Summit Therapeutics Q3 2024 Earnings Call Transcript

Quartr
Provided by Quartr
October 30, 2024

There are 9 speakers on the call.

Operator

Good morning, and welcome to Summit Therapeutics 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. We do not expect any technical difficulties today. However, in the event that we lose the webcast connection and are unable to provide any updates, please wait up to 10 minutes for resolution. Please refer to the company's website for updates.

Operator

Please note that today's call is being recorded. After the speakers' remarks, there will be a question and answer session.

Speaker 1

Thank

Operator

you. At this time, I would like to turn the call over to Dave Gankars, Summit Therapeutics' Chief Business and Strategy Officer. You may proceed.

Speaker 2

Good morning and thank you for joining us. Our press release was issued earlier this morning and is available on the homepage of our website. Our Form 10 Q was also filed earlier this morning 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.smmttx.com. Joining me on the call today is Bob Duggan, our Chairman of the Board and Chief Executive Officer Doctor.

Speaker 2

Matthew Zangadeh, our Chief Executive Officer and President Manmeet Soni, our Chief Operating Officer and Chief Financial Officer and Doctor. Alan Yang, our Chief Medical Officer. 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. 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.

Speaker 2

Summit undertakes no obligation to update these forward looking statements, except as required by law. Following comments from Bob McKee and Manmeet, we will take questions. And with that, I'd like to turn the call over to Bob.

Speaker 3

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 abanizumab, our lead investigational asset. There have been several meaningful achievements around the progress of Ibenizumab since our last earnings call, both with our partners in China as well as here in the U.

Speaker 3

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, we intend to amend the protocol for our multi regional Phase III 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. The prior trial design previously included only tumors of squamous histology.

Speaker 3

This is a significant immediate expansion of total addressable market of our current Phase III clinical trial portfolio. We will provide additional context in a few moments around HARMONY 3's expanded patient population. 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 3rd generation EGFR Tyrosine Kinase inhibitor or TKI. As previously announced, we expect HARMONY top line data in mid-twenty 25. In addition, we received fast track designation from the FDA for this setting in the United States.

Speaker 3

Following the positive results of HARMONY-two, we announced our intentions for launching a 3rd global Phase 3 trial, HARMONY-seven, studying Ibenizumab monotherapy in patients with first line metastatic non small cell lung cancer whose tumors have high PD L1 expression. Additionally, encouraging Phase 2 data featuring ivinizumab from China was featured at World Lung and the 2024 European Society For Medical Oncology or ESMO Annual Meeting in perioperative non small cell lung cancer, as well as indications outside of non small cell lung cancer, including advanced triple negative breast cancer, recurrent metastatic head and neck cancer and microsatellite stable metastatic colorectal cancer. Each of these Phase 2 studies were sponsored by Ocasio with data generated and analyzed by Ocasio. These encouraging data reflect why we are continuing to explore the expansion of our clinical development of Ibenizumab outside of metastatic non small cell lung cancer. In addition, we raised $235,000,000 from leading biotech investors and individuals, including insiders, extending our cash runway and increasing our resources to execute upon expansive goals.

Speaker 3

Manmeet will provide more details about our financial position in a few minutes. These accomplishments have been foundational to our 2024 goals of successfully executing on our registrational Phase III trials, while expanding our clinical development plan. McKee will further discuss these accomplishments, including additional strides taken to drive our continued belief and conviction in Team Summit and the potential of abenizumab 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, increase potential duration of life and resolve serious medical needs. We believe we have the right team and the right molecule in ivenizumab to help us realize this goal.

Speaker 3

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

Speaker 4

Thank you, Bob, and good morning, everyone. As Bob said, I remain incredibly enthusiastic about the accomplishments of Team Summit and our partnership with Ekheso. Before providing on some of the highlights, as Bob mentioned, I would like to discuss the clinical work that has been conducted with abonizumab. There are more than 25 clinical trials around the globe evaluating abonizumab across 17 tumor settings, including 9 Phase III trials planned, ongoing or completed either in China or globally. While 6 of the Phase III programs across SUMMIT and EKESO are currently focused in non small cell lung cancer, 3 additional Phase III clinical trials have been announced by EKESO evaluating our lead candidate in solid tumor settings beyond non small cell lung cancer.

Speaker 4

This include BTC, head and neck cancer and pancreatic cancer. At SUMMIT, we are sponsoring 2 ongoing Phase III clinical trials, HARMONY and HARMONY 3. We are planning to initiate HARMONY 7 in early 2025. 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. As a reminder, avanecimab is the only PD-one VEGF bispecific antibody in Phase III in our licensed territories.

Speaker 4

Avanecimab brings these 2 highly validated mechanism of together into one novel molecule targeting simultaneously both PD-one and VJAS. Next, I would like to review the many achievements completed as well as discuss some upcoming catalysts for the remainder of this year. The Q3 of 2024 was a landmark moment for Ibonizumab and its development, with significant catalyst events in the form of data releases in September at the World Long and ESMO Conferences. Last month at the World Long Conference, HARMONY II results were featured as part of the presidential symposium and received a tremendous response from leading KOLs. In this head to head trial comparing abanizumab versus pembro, both as monotherapy, HARMONY 2 met its primary endpoint of progression free survival with Ibanezimab achieving a 49% reduction in the risk of disease progression or death compared to pembro.

Speaker 4

Ibonizumab 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. Consistent with previous studies, Ibonizumab demonstrated an acceptable and manageable safety profile. With the additional Phase 2 data released in the Q3 at both WordLanc and ESMO, we continue to expand the meaningful data that has been generated with Ibanezimab in various solid tumor settings beyond non small cell lung cancer. We are fortunate to have created such a strong partnership in our ongoing collaboration with AKECO as we leverage data from multiple solid tumor studies, supporting and informing Summit's own late stage clinical development strategy in our licensed territories. In addition to touching on our current clinical development plans, we initiated our strategic alliances with the University of Texas MD Anderson Cancer Center this quarter, providing additional opportunities to evaluate abanizumab in tumor types and settings in which we have not yet tested its potential.

Speaker 4

Patients are expected to soon begin treatment and clinical development effort will soon begin via this collaboration. After the HARMONY-two data was announced, we have received inbound interest from physicians regarding approximately 75 proposed investigator sponsored trials or ISTs in a wide range of cancer types. With meaningful updates this past quarter from AKSO's HARMONY-two study and several Phase II studies, we wanted to take the opportunity to review the respective study designs and further highlight key results. We will start with HARMONY 2. HARMONY 2 is a randomized, double blind clinical trial evaluating frontline monotherapy, Ibanezimab as compared to monotherapy pembro in patients with locally advanced or metastatic non small cell lung cancer with positive PD L1 expression.

Speaker 4

This is a single region, multicenter Phase III clinical trial conducted and sponsored by AKSO in China. Our partners at AKSO generated and analyzed the data in HARMONY-two. Here is the primary endpoint of progression free survival by blinded independent Radiologic Review Committee for the ENTARIS study at the time of the first planned interim analysis with a median follow-up of 8.67 months demonstrating a significant improvement for iwanizumab with a hazard ratio of 0.51 corresponding to a 49% improvement over the control arm. The median PFS was 11.1 months versus 5.8 months in the Ibanezumab and pembro arms respectively. 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 4

The analysis of PFS subgroups reveals that the PFS benefit with ibonasimab was observed across nearly all subgroups. 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. As previously discussed, and this is particularly true in the United States and Europe, monotherapy checkpoint inhibitor usage is a standard of care for patients with high PD L1 expression. 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 avanizumab and those patients with tumors of non squamous histology with a hazard ratio of 0.54 favoring Ibonizumab. 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 4

For safety, we see that there was a numerically higher rate of serious treatment related adverse event with abanecimab 20.8% compared to 16.1%. This did not translate to greater treatment discontinuation or treatment related events events leading to death, both of which were numerically higher in the pembro arm. This pattern held true in patients with squamous non small cell lung cancer as well, a place where anti V drug therapy has historically demonstrated safety risk where there were comparable rates of serious treatment related advanced events, discontinuation and death in the Ibanezumab are compared with the pembro arm. This is the 1st randomized Phase III clinical trial evaluating the safety profile of ibonizumab in the squamous population, especially confirming its tolerability in this group. In more detail, we see that nearly all of the higher rate of treatment related adverse events were lab related abnormalities, hypertension and proteinuria, but generally did not lead to discontinuation of dosing.

Speaker 4

These are conditions that are often seen by oncologists who in general are experienced managing these AEs. Finally, looking at the immune related and possibly VJF related events events in the table to the left, we see comparable immune related AEs with avonizumab compared to pembro. On the right, we see that as expected avonizumab was associated with more possibly VEGF related AEs both in all grades and grade 3 or higher. 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 VEGF related in either arm of the study.

Speaker 4

The table in the bottom line showed that most of the possible VEGF related events represented proteinuria and hypertension. There is no evidence of life threatening or fatal bleeding complications, including among patients with advanced squamous non small cell lung cancer and in patients with central tumors, cavitory lesions and or tumor encasing large blood vessels in this Phase III study. As a result of the successful HARMONY-two study and our analysis of the underlying data, we announced our plan to initiate HARMONY 7, a randomized global Phase 3 study evaluating abanizumab versus pembro, both monotherapy in frontline non small cell lung cancer in the PD L1 high expressed oral population. HARMONY 7 is planned with the 2 primary endpoints, progression free survival and overall survival. We are planning for an estimated 780 patients in this registration enabling study.

Speaker 4

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. As part of the trial amendment, the primary endpoint is intended to be updated to include 2 primary endpoints of progression free survival and overall survival. The total sample size for this randomized multi regional Phase 3 clinical trial has been adjusted to include an estimated 10 80 patients. Expanding HARMONY-three is the most efficient way to cover all metastatic non small cell lung cancer patients without driver mutation.

Speaker 4

HARMONY 3 will now cover metastatic non small cell lung cancer, both squamous and non squamous tumors in combination with chemotherapy and HARMONY 7 intend to cover PD L1 high expressing tumors via monotherapy, Ibonezumab now providing the opportunity to capture a significantly broadened addressable market as quickly as possible. Supporting this proposed amendment in part is both the result of HARMONY-two showing benefit to patients with both squamous and non squamous tumors as well as the Phase 2 data that has been previously presented. As a reminder, updated Phase 2 data for this setting was announced at the 24 European Lung Cancer Conference in March from the AK112-two zero one clinical trial centered around the cohort of patients in which Ibanezumab 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. First line patients with advanced or metastatic non squamous tumors experienced a median progression free survival of 13.3 months.

Speaker 4

In addition, 1st line advanced or metastatic squamous patients experienced median progression free survival of 11.1 months. Both metrics are encouraging considering the expectation for the current standard of care in this patient population largely driven by PD-one inhibitors plus chemotherapy. Median overall survival was not reached in either subset of patients after a median follow-up time of approximately 22.1 months. The frequency of treatment emergent events leading to the discontinuation of Ibonizumab was 11.1% and 2.8% respectively in patients with squamous and non squamous tumor. We are highly encouraged by the opportunity of Ibonizumab to demonstrate its potential across non small cell lung cancer in multiple clinical settings.

Speaker 4

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 II data announced this past quarter at Ward, Lung and ESMO, starting with an overview of the respective study designs. At the Wardleung perioperative non small cell lung cancer Phase 2 data was featured from AK112205, a single region, multicenter, open label study of patients with Stage II or III resectable non small cell lung cancer with data generated analyzed by AKCELL. The study was designed to assess patients receiving either Ibonizumab monotherapy or Ibonizumab plus chemotherapy prior to surgical resection and then ivanissimab monotherapy after surgery. Due to the maturity of the data and the timing of the data cutoff, the results were mature for the no adjuvant portion of the clinical trial.

Speaker 4

In September 2024, promising anti tumor activity and safety data for Ivanecimab were presented at ESMO. Featuring updated data in advanced triple negative breast cancer, recurrent metastatic head and neck squamous cell cancer, carcinoma and metastatic microsatellite stable colorectal cancer. The head and neck study assessed patients who receive abonizumab with or without legofalumab with PD L1 positive, locally advanced or metastatic recurrent head and neck squamous cell carcinoma. Note that legofalumab or AK117 is AKSO's priority investigational product that is not approved by any regulatory authority and to which SUMMIT does not have any license or ownership rights. The colorectal study was designed to assess patients who were randomly assigned to receive abonizumab plus full Faxillary with or without legofalumab and investigational anti CD47 monoclonal antibody.

Speaker 4

The triple negative breast cancer study assessed patients who receive Ibonizumab plus chemotherapy either paclitaxel or nab paclitaxel with locally advanced or metastatic TNBC. Turning now to antitumor activity and safety data from this Phase II studies. In preoperative non small cell lung cancer at the time of data cutoff, 49 patients had been enrolled into the evonisma plus chemotherapy arm in the no adjuvant setting. Of these 49 patients, 39 went on to complete surgery. Of the 39 patients who received abonizumab 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 4

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 months event free survival rate was 80.3%. 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 2 study was acceptable and manageable. No surgeries were delayed or canceled due to the treatment related events.

Speaker 4

In colorectal cancer, at the time of data cut off, 22 patients received abonizumab plus falcillary with a median follow-up time of 9 months. 18 patients received abonizumab plus legofelimab plus folfuxiliary with a median follow-up time of 9.6 months. 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 1 post baseline tumor assessment was 84.6% 100%, respectively. Median progression free survival was not reached in either group at the time of this analysis.

Speaker 4

The safety profile in this Phase 2 study was acceptable and manageable. This response rate are very encouraging considering historical benchmarks in this setting. In addition, these patients have tumors that are considered microsatellite stable, a setting where PD-one therapy has been has not been historically successful. This is another indicator of Ibonizumab potential beyond the current PD-one landscape. 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, 60% of patients had previously received taxant based chemotherapy in either the no adjuvant or adjuvant settings in this Phase II data set.

Speaker 4

All patients experienced a reduction in their tumor burden compared to their baseline tumor assessment. The overall response rate and DCR for the 29 patients who had at least 1 post baseline tumor assessment were 72.4% and 100% respectively. Median progression free survival was 9.3 months at the time of this analysis. The safety profile in this Phase 2 study was acceptable and manageable. The PD L1 low or negative TNBC is yet another clinical setting without PD-one therapy as a standard of care.

Speaker 4

Moving to head and neck, at the time of data cutoff, 10 patients received abonizumab with median follow-up of 3.3 months and 20 patients received abonizumab plus legofalumab with median follow-up 4.1 months. All patients had tumors with PD L1 expression. The overall response rate and DCR for the 30 patients combined was 50% 86.7% respectively. The safety profile in this Phase 2 study was acceptable and manageable. The Q3 of 2024 was a pivotal moment in cementing the growing confidence of Erbanesima.

Speaker 4

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. As Bob and I have described all of the accomplishments we have achieved over the past 7 quarters with Arvanisimab, 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. 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 member. With that update, I would now ask Manmeet to provide details on our financial position and operational update.

Speaker 1

Thank you, Mickey, and good morning, everyone. We issued this morning our earnings release for the Q3 of 2024. Today, in addition to providing you with an update on our cash position, recent financing and Q3 operating expenses, I will also be providing an update on our clinical operations. On the clinical operations front, I'm really proud of the Team Summit for completing the enrollment ahead of schedule for our 1st registrational global trial HARMONY in patients with EGFR mutations post targeted therapy. We expect to have the top line data from our HARMONY trial, including patients from U.

Speaker 1

S. And Europe in mid-twenty 25. Also, since the release of avanosimab 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. Additionally, we have seen lots of excitement and outreach from both academic and community physicians to participate in the development of avanosimab. We believe this interest will help us in accelerating activation of additional sites and ultimately enrolling patients faster for the 2 planned trials.

Speaker 1

HARMONY-three for addition of non squamous arm and also for recently announced Harmony 7 trial, which we had in 2025. On the financials front, let me start with our cash position. We ended the Q3 of 2024 with a cash position of approximately $487,000,000 This cash position was strengthened at the end of Q3 with the closing of a $235,000,000 private placement in September 2024 from multiple leading biotech and institutional investors and insiders. 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 1

To remind, non GAAP expenses exclude stock based compensation and one time charges related to acquired in process R and D expenses. Our GAAP R and D expenses during the Q3 were $37,700,000 compared to $30,800,000 for the Q2 of 2024. And non GAAP R and D expenses were $31,900,000 in the Q2 of 2024 compared to $27,300,000 for the Q2 of 2024. Turning to G and A, our GAAP G and A expenses during the Q3 of 2024 totaled $20,400,000 compared to $14,000,000 for the Q2 of 2024. And non GAAP G and A expenses were $6,800,000 during the Q3 of 2024 compared to $6,400,000 for the Q2 of 2024.

Speaker 1

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 and an increase in R and D expenses due to expansion of clinical study and development costs related to avanisumab and increase in people cost as we continue to build our R and D team. On a non GAAP basis, which excludes stock based compensation, our non GAAP operating expenses during the Q3 2024 were $38,700,000 compared to $33,700,000 for the Q2 of 2024. We have been executing efficiently on our 2 registrational studies, HARMONY and HARMONY III, with quarterly cash burn in our operating activities keeping it below $35,000,000 Finally, to conclude, we believe our current cash balance at quarter end aggregating to $487,000,000 provides us enough cash to continue to invest in the VANASweb trials planned to be expanded and initiated in 2025. And with that, I'll hand it back over to Dave.

Speaker 2

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? Thank

Speaker 5

you.

Operator

Our first question comes from the line of Mitchell Kapoor with H. C. Wainwright. Your line is open.

Speaker 5

Hey, everyone. Thanks for taking the questions. Just wanted to know on the expansion of the HARMONY-three 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 6

Yes. Thanks Mitchell for the question. So the expansion is basically similar to the population that was treated in the KEYNOTE-one hundred and eighty nine study. So these are going to be non squamous patients following adeno patients. And I think McKee reviewed the trial.

Speaker 6

I think the key here will be the chemo will be slightly different. It will be platinum pemetrexate for these patients. However, we have extensive experience with that from the HARMONY studies, HARMONY A and HARMONY.

Speaker 5

Okay, great. And do you have a target enrollment for the split between non squamous and squamous for this trial?

Speaker 1

We have not disclosed that. We're just in the planning phase right now. As we said, we did the we gave the combined number 10 80 patients, which we plan to enroll in both squamous and non squamous. We have not given further splits yet.

Speaker 5

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 1

Harmony has always been our path to market strategy. And as you know, we announced that we completed the enrollment earlier this month and now we expect the data in mid-twenty 25. Obviously, based on the data, right, obviously, we'll be assessing our regulatory strategy and then providing further updates.

Speaker 5

Great. Thank you all.

Speaker 6

Just to clarify, there's two parts to that question in terms of the PFS, right. So 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. And so just for the precedent in this eGFR second line space, the approval has been on PFS, right? And unfortunately, it is second line. It's a large unmet need.

Speaker 6

So the time between PFS and OS readouts may not be significantly different, right?

Speaker 2

Yes. The only thing I would add to that, Mitchell, just to round it out. I think you asked the question in terms of 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 patients already with squamous. So we'll keep that cohort.

Speaker 2

We'll add patients who are non squamous, but they'll be without actionable genomic alterations, right? So without driver mutations. Our HARMONY trial, will is focused on those with EGFR mutant driver the driver mutation of EGFR mutations, right? So that is they are separate. They're not overlapping populations, Harmony and Harmony 3.

Speaker 2

I just want to

Speaker 6

make sure that that's clear. And just to further clarify, I just want to clarify for the Harmony 3, as Mickey 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 5

Great. Thank you all very much.

Speaker 7

Welcome.

Operator

Our next question comes from the line of Brad Canino with Stifel. Your line is open.

Speaker 8

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? And then related and sorry to push with a question like this, but we all know that investors are keenly aware and awaiting for an OS answer from your partner, Acheso. 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 Hmong setting. So can you talk about both of those elements?

Speaker 6

Yes. 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 and it was unrelated, but the magnitude of the PSS benefit in HARMONY 2 was so striking.

Speaker 6

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, addition of the PFS endpoint as a primary endpoint for the HARMONY-three study in both timing and availability and benefit to patients.

Speaker 2

And just to answer the other part of your question there, Brad, you asked about regulatory feedback. So as we've promised from the beginning of this relationship with AGESO and our licensing of evanesimab, 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. Yes.

Speaker 8

Great. And now that Harmony 3 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? 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, etcetera?

Speaker 2

Yes. So at the highest level, what I would say there, Brad, is this is a single trial. So it's a single analysis set. So we wouldn't necessarily look to break out timing in there. Now we did say in the slides that we presented this morning that like and as would be expected from a stratification perspective, we would stratify by histology.

Speaker 2

But it wouldn't be from a timing perspective broken out. I would say without going too far into the details, just given that we're intending to amend this shortly, there's a significantly broader population of non squamous patients as well. And so from a timing perspective, there's more availability of those patients and there's a broader, availability to enroll patients with non squamous tumors.

Speaker 8

Okay. And then last for me, I think as we see multiple PD-one and L1 by VEGF bispecifics 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 Ibanezumab and its credible profile to date or viewed as potentially different? Thank you.

Speaker 2

Sure. Thanks, Brad. So what I would say, when we entered into the deal with Akesso, 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. 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 Ibanezumab had created at that point. And so most of these assets, I would point out, are very early.

Speaker 2

A majority a vast majority of preclinical with no in human data. However, we do review the construct 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, ivenezumab was specifically engineered to improve anti tumor activity and reduce toxicities associated with these two targets. And this specific engineering was associated with these two targets. And this specific engineering was not accidental, it was not serendipitous.

Speaker 2

And we're very happy with Ibanezumab in its construct in particular in that Ibanezumab is our asset. And we've yet to find one that we would rather have versus ibenesumab. 2 successful randomized Phase III clinical studies involving ibenesumab only kind of bolster that perspective.

Speaker 7

All right.

Speaker 8

Thanks for the call.

Speaker 2

Thanks, Brett.

Operator

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

Speaker 7

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-three? Or is the argument that because you're amending to PFS, you're going to win back time on the time to primary endpoint since you're no longer looking at OS?

Speaker 1

Hey, Gal. This is Amit. Yes. Now we totally understand and we evaluate it. But as you know, right, in order to capitalize on our existing sites, which we already have on the Squamous And this timeline to amend was much faster to add the non squamous arm.

Speaker 1

And as Dave just mentioned, right, non squamous is almost double the population and it increases our total market size, right, and the potential. And there are long lead times if we have to start another trial with new sites and new clinical trial agreements, the lead time is much longer. So this would allow us to enroll patients on 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 non squamous opportunity and get non squamous much faster and earlier into the market.

Speaker 6

Yes. If I can Yigal, this is Alan. 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.

Speaker 6

So it just increased sort of participation and excitement around the study.

Speaker 7

Okay. Well, yes, no, I mean, clearly, it makes sense given 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, we've gotten a lot of questions on Harmony 2 hitting on OS. As you know, it's been a significant debate. I'm just wondering if you could kind of walk through the logic as far as the confidence you have that Harmony 2 will eventually hit on OS.

Speaker 7

Obviously, people have been making comparisons, perhaps inappropriate comparisons to Harmony A and the strong PFS there, and then the OS, which is trending well, but obviously not hitting STAT SID yet. So just wondering if you could frame that and talk about how you see the path to confidence on hitting OS in Harmony 2, which would obviously be a very big win and translate positively to everything you're doing over in the United States?

Speaker 6

Yes. Again, I think our confidence hasn't changed. I think if you look back at data from multiple frontline non small cell lung cancer studies, remember the HARMONY A study was a second line study in patients refractory dose of imirtinib or other TKIs. If the probably the classic study, if you look at the criticism around bevacizumab, the ECOG study that led to the approval of bevacizumab had a strong hazard ratio, I think, but it was well above 0.6 and it still hit its OS endpoint. Etezo, bev studies as well, the EMPOWUR studies as well.

Speaker 6

And so with this strong of a hazard ratio in PFS, it's unlikely that the OS won't be there, the OS benefit won't be there. But I just want to remind everybody for HARMONY-two, the primary endpoint was PFS and this study was designed for PFS. And the question around statistical significance, that's a numeric value that the people are after. And the question is, is how long will it take to show that given the sample size.

Speaker 7

Got it. Thank you very much.

Operator

There are no further questions at this time. I would like to hand things back over to Dave Kankars for some closing remarks.

Speaker 2

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.

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Earnings Conference Call
Summit Therapeutics Q3 2024
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