Marker Therapeutics, Inc. Aktie

Good morning, and welcome to Marker Therapeutics webcast to discuss the Phase I clinical update from the APOLLO study, MT-601 in relapsed lymphoma. [Operator Instructions] Please note, this call is being recorded and will be available for replay on the company's website following today's event. I'd now like to turn the call over to Maria-Bernadette Madel, Director of Corporate Operations for Marker Therapeutics. Maria, please go ahead.

Thank you, and welcome, everyone, to today's webcast. Before we begin, we would like to remind everyone that today's webcast will include forward-looking statements. These statements are based on current expectations and are subject to risks and uncertainties that may cause actual results to differ materially. We encourage you to review the cautionary statements and risk factors described in our most recent SEC filings. We will now pause for a moment to allow you to read our forward-looking statements. Thank you.

With that, I'm pleased to introduce Dr. Juan Vera, President and CEO of Marker Therapeutics as well as Co-Founder of the company and one of the developers of the technology. Dr. Vera will provide an overview of the data from the company's Phase I APOLLO study MT-601 in relapsed lymphoma, which was announced in the press release earlier this morning. We're also happy to have Dr. Geoffrey Shouse joining us today. Dr. Shouse is Assistant Professor at the Department of Hematology and Hematopoietic Cell Transplantation at City of Hope, Duarte, California and he's one of the PIs in Marker's Phase 1 APOLLO study. Dr. Shouse will share his perspective on the study and the broader competitive landscape. Before we open the floor to your questions, we will return to Dr. Vera for final comments. As a reminder, questions can be submitted at any time throughout the session using the chat box.

With that, it's my pleasure to hand things over to Dr. Vera.

Thank you, Maria, and thank you, everyone, for listening. We're really excited to be here today to highlight our progress in our clinical study in MT-601 in patients with lymphoma. Marker Therapeutic is advancing the MAR-T cell technology, a technology that relies on millions of years of immunological evolution to provide a product that is capable of recognizing hundreds of epitopes present within the tumor and in this manner, providing a treatment that can avoid the heterogeneous makeup present within the cancer cells. This technology was developed at Baylor College of Medicine where we have generated clinical proof of concept. And in addition to that, the company has been a sponsor by nondiluted funding, including NIH, FDA and CPRIT. And today, we're going to be providing a clinical update on MT-601 in patients with lymphoma into APOLLO clinical study. But before we do that, let me just walk you through the MAR-T cell technology and the mechanism of action. Next slide, please. Next slide. Thank you.

So if you look at this representation, we see that the MAR-T cell product is generated from peripheral blood T cells, which are isolated, stimulated with overlapping peptides with the purpose of enriching for tumor-reactive T cells and in this manner, providing patients a product that is capable of recognizing multiple targets present within the cancer cells. And importantly, we're able to do so without the need for genetic modification or genetic enhancement. So in this manner, this is a natural product that we have now tested in the clinic with now early evidence of clinical activity and excellent safety profile. Next slide, please.

This is a quick overview into our manufacturing process. We're really excited now to start a strategic collaboration with Cellipont CDMO located in Houston, Texas, vendor that will be responsible for the manufacture of this product in our future pivotal study as well as commercial launch. Now illustrating this schematic, this is an autologous process, which our current vein-to-vein time is about 20 to 25 days. The final drug product is collected, cryopreserved and sent to the clinical site in a cryo manner where it can be then administered. Next slide, please. This is a representation of our current pipeline. And as illustrated here, our lead asset is MT-601. And today, we're going to review those clinical results. Next slide, please.

MT-601 is a clinical study that we're really excited and is now developing a MAR-T technology, which recognized 6 different tumor-associated targets. And the results that we're going to be reporting today are results from a multicenter clinical study across the U.S. Next slide, please.

The reason we are excited about these results is, one, the first objective is to recapitulate in a multicenter clinical setting, observations from academic study at Baylor, this study was published in the Journal of Clinical Oncology, where we were able to demonstrate the clinical activity of this technology in patients with lymphoma. Now as part of the APOLLO study, our objective is, first, to recapitulate these results in a multi-clinical trial setting, and two, see we can even improve upon these results as now we have performed certain enhancements to the process as highlighted in the right-hand side. More antigens, more dose and that simplified manufacturing process that can yield a product that is 4x more potent. Next slide, please.

We can see here that this is the clinical study design. And let me walk you through the structure. This clinical study has 2 components, a dose escalation followed by a dose expansion. As shown here, the dose escalation range from 100 million to 400 million cells. And as shown on the right-hand side, this is open to patients with different types of histopathologies, including DLBCL. Today, we're going to show data on 24 of these patients. Importantly, as shown on the bottom of this slide, since June 17, the SRC has deemed the dose to be safe. And as a consequence, we're now going into our highest dose level, ever exploring humans, which is 400 million cells as our dose expansion in patients with DLBCL CAR relapse. And this is important as this will be the foundation of our future pivotal study. Next slide, please.

So these are the results that we have today. So really excited to report CRR rate of 50% and an overall response rate of 66% in our patients with non-Hodgkin lymphoma, patients are heavily pretreated and for many of which there's no treatment options. So we consider this to be really remarkable in terms of the clinical benefit that it can provide to patients. If we go then to the next slide, and we examine the durability of responses, we see that of these patients, 3 of these patients have been in complete response for more than a year and 5 patients have received the benefit of clinical responses for more than 6 months. If we go to the next slide and looking into this data in more detail, we see that many of these patients have different type of histopathologies, many of them are DLBCL. They have received CAR-T cells as well as bispecific.

And despite failing to these prior lines of treatment, we are observing that MT-601 is capable of providing complete responses, which are durable. Now if you pay attention in the left-hand side, I will point out that these patients have received -- they have received clinical benefit despite receiving the lowest cell dose exploring the study today, which is 100 million to 200 million cells. And from this perspective, I'm really excited and believe that these results we're going to be able to recapitulate if not improve as now we move into our highest dose level of 400 million cells.

Now if we go to the next slide, we can see that the highest dose level ever tested in humans which is 400 million cells have shown not only to be safe, but we also have seen objective responses. This is 9 patients, Hodgkin lymphoma patients that have received the highest dose level of 400 million cells, where we're seeing an overall response rate of 78% and a complete response rate of 11%. And these are clinically meaningful observations. As illustrated here on the right-hand side, this is actually a patient with Hodgkin lymphoma from which is one of our PIs from the study from . This patient had a partial response. But despite this being classified as a partial response, you can see that this patient had a high level of disease burden and it was controlled after the administration with MT-601. Next slide, please.

And perhaps one of the elements that makes this technology very different to other alternative is the safety profile. And what we have seen today is as we explored 200 and the highest dose level 400 million cells, we have seen an excellent safety profile without DLTs, no ICANS. And the only CRS has been reported has been Level 1 in 2 patients that have been just really fever and response in absence of additional treatment. In addition to that, we continue to monitor the long-term toxicities.

But again, remember, this is a natural T cell product that does not require genetic modification and as a consequence, is not really subject to some of the long-term cell transformation that has been observed in cell therapy space using CAR-T cells. So without a doubt, we're really excited to report today these clinical observations showing the efficacy of our technology in patients that are heavily pretreated as well as confirming an excellent safety profile even as we go now to the highest dose level.

With that, let me hand over to Maria. Maria?

Thank you, Dr. Vera, for the insightful presentation. That was really a great overview of the data and what it could mean going forward. To build on that, we are happy to have Dr. Shouse with us today, who has been directly involved in the study as a principal investigator at City of Hope. Welcome, Dr. Shouse, and thanks for joining us today. We are looking forward to hearing your perspective on the trial and how Marker's finding compare with the current treatment landscape.

Thank you. Thanks for the opportunity to speak about some of the exciting results that we've seen on the study. So I'll start out by going through the results on several of the patients that have enrolled with large cell lymphoma. The first 1 shown here was refractory to 3 prior lines of therapy, including CAR- T cell therapy. And with MT-601, you can see at the 8-week time point that their disease it's gone into remission. Importantly, the patient had no toxicity associated with the treatment.

On this next slide, you can see another patient this one going through 8 prior lines of therapy, including CAR-T cell therapy. Again, showing at 8 weeks complete metabolic response was achieved. And again, minimal toxicity seen in this patient, no CRS, no neurologic toxicity. This patient, shown on this next slide, achieved complete metabolic remission with bulky -- prior bulky involvement of the spleen by 4 weeks after MT-601 treatment. And this patient had both prior bispecific antibody and prior CAR-T in a total of 10 prior lines of therapy. This last patient had cutaneous only relapse of DLBCL, was initially treated without lymphodepletion, had a partial response, then was retreated with remaining cells with lymphodepletion and ended up achieving a complete metabolic response. Again, with minimal toxicity.

So seeing this promising preliminary efficacy and this, in my opinion, incredible safety profile, we can dive in and see what the treatment landscape in CAR relapse DLBCL looks like. And on this next slide, you can see unmet needs in DLBCL persists. So the treatment landscape is seeing dramatic changes and continues to undergo changes associated with incorporation of novel therapies, including cell dose based therapies like CAR-T and bispecific antibodies, even with these changes, however, unmet needs persist, including patients that relapse after CAR-T or patients who are ineligible for CAR-T due to toxicity. MT-601 has demonstrated exceptional safety, and we've seen the preliminary efficacy and it carries the potential to fill many of these unmet needs.

On the next slide, we've outlined some of the basics for the current treatment landscape in CAR relapsed DLBCL. And in the upper left, you can see bispecific antibodies are likely the best available treatment we have that's FDA approved in this setting. However, long-term follow-up suggests the durability of response is not completely clear and it's unclear whether these are curative therapies or just treatments that can buy patients more time. Below that, we see the combination of tafasitamab and lenalidomide, which itself has limitations in terms of efficacy and durability and also in the pivotal study leading to its approval, high-risk patients were excluded from the study.

And at the right, antibody-drug conjugates such as polatuzumab and loncastuximab have shown efficacy. For Pola, it's mainly been shown to be efficacious in combination with other treatments. And right now, the most common use of Pola is in the frontline setting as part of Pola-R-CHP. And if it's being used in the front line, utility in subsequent lines of therapy comes into question. Condition with Lonca, although it has some efficacy in the relapsed -- CAR relapse setting, the number of patients included in the study that were CAR relapsed was rather small. And the toxicity profile of loncastuximab is significant, a significant proportion of patients on the study having just a [indiscernible].

And then on the bottom right, we have other treatments like selinexor and the recent approval of BBR squared. However, these have not been widely adopted and have limitations in terms of their efficacy and toxicity as well. Looking to the future, there are many therapies currently in development. These include allogeneic CAR-Ts, humanized CD19 CAR-T with IL-18 expression, in vivo CAR-Ts, other T cell engagers, dual and trispecific CAR -- Ts, CAR-NKs and other small molecules. The main limitation of these therapies that are in development is their limited scope. Many target 1, possibly 2 antigens up to 3 at times. But that leads to a limitation of antigen escape for a mechanism aligned for resistance and relapse. They also have short-term durability based on an initial study and then maybe increased toxicity as the number of targets are expanded in CAR-T.

In addition, the bispecific antibodies and T cell engagers may end up moving earlier -- to earlier lines of therapy. And as that will still be an unmet need in this study. So taking this all together on the next slide, we see that the current therapies have narrow recognition and short-term durability. And unlike T cell engagers and CAR-T cells, the MT-601 product does not depend on antigen expression for efficacy. And agnostic molecules like MT-601 could address the current unmet medical needs in large cell lymphoma.

So in summary, the last slide, MT-601 is poised to fill the unmet needs in DLBCL. And despite the promise of the current novel therapies being evaluated, an unmet need persists and MT-601 has demonstrated again exceptional safety and preliminary efficacy and carries the potential to fill many of those unmet needs.

Thank you, Dr. Shouse for sharing your valuable perspective and this great overview in the treatment landscape in lymphoma. And always important to hear actually the insights from those working directly with patients and your comments really highlight the potential MT-601 could hold for patients and how it could fit into today's evolving treatment landscape. Before we go into the Q&A session, we will hand it back to Dr. Vera for final comments.

Thank you, Maria, and thank you, Dr. Shouse. I really appreciate your insight. If we go to the next slide, please. I would just like to make some closing remarks. I think that definitely with our technology, we have something that it is quite unique and different. And that difference is precisely derived out of the mechanism of action. The ability of MT-601 to target multiple antigens in a natural manner address perhaps one of the major obstacles of what I will consider as an effective immunotherapy. And I think Dr. Shouse alluded to that, which is the restricted target profile that multiple of the current strategies are limited by. MT-601 is able to recognize multiple antigens simultaneously and in that manner addressing and overcoming one of the barriers, which multiple technologies are currently limited by.

We're really excited about the results we're seeing today. We thank all the participators in the study, the physicians, risk coordinator and definitely the patients. We will continue to work diligently to advance this clinical study with the objective of taking this product into the market. As illustrated in this slide, I think that this highlights a significant milestone as we have now finalize our dose escalation. We have observed no limiting toxicity. We have confirmed the early observations from the Baylor clinical studies. And now we're really excited moving into the dose expansion which will concentrate enrollment in DLBCL CAR relapse and bispecific relapse patients, which will be the foundation of our future pivotal study. We look forward to continue communicating our progress and clinical outcome. And if you guys have any questions, please feel free to reach out to the company. I will be always available. Thank you very much.

Thank you, Dr. Vera. Thank you, Dr. Shouse. At this time, we will begin the Q&A session of the webcast.. So the first question, Dr. Vera, the APOLLO study shows that 50% of the non-Hodgkin lymphoma patients have a complete response with several patients maintaining responses more than 12 months despite the median of 5 prior lines of treatment. How do you view this durability profile relative to CAR-T cells and where do most of the relapse is occur within a year? So how would you compare the durability of MT-601 relative to CAR-T cells as well as bispecifics, which have shown shorter remission duration.

Sure. Yes. Good question. Let me characterize the clinical landscape, right? And I think these observations are considered to be remarkable, particularly given that we're seeing that, I mean patients are CAR relapsed and some of them, which are also bispecific relapse. And there is not a lot of literature in that regard when we're looking to the overall survival of these patients. However, from our first assessment, you basically see an overall survival for patients that are DLBCL CAR relapse, which is about 5 months, right? So without a doubt, durability of responses that extend beyond 6 months to a year are very meaningful from a clinical perspective when you're looking into that particular clinical context, DLBCL CAR relapsed bispecific relapsed patients.

And also, as we just heard a moment ago from Dr. Shouse, the clinical alternatives despite many of the things that are characterized in the literature are not that great when it comes down to a patient that is DLBCL and had failed CAR-T cells, right? I think that there's a lot of limitations in terms of what current treatments can bring to these patients in terms of the efficacy as well as the associated toxicity. So I think that the question is valid, right, which is the -- how do we characterize the results we're seeing today against a competitive landscape related to products that are approved, products that are coming into the market, and the overall survival of these patients.

And I think that is quite significant during the fact that, again, you're talking about heavily pretreated patients that the current treatment options are not really effective. And you have to combine that with an excellent safety profile. I think that the combination makes this very exciting and powerful clinical observations.

Perfect. And CAR-T cells are usually used with lymphodepletion. But in your study, you observed results with and without lymphodepletion. How do you interpret these findings in future trial design?

Yes, that's an excellent question. I think that we have seen objective responses from our technology even in the absence of lymphodepletion, right? And I think we briefly reported those observations in our path clinical release. The incorporation of lymphodepletion has been performed with the objective of influencing in a positive manner, the expansion and persistence of the T cells. This phenomenon has been, I think, recognized across multiple different adoptive T-cell treatment programs. And we have been able to recapitulate those observations. And a few months ago, we actually reported our findings, what we actually have seen in our data set when we compare patients with or without lymphodepletion, that the incorporation of lymphodepletion is able to influence the expansion and the persistence of the T-cells when given to patients.

Now the thing that it is important to recognize is that despite the incorpoeration of lymphodepletion, we have not seen a detrimental effect in the safety profile. And again, 1 thing that from my perspective I wanted to point out is lymphodepletion is not a problem. The problem is the side effects derived when lymphodepletion is combined with other cell treatments such as CRS and long-term neutropenias and infections and so on and so on. And I think that from that context, the incorporation of lymphodepletion has not had dose effect with our technology, right?

And the importance of that is that, that has provided a very clear guidance in terms of our direction going forward for a registration study. And going forward, and the large database that was presented today include patients that have included -- that have received lymphodepletion. And going forward, patients will be conditioned with a standard lymphodepletion as a regimen for the administration of the cells.

Talking about the registrational study, maybe you can walk us through anticipated timelines for approval of MT-601 as well as the market opportunity.

Yes, that's an excellent question. I think that this is something that is going to become our next critical milestone, which is advancing and contextualizing these results for a future approval. And to that end, I think what it becomes the most important is how this is a high unmet medical need, right? And I think that, that is characterized by the limited options that many of these patients have, the high level of toxicities with the approved current treatment. And I think that when you take that in context with the results that we have seen today, I think we have a very strong case to make in order to have this product advance for accelerated approval, right? We still have to meet with the FDA and present our proposal. But I believe that our clinical data have a strong support for that particular developmental plan. And in that context, I believe we'll be able to get the product approved with a single-arm Phase IIb clinical study. But again, they find details in terms of the size of the clinical study is still have to be discussed in the upcoming conversation with the agency.

Thank you. And what are your thoughts on MT-601 eventually into earlier lines of treatment?

Yes, absolutely. I think that, that is definitely the future, right? We recognize the reality and we are very strategic when it comes down to deploying our product. And as a consequence, we are advancing MT-601 in DLBCL CAR relapse patients with the objective of demonstrating in a patient population with an unmet medical need that without a doubt this treatment works and that it does so in while providing an excellent safety profile. And the reason to do that is that we can get approval in nevertheless, with a restricted label, but we get approval and start changing the dynamics of the company and get to a point of revenue. With the objective of soon after that is on extending this to an early line of treatment. And I think that from what we have seen today based on our data, the Baylor data, I think that it's reasonable to assume that, that is a realistic future where we'll be able to move this treatment even before CAR-T cells.

So for the dose expansion, you mentioned that you will focus on patients with DLBCL who have relapsed after CAR-T cells. And you also mentioned the favorable safety profile of MT-601. Would you also consider enrolling patients who relapse after bispecific in the dose expansion cohort?

Yes. That's an excellent question. And allow me then to clarify -- and I think that the first thing to understand here is that when you look at DLBCL, that's a highly fluid clinical space, right? And I think that recently, we have seen the approval of bispecifics. We also see bispecifics now moving into an early line of treatment and what I'm trying to say is that at this point, very difficult to predict the final evolution of the clinical landscape for DLBCL CAR relapse patients, right? But it is likely to assume that bispecifics will move potentially in a clinical application before CAR-T cells due to the fact that easier to administer given the fact that they are off the shelf. And as a consequence, what we are envisioning for the patient population is to treat patients that are DLBCL, CAR and/or bispecific relapse. And from that perspective, we have a more inclusive criteria that will be able to encompass patients that will fail 1 or the other or both, given the fact that this is still an evolving clinical landscape.

Thank you. We received many questions but I think we have time for 1 more, at least. So building back more in scientific part. So given the strong efficacy that was seen with the lower doses that you tested at 100 million to 200 million cells, what is now the scientific and clinical rationale to move into the higher doses in the dose expansion in patients with DLBCL?

Yes. That's an excellent question. And I think that the overall premise and which is very simple is that more is better, right? And I think that there is a precedent for that viewpoint. I think that especially in the field, we have seen a correlation with other cellular products, including CAR-T cells, where there is an association as to increase the number of cells and the ability for self to expand there is an effector to target ratio that basically is able to provide more reliable and reproducible objective responses, right? So again, the overall viewpoint is that more T cells will basically will provide a higher effective target ratio and therefore, deeper responses to patients. Now I think that many different programs have a limitation in terms of pushing the boundary as you get to more cells, but there also increases toxicities.

I think that what we have here that it is different is that despite going to the highest dose level, which is 400 million cells, we haven't seen anything detrimental from a safety perspective. So with that said, if you take a step back and look at those 2 points, we are advancing the expansion cohort, which is the DLBCL CAR relapse and/or bispecific relapsed patient population with our highest dose level with the attempt of recapitulating if not improving the clinical responses that we presented today, as we now are going to be treating patients with more cells. And without necessarily affecting the excellent safety profile, which again makes this treatment very different.

So again, we still have to collect that data, but I think that there is a good scientific and clinical rationale from other programs that suggests that more cells will be able to have a deeper responses. But again, I'm really excited as now we move into the second part of the year and concentrate enrollment in patients that are DLBCL and/or bispecific relapse into the higher dose levels. And I think that, that will be a very strong foundation as now we go into a future pivotal study for next year.

Wonderful. Thank you very much for the overview and the nice summary. So we received a lot of questions, as I mentioned, and I would like to thank everyone for your questions. We hope we addressed most of them. On behalf of Marker Therapeutics, we would like to thank Dr. Vera and Dr. Shouse and all of you, of course, for joining us today, and we appreciate your interest and engagement and wish you a wonderful day.

This concludes the conference call. You may now disconnect.