Q3 2024 Summit Therapeutics Inc Earnings Call
Speaker Change: Good morning and welcome to Summit Therapyutics, third quarter 2024 earnings and update call. All participants will be in a listen-only mode until the question and answer portion of the call.
Speaker Change: We do not expect any technical difficulties today, however, in the event that we lose the webcast connection and are unable to provide in the updates, please wait up the 10 minutes for Resolute. Please refer to the company's website for updates. Please note that today's call is being recorded.
Speaker Change: After the speakers remarks, there will be a question in the answer session. If you would like to ask a question during this time, simply press star, followed by the number one on your telephone keypad. If you would like to withdraw your question, again, press star one. Thank you.
Speaker Change: At this time, I would like to turn a call over to Dave Gancarz, Summit Therapeutics, Chief Business and Strategy Officer. You may proceed.
Dave Gancarz: Good morning and thank you for joining us. Our press release was issued earlier this morning and is available on the home page of our website.
Dave Gancarz: Our Form 10Q was also filed earlier this morning in its available on our website. Today's call is being simultaneously webcast and an archives replay will also be made available later today on our website www.smntx.com
Dave Gancarz: Joining me on the call today is Bob Duggan, our chairman of the board and chief executive officer, Dr. MacKee Zanganeh, our chief executive officer and president, Manmeet Soni, our chief operating officer and chief financial officer, and Dr. Alan Yang, our chief medical officer.
Dave Gancarz: Before we get started with the rest of the call, I would like to note that some of the statements made by our management team today and some responses to questions that we will make may be considered forward-looking statements based on our current expectations.
Dave Gancarz: Summit cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Please refer to our SEC filings for information about these risks and uncertainties.
Dave Gancarz: Summit undertakes no obligation to update these forward-looking statements except as required by law.
Speaker Change: Following comments from Bob, Mekhi, and Manmeet, we will take questions. And with that, I'd like to turn the call over to Bob.
Bob Duggan: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Bob Duggan: Thank you, Dave. Good morning, everyone. Thank you for joining us today. I'm very proud of the recent accomplishment of Team Summit and the continuing positive information to be shared surrounding Ivanismab, our lead investigational asset.
Bob Duggan: There have been several meaningful achievements around the progress of Ibanez-Madison since our last earnings call.
Bob Duggan: both with our partners in China as well as here in the U.S. and Western markets. We continue to progress towards our mission of building an organization making a significant positive difference in serious unmet medical needs, specifically.
Bob Duggan: We intend to amend the protocol for our multi-regional phase 3 trial, Harmony 3, to now evaluate patients with first-line treatment for metastatic non-small-cell lung cancer with both squamous and non-squamous histologies.
Bob Duggan: The prior trial design previously included only tumors of squamous histology.
Bob Duggan: This is a significant, immediate expansion of total addressable market of our current phase 3 clinical trial portfolio. We will provide additional context in a few moments around Harmony 3's expanded patient population.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: We have completed enrollment of our global Phase III Harmony Trial in patients with EGFR-mutated advanced non-small cell lung cancer who have progressed after treatment with the third generation EGFR tyrosine kinase inhibitor, or TKI.
Speaker Change: As previously announced, we expect Harmony top-line data in mid-2025. In addition, we receive fast-track designation from the FDA for this setting in the United States.
Speaker Change: Following the positive results of Harmony 2, we announced our intentions for launching a third global Phase 3 trial, Harmony 7, studying ibanisumab monotherapy in patients with first-line metastatic non-small cell lung cancer whose tumors have high PD-L1 expression.
Speaker Change: Additionally, encouraging Phase II data featuring Ivanissimab from China was featured at World Lung and the 2024 European Society for Medical Oncology, or ESMO.
Speaker Change: Annual meeting in Prairie Operative non-small cell lung cancer, as well as indications outside of non-small cell lung cancer, including advanced triple negative breast cancer.
Speaker Change: recurrent metastatic head and neck cancer and microsatellite stable metastatic colorectal cancer. Each of these phase 2 studies were sponsored by Okeso with data generated and analyzed by Okeso.
Speaker Change: These encouraging data reflect why we are continuing to explore the expansion of our clinical development of ibinizumab outside of metastatic non-small cell lung cancer.
Speaker Change: In addition, we raised $235 million from leading biotech investors and individuals, including insiders, extending our cash runway and increasing our resources to execute upon expansive goals. Mahmeet will provide more details about our financial position in a few minutes.
Speaker Change: These accomplishments have been foundational to our 2024 goals of successfully executing on our registrational phase 3 trials while expanding our clinical development plan.
Speaker Change: McKee will further discuss these accomplishments, including additional strides taken to drive our continued belief and conviction in Team Summit and the potential of avinicimab in non-small cell lung cancer and indications beyond lung. We are a mission-driven organization with the collective goal to improve quality of life.
Speaker Change: increase potential duration of life and resolve serious medical needs. We believe we have the right team and the right molecule in Ivanisimab to help us realize this goal. With that, I will turn the call over to Maike for additional context and recent highlights for consideration.
Maike: Thank you, Bob, and good morning, everyone. As Bob said, I remain incredibly enthusiastic about the accomplishments of Team Summit and our partnership with EKESO.
Speaker Change: Before providing on some of the highlights, as Bob mentioned, I would like to discuss the clinical work that has been conducted with Ibonissima.
Speaker Change: There are more than 25 clinical trials around the globe evaluating abonisimab across 17 tumor settings, including nine phase 3 trials planned, ongoing, or completed, either in China or globally.
Speaker Change: While six of the Phase III programs across Summit and Equeso are currently focused in non-small cell lung cancer, three additional Phase III clinical trials have been announced by Equeso.
Speaker Change: evaluating our lead candidate in solid tumor settings beyond non-small cell lung cancer. This includes BTC, head and neck cancer, and pancreatic cancer.
Speaker Change: At Summit, we are sponsoring two ongoing Phase 3 clinical trials, Harmony and Harmony 3. We are planning to initiate Harmony 7 in early 2025.
Speaker Change: Based on the data Bob mentioned that was released at ESMO, that I will speak more to it in a moment, we are excited to and are actively exploring expanding our summit-led clinical development plan beyond metastatic non-small cell lung cancer.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: As a reminder, Ibanezimab is the only PD-1 VGF bispecific antibody in phase 3 in our licensed territories. Ibanezimab brings these two highly validated mechanisms of action together into one noble molecule, targeting simultaneously both PD-1 and VGF.
Speaker Change: Next, I would like to review the many achievements completed as well as discussed some upcoming catalysts for the remainder of this year.
Speaker Change: The third quarter of 2024 was a landmark moment for Ibanezema.
Speaker Change: and its development, with significant catalyst events in the form of data releases in September at the World Log and ESMO conferences.
Speaker Change: Last month, at the world's long conference, Harmony 2 results were featured as part of the presidential symposium and received a tremendous response from leading KOLs.
Speaker Change: In this head-to-head trial comparing Ibanezema versus Pembroke, both as monotherapy, Harmony 2 met its primary endpoint of progression-free survival, with Ibanezema achieving a 49% reduction in the risk of disease progression or death compared to Pembroke.
Speaker Change: Ibanezimab showed consistent, clinically meaningful benefit across key subgroups, including patients with either PD-L1 low or PD-L1 high-expressing tumors and in squamous and non-squamous histologies.
Speaker Change: Consistent with previous studies, Ibonissima demonstrated an acceptable and manageable safety profile.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: with the additional phase 2 data released in the third quarter at both Ward Long and Esmo.
Speaker Change: We continue to expand the meaningful data that has been generated with ivernessimab in various solid tumor settings beyond non-small cell lung cancer.
Speaker Change: We are fortunate to have created such a strong partnership in our ongoing collaboration with EKESO as we leverage data from multiple solid tumor studies, supporting and informing Summit's own late-stage clinical development strategy in our licensed territories.
Speaker Change: In addition to touching on our current clinical development plans, we initiated our strategic alliances with the University of Texas and the Anderson Cancer Center this quarter.
Speaker Change: Providing additional opportunities to evaluate abanisimab in tumor types and settings in which we have not yet tested its potential. Patients are expected to soon begin treatment and clinical development effort will soon begin via this collaboration.
Speaker Change: After the Harmony-2 data was announced, we have received inbound interest from physicians regarding approximately 75 proposed investigator-sponsored trials or ISDs in a wide range of cancer types.
Speaker Change: With meaningful updates this past quarter from EKSO's Harmony 2 study and several Phase 2 studies, we wanted to take the opportunity to review the respective study designs and further highlight key results.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: We will start with HARMONY-2. HARMONY-2 is a randomized, double-blind clinical trial evaluating front-line monotherapy ibonesimab as compared to monotherapy Pembro in patients with locally advanced or metastatic non-cell lung cancer with positive PD-L1 expression.
Speaker Change: This is a single-region, multi-center Phase III clinical trial conducted and sponsored by EKSO in China. Our partners at EKSO generated and analyzed the data in Harmony2.
Speaker Change: Here is the primary endpoint of progression-free survival by Blinded Independent Radiologic Review Committee for the entire study at the time of the first planned interim analysis.
Speaker Change: With a median follow-up of 8.67 months, demonstrating a significant improvement for Ibanezema, with a hazard ratio of 0.51, corresponding to a 49% improvement over the control arm.
Speaker Change: The median PFS was 11.1 months versus 5.8 months in the Ibanezema and Pembroke arms respectively.
Speaker Change: Of note, the curves begin to separate at the first point of radiographic assessment and maintain separation over the entire duration of follow-up thus far.
Speaker Change: The analysis of PFS subgroups reveals that the PFS benefit with Ibanezimab was observed across nearly all subgroups.
Speaker Change: Specifically, the benefit is quite comparable across the spectrum of PD-L1 expression with a hazard ratio of 0.54 for patients with PD-L1 low-expressing tumors and 0.46 for patients with tumors of high PD-L1 expression.
Speaker Change: As previously discussed, and this is particularly true in the United States and Europe, monotherapy checkpoint inhibitory usage is a standard of care for patients with high PD-L1 expression.
Speaker Change: With regard to non-small-cell lung cancer histology, the benefit was also similar for patients with squamous non-small-cell lung cancer who showed a hazard ratio of 0.48, favoring ibonicemab, and those patients with tumors of non-squamous histology with a hazard ratio of 0.54, favoring ibonicemab.
Speaker Change: This slide is a strong indicator that the benefit was seen across clinical subgroups and underscores that the success of the trial overall was not driven by an especially strong performance of a subgroup.
Speaker Change: For safety, we see that there was a numerically higher rate of serious treatment-related adverse events with Ibanezimab 20.8% compared to 16.1%.
Speaker Change: This did not translate to greater treatment discontinuation or treatment-related advanced events leading to death, both of which were numerically higher in the Pembroke arm.
Speaker Change: This pattern held true in patients with squamous non-small cell lung cancer as well, a place where anti-VGF therapy has historically demonstrated safety risk, where there were comparable rates of serious treatment-related advanced events.
Speaker Change: This is the first randomized phase 3 clinical trial evaluating the safety profile of Ibunisimab in the squamous population, especially confirming its tolerability in this group.
Speaker Change: In more detail, we see that nearly all of the higher rates of treatment-related adverse events were lab-related abnormalities, hypertension, and proteinuria, but generally did not lead to discontinuation of dosing.
Speaker Change: These are conditions that are often seen by oncologists who, in general, are experienced managing these AEs.
Speaker Change: Finally, looking at the immune-related and possibly V-DRIF-related events in the U.S.
Speaker Change: event, in the table to the left, we see comparable immune-related AEs with Ivonissimab compared to Pembro. On the right, we see that, as expected, Ivonissimab was associated with more possibly VGEF-related AEs, both in all graders and grade 3 or higher.
Speaker Change: Importantly, however, all grade 3 or higher AEs were all classified as grade 3. There were no grade 4 or grade 5 AEs that were possibly VJF-related in either arm of the study.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Proteinura, and Hypertation.
Speaker Change: There is no evidence.
Speaker Change: of life-threatening or fatal bleeding complications, including among patients with advanced squamous non-small cell lung cancer and in patients with central tumors, cavitary lesions, and or tumor-encasing large blood vessels in this Phase III study.
Speaker Change: as a result of the successful HARMONY II study.
Speaker Change: and our analysis of their underlying data, we announced our plan to initiate Harmony 7, a randomized global phase 3 study evaluating Ibanezema versus Pembroke, both monotherapy in frontline non-small cell lung cancer in the PD-L1 high expressor population.
Speaker Change: Harmony 7 is planned with the two primary endpoints, progression-free survival and overall survival. We are planning for an estimated 780 patients in this registration enabling study.
Speaker Change: Turning to Harmony 3, as Bob mentioned, we intend to amend this randomized global phase 3 clinical trial to include patients with tumors of non-squamous histology in addition to continuing to enroll squamous patients.
Speaker Change: As part of the trial amendment, the primary endpoint is intended to be updated to include two primary endpoints of progression-free survival and overall survival.
Speaker Change: The total sample size for this randomized multi-regional phase 3 clinical trial has been adjusted to include an estimated 1,080 patients.
Speaker Change: Expanding Harmony 3 is the most efficient way to cover all metastatic non-small cell lung cancer patients without driver mutations.
Speaker Change: Harmony 3 will now cover metastatic non-sponsored lung cancer, both squamous and non-squamous tumors, in combination with chemotherapy. And Harmony 7 intends to cover PD-L1 high-expressing tumors via monotherapy ibonesimab, now providing the opportunity to capture a significantly broadened, addressable market as quickly as possible.
Speaker Change: Supporting this proposed amendment, in part, is both the result of Harmony 2 showing benefit to patients with both squamous and non-squamous tumors, as well as the Phase 2 data that has been previously presented.
Speaker Change: As a reminder, updated Phase 2 data for this setting was announced at the 2024 European Lung Cancer Conference in March from the AK112-201 clinical trial centered around the cohort of patients in which ibonicimab is combined with chemotherapy for first-line treatment of squamous and non-squamous advanced or metastatic non-small cell lung cancer in patients without actionable genomic alterations. This data was generated and analyzed by EKESO.
Speaker Change: First-line patients with advanced or metastatic non-squamous tumors experienced a median progression-free survival of 13.3 months.
Speaker Change: In addition, first-line advanced or metastatic squamous patients experience a median progression-free survival of 11.1 months.
Speaker Change: Both metrics are encouraging considering the expectation for the current standard of care in this patient population largely driven by PD-1 inhibitors plus chemotherapy.
Speaker Change: The frequency of treatment emergent events leading to the discontinuation of Iburnissima was 11.1% and 2.8% respectively in patients with squamous and non-squamous tumors. We are highly encouraged by the opportunity of Iburnissima to demonstrate its potential across non-small cell lung cancer in multiple clinical settings.
Speaker Change: Finally, as we have stated, we are evaluating opportunity to expand our clinical development beyond metastatic non-small cell lung cancer. We will review the encouraging Phase 2 data announced this past quarter at Ward, Lung, and Esmo, starting with an overview of the respective study designs.
Speaker Change: The study was designed to assess patients receiving either Ibonicimab monotherapy or Ibonicimab plus chemotherapy prior to surgical resection and then Ibonicimab monotherapy after surgery.
Speaker Change: Due to the maturity of the data and the timing of the data cut-off, the results were mature for the neoadjuvant portion of the clinical trial. In September 2024, promising anti-tumor activity and safety data for ibanezema were presented at ESMO.
Speaker Change: featuring updated data in advanced triple negative breast cancer, recurrent metastatic head and neck squamous cell cancer, carcinoma, and metastatic microsatellite stable colorectal cancer.
Speaker Change: The HEAD and NECK study assessed patients who receive ibonisimab with or without ligofilamab with PD-L1 positive, locally advanced or metastatic recurrent HEAD and NECK squamous cell carcinoma.
Speaker Change: Note that Legal File Map or AK117 is a KSOS property, investigational product that is not approved by any regulatory authority and to which Summit does not have any license or ownership rights.
Speaker Change: The colorectal study was designed to assess patients who were randomly assigned to receive Ibunisimab plus folfaxillary with or without oligofilimab, an investigational anti-CD47 monoclonal antibody.
Speaker Change: The triple-negative breast cancer study assessed patients who receive ibuprofen plus chemotherapy, either paclitexel or nabpaclitexel with locally advanced or metastatic TNBC.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz, Ankur Dhingra, Robert Duggan,
Speaker Change: Turning now to anti-tumor activity and safety data from these Phase 2 studies. In pre-operative non-small cell lung cancer at the time of data cut-off, 49 patients had been enrolled into the Evonissima Plus chemotherapy arm in the neoadjuvant setting.
Speaker Change: Of these 49 patients, 39 went on to complete surgery.
Speaker Change: Of the 39 patients who received abonisima plus chemotherapy in the neoadjuvant stage and completed surgery, 71.8% of patients experienced a major pathological response, and 43.6% of patients experienced a pathological complete response.
Speaker Change: In the 49 patients enrolled in this cohort, median event-free survival was not yet reached after 8.9 months of the median follow-up time. The 12-month event-free survival rate was 80.3%.
Speaker Change: These results are encouraging compared to the historical data that has been observed in global pivotal studies in a similar setting. The safety profile in this Phase II study was acceptable and manageable. No surgeries were delayed or cancelled due to the treatment-related advance events.
Speaker Change: In colorectal cancer, at the time of data cut-off, 22 patients receive abonisima plus folfoxillery, with a median follow-up time of 9 months. Eighteen patients receive abonisima plus ligofilamab plus folfoxillery, with a median follow-up time of 9.6 months.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: All patients in both groups experienced a reduction in their tumor burden compared to their baseline tumor assessment. The overall response rate and DCR for the 39 patients combined from both groups who had at least one post-baseline tumor assessment was 84.6% and 100% respectively.
Speaker Change: Median progression-free survival was not reached in either group at the time of this analysis.
Speaker Change: The safety profile in this Phase 2 study was acceptable and manageable. These response rates are very encouraging considering historical benchmarks in this setting.
Speaker Change: In addition, these patients have tumors that are considered microsatellite-stable, a setting where PD-1 therapy has not been historically successful. This is another indicator of ibonesma potential beyond the current PD-1 landscape.
Speaker Change: In triple-negative breast cancer, at the time of data cutoff, 30 patients received Ibonizumab plus chemotherapy with median follow-up time of 10.2 months.
Speaker Change: 60% of patients had previously received taxon-based chemotherapy in either the neoadjuvant or adjuvant settings in this Phase II dataset.
Speaker Change: All patients experience a reduction in their tumor burden compared to their baseline tumor assessment.
Speaker Change: The overall response rate and DCR for the 29 patients who had at least one post-baseline tumor assessment were 72.4% and 100% respectively.
Speaker Change: Median progression-free survival was 9.3 months at the time of this analysis.
Speaker Change: The safety profile in this phase 2 study was acceptable and manageable.
Speaker Change: The PD-L1 low or negative CNBC is yet another clinical setting without PD-1 therapy as a standard of care.
Speaker Change: Moving to head and neck, at the time of data cutoff, 10 patients received Ibonecimab with median follow-up of 3.3 months, and 20 patients received Ibonecimab plus Ligofalimab with median follow-up
Speaker Change: 4.1 months. All patients had tumors with PD-L1 expression.
Speaker Change: The overall response rate and DCR for the 30 patients combined was 50% and 86.7% respectively. The safety profile in this Phase 2 study was acceptable and manageable.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: The third quarter of 2024 was a pivotal moment in cementing the growing confidence of Ibanezema.
Speaker Change: Before I turn it over to Manmeet to provide a financial update, I would like to take a moment to thank our incredible team at Summit.
Speaker Change: As Bob and I have described all of the accomplishments we have achieved over the past seven quarters with Advanacima, this team has done a remarkable job across every team in making our goals a reality and condensing time where and when possible to accelerate our timeline in bringing additional therapeutic options to patients with cancer.
Speaker Change: It is a tremendous honor and privilege to work with each member of Team Summit and I would like to express my heartfelt thanks to everyone of our phenomenal team members. With that update, I would now ask Manmeet to provide details on our financial position and operational updates.
Speaker Change: Thank you. Thank you.
Manmeet Soni: Thank you, Micky, and good morning, everyone. We issued this morning our earnings release for the third quarter of 2024.
Manmeet Soni: Today, in addition to providing you with an update on our cash position, recent financing, and third quarter operating expenses, I will also be providing an update on our clinical operations.
Manmeet Soni: On the clinical operations front, I'm really proud of the team summit for completing the enrollment ahead of schedule for our first registrational global trial Harmony in patients with EGFR mutations post-targeted therapy.
Manmeet Soni: Also, since the release of AvanosMap data during September 2024 at World Conference on Lung Cancer and ESMO Annual Meeting, we have seen an increase in the screening and enrollment activity for the squamous patients at our existing sites in our Harmony trial.
Manmeet Soni: Additionally, we have seen lots of excitement and outreach from both academic and community physicians to participate in the development of Avanasamad.
Manmeet Soni: We believe this interest will help us in accelerating activation of additional sites and ultimately enrolling patients faster for the two planned trials.
Manmeet Soni: Harmony 3 for addition of non-squamous arm and also for recently announced Harmony 7 trial which we intend to initiate in early 2025.
Manmeet Soni: This cash position was strengthened at the end of third quarter with the closing of a 235 million dollar private placement in September 2024 for multiple leading biotech institutional investors and insiders.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Turning to operating expenses, I'll provide details to 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.
Speaker Change: To remind, non-GAAP expenses exclude stock-based compensation and one-time charges related to acquired in-process R&D expenses.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Our GAAP R&D expenses during the third quarter were $37.7 million compared to $30.8 million for the second quarter of 2024.
Speaker Change: And non-GAAP R&D expenses were $31.9 million in the second quarter of 2024 compared to $27.3 million for the second quarter of 2024.
Speaker Change: Turning to GNA, our GAAP GNA expenses during the third quarter 2024 totaled $20.4 million compared to $14 million for the second quarter of 2024.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: And non-GAAP GNA expenses were $6.8 million during the third quarter of 2024 compared to $6.4 million for the second quarter of 2024.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: The increase in GAAP operating expenses was primarily related to the increase in stock-based compensation expense during the quarter related to charges from the achievement of certain market conditions on performance stock option awards.
Speaker Change: and an increase in R&D expenses due to expansion of clinical study and development costs related to AvanisMap and increase in people cost as we continue to build our R&D team.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: On a non-GAAP basis, which excludes stock-based compensation, our non-GAAP operating expenses during the 3rd quarter 2024 were $38.7 million compared to $33.7 million for the 2nd quarter of 2024.
Speaker Change: We have been executing efficiently on our two registrational studies, Harmony and Harmony 3, with quarterly cash burn in our operating activities, keeping it below $35 million.
Speaker Change: Finally, to conclude, we believe our current cash balance at quarter-end, aggregating to $487 million, provides us enough cash to continue to invest in the AvanosMap trials planned to be expanded and initiated in 2025.
Speaker Change: And with that, I'll hand it back over to Dave.
Dave Gancarz: Thank you. Thank you. Thank you.
Dave Gancarz: Thank you, Bob McKee and Manmeet. Now we'd like to see if there are any questions that our team can help answer. Operator, would you please open the line for questions?
Speaker Change: Thank you. As a reminder, to ask a question, please press star followed by the number one on your telephone keypad. Once again, that is star followed by the number one. We'll pause for just a moment to compile the Q&A roster.
Speaker Change: Our first question comes from the line of Mitchell Kapoor with HC Wainwright. Your line is open.
Mitchell Kapoor: Hey, everyone. Thanks for taking the questions. Just wanted to know, on the expansion of the Harmony 3 trial, who are the likely first-line non-squamous patients that you could likely enroll? And specifically, how do you think about recruiting patients who would otherwise be good candidates for Keytruda? How do you think about getting those patients to participate in this study?
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Yeah, thanks Mitchell for the question. So the expansion is basically similar to the population that was treated in the Keynote 189 study. So these are going to be non squamous patients, probably adeno patients.
Speaker Change: And I think McKee reviewed the trial. I think the key here will be that the chemo will be slightly different. It will be platinum pemotrexate for these patients. However, we have extensive experience with that from the Harmony studies. Harmony A and Harmony.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Okay, great. And do you have a target enrollment for the split between non-Squamish and Squamish for this trial?
Speaker Change: We've not disclosed that. We're just in the planning phase right now as we said we did that we gave the combined number 1080 patients which we plan to enroll in both squamous and non squamous. We have not given further splits yet.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Okay, great, and then the last one for me is just on Harmony. Can you talk about the potential for accelerated approval? Could you file on PFS and how does that differ in terms of the unmet need from the strategy with Harmony 3 and Harmony 7?
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Harmony has always been our fast-to-market, you know, strategy and as you know we announced that we completed the enrollment earlier this month and now we expect the data in mid-2025. Obviously based on the data, right, obviously we'll be assessing our regulatory strategy and then providing further updates.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Great, yeah, thank you all. Just to clarify, there's two parts to that question in terms of the PFS, right?
Speaker Change: There's could you file only on PFS data and then the timing of which could you file with the PFS data before you have the OS readout. So just for the precedent in this EGFR second line space, the approval has been on PFS.
Speaker Change: And unfortunately, it is second line, it's a large unmet need, so the time between PFS and OS readouts may not be significantly different, right?
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: And the only thing I would add to that, Mitchell, just to round it out, I think you asked the question in terms of, you know, the difference between the Harmony and the Harmony 3 perspective. So just to reiterate, so Harmony 3 is when we, with our intention to expand that population, that is...
Speaker Change: patients already with squamous, so we'll keep that cohort, we'll add patients who are non-squamous, but they'll be without actionable genomic alterations, right, so without driver mutations.
Speaker Change: Our HARMONY trial is focused on those with EGFR mutant...
Speaker Change: the driver mutation of EGFR mutations, right? So that is, they are separate, they're not overlapping populations, Harmony and Harmony 3, I just wanna make sure that that's clear.
Speaker Change: And just to further clarify, I just want to clarify for the Harmony 3, as McKee mentioned, now the endpoint is PFS and OS, and the question around PFS filing versus OS timing of filing is relevant for that study.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Great. Thank you all very much.
Speaker Change: Welcome.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Our next question comes from the line of Brad Canino with Stifle. Your line is open.
Brad Canino: Good morning, and thanks for all the updates. Like on the addition of PFS to the primary endpoint of Harmony 3, can you talk about what types of regulatory feedback and clinical investigator feedback that went into that decision?
Brad Canino: and then related and started to...
Brad Canino: push with a question like this, but we all know that investors are keenly aware and waiting for an OS answer from your partner or KESO. And a change like this before we get that naturally makes one wonder what the confidence of management is to achieve a clinically meaningful OS benefit in the frontline lung setting. So can you talk about both of those elements?
Speaker Change: Yeah, Brad, thanks for the question. So let me answer the last one first. There's no change in our confidence for the Harmony 2 data around the OS, right? I think the opportunity was, you know, and it was unrelated, but the magnitude of the PFS benefit in Harmony 2 was so striking.
Speaker Change: You know, you don't want to have a therapy that provides such a significant benefit and not make that benefit available to patients, right, just based on that number. Granted, there's a lot of issues that we won't get into about payer reimbursement and the value of OS versus PFS, but we think that this is a positive thing, the addition of the PFS endpoint.
Speaker Change: as a primary endpoint for the Harmony 3 study in both timing and availability and benefit to patients.
Speaker Change: Yeah, and just to answer the other part of your question that, Brad, you asked about regulatory feedback. So, as we've promised from the beginning of this relationship, you know, with ACASO and our licensing of Ivanessamab,
Speaker Change: We would be speaking in particular with the FDA prior to these changes so that we have had communications with the FDA here. Especially for such an important change. Yeah.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Great. And now that Harmony3 does have both histologies, do you plan to wait for them both to have data to do the top-line, or can they be reported separately? You know, right now the NCT, before you've updated, says the primary completion estimate is September 27. Now that the trial has changed, how should we think about data flow, both histologies together, etc.?
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Yeah, so so at the highest level what I would say there Brad is this is a single trial so it's a single
Speaker Change: So we wouldn't necessarily look to break out timing there. Now we did say in the slides that we presented this morning that, you know,
Speaker Change: And as would be expected from a stratification perspective, we would stratify by histology.
Speaker Change: But it wouldn't be, from a timing perspective, broken out.
Speaker Change: You know, I would say without going too far into the details, you know, just given that we're intending to amend this shortly, there's a significantly broader population of nonsquamous patients as well.
Speaker Change: and so from a timing perspective, you know, there's more availability of those patients and there's a broader availability to enroll patients with non squamous tumors.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Okay, and then last for me, I think as we see multiple PD-1 and L-1 by VEGF by specifics
Speaker Change: advance across multiple companies. I mean, every day there seems to be a press release. It would be great to hear your thoughts on whether other designs and constructs, be they those that leverage PD-L1 or maybe broader VEGF isoform inhibition, are viewed internally as close replications of Ivanessa Mab and its incredible profile to date or viewed as potentially different. Thank you.
Speaker Change: Sure, thanks Brad. So what I would say, when we entered into the deal with Acesso, we naturally expected to see a few more assets emerge with a similar construct in general, as you mentioned, given the data that had been produced to date and our willingness to enter into a deal of that size and magnitude that we did.
Speaker Change: Of course, once the data from Harmony 2 emerged, we expected to continue to see a rapid emergence of products looking to capitalize on the potential that Ivanessa MAP had created at that point.
Speaker Change: And so most of these assets
Speaker Change: I would point out it very early, a majority, a vast majority of preclinical with no inhuman data.
Speaker Change: However, we do review the constructs of each of these compounds individually, and while we're not going to comment on any individual asset particularly, what I would say is that ibanesimab was specifically engineered to improve anti-tumor activity and reduce toxicities associated with these two targets.
Speaker Change: And this specific engineering was not accidental, it was not serendipitous.
Speaker Change: And we're very happy with Ivan-SMF and its construct in particular and that Ivan-SMF is our asset And we've yet to find one that we would rather have versus Ivan-SMF Two successful randomized phase three clinical studies involving Ivan-SMF will only kind of bolster that perspective
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Alright, thanks for the call.
Brad Canino: Thanks, Brad.
Brad Canino: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Our next question comes from the line of Yigal Notchomovich with Citi. Your line is opened.
Speaker Change: Thank you.
Yigal Notchomovich: Hi guys, thank you so much for taking the question. So just thinking a little bit more about the Harmony 3 amendment which you announced, I'm just curious, did you consider just simply starting a new study in non-squamous so you could preserve the timelines for Harmony 3? Or is the argument that because you're amending to PFS, you're going to win back time on the time to primary end point since you're no longer looking at OS?
Speaker Change: Anmeet Soni, Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz, Ankur Dhingra,
Speaker Change: And this timeline to amend was much faster to add the non-squamous arm. And as Dave just mentioned, right, non-squamous is almost double the population and it increases our, you know, total market size, right, and the potential.
Speaker Change: And there are long lead times. If we have to start another trial with, you know, new sites and new clinical trial agreements, the lead time is much longer.
Speaker Change: So this would allow us
Speaker Change: to enroll patients on you know both arms quicker and expand our market like almost like tripling our market opportunity. Yes, we had not provided you timelines because we were still enrolling and activating sites for squamous so we had not provided you earlier so we don't see this as a material change in delaying squamous but it adds.
Speaker Change: non-squamous opportunity and get non-squamous much faster and earlier into the market.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: If I can give some physician feedback that we've been receiving, they're very excited about this change, they see the logic in this change. This is a type of patient that they see more commonly in their practices, so it just increased participation and excitement around the study.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Okay, well, yeah, no, I mean clearly it makes sense given you you fill the gap in terms of the spectrum of all the non-small cell patients that are addressable. The other question I had was regarding, you know, we've gotten a lot of questions on
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Obviously, people have been making comparisons.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: A very big win and translate positively to everything you're doing over in the United States.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Yeah, again, I think our confidence hasn't changed. I think if you look back...
Speaker Change: at data from multiple frontline non-small cell lung cancer studies. Remember the Harmony A study was a second line study.
Speaker Change: and patients with refractory dose semertinib or other TKIs.
Speaker Change: You know, probably the classic study, if you look at the criticism around Bevacizumab, the ECOG study that led to the approval of Bevacizumab,
Speaker Change: had a strong hazard ratio, I think, but it was well above 0.6, and it still hit its OSN point. The Atezo, Bev studies as well, the Empower studies as well.
Speaker Change: And so, with this strong of a hazard ratio in PFS, it's unlikely that the EOS
Speaker Change: won't be there. The OS benefit won't be there. But I just want to remind everybody for Harmony 2, the primary endpoint was PFS, and this study was designed for PFS.
Speaker Change: and you know the statistical significance of you know that's a numeric value that the people are after and the question is how long will it take to show that given the sample size?
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Got it. Thank you very much.
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: Ankur Dhingra, Robert Duggan, Mahkam Zanganeh, Dave Gancarz
Speaker Change: There are no further questions at this time. I would like to hand things back over to Dave Gancarz for some closing remarks.
Dave Gancarz: Thank you, Ian. I just want to take the time to thank everybody for attending today's earnings call. An archived version of this webcast will be available on our website, www.smmttx.com. Thank you for taking the time to join us and enjoy the rest of your day. Thank you.