Summit Therapeutics Q1 2025 Earnings Report

Summit Therapeutics EPS Results

• Actual EPS: -$0.09
• Consensus EPS: -$0.10
• Beat/Miss: Beat by +$0.01
• One Year Ago EPS: N/A

Summit Therapeutics Revenue Results

• Actual Revenue: N/A
• Expected Revenue: N/A
• Beat/Miss: N/A
• YoY Revenue Growth: N/A

Summit Therapeutics Announcement Details

• Quarter: Q1 2025
• Date: 5/1/2025
• Time: After Market Closes
• Conference Call Date: Thursday, May 1, 2025
• Conference Call Time: 4:30PM ET

Summit Therapeutics (NASDAQ:SMMT), a biopharmaceutical company, focuses on discovery, development, and commercialization of patient, physician, caregiver, and societal friendly medicinal therapies in the United States, and the United Kingdom. The company's lead development candidate is Ivonescimab, a bispecific antibody for immunotherapy through blockade of PD-1 with the anti-angiogenesis; and anti-infectives portfolio includes SMT-738, a novel class of precision antibiotics for the treatment of multidrug resistant infections, which primarily includes carbapenem-resistant Enterobacteriaceae infections. It has a collaboration and license agreement with Akeso, Inc. and its affiliates to develop and commercialize ivonescimab, as well as strategic collaboration with The University of Texas MD Anderson Cancer Center for the purpose of accelerating the development of ivonescimab. The company was founded in 2003 and is headquartered in Miami, Florida.

Summit Therapeutics Q1 2025 Earnings Call Transcript

Key Takeaways

• Partner Akeso’s investigational bispecific antibody ivanismab received NMPA approval in China as frontline monotherapy for PD-L1 positive NSCLC, with an early OS trend showing a hazard ratio of 0.777 at 39% maturity versus pembrolizumab.
• Akeso’s HARMONY-6 Phase III trial met its primary PFS endpoint for ivanismab plus chemotherapy over tislelizumab plus chemotherapy in squamous NSCLC, marking the first head-to-head improvement versus a PD-1/L1 inhibitor in a chemo-combination setting.
• Summit’s global registrational HARMONY trial in EGFR-mutant NSCLC post-third-generation TKI completed enrollment and expects top-line PFS and OS data mid-2025, while HARMONY-3 (combo vs pembrolizumab+chemo) and HARMONY-7 (monotherapy in PD-L1 high) are actively enrolling.
• The ivanismab platform now encompasses 11 Phase III studies across NSCLC and other tumors, supported by collaborations with MD Anderson for cutaneous squamous and glioblastoma studies and a Pfizer agreement to test combinations with novel ADCs.
• Summit ended Q1 2025 with approximately $361 million in cash and no debt, increased G&A spending to build its commercial team—appointing a new Chief Commercial Officer—and advanced tech transfer to third-party manufacturers for future supply.

Presentation

[Operator]

Thank you for standing by. Hello, and welcome to the Summit Therapeutics Q1 twenty twenty five Earnings Conference Call. I would now like to turn the call over to our Chief Business and Strategy Officer, Dave Van Carrs. Please go ahead, sir.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Good afternoon, and thank you for joining us. A press release was issued earlier this afternoon and is available on the homepage of our website. Our Form 10 Q was also filed and is available on our website. Today's call is being simultaneously webcast and an archived replay will also be made available later today on our website www.smmtx.com. Joining me on the call today is Bob Duggan, our Chairman of the Board and Co Chief Executive Officer Doctor.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Mahesh Zangane, our Co Chief Executive Officer and President Manmeet Soni, our Chief Operating Officer and Chief Financial Officer Doctor. Alan Yang, our Chief Medical Officer and Doctor. Jack West, Vice President and our Thoracic Oncology TA Head. Before we get started with the rest of the call, I would like to note that some of the statements made by our management team and some responses to questions that we make today may be considered forward looking statements based on our current expectations. 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.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

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. Following comments from Bob, Meki and Manmeet, we will take questions. With that, I would like to turn the call over to Bob.

[Robert Duggan, Co-CEO & Executive Chairman at Summit Therapeutics]

Thank you, Dave. Good afternoon, everyone, and thank you for joining us today. As you can imagine, I'm very proud of as well as encouraged by the ongoing accomplishments of Team Summit and the continuing positive information and enthusiasm surrounding ivanismab, our lead medicinal investigational asset. We have begun 2025 with excellent progress and continue to take meaningful steps in the development of ivanismab. We continue to advance our mission of building a viable organization making a significant positive difference in serious unmet medical needs.

[Robert Duggan, Co-CEO & Executive Chairman at Summit Therapeutics]

Specifically, last week our partner Akeso made two important as well as material announcements. First, avenizumab received approval from NMPA, the health authority in China as frontline monotherapy treatment for patients with NSCLC whose tumors have positive PD L1 expression. This marks an important regulatory milestone for our partners at Akeso and adds to the growing evidence of ipadimumab's differentiated profile and its potential to make a significant difference in the lives of patients dealing with hard to treat cancers. On behalf of the Summit team, we want to extend our congratulations to our partners at Akeso for this achievement and our gratitude for our strong ongoing partnership. This approval was based on positive PFS results from Akezos HARMONY-two trial, which was disclosed at last year's World Conference on Lung Cancer.

[Robert Duggan, Co-CEO & Executive Chairman at Summit Therapeutics]

Additionally, to supplement this groundbreaking PFS data that represented the first drug to achieve a statistically significant benefit over pembrolizumab in a Phase three clinical trial, the NMPA requested that Akeso perform an interim analysis of overall survival. Last week, Akeso reported on the health authority requested early interim analysis. The analysis showed a clinically meaningful and strongly positive trend favoring ivanismab at thirty nine percent data maturity with a hazard ratio of 0.777 implying a potential twenty two percent reduction in the risk of death compared to pembro. To be clear at Summit, we are pleased and excited about this remarkable outcome. McKee will discuss this a little further in a few moments.

[Robert Duggan, Co-CEO & Executive Chairman at Summit Therapeutics]

Additionally, AKSO's HARMONY six Phase three clinical trial met its primary endpoint of progression free survival at a pre specified interim analysis conducted by an independent data monitoring committee. This trial evaluated ipinimumab in combination with chemotherapy against tislelizumab a PD-one inhibitor in combination with chemotherapy in patients with advanced squamous non small cell lung cancer regardless of PD L1 expression. Conducted in China by our partners at Aikesto, the trial showed statistically significant and clinically meaningful improvement in progression free survival for ibanisumab plus chemotherapy. Akeso noted that no new safety signals were identified. This marks the first known Phase three trial in NS CLC to show significant improvement over a PD-one or PDL-one inhibitor combined with chemotherapy in a head to head setting.

[Robert Duggan, Co-CEO & Executive Chairman at Summit Therapeutics]

Following the success of Akezos HARMONY-two study, this is the second instance where ivenizumab based regimens have demonstrated significant benefits in frontline treatment in non small cell lung cancer. The full dataset for HARMONY-six is planned to be presented at an upcoming major medical conference later this year. Turning to our own global Phase three trials, we expect top line data in mid-twenty twenty five from Harmony, our global Phase three trial in patients with EGFR mutated advanced non small cell lung cancer who have progressed after treatment with a third generation EGFR tyrosine kinase inhibitor. As a reminder, HARMONY is Summit's first global registrational Phase three trial and received Fast Track designation from the U. S.

[Robert Duggan, Co-CEO & Executive Chairman at Summit Therapeutics]

FDA. We are also excited to see progress and the expansion of our venezomib studies through collaborations with leading organizations for which McKee will provide additional data. We will provide details in the future on additional catalysts including top line results from our first registrational Phase three HARMONY trial and our clinical development plans beyond non small cell lung cancer both of which will be provided later in 2025. McKee will further discuss these accomplishments driving our strong unyielding belief in what can be accomplished by Team Summit and our conviction in the potential of evinisemet. We are a mission and purpose driven organization with a collective goal to improve quality of life, increase potential duration of life and resolve serious medical needs.

[Robert Duggan, Co-CEO & Executive Chairman at Summit Therapeutics]

We believe we have the right team and the right molecule in ivenizumab to realize this goal. Not only do we have the right team, we have the right partner. The courage displayed by Michelle Shaw and the Kesso team to conduct a head to head study against pembro was rewarded by the results and well deserved second approval for ibunitsumab in China. However, it also served to raise the awareness of ibunitsumab globally when Ivo became the first drug to demonstrate an improvement head to head in a Phase three trial versus pembro. Blockbuster drug development takes courage and Ocaseo has demonstrated this courage on more than a few occasions unlike many companies that have tried to but failed.

[Robert Duggan, Co-CEO & Executive Chairman at Summit Therapeutics]

With that, I will turn the call over to McKee for additional context and recent highlights for your consideration. McKee, you

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

Thank you, Bob, and good afternoon, everyone. As Bob said, I remain incredibly enthusiastic about the future of Summit and the possibilities of what can be accomplished with our lead candidate, abonizumab, especially as we approach our first global Phase three readout and begin to grow our commercial team. Before providing some additional detail and reviewing the current pipeline, I would like to highlight our current progress in developing ibonesumab and dive a bit deeper on a few concepts that Bob touched upon. Since 2019, more than two thousand three hundred patients have been treated in clinical trials with abanisumab. Currently combined between our partners at AKSO and our team at Summit, four Phase three trials have completed enrollment, three of which have had top line data readouts and the other, the summit sponsored HARMONY trial, we expect top line data in the middle of this year.

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

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

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

Turning specifically to the summit sponsored pipeline. Our first global Phase three trial, HARMONY, is evaluating ivanismab in patients with EGFR mutant non small cell lung cancer after progressing on a third generation TKI such as Osimertinib. While this is a limited market opportunity compared to frontline treatment for non small cell lung cancer, Harmony represents our initial fast to market strategy with ibonesumab. Historically, PD-one inhibitors, including pembro, have tried and failed to demonstrate a benefit in PFS or OS in the EGFR mutant non small cell lung cancer setting. This provides garganizumab the opportunity to differentiate itself from current PD-one therapies, as well as a novel mechanism and a new treatment option for patients.

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

The enrollment for the HARMONY trial completed in October of last year and top line data is expected mid-twenty twenty five. This data is expected to contain data associated with both primary endpoints, progression free survival and overall survival. Subsequently, we started two additional global Phase three studies, HARMONY three and HARMONY seven, which both evaluate ibunisimab head to head versus pembro, either with or without chemotherapy in frontline non small cell lung cancer. HARMONY three evaluates ibunisumab in combination with chemotherapy and HARMONY seven evaluates ibunisumab as monotherapy. Last October, HARMONY three was amended by

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

HARMONY three

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

is now an all comers study from a histology perspective and a PD L1 expression perspective in frontline non small cell lung cancer covering an addressable patient population

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

two to three times larger than prior to the amendment. As a reminder, this trial enrolls patients irrespective of PD L1 expression, including those patients whose tumors do not express PD L1. Additionally, we have now begun enrolling patients in HARMONY seven as we continue to activate clinical trial sites in The United States and will expand beyond The U. S. In the coming months.

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

Later this year, we expect to announce additional details expanding our clinical development plan around ibonesumab, including beyond lung cancer. We continue to receive strong interest for investigator sponsored trials, including in the most recent open window, which closed just two weeks ago. To date, we have approved over 30 ISTs with a review of meaningful submissions from the last window to be performed shortly. These collaborations enhance our sponsored clinical development activities and can show signals in settings where evanicimab has not yet been explored. Our strategic collaboration with MD Anderson, which commenced in July 2024, now has two studies that are activated and are enrolling in Houston with either cutaneous squamous cell carcinoma or glioblastoma.

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

We committed $15,000,000 to this collaboration to quickly discover additional opportunities for ibunisimab, including several tumor settings outside of this current development plan, as well as the possibility of identifying biomarkers through additional research activities. Separately, we continue to support investigator sponsored trials or ISDs, two of which have begun enrolling at the Memorial Sloan Kettering Cancer Center and Dana Farber Cancer Institute. We are also looking forward to the initiation of clinical trials as part of our collaboration with Pfizer, which are expected later this year. This collaboration allow us to quickly advance beyond our current promising late stage development plan to evaluate ivanismab in combination with some of the most innovative ADCs from Pfizer. Pfizer will be responsible for the operations and costs associated with these trials.

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

Summit will provide ivanisma and both parties will jointly oversee the studies. As you recall, ivanisma brings two highly validated targets together into one novel bispecific antibody that targets both PD-one and VEGF and hold a meaningful lead in terms of time and data generation in the clinical development of this novel class of compounds. Next, I would like to review some of the catalysts that we previously announced for this year. As we touched on a moment ago, we are anticipating HARMONY top line data in mid-twenty twenty five, which we expect will include data related to both primary endpoints of progression free survival and overall survival. This will be the first global Phase III clinical trial readout for ivanismab, which will provide information related to clinical profile of ivanismab beyond China, as well as data that may lead to a potential path to applying for marketing authorization in our territories, including The United States.

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

As we stated previously, this trial was conducted with patients whose non small cell lung cancer was positive for EGFR mutations and had progressed after third generation TKI therapy. This is a setting where PD-one inhibitors, including pembro, had failed to show an improvement in either progression free survival or overall survival, providing an opportunity to demonstrate the differentiated mechanism of action for ibonesimab beyond currently available immunotherapy options. As a reminder, this study contains a subset of patients study from the HARMONY A study conducted by AKSO in China who received a third generation EGFR TKI. HARMONY A led the first approval and commercial launch of ivanesevab in China in patients with EGFR mutant non small cell lung cancer. Additionally, HARMONY six as a catalyst event is intended to answer a proposed question as to whether the PFS benefits seen with ibunisimab monotherapy compared to PD-one monotherapy would carry over to chemo combination settings, in this case in frontline non small cell lung cancer.

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

As was announced last week, in HARMONY six, ivanizumab in combination with chemotherapy achieved statistically clinically meaningful PFS benefit over tislelizumab in combination with chemotherapy in frontline patients with squamous non small cell lung cancer patients. Cislelizumab is a standard of care, anti PD-one therapy in China and Europe, and PD-one or PD L1 therapy plus chemotherapy is standard of care for first line patients without driver mutations in a non small cell lung cancer in nearly all major markets globally. The full HARMONY six data set is planned to be presented at a major medical meeting later this year. Finally, data from the HARMONY two trial conducted by our partners at EKESO in China provide insights regarding how the benefits seen with ibonesumab in progression free survival can translate to overall survival. After its groundbreaking PFS benefit over monotherapy pembro, an early look at OS requested by the health authorities in China showed a strongly positive overall survival trend with a hazard ratio of zero point seven seven seven at thirty nine percent data maturity, implying a potential decrease of more than twenty two percent in the risk of death for those patients receiving abanisumab compared to pembro.

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

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

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

Recall as well that this trial was sufficiently powered to show a statistically significant PFS benefit in order to gain approval in China, which it has already done. It was not powered and the design was not intended to show a statistically significant OS benefit. When considering what an early look at OS requested by the Chinese health authorities, which feel relative events in the trial not powered for overall survival means statistical significance was not part of

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

our

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

consideration, focus or expectations as indicated by AKCel's minimal alpha spend. As we previously announced, a planned interim analysis is expected roughly by the end of this year, which will have a greater number of OS events. Note that HARMONY-seven, our global study of frontline patients with PD L1 high expressing non small cell lung cancer, which intends to enroll seven eighty patients, nearly double the enrollment of HARMONY-two is sufficiently powered to show a benefit in both PFS and OS. Context matters here. What this health authority requested interim analysis did show was that at this early stage, an early look at the data, if you will, overall survival already shows a strongly positive trend that is clinically meaningful.

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

If HARMONY seven were to show similar results at its final OS analysis, it is highly probable that this would result in a statistical significant overall survival benefit being achieved. This first look at overall survival data for HARMONY-two combined with a strong PFS result in HARMONY six is remarkable. This data in totally with previously disclosed data for HARMONY A and PFS data for HARMONY two as well as the earlier phase trials in and outside of non small cell lung cancer conducted by AKSO further validate that ivanicimab is mechanistically distinct from PD-one inhibitors and has the potential to make a meaningful positive impact for patients facing difficult cancer diagnosis. We are thrilled with the data released last week in both the statistically significant PFS results from the first interim analysis in HARMONY six and the early look requested by NPA at survival in HARMONY two. In speaking with the key opinion leaders, we have received very positive feedback.

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

Our KOLs are highly encouraged by the potential of ivonilizumab. This is consistent with the published feedback of multiple top thoracic KOL in media articles over the past week. Additionally, AKSO continues to enroll multiple Phase III clinical trials, including biliary tract cancer, pancreatic cancer, triple negative breast cancer and head and neck cancer and intends to launch an additional Phase III study in second line or later non small cell lung cancer after progression on immunotherapy. Now I would like to take a moment to review study design for our two ongoing global Phase three trials, HARMONY three and HARMONY seven. For those on the webcast, this slide shows the study design for HARMONY three.

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

HARMONY three is a randomized double blind global Phase three clinical trial evaluating abanisumab in combination with chemotherapy against pembro, in combination with chemotherapy as first line treatment for patients with metastatic non small cell lung cancer. This trial includes patients with squamous or non squamous histology with no activating genomic alterations regardless of PD L1 expression, including high, low and negative PD L1 expressing tumors. Dual primary endpoints for ARMONY-three include progression free survival and overall survival and results will be stratified by squamous and non squamous histology. As we have discussed, HARMONY six from our partner AKSO in China met its primary endpoint achieving statistically significant and clinically meaningful improvement in progression free survival for ivonesumab with chemotherapy against PD-one therapy, with chemotherapy in frontline treatment of patients with squamous non small cell lung cancer regardless of PD L1 expression. These results from a case of trial conducted in China further validate our conviction in the potential for this study.

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

We look forward to the full HARMONY six data set being presented at a major medical conference later this year. Next, we have the study design for HARMONY-seven, a randomized double blind global Phase three clinical trial evaluating abanisumab monotherapy against pembro, monotherapy as first line treatment for metastatic non small cell lung cancer patients with tumors with high PD L1 expression. Dual primary endpoint for HARMONY seven includes progression free survival and overall survival and results will be stratified by square month and non square month histology. As a reminder, our HARMONY seven study shares similarity with the AKSO sponsored HARMONY two Phase three trial, but focuses on those patients whose tumors have a high PD L1 expression for which monotherapy pembro is a current standard of care in The United States and other major Western markets. Turning to the market opportunity, ibonisibam has the potential to be a platform blockbuster drug and is well positioned to make a significant impact across the treatment landscape of non small cell lung cancer and beyond.

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

In non small cell lung cancer alone, there are combined seven announced or ongoing Phase three study conducted by either EKESO or SUMMIT. According to third party research, including T. D. Cohen and others, the non small cell lung cancer addressable market is expected to approach $20,000,000,000 for checkpoint inhibitors. With the recent data announced by our partner, AKSO in China, our belief is further validated in the potential for ibunitsumab to make a significant difference for patients with non small cell lung cancer.

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

Beyond non small cell lung cancer across all checkpoint inhibitor indications, the addressable market approaches $90,000,000,000 globally in future years according to IQVIA research. But as we have been discussing, while the checkpoint inhibitor market opportunity is significant, the potential opportunity that I just mentioned does not include the full impact that avenizumab could have, given it has shown promising data in multiple tumor types where checkpoint inhibitors have not been effective. This includes microsatellite stable colorectal cancer, PD L1 low and negative triple negative breast cancer and EGFR mutant non small cell lung cancer after targeted therapy based on the Phase II studies conducted by ECCEL. In total, there are more than 50 indications where PD-one, PD L1 or VGEL therapies have been approved, all areas for ivanismab to potentially offer patients with cancer and improved treatment option. Ivanismab will continue to be appropriately, rapidly tested and developed beyond non small cell lung cancer.

[Maky Zanganeh, Co-CEO & President at Summit Therapeutics]

I continue to applaud the work of TIP Summit and its rapid advancement in the development of ivanismab, which only two years ago began to open the first clinical site ever in The United States for ibonesumab. We persistently evaluate opportunities to accelerate our timeline in bringing additional therapeutic options to patients with high unmet cancer needs and look forward to upcoming announcements regarding expansions to our clinical development pipeline. With that update, I will now ask Manmeet to provide details on our financial and operational update.

[Manmeet Soni, COO, CFO & Director at Summit Therapeutics]

Thank you, Mickey, and good afternoon, everyone. We issued this afternoon our earnings release for the first quarter of twenty twenty five. Today, in addition to providing you with an update on our cash position and operating expenses, I will also provide you color on our clinical, commercial and manufacturing operations. Let me start with an update on the clinical operations front. As Mickey mentioned earlier, we expanded Harmony III clinical trial during the fourth quarter of twenty twenty four to add non squamous patients.

[Manmeet Soni, COO, CFO & Director at Summit Therapeutics]

We are very pleased with the rate of enrollment across the HARMONY three trial for both squamous and non squamous patients in The United States and Europe. In addition, very recently in 2025, we have initiated enrollment for patients in HARMONY seven clinical trial in The United States. We expect to initiate enrollment for the other regions during the next quarter based on the regulatory clearances to begin activating sites later this quarter. With our expected top line results from HARMONY trial during middle of this year, we have initiated preparations for our first potential commercial launch of avanizumab. We recently strengthened our leadership team with the appointment of Robert Lacais as our Chief Commercial Officer.

[Manmeet Soni, COO, CFO & Director at Summit Therapeutics]

Robert is a seasoned biopharmaceutical executive with over thirty years of extensive leadership experience in commercial strategy and execution. Prior to joining Summit, he held senior positions at major pharmaceutical companies including Bayer Healthcare and Bristol Myers. With a proven track record of launching and growing blockbuster oncology franchises, Robert joins our team at the right time as we continue to refine our commercial strategy and expand our capabilities. In addition to Robert, we have also hired key hires for MarketAxess, marketing and sales to optimize the commercial launch strategy. On the drug manufacturing front, in addition to our current supply source for avanasumab from Acaiso, our collaboration partner, we have made significant progress in transferring relevant know how to certain third party contract manufacturers in our license territory.

[Manmeet Soni, COO, CFO & Director at Summit Therapeutics]

Also, we are very pleased with the first approval of Acaiso's PD-one inhibitor pembrolizumab by the U. S. FDA, which demonstrates Acaiso's capability to adhere to global manufacturing and quality standards. On the financials front, let me start with our cash position. We ended the first quarter of twenty twenty five with a strong cash position of approximately $361,000,000 Let me remind you that we paid off our debt in entirety during the fourth quarter of twenty twenty four and are now debt free.

[Manmeet Soni, COO, CFO & Director at Summit Therapeutics]

Turning to operating expenses, I'll provide details on both GAAP and non GAAP numbers. You can refer to our press release issued this afternoon for a reconciliation of GAAP to non GAAP financial measures. As a reminder, non GAAP expenses exclude stock based compensation expenses. Our GAAP R and D expenses during the first quarter of twenty twenty five were $51,200,000 compared to $51,400,000 for the fourth quarter of twenty twenty four. And non GAAP R and D expenses were $47,100,000 for both first quarter twenty twenty five and for the fourth quarter of twenty twenty four.

[Manmeet Soni, COO, CFO & Director at Summit Therapeutics]

Our GAAP R and D expenses for the first quarter of twenty twenty five remained flat as compared to the last quarter of twenty twenty four. Our GAAP G and A expenses during the first quarter of twenty twenty five were $15,600,000 compared to $14,200,000 for the fourth quarter of twenty twenty four. And non GAAP G and A expenses were $8,600,000 during the first quarter of twenty twenty five compared to $7,500,000 for the fourth quarter of twenty twenty four. Our GAAP G and A expenses primarily increased due to an increase in professional services to support the development of avanizumab. Overall, our non GAAP operating expenses during the first quarter of twenty twenty five were $55,700,000 compared to $54,600,000 for the previous quarter.

[Manmeet Soni, COO, CFO & Director at Summit Therapeutics]

The increase in non GAAP operating expenses were primarily related to an increase in G and A expenses as noted above. And with that, I'll hand it back over to Dave.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Thank you, Bob, Makhi and Mamit. We are now we will now see if there are any questions that our team can help answer. Dustin, please open the line for

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

questions.

[Operator]

Thank

[Operator]

And with our first question comes from the line of Salveen Richter from Goldman Sachs. Your line is open.

[Mark Aleynick, Biotechnology Equity Research at Goldman Sachs]

Hey, team. This is Mark on for Salveen. Thank you so much for taking our question and congrats on the quarter. A couple of questions on the upcoming HARMONY eGFR dataset. So I think everyone's going be focused on sort of the subgroup data to confirm if AKHEA's prior data generated in China translates to Western regions.

[Mark Aleynick, Biotechnology Equity Research at Goldman Sachs]

So what do you believe the bar for success here is in this context? Like how closely does the data have to mirror Harmony A to support the translatability? And also, in the context of Ribrovant's approval on Mariposa two, what profile are you hoping to see from Harmony to and sort of what level of benefit do you believe would convince docs to use Ivo in second line EGFR? Thanks.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Thanks Mark for the question. I'll give a couple of words and then I'm going to hand it over to Jack West, our thoracic oncology lead. I think in terms of your first question, we're not going to necessarily prescribe a bar or a specific number that we're looking to achieve. I think the overall data package consistency or the data package and the general consistency with the data that comes from China will be the important piece, the global consistency, if you will. We're not interested in setting a bar.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

That will be part of the discussions with the agency. But with respect to, the second part of the question, I'll I'll hand that over to Jack.

[Jack West, VP of Clinical Development at Summit Therapeutics]

Hi. This is Jack West. So I would comment that, obviously the entire field of EGFR mutation positive non small cell has become much more complex over the last couple of years with a lot of new options, but that still leaves plenty of open space for new choices. One would be that with the potential for amivantamab and lisertinib to be used in the first line setting, that leaves a need for another option that is very appropriate for the Harmony platform to fill. Obviously, that's not going to be everybody, and there's going to be patients who get osimertinib monotherapy or the FLORA two approach with combination of chemotherapy and osimertinib, but obviously, amivantamab with chemo has a combination of efficacy with toxicity liabilities that looks very different from what chemo and ivanesumab offers.

[Jack West, VP of Clinical Development at Summit Therapeutics]

I have had extensive discussions with clinicians in all sorts of settings, academic and community based, and there's really a strong sense that there's a value and a great need for alternatives that have a very different and potentially less challenging toxicity profile. Obviously, efforts are made in ways to ameliorate the toxicities with amivantamab, but there will always be a value in choices.

[Mark Aleynick, Biotechnology Equity Research at Goldman Sachs]

That makes sense. Thank you.

[Operator]

Thank you. Our next question comes from the line of Ygal Lachomovitz from Citigroup. Your line is open.

[Yigal Nochomovitz, Director at Citigroup]

Hi, everyone. Thank you very much for taking the questions and congrats on the very positive recent developments. My question also on Harmony. Could you just be more specific in terms of what will we see with respect to the geographic data, meaning China versus ex China patients? Are we going to be getting separate hazard ratios on PFS and OS for each of these geographies?

[Yigal Nochomovitz, Director at Citigroup]

Would it be something in the form of a forest plot? Or would it just be some kind of a more qualitative statement around potential comparability?

[Yigal Nochomovitz, Director at Citigroup]

That's my first question. Thank you.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Thanks, Higal. This is Dave. I think the I would break that down into two points, one of which is the true top line, data, if you will. That typically will be a little bit more qualitative, right? Major medical conferences, that presentation obviously will have a bit more detail.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

It'll certainly give some context to geographic breakdowns in a forest plot is certainly one way to do that. We'll make those final decisions, but the goal will be to give appropriate context with respect to the breakdowns between North American and European patients as compared to those enrolled in China.

[Yigal Nochomovitz, Director at Citigroup]

Okay. Thanks. And then two more on HARMONY. With respect to timing, you just only said mid-twenty twenty five. Is it fair to assume that we would see Harmony before we see Harmony two and Harmony six, which you've alluded to at the fall medical meetings?

[Yigal Nochomovitz, Director at Citigroup]

And then also with Harmony, what is your view on whether you need OS to be stat sig for a competitive filing in The United States? Thanks.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Sure. With respect to the timing of the excuse me, the timing of the data releases, that will that will come down ultimately to which conference, especially in the fall, you know, takes which which presentation and whatnot and some of that strategic in terms of, where and when that'll be displayed. In terms of the timing across them, don't know that we have a specific order in terms of one versus, the other. What I would say is we would expect top line data for Harmony in the middle of twenty twenty five. I would think by the time you get into ESMO that's more in October, you're a little later there.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

So I can't give you, Ygal, yet which conference different data will go where, but there should certainly be at least top line before we get to the end of Q3 beginning of Q4. Hopefully, that's helpful. Can you repeat your second question, Ygal?

[Yigal Nochomovitz, Director at Citigroup]

I was just curious about the relative importance of hitting on OS in Harmony to have a competitive BLA filing.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Yes. I think at this point it's important to say we have two primary endpoints. We want to be clear on that. I think the other piece becomes the totality of the package. Importantly, I'll ask Jack or Alan to add any context here.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

But in the second line EGFR mutant non small cell lung cancer space post the TKI, overall survival hasn't been seen at this point to show a statistically significant benefit in any regimen. And so that will be part of the context. But importantly, as you noted, we have two primary endpoints. So it'll be a total package there.

[Allen Yang, Chief Medical Officer at Summit Therapeutics]

Yes. This is Alan Yang, Yigal. I don't have much to add except that the precedent in this space has not been it's not been needed to hit OS to get an approval. Of course, we would like to show clear benefit for ibonesumab in this space. But I think it's wonderful for patients that there's going to be multiple choices for them, as Jack alluded to.

[Allen Yang, Chief Medical Officer at Summit Therapeutics]

I think this is unfortunately a palliative setting. So I think a lot of things will go into the physician's mind about what to use, efficacy as well as toxicity profiles and so forth.

[Yigal Nochomovitz, Director at Citigroup]

Maybe if I could just squeeze one in, for you, Alan, or maybe Jack. Obviously, the Pfizer partnership for the ADCs is great. However, that one is missing some of the more perhaps relevant targets in non small cell lung cancer such as a trope two or HER2, HER3. So how are you thinking about that aspect of a longer term strategy in lung cancer to combine potentially down the road with those types of ADCs?

[Allen Yang, Chief Medical Officer at Summit Therapeutics]

Yes, Yigal. That's a great question. So again, I think the landscape of cancer is changing very quickly, which is terrific. I think Pfizer is a great partnership. They have a great pipeline of ADCs.

[Allen Yang, Chief Medical Officer at Summit Therapeutics]

We're not sort of wedded to the pipeline. We're open to it. Evenesumab is our only child, really. And so we are open to other collaborations as well. And so we continue to follow the lung cancer landscape and we're open to whatever is the best treatment for patients.

[Allen Yang, Chief Medical Officer at Summit Therapeutics]

And we this is Jack West. We do

[Jack West, VP of Clinical Development at Summit Therapeutics]

have other combinations that are being evaluated in potential development in in settings like ISTs and even cooperative group efforts. So we're we're quite open to an array of options that'll give us a lot of combination opportunities.

[Yigal Nochomovitz, Director at Citigroup]

Okay. Thank you so much.

[Operator]

Thank you. Our next question comes from the line of Cory Kasimov from Evercore. Your line is open.

[Cory Kasimov, Senior Managing Director at Evercore]

Hey, good afternoon guys. Thanks for taking the questions. I'll take the two of them. I guess first one is for HARMONY two, you obviously showed pretty profound PFS benefits across all cuts of the data and histology is everything else. Would you expect that to broadly hold for overall survival as well?

[Cory Kasimov, Senior Managing Director at Evercore]

And then I have a follow-up.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Hey, Corey, great question. This is Dave. At this point, the only data that's been released publicly from our partners at I guess has the top line hazard ratio for HARMONY two. So to your point, you are correct in the consistency of the PFS data, within Harmony two. But I don't want to get in front of our partners in terms of data release with respect to, subgroups or anything like that.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

But the, beyond going beyond the the top line overall survival, hazard ratio that they provided.

[Cory Kasimov, Senior Managing Director at Evercore]

Okay, understood. And then a question we get a lot of want to ask you is do you expect safety trends in global population whether it's the HARMONY study or some of your follow on ones to match what's been seen in the datasets coming out of China. What would be the rationale as to why it could be different?

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

So, Corey, I just wanna make sure I understand your question. You're asking for the rationale in terms of why the data would be different between China and Yeah.

[Allen Yang, Chief Medical Officer at Summit Therapeutics]

On on the safety front.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Okay. I'll I'll hand that one over to Jack if you want to, you know, speak to to that at all.

[Allen Yang, Chief Medical Officer at Summit Therapeutics]

Yeah. This is, Alan Yang. Corey, I think I understand the question. So let me say one thing first. So there's now at least two randomized data sets that have been publicly disclosed, the HARMONY A and the HARMONY-two, in terms of safety.

[Allen Yang, Chief Medical Officer at Summit Therapeutics]

And we're really happy with the safety profile reported to ivonesumab. This is against double blinds. One is placebo controlled and the other one is against pembrolizumab. So we believe that the safety profile looks really good, especially since the investigators didn't know which drug was they're getting, and so they're reporting the adverse events sort of in an unbiased approach. In terms of differences in safety reporting in China versus The U.

[Allen Yang, Chief Medical Officer at Summit Therapeutics]

S, I don't think there's going to be anything significant. Remember, even in global studies today, especially in lung cancer, a large proportion of the studies report data from China. The investigators are Chinese, and now they're being significant contributors to those global studies. There are slight differences in standard of care or cultural differences in reporting AEs. We've noticed that in the HARMONY A study, a lot of lab values were reported.

[Allen Yang, Chief Medical Officer at Summit Therapeutics]

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

[Jack West, VP of Clinical Development at Summit Therapeutics]

I would also just add, this is Jack West, that the things that to the clinicians are going to be of greatest concern are serious bleeding issues or things that are not nuanced questions that would be subject to that kind of interpretation. Think the and the data that we've seen have been so well ensconced in a place where clinicians are happy that it would have to be a very notable departure from anything that's been seen at this point in larger trial settings prospectively moving forward.

[Cory Kasimov, Senior Managing Director at Evercore]

Okay. Yeah. We found the safety language in the QEZO press release on Harmony six to be very reassuring. But that answer is very helpful. Appreciate it, guys.

[Cory Kasimov, Senior Managing Director at Evercore]

Thank you.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Thanks Corey.

[Operator]

Thank you. Our next question comes from the line of Kelly Hsieh from Jefferies. The line is open.

[Kelly Shi, SVP & Senior Research Analyst - Biotechnology at Jefferies]

Congrats on the progress. And my first question is for HARMONY-three, the chemo combo trial in frontline. Do you set enrollment target for squamous and non squamous versus non squamous patients? Is it expected to be split equally across two subtypes? And also have a follow-up.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Alan, do you want to take that question?

[Allen Yang, Chief Medical Officer at Summit Therapeutics]

Yes. We do have sort of enrollment objectives for both the pathologies so that we would have enough scientific information to have an informed decision on both histologies. We haven't disclosed the exact numbers, and they're not precise. They're sort of ranges of the expectations. So there ought to be equal amounts of squamous and non squamous at the end of the study.

[Kelly Shi, SVP & Senior Research Analyst - Biotechnology at Jefferies]

Great. And also for Harmony7, the global trial running by Summit in the PD L1 positive patient, what kind of media overall survival benefit in terms of like how many months of improvement over PD-one would be considered transformative and replace PD-one standard of care in this frontline settings?

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Hey, Kelly, this is Dave. I would just want to say we haven't given our statistical plan yet in terms of this. I'll let the physicians comment on the clinically meaningful, thresholds and whatnot. But I in terms of what we're like gearing the trial for and whatnot, that's not necessarily a plan we've given. The only thing I would say from a top line perspective, I think we're we've been pretty clear publicly that as we look at overall survival, being around or under the 0.8 hazard ratio has been a focus for us.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

But I'll let, Jack if there's anything else or Alan you want to add to that.

[Jack West, VP of Clinical Development at Summit Therapeutics]

Yeah. This is Jack West. I I think that Dave underscored all the right points that, in general, I would say that if it is statistically significant to make this a positive trial, it is extremely likely that it will be more than sufficient from a clinician standpoint to be clinically significant and revise the standard of care. I would say that statistical plan is likely to be more stringent than what clinicians or patients are looking for as a clinically meaningful improvement and that as a general statement that most clinicians looking for are looking for two or three months at least of an improvement in overall survival. So that's not specific to this trial, but just is a general benchmark of practice changing.

[Allen Yang, Chief Medical Officer at Summit Therapeutics]

Yes. I would just underscore what Jack said, that we haven't really released those specifics around our statistical analysis plan. But if this HARMONY seven study is positive as designed, it would be very clinically meaningful and an important change in the standard of care. I'd also add, like, if you look at the HARMONY two data presented to date, if those numbers hold up, I think that's very clinically meaningful and important data. Our

[Operator]

next question comes from the line of Aslika Gundwatin from Tru Securities.

[Karina Rabayeva, VP - Biotech Equity Research at Truist Securities]

This is Karina for Asika. Congrats on the progress. First one is when do you guys expect the Chinese NMPA label to be publicly available by Keystone for Harmony II? And have you seen what the OS curves look like? And since it's now approved in China, can you tell if they show consistent or widening separation over time?

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Karina, this is Dave. So in terms of label being available from the NMPA, typically it's a little bit different in terms of how it works from The U. S. Perspective. It's not necessarily published on the in The U.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

S. Case, the FDA website. So it becomes part of the next round of shipment in the physical product is kind of the official update. But it typically will be made available in a period of time shorter than that. But it's the short term aspect from that perspective.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

With respect could you repeat your second question, Karina?

[Karina Rabayeva, VP - Biotech Equity Research at Truist Securities]

Yeah. If you've seen the OS curves, what they look like and since it's already approved in China, can you tell, like, whether they're, consistent or they're writing over time?

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Yeah. And so I similar to what I mentioned before, this is Dave again, we're the trial was, sponsored and conducted by our partners at Akeksa. So we're gonna allow them to release, you know, the information with respect to their clinical trials. So we're not going to get into the specifics of things that they haven't yet disclosed publicly. But appreciate the interest and that would likely come when they choose to disclose that at a medical meeting or otherwise.

[Karina Rabayeva, VP - Biotech Equity Research at Truist Securities]

Okay.

[Karina Rabayeva, VP - Biotech Equity Research at Truist Securities]

And also one more on HARMONY '3. Have you guys had discussions with FDA about leveraging Project Front for accelerated approval?

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

I didn't you cut out when you said project. Sorry. Sorry, Karina, do you mind repeating the question?

[Karina Rabayeva, VP - Biotech Equity Research at Truist Securities]

I am bad, sorry. Sorry. Project front runner for an accelerated commission of filing.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

So in in general, we don't typically get too far into our, you know, discussions with the agency. We wanna respect, you know, what the agency, and we talk about in general. We have had conversations with the agency multiple times with respect to Harmony three just to be clear. And we align our trials based on feedback from the agency. But we don't necessarily want to get into the individual details of the conversations per se.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

But I appreciate the question.

[Karina Rabayeva, VP - Biotech Equity Research at Truist Securities]

All right. Thank you.

[Operator]

Thank you. Our next question comes from the line of Mohit Bansal from Wells Fargo. Your line is open.

[Mohit Bansal, Managing Director at Wells Fargo Securities]

Great. Thank you very much for taking my question and congrats on all the progress. I have two questions. I'll start one by one. So regarding HARMONY-two, is it fair to assume that the majority of the OS events would have happened only among the low PD-one patients given that OS for KEYTRUDA tends to be significantly longer for PD-one high patients and by extension, ivonismar?

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Hey, Mohit, this is Dave. I very much appreciate that question in the sense of the expectation that you set there. And your baseline comment is true in the sense of the difference in the medians on the pembrolizumab side. But at this point that becomes kind of a subgroup analysis piece. And so again, we'll defer to our partners at Acasso in terms of the timing of the detailed releases there.

[Mohit Bansal, Managing Director at Wells Fargo Securities]

Got it. Okay. So let me ask you other one. Thank you. I appreciate that.

[Mohit Bansal, Managing Director at Wells Fargo Securities]

So look, I mean, the lung cancer, non small cell lung cancer, you are going after, an indication that pembro is pretty strong. Are there other indications where the delta for VEGF p one combination could be much more pronounced versus the p one inhibitor, where, you know, VEGF could add a lot more value than than just lung cancer? And then where are you in terms of pursuing those indications outside of lung cancer? Thank you.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Thanks, Mohit. Yes. And I'll take the first part of that and then I'll hand it over to Alan for some details there. But I think I would what I'd probably refer you to is the ESMO 2024 Phase two data that was published by AKSO. And so there are indications or tumor settings more appropriately there that would not typically be places where PD-one inhibitors in and of themselves have been particularly successful.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Examples of that include microsatellite stable colorectal cancer as well as the PD L1 low and negative triple negative breast cancer tumor settings. In terms of the more specifics on our development plan, I think as McKee mentioned in the prepared remarks, we do plan on giving a little bit more context over the course of this year as opposed to kind of the individual leaking out of or dripping of details. But we want to make sure we have the right alignment with the agencies, and so on. But maybe biologically or whatnot, Alan, if you want to add any context to that.

[Allen Yang, Chief Medical Officer at Summit Therapeutics]

No, I think it's a good question. Again, we sort of boil the ocean. We've looked at the PD-one approvals. We've looked at the VEGF approvals. And then there's clearly tumors where the VEGF and PD-one activity overlap, and we're looking at those.

[Allen Yang, Chief Medical Officer at Summit Therapeutics]

The things to consider about that is what it be the control arm for that study, what regions are those tumor types more prevalent in. And I think you can sort of guess what I'm alluding to if you look at the specific tumor types. And then what is the Phase II data Acasto generates? That's probably the most important thing and how we're thinking about which tumor types to go into next. So we do have a very clear plan of where we want to go next, and we're very excited about the IBO data.

[Allen Yang, Chief Medical Officer at Summit Therapeutics]

And all of those considerations, including the PD-one and VEGF activity, are taken into consideration.

[Jack West, VP of Clinical Development at Summit Therapeutics]

I would just potentially add that in addition to specifically the VEGF component, the cooperative binding is relevant here. That if we look at settings where we've demonstrated success, you have EGFR mutation positive. It's a setting, yes, where VEGF may be particularly relevant. It's also a setting where other PD-one inhibitors have not proven successful. You can also look at HARMONY two and see that in the setting of high PD L1 where pembro has been very favorable, we also saw great success for Ivo relative to pembro, but also see benefits for ivonesumab in the low PD L1 setting against pembro, where pembro has not been as commanding of a choice.

[Jack West, VP of Clinical Development at Summit Therapeutics]

And so I think that that can be extrapolated potentially into other settings, whether that is because specifically of the VEGF component that it brings, but it also may be because of the cooperative binding that may render ivonesumab a more effective immunotherapy.

[Mohit Bansal, Managing Director at Wells Fargo Securities]

Helpful. Thank you.

[Operator]

Thank you. Next question comes from Mitchell Kapoor from H. G. Wainwright. Your line is open.

[Mitchell Kapoor, Director, Senior Biotechnology Analyst at H.C. Wainwright & Co., LLC]

Hey, team. Congrats on the recent progress and thank you for taking the questions. I wanted to ask, so the NMPA granted the first line approval in PL1 positive non small cell lung cancer patients in China based on HARMONY-two. But wanted to understand what it's going to take to get approval in the PD L1 low patients. Why didn't they grant this approval?

[Mitchell Kapoor, Director, Senior Biotechnology Analyst at H.C. Wainwright & Co., LLC]

Did they indicate anything like they need to see more data? Or is that indicative of anything they're seeing in

[Mitchell Kapoor, Director, Senior Biotechnology Analyst at H.C. Wainwright & Co., LLC]

the HARMONY-two trial so far?

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Hey, Mitchell, it's Dave. Let me clarify that because I just want to make sure this is clear. So in so we generally break down PD L1 expression by negative less than one, low one to 49 or high 50 plus. And then in the case of Harmony two, when we say PD L1 positive, that was really one plus, if you will. So the high and the low, but not the negative.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

So the approval, as we understand it in China from the NMPA, was in PD L1 positive. So great PD L1 expression, you know, greater than one, if you will, if you use the TPS scoring system. And so that is what the HARMONY two trial was designed as PD L1 positive. For HARMONY seven, because of the standard of care, in the western markets, our trial is designed, it is a PD L1 high expressing patient population. Just want to clarify and make sure that's clear, Mitchell.

[Mitchell Kapoor, Director, Senior Biotechnology Analyst at H.C. Wainwright & Co., LLC]

Yeah. Thank you. Sorry. So what I meant to ask is the PD L1 negative, patients, is there something that needs to be shown there that would be able to, gain approval in that population?

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

So that wasn't part of the HARMONY two study. And so what would need to be shown there is really a separate trial for lack of a better way of putting it. So the other thing that's important is if you look at the HARMONY six data, that AKSO announced top line results for that is PD L1 all comers. So that would have the PD L1 negative for the less than one percent if you use the TPS score. And that's a chemo combination study, right?

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

And so I think and I'll hand this over to Jack to comment, next. But if you look at the PD L1 negative population, really that's more of a chemo combination or something else akin to either our HARMONY three squamous and non squamous or Kessos HARMONY six and squamous only.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Thank you, Jack.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Go ahead.

[Jack West, VP of Clinical Development at Summit Therapeutics]

Yeah. I just think Dave articulated it very well. That's HARMONY two just doesn't speak to that population. It's not clinically that's just not clinically what it what it would cover, but HARMONY six as well as our own data, HARMONY three would and Harmony well, Harmony three in particular would be very relevant there. So that's just what it's going to take to be able to answer that question.

[Jack West, VP of Clinical Development at Summit Therapeutics]

Yes.

[Allen Yang, Chief Medical Officer at Summit Therapeutics]

And this is Alan Mitchell. So just to be clear, there is some variability in what physicians do based on the PD L1 expression levels. But to be clear, HARMONY three and HARMONY seven will cover the whole gamut of metastatic and advanced non small cell lung cancer.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Perfect. Thank you. I appreciate that.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

And then last one for me. Just on the next update for HARMONY-two, are you able to appreciate the nominal alpha, but are you

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

able to say if we'll

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

be able to see p value, reported along with that nominal alpha level?

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Just to make sure I'm clear, Mitchell, you asking when the next analysis would be or when the when the more detailed data for the, NMPA requested analysis would be?

[Mitchell Kapoor, Director, Senior Biotechnology Analyst at H.C. Wainwright & Co., LLC]

Sorry. Yeah. So then basically the next overall survival, update, obviously, you're at 30, you know, the, the 39% data maturity. But at the next update, would we be able to see the p value in addition to that nominal alpha level, you know, trying to search for statistical significance?

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Yes. I think what I would so a bit of that does come down to the choice by, Akesso given its their trial. But I think the if you will, the next analysis would be more of the planned analysis, in the intent. So it would be more likely it would be more likely mature data. Right?

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

And so you'd have a little bit more alpha spend that would come with that as well.

[Mitchell Kapoor, Director, Senior Biotechnology Analyst at H.C. Wainwright & Co., LLC]

Got it.

[Mitchell Kapoor, Director, Senior Biotechnology Analyst at H.C. Wainwright & Co., LLC]

Thank you very much.

[Operator]

Thank you. Our next question comes from the line of Eric Schmidt from Cantor Fitzgerald. Your line is open.

[Eric Schmidt, Biotechnology Analyst at Cantor Fitzgerald]

Thank you for taking my questions. One on HARMONY and one on HARMONY two. First on HARMONY, when we see the data in mid-twenty twenty five on overall survival, will that OS result be a mature one? And what is required, via your conversations with the FDA around The U. S.

[Eric Schmidt, Biotechnology Analyst at Cantor Fitzgerald]

Approval either in terms of what you need to see with OS or PFS the Western population?

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Yes. I think, Eric this is Dave. I think what we had said earlier, I think I'll kind of stick to that in terms of we won't get into the explicit details back and forth of the discussions. But I'd remind you that we have two primary endpoints. And so I think it'll become a total package review, irrespective of anything in terms of what the decisions would be.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

But, yes, I think I'd leave it there.

[Eric Schmidt, Biotechnology Analyst at Cantor Fitzgerald]

And the OS maturity?

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

So we haven't commented on that, Eric. So what we've said is and I think in McKee's prepared remarks, they were we will have data associated with both primary endpoints. But in terms of the specifics on how much maturity on different points, we haven't really disclosed that just yet. We're we're doing data on both endpoints.

[Eric Schmidt, Biotechnology Analyst at Cantor Fitzgerald]

Great. Thank you for that. Second question on the CARMONY-two hour that you've given, point seven seven seven seven, the pre interim analysis, let's call it. I guess the number one question I get is whether with time that hazard ratio is likely to mature in a favorable or unfavorable direction. Do you have a view on that?

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Sure. So I think and I'll ask Jack to comment on this in terms of different trials, that he's seen as well. But, I you know, it's a lower side of maturity. I think part of know, from a statistical perspective is there's a little bit more variability that exists there. But I certainly wouldn't expect, there's only one direction it can go.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

And and I certainly what I wouldn't do in particular is I would not analogize from the Harmony a data that I think, you know, occasionally, we hear some chatter on with respect to, you know, the initial NMPA request, you know, showed a 0.72 and then a follow-up with 0.8 on on the OS there. There's some very clear differences between these trials, second line versus first line, EGA positive, EGFR specifically versus non driver mutation positive, combination with chemotherapy versus monotherapy. So very important that, we've seen if we look at the PD-one inhibitors as a whole, if you will, for example, we've seen movements up and higher or lower, in terms of more maturity. But I think the point that we take here is that this early on in the overall maturity to see a clinically meaningful strongly positive trend is very encouraging from our perspective. Jack, any additional color that you'd add there?

[Jack West, VP of Clinical Development at Summit Therapeutics]

I would add that speaking with clinicians extensively since the initial release that essentially that clinicians don't consider the OS to be as binary as that, especially so when it's in the setting of early preliminary data. But that recognizing that this is going against pembrolizumab, which is an extremely respected comparator that has good activity. So if you are seeing just a nominal hazard ratio of 0.7 to eight or better against a comparator that is active and respected without the significant notable difference in toxicity, this is something that clinicians are absolutely welcoming and seeing in a very positive light, both for this particular setting and for what it may well represent outside of this particular test of monotherapy and PD L1 positive. But just for given the breadth of where pembrolizumab has historically been used in lung cancer and elsewhere, showing an improvement against that with a hazard ratio below point eight, especially in a preliminary setting, is it has really gotten people's notice and they are not remotely deterred by the statistical issues or the preliminary nature. For where it is and where it should be, I think that the clinicians by and large are quite impressed and happy with that.

[Eric Schmidt, Biotechnology Analyst at Cantor Fitzgerald]

Very helpful. Thank you both.

[Operator]

Thank you. And our last question comes from the line of Ren Benjamin from Citizens. Line is open.

[Reni Benjamin, Managing Director at Citizens JMP Securities, LLC]

Hey, good afternoon. Thanks for

[Reni Benjamin, Managing Director at Citizens JMP Securities, LLC]

taking the

[Reni Benjamin, Managing Director at Citizens JMP Securities, LLC]

questions. I guess one, in the HARMONY study, is the PFS and OS going to be evaluated as a co primary endpoint? Or as Mickey mentioned with HARMONY three and seven dual endpoints? And can you remind us why you'd favor, let's say, one over the other? And a more broader question, just given recent geopolitical tensions, can you kind of give us your thoughts on how you're thinking about potential impact of tariffs, how you're thinking about manufacturing and any IP and API based scenarios?

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Yes. Thanks, Ren. So for the first question, think we look at it more as dual primary endpoints in terms of passing the alpha in hierarchical testing PFS first and then OS. With respect to the second question, I will hand that over to Manmeet to speak to.

[Manmeet Soni, COO, CFO & Director at Summit Therapeutics]

Sure. Hi, this is Manmeet. On manufacturing front, as I mentioned earlier on the call, right, we already have our current supply source from our partner Acaiso. But in addition to that, we have made significant progress in starting our transferring the know how to certain CMOs, contract manufacturers in our territories, is U. S.

[Manmeet Soni, COO, CFO & Director at Summit Therapeutics]

And Europe, and other territories, which is continuing over there. And that covers our concern on the manufacturing part. In regard to IP, as you mentioned, we have our IP continues until like late two thousand thirty nine, 2040s, right? So we have no concern even on the IP part and we believe pretty good on that perspective too.

[Reni Benjamin, Managing Director at Citizens JMP Securities, LLC]

And just as a follow-up, I mean, the manufacturing from the CDMOs, will that product find its way into the ARMONY three and ARMONY seven trials so that upon potential approval, this is going to be quite kind of seamless in terms of the utilizing the material or will there need to be a bridging study? How do we think about that?

[Manmeet Soni, COO, CFO & Director at Summit Therapeutics]

No, it's like any because every, I would manufacturer or any pharma company will have multiple sources of production and we are also planning to add, right? Okay. So as one source, we'll have another source from our contract manufacturers and you will have to do certain regulatory filings in order to not bridging studies, but filings to compare the production batches and all those things that how they are comparing the batches with the specifications and that would be required to do done. And they obviously, first would be to use them in clinical supplies, but those happen on a very regular basis for all the pharma companies.

[Reni Benjamin, Managing Director at Citizens JMP Securities, LLC]

Great. Thanks for taking the questions. Sure. Thanks, Ren.

[Operator]

Thank you. There are no further questions. I turn the call back over to Dave Gancars for final remarks.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Thank you, Justin. And thank you everyone for the amount of interesting questions. I think the thing I'd like to do just to make sure we fully address is, I'll hand it over to Jack West for just given his extensive experience obviously in thoracic oncology and whatnot. Any final comments, Jack that you have with respect to the announcement with respect to the hazard ratio and the overall survival of the early look for HARMONY two?

[Jack West, VP of Clinical Development at Summit Therapeutics]

Yeah. I have had the opportunity over the last three to six months to have dozens and dozens of conversations with various thought leaders in thoracic oncology. Obviously, some of the biggest questions, the biggest questions for ivonesumab after a great year last year was how does this look outside of China? We will see information about that in the next several months. As well as does the benefit hold up when added to chemo or how much does the addition of chemo to both arms kind of aggregate the difference?

[Jack West, VP of Clinical Development at Summit Therapeutics]

HARMONY six is going to address that, and we already know that's in a favorable way, that that's not mitigated clearly, just it's not a phenomenon of monotherapy. And then the bigger question, and we'll be able to speak to this somewhat with Harmony and Harmony two, now we have some insights about PFS to OS. That's always a question in lung cancer and other tumor types. It's always question with various treatment approaches, but that's been a particular thorn in the side of VEGF inhibition, bevacizumab and and my colleagues and I have really thought about it that regardless of that specific p value associated, especially early and especially in a trial like ARMONY-two that was not powered for overall survival. The key thing is, is that hazard ratio for OS after that PFS that we saw, is that going to be 0.7 something or 0.9 something?

[Jack West, VP of Clinical Development at Summit Therapeutics]

That's really exactly what I've been saying with them, and nobody knew until we saw that press release where that was. But it is in the point seven something range, and and that is what people have been looking for just to get a sense of is this does this track or does it not? And the answer is it absolutely does track. So to me that addresses that question and allays some of those many of those concerns just we'll get more details. But this in broad strokes was what we were hoping to clarify if it gives it back or if it doesn't.

[Jack West, VP of Clinical Development at Summit Therapeutics]

Of course, it's likely to erode somewhat with subsequent treatments, but I and my colleagues prospectively had been looking for 0.7 something is exactly what we've been hoping to see.

[Dave Gancarz, Chief Business & Strategy Officer at Summit Therapeutics]

Really appreciate it, Jack. And I want to take the time to thank everybody for attending today's earnings call. We are unfortunately out of time now at this point, but, I want to say thank you and an archived version of the, of this webcast will be available on our website, www.smmtx.com. Thank you very much and enjoy your evening.

[Operator]

The meeting has now concluded. Thank you all for joining. Have a pleasant day and you may now disconnect.

Participants

Executives

• Dave Gancarz, Chief Business & Strategy Officer
• Robert Duggan, Co-CEO & Executive Chairman
• Maky Zanganeh, Co-CEO & President
• Manmeet Soni, COO, CFO & Director
• Jack West, VP of Clinical Development
• Allen Yang, Chief Medical Officer

Analysts

• Mark Aleynick, Biotechnology Equity Research at Goldman Sachs
• Yigal Nochomovitz, Director at Citigroup
• Cory Kasimov, Senior Managing Director at Evercore
• Kelly Shi, SVP & Senior Research Analyst - Biotechnology at Jefferies
• Karina Rabayeva, VP - Biotech Equity Research at Truist Securities
• Mohit Bansal, Managing Director at Wells Fargo Securities
• Mitchell Kapoor, Director, Senior Biotechnology Analyst at H.C. Wainwright & Co., LLC
• Eric Schmidt, Biotechnology Analyst at Cantor Fitzgerald
• Reni Benjamin, Managing Director at Citizens JMP Securities, LLC