Q4 2023 Summit Therapeutics Inc Earnings Call

Participants

David Ganzarcz; Chief Business & Strategy Officer; Summit Therapeutics Inc

Bob Duggan; CEO & Chairman; Summit Therapeutics Inc

Maky Zanganeh; CEO & President‍; Summit Therapeutics Inc

Ankur Dhingra; Chief Financial Officer; Summit Therapeutics Inc

Allan Yang; CMO; Summit Therapeutics Inc

Brad Canino; Analyst; Stifel Financial Corp.

Presentation

Operator

Hello, everyone. First and foremost, we'd like to apologize for the delay of this event.
Good morning, and welcome to Summit Fourth Quarter and Year End 2023 earnings call. All participants, all participants will be able to will be able to listen only until the question-and-answer portion of this call. We do not expect any technical difficulties today for worried However, in the event that we lose the webcast connection and we are unable to provide any updates, lease rate up to 10 minutes for resolution, please refer to the company's website for updates. Please note that today's call is being recorded. (Operator Instructios)
At this time, I would like to turn the call over to Dave Gancarz, Summit Therapeutics, Chief Business and Strategy Officer. You may now proceed, please.

David Ganzarcz

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 Forms 10K and S. three were also filed earlier this morning and are 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, w. w. w. dot SMMTTX. dot com.
Joining me on the call today is Bob Duggan our Chairman of the Board and Chief Executive Officer, Dr. Matthews on getting our Chief Executive Officer and President, Manmeet Soni, our Chief Operating Officer, Oncor, Dan Gray, our Chief Financial Officer, and Dr. Allen Yang, our Chief Medical Officer.
Before we get started with the rest of the call, I would like to note that some statements made by our management team and some responses to questions that we may make today may be considered forward looking statements based on our current expectations. Some and 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. Summit undertakes no obligation to update these forward-looking statements, except as required by law.
Following comments from Bob Mackie and Oncor, we will take questions.
With that, I will turn the call over to Bob Thank you, Dave.

Bob Duggan

Good morning, everyone, and thank each of you for joining us today. I'd like to say a few words about our progress and what team Summit has accomplished that I will hand it over to Mickey to add more color and then offer will provide financial updates.
It has been just one year since we closed on our partnership with cash so I'm very proud of the accomplishments and impressive progress team Summit has made in this period of time of initial mAb, our lead investigational compound and the only PD-1 VEGF bispecific antibody in Phase 3 in some U.S. territories continues to actively enroll two registrational Phase 3 trials in non-small cell lung cancer, our Harmoni and HARMONi-3 trials in Harmoni. We are looking at evidence I-Mab in combination with chemotherapy as a second-line treatment for non-small cell lung cancer patients with EGFR mutations with disease progression after receiving a third generation TKI in HARMONi-3. We are studying this I-Mab in combination with chemotherapy as first-line treatment for patients with squamous cell carcinoma of the lung in a head-to-head trial against the current standard of care we treated our first patient in the HeartMate three study, our second Phase 3 study in the fourth quarter of 2023. Combine the two populations represented by these two clinical trials account for approximately 120,000 patients in our licensed territories for whom evidence I-Mab could potentially offer a better treatment option team, so much conviction and our belief in our business, and that continues to drive our progress forward in our efforts to collapse time and reach critical milestones faster. We approach these efforts with the intent of helping patients improve quality of life, increase the potential duration of life and resolves serious medical need in line with somewhat strongly held mission statement. Mickey and I are appreciative and honored to be leading team Summit, where our accomplished leaders and team members have unparalleled track records for high-speed execution that delivers intended results. This experience and our expertise are foundational to achieving our goals for 2024 and beyond, continuing to execute on our Phase 3 clinical trials while expanding our clinical development plan.
With that, I would like to turn it over to Mickey to provide additional context for our accomplishments and next steps.

Maky Zanganeh

Thank you, Bob, and good morning, everyone. As Bob discussed, I remain incredibly enthusiastic about our new CMO and its potential. This rate of team Summit and the accomplishments we have made just one year into our partnership with Aircastle across the globe. Over 1,006 of 1,600 patients have now been treated with Avonex sema. Currently a case is conducting or participating in 19 clinical trials evaluating our new CMO, four of which are in Phase 3 and seven trials are evaluating our Seamap in solid tumor settings beyond non-small cell lung cancer. We are fortunate to have such a strong partnership and ongoing collaboration with AK., so including the ability to leverage data generated for Ivernia sema across multiple solid tumors studies in support of some its own clinical development in our licensed territories, the US, Canada, Europe and Japan, and turning specifically to some its own Phase 3 trials. Active enrollment continues in Harmoni and Harmoni tree. As a reminder, Harmoni, our fast to market approach is in non-small cell lung cancer patients with EGFR mutations to have progressed following a third-generation TKI such as osimertinib. We intend to complete enrollment in this trial in the second half of 2024. Our Harmoni two trial is seeking a front-line treatment indication for patients with squamous non-small cell lung cancer. This head to head trial is designed to compare obinutuzumab plus chemotherapy against the current standard of care pembrolizumab plus chemotherapy. We continue to progress as well as collapse time in order to achieve our aggressive but realistic goals for Ivernia Seamap to ultimately improve up and existing treatment options so there are many lung cancer patients with serious ongoing unmet need, our conviction and belief in the potential of Ionis Sema and our decision to quickly pursue two registrational Phase 3 trials has come in part from data generated from Phase 2 clinical trials conducted by a castle. These data evaluating of Anetumab plus chemotherapy in multiple lung cancer settings, eight K. one one two two oh one was updated by a case or last month, notably in patients with first line advanced or metastatic squamous non-small cell lung cancer without actionable genomic alterations in a Phase 2 population supporting our Harmoni treat trial at 24 months, overall survival rate of 64.8% was observed. Median overall survival has not yet been reached after a median follow-up time of 21 months. Furthermore, in patients with advanced or metastatic non-small cell lung cancer with tumors positive for EGFR mutations and having progressed following an EGFRTKI., the Phase 2 trial cohort supporting our Harmoni trial in median overall survival of 22.5 months was observed in both settings. I want to see MAP has had an acceptable safety profile in the Phase 2 clinical trial. We believe that this study data is very promising. Also when considering the current standard of care in this patient population and the Phase 2 data supports our decision to directly move forward in both of our Phase 3 clinical trials.
Slide 5, please. I would also like to spend a moment to remind everyone of the differentiated mechanism of action for hypoglycemia.
To start, I want to see my brings two highly validated mechanism in oncology together into one novel molecule targeting both PD-1 and BJ. And as Bob mentioned earlier, we are the only Phase 3 PD. one VEGF bispecific in our licensed territories, making it the most clinically advanced compound of its kind in the US, Canada, Europe and Japan. What differentiates I panitumumab in its intention of design is a concept known as corporative binding specifically in the presence of each of the binding of Avon is earmarked to be the one in vitro increases by 18 fold in the presence of PD-1. We have affinity increases by over fourfold and when I say, maps cooperating binding qualities lead to the potential to steer more drug to the tumor and tumor microenvironment. The area around the tumor where high higher levels of PD-1 and reach of our Express and comparatively less drug, we believe is steered towards normal healthy tissue.
On Slide 6, you can see in addition, because of the increased presence of PD-1 and rejects in the tumor microenvironment. There is not only increased affinity, but also increased advocacy because we do have is expressed as a dimer. There is an opportunity to bind multiple avenues of our compounds to this VEGF dimers in the tumor microenvironment as what we believe I wouldn't assume a corporative binding goes further than the sequential administration of an anti-PD-1 and anti-VEGF therapy. Our goal is to improve upon previously established efficacy standards. In addition to side effects and safety profile associated with these two targets, we believe I have on this map has the potential to achieve this.
Moving to Slide 7. Looking at meaningful near term catalysts for Avon and sema, we are expecting multiple events to occur in 2020 for next quarter. There are two key milestones expected from randomized Phase 3 clinical trials in China from our partners at Acacia data from the Chinese patients enrolled in AK. one one two three oh one, a large portion of which represent the Chinese patients included in the modified intent to treat population of our multi-regional study, also known as Harmoni was submitted to the Chinese regulatory authority, the CDE. last year, specifically seeking marketing approval in China. A decision is expected in the second quarter of this year from the CD. We also expect that it has always provide a data read out of the top line results of their Phase 3 trial at this time. Additionally, a case or has an interim analysis planned for next quarter for each study comparing Ivernia sema to pembrolizumab in a monotherapy setting for first line advanced lung cancer patients harboring tumors with positive PDL. one expression referred to as AK. one one two three or three. This head-to-head trial against pembrolizumab is a major milestone for Ivernia Sema, both in differentiating our initial remark from a PD-1 antibody as well as illustrating the potential of its novel mechanism of action that simply does not exist in oncology therapeutics today, given the direct implications of the AK. one one two three oh one results on our Harmoni study as well as the potential ability to compare Ionis Seamap pembrolizumab in a one one, two, three or three. We believe these events will be pivotal moment drivers in IONA's SIMOPS development globally. As mentioned earlier, we also plan to complete enrollment in the Harmoni study in the second half of this year, providing momentum towards a submission for Ivernia Seamap in our licensed territories. While non-small cell lung cancer indication represent our initial development plans for opening remarks, we will continue to expand our clinical program, Harmoni and HARMONi-3 represent the first step in our strategy, and we believe our new CMO has potential in both additional non-small cell lung cancer indications and in other solid tumors. In addition, to progressing our internal development program. We appreciate the high level of enthusiasm we are hearing from key opinion leaders and other physician leaders for what I've only seen map can do to make significant positive difference in and outside of lung cancer, we continue to receive and are considering multiple inquiries for potential investigator-sponsored trials or IC programs. We expect to share additional information later in 2024.
Finally, to capitalize on and expand our reach with physicians from KOLs and academic leaders to community physicians and local caregivers. Seeing so many cancer patients we are participating in a few upcoming conferences. There will be at the slide targeted therapies for lung cancer or TTLC. meeting later this week in Santa Monica, California In addition, we plan to participate in a small European Lung Cancer Congress 2020 for next month in Prague where we have submitted along with our partners at.

Ankur Dhingra

Okay.

Maky Zanganeh

So multiple abstracts for presentation on Ivernia sema. We intend to educate and activate as many physicians as possible regarding Ivernia Seamap and its potential as we ramp up Phase 3 clinical trials in the United States, Europe, Canada and Japan.
With that update, I will now ask our Ankur to provide details on our financial position and outlook.

Ankur Dhingra

Thank you, Maggie and Bob and good morning, everyone. Echoing the sentiment, we're very pleased with the speed of execution of team Summit and our partners at Puma co-sell in the development of Avanex amounts seem Moving to slide 8, I'll give you an update on some its cash position, the extended cash runway guidance, Andy and the P&L. We have a strong cash position with $186 million in cash and investments as of end of year 2023. This position provides us a strong ability to continue our investments in the development of either Nassib. In addition, we have taken steps to extend our cash runway going into the first quarter of 2025. As you may recall, our previous guidance for cash runway was going into September of 2024. As we announced earlier, we have amended the $100 million note to extend the maturity date to April first, 2025 and the future interest payments will also be paid at maturity. This extension, coupled with our strong cash position, provides funding to make significant progress in the development of NSMA. as well as covering some of the key milestones that Maggie spoke about.
Going to the P&L, I will speak about non-GAAP OpEx, which excludes stock-based compensation, in-process R&D and certain impairment charges. You can refer to our press release for reconciliation of GAAP to non-GAAP financial measures during the fourth quarter of 2023, our non-GAAP operating expenses were $27.7 million aligned with the company's focus. The majority of our spending is towards research and development, which is $22.4 million for the quarter on a non-GAAP basis and is focused towards clinical development of IV and SMM, including the clinical trials, the technology transfer and people costs and the G&A spend of $5.3 million for the quarter on a non-GAAP basis represents all the functions that provide infrastructure and support for this development.
So in summary, we're excited about the potential of Fibernet I-Mab and have made a lot of progress in its in its development during 2023. We have a strong cash position and we have extended our cash runway going into 2025. And with that, I will hand it back over to Dave.

David Ganzarcz

Thank you, Bob. Mackie and Oncor. We can now transition to see if there are any questions that we can help answer. Operator, if you could please open the line for questions.

Question and Answer Session

Operator

I'm opening the floor for the Q&A question. (Operator Instructions)
Brad Canino, Stifel.

Brad Canino

Hi, good morning and thank you for the updates. And having me Andrew Hall and I just wanted to get your thoughts on how to best interpret the upcoming Chinese regulatory action on. I have an estimate for EGFR mutant lung, in particular in relation to your ongoing Harmoni study and I'm asking in light of some of the differences between the two studies, thinking about the third-generation TKIs pretreatment requirements and then your study also adding the co-primary of survival. Thank you.

David Ganzarcz

Thank you, Brad. I'll hand that question to Fibra.

Allan Yang

Thanks for the question. This is owning the Chief Medical Officer. So I think you should view it positively. The fact that as you know, the Chinese version of the Harmoni study enrolled 320 patients, approximately 300,000 patients, of which about 50 of them received a first or second generation TKIs, which is still considered standard of care in China.
And we will be using 270 patients so that there are approximately 270 patients. So that data of which only received a third-generation TKI or received a third-generation TKIs such as osimertinib somewhere along the course of their treatment. And that represents about 85% of the data. So I think the data should correlate pretty well for the global study. Now, remember, we're adding 150 patients from North America and Europe to that, and you know, I'm not aware of any treatment differences between Chinese and U.S. patients. In addition, I think the key question is, is there any difference of receiving a first or second generation TKIs prior to receiving a third-generation or receiving a third generation to guy on the impact of chemo immunotherapy. And the answer is I'm not aware of any such data. I don't think that data exists.
And then I think the last question you asked was around PFS and OS X and so PFS seems to track pretty well with U.S. That's why it's used as a surrogate endpoint as often, especially in patients with sort of survival periods. So the shortest survival period, the more likely that PFS will progress of corporate and retail, but it is an unknown at this time. And so the fact that we have co-primary endpoints is a little bit different than the case of study.
Thanks for the question, Brett.

Brad Canino

Great. Thank you very much.

Operator

Hartaj Singh from Oppenheimer.

Ankur Dhingra

Great.
Thank you, Tom, and thanks for the question. I've just got a couple one is your head to head study against pembro and chemo combo against non-small cell lung cancer. Can you just talk a little bit about what's the differentiation driving this demand and then maybe a little bit more into and I guess what's the hurdle or is it just the study on which pembro chemo combo data proved? Just how to think about the hurdle that that you're looking to either be equal to or surpass? And I just got a quick follow-up.

David Ganzarcz

Thanks, Hartaj. So I think I heard two questions there. One, the differentiation between pembro, the standard of care. And I've been at I-Mab with respect to our HARMONi-3 study and then what that what other hurdle we may have in HARMONi-3 study or what the standard of care of what we need to be in that particular study is.
So again, I'll hand that question to Alan.

Allan Yang

Akash, thanks for the question. So I'll answer the second part first.
Well, let me just review the two studies. As Mackey mentioned earlier, there's the Harmoni study, which is our fast-to-market site about with Brad's question in the second line EGFR mutant population, the HARMONi-3 study, which is sort of the first frontline study in squamous non-small cell lung cancer.
The second question about the benchmark is pretty easy it's the KEYNOTE 47 study, right? So this is where Merck got approval for pembrolizumab in a similar population. There are sort of expansion studies that look at the Chinese population so you can look those studies up to get the proper benchmark in terms of what distinguishes I've in SMA, it's a very clean study of five and SMS chemotherapy. And then pembro using the same chemotherapy and that pembro chemotherapy was before oh seven study based on the 47 study. So I think there's a couple of ways that are different right so I've in SMA from the simplest way to think about it has digest component to it. So if you think about the two targets independently pembro or PD-1 and the second one is that, Jeff. And so we have that VEGF component. And so we think that that adds sort of value to patients and important for patients. And then there's the opportunity that we think accentuates not only the VEGF but also the PDY. And so you can sort of distinguish that. And looking at that data, it will be very interesting to look at the data of both BI, PD-1, PD-L1 status, you know, are how much are we beating in the high PD-L1 expressors, which is part of the PD. one component, how much are we bidding in the lower PD-L1 expression, which is the that just compound, I would say some other bispecifics that target like take PD-1 and CTLA-4 are concentrating on the non expressing we're going to go after all of those.
So the last component to think about is that we know that Avastin was trying to be developed in this space. And then after Phase 2, they halted development. There was a concern about bleeding risks early on. And therefore, I think lung cancer patients in the squamous setting never really fully realize the potential of anti-VEGF. And we believe that the safety profile demonstrated to date in the Phase 2 as well as large large database is supportive of developing a bad Jeff that has been attached to PD-1 with cooperative binding in this space. So there's a number of different aspects where we think we can have an advantage.
Puts your follow-up question, Hartaj Yes, great. And thank you so much that. So that's really good. Good detail on, you know, if we if you can just kind of give us what is the next sort of clinical and regulatory staff for Harmoni and HARMONi-3, I know I'm going to make a little bit into the future, but just not looking for guidance, but just kind of a rough cadence of events there?

Ankur Dhingra

Thank you.

Allan Yang

Around HARMONi-3, I don't think we've disclosed it. So I'll turn to Dave, but I'll just say that you can sort of calculate enrollment based on the KEYNOTE 47. I think that's the key benchmark. And you know, it's what's interesting, Hartaj is the squamous non-small cell lung cancer population or that space has become a lot less crowded recently. So I think that will give us a lot of freedom to operate. I don't know, Dave, if you want to add anything to our disclosures Thanks, Alan.

David Ganzarcz

So at this point, what we have disclosed is that the Harmoni study is we plan to complete enrollment in the second half of 2020 for the second half of this year. We haven't given further guidance with respect to the regulatory process there, except that we have our co-primary endpoints from a Harmoni free perspective. We just began enrollment in the fourth quarter of 2023. And we've yet to give the guidance in terms of when that will complete. But we're currently enrolling and are excited about moving quickly in that space setting as well.
Well, thank you, everyone. Thanks for the updates.

Operator

Don't have any raised hands right now. So I'd now like to hand back over to to Dave again, guys. Thank you.

David Ganzarcz

I just want to thank everyone for attending our call and your continued interest in Summit. An archived version of this webcast will be available later today on our website, w. w. w. dot SMTTX. dot com. I want to thank everyone again and enjoy the rest of your day. Thank you.

Operator

Yes, thank you so much for attending today's session. Have a wonderful day.
I mean, I mean, no, yes.