Hello, and welcome to the Marker Therapeutics First Quarter twenty twenty one Operating and Financial Results Conference Call and Webcast. At this time, all participants are in a listen only mode. As a reminder, this conference is being recorded. It's now my pleasure to turn the call over to CFO, Tony Kim. Please go ahead, sir.
Thanks, and welcome, everyone. The press release reporting our financial results is available in the News section of our corporate website at www.markettherapeutics.com. As a reminder, we will be making forward looking statements regarding our financial outlook in addition to regulatory, product development and commercialization plans and research activities. These statements are subject to risks and uncertainties that may cause actual results to materially differ from those forecasted. A description of these risks can be found in our most recent Form 10 Q and 10 ks on file with the SEC.
I would now like to turn the call over to Peter.
Thanks, Tony. Good afternoon, and thank you for joining us today. I'm pleased to say that we're off to a productive start to the year. During the first quarter, we completed a 56,500,000 public offering of common stock that will support the continued growth of our pipeline, and we're making steady progress on both the clinical and the manufacturing fronts. In March, we treated the first patient with m t four zero one in the safety lead in portion of our phase two trial in post transplant acute myeloid leukemia or AML.
This is a significant milestone for us as it is our first company sponsored trial with multi TA therapy, but also a critical first step towards developing what we believe could be a potentially transformative therapy for these patients who, at present, have only a twenty five percent chance of surviving five years. We currently have several sites open and enrolling, and our clinical team is hard at work getting additional clinical sites online. Our chief medical officer, doctor Michael Canaru, will provide further details surrounding our AML trial in just a moment, and we look forward to taking your questions at the end of today's call. In parallel with the clinical developments, we continue to optimize the m t four zero one cell therapy manufacturing process as we prepare to operationalize our new in house manufacturing facility in the first half of this year. In brief, we're excited to explore how these modifications can be applied across our multi TAA therapies and could potentially result in an increase in the number of T cells available for patient administration amongst other benefits.
Our chief development officer, doctor Juan Vera, has joined us today to provide details about the important process improvements that we've implemented. We look forward to completing the technology transfer from Baylor College of Medicine and manufacturing in house all of the study drug for our AML trial and future trials. This year, our primary focus is on completing treatment of the patients in the safety lead in portion of our AML study with m p four zero one and enrolling patients in the phase two portion of the trial. As you may recall, our cell therapy was designed to address the shortcomings of current treatments while maintaining patient safety. Many cell therapies in development today are pursuing single or even dual targets.
However, this approach has demonstrated little limited improvement in patient outcomes. By contrast, we believe that our multi antigen approach has the potential to induce a lasting antitumor effect by allowing the patient's own T cells to expand and kill cancer cells alongside our therapy. By targeting multiple antigens and epitopes present within the tumor, we believe that our multi TAA T cell therapy can effectively address the tumor heterogeneity while recruiting the endogenous immunity to amplify the immune response through epitope spreading. At this time, I'd like to hand over the call to doctor Michael O'Connor, our chief medical officer, to review details of our phase two trial and our progress to date. Michael?
Thank you, Peter. As you just heard, this has been an important quarter for us as we dose the first patient within the safety lead in portion of our phase two trial in post transplant AML. Just as a reminder, we plan to enroll approximately six patients in this portion of the trial. Three patients will be dosed with m t four one, our lead product candidate, manufactured with a legacy reagent, which was used in the phase one trial conducted by our partners at the Baylor College of Medicine. The remaining three patients will be dosed with study drug manufactured using a new reagent from an alternative supplier.
Our clinical operations team has made considerable progress on getting sites open and have currently nine sites activated. Additionally, we plan on opening approximately 20 sites in total for the phase two portion of the study and anticipate being able to treat the first patient in the main portion of the protocol in q three of this year. M t '4 zero '1, which was granted orphan drug designation in post transplant AML, has been well tolerated in an ongoing phase one clinical trial conducted by our academic collaborators at Baylor College of Medicine in this setting. Overall, results showed that MT four zero one was well tolerated with no incidence of cytokine release syndrome, neurotoxicity, or grade three four GVHD in a post allogeneic setting and demonstrated an antitumor effect with significant in vivo expansion of T cells. In brief, as reported in a recent publication by Lula et al.
In December 2020, '11 of the 17 patients in the adjuvant disease setting dosed with multi TA specific T cell therapy after receiving an allogeneic stem cell transplant never relapsed. Median leukemia free survival or LFS was not reached at a median follow-up of one point nine years. With with eleven of the fifteen patients remaining alive, estimated two years overall survival of seventy seven percent at a median follow-up of one point nine years post infusion, which compares favorably with transplant outcomes for risk matched AML MDS patients post transplant. Additionally, eight patients were treated for active disease that was resistant to salvage therapy post transplant with a median of five prior lines of therapy. The range was four to ten.
Two of the eight patients achieved objective responses with one complete response and one partial response with six patients continuing with stable disease, some of which had reduction in tumor burden. Now based on these results, we are optimistic about m t four zero one's potential in this patient population. To briefly recap, this multicenter AML study will be evaluating clinical efficacy of our product in patients with AML in both adjuvant and active disease settings following an allogeneic stem cell transplant. In the adjuvant setting, approximately a hundred twenty patients will be randomized one to one to either MT four zero one at ninety days post transplant versus standard of care observation, while about forty patients with active disease will receive m t four zero one as part of a single arm group. The primary objectives of the trial are to evaluate relapse free survival in the adjuvant group and determine the complete remission rate and duration of complete remission in active disease patients.
Additional objectives include for the adjuvant group overall survival and graft versus host disease relapse through survival, while additional objectives for the active disease group include overall response rate, duration of response, progression free survival, and overall survival. And with that, I'd like to hand the call over to doctor Juan Vera, our chief development officer.
Thank you, Myceli. In parallel to the progress we have made on the clinical front, we continue to work on simplifying and streamline our manufacturing process while improving the T cell phenotype and antigen specificity of the final drug product. We believe these improvements may have an impact on the clinical performance of the drug product in our phase two clinical study. These manufacture optimizations fall under two major categories, technical and biological improvements. At present, we have incorporated several technical improvements including, first, a 50% reduction in the manufacturing time, resulting in a sixteen days manufacturing process decreasing in this manner the vein to vein time while improving the manufacturer throughput.
Second, a decrease in the number of technical interventions by approximately 95%, reducing in this way the risk of contaminations. Third, an improved manufacturing process, which will reduce the risk of manufacturing failures. And fourth and final, despite the reduction in the manufacturing time, we're able to produce sufficient cell numbers to patients in the current clinical study. In addition to these technical improvements, we're now capable of producing a final drug product with a more favorable cell phenotype, a greater magnitude of antigen specificity, and a broader targeted recognition profile. We believe the combination of these technical and biological improvements might result in a clinical benefit in the upcoming study in AML.
Importantly, these CMC changes have already been approved by the FDA and are currently implemented in the safe to leading portion of the clinical study. With that, I will turn the call back to Tony, our chief financial officers, to review the financials. Tony?
Thanks, Juan. We ended the first quarter with $64,500,000 in cash and cash equivalents. We expect that our current cash balance will support operations into the first quarter of twenty twenty three. Net loss for the quarter ended 03/31/2021 was 8,800,000.0 compared to a net loss of 6,500,000.0 for the quarter ended 03/31/2020. Research and development costs during the three months ended 03/31/2021 was 5,600,000.0 compared to 3,800,000.0 during the three months ended 03/31/2020.
The increase of 1,800,000.0 was primarily attributable to increases in headcount related expenses and infrastructure expenses due to growth of research and development operations. General and administrative expenses were 3,100,000 during the three months ended 03/31/2021 compared to $2,800,000 during the three months ended 03/31/2020. At this time, we'd like to open the call up to questions. Operator?
Thank you. And I'll be conducting a question and answer session. You. Our first question today is coming from Joe Catanzaro from Piper Sandler. Your line is now live.
Hey guys, thanks so much for taking my questions here. Maybe just two for me. So with so with regards to the safety lead in in those six patients, just wondering if we should expect any disclosures from you once that part of the trial has been completed. And if so, what should we, what could we expect to hear out of those six patients?
Sure, Joe. That's a great question. Let me turn that over to doctor Maisel Conero who can talk about, the safety lead in.
Yes. Thank thank you for your question. Regarding the safety lead in six patients, the primary objective is obviously safety. So we'll be looking specifically at dose limiting toxicities. In in terms of timing, you know, as we've mentioned, we are looking on track to completing the safety lead in for the six patients mid this year and to open up the main portion of the phase two.
We you may anticipate a potential announcement for for when the main two main portion of the phase two is is opened potentially, and and then the safety lead in for the dose limiting toxicities has been cleared safely.
Okay. Got it. That's helpful. And maybe quickly my second question. Peter, you noted that the optimized manufacturing process generates a greater quantity of T cells.
Is there any possibility or thinking that the main portion of the phase two could use higher doses of four zero one than what's being used during the safety lead in, or should we just be thinking more along the lines of improved T cell phenotype and and antigen specificity? Thanks.
Thanks, Joe. That's a great question. I think that we are very optimistic about what effects we might see from the improvement in the manufacturing process. But let me turn that question over to Juan who's closest to the the CMC and process improvements that that we've implemented.
Sure. Yes. We actually feel very comfortable with the improvement that we have seen in the final product in term of the analytical comparison. Right? And I'm referring specifically to the comparison in regards to the antigen specificity and the cell phenotype, both which have shown that the current the new process is able to yield a product of greater analytical characteristics.
So from from that, I think that the the product that will be manufactured for the ongoing study should yield a product of of biological characteristics that would be superior to what we initially tested in the Baylor studies. In regard to the question on the cell dose, this new manufacturing process opened that opportunity. Right? I think that now being able to simplify the manufacturing process and also being able to increase the overall cell numbers will give us the opportunity to explore even higher cells. With that, maybe I don't know if if Mike Kelly wants to comment in term of the the prospect of of doing a higher cell dose in in the clinical setting.
Mike?
Thank you, Juan. The phase one AML MDSA that was done at Baylor College of Medicine has been exploring higher doses and shown, you know, shown them to to be safe. So there is an opportunity for us to increase the dose in the main portion of this phase two based on that data and to do so without, you know, necessarily doing any, you know, additional safety readings per se.
Okay. Got it. Thanks thanks for taking my questions.
Thanks, Jim. Thank you. Our next question today is coming from Kristen Kluska from Cantor Fitzgerald. Your line is now live.
Hi. Good afternoon, everyone. Thanks for taking my questions. And I like the new look of your website. I wanted to first ask with all of these manufacturing, technical and biological improvements that you laid out, how are you thinking about how this could impact the cost and time savings on a larger scale?
And then do you believe that this process could be utilized long term, or will you continue to look at other items?
Thanks for the question, Kristen. Let me turn that over to Juan.
Thank you. That's excellent question. We've although we don't necessarily highlight that aspect, I think that the new simplified manufacturing process should have a significant impact in terms of yield and more economic final product that mainly result from a reduction in the overall cell culture time and the overall simplification and decrease in the number of interventions. So without a doubt, that's gonna have a positive impact in the cost of the final drug product. Right?
And but I have to highlight that we we are aware that the there's still aspect that can be further improved in the manufacturing process. I believe that what we have here is something that is a very solid an a a very solid manufacturing process that would be suitable for even future commercialization. However, it it give a very strong foundations from this process to be optimized and to have a closed system and to incorporate certain elements that would allow optimization of this process to simplify and speed up some of the components itself in the manufacturing. So to summarize, I I I think that I agree that with your statement that this simplification has an impact also in the economics, not not just in the biology. And I think that this basically now has a very strong basis for future areas of improvement that I I will consider at this point will be minimal, but nevertheless significant.
Thank you. And yesterday, you had a poster presentation with some comments from doctor Smith at ASGCT with AVB evaluating the potentials of the robotics implementation. So I wanted to ask based on these early findings, if you could discuss if you're looking to further expand on this collaboration and what any next steps might look like?
I think we're very excited about the collaboration with ABB. I think that what what we're finding is is that with the with the implementation of robotic technology, we can improve the consistency of the manufacturing process, which is extraordinarily important in cell therapies. But, Juan, I I I think that, your your comments here would be, would be valuable.
Sure. Thank you, Peter. I I completely agree. Without a doubt, an area of high variability currently in the field associated with this generation of these patient specific products is still rely on the operator. Right?
It's definitely an inherent variability from the stuff in material. But I think that by being able to incorporate that robotic process, you're basically removing in the future a potential unknown, right, which basically is the addition of variability from the operator itself. So I think that this is something that, as Peter mentioned, we're really excited about the collaboration with ABB, and we're looking forward to continue working towards the integration of a robotic process in the manufacture of m t four zero one. And and we believe that this is something that could really transform a process and make it more suitable for future commercialization. So we're we're really excited about that line of work.
Thank you. And then the last question I have is that while I know you're focused on AML, could you talk about how you're thinking about any next potential indications to bring in house based on the BCM proof of concept? And maybe specifically, what are gonna be some of the key decision criteria?
I think that this is this is appropriate for you.
Thank thank you, Peter. Thanks for the question. Yeah. Absolutely. I mean, I think you're right in the sense that we have been working very closely with Baylor and to, you know, follow and understand the the phase one data very closely so that we can appreciate, you know, where the opportunity lies in terms of unmet need for a patient population and where the data is really taking us.
Obviously, the pancreatic cancer data was presented last year at ASCO and, you know, continues to to look, you know, promising. So, you know, I think this being an allogeneic IND for the AML, we're we're obviously looking at other indications in the autologous program, you know, to move forward, including pancreas and potentially other indications. It's really trying to see where the data leads us and where the unmet need is, you know, and finding the appropriate time to do so.
Yeah. Kristen, obviously, we think that the the lymphoma data is quite striking. And, you know, we we believe strongly that the pancreatic results are are continuing to accrue evidence that that the MT that the multi TAA therapy is driving a meaningful therapeutic benefit for those patients with pancreatic adenocarcinoma. However, I would ask you to just bear with us because at this point, I don't think that we have we've officially announced further plans beyond our AML study, and that is currently where our focus is, is driving enrollment in that study.
Great. Thank you.
Thank you. Our next question today is coming from Matt Begleiter from Oppenheimer. Line is now live.
Hey, guys. Thanks for the questions. Yeah. I'll tag on to that last one. Peter, can you can you give us an update on where Baylor is in their own, AML trial?
I think Mai mentioned the trial was testing a higher dose of multi TAA. Any idea when we might see updated data from that trial or or any of the other Baylor trials for that matter?
Yeah. That's a great question, Matt, and thanks for the question. Let me turn it over to Michael who who coordinates and talks to doctor Prima Alula, our primary investigator at Baylor on a on a fairly consistent basis for for the latest update on the dose escalation portion of the Baylor phase one trial.
Thanks, Matt, for your question. So if you look at the recent publication of from that group from doctor Pomalulula on the phase one AML MDS study, there was some some data included on some of the higher dose levels in that paper. So I think they are nearly complete with that last dose level. I so that paper, I think, more or less is up to date on the current status on those two additional dose cohorts. And I think it's very close completion of that last cohort with the highest dose.
Yeah. My my understanding
I'm sorry, ma'am. My understanding is is that Baylor was set to complete the last dose s the last patient in the dose escalation phase, the the dose level five last year, but due to disruptions because of COVID, they've they've they're still in the process of of finding an a play a patient to replace the patient that they had originally planned to to treat but were unable to because of coronavirus.
Yeah. That makes sense. I'll have to I'll have to check out that publication. I I had a quick follow-up on manufacturing. Just any any plans to present side by side, comparisons of the drug product manufactured, with the new approach versus the the old Baylor approach?
Yeah. Let me let let me direct that question to Juan.
Thank you. Yes. That that's actually a good point. I we feel really proud in the progress we have made on the manufacturing front. And, actually, we're presenting a a small snip of that information at the ISCT meeting and ASCGT.
So the the poster is really focused on how we can best improve the manufacture of m t four zero one where we disclosed the collaboration with ABB in incorporating a robotic process. However, I encourage you to to look at the results where we actually disclose some information, the first part of the work, which is geared towards simplifying the manufacturing process. And and there, you will be able to see the impact from a biological standpoint when we compare the old and the new manufacturing process.
Alright. Great. Thanks, guys.
No problem. Thanks, Zach.
Thank you. Our next question is coming from Tony Butler from Roth Capital. Your line is now live.
Yes. Thanks very much. Peter or Maithili, you made a reference to the first six patients, in which case you would look at, of the lead in, portion of the study in which you would look for, some side effects that may occur from one from from from one group versus the other group, one of the three patients versus the other three patients. And the question is, is there any other biological data that you need to feed to the FDA to actually demonstrate that there's really no difference between the two, particular, reagents that are being utilized. And effectively, three patients from one reagent versus three patients from the second reagent are literally identical.
And I'm curious what that biological data might be. Thanks.
Sure, Tony. Let me turn the question over to Maithili, but, let me start by clarifying something, which is that the patients in the safety lead in are being primarily monitored for safety. That is that none of them have dose limiting toxicities, and that is, the primary endpoint for these six patients in the safety lead in. But from a practical standpoint, we won't be doing anything meaningfully different with these patients than we will be for the patients that will be enrolled in the official phase two. So with respect to efficacy, if we see efficacy from these patients, you know, we we will plan to continue to monitor and report them, just the same way that we would the phase two patients.
But mindfully, you know, why don't I turn it over to you for the the technical answer to to Tony's question?
Yeah. Thank you for your question, Tony, and and Peter's exactly right. You know, we're really only focused on the dose limiting toxicities that will, you know, be reported to to the FDA if any any issues arise. You know, we don't anticipate any differences in terms of the safety profile between the two cohorts. And beyond that, there's really nothing additional that we need to report to the FDA.
So in terms of, you know, other biological data, that's already you know, in terms of, you know, the reagents manufacturing and and similarities, all all of that has already been provided. So it's really just this last piece of safety data that will be provided before opening up the main portion of the phase two.
I appreciate the clarity. Thank you.
Thanks, Michael. Yeah. Yeah, Tony. That that's a distinction that, that is sometimes lost and that the safety lead in is really only, intended to, to ensure that there are no DLTs, from, from the product. But the issue of comparability has already been settled with the agency.
Thank you. We've reached the end of our question and answer session. I'd like to turn the floor back over to Peter for any further or closing comments.
Thank you all for joining us today here on our first quarter earnings call. We appreciate your support, and we hope that you all stay safe and well during this pandemic. Have a nice evening.
Thank you. That does conclude today's teleconference and webcast. You may disconnect your line at this time, and have a wonderful day. We thank you for your participation today.