer, regardless of PD Lone nutrition conducted in China by our partners added Casto to trial showed statistically significant and clinically meaningful improvement in progression free survival for <unk> plus chemotherapy Castle noted that no new safety signals were identified this march.

Speaker Change: First known phase III trial.

Speaker Change: CLC to show significant improvement over a PD, one or PDL, one inhibitor combined with chemotherapy in a head to head setting.

Robert Duggan: Following the success of Akeso's Harmony 2 study, this is the second instance where Ivanissimat-based regimens have demonstrated significant benefits in frontline treatment in non-small cell lung cancer.

Speaker Change: Following the success of the cast as harmony to study. This is the second instance, where <unk> based regimens have demonstrated significant benefits in frontline treatment in non small cell lung cancer. The full dataset for harmony six is planned to be presented at an upcoming major medical conference later this year.

Robert Duggan: The full data set for Harmony 6 is planned to be presented at an upcoming major medical conference later this year.

Robert Duggan: Turning to our own global phase three trials, we expect top line data in mid 2025 from Harmony, our global phase three trial in patients with EGFR mutated advanced non-small cell lung cancer who have progressed after treatment with a third generation EGFR tyrosine kinase inhibitor. Reminder, Harmony is Summit's first global registrational Phase III trial and received Fast-Track designation from the U.S. We are also excited to see progress and the expansion of our administrative studies through collaborations with leading organizations for which McKee will provide additional. We will provide details.

Speaker Change: Turning to our own global Phase III trials, we expect top line data in mid 2025 from harmony, our global Phase III trial in patients with Egfr mutated advanced non small cell lung cancer, who have progressed after treatment with a third generation Egfr tyrosine kinase inhibitor.

Speaker Change: As a reminder, harmony as summit's first global Registrational Phase III trial and received fast track designation from the U S. FDA. We are also excited to see progress in the expansion of our <unk> studies through collaborations with leading organizations for which <unk> will provide additional data.

Speaker Change: We will provide details in the future on additional catalysts, including top line results from our first Registrational phase III harmony trial, and our clinical development plans beyond non small cell lung cancer, both of which will be provided later in 2025 Mckee will further discuss these accomplishments driving our.

Robert Duggan: for the Future on additional catalysts, including top-line results from our first Registrational Phase III Harmony Trial and our clinical development plans beyond non-small cell lung cancer, both of which will be provided later in 2025. McKee will further discuss these accomplishments, driving our strong, unyielding belief in what can be accomplished by Team Summit and our conviction in the potential of Ivanissimap. We are a mission- and purpose-driven organization with the collective goal to improve quality of life, increase potential duration of life, and resolve serious medical needs. We believe we have the right team and the right molecule and Ivanissimap to realize this goal.

Ron: Ron Unyielding belief and what can be accomplished by teams summit and our conviction in the potential of <unk>. We are a mission and purpose driven organization with the collective goal to improve quality of life and increased potential duration of life and resolved a serious medical needs. We believe we are.

Ron: The right team and the right molecule agonist to realize this goal not only do we have the right team. We have the right partner encourage displayed by Vishal Shah and Casco team to conduct a head to head study against <unk> was rewarded by the results and well deserved second approval for <unk>.

Robert Duggan: Not only do we have the right team, we have the right partner. The courage displayed by Michelle Shaw and the ACASO team to conduct a head-to-head study against Pembroke was rewarded by the results and well-deserved second approval for Ivanissimap in China. However, it also served to raise the awareness of Ivanissimap globally when Ivo became the first drug to demonstrate an improvement head-to-head in a Phase III trial versus Pembroke. Blockbuster drug development takes courage. Kesow has demonstrated this courage on more than a few occasions, unlike many companies that have tried to, but failed.

Ron: However, it also serve to raise the awareness of <unk> globally. When <unk> became the first drug to demonstrate an improvement head to head in a phase III trial versus Pembroke blockbuster drug development takes courage and cast. So has demonstrated this courage on more than a few occasions.

Ron: Unlike many companies that have tried to book sales with that I will turn the call over to Mickey for additional context and recent highlights for your consideration.

Mahkam Zanganeh: With that, I will turn the call over to Maikeet for additional context and recent highlights for your consideration. Maikeet, are you ready to jump in? Thank you, Bob, and good afternoon, everyone. As Bob said, I remain incredibly enthusiastic about the future of Summit and the possibilities of what can be accomplished with our lead candidate, Avanesh.

Mickey: Ready to jump in thank you, Bob and good afternoon, everyone.

Speaker Change: Bob said I remain incredibly enthusiastic about the future of summit and the possibilities of what can be accomplished with our lead candidate <unk>.

Mahkam Zanganeh: Especially as we approach our first global phase 3 readout and begin to grow our commercial Before providing some additional detail and reviewing the current pipeline, I would like to highlight our current progress in developing Agonesimap and dive a bit deeper on a few concepts that Bob touched upon. Since 2019, more than 2,300 patients have been treated in clinical trials with ibuprofen. currently combined between our partners at Equeso and our team at Summit. Four phase three trials have completed enrollment, three of which have had top-line data read out, and the other, the summit-sponsored Harmony trial, we expect top-line data in the middle of.

Speaker Change: Especially as we approach our first global phase III readout and begin to grow our commercial team before providing some additional detail and reviewing the current pipeline I would like to highlight our current progress in developing our lending team up and dive a bit deeper on a few concepts that Bob touched up here.

Speaker Change: Since 2019 more than 2300 patients have been treated in clinical trials. We died when it came out.

Speaker Change: Currently combined between our partners at AK steel and our team at summit.

Speaker Change: Four phase III trials have completed enrollment three of which have had top line data read outs and the other semi sponsored harmony trial, we expect topline data in the middle of this year.

Mahkam Zanganeh: Five phase three trials are currently ongoing. Two of these are Summit-sponsored trials in first-line non-small cell lung cancer, and three are a Keso-sponsored trial studying Ibanezimab in head and neck, biliary tract, and triple negative breast cancer. Akeso has also announced its intention to conduct phase 3 clinical trials in pancreatic cancer as well as immunotherapy, refractory, non-small cell lung cancer patients. With the addition of these trials, the cumulative number of phase three trials for ibonosema that have been announced are ongoing or have completed is now 11. On top of this, a significant amount of relevant data is being generated in additional indications, including colorectal cancer, ovarian cancer, gastric cancer, and hepatocellular carcinoma to further support our broad platform cancer program.

Speaker Change: <unk> phase III trials are currently ongoing to ask these are semi sponsored trials in first line non small cell lung cancer and three <unk> sponsored trials studying <unk> in head and neck binary track and triple negative breast cancers.

Speaker Change: AK steel has also announced its intention to conduct phase III clinical trials in pancreatic cancer as well as immunotherapy refractory non small cell lung cancer patients.

Speaker Change: With the addition of these trials they come in at a number of phase III trials for <unk> that has been announced.

Speaker Change: Boeing or have completed is now 11.

On top of a significant amount of relevant data is being generated in additional indications, including colorectal cancer.

Speaker Change: Varian cancer, gastric cancer, and <unk> carcinoma to further support our broad platform cancer program.

Mahkam Zanganeh: Turning specifically to the Summit-sponsored Pipeline. Our first global phase 3 trial, Harmony, is evaluating ibanezimab in patients with EGFR mutant non-small cell lung cancer after progressing on a third generation TKI such as osmotic While this is a limited market opportunity compared to front-line treatment for non-small cell lung cancer, Harmony represents our initial fast-to-market strategy with Ibanez. Historically, PD-1 inhibitors, including Pembroke, have tried and failed to demonstrate a benefit in PFS or OS in the EGFR mutant non-small cell lung cancer. This provides Ibanezema the opportunity to differentiate itself from current PD-1 therapies as well as a novel mechanism and a new treatment option for patients.

Speaker Change: Turning specifically to the summit sponsored pipeline.

Speaker Change: Our first global Phase III trial harmony is evaluating <unk> in patients with Egfr mutant non small cell lung cancer. After progressing on a third generation PKI such as putting us in March and April while this is a limited market opportunity compared to frontline treatment for non small cell lung cancer.

Speaker Change: <unk> represents our initial fast to market strategy with Cmos.

Speaker Change: <unk> PD, one inhibitors, including Pembroke have tried and failed to demonstrate a benefit in PFS or OS in the Egfr mutant non small cell lung cancer setting.

Speaker Change: This provides <unk> the opportunity to differentiate itself from current PD, one therapies as well as in Nobel mechanics, and a new treatment option for patients.

Mahkam Zanganeh: The enrollment for the Harmony trial completed in October of last year and top-line data is expected mid-2025. This data is expected to contain data associated with both primary endpoints, progression-free survival and overall survival. Subsequently, we started two additional global phase 3 studies, Harmony 3 and Harmony 7, which both evaluate Ibanezumab head-to-head versus Pembro, either with or without chemotherapy. Frontline, Nance Marcello. Harmony T evaluates Ibonicimab in combination with chemotherapy and Harmony 7 evaluates Ibonicimab as well. Last October, Harmony Tree was amended by significantly expanding the addressable patient population to include all frontline metastatic non-small cell lung cancer patients without driver mutations by including patients with non-squamous tumors in addition to With this amendment, Harmony 3 is now an all-comer study from a histology perspective and a PD-L1 expression perspective in frontline non-small-cell lung cancer, covering an addressable patient population.

Speaker Change: The enrollment for the harmony trial completed in October of last year and top line data is expected to meet 2025.

Speaker Change: These data is expected to contain data associated with both primary endpoints progression free survival and overall survival.

Speaker Change: Subsequently, we started two additional global phase III studies harmony tree, and harmony, seven which both evaluating <unk> head to head versus camera, either with or without chemotherapy in frontline non small cell lung cancer harmony to evaluate <unk> in combination with.

Speaker Change: Chemotherapy and harmony seven evaluate our new semi as monotherapy.

Speaker Change: Last October harmony tree was amended by significantly expanding the addressable patient population to include all frontline metastatic non small cell lung cancer patients, we don't driver mutations by including patients with non squamous tumors. In addition to squamous tumors with this amendment harmony tree.

Speaker Change: He is now an all commerce study from a histology perspective, and a PDL one expression perspective in frontline non small cell lung cancer, covering an addressable patient population two to three times larger than prior to the amendment as a reminder.

Mahkam Zanganeh: As a reminder, this trial enrolls patients irrespective of PD-L1 expression, including those patients whose tumors do not express PD-L1. Additionally, we have now begun enrolling patients in Harmony 7 as we continue to activate clinical trial sites in the United States and will expand beyond the U.S.

Speaker Change: Under this trial enrolls patients irrespective of PDL, one expression, including those patients whose tumors do not express PD one.

Speaker Change: Additionally, we have now begun enrolling patients in harmony seven as we continue to activate clinical trial sites in the United States and will expand beyond the U S. In the coming two months.

Mahkam Zanganeh: in the coming Later this year, we expect to announce additional details expanding our clinical development plan around ivermectin map, including beyond lung cancer. We continue to receive strong interest for investigator-sponsored trials, including the most recent open window which closed just two weeks ago. To date, we have approved over 30 ISDs with a review of meaningful submissions from the last window to be performed shortly. These collaborations enhance our sponsored clinical development. and can show signals in settings where Ibanisibab has not yet been explained.

Speaker Change: Later this year, we expect to announce additional details expanding our clinical development plan around lithium up including beyond lung cancer.

Speaker Change: We continue to receive strong interest for investigator sponsored trials, including in our most recent open window, which closed just two weeks ago to date, we have approved over Turkey, Isps with a review of meaningful submissions from the last window to be performed shortly these collaborations and hence.

Speaker Change: Our sponsored clinical development activities and can show signals in settings, where <unk> has not yet been explored.

Mahkam Zanganeh: Our strategic collaboration with MD Anderson, which commenced in July 2024, now has two studies that are activated and are enrolling in Houston with either cutaneous squamous cell carcinoma or glioblastoma. We committed $15 million to this collaboration to quickly discover additional opportunities for ibonicemab, including several tumor settings outside of this current development plan, as well as the possibility of identifying biomarkers through additional research activities. Separately, we continue to support investigator-sponsored trials or ISDs, two of which have begun enrolling at the Memorial Sloan Kettering Cancer Center and Dana-Farber Cancer Center.

Speaker Change: Our strategic collaboration with MD Anderson, which commenced in July 2024, now has two studies that are activated and are enrolling in Houston.

Speaker Change: Catenulate squamous cell carcinoma glioblastoma.

We are committed 15 million to these collaborations to quickly discover additional opportunities for <unk>, including several tumor settings outside of this current development plan as well as the possibility of identifying biomarkers through additional research activities.

Speaker Change: Separately, we continue to support investigator sponsored trials or isds, two of which have begun enrolling at the memorial Sloan Kettering Cancer Center, and Dana Farber Cancer Institute we.

Mahkam Zanganeh: We are also looking forward to the initiation of clinical trials as part of our collaboration with Pfizer, which are expected later this year. This collaboration allows us to quickly advance beyond our current promising late-stage development plan to evaluate Ibonicima in combination with some of the most innovative ADCs from Pfizer will be responsible for the operations and costs associated with these trials, Summit will provide Advanesima, and both parties will jointly oversee the study. As you recall, Ibanezema brings two highly validated targets together into one novel bispecific antibody that targets both PD-1 and VGEF and holds a meaningful lead in terms of time and data generation in the clinical development of this novel class of therapy.

Speaker Change: We are also looking forward to the initiation of clinical trials as part of our collaboration with Pfizer, which are expected later this year. These collaborations allow us to quickly advance beyond our current promising late stage development plan to evaluate <unk> in the nation with some of the most innovative adcs.

Speaker Change: Fraser.

Speaker Change: Pfizer will be responsible for the operations and costs associated with these trials summit will provide advanced Cmos and both parties will jointly oversee their studies.

Speaker Change: As you recall I only see Matt brings to highly validated targets together into one novel bi specific antibody that targets, both PD, one and VEGF and hold a meaningful need in terms of time and data generation and the clinical development of this novel class of compounds.

Mahkam Zanganeh: Next, I would like to review some of the catalysts that we previously announced for this. As we touched on a moment ago, we are anticipating Harmony top line data we expect will include data related to both primary endpoints of progression-free survival and overall survival. This will be the first global phase 3 clinical trial readout for Iobinazumab which will provide information related to clinical profile of Iobinazumab beyond China as well as data that may lead to a potential path to applying for marketing authorization in our territories including the United States. As we stated previously, trial was conducted with patients whose non-small cell lung cancer was positive for EGFR mutations and had progressed after third generation TKI therapy.

Speaker Change: Next I would like to review some of the catalysts that we previously announced for this year.

Speaker Change: As we touched on a moment ago, we are anticipating harmony topline data in mid 2025.

Speaker Change: We expect will include data related to both primary endpoints of progression free survival and overall survival. This will be the first global phase III clinical trial read out for <unk>, which will provide information related to clinical profile of I've only seen might be on China as well as data that's may lead to a potential pause.

Speaker Change: So applying for marketing authorization in our territories, including the United States. As we stated previously this trial was conducted with patients whose non small cell lung cancer was positive for the Egfr mutations and had progressed after a third generation <unk> therapy. This is setting.

Mahkam Zanganeh: This is a setting where PD-1 inhibitors, including Pembroke, have failed to show an improvement in either progression-free survival or overall survival, providing an opportunity to demonstrate the differentiated mechanism of action for ibonesema beyond currently available immunotherapy options. As a reminder, this study contains a subset of patients from the Harmony-A study conducted by Ekeso in China, who received a third-generation EGFR TKI. Harmony-A led the first approval and commercial launch of Ibanezumab in China EGFR Meetings, North Small Cell Long-Calf. Additionally, Harmony Six, as a catalyst event, is intended to answer a proposed question as to whether the PFS benefits with Ibanezima monotherapy compared to PD-1 monotherapy would carry over to chemo combination setting.

Speaker Change: Where PD, one <unk>, including Pembroke at failed to show an improvement in Idaho progression free survival or overall survival, providing an opportunity to demonstrate the differentiated Mccann. This fall for <unk> beyond currently available immunotherapy auctions as a reminder, this study contained.

Speaker Change: Set of patients from the harmony a study conducted by <unk> in China, who received a third generation Egfr Teekay I Eharmony, a led the first approval and commercial launch of <unk> in China in patients with Egfr mutant non small cell lung cancer.

Speaker Change: Additionally, harmony six as a catalyst event is intended to answer a proposed question as to whether the PFS benefit seen with <unk> monotherapy compared to PD, one monotherapy with carry over to chemo combination settings. In this case in front line non small cell lung cancer.

Mahkam Zanganeh: Case in Frontline Non-Small Cell Lung as was announced. In Harmony 6, Ibanezimab in combination with chemotherapy achieves statistically clinically meaningful PFS benefit over Tislazumab in combination with chemotherapy in frontline patients with squamous non-small cell lung cancer patients. This map is a standard of care anti-PD-1 therapy in China and Europe, and PD-1 or PD-L1 therapy plus chemotherapy is standard of care for first-line patients. without driver mutations in a non-small cell lung cancer in nearly all major markets globally.

As was announced last week in harmony six <unk> in combination with chemotherapy achieves statistically and clinically meaningful PFS benefit over <unk> in combination with chemotherapy in frontline patients with squamous non small cell lung cancer patient.

Speaker Change: This list is the map is a standard of care anti PD, one therapy in China, and Europe, and PD, one or PDL, one therapy, plus chemotherapy standard of care for first line patients without driver mutations in a non small cell lung cancer in nearly all major markets globally.

Mahkam Zanganeh: The Full Harmony 6 dataset is planned to be presented at a major medical meeting later this year. Finally, data from the Harmony 2 trial conducted by our partners at EKSO in China provide insights regarding the how the benefits seen with Ibanez. in China. After its groundbreaking PFS benefit over monotherapy PEMBRO, an early look at OS requested by the health authorities in China showed a strongly positive overall survival trend with a hazard ratio of 0.777 at 39% data maturity. applying a potential decrease of more than 22% in the risk of death for those patients receiving Ibanezimab compared to Pembroke.

Speaker Change: Therefore harmony six data set is planned to be presented at a major medical meeting later this year.

Speaker Change: Finally data from the harmony to trial conducted by our partners at AK steel in China provide insights regarding to how the benefits seen with <unk> in progression free survival can translate to overall survival.

Speaker Change: After its ground breaking PFS benefit over mono therapy, Pembroke and early look at OS requested by the health authorities in China showed a strongly positive overall survival trend with a hazard ratio of 0.777 at 39% data.

Speaker Change: <unk>, implying a potential decrease of more than 22% and the risk of death for dose patients receiving <unk> compared to Pembroke.

Mahkam Zanganeh: I would like to pause a moment to expand on these results. The early interim analysis for Harmony 2 was conducted at the request of the Chinese health authorities during the review of the study overall, which led to the second approval and label expansion for Ibonecimab. This early look was conducted at just 39% data maturity in the trial. Because it was conducted at the request of the health authorities and had so few total events, the alpha allocated to this analysis was minimal at 0.0001. When we say alpha, this is statistical nuance, but effectively, the goal was to provide the planned interim analysis and final analysis with the best statistical chance of success.

Speaker Change: I would like to pause a moment to expand on these results. The early interim analyses for harmony too was conducted at the request of the Chinese health authorities. During the review of the study overall, which led to the second approval and label expansion for <unk> in China.

Speaker Change: This early look was conducted at just 39% data maturity in the trial.

Speaker Change: It was conducted at the request of the health authorities and had so few total events. The alpha allocated to this analysis was minimal at zero point zero zero zero what.

Speaker Change: When we say Alfa this is statistical nuance, but effectively the goal was to provide the planned interim analysis and final analysis with the best statistical chance of success.

Mahkam Zanganeh: Recall, as well, that this trial was sufficiently powered to show a statistically significant PFS benefit. In order to gain approval in China, which it has already It was not powered, and the design was not intended to show a statistically significant OS. when considering what an early look at OS requested by the Chinese health authority. View Relative Events in the Trial Not Powered for Overall Survival Statistical significance was not part of our considerations, focus, or expectations as indicated by ACASO's Minimal Alpha Spent.

Speaker Change: Recall as well that this trial was sufficiently powered to show a statistically significant PFS benefit in order to gain approval in China, which it has already done it was not powered and the design was not intended to show a statistically significant OS benefit.

Speaker Change: When considering what an early look at always requested by the Chinese health authorities, we feel relative events in the trial not powered for overall survival means statistical significance was not part of our consideration forecast or expectations as indicated by a queso.

Speaker Change: Alpha spent.

Mahkam Zanganeh: As we previously announced, a planned interim analysis is expected roughly by the end of Year, which will have a greater number of OS events. Note that Harmony 7, our global study of frontline patients. PDL-1 High-Expressing Non-Small Cell Lung Cancer, which intends to enroll 780 patients, nearly double the enrollment of Harmony 2, is sufficiently powered to show a benefit in both PFS and OS. Context matters. What this health authority requested interim analysis did show was that at this early stage, an early look at the data, if you will, overall survival already shows a strongly positive trend that is clinically.

Speaker Change: As we previously announced a planned interim analysis is expected at roughly by the end of this year.

Speaker Change: Yes, which will have a greater number of OS events note that harmony seven our global study of frontline patients with PDL, one high expressing non small cell lung cancer, which intends to enroll 780 patients nearly double the enrollment of harmony too is sufficiently powered to show.

Speaker Change: <unk> a benefit in both PFS and OS context matters here.

Speaker Change: What is health authority requested interim analysis did show was that at this early stage and early look at the data. If you will overall survival already shows a strongly positive trend that is clinically meaningful if harmony seven were to show a similar result at its final always analogy.

Mahkam Zanganeh: If Harmony7 were to show similar results at its final OS analysis, it is highly probable that this would result in a statistical significant overall survival benefit being achieved. This first look at overall survival data for Harmony 2, combined with a strong PFS result in Harmony 6, is remarkable. This data, in totally with previously disclosed data for Harmony A and PFS data for Harmony 2, as well as the earlier phase trials in and outside of non-small cell lung cancer conducted by AKSO, further validate that Ivanissimab is mechanistically from PD-1 inhibitors and has the potential to make a meaningful positive impact for patients facing difficult cancer diagnosis.

Speaker Change: It is highly probable that this would result in a statistically significant overall survival benefit being achieved.

Speaker Change: These first look at overall survival data for harmony to combined with a strong PFS result in harmony six is remarkable these data in totally with previously disclosed data for harmony and PFS data for harmony too as well as the earlier phase trial in and outside of non small cell lung cancer conducted by Ey.

Speaker Change: So further validate that I've only semi is mechanics, particularly distinct from PD, one <unk> and has the potential to make a meaningful positive impact for patients facing difficult cancer diagnosis.

Mahkam Zanganeh: We are thrilled with the data released last week in both the statistically significant PFS results from the first interim analysis in Harmony 6 and the early look requested by NPA at survival in Harmony 6.

Speaker Change: With the data released last week and both the statistically significant PFS results from the first interim analysis in harmony six and the early look requested by and NPA at survival in harmony too.

Mahkam Zanganeh: I am speaking with the key opinion leaders. We have received very positive feedback. Our KOLs are highly encouraged by the potential of our network. This is consistent with the published feedback of multiple top Taurasi KOL in media articles over the past year.

Speaker Change: In speaking with key opinion leaders, we have received very positive feedback our kols are highly encouraged by the potential of an inch smart. This is consistent with the published feedback of multiple top toward IC Kols and media articles over the past week.

Mahkam Zanganeh: Additionally, ECKESO continues to enroll multiple Phase III clinical trials, including biliary tract cancer, pancreatic cancer, triple negative breast cancer, and head and neck cancer, and intends to launch an additional Phase III study in second-line or later non-small cell lung cancer after progression on immunotherapy.

Speaker Change: Additionally, AK steel continues to enroll multiple phase III clinical trials, including by Larry tract cancer, pancreatic cancer triple negative breast cancer, and head and neck cancer and intends to launch and additional phase III study in second line or later non small cell lung cancer after progression on immunotherapy.

Mahkam Zanganeh: Now I would like to take a moment to review study design for our two ongoing global phase three trials, Harmony 3 and Harmony 7. For those on the webcast, this slide shows the study designed for Harmony3. Harmony3 is a randomized, double-blind, global phase 3 clinical trial evaluating. in combination with chemotherapy against PEMBRO, in combination with chemotherapy as first-line treatment for patients with metastatic non-small cell... This trial includes patients with squamous or non-squamous histology, with no active variation. Activating genomic alterations regardless of PD-L1 expression including high, low, and negative PD-L1 expression. Your primary endpoints for Harmony 3 include progression-free survival and overall survival, and results will be stratified by squamous and non-squamous histology.

Speaker Change: Now I would like to take a moment to review study design for our ongoing global phase III trials harmony, three and <unk> seven.

Speaker Change: For those on the webcast. The slide shows the study design for harmony treat harmony tree is a randomized double blind global phase III clinical trial evaluating <unk> in combination with chemotherapy against <unk> in combination with chemotherapy as first line treatment for patients with metastatic non small cell lung cancer. This trial include.

Patients with squamous or non squamous histology with no activating activating genomic alteration, regardless of PD lone expression, including high low and negative PD lone expressing tumors.

Speaker Change: You all primary endpoints for Armani, three includes progression free survival and overall survival and results would be stratified by squamous and non squamous histology.

Mahkam Zanganeh: As we have discussed, Harmony Six, from our partner Ekeso in China, met its primary end point, achieving statistically...

Speaker Change: As we have discussed harmony six from our partner <unk> in China met its primary endpoint, achieving statistically significant and clinically meaningful improvement in progression free survival for <unk>, which came off therapy against PD, one therapy, which chemotherapy in frontline treatment of patients with squamous non small cell lung cancer.

Mahkam Zanganeh: Thank you very much We look forward to the full Harmony 6 data set being presented at the major medical conference later.

Speaker Change: Or regardless of PDL one expression. This results from <unk> trial conducted in China further validate our conviction in the potential for this study we look forward to the full harmony six data sets being presented at a major medical conference later this year.

Mahkam Zanganeh: Next, we have the study designed for Harmony 7, a randomized double-blind global phase 3 clinical trial evaluating avanissimab monotherapy against Pembroke. Monotherapy as first-line treatment for metastatic non-small cell lung cancer patients with tumors with high PD-L1 expression. Dual primary endpoints for Harmony 7 include progression-free survival, and overall survival and results will be stratified by squamous and non-squamous histologies. As a reminder, our Harmony 7 study shares similarity with the EKSO-sponsored Harmony 2 Phase 3 trial, but focuses on those patients whose tumors have a high PD-L1 expression, for which monotherapy PEMBRO is a current standard of care in the United States and other major Western markets.

Speaker Change: Next we have the study design for <unk> <unk> seven a randomized double blind global phase III clinical trial evaluating <unk> monotherapy against Hambro monotherapy as first line treatment for a metastases non small cell lung cancer patients with tumors with high PD Lone expression dual primary endpoints for harmony.

Speaker Change: Seven includes progression free survival and overall survival and results will be stratified by squamous and non squamous histology as a reminder, our harmony seven study shared similarity with the Aircastle sponsored harmony two phase III trials, but focuses on those patients with.

<unk> tumors have a high PD lone expression for reach monotherapy Pembroke is a current standard of care in the United States and other major western market.

Mahkam Zanganeh: Turning to the market opportunity, Iobinizumab has the potential to be a platform blockbuster drug and is well-positioned to make a significant impact across the treatment landscape of non-small cell lung cancer and beyond. In non-small cell lung cancer alone, there are a combined seven announced or ongoing phase three study conducted by either ECKES or Summit. According to third-party research, including T.D. Cohen and others, the non-small cell lung cancer addressable market is expected to approach $20 billion for checkpoint inhibitors With the recent data announced by our partner ECKESO in China, our belief is further validated in the potential for Iobinizumab to make a significant difference for patients with non-small cell lung cancer.

Speaker Change: Turning to the market opportunity I want to say Bob has the potential to be a platform blockbuster drug and is well positioned to make a significant impact across the treatment landscape of non small cell lung cancer and beyond in non small cell lung cancer alone. There were a combined seven announced or ongoing phase III study conducted by either HSR summit According to <unk>.

Speaker Change: <unk> Party research, including TD, corn, and others. The non small cell lung cancer addressable market is expected to approach 20 billion for checkpoint inhibitors with our recent data announced by our partner <unk> in China. Our belief is further validated in a potential for <unk> to make a significant difference for patients with non small cell.

Mahkam Zanganeh: Beyond Non-Small Cell Lung Cancer Across All Checkpoint Ages. The Addressable Market Approaches $90 Billion Globally in Future Years, according to IQVIA Research. But as we have been discussing, while the Checkpoint Inhibitor Market Opportunity Stick The potential opportunity that I just mentioned does not include the full impact that Ionisimab could have, given it has shown promising data in multiple tumor types where checkpoint inhibitors have not been affected. Includes macrosatellite-stable colorectal cancer, PD-L1 low and negative triple negative breast cancer, and EGFR mutant non-small cell lung cancer after targeting. Targeted Therapy Based on the Phase 2 Studies Conducted by In total, there are more than 50 indications where PD-1, PD-L1, or VGS therapies have been approved.

Speaker Change: Cancer beyond non small cell lung cancer across all checkpoint inhibitors and indications the addressable market approaches 90 billion globally and further in future years. According to <unk> research.

Speaker Change: But as we have been discussing while the checkpoint inhibitor market opportunity is significant the potential opportunity that I. Just mentioned does not include the full impact that I want to see Bob could have given it has shown promising data in multiple tumor types, where checkpoint inhibitors have not been effective.

Speaker Change: These include microsatellite stable colorectal cancer, PD, lone low or negative triple negative breast cancer in Egfr mutant non small cell lung cancer after targeting targeted therapy based on the phase II studies conducted by <unk>.

Speaker Change: In total there are more than 50 indications, where PD one PDL one or we just had our PS have been approved all areas for you when it came out to potentially offer patients with cancer.

Mahkam Zanganeh: All areas for Ibanezimab to potentially offer patients with cancer and Abonissima will continue to be appropriately, rapidly tested and developed beyond non-sponsored I continue to applaud the work of TAFE Summit and its rapid advancement in the development of iobinazumab, which only two years ago began to open the first clinical site ever in the United States for iobinazumab.

Speaker Change: Improved treatment option.

Speaker Change: <unk> would continue to be appropriately rapidly tested and develop beyond non small cell lung cancer <unk>.

Speaker Change: I continue to applaud the award update summit and its rapid advancement in the development of high when it came up which only two years ago began to open the first clinical site ever in the United States, we're going to see Marc B.

Mahkam Zanganeh: We persistently evaluate opportunities to accelerate our timeline in bringing additional therapeutic options to patients with high unmet cancer needs and look forward to upcoming announcements regarding expansions to our clinical development program.

Speaker Change: Persistently evaluate opportunities to accelerate our timeline and bringing additional therapeutic options to patients with high unmet cancer needs and look forward to upcoming announcements regarding expansions to our clinical development pipeline with that update I would now osmond mutual provide details on our financial and operational.

Manmeet Soni: With that update, I will now ask Manmeet to provide details on our financial... Thank you, Micky, and good afternoon, everyone. We issued this afternoon our earnings release for the first quarter of 2025. Today, in addition to providing you with an update on our cash position and operating expenses, I will also provide you color on our clinical, commercial, and manufacturing operations. Let me start with an update on the clinical operation. As Mickey mentioned earlier, expanded Harmony 3 clinical trial during the fourth quarter of 2024 to add non-squamous patients. We are very pleased with the rate of enrollment across the Harmony 3 trial for both squamous and non-squamous patients in the United States and Europe.

Speaker Change: Update.

Speaker Change: Thank you Mickey and good afternoon, everyone.

Speaker Change: We issued this afternoon, our earnings release for the first quarter of 2025.

Speaker Change: Today in addition to providing you with an update on our cash position and operating expenses I will also provide you color on our clinical commercial and manufacturing operations.

Speaker Change: Let me start with an update on the clinical operations front.

Speaker Change: As Mick mentioned earlier, we expanded how many three clinical trial during the fourth quarter of 2024th to add non squamous patients.

Speaker Change: We are very pleased with the rate of enrollment across the hanmi through trial for both squamous and non squamous patients.

Speaker Change: United States and Europe.

Manmeet Soni: In addition, very recently in 2025, we have initiated enrollment for patients in Harmony 7 clinical trial in the United We expect to initiate enrollment for the other regions during the next quarter based on the regulatory clearances to begin activating sites later this quarter.

Speaker Change: In addition, very recently in 2025, we have initiated enrollment for patients and how many seven clinical trial in the United States.

Speaker Change: We expect to initiate enrollment for the other regions during the next quarter based on the regulatory clearances to begin activating sites later this quarter.

Manmeet Soni: With our expected top-line results from Harmony Trial during middle of this year, we have initiated preparations for our first potential commercial launch of Havana's Mask.

Speaker Change: With our expected top line results from harmony trial during middle of this year, we have initiated preparations for our first potential commercial launch of honest mob.

Manmeet Soni: Recently strengthened our leadership team with the appointment of Robert Lacaze as our Chief Commercial Officer. Robert is a seasoned biopharmaceutical executive with over 30 years of extensive leadership. Commercial Strategy, and Prior to joining Summit, he held senior positions at major pharmaceutical companies including Bayer Healthcare and Bristol Myers. With a proven track record of launching and growing blockbuster oncology franchises, Robert joins our team at the right time as we continue to refine our commercial strategy and expand our capabilities.

Speaker Change: We recently strengthened our leadership team with the appointment of Robert luck, guys as our Chief commercial officer.

Speaker Change: Robert is a seasoned biopharmaceutical executive with over 30 years of extensive leadership experience and commercial strategy and execution.

Speaker Change: Yes.

Speaker Change: Prior to joining summit he held senior positions at major pharmaceutical companies, including Bayer healthcare and Bristol Myers.

Speaker Change: With a proven track record of launching and growing blockbuster oncology franchises Robert joins our team at the right time as we continue to refine our commercial strategy and expand our capabilities.

Manmeet Soni: In addition to Robert, we have also hired key hires for market access, marketing and sales to optimize the commercial launch strategy. On the drug manufacturing front, in addition to our current supply source for imanisimab from Acaso, our collaboration partner, we have made significant progress in transferring relevant know-how to certain third-party contract manufacturers in our licensed territory.

Speaker Change: In addition to Robert we have also hired key higher spot market exists marketing and sales.

Speaker Change: The commercial launch strategy.

Speaker Change: On the drug manufacturing front. In addition to our current supply source bought a modest amount from our castle. Our collaboration partner, we have made significant progress in transferring relevant knowhow to certain third party contract manufacturers and our licensed territory.

Manmeet Soni: Also, we are very pleased with the first approval of Akeso's PD-1 inhibitor, Penpolimab, by the USFDA, which demonstrates Akeso's capability to adhere to global manufacturing and quality standards.

Speaker Change: Also we are very pleased with the first approval of a <unk> PD one inhibitor than pull about by the U S FDA, which demonstrates our gives us capability to adhere to global manufacturing and quality standards.

Speaker Change: Yeah.

Manmeet Soni: On the financials front, let me start with our cash. We ended the first quarter of 2025 with a strong cash position of approximately $361 million. Let me remind you that we paid off our debt in entirety during the fourth quarter of 2024 and are now debt free.

Speaker Change: On the financial front, let me start with our cash position.

Speaker Change: The first quarter of 2025 with a strong cash position of approximately $361 million.

Speaker Change: Let me remind you that we paid off our debt and <unk> during the fourth quarter of 2024 and are now debt free.

Manmeet Soni: Turning to operating expenses, I'll provide details on both GAAP and non-GAAP numbers. And refer to our press release issued this afternoon for a reconciliation of GAAP to non-GAAP financial institutions. As a reminder, non-GAAP expenses exclude stock-based compensation Our GAAP R&D expenses during the first quarter of 2025 were $51.2 million compared to $51.4 million for the fourth quarter of 2024. and non-GAAP R&D expenses were $47.1 million for both first quarter 2025 and for the fourth quarter of 2024. Our GAAP R&D expenses for the first quarter of 2025 remain flat as compared to the last quarter of 2025.

Speaker Change: Turning to operating expenses I will provide details on both GAAP and non-GAAP numbers you can refer to our press release issued this afternoon for a reconciliation of GAAP to non-GAAP financial measures.

Speaker Change: As a reminder, non-GAAP expenses exclude stock based compensation expenses.

Speaker Change: Our GAAP R&D expenses during the first quarter of 2025 were $51 2 million compared to $51 4 million for the fourth quarter of 2024.

Speaker Change: Our non-GAAP R&D expenses were $47 1 million for both fourth quarter 2025, and for the fourth quarter of 2024.

Speaker Change: GAAP R&D expenses for the first quarter of 2025 remained flat as compared to the last quarter of 2024.

Manmeet Soni: Our GAAP, G&A expenses during the first quarter of 2025 were $15.6 million. Compared to $14.2 million for the fourth quarter of 2024. and non-GAAP G&A expenses were $8.6 million during the first quarter of 2025, compared to $7.5 million for the fourth quarter of 2025.

Speaker Change: Our GAAP G&A expenses during the first quarter of 2025 or $15 6 million.

Speaker Change: <unk> grew $14 2 million for the fourth quarter of 2024.

Speaker Change: Our non-GAAP G&A expenses were $8 6 million during the first quarter of 2025 compared to $7 $5 million for the fourth quarter of 2024.

Manmeet Soni: Our GAP-GNA expenses primarily... between Increase and Professional Services to support the development of awareness. Overall, our non-GAAP operating expenses during the first quarter of 2025 were $55.7 million compared to $54.6 million for the previous quarter. The increase in non-GAAP operating expenses were primarily related to an increase in G&A expenses as noted above.

Speaker Change: Our GAAP G&A expenses, primarily increased due to an increase in professional services to support the development of Atlantis them up.

Overall, our non-GAAP operating expenses during the first quarter of 2025, or $55 7 million compared to $54 $6 million for the previous quarter.

Speaker Change: The increase in non-GAAP operating expenses were primarily related to an increase in G&A expenses as noted above.

Dave Gancarz: And with that, I'll hand it back over to Dave. Thank you, Bob.

Dave Cars: And with that I'll hand, it back over to Dave.

Speaker Change: Thank you, Bob Mckee and Miami.

Unknown Executive: We will now see if there are any questions that our team can help answer. Please open the line for questions. As a reminder, if you'd like to ask a question, please press star and the number one on your telephone keypad. Again, that is star and the number one on your telephone keypad.

Speaker Change: We are now we will now see if there are any questions that our team can help answer.

Speaker Change: Justin Please open the line for questions.

Speaker Change: Thank you.

Speaker Change: As a reminder, if you'd like to ask a question. Please press star and the number one on your telephone keypad again that is star and the number one on your telephone keypad.

Solveen Richard: And with our first question comes from the line of Solveen Richard from Goldman Sachs.

Speaker Change: And with your first question comes from the line of Olivine Ritchie from Goldman Sachs.

Mark: The lines of Hey team, this is Mark on First Alibi and thank you so much for taking our question and congrats on the quarter. A couple questions on the upcoming Harmony EGFR dataset. So I think everyone's going to be focused on sort of the subgroup data to confirm if Ikezo's prior data generated in China translates to Western Russia. So, what do you believe the bar for success here is in this context? Like how closely does the data have to mirror Harmony A to support the translatability? And also, in the context of Ribervan's approval on Mariposa 2, what profile are you hoping to see from Harmony to, and sort of what level of benefit do you believe would convince docs to use Ivo and second line EGFR?

Speaker Change: The line is open.

Mark: Hey, Tim This is mark on first of all I mean, thank you so much for taking my question and congrats on the quarter.

Speaker Change: Couple of questions on the upcoming harmony Egfr dataset, I think everyone's going be focused on sort of the subgroup data to confirm it because those prior data generated in China translates to western regions. So what do you believe the bar for success here is in this context like how closely does the data have to mirror harmony as to support the translate ability.

Mark: And also in.

Mark: In the context of <unk> approval on Mariposa to profile are you, hoping to see from harmony.

Mark: Two and sort of what level of benefit do you believe would convince docs to use <unk> in second line as Youre far thanks.

Dave Gancarz: Thanks, Mark, for the question.

Speaker Change: Thanks, Marc for the question I'll give a couple of words, and then I'm going to hand, it over to Jack West our thoracic oncology lead I think in terms of.

Dave Gancarz: I'll give a couple words, and then I'm going to hand it over to Jack West, our thoracic oncologist. I think in terms of your first question, we're not going to necessarily prescribe a bar or a specific number that we're looking to achieve. I think the overall data package or the data package in the general. with the data that comes from China will be the important piece.

Speaker Change: Your first question, we're not going to necessarily prescribe a bar or a specific number that we're looking to achieve I think the overall data package consistency.

Speaker Change: Or the data package and the general consistency with the data that comes from China will be the important piece. The global consistency. If you will we're not interested in setting a bar that'll be part of the discussions with the agency.

Jack West: We're not interested in setting a bar that will be part of the discussions with the But with respect to the second part of the question, I'll hand that over to Hi, this is Jack West. So, I would comment that obviously the entire field of EGFR mutation positive non-small cell has become much more complex over the last couple of years with a lot of new options, but that still leaves plenty of open space for new choices. One would be that with the potential for amivantumab and lasertinib to be used in the first-line setting, that leaves a need for another option that is very appropriate for the Harmony platform to fill.

Jack West: But with respect to the second part of the question I'll hand that over to Jack.

Speaker Change: Hi, this is <unk>.

Speaker Change: <unk>, so I would comment that obviously the entire field of Egfr mutation positive non small cell has become much more complex over the last couple of years with a lot of new options, but that.

Speaker Change: That still leaves plenty of open space for four new choices, one would be that.

With the potential for Amazon to Mab and was hurt NIM to be used in the first line second setting that leave us.

Speaker Change: Need for another option that is very appropriate for the harmony platform to Phil obviously, that's not going to be everybody and there is.

Jack West: Obviously, that's not going to be everybody, and there's going to be patients who get osomertinib monotherapy or the FLORA2 approach with a combination of chemotherapy and osomertinib, but obviously amivantumab with chemo has a combination of efficacy with toxicity and reliability that looks very different from what chemo and ivanesimab offers. I have had extensive discussions with clinicians in all sorts of settings, academic and community-based, and there's really a strong sense that there's a value and a great need for alternatives that have a very different and potentially less challenging toxicity profile. Obviously, efforts are made in ways to ameliorate the toxicities with amivantumab, but there will always be a value in choices.

Speaker Change: Going to be patients, who get <unk> Martin.

Speaker Change: Monotherapy or the Florida to approach with a combination of chemotherapy and those Martin it but.

Speaker Change: Obviously, Amazon to Nab with chemo has a.

Speaker Change: A combination of.

Speaker Change: Efficacy with with toxicity liabilities that looks very different from <unk>.

Speaker Change: What chemo and <unk> all firms have had extensive discussions with cowen.

Speaker Change: Clinicians in all sorts of savings academic and community based and Theres really a strong sense that there is a value and a great need for alternatives.

Speaker Change: <unk> that have a very different and potentially less challenging toxicity profile. Obviously efforts are made in ways to ameliorate the toxicities with <unk>.

Speaker Change: <unk>, but.

Speaker Change: There will always be a value and choices.

Unknown Executive: That makes sense.

Speaker Change: That makes sense. Thank you.

Unknown Executive: Thank you.

Speaker Change: Thank you.

Yigal Nochomovitz: Our next question comes from the line of Yigal Nochomovitz. from C Group. The line's open. Hi. Hi, everyone. Thank you very much for taking the questions and congrats on the very positive recent developments. My question also on Harmony, could you just be more specific in terms of what will we see with respect to the geographic data, meaning China versus ex-China patients? Are we going to be getting separate hazard ratios on PFS and OS for each of these geographies? Would it be something in the form of a forest plot or would it just be some kind of a more qualitative statement around potential comparability?

Speaker Change: Our next question comes from the line of eager not so much.

Speaker Change: From Citigroup.

Speaker Change: Your line is open.

Speaker Change: Hi, Hi, everyone. Thank you very much for taking the questions and congrats on the very positive recent developments.

Speaker Change: My question also on harmony could you just be more specific in terms of what will we see with respect to the geographic data, meaning China versus ex China patients are we going to be getting.

Speaker Change: Separate hazard ratios on PFS and OS for each of these geographies would it be something in the form of a forest plot.

Speaker Change: Or would it just be some kind of a more a qualitative statement around potential comparability. That's my first question. Thank you.

Yigal Nochomovitz: That's my first question. Thank you.

Dave Gancarz: Thanks Yigal, this is Dave. I think I would break that down into two points, one of which You know, the true top line data, if you will, that typically will be a little bit more qualitative, right? Major medical That presentation, obviously, will have a bit more detail. It'll certainly give some context to geographic breakdowns, and a forest plot is certainly one way to do that. We'll make those final decisions, but the goal will be to give appropriate context with respect to the breakdowns. North American and European patients as compared to those Okay, thanks.

Dave Cars: Thanks, Hey, Kyle this is Dave.

Speaker Change: Thank you.

Kyle: I would break that down into two points, one of which is the true top line.

Speaker Change: Data if you will.

Speaker Change: That typically will be a little bit more qualitative right major medical conferences.

Speaker Change: Presentation, obviously, we will have a bit more detail. It will certainly give some context to geographic breakdowns in a forest plot is certainly one way to do that we will make those those final decisions, but the goal will be to give appropriate context with respect to the breakdowns between.

Speaker Change: North American and European patients as compared to those enrolled in China.

Speaker Change: Okay. Thanks.

Dave Gancarz: And then two more on Harmony. With respect to timing, you consistently said mid-2025. Is it fair to assume that we would see Harmony before we see Harmony 2 and Harmony 6, which you alluded to would be at the fall medical meetings? And then also with Harmony, what is your view on whether you need OS to be StatSig for a competitive filing in the United States? Thanks. Sure, with with respect to the timing of the, excuse me, the timing of the data. That will, that'll come down ultimately. which conference, especially in the fall, you know, takes which presentation and whatnot and some of that.

Speaker Change: And then two more on harmony with respect to timing.

Speaker Change: <unk> consistently said mid 2025 is it fair to assume that we would see harmony before we see harmony to an army six which you've alluded to at the fall medical meetings.

Speaker Change: And then also with harmony what is your view on whether you need <unk> to be stat Sig for competitive filing in the United States.

Speaker Change: Sure.

Speaker Change: With respect to the timing of the.

Speaker Change: The timing of the data releases that will that will come down ultimately to which conference, especially in the fall, it takes which which presentation and whatnot and some of that strategic in terms of.

Dave Gancarz: where and when that will be displayed. In terms of The timing across them, I don't know that we have a specific order in terms of one versus the other. What I would say is we would expect top line data for Harmony in Middle of 2025. You know, I would think by the time you get You know, ESMO, that's more in October, so you're a little later there. So I can't give you, Yigal, yet which conference, different data will go where, but there should certainly be at least top line before we get to... the end of Q3 beginning of Hopefully that's helpful.

Where and when.

Speaker Change: That will be displayed in terms of.

Speaker Change: The timing across them I don't know that we have a specific order in terms of one versus the other what I would say is we would expect top line data.

Speaker Change: For harmony in in the middle of 2025.

Speaker Change: I would think by the time you get into.

Speaker Change: Mo that's more in October so youre a little later, there so I can't give you <unk>, yet which conference with different data will go where boat.

Speaker Change: There should certainly be at least top line before we get to the.

Speaker Change: End of Q3 beginning of Q4.

Dave Gancarz: Can you repeat your second question, Yigal? Oh, I was just curious about the relative importance of hitting on OS in Harmony to have a competitive BLA final. Yeah, I think at this point, it's important to say, you know, we have two primary endpoints. We want to be clear on that. I think the other piece becomes the totality of the package. You know, importantly, I'll ask Jack or Allen to add any context here, but in the second line EGFR mutant non-small cell lung cancer space, POSA-TKI, overall survival hasn't been Dean, at this point to show us.

Speaker Change: Hopefully that's helpful.

Speaker Change: Can you repeat your second question Heiko.

Heiko: Oh I was just curious about the <unk>.

Heiko: Relative importance of hitting on OS and harmony to be hyper competitive.

Heiko: And BLA filing yes.

Heiko: I think at this point, it's important to say.

Heiko: We have two primary endpoints, we want to be clear on that I think the other piece becomes the totality of the package.

Heiko: Importantly, I'll I'll I'll ask.

Speaker Change: Jack Allen to add any context here, but in the second line Egfr mutant non small cell lung cancer space posted PKI overall survival hasnt been.

Speaker Change: At this point to show a statistically significant benefit in any regimen.

Allen Yang: and Benefit in any regimen, and so that would be part of the context, but importantly, you know, as you noted, we have two primary endpoints, so it'll be a total package.

Speaker Change: And so that'll be part of the context, but importantly, as you noted we have two primary endpoints. So it'll be a total package consideration there.

Allen Yang: Yeah, this is Allen Yang. Yigal, I don't have much to add except that, you know, the precedent in this space has not been – it's not been needed to hit OS to get an approval. Of course, we would like to show clear benefit for Ivanesimab in this space, but I think, you know, it's wonderful for patients that there's going to be multiple choices for them, as Jack alluded to. I think this is, unfortunately, a palliative setting, so I think a lot of things will go into the physician's mind about what to use, efficacy as well as toxicity profiles and so forth.

Speaker Change: Yes. This is Allen Yang.

Speaker Change: I don't have much to add except that.

Speaker Change: The precedent in this space has not been it's not been needed to hit OS to get an approval of course, we would like to show a clear benefit for <unk> in this space.

But I think it's wonderful for patients that theres going to be multiple choices for them as Jack alluded to I think this is unfortunately, a palliative settings. So I think a lot of things will go into the physicians' behind about what to use efficacy as well as toxicity profiles and so forth.

Yigal Nochomovitz: And maybe if I could just squeeze one in, maybe for you, Allen, or maybe Jack, you know, obviously the Pfizer partnership for the ADCs is great, however, that one is missing some of the, you know, the more perhaps relevant targets in non-small cell lung cancer, such as a TROP2 or HER2, HER3, so how are you thinking about that aspect of a longer-term strategy in lung cancer to combine potentially down the road with those types of ADCs? Yeah, Yigal, that's a great question. So, again, I think the landscape of cancer is changing very quickly, which is terrific.

Alan: And if I could just squeeze one in maybe for you Alan.

Speaker Change: Maybe Jack.

Speaker Change: Obviously, the Pfizer partnership for the ADC is great.

Speaker Change: However that one is missing some of the more perhaps relevant targets in non small cell lung cancers, such as <unk>, two or <unk>, two or three so how are you thinking about that aspect of our longer term strategy in lung cancer to combine potentially down the road with with those types of Adcs.

Speaker Change: Yeah.

Speaker Change: Yes, that's a great question. So again I think the landscape of cancer is changing very quickly, which is terrific. I think Pfizer is a great partnership to have a great pipeline of.

Jack West: I think Pfizer is a great partnership. They have a great pipeline of ADCs. We're not sort of wedded to the pipeline. We're open to it. You know, Ivan Esenbab is our only child, really, and so we are open to other collaborations as well. And so we continue to follow the lung cancer landscape, and we're open to whatever is the best treatment for our patients. And we, this is Jack West, we do have other combinations that are being evaluated and in potential development in settings like ISTs and even cooperative group efforts. So we're quite open to an array of options that will give us a lot of combination opportunities.

Speaker Change: Adcs.

Speaker Change: What sort of went into the pipeline we're open to it either in SMA is our is our only child really and so we are open to other collaborations as well and so we continue to follow the lung lung cancer landscape and we're open to whatever is the best treatment for patients.

Jack West: This is Jack question, we do have.

Jack West: Other combinations that are being evaluated and potential development.

Jack West: Settings, like <unk>, and even cooperative group effort so.

Jack West: We are quite open to an array of options that will give us a lot of combination opportunities.

Unknown Executive: Okay, thank you so much.

Jack West: Okay. Thank you so much.

Jack West: Thank you.

Corey Casimo: Our next question comes from the line of Corey Casimo from Evercore. Hey, good afternoon, guys. Thanks for taking the questions. I'll stick to two of them. I guess first one is for Harmony 2, you obviously showed pretty profound PFS benefits across all cuts of the data and histologies, everything else. Would you expect that to broadly hold for overall survival as well? And then I'll have a follow-up.

Speaker Change: Our next question comes from the line of Cory <unk> from Evercore.

Speaker Change: Your line is open.

Cory: Hey, good afternoon, guys. Thanks for taking my questions.

Take the two of them I guess first one is for for harmony to you, obviously show a pretty profound PFS benefits across all cuts of the data in histology as everything else would you expect that to be broadly hold for overall survival as well and then I have a follow up.

Dave Gancarz: Hey, Corey, great question. This is Dave. At this point, the only data that's been released publicly from our partners at ACASO has been the top line hazard ratio for Harmony 2. So to your point, you are correct in the consistency of the PFS data within Harmony 2, but I don't want to get in front of our partners in terms of data release with respect. Subgroups or anything like that, but the beyond going beyond the top-line overall survival has a rate Okay, understood.

Cory: Hey, Cory Great question. This is Dave.

Dave Cars: At this point the only data that's that's been released publicly from our partners at a guess at what has been the top.

Cory: Topline hazard ratio.

Dave Cars: For <unk> two.

Dave Cars: To your point.

Dave Cars: You are correct and the consistency of the PFS data within harmony too, but I don't want to get in front of our partners in terms of data release with respect to subgroup.

Dave Cars: Subgroups or anything like that.

Dave Cars: Beyond going beyond the topline overall survival hazard ratio that they provided.

Jack West: And then a question we get a lot of one to ask you is, do you expect safety trends in the global population, whether it's the Harmony Study or some of your following ones, to match what's been seen in the data sets coming out of China? What would be the rationale as to why it could be different? So, Corey, I just want to make sure I understand your question. You're asking for the rationale in terms of why the data would be different between China and... Yeah, on the safety front.

Speaker Change: Okay understood and then a question we get a lot of wanted to ask you is it do you expect.

Dave Cars: Safety trends and.

Dave Cars: The global population, whether its the harmony study of some of your follow on ones to match, what's been seen in the data thats coming out of China, what would be the rationale as to why it could be different.

Speaker Change: So Corey I just want to make sure I understand your question you are asking for the rationale in terms of why the data would be different between China.

Dave Cars: Yes on the safety front.

Allen Yang: Okay, I'll hand that one over to Jack if you want to, you know, speak to that. Yeah, this is Allen Yang. Corey, you know, I think I, I think I understand the question. So let me let me say one thing first. So there's now at least two randomized data sets that have been publicly disclosed, the Harmony A and the Harmony 2 in terms of safety. And we're really happy with the safety profile reported to Ivan SMM. This is against double blind, one is placebo controlled, and the other one is against pembrolizumab. So we believe that the safety profile looks really good, especially since the investigation has been done on the safety profile.

Dave Cars: Okay, I'll hand that one over to Jack if you want to speak.

Dave Cars: Speak to that at all.

Allen Yang: Yes. This is Allen Yang.

Dave Cars: Corey.

Dave Cars: I think.

Dave Cars: I think I understand the question. So let me let me say one thing first.

Dave Cars: So there is now at least two randomized data sets that have been publicly disclosed the harmony and the army to in terms of safety and we're really happy with the safety profile reported high Vanessa This is against double blind one is placebo controlled and the other one is against parallelism out.

Dave Cars: So we believe that the safety profile looks really good, especially since the investigators didn't know which drug was.

Jack West: Investigators didn't know which drug was going, they're getting and so they're reporting the adverse events sort of, you know, in an unbiased approach. In terms of differences in safety reporting in China versus the US, I don't think there's going to be anything significant. Remember, even in global studies today, especially in lung cancer, a large portion of the studies report data from China, the investigators are Chinese, and now they're being significant triggers. Contributors to those global studies, you know, there are slight differences. Standard of Care or cultural differences in reporting AEs. We've noticed that in the Harmony A study, a lot of lab values were reported.

Dave Cars: They are getting and so they're reporting the adverse events sort of.

Dave Cars: In an unbiased approach in terms of differences in safety reporting in China versus the U S. I don't think there's going to be anything significant remember even in global study today, especially in lung cancer, a large proportion of the studies report data from China that investigators are Chinese.

Dave Cars: And now there.

Dave Cars: Being significant traduce contributors to those global studies.

Dave Cars: Slight differences.

Dave Cars: Standard of care or cultural differences in reporting Aes, we've noticed that in the harmony study a lot of lab values were reported.

Jack West: The Chinese investigators seem to be more conservative in reporting lab value abnormalities as adverse events, even though there may not be clinically significant or meaningful adverse events associated with those lab value abnormalities. So, with that said, I don't expect there to be differences, but there are some sort of cultural or minor differences, but I don't think that they will be impactful on the data.

Dave Cars: The Chinese investors seem to be more conservative and reporting lab value abnormalities.

Dave Cars: As adverse events, even though there may not be clinically significant or meaningful adverse events associated with those lab value abnormality. So with that said I don't expect there to be differences.

Dave Cars: But there are some sort of cultural or minor differences, but I don't think that there will be impactful in the data.

Jack West: And I would also just add, Jack West, that, you know, the things that to the clinicians are going to be of greatest concern are serious bleeding issues or things that are not nuanced questions that would be subject to that kind of interpretation, I think. And the data that we've seen have been... so well ensconced in a place where clinicians are happy that it would have to be a very notable departure from anything that's been seen at this point in larger trial settings prospectively moving forward. Okay, yeah, we found the safety language in the Kezzo press release on Harmony Six to be very reassuring, but that that answer is very helpful.

Speaker Change: And I would also just add Jack West.

Speaker Change: The things that to the clinicians are going to be of greatest concern our.

Speaker Change: Serious bleeding issues are things that are not nuanced questions that would be subject to that kind of interpretation I think.

Speaker Change: And the data that we've seen have been.

Speaker Change: So well ensconced in AR and AR.

Speaker Change: A place where clinicians are happy that it would you would have to be a very.

Speaker Change: Very notable departure from anything Thats been seen at this point in larger trials settings prospectively moving forward.

Speaker Change: Okay, Yes, we found the safety language in the press release on <unk> to be very reassuring, but that answers very helpful. I. Appreciate it guys. Thank you.

Unknown Executive: I appreciate it, guys. Thank you. Thanks.

Corey: Thanks Corey.

Kelly Shih: Thank you. Our next question comes from the line of Kelly Shih from Jefferies. The line's open.

Corey: Thank you.

Speaker Change: Our next question comes from the line of Kelly <unk> from Jefferies.

Corey: Line is open.

Kelly Shih: Congrats on the progress, and my first question is for Harmony 3, the chemocombo trial in front line. Do you set enrollment target for squamous and non-squamous versus non-squamous patients? Is it expected to be split equally across two subtypes and also have follow-up? Allen, do you want to take that question? Yeah, we do have sort of enrollment objectives for both the pathologies so that we would have enough scientific information to have an informed decision on both histologies. We haven't disclosed the exact numbers and they're not precise. They're sort of ranges of the expectation. So there ought to be equal amounts of squamous and non-squamous at the end of the study.

Kelly: Congrats on the progress and my first question is for how many three the chemo combo trial in frontline do you said enrollment target for squamous and non squamous.

Kelly: Versus non squamous patients is it is it expected to be split equally across two subtypes and also have a follow up.

Alan Yang: Alan do you want to take that question.

Alan Yang: Yes, we do have sort of enrollment.

Speaker Change: Objectives for both the pathologies.

Speaker Change: So that we would have enough scientific information to have an informed decision on both histology, we haven't disclosed the exact numbers and theyre not precise sort of ranges of the expectation so there'll probably be equal amounts of squamous and non squamous at the end of the study.

Kelly Shih: And also for Harmony 7, the global trial running by Summit. in the PD-L1 positive patient, what kind of media overall survival benefit in terms of like how many months of improvement over PD-1 would be considered transformative and replace PD-1 standard of care in this frontline setting? Hey Kelly, this is Dave. I would just want to say we haven't given our statistical plan yet in terms of this. I'll let the physicians comment on the clinically meaningful thresholds and whatnot. But in terms of what we're gearing the trial for and whatnot, that's not necessarily a plan we've given.

Speaker Change: Great and also how many seven.

Speaker Change: Global trial running by summit.

Speaker Change: In the PDL one positive.

Speaker Change: Patient what kind of media overall survival benefit in terms of like how many months of improvement over PD, one would it be considered a transformative and replace PD, one and standard of care.

Speaker Change: Frontline settings.

Speaker Change: Hey, Kelly this is Dave.

Speaker Change: I would just wanted to say, we haven't given our statistical plan yet in terms of this outlet.

Speaker Change: The physicians comment on the the clinically meaningful threshold and whatnot.

Speaker Change: In terms of what we're like gearing the trial for and whatnot.

Speaker Change: <unk> plan, we have given the only thing I would say from a top line perspective, I think we've been pretty clear publicly that.

Dave Gancarz: The only thing I would say from a top line perspective, I think we've been pretty clear publicly that, you know, as we look at overall survival, being around or under the 0.80 hazard ratio has been a focus for us. But I'll let Jack, if there's anything else, or Allen, you want.

Speaker Change: As we look at overall survival.

Speaker Change: Being around or under the 0.80 hazard ratio has been.

Speaker Change: Our focus for us, but I'll let.

Speaker Change: Jack if theres anything else or Alan you want to add to that.

Jack West: Yeah, this is Jack West. I think that Dave underscored all the right points. In general, I would say that if it is statistically significant to make this a positive trial, it is extremely likely that it will be more than sufficient from a clinician's standpoint to be clinically significant and revise the standard of care. I would say that the statistical plan is likely to be more stringent than what clinicians or patients are looking for as a clinically meaningful improvement and as a general statement that most clinicians are looking for two or three months at least of an improvement in overall survival.

Jack West: Yes. This is Jack West I.

Dave Cars: Thanks, Dave underscored all the right points.

Dave Cars: In general I would say that is statistically significant to make this a positive trial. It is extremely likely that it will be more than sufficient from a clinician standpoint too.

Dave Cars: To be clinically significant and revise the standard of care I would say that the.

Dave Cars: Statistical plan is likely to be more stringent than that what clinicians or patients are looking for as a clinically meaningful improvement.

Dave Cars: And as a general statement that most clinicians looking for are looking for two or three months at least.

Dave Cars: Improvement in overall survival, so, but that's not specific to this trial that just as a general benchmark.

Dave Gancarz: But that's not specific to this trial that just is a general benchmark of practice changes. Yeah, I just underscore what Jack said, you know, that we haven't really released those specifics around our statistical analysis plan. But if the Harmony 7 study is positive as designed, it would be very clinically meaningful and an important change in the standard of care. I'd also add, like, if you look at the Harmony 2 data presented to date, if those numbers hold up, I think that's very clinically meaningful and important data. Agreed.

Dave Cars: Practice changing.

Speaker Change: Yes, I would just underscore what Jeff said.

Speaker Change: That we Havent really released those specifics around our statistical analysis plan, but if the <unk>. Seven study is positive best decided it would be very clinically meaningful and important change in the standard of care I would also add if you look at the Hanmi two data presented to date, if those numbers hold up I think thats very clinically meaningful and important day.

Speaker Change: Hey, great.

Unknown Executive: Thanks very much.

Speaker Change: Okay. Thanks very much.

Speaker Change: Thanks Kelly.

Unknown Executive: Thank you.

Speaker Change: Thank you.

Karina: Our next question comes from the line of Afrika Gunn-Warden from True Security. The line's open.

Speaker Change: Our next question comes from the line of Oscar Awards.

Speaker Change: True Securities.

Karina: Hi, this is Karina for ASCA. Thanks for taking the question and congrats on the progress. First one is, when do you guys expect the Chinese and MPA label to be publicly available by PISA for Harmony 2? And have you seen what the OS curves look like? And since it's now approved in China, can you tell if they show consistent or widening separation over time?

The lines are and this is great effort.

Speaker Change: Cleanup Oscar Thanks for taking my question and congrats on the progress.

Speaker Change: First one is when do you guys expect the Chinese on the MTA label to the publicly available so for harvesting tool and have you seen what the OS curves look like since it's now approved in China can you tell a base, you'll consistent or widening separation over time.

Dave Gancarz: Hey, Karina, this is Dave. So in terms of label, being available from the NMPA, typically, it's a little bit different in terms of how it works from the US perspective, it's not necessarily, you know, published on the in the US case, the FDA website. So it becomes part of the next round of shipment in the The physical product is kind of the official update, but it typically will... You know, made available in a period of time shorter than that. But it's it's a short term aspect from that perspective.

Dave Cars: Hey, Curt this is Dave so in terms of label.

Dave Cars: Being available from the NPA typically it's a little bit different in terms of.

Dave Cars: How it works from the U S perspective, it's not necessarily published on the in the U S case, the FDA website.

Dave Cars: Prior to the next round of shipments in the.

Dave Cars: And the physical product is kind of the official update but it typically will be.

Dave Cars: <unk> made available at a period of time shorter than that but it's short term aspect from that perspective.

Dave Cars:

Dave Gancarz: With respect, could you repeat your second question, Corinne? Yeah, if you've seen the OS curves, what they look like, and since it's already approved in China, can you tell like, whether they're consistent or they're running over time? Yeah, and so I similar to what I mentioned before, this is Dave again. We're the trial was sponsored and conducted by our partners at ACESA. So we're going to allow them to. You know, the information with respect. to their clinical trials. So we're not going to get into the specifics of things that they haven't yet done. Appreciate the interest in that.

Dana: With respect could you repeat your second question Dana.

Dave Cars: Yes.

Dave Cars: In the OS crabs, where they look like and since it's already approved in China can you tell us whether there.

Dave Cars: Distant or their wedding overtime, yes.

Dave Cars: Similar to what I had mentioned before this is Dave again.

Dave Cars: The trial was sponsored and conducted by our partners and of course, we're going to allow them to release the information with respect to their clinical trial. So we're not going to get into the specifics of things that they haven't yet disclosed publicly but I appreciate the interest in that.

Dave Gancarz: likely come when they when they choose to disclose that. Medical Meeting, or otherwise.

Dave Cars: Likely come when they when they choose to disclose that.

Dave Cars: Medical meeting or otherwise sparkle.

Karina: And also one more on Harmony 3, have you guys had discussions with FDA about leveraging Project Honor for accelerated approval? I think you cut out when you said project, sorry. Sorry, Karina, do you mind repeating that? Project. I am bad, sorry, sorry. Project Frontrunner. So in general, we don't typically get too far into our, you know, discussions with the agency, we want to respect, you know, what the agency, you know, and we talked about in general, we have had conversations with the agency multiple times with respect to Harmony Three, just to be clear. And we align, you know, our trials based on feedback from the agency.

Dave Cars: And also one more on harmony three have you guys had discussions with FDA about leveraging project R&R pork salary pool.

Speaker Change: I think you cut out when you said project, sorry, sorry, Draino do you mind repeating the project.

Dave Cars: Got it bad terrorists project front runner on accelerated conditional filing.

Speaker Change: Okay.

Speaker Change: So in general we don't typically get too far into our discussions with the agency we want to respect what the agency.

Speaker Change: And we talked about in general we have had conversations with the agency multiple times with respect to harmony three just to be clear.

Speaker Change: And we align our trials based on feedback from the agency but.

Dave Gancarz: But we don't necessarily want to get into, you know, the individual details I appreciate the question.

Speaker Change: But we don't necessarily want to get into the individual details of the conversations per se, but I appreciate the question.

Unknown Executive: All right. Thank you.

Speaker Change: Alright, thank you.

Mohit Bansal: Our next question comes from the line of Mohit Bansal from Wells Fargo. The line's open. Great. Thank you very much for taking my question, and congrats on all the progress. I have two questions. I'll ask one by one. So regarding Harmony 2, is it fair to assume that the majority of the OS events would have happened only among the low PD-1 patients, given that OS for tetruda tends to be significantly longer for PD-1 high patients, and by extension, Ionis map?

Speaker Change: Thank you.

Speaker Change: Our next question comes from the line of Mohit Bansal from Wells Fargo.

Speaker Change: Your line is open.

Mohit Bansal: Great. Thank you very much for taking my question and congrats on all the progress as two questions I'll ask one by one so regarding how many too is it fair to assume that the majority of the worst events would have happened on the amongst the low PD lone patients given that led us to that tends to be cigna.

Mohit Bansal: Significantly longer slip even high patients and by extension I Wanna Smith.

Dave Gancarz: Hey Mohit, this is Dave. I very much appreciate that question in the sense of, you know, the expectation that you set there. And your baseline, you know, comment is true in the sense of the difference. on the Pemberlizumab side. But at this point, that becomes kind of a subgroup analysis piece.

Mohit Bansal: Hey, Mohit. This is Dave very much I appreciate that question in the sense of.

Mohit Bansal: The expectation these out there in your baseline.

Mohit Bansal: Comment is true in the sense of the difference in the medians.

Mohit Bansal: Timber elysium outside.

Mohit Bansal: But at this point that becomes kind of a subgroup analysis piece.

Dave Gancarz: And so again, we'll defer to our partners at ACASO in terms of the timing of the Got it. Okay, so let me ask you other one. Thank you. I appreciate that. So, look, I mean, in the lung cancer, especially non-sponsored lung cancer, you're going after an indication that PAMBRO is pretty strong. Are there other indications where the delta for VEGF-PD-1 combination could be much more pronounced versus a PD-1 inhibitor, where VEGF could add a lot more value than just lung cancer, and where are you in terms of pursuing those indications outside of lung cancer? Thank you.

Mohit Bansal: Again, we'll defer to our partners that are also in terms of the timing of the detailed releases there.

Got you Okay. So let me ask you other than thank you I appreciate that.

Mohit Bansal: So look I mean in the lung cancer, especially in non small cell lung cancer youre going after <unk> and.

Mohit Bansal: An indication that <unk> is pretty strong.

Mohit Bansal: Are there other indications where the data is therefore <unk> PD, one combination could be much more pronounced versus a PD one inhibitor.

Mohit Bansal: We're glad you could add a lot more value than just lung cancer.

Mohit Bansal: And where are you in terms of pursuing those indications outside of lung cancer. Thank you.

Dave Gancarz: Thanks, yeah, and I'll, I'll take the first part of that. And then I'll hand it over to Allen for for some details there. But I think I would what I'd probably refer you to is the ESMO 2024 phase two data that was published by IKESO. And so there are indications or tumor settings, more appropriately there that would not typically be places where PD-1 inhibitors in and of themselves. Examples of that include microsatellite-stable colorectal cancer, as well as the PD-L1 low and negative triple negative breast cancer tumor settings. In terms of, you know, the more specifics on, you know, our development plan, you know, I think as McKee mentioned in the prepared remarks, we do plan on giving a little bit more context over the course of this year, as opposed to kind of the individual.

Mohit Bansal: Thanks Mohit.

Alan Yang: I'll take the first part of that and then I'll hand, it over to Alan for a for some details there, but I think I would what I would probably refer you to is the ESMO.

Speaker Change: 2024 phase two data.

Speaker Change: That was published by <unk>, and so there are indications or tumor settings more appropriately there that.

Speaker Change: Would not typically be places, where PD, one inhibitors in and of themselves have been particularly successful.

Speaker Change: Examples of that include microsatellite stable colorectal cancer as well as the PDL, one low and negative triple negative breast cancer tumor settings.

Speaker Change: In terms of the more specifics on.

Speaker Change: <unk>.

Speaker Change: Our development plan I think as Micky mentioned in the prepared remarks, we do plan on giving a little bit more context over the course of this year as opposed to kind of the individual.

Allen Yang: You know, leaking out of or dripping of details, but we want to make sure we have the right alignment with the agencies and so on, but maybe biologically or whatnot, Allen, if you want to add anything. I think it's a good question. You know, again, we sort of boiled the ocean. We've looked at the PD-1 approvals. We've looked at the VEGF approvals. And then there's clearly tumors where the VEGF and PD-1 activity overlap, and we're looking at those. You know, the things to consider about that is, you know, what would be the control arm for that study?

Speaker Change: Leaking out of or dripping of details but.

Speaker Change: We want to make sure we have the right alignment with the agencies.

Speaker Change: And so on but maybe biologically or whatnot, Alan if you want to add any context it up.

Speaker Change: No I think it's a good question.

Speaker Change: Again, we sort of boil the ocean, we've looked at the PD one approvals we've looked at the bed, Jeff approvals, and then Theres clearly tumors, where the digest and PD one activity overlap then we're looking at those the things to consider.

Speaker Change: <unk> about that is what it would be the control arm for that study what regions are those tumor types more prevalent and then I think you can sort of.

Allen Yang: What regions are those tumor types more prevalent in? And I think you can sort of guess what I'm alluding to if you look at the specific tumor types. And then what is the Phase II data that a TESO generates? That's probably the most important thing in how we're thinking about which tumor types to go into next. So we do have a very clear plan of where we want to go next, and we're very excited about the IBO data. And all of those considerations, including the PD-1 and VEGF activity, are taken into consideration. I would just potentially add that, in addition to specifically the VEGF component, the cooperative binding is relevant here.

Speaker Change: That's what I'm alluding to if you look at the specific tumor types.

Speaker Change: And then what is the phase II, David Kessler generate that's probably the most important thing and how we're thinking about which tumor types to go into next so we do have a very clear plan of where we want to go next and we're very excited about the hydro data and all of those considerations, including the PD, one and bedrock activity are taken into consideration.

Speaker Change: I would just potentially add that in addition to specifically the value of component. The cooperative binding is relevant here that if we look at settings, where we've demonstrated success you have egfr mutation positive it's a setting.

Jack West: That if we look at settings where we've demonstrated success, you have EGFR mutation positive. It's a setting, yes, where VEGF may be particularly relevant. It's also a setting where other PD-1 inhibitors have not proven successful. You can also look at Harmony-2 and see that in the setting of high PD-L1, where PEMBRO has been very favorable, we also saw great success for IBO relative to PEMBRO, but also see benefit for Ivan SMV in the low PD-L1 setting against PEMBRO, where PEMBRO has not been as commanding of a choice. And so I think that that can be extrapolated potentially into other settings, whether that is because specifically of the VEGF component that it brings, but it also may be because of the cooperative binding that may render Ivan SMV a more effective immunotherapy.

Speaker Change: Where that Jeff Navy, particularly relevant it's also a setting where other.

Speaker Change: Other PD one inhibitors have not proven successful you can also look at <unk>, two and see that in the setting of high PDL, one where <unk> has been very favorable.

Speaker Change: We also saw a great success for Ivo relative to pet row, but also see benefit for <unk> in the low PDL one setting against <unk> has not been as as commanding of choice and so I think that that can be extrapolated potentially into other settings, whether that is because.

Speaker Change: Quickly.

Speaker Change: VEGF component that it brings.

Speaker Change: But it also maybe because of the cooperative binding that may render Ivan SMA have a more effective immuno therapy.

Unknown Executive: Household. Thank you.

Speaker Change: Helpful. Thank you.

Mitchell Kapoor: Next question comes from Mitchell Kapoor from H.E. Wainwright. The line's open. Hey team, congrats on the recent progress. And thank you for taking the questions.

Speaker Change: Thank you next question comes from Mitchell Kapoor from H C. Wainwright Your line is open.

Mitchell Kapoor: Hi team congrats on the recent progress and thank you for taking the questions I wanted to ask so the NPA granted the first line approval in PD lone positive non small cell lung cancer patients in China based on harmony too, but wanted to understand what it's going to take to get approval in the <unk>.

Mitchell Kapoor: I wanted to ask, so the NMPA granted the first line approval and PD-L1 positive non small cell lung cancer patients in China, based on Harmony-2, but wanted to understand what it's going to take to get approval in the PD-L1 low patients. Why didn't they grant this approval? Did they indicate anything like they need to see more data? Or is that indicative of anything they're seeing in the Harmony-2 trial?

Mitchell Kapoor: PD lone low patients why didn't they grant us approval debate indicate anything like they need to see more data or is that indicative of anything that you're seeing in the harmony to trial so far.

Dave Gancarz: Hey, Mitchell, it's Dave. Let me clarify that because I just want to make sure this is clear. So we generally break down PD-L1 expression by negative less Low 1 to 49 or high. And then in the case of Harmony 2, when we say PD-L1 positive, that was really one. You will. So the high and the low, but not. So the approval, as we understand it in China, from the NMPA was in PD-L1 positive, so PD-L1 expression, you know, greater than one. So that is what the harmony Trial was designed as PD-L1 positive. For Harmony 7, because of the standard of care in the Western markets, our trial is designed...

Mitchell Kapoor: Hey, Mitchel, it's Dave let me clarify that because I just want to make sure. This is clear so in.

Speaker Change: So we generally breakdown PDL, one expression by negative less than one low 1% to 49 or high.

Mitchell Kapoor: 50, plus.

Mitchell Kapoor: And then in the case of harmony to when we say PD lone positive that was really one plus if you will so the high and the low but not the negative.

Mitchell Kapoor: So the approval as we understand it in China from the NPA was in PD Lone positive so great PDL, one expression greater than one if you will if you use the GBS scoring system.

Mitchell Kapoor: So that is what the harmony two trial was designed as PD lone positive.

Mitchell Kapoor: For harmony seven because of the standard of care.

Mitchell Kapoor: In the western markets are trial as designed.

Dave Gancarz: PDL-1 high-expressing patient. Just want to clarify and make sure that. Yeah, thank you. Sorry.

Mitchell Kapoor: It is a PD lone high expressing patient population.

Mitchell Kapoor: Just wanted to clarify and make sure Thats clear Mitchell.

Speaker Change: Yes. Thank you sorry, so what I meant to ask is the PD lone negative patients is there is there something that needs to be shown there that would be able to.

Dave Gancarz: So what I meant to ask is that PD-L1 negative patients, is there, you know, something that needs to be shown there that would be able to gain approval in that population? that wasn't part of the Harmony 2 study. And so what would need to be shown there is really a separate trial, for lack of a better way of putting it. So the other thing that's important is if you look at the Harmony 6 data that Akeso announced top line results for, that is PD-L1 all comers. So that would have the PD-L1 negative for the less than 1% if you use the TPS score.

Mitchell Kapoor: Gain approval on that population.

Mitchell Kapoor: So that wasn't part of the harmony to study.

Mitchell Kapoor: And so what would need to be shown there is really a separate trial for lack of a better way of putting it. So the other thing. That's important is if you look at the harmony six data.

Mitchell Kapoor: Okay. So.

Mitchell Kapoor: Its topline results for that is PD lone all comers, so that would have the PD lone negative or the less than 1% of use the GPS score.

Unknown Executive: And that's a chemo combination study, right?

Mitchell Kapoor: And Thats, a chemo combination study right and so I think.

Jack West: And so I think, and I'll hand this over to Jack to comment next. But if you look at the PD-L1 negative population, you really, that's more of a chemo combination or something else akin to either a Harmony 3 squamous and non-squamous or Akesos. Yeah, I just think Dave articulated it very well. Harmony 2 just doesn't speak to that population, it's not clinically, that's just not clinically what it would cover, but Harmony 6 as well as our own data, Harmony 3 would, and Harmony, well Harmony 3 in particular, would be very relevant there, so that's just what it's going to take to be able to answer that question.

Jack West: I'll hand, this over to Jack to comment next but if if you look at the PD Lone negative population you really that's more of a chemo combination or something else akin to either our harmony three squamous and non squamous or accursed those harmonies six in squamous only.

Jack: Yes, yes, thank you Jack.

Jack West: Yes.

Jack West: Thanks.

Jack West: Dave articulated it very well.

Speaker Change: Harmony to just doesn't speak to that population it's not.

Jack West: Clinically.

Jack West: It's just not clinically what it what it would cover but harmony six as well as our own data harmony.

Jack West: Harmony <unk> III.

Jack West: Wood and harmony.

Jack West: <unk> in particular would be very relevant there. So that's that's just what it's going to take to be able to answer that question, Yes, and this is Allen Mitchell. So just to be clear there is some variability in what physicians do based on the PD lone expression levels, but to be clear Harmeet <unk> already seven will cover the whole gambit of metastatic.

Allen Yang: Yeah, and this is Allen Mitchell. So just to be clear, there is some variability in what physicians do based on the PD-L1 expression levels, but to be clear, Harmony 3 and Harmony 7 will cover the whole gambit of metastatic and advanced non-small cell lung cancer. Perfect. Thank you. I appreciate that.

Speaker Change: In advanced non small cell lung cancer.

Speaker Change: Perfect. Thank you I appreciate that and then last one for me just on the next update for harmony to are you able to just.

Mitchell Kapoor: And then last one for me, just on the next update for Harmony 2, are you able to, you know, appreciate the nominal alpha, but are you able to say if we'll be able to see P value reported along with that nominal alpha level? Just to make sure I'm clear, Mitchell, are you asking when the next analysis would be or when the more detailed data for the NMPA-requested analysis? Sorry, yeah, so then basically, the next overall survival update, obviously, you're at 30, you know, the, the 39% data maturity, but at the next update, would be able to see the P value in addition to that nominal alpha level, you know, trying to search for Yeah, I think what I would, so a bit of that does come down to the choice by Akeso given as their trial.

Speaker Change: I appreciate the nominal alphabet are you able to say, if we'll be able to see P value reported along with that nominal alpha level.

Speaker Change: Just to make sure Im clear Michal Youre asking when the next analysis would be a win win the more detailed data for the <unk>.

Speaker Change: EMEA requested analysis would be.

Speaker Change: Sorry, yes, so basically the next overall survival update obviously youre at 30.

Speaker Change: The 39% data maturity, but at the next update would you be able to see the P value. In addition to that nominal alpha level trying to search for statistical significance.

Speaker Change: Yes, I think so so a bit of that does come down to the choice by.

Dave Gancarz: But I think the If you will, the the next analysis would be more of the planned analysis in the intent. So it would be more likely it'd be more likely mature data, right? And so you'd have a little bit more alpha spend that would come with that. Got it. Thank you very much.

Speaker Change: Okay, so given us their trial, but I think that the.

Speaker Change: If you will the next the analysis would be more of the planned.

Speaker Change: Analysis in the intent so it would be more likely it would be more likely mature data right and so you'd have a little bit more alpha spend that would come with that as well.

Speaker Change: Got it thank you very much.

Eric Schmidt: Thank you. Our next question comes from the line of Eric Schmidt from Cancer Fitzgerald. The line's open. Thank you for taking my questions, one on Harmony and one on Harmony 2. First on Harmony, when we see the data in mid-2025 on overall survival, will the OS result be a mature one? And what is required via your conversations with the FDA around the U.S. approval, either in terms of what you need to see with OS or PS? and I sold a Western pot.

Speaker Change: Thank you.

Speaker Change: Our next question comes from the line of and Schmid from Cantor Fitzgerald.

Speaker Change: One is open.

Speaker Change: Good morning, Thank you for taking my questions.

Speaker Change: Harmonious and one of them.

Speaker Change: Only two first on harmonium.

Speaker Change: When we see the data in mid 2025 on overall survival will Lewis result, the mature one.

Speaker Change: What is required.

Speaker Change: Via your conversations with the FDA around the U S approval either in terms of what you need to see with a lessor PFS.

Speaker Change: I just want the western population.

Dave Gancarz: Yeah, I think Eric, this is Dave, I think what we had said earlier, I think I'll kind of stick to that in terms of, you know, we won't get into the explicit details back and forth. of the Discussions, but, you know, I'd remind you that we have, you know, two primary endpoints, and so I think it'll become a total package. You, uh, irrespective of anything in terms of what the, you know, decisions would be. But, um, yeah, I think. and the OS maturity. So, yeah, we haven't commented on that, Eric, so what we've said is, and I think in McKee's prepared remarks, they were, you know, we will have data associated with both primary endpoints, but in terms of the specifics on how much maturity on different points, we haven't.

Speaker Change: Yeah, I think Eric this is Dave I think what we had said earlier I think I'll kind of stick to that in terms of you know we won't get into the explicit details back and forth of.

Speaker Change: Discussions, but I would remind you that we have.

Speaker Change: Two primary endpoints and so I think it will become.

Speaker Change: A total package review irrespective of anything in terms of what the.

Speaker Change: Decisions would be but.

Speaker Change: Yes, I think I'd leave it there.

Speaker Change: And the lowest maturity.

Speaker Change: So we haven't commented on that Eric So what we've said is and I think in Mickey's.

Speaker Change: Prepared remarks, they were we will have.

Speaker Change: Data associated with with both primary endpoints.

In terms of the specifics on how much maturity on different points, we haven't really disclosed that just yet.

Dave Gancarz: What we're doing is we're doing this by getting data on it. Great. Thank you for that. Second question on the Harmony 2 HR that you've given 0.7777, the pre and term analysis, let's call it. I guess the number one question I get is, is whether with time that hazard ratio is likely to mature. Unfavorable or Unfavorable Direction. Do you have a view on that? Sure, so I think, and I'll ask, you know, Jack to comment on this in terms of different trials that he's seen as well, but, you know, lower side of maturity, I think part of, you know, from a statistical perspective is there's a little bit more variability.

Speaker Change: We do thank you Dave.

Speaker Change: But you're showing data on both both endpoints.

Speaker Change: Great. Thank you for that second question on the promote too.

Speaker Change: HR that you've given point.

Speaker Change: 770, 717 pretty interim analysis, let's call it.

Speaker Change: I guess the number one question I get is is whether with time that hazard ratio is likely to be sure.

Speaker Change: And a favorable or unfavorable direction do you have a view on that.

Speaker Change: Sure, So I think and I'll ask.

Jack: Jack to comment on this in terms of different trials.

Speaker Change: That <unk> seen as well, but.

Speaker Change: A lower side of maturity I think part of from a statistical perspective is there is a little bit more variability that exists there, but I certainly wouldn't expect.

Dave Gancarz: But I certainly wouldn't expect, um, there's only one direction it can go. And I certainly, what I wouldn't do in particular is I would not analogize from the Harmony A data that I think, uh, you know, occasionally we hear some chatter on with respect. You know, the initial NMPA request showed a 0.72 and then a follow-up with 0.80 on the OS there. There's some very clear differences between these trials, second line versus first line, AGA positive, EGFR specifically, versus non-driver mutation positive, combination with chemotherapy versus monotherapy. So very important that, you know, we've seen, if we look at the PD-1 inhibitors as a whole, if you will, for example, we've seen Movements up and higher or lower in terms of more maturity.

Speaker Change: Theres only one direction. It can go in and I certainly what I wouldn't do in particular is I would not analogize from the harmony.

Speaker Change: Data that I think.

Speaker Change: Occasionally we hear some chatter on with respect to.

Speaker Change: The initial MPA request.

Speaker Change: It showed a 0.72 and then a follow up with 0.80 on on the OS there. There's some very clear differences between these trials second line versus first line Egfr positive Egfr, specifically versus non driver mutation positive.

Speaker Change: The combination with chemotherapy versus monotherapy.

Speaker Change: So very important.

Speaker Change: We've seen if we look at the PD one inhibitors as a whole if you will for example, we've seen.

Speaker Change: Movements up and.

Speaker Change: Higher or lower.

Speaker Change: In terms of more maturity, but I think the point that we take here is that this early on.

Jack West: But I think the point that we take here is that this early on in the overall maturity to see a clinically. You know, a strongly positive trend. He's very encouraging from our perspective.

Speaker Change: And the overall maturity to see a clinically meaningful.

Speaker Change: Strongly positive trend is very encouraging from our perspective, Jack any any additional color.

Jack West: Jack, any additional color that you'd add? I would add that speaking with clinicians extensively since the initial release, that essentially that clinicians don't consider the OS to be as binary as that, especially so when it's in the setting of early preliminary data. But recognizing that this is going against Pembrolizumab, which is an extremely respected comparator that has good activity. So if you are seeing just a nominal hazard ratio of .78 or better against against a comparator that is active and respected without the significant notable difference in toxicity, this is something that clinicians are absolutely welcoming and seeing in a very positive light, both for this particular setting and for what it may well represent outside of this particular test of monotherapy and PD-L1 positive, but just for given the breadth of where Pembrolizumab has historically been used in lung cancer and elsewhere, showing an improvement against that with a hazard ratio below .8, especially in a preliminary setting, it has really gotten people's notice and they are not remotely deterred by the statistical issues or the preliminary nature.

Speaker Change: Ed.

Mike: Hey, Mike.

Speaker Change: That.

Speaker Change: Speaking with clinicians extensively since the initial release.

Speaker Change: Hi.

Speaker Change: Net.

Speaker Change: Essentially that clinicians don't consider the.

Speaker Change: OS to be.

Speaker Change: Buying areas that especially so when that's in the setting of.

Speaker Change: Early preliminary data but.

Speaker Change: Recognizing that this is going against embolism, App, which is an extremely respected.

Speaker Change: Comparator that has good activity. So if you are seeing just a nominal.

Speaker Change: The hazard ratio of <unk>.

Speaker Change: Seven 8% or better.

Speaker Change: Against.

Speaker Change: Against a comparator that is active and respected.

Speaker Change: Without the significant notable difference in toxicity. This is something that the <unk>.

Speaker Change: Clinicians are are absolutely welcoming and seeing in a very positive light both for this particular setting and for what it may well represent outside of this particular test mono therapy in PD lone positive, but just for given the breadth of where <unk>.

Speaker Change: <unk> has historically been used in lung cancer and elsewhere, showing an improvement against that with the hazard ratio below 0.8, especially in our preliminary setting.

Speaker Change: Is it has really gotten people's notice and they are not remotely deterred by the.

Speaker Change: The statistical issues or the preliminary nature for where it is and where it should be I think that the clinicians and by and large are quite impressed and happy with that.

Unknown Executive: For where it is and where it should be, I think that the clinicians by and large are quite impressed and happy with that. Very helpful. Thank you both. Thank you.

Speaker Change: Very helpful. Thank you both.

Ren Benjamin: And our last question comes from the line of Ren Benjamin from Citizens. Line's open. Hey, good afternoon. Thanks for taking the questions.

Speaker Change: Thank you and our last question comes from the line of Ren Benjamin from citizens loans open.

Speaker Change: Hey, good afternoon, thanks for taking the questions.

Ren Benjamin: I guess, one, in the Harmony study, is the PFS and OS going to be evaluated as a co-primary endpoint or, as McKee mentioned, with Harmony 3 and 7, dual endpoints? And can you remind us why, you know, you'd favor, let's say, one over the other?

Speaker Change: I guess one in the Harmony study is the PFS and how it's going to be evaluated as a co primary endpoint or is.

Speaker Change: Ricky mentioned with pardon me $3 seven dual endpoints.

Speaker Change: Can you remind us why you would favor, let's say one over the other.

Dave Gancarz: And a more broader question, you know, just given recent geopolitical tensions, can you kind of give us your thoughts on how you're thinking about potential impact of tariffs, how you're thinking about manufacturing and any IP and API, you know, based scenarios? Yeah, thanks, Ren. So for the first question, I think, I think we look at it more as dual primary endpoints in terms of Passing the Alpha in hierarchical testing, PFS first and then OS. With respect to the second question, I will hand that over.

Speaker Change: On a more broader question.

Speaker Change: Just given recent geopolitical tensions can you kind of give us your thoughts on how youre thinking about potential impact of tariffs, how youre thinking about manufacturing.

Speaker Change: And any IP and API.

Speaker Change: Base scenarios.

Speaker Change: Yes, Thanks Ryan.

Speaker Change: So for the first question I think.

Speaker Change: I think we look at it more as dual <unk>.

Speaker Change: Primary endpoints in terms of.

Speaker Change: Passing the alpha.

Speaker Change: And higher article testing PFS first and then OS.

Speaker Change: With respect to the second question I will hand that over to mud meets to speak too sure. Hi. This is <unk> on manufacturing front as I mentioned earlier on the call right we already have.

Manmeet Soni: Sure. Hi. On manufacturing front, as I mentioned earlier on the call, right, we already have our current supply source from our partner. But in addition to that, we have made significant progress in starting our transferring the know-how to students. in Europe. Thank you. Which is continuing over there and... that covers our concern on the manufacturing part. In regard to IP, as you mentioned, we have, you know, our IP continues until like late 2039, 2040s, right? So we have no concern even on the IP part. Good on that.

Speaker Change: We have our current supply source from our partner our queso, but in addition to that we have made significant progress in.

Speaker Change: Starting are transferring the knowhow to certain cmo's contract manufacturers and our territories, which is U S and Europe.

Speaker Change: Other territories.

Speaker Change: But just continuing over there and.

Speaker Change: Yeah.

Speaker Change: That covers our concern on the manufacturing box and.

Speaker Change: In regard to IP as you mentioned we have.

Speaker Change: Our IP continues until like late.

Speaker Change: 239040, <unk> right. So we have no concern even on the IP part and we believe pretty good on that.

Speaker Change: Perspective too.

Manmeet Soni: And just as a follow up, in the manufacturing, you know, from the CDMOs, will that product find its way into the Harmony 3 and Harmony 7 trials so that, you know, upon potential approval, this is going to be quite kind of seamless in terms of the, you know, utilizing the material or will there need to be a bridging study? How do we think about that? No, it's like any, you know, Every, I would say, manufacturer or any pharma company will have multiple sources of production and we are also planning to add, right? A Queso is one source, we'll have another source from our contract manufacturers, and you will have to do certain regulatory filings in order to, not bridging studies, but filings to compare the production batches and all those things and how they are comparing the batches with the specifications, and that would be required to do, done.

Speaker Change: And just as a follow up on the.

Speaker Change: Manufacturing.

Speaker Change: From the <unk> product.

Speaker Change: Weigh into the army three in harmony seven trials so that.

Speaker Change: Upon potential approval. This is going to be quite seamless in terms of the utilizing the material or what needs to be a bridging study how do we think about that.

Speaker Change: It's like any.

Speaker Change: Hum.

Speaker Change: Because every.

Speaker Change: I would say manufacturer or pharma company will have multiple sources of production and we are also planning to add right. I guess was one source will have another source from our contract manufacturers and you will have to do certain regulatory filings in order to not bridging studies, but filings to compare the production batches all of those things that how they're comparing the batches with.

Speaker Change: The specifications and that would be required to do done and.

Unknown Executive: And, obviously, yes, first would be to use them in clinical supplies, but those happen on a very regular basis for all. Great. Thanks for taking the questions. Sure. Thanks. Thank you. There are no further questions.

Speaker Change: You don't think obviously you had first first would be to use them in clinical supplies, but those happen on a very regular basis for all the pharma companies.

Speaker Change: Great. Thanks for taking my questions sure. Thanks, Ron.

Speaker Change: Okay.

Thank you.

Dave Gancarz: I turn the call back over to Dave Gancarz for final remarks. Thank you, Dustin, and thank you, everyone, for the amount of interesting questions.

Speaker Change: No further questions I'll turn the call back over to Dave <unk> for final remarks.

Dave Cars: Thank you Dustin.

Speaker Change: Thank you everyone for.

Speaker Change: The amount of interesting questions I think the last the last thing I'd like to do just yet.

Jack West: I think the last thing I'd like to do, just to make sure we fully address this, I'll hand it over to Jack West for, just given his extensive experience, obviously, in thoracic oncology and whatnot. Any final comments, Jack, that you have with respect? The announcement with respect to the hazard ratio and the overall survival of the early look for harm. Yeah, I have had the opportunity over the last three to six months to have dozens and dozens of conversations with with various thought leaders in thoracic oncology. Obviously, the some of the biggest questions, the biggest questions for Ivan SMAB after a great year last year was How does this look outside of China?

Speaker Change: To make sure we fully addresses.

Speaker Change: I'll hand, it over to Jack West for.

Speaker Change: Just given his extensive experience obviously in thoracic oncology and whatnot any final comments Jack that you have with respect to.

Speaker Change: The announcement with respect to the hazard ratio and the overall survival at the early look for harmony too.

Speaker Change: Yeah.

Speaker Change: I have had the opportunity over the last three to six months to have dozens and dozens of conversations with with various thought leaders in thoracic oncology.

Speaker Change: Obviously.

Speaker Change: Some of the biggest questions.

Speaker Change: The biggest question for either an SMA or after.

Speaker Change: Great year last year was.

Speaker Change: How does this look outside of China, we will see information about that in the <unk>.

Jack West: We will see information about that in the next several months, as well as does the benefit hold up when added to chemo or how much does the addition of chemo to both arms kind of aggregate the difference? Harmony 6 is going to address that, and we already know that's in a favorable way, that that's not mitigated clearly, just it's not a phenomenon of monotherapy. And then the bigger question, and we'll be able to speak to this somewhat with Harmony, and Harmony 2, now we have some insights about PFS to OS. That's always a question in lung cancer and other tumor types.

Speaker Change: Next several months.

Speaker Change: As well as.

Speaker Change: Just does the benefit hold up when added to chemo or how much does the addition of chemo to both arms kind of aggregate. The difference harmony six is going to address that and we already know thats in a favorable way that thats not mitigated clearly just it's not a phenomenon of monotherapy.

ERP and then the bigger question and we'll be able to speak to this somewhat with harmony and harmony to now we have some insights about PFS OS that's always a question in lung cancer and other tumor types. It's always a question with various.

Jack West: It's always a question with various treatment approaches, but that's been a particular thorn in the side of VEGF inhibition, Bevacizumab, and my colleagues and I have really thought about it, that regardless of that specific P-value associated, especially early and especially in a trial like Harmony 2, that was not powered for overall survival, the key thing is, is that hazard ratio for OS after that PFS that we saw, is that going to be .7 something or .9 something? That's really exactly what I've been saying with and nobody knew until we saw that press release where that was, but it is in the .7 something range, and that is what people have been looking for, just to get a sense of does this track or does it not?

Speaker Change: Treatment approaches, but that's been a particular thorn in the side of VEGF inhibition Bevacizumab and <unk>.

Speaker Change: And my colleagues and I have really thought about it that regardless of that specific P value associated especially early and especially in a trial like Armani two that was not powered for overall survival.

Speaker Change: The key thing is is that hazard ratio.

Speaker Change: OS after that PFS that we saw is that going to be seven something or nine something that's really good.

Speaker Change: Exactly what what I've been saying with that and then nobody knew until we saw that press release, where that was but it is in the seven something right and that is what people have been looking for just to get a sense of is this does this track or does it.

Jack West: And the answer is it absolutely does track. So to me, that addresses that question and some of those concerns. We'll get more details, but this in broad strokes was what we were hoping to clarify, if it gives it back or if it doesn't. Of course, it's likely to erode somewhat with subsequent treatments, but I and my colleagues prospectively have been looking for 0.7 something is exactly what we've been hoping to see.

Speaker Change: Not and the answer is it absolutely does track so to me that that addresses that question in Elas.

Speaker Change: Some of those many of those concerns just we'll get more details, but this in broad strokes was what we were hoping to clarify.

Speaker Change: It gives us back or if it doesn't of course, it's it's likely to erode somewhat with subsequent treatments but.

Speaker Change: I and my colleagues prospectively, you had been looking for seven something is exactly what we've been hoping to see.

Jack West: Really appreciate it, Jack, and I want to take the time to thank everybody for attending today's earnings call. We are unfortunately out of time now at this point, but I want to say thank you, and an archived version of this webcast will be available on our website, www.smmtx.com. Thank you very much and enjoy your evening. The meeting has now concluded. Thank you all for joining. Have a pleasant day and you may now disconnect. [music]

Speaker Change: Really appreciate it Jack and I want to take the time to thank everybody for attending today's earnings call. We are unfortunately out of time now at this point, but I want to say, thank you and an archived version of the.

Speaker Change: This webcast will be available on our website www dot SMT, TX dot com. Thank you very much and enjoy your evening.

Speaker Change: Okay.

Speaker Change: The meeting is now concluded. Thank you all for joining have a pleasant day and you may now disconnect.

Speaker Change: Okay.

Speaker Change: [music].

Speaker Change: Yes.

Speaker Change: Yes.

Speaker Change: [music].

Speaker Change: Yes.

Speaker Change: Yeah.

Speaker Change: Okay.

Speaker Change: [music].

Speaker Change: Sure.

Speaker Change: [music].

Speaker Change: Okay.