Q3 2025 Summit Therapeutics Inc Earnings Call and Business Update Call

I will be your conference operator today.

At this time I would like to welcome everyone to the summit Therapeutics Q3, 2025 earnings and ESMO data update call.

All lines have been placed on mute to prevent any background noise.

After the Speakers' remarks, there will be a question and as recession. If you would like to ask a question. During this time simply press star followed by the number one on your telephone keypad. If you would like to withdraw your question breast Star. One again. Thank you I would now like to turn the call over to Dave Gancarz. Please go ahead.

Good day, and thank you for joining us.

We issued a press release on Friday morning.

<unk> the exclusion of our phase three clinical development programs unveiling the global Phase III study in <unk>.

First line colorectal cancer.

Yesterday, we issued a press release relating to the phase III harmony six data featuring I've been asked about presenting it as a part of the presidential symposium at the European Society for medical Oncology 2025 copper Congress.

Otherwise known as <unk> in 2025.

The harmony six study was conducted in China.

And by our partners that are canceled.

All relevant data was exclusively generated managed analyzed by a catch up.

And finally this morning, we announced our intention to submit a BLA this quarter, Brian and SMS based on the results of the harmony study as well as expand our phase III study plan with additional color to be provided in the first quarter.

Additionally, on today's call, we will provide an update on our third quarter financial results and operational progress.

Press releases are available on our website www Dot <unk>, and then Qi, TX Dot com our form 8-K and Form 10-Q were also filed today and are available on our website and via the Sec's website.

Today's call is being simultaneously webcast and an archived replay will be made available later today on our website.

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

Speaker #1: I need an update on our third quarter financial results and operational progress.

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

Speaker #2: Press releases are available on our website, www.smmtx.com. Our Form 8-K and Form 10-Q were also filed today and are available on our website and via the SEC's website.

Dr also geico, our chief regulatory quality and safety officer.

Dr Allen Yang our head of R&D strategy.

Dr. Jack West, our VP of clinical development and Dr. Phung cloud, our Chief Biometrics Officer.

Speaker #1: Today's call is being simultaneously webcast, and an archived replay will be made available later today on our website. Joining me on the call today is Bob Duggan, our Chairman of the Board and Chief Executive Officer.

Before we get started with the rest of the call I would like to note that some statements made by our management team. Some responses to questions that we make today may be considered forward looking statements based on our current expectations.

Speaker #1: Dr. Mahkam Zanganeh, our Coaching Executive Officer and President. Manmeet Soni, our Chief Operating Officer and Chief Financial Officer. Dr. Alta Gayko, our Chief Regulatory, Quality, and Safety Officer.

<unk> 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.

These refer to our SEC filings for information about these risks and uncertainties summit undertakes no obligation to update these forward looking statements except as required by law.

Speaker #1: Dr. Alan Yang, our Head of R&D Strategy; Dr. Jack West, our VP of Clinical Development; and Dr. Juan Clau, our Chief Biometrics Officer. Before we get started with the rest of the call, I would like to note that some statements made by our management team and some responses to questions that we make today may be considered forward-looking statements, based on our current expectations.

One item of note. This presentation is being webcast with slides, we'll be referring to information on the slides being displayed in the webcast link I'd encourage you to use the webcast link see these slides being presented this morning that will accompany our comments and these.

Speaker #1: Summit cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements.

Slides are also available on our website.

Following comments from our team we will take questions.

Speaker #1: Please refer to our SEC filings for information about these risks and uncertainties. Summit undertakes no obligation to update these forward-looking statements, except as required by law.

With that I would like to hand, it over to Jack to walk through the beginning of the presentation.

Yesterday as Youre aware Ive announced map data were featured in the presentation at ESMO 2025, as part of the presidential Symposium.

Speaker #1: One item of note: this presentation is being webcast with slides, so we'll be referring to information on these slides being displayed in the webcast link.

The presentation titled Phase III study of <unk>, plus chemotherapy versus <unk> plus chemotherapy as first line treatment for advanced squamous non small cell lung cancer <unk> six was given by Dr. <unk> M D ph D G.

Speaker #1: I encourage you to use the webcast link to see these slides being presented this morning, which will accompany our comments. These slides are also available on our website.

Speaker #1: Following comments from our team, we'll take questions. With that, I would like to hand over to Jack to walk through the beginning of the presentation.

<unk> of Shanghai lung cancer Centre in Shanghai Chest Hospital Professor of Medicine, and Shanghai, Joan Tong University, and associate editor for the journal of thoracic oncology.

Speaker #2: Thank you, Dave. Yesterday, as you're aware, I received an estimate of data we're featuring in the presentation at ESMO 2025 as part of the presidential symposium.

Revisiting the schema for the harmony six trial. This study evaluated <unk> in combination with platinum based chemotherapy.

Speaker #2: The presentation, titled "Phase 3 Study of Ivanesmab + Chemotherapy vs. Tizolizumab + Chemotherapy as First-Line Treatment for Advanced Squamous Non-Small Cell Lung Cancer, Harmony 6," was given by Dr. Shanu, MD-PhD, Chief of Shanghai Lung Cancer Center at Shanghai Chest Hospital, Professor of Medicine at Shanghai Zhongtong University, and Associate Editor for the Journal of Thoracic Oncology.

Paired with <unk> with a PD one inhibitor in combination with platinum based chemotherapy in patients with locally advanced or metastatic squamous non small cell lung cancer irrespective of PD lone expression.

<unk> six is a single region multicenter phase III study conducted in China sponsored by a catch up with.

With all relevant data exclusively generated managed and annualize that.

Speaker #2: Revisiting the schema for the Harmony 6 trial, this study evaluated Ivanesmab in combination with platinum-based chemotherapy compared with Tizolizumab, a PD-1 inhibitor, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous non-small cell lung cancer, irrespective of PD-L1 expression.

Key eligibility criteria are shown here.

<unk> were randomized one to one stratified by stage cancer, and PD lone tumor expression at baseline.

Patients received either <unk> at 20 milligrams per kilogram, plus carboplatin, paclitaxel or <unk>, plus carboplatin and Paclitaxel for up to four cycles, and then receiving either <unk> as maintenance therapy for up to 24 months treatment was to be discontinued for Intel.

Speaker #2: Harmony 6 is a single-region, multi-center phase 3 study conducted in China, sponsored by AKESA. All relevant data is exclusively generated, managed, and analyzed by AKESA.

Our ability progressive disease or initiation of a new anti tumor therapy.

Speaker #2: Key eligibility criteria are shown here. Patients were randomized one-to-one, stratified by stage of cancer and PD-L1 tumor expression at baseline. Patients received either Ivanesmab at 20 milligrams per kilogram plus carboplatin/paclitaxel or Tizolizumab plus carboplatin/paclitaxel for up to four cycles, and then received either Ivanesmab or Tizolizumab as maintenance therapy for up to 24 months.

The studies single primary endpoint was progression free survival by independent Radiological Review Committee.

Secondary endpoints included response rate duration of response safety and overall survival.

The trial included a total of 532 patients.

Baseline characteristics show that this was a predominantly male population nearly all with stage four disease and it's important to underscore that these patients with advanced squamous non small cell lung cancer, including those with characteristics that we have traditionally considered as potentially associated with bleeding on anti.

Speaker #2: Treatment was to be discontinued for intolerability, progressive disease, or initiation of new anti-tumor therapy. The study's single primary.

Angiogenic therapies, specifically approximately two thirds had a central tumor 17% had encasement of major blood vessels in the chest, 9% had tumor cavitation and nearly one in three had a history of some amount.

The breakdown of PDL, one expression showed approximately 40% had a PD lone negative cancer with the remaining 60% of PD lone positive cancers.

40% in the low range of 1% to 49% and about 20%.

High PD lone expression of 50% or greater.

The figure for progression free survival by independent Radiological Review Committee and analysis.

The trial was positive for the primary endpoint.

The hazard ratio of 060.

And a corresponding P value less than zero point zero zero zero what.

Median progression free survival was $11 one four months for the IV <unk> plus chemotherapy arm compared to 690 months for those patients receiving <unk> plus chemotherapy a difference of 424 months favoring the <unk> plus chemotherapy.

PFS by investigator assessment showed a consistent hazard ratio of <unk> 64.

When we look at various subgroups, it's important to highlight that the size of the subgroups or smaller by definition and not designed to show statistically show Ed.

Physically significant on their own but they can be informed.

The subgroup analyses for progression free survival confirms benefit in all Preplanned subgroups as indicated by point estimates for each subgroup landing on the left side of the dividing line favoring I Vanessa overall showing that the study results were observed broad and not driven by a specific <unk>.

Speaker #1: Receiving Tesla Lysimath plus chemotherapy, there is a difference of 4.24 months favoring the IVANESMAP plus chemotherapy arc. Progression-free survival (PFS) by investigators' assessment showed a consistent hazard ratio of 0.64.

SaaS or subsets of patients.

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

These progression free survival curves show the benefit in patients with negative low and high PD lone expression.

Represents a PD lone TPS scores less than 1%, 1% to 49% and 50% or more respectively at baseline.

Speaker #1: Treatment-related adverse events leading to discontinuation of Ivan Asmat Plus Chemotherapy or Tizolizumab Plus Chemotherapy occurred in 3.4% versus 4.2%, respectively. Based on the dual targeting of Ivan Asmat against PD-1 and VEGF, we analyzed adverse events that were thought to be immune-related or possibly VEGF-related.

Speaker #1: The subgroup analyses for progression-free survival confirm benefit in all clinically pre-planned subgroups, as indicated by point estimates for each subgroup landing on the left side of the dividing line, favoring IVANESMAP.

Patients with negative PD lone tumor expression had a hazard ratio of 055.

Those with low tumor PD lone expression.

Speaker #1: Overall, this study result shows that the findings are broadly observed and not driven by a specific subset of patients. These progression-free survival curves demonstrate a benefit in patients with negative, low, and high PD-L1 expression, representing PD-L1 TPS scores of less than 1%, 1% to 49%, and 50% or more, respectively, at baseline.

Had a hazard ratio of <unk>, six three and those with high tumor PD Lone expression had a hazard ratio of 0671.

Speaker #1: For the Ivan Asmat plus chemotherapy arm, compared to the Tizolizumab plus chemotherapy arm, grade 3+ potentially immune-related events were 10.2% versus 9%, and potentially VEGF-related events increased from 2.3% to 7.5%.

In other words.

I have an SMA demonstrated benefit relative to <unk> across the entire spectrum of tumor PD lone expression.

Objective response rate irrespective of PD Lone expression was improved for <unk> by an absolute difference of nine 4%.

Speaker #1: Patients in Q2 for Ivan Asmat Plus Chemotherapy showed only a small increase in treatment-related adverse events. Any grade events were 99.2% versus 98.5%, and serious treatment-related adverse events were 32.3% versus 30.2% in the Ivan Asmat and Tizolizumab arms, respectively.

Speaker #1: These events will be characterized further in the next slide. On the right, events are split out by the specific terms for adverse events. The most common events for Ivan Asmat treatment in combination with chemotherapy were common chemotherapy-related adverse events, including alopecia, anemia, and various laboratory abnormalities, including decreases in neutrophils, white blood cells, and platelet count.

In patients with PD lone expression less than 1% and those with PDL, one expression of 1% or greater objective response rate were improved for either NASA mab by an absolute difference of eight 5% and nine 9% respectively.

The median duration of response was also improved from eight four months statistical <unk> plus chemotherapy to 11, two months for IV <unk> plus chemotherapy.

Speaker #1: As such, these rates were similar and manageable between the two arms. Focusing further on immune and VEGF-related events, we see that most events were low-grade, with approximately 9-10% of immune-related adverse events reaching grade 3 or higher in either arm.

Treatment related adverse events showed only a small increase in the iron SMA.

Any great events, where 99, 2% versus 98, 5% and a serious treatment related adverse events were 32, 3% versus 32% in the <unk> antigen with Nab arms, respectively.

Speaker #1: Of interest, grade 3 or higher IRAEs, serious IRAEs, and IRAEs leading to discontinuation of Ivan Asmat or Tizolizumab were all numerically lower in the Ivan Asmat group.

Treatment related adverse events, leading to discontinuation of <unk>, plus chemotherapy or <unk> chemotherapy.

Speaker #1: Among the possibly VEGF-related events, proteinuria was seen in 27.1%, hemorrhage in 21.4%, and hypertension in 10.2% of patients, the vast majority being generally low-grade.

Occurred in three 4% versus four 2% respectively.

Based on the dual targeting of <unk> and SMA against PD, one and veg F. We annualized the adverse events that were thought to be immune related or possibly bed jetblue.

For the <unk>, plus chemotherapy arm compared to the two <unk> plus chemotherapy arm grade III plus potentially immune related events.

10, 2% versus 9%.

And potentially <unk>.

Jeff related events increased from two 3% to seven 5%. These.

These events will be characterized further in the next slides.

On the right events are split out by the specific terms for adverse events.

The most common events for IV <unk> treatment in combination with chemotherapy.

Our common chemotherapy related adverse events, including alopecia anemia, and various laboratory abnormalities, including neutrophil white blood cell and platelet count decreases.

These rates were similar and manageable between the two arms.

Focusing further on immune and VEGF related events, we see that most events were low grade with approximately 9% to 10% of immune related adverse events, reaching grade three or higher in either arm.

Of interest grade three or higher IRR aes serious iras and hiring these leading to discontinuation of either <unk> or 10th Louis Matt for all numerically lower in the eye of an estimate.

Among the possibly VEGF related events proteinuria was seen in 27, 1% hemorrhage in 21, 4% and hypertension and 10, 2% of patients the vast majority being generally low grade with.

With the rate of grade three hemorrhage under 2%.

Venous and arterial thrombotic events were zero in the control arm.

<unk> to 1% for each in the iron and estimate.

I want to pause here for a moment and speak to the validating and convincing safety profile seen yet again with either NASA that in the results of this study now in combination with Milo superb suppressive platinum doublet chemotherapy in a population of patients with advanced squamous non small cell lung.

<unk> cancer that was a real world experience that included patients.

With central potentially cavitary tumors and casing vessels in some cases and a history of hemostasis.

Speaker #1: With the rate of Grade 3 hemorrhage under 2%, venous and arterial thrombotic events were zero in the control arm, compared to 1% for each in the Ivan Asmat arm.

And a significant fraction this clearly differentiate Si and S map from what is feasible with a combination of routinely use PD, one or PD lone directed immune checkpoint inhibitor, plus VEGF monoclonal antibody therapies administered together.

Speaker #1: I want to pause here for a moment and speak to the validating and convincing safety profile seen yet again with Ivan Asmat in the results of this study, now in combination with myelosuppressive platinum doublet chemotherapy, in a population of patients with advanced squamous non-small cell lung cancer. This was a real-world experience that included patients with central, potentially cavitary tumors encasing vessels in some cases, and a history of hemoptysis in a significant fraction.

In summary, Ivan SMA provided a significant and clinically meaningful progression free survival benefit for advanced squamous non small cell lung cancer as first line treatment of patients in harmony six with an <unk> ratio of 0.60 that was consistent across all key key sub.

Groups, including those with negative low or high tumor PD lone expression and those with liver or brain metastases.

Speaker #1: This clearly differentiates Ivan Asmat from what is feasible with a combination of routinely used PD-1 or PD-L1 directed immune checkpoint inhibitor plus VEGF monoclonal antibody therapies administered together.

Third ratios and patients with negative low and high tumor PD lone expression, where 0.55, <unk> 63, and <unk> 71, respectively.

Speaker #1: In summary, Ivan Asmat provided a significant and clinically meaningful progression-free survival benefit for advanced squamous non-small cell lung cancer as the first-line treatment of patients in Harmony 6, with a hazard ratio of 0.60 that was consistent across all key subgroups, including those with negative, low, or high tumor PD-L1 expression, and those with liver or brain metastases.

<unk> strong performance across all levels tumor PD lone expression is important as Ivan SNF appears to provide clinically meaningful improvements to patients regardless of the degree of PD lone expression.

Sponsoring and duration of response, we're also increased.

<unk> was well tolerated with less than 2% grade three or higher bleeding events.

Low rates of adverse events, leading to discontinuation of debt both comparable to the <unk> plus chemotherapy.

Speaker #1: Hazard ratios in patients with negative low and high tumor PD-L1 expression were 0.55, 0.63, and 0.71, respectively. Ivan Asmat's strong performance across all levels of tumor PD-L1 expression is important, as Ivan Asmat appears to provide clinically meaningful improvements to patients regardless of the degree of PD-L1 expression.

The incidences of any grade <unk> treatment related adverse events were similar between the two arms.

Prior to harmony six there were no known phase III clinical trials in non small cell lung cancer that have shown a statistically significant improvement compared to PD, one or PDL, one inhibitor therapy in combination with chemotherapy in a head to head set false.

Speaker #1: Response rate and duration of response were also increased. Ivan Asmat was well tolerated, with less than 2% of grade 3 or higher bleeding events and low rates of adverse events leading to discontinuation or death.

Showing the success of our <unk> harmony to study in China, where the PFS benefit was observed in a monotherapy setting for patients who had squamous or non squamous tumors that were positive. One expression. This is now the second time in which we see <unk> based regimens becoming them.

Speaker #1: Both comparable to the Tizolizumab plus chemotherapy arm. The incidences of any grade treatment-related adverse events were similar between the two arms. Prior to Harmony 6, there were no known Phase 3 clinical trials in non-small cell lung cancer that have shown a statistically significant improvement compared to PD-1 or PD-L1 inhibitor therapy in combination with chemotherapy in a head-to-head setting.

First known investigational therapy to demonstrate a statistically significant benefit compared to standard of care PD, one or <unk>, one inhibitor based regimens.

This underscores the specific value that Ivan SNF and the harmony six regimen could bring to patients in this setting.

Speaker #1: Following the success of AKESO's Harmony 2 study in China, where the PFS benefit was observed in a monotherapy setting for patients who had squamous or non-squamous tumors that were positive for PD-L1 expression, this is now the second time in which we see Ivan Asmat-based regimens becoming the first known investigational therapy to demonstrate a statistically significant benefit compared to standard of care PD-1 or PD-L1 inhibitor-based regimens.

With the opportunities to include a differentiated mechanism of action for physicians and patients to choose.

<unk> has the potential to become a new standard of care for advanced squamous non small cell lung cancer, and we look forward to harmony three a global phase III study reading out in the coming months and years.

Importantly, we want to thank the patients and their families.

The clinical site personnel and the Casco team for carrying out the harmony six trial.

Speaker #1: This underscores the specific value that Ivan Asmat and the Harmony 6 regimen could bring to patients in this setting. With the opportunity to include a differentiated mechanism of action for physicians and patients to choose, Ivan Asmat has the potential to become a new standard of care for advanced squamous non-small cell lung cancer. We look forward to Harmony 3, a global Phase 3 study, reading out in the coming months and years.

And now I'd like to turn it over to Ricky Thanks, Jack I would like to Echo Jack's comments around our grad students by the patients who enrolled in harmony six how many members trial site personnel investigators and of course I cannot.

We are highly encouraged by the readout of the study.

Our other ongoing phase <unk> study in frontline non small cell lung cancer Carmony three harmony, seven PD, one therapy wheat or without chemotherapy, depending on the PDL one status.

Speaker #1: Importantly, we want to thank the patients and their families, the clinical site personnel, and the AKESO team for carrying out the Harmony 6 trial.

Is that what we're lending standard of care in frontline driver mutation negative lung cancer.

Speaker #1: And now, I'd like to turn it over to the key.

Avenue cannot both as monotherapy and in combination with chemotherapy compares favorably to the result of the PD one monoclonal antibody previous study right.

Speaker #2: Thanks, Jack. I would like to echo Jack's comments regarding our gratitude for the patients who enrolled in Harmony 6, family members, trial site personnel, investigators, and, of course, the AKESO team.

While additional overall survival data will be important in the future and consistent plenty plenty meaningful statistically significant results and progression free survival in harmony.

Speaker #2: We are highly encouraged by the readout of this study to our other ongoing Phase 3 studies in frontline non-small cell lung cancer. Harmony 3, Harmony 7, and PD-1 therapy with or without chemotherapy, depending on the PD-L1 status, is the overwhelming standard of care in frontline driver mutation-negative lung cancer.

And progression free survival and interim overall survival data for apartments.

Announced previously.

Very encouraging when we look to global studies currently treat already setup and beyond.

Yesterday's harmony six results presented at ethanol and subsequently published in the lancet are highly encouraging and showing the consistent performance.

Speaker #2: Ivan Asmat, both as monotherapy and in combination with chemotherapy, compares favorably to the results of the PD-1 monoclonal antibodies from previous studies. While additional overall survival data will be important to see in the future, the consistent, clinically meaningful, statistically significant results in progression-free survival in Harmony 6 and progression-free survival and interim overall survival data from Harmony 2 announced previously are very encouraging when we look to global studies Harmony 3, Harmony 7, and beyond.

And its ability to break into a setting where existing anti VEGF therapy is not an option due to historically observed tolerability concerns from early phase clinical trials harmony continues to validate the opportunity presented by <unk> to make a significant difference.

Across a vast number of patients facing solid tumor diagnosis.

I would also like to highlight several important updates to our phase III clinical development program that we have announced over the past few days.

Speaker #2: Yesterday's Harmony 6 results presented at ECMO and subsequently published in The Lancet are highly encouraging in showing the consistent performance of Ivan Asmat and its ability to break into a setting where existing anti-VEGF therapy is not an option, due to historically observed tolerability concerns from early-phase clinical trials.

It can be announced Friday, our clinical development plan has expanded beyond lung with the addition of our global phase III harmony Gi intrigue trial.

And brand New study evaluating <unk> as first line therapy.

First Brian Unresectable colorectal cancer.

Speaker #2: Harmony 6 continues to validate the opportunity presented by Ivan Asmat to make a significant difference across a vast number of patients facing solid tumor diagnoses.

Including study sponsored by our partner Okay. So this brings the number of planned or ongoing phase III clinical trials to 14 into <unk>.

Evaluating <unk> in multiple solid tumors, including lung colorectal breast head and neck.

Speaker #2: I would also like to highlight several important updates to our Phase 3 clinical development program that we have announced over the past few days.

They track and pancreatic cancer.

Speaker #2: As we announced Friday, our clinical development plan has expanded beyond lung cancer with the addition of our global Phase 3 Harmony GI-3 trial, a brand new study evaluating Ivan Asmat as first-line therapy in unresectable colorectal cancer.

This is the global Phase III study and the first global Phase III study to be conducted.

Thank you Matt beyond lung cancer.

We already have the harmony Gi tree study design and what drove our conviction to initiate this study shortly but wanted to take a moment to remind everyone of the impressive development effort behind that growing.

Speaker #2: Including studies sponsored by our partner AKESO, this brings the number of ongoing phase 3 clinical trials to 14 in total, evaluating Ivan Asmat in multiple solid tumors, including lung, colorectal, breast, head and neck, biliary tract, and pancreatic cancer.

Collective pipeline.

Turning to our ongoing phase III trials, I will provide a regulatory update on harmony and as well as updates related relating to harmony three protocol amendment.

<unk> expectations for data Readouts.

Speaker #2: This is the fourth global Phase 3 study and the first global Phase 3 study to be conducted with Ivan Asmat beyond lung cancer. I will review the Harmony GI-3 study design and what drove our conviction to initiate this study shortly, but I wanted to take a moment to remind everyone of the impressive development effort behind the growing collective pipeline of Ivan Asmat.

I would like to take a moment to express our gratitude and working thus far with the FDA regarding our clinical development of <unk>.

<unk> for Phase III <unk> study, we have had a number of interactions.

The agency and their feedback and advice are invaluable.

When we plan to move forward with the harmony study up and signing the collaboration agreement to acquire the rights I have any spot we have.

Speaker #2: Turning to our ongoing Phase 3 trials, I will provide a regulatory update on Harmony, as well as updates related to a Harmony 3 protocol amendment, including expectations for data readouts.

Multiple interactions with the agency regarding how to proceed.

That collaboration demonstrated our ability to move forward with a clinical study based on early phase clinical trial data that had been generated in China. Prior to our acquisition of a right even the strong potential of Ione Cmos and opportunity to make a meaningful difference to patients in a setting that has very limited.

Speaker #2: I would like to take a moment to express our gratitude for working thus far with the FDA regarding our clinical development of Ivan Asmat.

Speaker #2: With four Phase 3 clinical studies, we have had a number of interactions with the agency, and their feedback and advice are invaluable. When we plan to move forward with a Harmony study upon signing the collaboration agreement to acquire the rights to Ivan Asmat, we have multiple interactions with the agency regarding how to proceed.

What are the options.

Something that really reflects the agency's commitment to patients facing difficult diagnosis with limited options.

We are incredible to work with the agency and appreciate the endless hours that members of the agency spend with the best interest of patients always in mind.

Speaker #2: The collaboration demonstrated our ability to move forward with a clinical study based on early phase clinical trial data that had been generated in China, prior to our acquisition of our rights, given the strong potential of Ivan Asmat and the opportunity to make a meaningful difference to patients in a setting that had very limited therapy options. This really reflects the agency's commitment to patients facing difficult diagnoses with limited options.

Based on the results of the Harmony study today, we announced that we submitted a biologics license application or BLA with the FDA in order to seek approval for <unk> plus chemotherapy for these proposed indication in the United States.

We intend to submit it BLA during the fourth quarter of 2025.

As previously disclosed the FDA noted that.

Speaker #2: We are incredibly proud to work with the agency and appreciate the endless hours that members of the agency spent with the best interests of patients always in mind.

Statistically significant overall survival benefit is necessary to support marketing authorization in the setting.

After careful consideration of the safety and efficacy profile of the current FDA approved option to patients in this setting the positive ratio consistent results of these phase III multi regional study as well as discussion with key opinion leaders and physicians who have.

Speaker #2: Based on the results of the Harmony study, today we announced that we will submit a Biologics License Application (BLA) with the FDA in order to seek approval for Ivan Asmat plus chemotherapy for this proposed indication in the United States.

At many start I've only came out to patients we believe that the safety and efficacy data generated in the harmony study demonstrate that patients suffer.

Speaker #2: We intend to submit the BLA during the fourth quarter of 2025. As previously disclosed, the FDA noted that a statistically significant overall survival benefit is necessary to support marketing authorization in this setting.

For Egfr mutated non small cell lung cancer in this setting can benefit from the I've only seen Margaret.

Speaker #2: After careful consideration of the safety and efficacy profile of the current FDA-approved options to patients in this setting, the positive regional consistent results of this Phase 3 multi-regional study, as well as discussions with key opinion leaders and physicians who have administered Ivan Asmat to patients, we believe that the safety and efficacy data generated in the Harmony study demonstrate that patients suffering from EGFR mutant non-small cell lung cancer in this setting can benefit from the Ivan Asmat regimen.

This is a monumental moment in the development up I've only Cmos and we are excited for the opportunity to work with the U S. FDA in order to discuss our application.

Yesterday, we also announced updates to our global Phase III Harmony study, which is intended to evaluate <unk> combined with chemotherapy compared to Pembroke and anti PD, one anti body combined with chemotherapy in patients with first line in the past I think squamous and non squamous non small cell lung.

Cancer.

The study is currently enrolling patients globally and is conducted with Registrational intent for the United States and other agents retain summit license territory.

Speaker #2: This is a monumental moment in the development of Ivan Asmat, and we are excited for the opportunity to work with the U.S. FDA in order to discuss our application.

The primary endpoint for this study are progression free survival and overall survival.

Speaker #2: Yesterday, we also announced updates to our global Phase 3 Harmony 3 study, which is intended to evaluate Ivan Asmat combined with chemotherapy compared to pembrol and anti-PD-1 antibody combined with chemotherapy in patients with first-line metastatic squamous and non-squamous non-small cell lung cancer.

Summit has amended the protocol for the <unk> study in order to separate the statistical analysis of data of their primary endpoints by histology. Therefore average third would be separate analysis conducted to evaluate <unk> plus chemotherapy compared to <unk> plus chemo in <unk>.

<unk> with squamous non small cell lung cancer and in patients with non squamous non small cell lung cancer.

Speaker #2: This study is currently enrolling patients globally and is conducted with registrational intent for the United States and other regions within Summit's licensed territories. The primary endpoints for this study are progression-free survival and overall survival.

As a result of having two separate intention to treat analysis in the harmony tree study that analysis for squamous tumors and non squamous tumors may be conducted at separate time as each analysis will be conducted up and reaching pre specified numbers of events in each cohort.

Speaker #2: Summit had amended the protocol for the Harmony 3 study in order to separate the statistical analysis of data for the primary endpoint by histology.

Ultimately it will allow us to read out data earlier for squamous non small cell lung cancer and ultimately potentially move forward more quickly in frontline lung cancer for patients seeking improved option over the existing standard of care.

Speaker #2: Therefore, there will be separate analyses conducted to evaluate Ivan Asmat plus chemotherapy compared to pembrol plus chemo in patients with squamous non-small cell lung cancer and in patients with non-squamous non-small cell lung cancer.

Currently we expect to complete enrollment in the squamous cohorts of <unk> three in the first half of 2026 and expect to reach the pre specified number of events for the progression free survival fueled primary endpoint analysis for disclaimers cohort in the second half of 2026 and interim analysis.

Speaker #2: As a result of having two separate intention-to-treat analyses within the Harmony 3 study, the analyses for squamous tumors and non-squamous tumors may be conducted at separate times, as each analysis will be conducted upon reaching phase-specified numbers of events in each cohort.

As for overall survival may be conducted at the similar time.

Speaker #2: Ultimately, this will allow us to read out data earlier for squamous non-small cell lung cancer and potentially move forward more quickly in frontline lung cancer for patients seeking improved options over the existing standards of care.

Turning to non squamous at present time sub summit expects to complete enrollment in the non squamous cohorts of <unk> three in the second half of 2026 and expect to reach the specified number of events further progression fee survival endpoint analysis for these non squamous cohort in.

Speaker #2: Currently, we expect to complete enrollment in the squamous cohort of Harmony 3 in the first half of 2026 and anticipate reaching the pre-specified number of events for the progression-free survival dual primary endpoint analysis for the squamous cohort in the second half of 2026.

The first half of 2027 and interim analysis for overall survival is planned to be conducted based up in reaching a pre specified number of EBIT.

In order to sufficiently powered each of their towards primary endpoints in both cohorts of the study summit plans to enroll approximately 600 patients. It's one less non small cell lung cancer and approximately 10000 patients with non squamous non small cell lung cancer for a total of approximately one.

Speaker #2: An interim analysis for overall survival may be conducted at a similar time. Turning to non-squamous, at this present time, Summit expects to complete enrollment in the non-squamous cohort of Harmony 3 in the second half of 2026 and expects to reach the pre-specified number of events for the progression-free survival endpoint analysis for this non-squamous cohort in the first half of 2027.

1600 patients enrolled in harmony tree, which is reflected in this updated harmony tree study design side.

While we are increasing the sample size, we are over 80% enrolled in the squamous cohorts and as I mentioned, we believe we will complete enrollment in the first half of next year and the non squamous cohort is enrolling fast and with complete enrollment short time thereafter.

Speaker #2: An interim analysis for overall survival is planned to be conducted based upon reaching a pre-specified number of events. In order to sufficiently power each of the dual primary endpoints in both cohorts of this study, Summit plans to enroll approximately 600 patients with squamous non-small cell lung cancer and approximately 1,000 patients with non-squamous non-small cell lung cancer, for a total of approximately 1,600 patients enrolled in Harmony 3, which is reflected in this updated Harmony 3 study design slide.

We projected to be the second half of next year.

Ultimately will allow us to have these technologies fully powered by cohort in order to allow for us to have a clear regulatory path forward for frontline lung cancer around the world.

As mentioned earlier, our phase III clinical development program has expanded beyond along with the intention of harmony Gi treat a global phase III.

Speaker #2: While we are increasing the sample size, we are over 80% enrolled in the squamous cohort, and as I mentioned, we believe we will complete enrollment in the first half of next year. The non-squamous cohort is enrolling fast and will complete enrollment shortly thereafter, currently projected to be in the second half of next year.

While evaluating <unk>, plus chemo compared to favor plus chemo.

As first line therapy in patients with funds Resectable metastatic colorectal cancer here, we see this study.

Speaker #2: This ultimately will allow us to have distinct analyses fully powered by cohorts, in order to allow for us to have a clear regulatory path forward for frontline lung cancer around the world.

Kim for Harmony, Gi tree, which has a primary endpoint of progression free survival.

Clinical trial sites in the United States are planned to begin activating by the end of this year.

Speaker #2: As mentioned earlier, our Phase 3 clinical development program has expanded beyond lung with the intention of Harmony GI-3, a global Phase 3 trial evaluating Ivan Asmat plus chemo compared to BEVA plus chemo as first-line therapy in patients with unresectable metastatic colorectal cancer.

And we currently expect to enroll a total of 600 patients in harmony Gi trip.

Each year at 48000 patients are estimated to be diagnosed wheat or have recurrent metastatic microsatellite stable in metastatic colorectal cancer also known as the mismatch repaired proficient colorectal cancer.

<unk> P M M. R C R.

Speaker #2: Here we see the study for Harmony GI-3, which has a primary endpoint of progression-free survival. Clinical trial sites in the United States are planned to begin activating by the end of this year, and we currently expect to enroll a total of 600 patients in Harmony GI-3.

There have been limited options approved in the United States in the last 20 years for those first line patients, whose tumors are not positive for certain biomarkers or other activating mutations.

Microsatellite stable metastases colorectal cancer is a setting where monocular PD one inhibitors, such as <unk> and needle have failed to show a clinically meaningful benefit anti VEGF therapy like <unk> plus chemotherapy is the standard of care for many patients with <unk>.

Speaker #2: Each year, 48,000 patients are estimated to be diagnosed with or have recurrent metastatic microsatellite stable metastatic colorectal cancer, also known as mismatch repair proficient colorectal cancer or PMMRCRC.

First line metastatic microsatellite stable.

Colorectal cancer.

Speaker #2: There have been limited options approved in the United States in the last 20 years for those first-line patients whose tumors are not positive for certain biomarkers or other activating mutations.

Based on extensive feedback with Kols and treating physicians in this space, we have opted to evaluate smart we've told folks in the study.

I will take a moment to walk through the data. We have previously shared in first line CRC as a brief reminder, as to the potential of <unk> and.

Speaker #2: Microsatellite-stable metastatic colorectal cancer is a setting where monoclonal PD-1 inhibitors such as pembrolizumab and nivolumab have failed to show a clinically meaningful benefit.

In this setting.

Why is the data is with Fox.

Proxy rate and more intense chemotherapy regimen. We also noted in our release that we enrolled patients in both the U S and China, which ballpark as well to test I want Cmos with much less chemotherapy auction.

Speaker #2: Anti-VEGF therapy, like bevacizumab plus chemotherapy, is the standard of care for many patients with first-line metastatic microsatellite stable metastatic colorectal cancer. Based on extensive feedback with KOLs and treating physicians in this space, we have opted to evaluate Ivan Asmat with FOLFOX in this study.

Fox in combination with a monoclonal antibody such as <unk> represent a preferred treatment regiments for physicians treating MSS CRC patients in the United States and other western territories.

Speaker #2: I will take a moment to walk through the data we have previously shared in first-line CRC as a brief reminder as to the potential of Ivan Asmat in this setting.

Last year at the 2024 annual Congress of the European Society of medical oncology or ESMO 2020 for Aircastle presented encouraging 8-K, 112, <unk> phase two data of <unk> in combination with PARP fluctuate chemotherapy in patients with <unk>.

Speaker #2: While the data is with FOLFOXIRI, a more intense chemotherapy regimen, we also noted in our release that we enrolled patients in both the U.S. and China with FOLFOX as well, to test Ivan Asmat with multiple chemotherapy options.

Microsatellite stable catastrophe colorectal cancer here, we see the figure for <unk> eight.

Speaker #2: FOLFOX in combination with a monoclonal antibody such as Bevacizumab (BEVA) represents a preferred treatment regimen for physicians treating MSS CRC patients in the United States and other Western territories.

<unk> eight <unk> study.

In the phase II study.

<unk> in combination with chemotherapy demonstrated an overall response rate of 81.

<unk>, 8% and a D C are 100% in 22 patients with.

Speaker #2: Last year, at the 2024 Annual Congress of the European Society of Medical Oncology, or ESMO 2024, AKESO presented encouraging Phase 2 data of AK112 206 from Ivan Asmat in combination with FOLFOXIRI chemotherapy in patients with microsatellite stable metastatic colorectal cancer.

Cohort of 8-K 112, <unk> was conducted in China sponsored by a queso with all relevant data exclusively generated manage and analyze by itself.

And I Wanna Sema, plus ballpark theory chemotherapy or there were no treatment emergent adverse events.

Speaker #2: Here we see the figure for AKESO AK112 206 study. In this Phase 2 study, Ivan Asmat, in combination with chemotherapy, demonstrated an overall response rate of 81.8% and a DCR of 100% in 22 patients.

Add to permanent discontinuation of <unk> as of the data cut off drove the ESMO 2020 for presentation.

Subsequently as I said this phase II study was expanded to include additional patients from the U S and China to steady agonists Cmos and.

In combination with <unk> chemotherapy.

Speaker #2: This cohort of AK112 206 was conducted in China, sponsored by Akeso, with all relevant data exclusively generated, managed, and analyzed by Akeso. In the Ivan Asmat Plus FOLFOXIRI chemotherapy arm, there were no treatment-emergent adverse events that led to permanent discontinuation of Ivan Asmat as of the data cutoff from the ECMO 2024 presentation.

The data from the initial patient cohort presented at ESMO 2024, <unk> <unk> to make measure in addition to the global Phase II data generated combination Beachball proxy you do not yet state in China, which support the design of some each phase III harmony <unk> study.

In addition to the announcements are many Gi treat a new global phase III study in first line Unresectable metastatic colorectal cancer semi today analysis its intention to expand its ironic kebob clinical development program with an additional set of phase III <unk> study, we intend to provide at this.

Speaker #2: Subsequently, as I said, this Phase 2 study was expanded to include additional patients from the U.S. and China to study Ivan Asmat in combination with FOLFOX chemotherapy.

Speaker #2: The data from the initial patient cohort presented at ECMO 2024 have continued to mature, in addition to the global Phase 2 data generated in combination with FOLFOX in the United States and China.

Ill color with respect to these phase III studies in the first quarter of 2026 with that I will now turn the call over time needs to provide an operational and financial updates for the quarter.

Speaker #2: With support, the design of the Summit Phase 3 Harmony GI-3 study is ongoing. In addition to the announcement, Harmony GI-3 is a new global Phase 3 study in first-line unresectable metastatic colorectal cancer. Summit today announces its intention to expand its Ivan Asmat clinical development program with an additional set of Phase 3 clinical studies.

Thank you Mickey and good morning, everyone.

In addition to providing the data update on our cash position and operating expenses I will also provide color on our clinical operations.

Can you start with an update on our clinical operations.

The harmony study is enrolling ahead of our goals and as Micky mentioned, we have enrolled over 80% of the annuity plan 600 squamous patient cohort.

Speaker #2: We intend to provide additional color with respect to this Phase 3 study in the first quarter of 2026. With that, I will now turn the call over to Manmeet to provide an operational and financial update for the quarter.

And now expect to complete enrollment for the squamous cohort of how many three during the first quarter of 2026.

Okay.

To remind you the non squamous cohort harmony III was initiated during first quarter of 2025 adopt two is enrolling ahead of our plan.

Speaker #2: Manmeet?

Speaker #3: Thanks, Mekti, and good morning, everyone. Today, in addition to providing the new update on our cash position and operating expenses, I will also provide color on our clinical operations.

And now we expect to complete enrollment 4000 patient during the second half of 2026.

Speaker #3: Let me start with an update on the clinical operations front. The Harmony 3 study is enrolling ahead of our goals, and as Mekti mentioned, we have enrolled over 80% of the newly planned 600 squamous patients cohort. We now expect to complete enrollment for the squamous cohort of Harmony 3 during the first quarter of 2026.

Or how many seven study was initiated during the first quarter of 2025, and we have activated over 50% of our selected sites globally.

And for our newly announced phase III. The <unk> III study, we have already started planning and sites are planned to begin activating in the United States prior to the end of the year 2025.

Speaker #3: To remind you, the non-squamous cohort in Harmony 3 was initiated during the first quarter of 2025, and that too is enrolling ahead of the plan.

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

<unk> ended the third quarter of 2025 with a cash position of approximately $248 6 million Boenning.

Speaker #3: And now we expect to complete enrollment for 1,000 patients during the second half of 2026. Our Harmony 7 study was initiated during the first quarter of 2025, and we have activated over 50% of the selected sites globally.

Turning to operating expenses I will provide details on both GAAP and non-GAAP numbers.

You can refer to our press release issued this.

Morning for a reconciliation of GAAP to non-GAAP financial measures.

As a reminder, our non-GAAP expenses exclude stock based compensation expenses.

Speaker #3: And for our newly announced Phase 3, the Harmony GI-3 study, we have already started planning, and sites are planned to begin activating in the United States prior to the end of the year 2025.

Our total GAAP operating expenses for the third quarter.

<unk> 2005 was $234 2 million.

Speaker #3: On the financials front, let me start with our cash position. We ended the third quarter of 2025 with a cash position of approximately $238.56 million.

Compared to $568 4 million for second quarter of 2025.

The decrease in GAAP operating expenses was primarily due to the higher stock based compensation expense of approximately $348 $2 million. A result of the modification of Unvested stock options recording during the previous quarter.

Speaker #3: Turning to operating expenses, I'll provide details on both GAAP and non-GAAP numbers. You can refer to our press release issued this morning for a reconciliation of GAAP to non-GAAP financial measures. As a reminder, our non-GAAP expenses exclude stock-based compensation expenses.

Overall, our non-GAAP operating expenses during the third quarter of 2025 were 103 or $4 million.

Compared to $89 $6 million for the previous quarter.

Speaker #3: Our total GAAP operating expenses for the third quarter of 2025 were $234.2 million compared to $568.4 million for the second quarter of 2025.

The increase in non-GAAP operating expenses was primarily related to an increase in R&D expenses related to how many <unk> and how many seven trucks.

And with that our 100 back over to Dave.

Speaker #3: The decrease in GAAP operating expenses was primarily due to the higher stock-based compensation expense of approximately $348.2 million as a result of the modification of unrestored stock options according to the previous quarter.

Sure.

Thank you Tim.

I'll now see if there are any questions that our team can help answer if you could please open the line for questions.

At this time I would like to remind everyone in order to ask a question Press Star then the number one on your telephone keypad, we encourage everyone to limit yourselves to one question and one follow up we will pause for just a moment to compile the Q&A roster.

Speaker #3: Overall, our non-GAAP operating expenses during the third quarter of 2025 were $103.4 million, compared to $89.6 million for the previous quarter. The increase in non-GAAP operating expenses was primarily related to an increase in R&D expenses associated with Harmony 3 and Harmony 7 trials.

Your first question comes from the line of Yigal <unk> with Citi. Your line is open.

Hi, great. Thank you very much for taking the questions.

Speaker #3: And with that, I will hand it back over to Dave. Dave?

So the first one I had is when could we expect to see the first OS cut from harmony six would it be before the second half of 2026 PFS readout for harmony three in squamous and then the other question is given harmony six was powered 86, 3% for hazard ratio of <unk> seven.

Speaker #4: Thank you, team. We'll now see if there are any questions that our team can help answer. Dave, if you could please open the line for questions.

Speaker #5: At this time, I would like to remind everyone that in order to ask a question, press star, then the number one on your telephone keypad.

Speaker #5: We encourage everyone to limit yourselves to one question and one follow-up. We will pause for just a moment to compile the Q&A roster. Your first question comes from the line of legal legitimates with Siri; your line is open.

But you hit on a lower hazard ratio of <unk> six I'm curious what that may imply about OIS powering for the study given that was powered at 80% for hazard ratio of <unk> 73, the implication potentially that you may have more RF power than originally designed.

Speaker #6: Hi, great. Thank you very much for taking the questions. So the first one I had is, when could we expect to see the first OS cut from Harmony 6?

Okay.

Very good question.

Speaker #6: Would it be before the second half, 2026 PFS readout for harmony 3 and squamous and then the other question is, given harmony 6 was powered 86.3% for hazard ratio of 0.7, but you hit on a lower hazard ratio of 0.6, I'm curious what that may imply about OS powering for the study given that was powered at 80% for hazard ratio of 0.73.

Thanks <unk> this is Dave.

One thing that I want to make sure.

As Larry mentioned this is a study that was conducted by our partners. So.

And so one thing that we don't do is get in front of us.

With respect to disclosing additional details beyond what the current disclosed and so.

If we look overall obviously.

Speaker #6: The implication is potentially that you may have more OS power than originally designed. Thanks.

Protocol.

Colocation.

And I want to congratulate you again.

I guess so.

For the patient.

Obligations that became available yesterday.

Speaker #1: Very good question.

Speaker #2: Dave?

Speaker #4: Thanks again. This is Dave. So one thing that I want to make sure is clear is that, as we mentioned, this is a study that was designed and conducted by our partners, AKESO.

But in terms of differentiating details between.

It's just the power and whatnot I believe that through our partners that are careful but I think one thing that you can see from in general.

Speaker #4: And so one thing that we don't do is get in front of AKESO with respect to disclosing additional detail beyond what they've currently disclosed.

<unk> four.

Testing is that there's likely something.

Thank you to reduce in 2026, but it can be it's important to remember fit from a time to event.

Speaker #4: And so I think if we look overall, obviously the protocol is included within the publication. And I want to congratulate again our partners, AKESO, for both the presentation and the Lancet publication that became available yesterday.

Perspective, and a pre specified number of events and an analysis.

We hope patients do well and we hope patients continue to exceed expectations and so knowing exactly.

Speaker #4: But in terms of differentiating details between planned and adjusted power and whatnot, I leave that to our partners at AKESO. But I think one thing that you can see from in general, the plan for testing is that there's likely something that can be reviewed in 2026, but it's it's important to remember that from a time to event perspective and a pre-specified number of events and an analysis, you know we hope patients do well and we hope patients continue to exceed expectations into knowing exactly the order of events becomes a little bit different difficult, excuse me, but this is events-driven.

The order of events it comes a little bit different difficult difficult excuse me.

But this is event driven so at some point.

Next year is probably a fair estimate, but more specific to that is a little bit.

Little bit beyond where we would like at this point.

Deferred to our partners there.

And then just the other follow up obviously, making you talked a lot about.

<unk> studies CRC and then you mentioned additional set of phase III, where you might get more details and might get more details on <unk> 26, so all of that points to the questions around around funding.

I'm just curious if you could speak at least to some extent as to what options are being evaluated.

To extend the runway what the priorities are in terms of how you may have.

Speaker #4: And so at some point, you know, next year is probably a fair estimate, but more specific than that is a little bit beyond where we would like to disclose at this point.

Raise additional capital thank you.

How does it all.

G preferreds are answered correctly.

Speaker #4: And defer to our partners there.

Okay, well that is cheaper than that.

Speaker #6: And then just the other follow-up, obviously Mekti, you talked a lot about new studies, CRC, and then you mentioned an additional set of Phase 3s.

Thanks.

Yes, we have an ATM out there.

Give or take $350 million.

<unk> had some inbound.

Interest.

And additional capital.

Just a few weeks ago additional capital so.

We'll move straightforward on that.

I'm happy to have the opportunity.

<unk>.

I think others are too so you'll see that as it plays out.

Predictive amount quite yet, but I'm aware of all the numbers.

Our plans going forward.

Empirical evidence.

As a product that is crying out for significant investments has demonstrated its capacity to enter into a business.

A leading player is generating roughly $34 million in revenue over the next three years.

Hi.

$1 billion in free cash flow so.

This is a significant opportunity.

We do not want to Miss it.

We also feel that.

Key to making that happen is for this team to add patrols start stop and change.

A number of variables leading to our ultimate success.

We're happy with the position that we have so all of that.

Gives you some adjustment to the issues of finance.

And a.

As soon as we have more <unk>.

Information regarding other clinical trials for Shire, we are going to communicate.

As.

<unk>.

Okay.

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

Hey, guys good morning, and congratulations on the unprecedented harmony six results.

I guess I wanted to ask about the BLA submission given the confirmation of the BLA by year end based upon the harmony data can you provide any color as to how your interactions with the FDA have gone and how the precedent approvals with have you been to mab or data might support.

Approval by Vanessa.

Thanks for the question.

Okay.

Should we just be.

Balanced today.

I think Joe pile in the fourth quarter.

Yes.

I think putting the package together.

We have continued interaction with the FCA.

And obviously after the events of sufficient we are looking forward to getting specific feedback.

Speaker #1: Any color as to how your interactions with the FDA have gone, and how the present approvals with ME/VantaMab or DATO might support the approval of IVINESAMAB?

Any color.

Olivia.

After the submission you haven't these reviews.

The most recent of post approval.

Accurate actually saw balances kubota optimism previously treated egfr patients.

Speaker #2: Thanks for the question. It's also, so yes, we announced today and also looked to release that we are planning to file in the fourth quarter of this year.

Okay.

Both.

And also previously Jeff.

Patients and.

Speaker #2: Yeah, I certainly finalized including the package together. We have continued interaction with the FDA, and obviously after we have made the submission, we are looking forward to, you know, getting specific feedback and giving some color early next year.

If you are aware in August we'll be aware of that.

Neither of those other peoples.

We added significant OS benefit.

Have also disclosed previously by <unk> and Fcs.

SaaS bookings expected.

In our study.

Speaker #2: After the submission, we have indeed reviewed the most recent, of course, approval and the accuracy. As you mentioned, the relevances, the approval for IVINESAMAB in previously treated EGFM patients, as well as the data CX approval.

But we do think that this with talent.

Peter.

Combination of efficacy and safety.

It's a strong package actually moved forward.

To becoming available for these patients. So therefore, we are.

Moving forward with sufficient.

Speaker #2: in also previously treated EGFR, patients. And, if you are aware and obviously we are fully aware that, neither of those other approvals that included a significant OS benefit, we have also disclosed previously, but I'm just reviewing it that FDA has told us that they are looking to expecting OS, in our setting.

You haven't announced.

That's great and just as a quick follow up did you discuss the latest overall survival data that surpass the statistical threshold at world lung with the FDA.

Yes, we are not going to go into the detail. So in fact discussions with the FDA, but I can confirm that <unk> contract.

Contact with them and sharing information whatever focus for yourselves.

Speaker #2: But we do think that the totality of our data, from a combination of efficacy and safety, is a strong package that should be moved forward to become available for these patients.

Your next question comes from the line of Brad <unk> with Guggenheim Securities. Your line is open.

Speaker #2: So therefore, we are moving forward with the submission, as we have announced.

Hey, Thanks, Steve Summit and great to see the data at ESMO and this panel large crowd yesterday.

Speaker #1: That's great. And just as a quick follow-up, did you discuss the latest overall survival data that surpassed the statistical threshold at World Lung with the FDA?

Maybe another follow up on the BLA I understand the logic of trying to get this drug to patients as quickly as possible given the data that you have but from a business perspective can you help me understand the strategic thinking of now.

Wanting to submit the harmony study and undertaking that review issue of how to deal with the OS is the first time, the FDA will review a BLA package driving enough map.

Especially when you have harmony.

Three you potentially coming as soon as second half 'twenty six for PFS and OS I guess, my thinking was that might be a better package to submit first and then have farm and E comm as a supplement or something like that so just how youre thinking about that would be helpful to hear thank you.

Sure.

We have had certainly many of those cash flows just to confirm insurer in India.

That scenario.

But in big in principal of our thinking is that each indication.

We'll have a full submission.

This particular package is making now.

How much was data capsule.

Got it.

In the data.

Our long term follow up between the west locations.

The age of patients.

And we think this is the right opportunity and get going forward.

That doesn't mean in the future continuing going to look at this business, we might earn two other packages in the future.

And separately can you talk to your <unk> comments.

We see also came from FDA.

We will make those adjustments for the future.

Okay. Thank you and then separately just quickly on the colorectal phase III you mentioned theres. Some undisclosed in house data can you talk qualitatively about what that is the extent of it and what species were explored and then when would we expect to see those data presented to further support the phase III.

Thank you.

Sure Brad This is Dave So I think one of the things that makes you spoke about was we had previously presented.

Yes.

Yes.

Data with our partners that are cast so in 2020 for it as well.

That was validated with respect to not just colorectal but at BEC.

Well as <unk>.

Triple negative breast cancer, what Ben has since happened both the peso as well.

An expansion of.

That phase III to include patients in the U S was conducted and so with that we've had multiple backbones of chemotherapy, which had been reviewed with I've been asked about as well as the novel novel combinations.

With <unk> in this setting and so what that's done is it's given a bit of exposure to the drug as well as the ability to compare historical results with different chemo backbones.

In order to kind of validate what we're seeing and the consistency of that data and so we ultimately chose based on the standard of care that existed.

Strong preference.

For both patients and physicians to move forward with the full box.

But theres quite a bit of data that's been generated across a number of different backbones, which gives us quite a bit of confidence and as I'm sure you're aware, but but also to note our partners and guests who are running a phase III study in this setting as well so.

Another just another data point with respect to confidence that we have for.

<unk> opportunity in the study.

Your next question comes from the line of solvent Ritchie with Goldman Sachs. Your line is open.

Thank you for taking my questions.

To harmony 16 PDL.

Status.

With interesting and we see.

PD lone.

The negative outperformed PD lone positive could you just help us.

Maybe understand what's playing out there and then.

Translational work that you are going to be doing to kind of help the oncologists with determining how to best position here.

Okay.

In terms of <unk> in the PDL, one expression I would say that.

It's not I don't see it as necessarily but the negatives are outperforming the others, but rather that.

The differential effect is a little greater.

In.

In the PD lone negative patients to me that's not that surprising I would say is clinician talking with Oliver by other clinician colleagues, we've long recognized that although.

Speaker #1: Let's play out there. And then the translational work that you're going to be doing to, you know, kind of help the oncologists with determining how to best position here.

Other regimens that are FDA approved here have some.

Some incremental benefit.

Speaker #2: In terms of Harmony 6 and the PD-L1 expression, I would say that it's not, I don't see it as necessarily that the negatives are outperforming the others, but rather that the differential effect is a little greater.

From the addition of the <unk>.

The checkpoint inhibitor.

That benefit is.

As tepid, it's rather minimal and these are patients. This whole group is one that that has disappointing outcomes, even with our current standards of care and so there is there's really a lot of room to do better.

Speaker #2: In the PD-L1 negative patients, to me, that's not that surprising. I would say that as a clinician talking with all of my other clinician colleagues, we've long recognized that although other regimens that are FDA-approved here have some incremental benefit from the addition of the checkpoint inhibitor, that benefit is tepid.

In this case I would say that it may be suggested that this is a setting where we're.

Where.

There are.

So this may be a setting where.

Jeff components may be especially relevant and I will say that it's important to also recognize this these are subsets.

Speaker #2: It's rather minimal and these are patients this whole group is one that, that has disappointing outcomes, even with our current standard of care. And so there's, there's really a lot of room to do better.

We're going to have additional information to look at these whether it's just a trend between harmony six in harmony three.

But that.

It's important to note that in the patients, particularly with high PDL, one that group had.

Speaker #2: in, in this case, I would say that it, it may be suggestive that this is a setting where there are--I'm sorry, this may be a setting where VEGF components may be especially relevant.

Our smaller that was about half of the size of the other groups and so I wouldn't want to put too fine a point on any of these subset analyses. There theyre just suggested and all of them showed the same trend.

Speaker #2: And, I, I will say that it's important to also recognize this, these are subsets, we're going to have additional information to look at these and whether it's consistent trends, between Harmony 6 and Harmony 3, but that, it's important to note that in the patients particularly with the high PD-L1, that group had a smaller--that was about half of the size.

Dave.

Overall conclusion of the superior with just.

Just to varying degrees.

[laughter].

Brad if I may just touch back on your question on Egfr.

We're really pleased to see.

FDA approved are taking that trial off there are a number of major issues to hand on that trial one of them was.

Speaker #2: Of the other groups. And so, I wouldn't want to put too fine a point on any of these subset analyses. They're just suggestive, and all of them showed the same trend or the same overall conclusion of being superior, with, I guess, just varying degrees.

China versus USA data translate ability.

That was we put a rope rather than the GAAP or that there is some significant translate ability is obviously.

Dynamic issues. It is also the issue leaders.

Egfr and we certainly put that one to rest there is also the issue of brain Mets.

Speaker #3: Brad, if I may just touch back on your question on EGFR, we were really pleased that the FDA approved taking that trial on.

Very seriously.

We are members of our family we put that issue to rest then there was the bi specific very novel.

And we've put that issue to reps so.

Speaker #3: There were a number of major issues to hand on that trial. One of them was China versus USA data translatability. That was, we put a real feather in the cap of that; there is some significant translatability as obviously a very dynamic issue.

That would not have happened to have the FDA has not allowed us to move forward.

In Eurasia.

Our trials.

We will always have to Chinese patients two thirds one third.

Two thirds.

We're very very pleased about that but on the record.

Speaker #3: There's also the issue of bleeders and EGFR, and we certainly put that one to rest. There was also the issue of brain mets. There's something very serious that has to do with members of my own family; we put that issue to rest.

<unk>.

I will perform probably well.

Progression free survival hazard ratio of <unk> five two we did better than.

Speaker #3: Then there was the bispecific, very novel, and, you know, we put that issue to rest. So, that would not have happened if the FDA had not allowed us to move forward.

That marketplace.

On the P value.

We had over five seven.

It's just not pass muster.

It's important to note that.

You will receive feedback from the FDA.

Speaker #3: Now, in a continuation, our trials will probably always have Chinese patients. It won't be two-thirds to one-third; it'll be more like one-third to two-thirds.

To gain you guys play and replace it.

150 at least patients from outside.

Speaker #3: And we're very, very pleased about that. But on the record, I will perform incredibly well. We had a progression-free survival ratio of 0.52.

China, and we were able to get to 175 well.

It really wasn't until we underestimated the degree of difficulty to get the doctors to take this trial.

Speaker #3: we did better than any other drug in that, that marketplace. on the P-value, we had a 0.057. it did not pass muster. It's important to note that when you receive feedback from the FDA, it's to gain new guideplay and we played it, we needed 150, at least, patients from outside of, China.

There wasn't inertia, there and nurture caused us to get off to a very slow start.

Sure.

We think there is all of that.

Please.

Available to others, they will look at it as.

Very successful human patient trial.

Certainly I appreciate the.

The fact that the FDA allowed us to.

Move forward on that.

That gives you a little background on why we will submit that we feel we are a patient based company and we feel patients can benefit and did benefit and we would like to see more of that and the FDA will make the final decisions there probably isn't a USA agency.

Speaker #3: And we were able to get to 175. What really wasn't told was we underestimated the degree of difficulty to get the doctor to take this trial on.

Speaker #3: There was an inertia there, and that inertia caused us to get off to a very slow start. So, we think as all that becomes incredibly available to others, they will look at it as a very successful human patient trial.

That has more respect around the world.

Sure we totally support that so that gives you a little bit of color as to we've made the investment and we will make further investments.

And if it goes well.

Sure.

Speaker #3: And we certainly appreciate the fact that the FDA allowed us to move forward on that. So, that gives you a little background on why we’ll submit.

Everybody will have around if it does it.

We certainly have tried to Mexico right.

Okay. Thank you Bob.

Yes.

Speaker #3: We feel we are a patient-based company, and we believe patients can benefit—and have benefited. We would like to see more of that.

Your next question comes from the line of quarry, because Cmos with Evercore. Your line is open.

Hey, good morning, guys. Thanks for taking my question.

Speaker #3: And the FDA will make the final decision. There probably isn't a U.S. agency today that has more respect around the world than the FDA.

Curious was there something in the harmony six data that prompted the protocol amendments to harmony three beyond the kind of the staggered enrollment run rates and what impact will these changes have on the powering of the harmony three subsets. Thank you.

Speaker #3: And we totally support that. So, I hope that gives you a little bit of color as to we've made the investment and we'll make a further investment.

Speaker #3: And if it goes well and we get into patient hands, everybody will have a win on it. If it doesn't, we certainly have tried to make it go right.

Hey, Cory this is Dave so thanks. Thanks for your question. So I think there are multiple reasons.

Updating the design of harmony III, so one and accelerates our frontline lung cancer opportunity as a whole since we began enrolling squamous cohort first we believe that we'll be able to complete enrollment in the first half of next year and this will allow for a data readout in the second half.

Speaker #1: Great. Thank you both.

Speaker #3: Yes.

Speaker #4: Hearing that, your next question comes from the line of Corey Gacimov with AvaCore. Your line is open.

Speaker #5: Hey, good morning, guys. Thanks for taking my question. I’m curious, was there something in the Harmony 6 data that prompted the protocol amendments to Harmony 3, beyond the kind of the staggered enrollment run rates?

We're rapidly enrolling the squamous cohorts as well, we can complete that enrollment.

<unk>.

In the second half of next year.

Speaker #5: And what impact will these changes have on the powering of the Harmony 3 subsets? Thank you.

But two it reduces regulatory risks by separating the two mythologies individual ICP analysis.

Speaker #3: Hey, Corey, this is Dave. So, thanks for your question. I mean, I think there are multiple reasons in terms of updating the design of Harmony 3.

Do not risk the overall population.

Really significant but one subgroup looking a little better than the other mainly through sample variability and this could lead to risks regarding approval for one solid the other and so and additionally, we've seen as advisory committees and the FDA earlier this year, but there is an increased importance on the results of U S patients.

Speaker #3: So, one, it accelerates our frontline lung cancer opportunity as a whole. Since we began enrolling the squamous cohort first, we believe that we will be able to complete enrollment in the first half of next year.

Speaker #3: And this will allow for data readout. The second half, and because we're rapidly enrolling the squamous cohort as well, we can complete that enrollment in the second half of next year.

Which becomes a <unk>.

Subset of the two histology, so without the change U S patients are effectively a subset of a subset at that point and now we have individually powered squamous separately powered non squamous histology for both primary endpoints of PFS and OS and so theyre individually powered.

Speaker #3: But two, it reduces regulatory risks. By separating the two histologies into individual ITT analyses, we do not risk the overall population being statistically significant, but one subgroup looking a little better than the other, mainly through, you know, sample variability.

You are up about two.

Two itg's separately powering the individual histology is effectively a cleaner assessments data.

Speaker #3: And this could lead to risks regarding the approval for one histology or the other. Additionally, we've seen an advisory committee from the FDA, earlier this year, that indicated there is an increased importance on the results of U.S. patients, which becomes a subset of the two histologies.

And three.

It allows us to keep pace in non squamous as well because given the PD, one plus chemotherapy performs a little bit more favorably in non squamous patients.

Typically it has a longer overall survival.

Ben squamous patients.

Speaker #3: So, without the change, U.S. patients are effectively a subset of a subset at that point. And now we have individually powered squamous and separately powered non-squamous histologies for both primary endpoints of PFS and OS.

Progress.

And additional targeted therapies that we see in non squamous patient variability.

<unk> results in non squamous trials really wanted to ensure that there is a little statistical variability.

Speaker #3: And so they're individually powered at the histology level now. And so two ITTs. Separately powering the individual histologies is effectively a cleaner assessment of the data.

And over performing control arm or something like that to create issues. So we again, we increased the sample size, but because we're rapidly enrolling the cohort the analysis is driven by.

Speaker #3: And three, it allows us to keep patient non-squamous as well because given the PD-1 plus chemotherapy performs a little bit more favorably in the non-squamous patients, i.e., you know, typically it has a longer overall survival than squamous patients. The progress in additional targeted therapies that we see in non-squamous mutations, variability, and some historical results in non-squamous trials.

Readout of defense, it's an event driven analysis.

Increasing the sample size for non squamous really had very little impact on the timing of the readout. There. So we don't see a change in probability of success in either of the opportunity to do that both the C. Cleaner. However, really specifically to your question Cory with respect to what we saw with Hermes six yesterday, what that does is allows for direct read throughout two at ITT population.

Speaker #3: We really want to ensure that there's little statistical variability, like an overperforming control arm or something like that, which can raise issues. So we, again, increase the sample size.

<unk> in the Heartmate III study so.

Secondly, the same comparison now Ivo plus chemo versus PD, one plus chemo in the squamous population.

Speaker #3: But because we're rapidly enrolling the cohort, the analysis is driven by a readout of events. It's an event-driven analysis. Increasing the sample size for non-squamous really has very little impact on the timing of the readout there.

Now just in a global setting incentives Sema region of China. There is a direct read through here, we've seen historical comparability in terms of the data generated in Asia versus rest of world and so we're very excited with.

Speaker #3: So we don't see a change in the probability of success in either of the opportunities. We view them both as being cleaner. However, really specifically to your question, Corey, with respect to what we saw with Harmony 6 yesterday, what that does is allow for direct read-through now to an ITT population in the Harmony 3 study.

The ability to have that direct read through and accelerating that squamous opportunity by breaking out.

ICT.

Great that's very helpful. Dave I appreciate it.

Your next question comes from the line of slowly counsel with Wells Fargo. Your line is open.

Speaker #3: So, it's, you know, effectively the same comparison now—IVO plus chemo versus PD-1 plus chemo in the squamous population. It's now just in a global setting instead of a single region in China.

Great. Thank you very much for taking my question and congrats on all the progress.

Repeat the question, we get from expert feedback when you compare that just PD one to a PD one.

Speaker #3: So there's a direct read-through here. We've seen historical comparability in terms of the data generated in Asia versus the rest of the world. And so we're very excited about the ability to have that direct read-through in accelerating that squamous opportunity by breaking out into separate ITTs.

It is.

Previous PD, one <unk> combo. It is very clear that the <unk> component is better than <unk>.

On the verge of component that was tested before but it's not clear that the PD one component is better.

Speaker #5: Great. That's very helpful, Dave. I appreciate it.

Where do you stand on that and if that is the case isn't that an issue with that because.

Speaker #4: Your next question comes from the line of Mohit Bansal with Balfargo. Your line is open.

It does seem like PD one.

Speaker #6: Great. Thank you very much for taking my question, and congrats on all the progress. One repeated question we get from experts is that when you compare a VEGF PD-1 to a PD-1, it is, or a previous PD-1 VEGF combo, it is very clear that the VEGF component is better than the VEGF component that was tested before.

Thank you Chuck causing the law.

The long.

In those five so.

I think coming back to that the biggest issue right now if you could help us understand the confidence around the west here. Thank you.

Yes. This is Jack West I E.

I think it's difficult to.

Speaker #6: But it's not clear that if the PD-1 component is better. Now, where do you stand on that? And if that is the case, isn't that an issue for OS benefit here? Because it does seem like PD-1s are the ones which are causing the loss or reducing the long tail in those trials.

In too much into the value of one side of a molecule or another we don't we.

We havent historically done that with other molecules that target met and Egfr and say well that does.

Smiths or minimize that because.

This is just working on the met side.

Sure.

Speaker #6: So, I think that's the biggest issue right now. If you could help us understand the confidence around OS here. Thank you.

I would say that the most important thing is we should see what the data show.

At the update.

Subsequent final ongoing reading so.

Speaker #3: Yeah. This is Jack West. I think it's difficult to impute too much into the value of one side of a molecule or another.

It.

Is it.

The efficacy is there.

And the Tolerability is favorable when you look at the totality of the data and you decide whether that is enough to change from whatever you're competing current standard.

Speaker #3: We haven't historically done that with other molecules that target MET and EGFR. And say, well, that does, you don't dismiss or minimize that because, oh, this is just working on the MET side.

Sure.

I don't think that we have or should have a separate.

Speaker #3: I would say that the most important thing is we should see what the data show at the subsequent final ongoing reading. So if the efficacy is there, and the tolerability is favorable, you look at the totality of the data.

Set of criteria for a presumption that this is working through a veg F action.

Immunotherapy action.

Thank you.

Just make inferences and I think different clinicians are others make inferences based on their own suppositions or biases.

So I would say that.

Speaker #3: And you decide whether that is enough to change from whatever your competing current standard. And I don't think that we have or should have a separate set of criteria for a presumption that this is working through a VEGF action or immunotherapy action.

Yes, Im not sure it really matter because I think that the reality is you look at the efficacy you look at the Tolerability and you weigh all of that against what the current prevailing options and standards are and if it bubbles up is better.

We have lots and lots of therapies that.

<unk>.

A benefit that is not.

Speaker #3: I think we just make inferences, and I think different clinicians or others make inferences based on their own suppositions or biases. So I would say that, yeah, I'm not sure it really matters.

Sustained over many many many years.

And that's still valuable. So there are many different signs of efficacy benefit that have varying degrees of.

Appreciated.

Speaker #3: I think that the reality is you look at the efficacy, you look at the tolerability, and you weigh all of that against what the current prevailing options and standards are.

<unk> to clinicians and patients so.

I would focus more on what the actual clinical outcomes are then a supposition.

Speaker #3: And if it bubbles up as better, we have lots and lots of therapies that have a benefit that is not sustained over many, many, many years.

Each side of a molecule is is more important to one setting or enough, yes, William I'll add this is Alan.

I'll add that we've always been under the hypothesis and I think the data are showing that the two put together are cooperating and better than the sum of its parts of cost. So smartly designed this molecule such that the PD, one and digest for together so the harmony six data reading out.

Speaker #3: And that's still valuable. So there are many different kinds of efficacy benefits that have varying degrees of appreciated utility to clinicians and patients. So I think I would focus more on what the actual clinical outcomes are than a supposition of which side of a molecule is more important in one setting or another.

Positive doesn't indicate that it's just the fact, Jeff and it's not just an indication, but again I think that Jeff is important and a lot of different diseases and this puts them together smart way. If you look back to the harmony to data remember there was an improvement not only in the low PD lone expressing.

Speaker #5: Yeah. William, I'll add, this is Alan Yates. I'll add that, you know, we've always been under the hypothesis that I think the data are showing that the two put together are cooperating and better than the sum of the parts.

Probably indicative of Badger, but also the high PD Lone expression. This is the sweet spot for PD. One so the Badger clearly makes it better I think John <unk> also alluded to in the discussion of that that that not only were they swap permitting but the bed Jeff may play a role of immunotherapy as well there is growing data to support that as well.

Speaker #5: The Caso smartly designed this molecule such that the PD-1 and VEGF work together, so the Harmony 6 data reading out positive doesn't indicate that it's just the VEGF and it's not just an indication.

So the answer to your question is we think again, both sides are important and how they're engineered and put together.

Speaker #5: But again, I think VEGF is important in a lot of different diseases, and this puts them together in a smart way. If you look back to the Harmony 2 data, remember there was an improvement not only in the low PD-L1 expressing, which was probably indicative of VEGF, but also the high PD-L1 expressing.

Bob.

Indicates that the moh and support I also want to add that the safety that we've seen across four randomized double blind placebo site suggest that this is not met Jeff.

Speaker #5: This is the sweet spot for PD-1. So the VEGF clearly makes it better. I think John Hamack also alluded to in the discussion that not only were they cooperating, but the VEGF may play a role in immunotherapy as well.

Your next question comes from the line of Sarah Doll with Jefferies. Your line is open.

Hi, guys. Thanks for taking my question and congrats on the impressive commonly six Dana I think Theres a lot of quick question on <unk>. So I want to actually talk about your plans for colorectal cancer.

Speaker #5: And there's growing data to support that as well. So the answer to your question is we think, again, both sides are important. And how they're engineered and put together indicates that the MOA is important.

For the Phase III study are there any plans to stratify or analyze our cost based on the presence of lumber prices and all of her mouth.

Speaker #5: I also want to add that the safety that we've seen across four randomized double-blind placebo sites suggests that this is not VEGF.

Given some some prevailing evidence of their impact on treatment responses seen MSS CRC and then.

Speaker #4: Your next question comes from the line of Clara Dong with Jefferies. Your line is open.

The global components of the phase two <unk> combination studies.

Speaker #7: Hi, guys. Thanks for taking my question, and congrats on the impressive Harmony 6 data. I think there's a lot of great questions on Harmony 6 already, so I want to actually talk about your plan for colorectal cancer.

What's the expected timeline for the next update on whether we should expect some U S data from this trial in the next update as well. Thank you.

Thanks, Claire I think all good questions and I think we do we certainly do have stratification factors within our current <unk>.

Speaker #7: So for the Phase 3 study, are there any plans to stratify or analyze outcomes based on the presence of liver versus non-liver mets? Given some, you know, some prevailing evidence of their impact on treatment responses in MSS CRC, and then you mentioned the global components of the Phase 2 FOLFOX combination study.

Trial I don't think at this point quite it's early we're looking to.

To make public all of those individual factors.

Factors, just yet, but your points are well taken in terms of.

The specific patient characteristics that you mentioned.

And I would say with respect to the publishing of additional data, including those data.

Speaker #7: So, what's the expected timeline for the next update, and whether we should expect some U.S. data from this trial in the next update as well?

Based on U S patients.

Speaker #7: Thank you.

We are determining the appropriate time.

Speaker #3: Thanks, Clara. I think all good questions. And I think we certainly do have stratification factors within our current trial. I don't think it's this point quite this early.

If and when that's.

If and when we do that in part of that as we continue to have phase III.

<unk>.

That becomes important.

Speaker #3: We're looking to make public all of those individual factors just yet. Your points are well taken in terms of the specific patient characteristics that you mentioned.

To prioritize that.

<unk> data across multiple different chemotherapy.

Lines for us or would there be options to support for us to make decisions, it's not necessarily something that.

Speaker #3: And I would say, with respect to the publishing of additional data, including those data that were based on U.S. patients, we're determining the appropriate time, if and when we do that.

We need to individual to go through.

And so I think theres, a piece, where the phase III will pick up very important to the publisher and obviously our partners that are kept so we're running a phase III as well, which will provide significant additional.

Context, when when that study concludes.

Speaker #3: And part of that is we continue to have Phase 3 readouts that become important to prioritize. Publishing data across multiple different chemotherapy lines for us, or chemotherapy options, is important for us to make decisions.

Thank you I appreciate the color.

Your next question comes from the line of Ash Sika can warden with <unk> Securities. Your line is open.

Hey, guys. Thanks for taking my question and I'll offer my congrats on all the progress.

Speaker #3: It's not necessarily something that we need to individually go through. And so I think there's a piece where Phase 3 will become very important to publish.

And the great data presented.

Yesterday.

To start off on.

Harmony.

Takeaway from World lung was that OS benefit.

Speaker #3: And obviously, our partners at Accesso are running a Phase 3 as well, which will provide significant additional context when that study concludes.

We've become more pronounced with the appropriate level of follow up so do the harmony filing with the FDA do you need to take a new data cut are you filing what you have right now.

Speaker #4: Thank you. I appreciate it, Corey. Your next question comes from the line of Ashley Ginwarden with Juris Securities. Your line is open.

Then I have a follow up.

Yeah. Thanks for the question Oscar and I appreciate the.

The words at the beginning I think we Havent public.

Speaker #8: Hey, guys. Thanks for taking my question, and I'm also off by congrats on all the progress and the great data presented yesterday. To start off on Harmony, the takeaway from World Lung was that your OS benefit would become more pronounced with the appropriate level of follow-up.

Publicly spoken to.

With respect to how we will.

Work with the agency.

As also mentioned earlier.

It maintain communication with the agency, it's important too to work through the submission process.

So.

She mentioned currently working on on the application.

At this point, so I think that is.

Speaker #8: So, with the Harmony filing with the FDA, do you need to take a new data cut, or are you filing what you have right now?

Clearly just given where we are today only a month and a half later from the data cut based on Aqua Shah.

Speaker #8: And then have a follow-up.

We're alone.

And I think in terms of next steps with that I think part of that Paul discussed.

Speaker #3: Yeah. Thanks for the question, Asuka, and I appreciate the words at the beginning. I think we haven't publicly spoken to the specific details with respect to how we'll work with the agency.

Got it thanks.

And then just on the.

The amendment to the <unk> III study the original Hanmi III study, which was in.

Speaker #3: It's also mentioned earlier that we maintain communication with the agency. It's important to work through the submission process. She mentioned that she is currently working on the application at this point.

<unk> could you just squamous patients that had about a trial recruitment of about 400 or 450 patients or so.

The Hanmi six data came out showing a really great benefit.

Speaker #3: And so, I think that, you know, is clearly just given where we are today, only a month and a half later from the data cut, you know, based on what we saw at World Lung.

In similar kind of patient population, but now you are expanding their recruitment for.

For the <unk> III squamous cohorts to 600 patients.

Speaker #3: And I think in terms of next steps with that, I think part of that will involve discussions with the agency.

I know that's also in line with what keynote 407 recruited but I just wanted to get your guys thoughts on.

Speaker #8: Got it. Thanks. And then just on the amendments to the Harmony 3 study, so the original Harmony 3 study, which was in original was restricted to just squamous patients, that had about a trial recruitment of about 400 or 450 patients or so.

On the rationale for increasing the target size.

So this is all time finding the site.

Dave This is Scott.

Separately.

Splitting.

Speaker #8: The Harmony 6 data came out showing a really great benefit in a similar kind of patient population. But now you're expanding the recruitment for the Harmony 3 squamous cohort to 600 patients.

Into two parts that will be separate analysis.

<unk>.

Yeah.

Pinpoints for Pms West.

And this is a very good sample size.

High confidence and the detail on Opex spend the scores.

Speaker #8: I know that's also in line with what Keynote 407 recruited, but I just want to get your guys' thoughts on the rationale for increasing the target size there.

<unk>.

Great. Thanks, guys.

Your next question comes from the line of David Dye. Your line is open with UBS.

Speaker #7: So this is Ota. I can respond to this side. I think Dave discussed with Q41; we are basically splitting the cohorts into two parts.

Oh, Great Hey, Thanks for taking my questions. I also wanted to add my congrats on the great data here.

So a couple of questions. One just a clarifying question on Hanmi three phase III trial update so Dave you mentioned that the child safety risks regulatory aspects I just want to clarify that does that mean that youre able to file each.

Speaker #7: There will be separate analyses, and that's very important. We are powering for both endpoints for PFS and OS, and this is a very good sample size.

Speaker #7: You know, we have obviously high confidence in the readout of the squamous cord, but this is appropriate to cover both endpoints.

Histologist separately lets say, if one histologist failed, whether you'll see others succeeds and some of you can file for successful win irrespective of histology.

Speaker #8: Great. Thanks, guys.

Is Europe, David Yes, they are independent.

Speaker #4: Your next question comes from the line of David Dye. Your line is open. With UBS.

With their independent analysis.

Speaker #6: Great. Hey, thanks for taking my questions. And I also wanted to add my congrats on the great data here. So, I have a couple of questions.

Got it.

Uh huh.

Yes, it's just the nature of important topics.

Speaker #6: One is just on the clarifying question on Harmony 3 Phase 3 trial update. So, Dave, you mentioned that the trial update differs from the regulatory aspects.

For several months.

Hi.

Got it okay, great and then secondly, just on the combo strategies for.

Speaker #6: So I just want to clarify that. Does that mean that you're able to file each histology separately? Let's say if one histology fails, what if the other succeeds?

For non small cell and all I know a lot of other companies are thinking about 280 season chemo combos.

Speaker #6: Does that mean you can file for the successful one irrespective of the failed histology?

What are your thoughts around combination strategies.

With all of this tomorrow.

In different solid tumors.

Speaker #3: In short, David, yes. They're independent ITTs, so they're independent analyses.

Yes.

David I think you are talking about novel novel combinations, if I understood that right and so yes.

Speaker #8: Got it. Great. So you could just file.

We've talked about this a little bit in the past, but we're very excited in terms of our clinical trial collaboration with Brett.

Speaker #7: Yeah. It's just the nature of what has happened, so that there will not read out exactly at the same time.

In terms of evaluating multiple RAF inhibitors in combination with I've been asked about it so I think we'll be able to.

Speaker #8: Got it. Okay. Great. And then secondly, just on the combo strategies for, you know, for non-small cell. I know a lot of other companies that are thinking about doing ADCs and chemo combos.

In collaboration with with Revlimid begin dosing.

Dosing patients earlier early 2026.

Speaker #8: What are your thoughts around combination strategies with, you know, Avenisumab, you know, in different solid tumors?

But in addition, there too I think.

Planning on multiple additional combinations and those would likely be with agencies to where I think you were heading with that David and so part of what we believe is a strategic advantage for.

Speaker #3: Yeah. And David, I think you're talking about novel combinations. So if I understood that right, and so, yeah, I think we've talked about this a little bit in the past, but we're very excited in terms of our clinical trial collaboration with Rep in terms of evaluating multiple RAS inhibitors in combination with Avenisumab.

Some of it as a whole I've asked about.

Global development.

<unk> mouth is.

Because we.

We don't have specific adcs that are.

Speaker #3: And so I think we'll be able to, you know, in collaboration with RepMed, begin dosing patients earlier in 2026. But in addition there too, I think we're planning on multiple additional combinations.

Part of our portfolio is well it allows us to follow up data and so we're working with multiple other companies in terms of.

Collaborating in order to.

Just I have enough <unk> in combination with with multiple adcs that are multiple.

Targets with multiple different payloads different structures.

Speaker #3: And those would likely be with ADCs to where I think you're heading with that, David. And so, part of what we believe is a strategic advantage for Summit as a whole, Avenisumab, and the global development of Avenisumab is because we don't have specific ADCs that are part of our portfolio as well.

That will allow us ultimately followed the data I think you've heard us speak to in the past realities, but we don't believe in similar too.

If you look at solid tumor therapy. Each day, there is not a single chemotherapy or chemotherapy regimen.

Likeable across solid tumors right. There are different regimens that are applicable even in non small cell lung cancer pemetrexed.

Speaker #3: It allows us to follow the data. And so we're working with multiple other companies in terms of collaborating in order to test Avenisumab in combination with multiple ADCs that are multiple targets with different payloads, different structures, and that will allow us ultimately to follow the data.

Used very frequently in non squamous tumors.

It is not used in squamous tumors and paclitaxel as the backbone and so as we think about just with the non small cell lung cancer key differences in terms of the chemo regimens.

That implies as you keep going beyond the two additional histology as traditional solid tumor settings.

Speaker #3: I think you've heard us speak to this in the past. In reality, what we don't believe in is similar to how, if you look at solid tumor therapy today, there is not a single chemotherapy or chemotherapy regimen that is applicable across solid tumors, right?

But certainly different.

Loads will be very important in terms of being most effective for tumors settings.

So the <unk> will be very important safety will be very important there are different tolerability.

Speaker #3: There are different regimens that are applicable even in non-small cell lung cancer. Chemotrexate is used very frequently in non-squamous tumors, and it is not used in squamous tumors.

Thresholds within different tumors.

Different settings, and so what we want to do is follow up data. So we won't be as encumbered by maximizing our own internal pipeline if you will.

Speaker #3: And paclitaxel is the backbone. As we think about just within non-small cell lung cancer, key differences in terms of the chemo regimens imply that as we keep going beyond into additional histologies and additional solid tumor settings, certainly different payloads will be very important in terms of being most effective for the tumors in those settings.

There've been steaks made it pass on that and we think we have the opportunity to follow the best data follow the right combination with I've asked about and ultimately maximize the potential for patients in terms of.

What can be done to take the power of I've enough math with with some of the novel.

Components that are in development that are exciting right now whether it be around if there are like rip met has multiple ras inhibitors or different agencies.

Speaker #3: And so the MOA will be very important; the safety will be very important. There are different tolerability thresholds within different tumors in different settings.

Structures.

And obviously, it's also has multiple adcs.

Speaker #3: And so what we want to do is follow the data. So what we won't be is encumbered by maximizing our own internal pipeline, if you will, and we think there have been mistakes made in the past on that.

In their pipeline as well as theyre going to be taking a look at that particular.

Their own.

Miles to starts and so that will also inform us going forward as well.

Speaker #3: And we think we have the opportunity to follow the best data, follow the right combination with Avenisumab, and ultimately maximize the potential for patients in terms of what can be done to take the power of Avenisumab with some of the novel components that are in development that are exciting right now, whether it be a RAS inhibitor like RepMed has multiple RAS inhibitors or different ADCs with unique structures.

Great. Thank you so much.

Your next question comes from the line of Ren Benjamin with Citibank. Your line is open.

Hey, good morning, guys. Thanks for taking the questions and congratulations on the very impressive data yesterday.

So first question of the harmony safety profile, I mean, really reaffirms thoughts like I have enough events tolerability.

Especially given this largely comparable to the control arm was there any specific like squamous specifically related events, that's different from the non squamous cohort and in harmony and related to that I think theres just.

Speaker #3: And obviously, Accesso has multiple ADCs in their pipeline as well that they're going to be, you know, taking a look at in particular, you know, in their own trials to start.

Speaker #3: And so that will also inform what's going forward as well.

Speaker #8: Great. Thank you so much.

And kind of appreciation for the safety profile.

Speaker #4: Your next question comes from the line of Benjamin with Citizens. Your line is open.

I think the discussion brought that up I was curious as to how you guys are are the lapsing that especially with kols.

Speaker #5: Hey, good morning, guys. Thanks for taking the questions, and congratulations on the very impressive data yesterday. I guess the first question is the Harmony 6 safety profile.

This is Jack West I would say there are differences between the screens in the non squamous.

Speaker #5: I mean, really reaffirms to us like Avenisumab's, you know, tolerability. Especially given it's largely comparable, you know, with the control arm. Were there any specific like squamous specific, you know, related events that's different from the non-squamous cohort in Harmony?

Largely based on the characteristics squamous tumors tend to be larger and more central than non squamous tumors and then.

A fraction of that.

Proportion of brain metastases as.

Speaker #5: And related to that, I think there's just an apparent kind of underappreciation for the safety profile, specifically regarding bleeding. I think the discussion brought that up.

Perhaps there are some.

In harmony, six and other squamous cohorts, but.

It's far less common.

Speaker #5: I'm kind of curious as to how you guys are addressing that, especially with KOLs.

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Patients with squamous, then with adenocarcinoma and especially.

Patients with Egfr mutation positive non small cell where brain metastases are.

Speaker #3: This is Jack West. I would say there's a difference between the squamous and the non-squamous, largely based on their characteristics. Squamous tumors tend to be larger and more central than non-squamous tumors.

Our leading concern.

But I would say.

As I had alluded in the presentation yesterday as well.

Is not just allowing patients with advanced squamous lung cancer, but this.

Speaker #3: And then the fraction of the proportion of brain metastases is present. There are some in Harmony 6 and in other squamous cohorts, but it's far less common in patients with squamous than with adenocarcinoma.

Was bold and courageous in enrolling patients with with several features that have historically been.

<unk>, if not prohibitive with Bevacizumab.

And frankly in China. They have years of experience many of these investigators and growing comfort with that.

Speaker #3: And especially patients with EGFR mutation-positive non-small cell lung cancer, where brain metastases are a leading concern. But I would say, as I alluded to in the presentation yesterday as well, this is not just about allowing patients with advanced squamous lung cancer; this was bold and courageous in enrolling patients with several features that have historically been challenging, if not prohibitive, with bevacizumab.

I would say that that clinical oncologists outside of China or anywhere where.

They have less experience.

Need to not only look at these data, it's definitely going to be.

Point of education.

We cannot be limited by and should not be limited by the historical precedence of a different drug with a very different safety profile. These are new times at the eligibility should be very different and liberalized and yes, I think that it will take a both a combination of education.

Speaker #3: frankly, in China, they And These are new times and the eligibility should be very different and liberalized. And yet I think that it will take both a combination of education and gradual experience for oncologists to get it treat patients and reassure, be reassured by their own favorable experiences with it over time.

Speaker #3: I have years of experience, and many of these investigators are growing comfortable with that. I would say that clinical oncologists outside of China, or anywhere where they have less experience, will need to not only look at these data; it's definitely going to be a point of education that we cannot be limited by and should not be limited by the historical precedence of a different drug with a very different safety profile.

Gradual experience for oncologists to get it treat patients and reassure be reassured by their own favorable experiences with it over time.

Got it and then just as a follow up.

Do you think that the.

Filling as the FDA kind of indicated that this goes to the <unk>, we'd be applying for accelerated or full approval and your thoughts on European filings.

Sure.

Yes.

This is a good solid xiaomi hospice statistically significant <unk> supportive OS data, which you think this is very meaningful and still be invited into context.

And because the data.

<unk> duration of response, so all things equal since the package.

Speaker #5: Got it. And then just as a follow-up, do you think that the filing is the FDA kind of indicated that this goes to ODAC?

For approval.

We cannot currently what exactly the comments and the opinions of the FCA are and as he said as we go into this.

Speaker #5: Will you be applying for accelerated or full approval? And your thoughts on European filings? Thank you.

Specific.

Inflammation of merchant and we will provide color.

Speaker #7: Yes. We think that this is a good solid package. We have statistically significant PFS. We have supportive OS data, which we think is very meaningful, and it will be evaluated in context.

Sure.

Other policy issues I cannot comment on can we look forward to FCA and all.

Sure Amazon split their plants are in terms of silver.

Silver feedback loop.

We'll be watching that.

Speaker #7: We have supportive efficacy data from OR and duration of response. So all of that is clinically equivalent to the package for full approval. We cannot foresee what exactly the comments and the opinions of the FDA are.

Your next question comes from the line of furniture Kapoor with H C. Wainwright. Your line is open.

Everyone. Thanks for taking the questions and congrats on the data.

0.2 relevant regulatory precedents, where a strong PFS benefit without a statistically significant benefit at the time of filing was still sufficient for FDA approval and how do you think that can you just remind us how these situations were handled by the FDA and then separately can you just comment on.

Speaker #7: And as we said, as we go into the review process and very specific information emerges, then we will provide color on that. Other policy issues I cannot comment on.

Speaker #7: We will all look forward to the FDA kind of sharing results and what their plans are in terms of external feedback. We will kind of think.

<unk> business development front on the change in the volume and the types of BD discussions you've been having lately. Thank you.

Speaker #7: So we will be watching that along with you.

Speaker #4: Your next question comes from the line of Mitchell Kapoor with HA WinRET. Your line is open.

I will take the first part.

So.

Speaker #6: Everyone, thanks for taking the questions, and congrats on the data. Can you point to relevant regulatory precedents where a strong PFS benefit without a statistically significant OS benefit at the time of filing was still sufficient for FDA approval?

And his executive meeting in Egfr positive previously treated.

Patients there were two relevant approvals both of them occurred last year.

The first one is for the advancement molecule based programmatic two study which was approved.

Speaker #6: And how do you think that, or can you just remind us how these situations were handled by the FDA? And then separately, can you just comment on this business development front on the change in the volume and the types of BD discussions you've been having lately?

It's significant.

PFS and was accompanied by a plus two trends across 200 kits at OFC.

Other approvals.

So accelerated approval.

Our next molecule.

In the morning is slightly different buckets previously treated patients.

Speaker #6: Thank you.

Speaker #7: Oh, good. I will take the first part. So, in this exact setting, meaning in EGFR-positive previously treated patients, there were two relevant approvals; both of them occurred last year.

Post chemo as follows.

Well to cancer therapy, Jeff their therapy and that accelerates approval was based on.

All of our visit to duration of response and that can also towards that the confirmatory study for that molecule Egfr positive in the frontline setting so there isn't going to be any additional generation.

Speaker #7: The first one is for the Avenisumab 402, based on the medical set 2 study, which was approved on statistically significant PFS. It was accompanied by a positive trend, but not significant in OS.

Statistically significant PFS west.

Speaker #7: The other approval that happened as an accelerated approval is the data length molecule. In the ruling, it is slightly different, but it's previously treated patients with both chemo as well as TKA therapy and EGF therapy.

What's coming.

So business development question.

Sure.

Mark do you want to continue with it.

And I think Thats fair.

Questions.

This is Bob.

Speaker #7: And that accelerated approval was based on ORR with a duration of response. I can also note that the confirmatory study for that molecule in EGFR-positive in the frontline setting.

We want to thank you for your attendance.

If you could be at ESMO.

People here.

We're really honored.

<unk>.

As the presidential.

Speaker #7: So there isn't going to be any additional generation of statistically significant PFS or OS in that setting forthcoming. Because this development question?

Fantasia 9000 people passed into.

Large program.

I've heard resoundingly.

Laws may hurt that data.

This is a breakthrough so breakthrough magnitude.

Speaker #5: Yeah.

Undeniably.

Speaker #6: So, Mark, do you want to conclude with their business development?

Product.

Lung cancer is the number one killer, it's not going to be that way for law. We really are at a mitigation hopefully in some areas.

Speaker #3: I think that's the answer to the question. This is Bob Duggan. We want to thank you for your attendance today. I only wish you could be at ESMO because at least 25,000 people are here. We were really honored, and Accesso was honored to be the first presenter at the presidential presentation, with 9,000 people packed into a very large auditorium that gave a resounding applause as they heard the data that this is a breakthrough.

Forward even into that range.

Our team is very excited we're very excited.

The doctors physicians.

To support them are really excited we've seen there's always other museums.

Packed agenda incentive appreciation you have to kind of the year, we'll see the snipers trip to.

Berlin, but I must say.

Speaker #3: It's a breakthrough of magnitude. Undeniably, we have an excellent product. Lung cancer is the number one killer; it's not going to be that way for long.

With respect to.

The business for some of the moves in Miami So.

Yes.

We're going Australia editors and we're enjoying ourselves.

Institutional it's incredibly dry October just like this I haven't changed my fleet.

Speaker #3: We really are in the mitigation, and hopefully in some areas, we'll move this forward even into the arena of clarity. Our team is very excited.

Vessel lifetime, I've, just really fiber dissolves, helping government patients here to make a significant difference for the better but I will say you see people from all cultures, all walks of life here.

Speaker #3: We're very excited to have the product in our hands that the doctors, physicians, and those that support them are really excited about. We've seen it in the hallways and in other meetings; we've been just packed with attendance and appreciation.

Health care business is one that.

Bringing the world together knutsen rates, yet and we're just really happy to play a significant role of banker thankful to our our Gaslog partners from China. After the FDA forgive us.

Speaker #3: You have to kind of be here to see it. It's my first trip to Berlin, but I must say it's a beautiful city, even though it's a bit nippy for someone who lives in Miami.

Speaker #3: So yeah, we're going straight ahead here, and we're enjoying ourselves. The future looks incredibly bright. Opportunities like this, I haven't seen in my brief investment lifetime.

The platform, which to really move forward. So thank you for being on the call or talking to you soon.

Operator.

Ladies and gentlemen that concludes today's call you can disconnect. Thank you and have a great day.

Speaker #3: I'm just really excited about helping patients here and making a significant difference for the betterment. I will say you see people from all cultures, all walks of life here.

Speaker #3: This healthcare business is one that brings the world together, not separates it. And we're just really happy to play a significant role and thankful to our Accesso partners, you know, from China, and for the FDA for giving us the platform to really move forward.

Speaker #3: So thank you for being on the call. I look forward to talking to you soon. Have a great day.