GT Biopharma, Inc.

greetings and welcome to the gt biopharma second quarter 2021 conference call all participants are currently in a listen-only mode following the formal presentation we'll open the call up for a question and answer session at this time i'd like to turn the conference call over to david castaneda investor relations for the company thank you you may proceed thank you operator good morning everyone and welcome to gt biopharma's second quarter 2021 conference call

Earlier this morning, we issued a press release summarizing the company's second quarter 2021 corporate updates that management will discuss on the call today. You can access the press release by going to the news and media section and then the press releases page on our website at gtbiopharma.com. GT Biopharma's following presentation and ensuing question and answer session will include statements that are or may be deemed forward-looking statements. In some cases, you can identify forward-looking statements by terminology, including anticipates, believes, can, continue, could, estimates, expects, intends, may, plans, potential, predicts, should, will, would, or is negative thereof. Other variations thereon are other comparable terminology. We operate in a very competitive and rapidly changing environment, and new risks emerge from time to time. As a result, it is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor or combination of factors may cause actual results to differ materially from those contained in any forward-looking statements we may make. In light of these risks, uncertainties, and assumptions, the forward-looking events and circumstances discussed in this presentation may not occur and actual results could differ. could differ materially and adversely from those anticipated or implied in the forward-looking statements. You are cautioned not to place undue reliance upon such forward-looking statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee that the future results, levels of activity, performance, or events and circumstances reflected in the forward-looking statements will be achieved or occur. We direct you to our annual report on Form 10-K for the year ended December 31, 2020, our subsequent current reports on Form 8 , our quarterly report on Form 10 for the quarter ended March 31, 2021, and our other filings with the Securities and Exchange Commission. Any forward-looking statement included in this presentation speaks only as of the date hereof. Except as required by law, we do not undertake any obligation to update or revise or to publicly announce any update or revision to any of the forward-looking statements, whether as a result of new information, future events, or any other reason after the date of this presentation. For all forward-looking statements, we claim the protection of the safe harbor for forward-looking statements contained in the Private Security Litigation Reform Act of 1995. Nothing in this presentation or discussion shall be deemed an offer to purchase or sell the company's securities. Now I'd like to turn the call over to Tony Cataldo, Chairman and CEO of GT Biopharma. Tony?

Thank you, David. Good morning, everyone, and thank you for joining us. As this is GT Biopharma's first scheduled conference call, I want to thank the investment community for paying attention to the progress that GT Biopharma has demonstrated in the first half of this year. Additionally, I want to thank my entire staff for their due diligence, hard work, and the contribution they have made for an amazing first half of the year. The last fiscal quarter has been marked with numerous events and milestones reflecting tremendous success for the company. We were added into the Russell 2000, the Chicago Options Exchange, and now have enough money to execute the company's business plans for the next couple of years, approximately $40 million. We also completed our new sponsored research agreement with the University of Minnesota, headed by the TRIKE creator, Dr. Jeffrey Miller, and his team at the University of Minnesota. This will further enhance our advancement of the TRIKE platform, adding more value to GT's expanding portfolio. Our GTB 3550 TRIKE clinical trial continues to show safety in clinical results and remains well tolerated with patients who have, for all intents and purposes, been written off. The triclinical data has shown that it is remarkably effective at activating patients' own NK cells, creating persistence of NK cells, proliferation of NK cells, and making NK cells serial killers of cancer cells. Unlike our competitors, we don't need ex vivo outside manufacturing of NK cells or combination drug therapies to supplement our product. Everything the trike does is inside the body. The trike stands alone in the field of NK cell technology companies as a true monotherapy. Additionally, the trike is a toolkit for other NK cell therapies. We have data that shows that. GT will continue to update the investment community as events unfold, as well as significant corporate development milestones. I often indicate to existing and prospective investors and analysts that I believe that it is the data and not the CEO that speaks most meaningfully to the merit and potential of GT Biopharma. As such, I will now turn the call over to Martin Schroeder, our Chief Technology Officer, and Dr. Greg Burke, our Chief Medical Officer, who will recap the impressive and encouraging data we observed and reported in recent months. We will close out the call with a Q&A session. To reiterate, I'm exceedingly pleased with our advancement over the last quarter, as clearly evidenced by our concurrent share price appreciation. And with that, I'll gladly pass this call over to Martin Schroeder. Martin, take it away.

Thank you, Tony. Hello, everyone. As an introduction for those who may be unfamiliar, GT Biopharma's core technology is centered around our proprietary trike platform, and this platform originates from the pioneering work of Dr. Jeffrey Miller at the University of Minnesota. TRIC is designed to harness and enhance the cancer-killing abilities of the patient's endogenous or own natural killer cells without the need for the addition of supplemental NK cell therapy. TRIC is administered to the patient by infusion, and once bound to the patient's NK cells, TRIC directs the MK cell to target certain tumor-specific proteins or tumor antigens that are expressed present on the surface of cancer cells, leading to the death of the cancer cell. Notably, and distinct to TRIK relative to other therapies, TRIK-activated MK cells target and kill multiple cancer cells in a very powerful and serial fashion. So what is TRIQ? TRIQ is made up of what we refer to as recombinant fusion proteins. These are proteins that recognize specific antigens, as I mentioned, on the surface of the cancer cell. And as such, they can be designed and engineered with great flexibility, allowing us to target a variety of tumor antigens present on hemologic malignancies, sarcomas, and solid tumors. TRIK, unlike cell therapies, does not require patient-specific customization. So, in addition to the compelling clinical data we are seeing with GTE-D3550 that's being evaluated in Phase I clinical trial, which my colleague Dr. Greg Burke will discuss momentarily, our pipeline consists of several additional TRIK products which target solid tumor cancers. Our clinical development pipeline includes trike product candidates which target PD-L1-positive solid tumor cancers, B7H3-positive solid tumor cancers, HER2-positive solid tumor cancers, and these cancers include lung cancers, breast cancers, ovarian cancers, gastric cancers, and prostate cancers to name but just a few. The trike product candidates are presently undergoing GMP manufacturing and scale-up in preparation for filing an investigational drug application with the US FDA for evaluation in humans. We are also working on several additional product, tri-product candidates that are in various stages of preclinical evaluation. At this point, I'd like to turn the call over to Greg Burke, our Chief Medical Officer, and he can proceed to discuss the details of our GTP 3550 clinical program. Greg?

Thanks, Martin. The early preclinical and clinical evidence with our first candidate, TRIKE, GTP 3550, for the treatment of relapsed refractory AML and MDS that was reported in the last fiscal quarter is very encouraging. We observed both a positive safety profile and an indication of biologic activity as measured by blast cell reductions. At the 150-microgram dose level, we have one case of grade 1 CRS, which was not a dose-limiting toxicity. There have been no other clinically significant toxicities observed. And in fact, next week, we are escalating to the next dose level, the 200-microgram cohort. To date, 12 patients have been treated in the GTP 3550 phase 1 trial. Patients 5, 7, 9, and 11 experienced 33%, 61%, 63%, and 50% reduction in the CD33 positive bone marrow blast levels, respectively. Fifty-seven percent of patients treated between 25 and 150 micrograms experienced a reduction in their AML or MDS blasts. Activation, proliferation, and persistence of functionally active NK cells occurred without the addition of supplemental NK cells. NK cell activation has been observed to increase early during treatment and is correlated with a proportional and overall increase of absolute number of NK cells. Targeted delivery of IL-15 to NK cells via the 3550 trike showed preferential proliferation of NK cells and significantly less effect on CD8 positive and CD4 positive T cells. We also observed no CD16 shedding by patients' NK cells, and saw enhanced HL60 AML target cell killing ex vivo. This data indicates that GTP3550 rescues the patient's exhausted and inhibited endogenous NK cells, resulting in their activation, proliferation, and persistence. This early data indicates GTP3550 therapy demonstrates significant bone marrow level reductions in AML and MDS patients. without the need for supplemental autologous and allogeneic cell therapies. This Phase I trial is expected to conclude later this fall, and updated safety and efficacy data will be presented in an oral session at the ESMO conference in September. With that, I'd like to turn the call over to the operator to open up for Q&A. Thank you.

Ladies and gentlemen, at this time, we'll begin the question and answer session. To ask a question, you may press star and then one using a touch tone telephone. To withdraw your questions, you may press star and two. If you are using a speaker phone, we do ask that you please pick up the handset before pressing the keys to ensure the best sound quality. Once again, that is star and then one to ask a question. Our first question comes from Justin Walsh from B Reilly Securities. Please go ahead with your question.

Hi, thanks for taking the questions. I have a couple. Starting off, can you provide any color on what we can expect to see at ESMO? How many patients? How long is the follow-up? Any details you can give?

Yeah, well, Greg, you go ahead and answer that. But just to remind everybody, because we are speaking at a major conference, there are certain embargoes that we can't articulate until that conference. All right. Go ahead, Greg.

Sure. Justin, at ESMO, which is on September 20th or around that time, we will present updated safety data, at least through 12 patients. We're literally dosing patient number 13 next week. So we most likely won't have data for that patient at ESMO. So it'll be up through 12 patients.

Got it. And maybe related to that, so you'd mentioned that there was the one case of CRS that didn't seem too severe. Can we get any more details on that? How long after treatment was it observed? How long did it last? What interventions were required? And anything else you can give on that front?

Yeah, sure. It's very simple. It was just fever. So fever that persists a certain amount of time is You know, if it's fever alone without other symptoms, it's a grade one CRS. So, you know, if infection is ruled out, which it was in this case, it's assessed as a possible CRS.

Perfect. Thanks. And I'll just have one more before jumping.

By the way, Justin, that's not a dose-limiting toxicity, a grade one fever or CRS. Got it.

All right, so I think the last one for me, maybe just some details on how Dr. Miller's involvement is expected to evolve following the sponsored research agreement and how that is expected to advance GT's platform.

Yeah, Martin, why don't you take that one? Martin?

Pardon me, I was muted. Forgive me. Yeah, so Jeff's involvement with the company will continue to be quite strong. He is one of our founders and, of course, preeminent key opinion leader in the field. The sponsored research agreement, we have several activities planned to help more fully understand TRIAC's capabilities as well as trikes influence on NK cell biology during the course of therapy. And as you're I'm sure aware, as I mentioned, we are developing several new trike product candidates. Some of those are quite interesting dual targeting trikes that simultaneously target two different tumor antigens the goal to help better cut off immune escape, particularly when we move into the solid tumor setting. So yes, so Jeff's efforts with the company will continue to be strong and he'll be quite actively engaged for the long term.

Got it. Thanks for taking the questions. I'll jump back to you.

Our next question comes from Ram. Silverahu from HC Wainwright, please go ahead with your question.

Thanks very much for taking my questions. Firstly, I was wondering if you could give us some color on the timing of release of final top-line data from the 3550 trial, and if you have a line of sight on which medical conference you expect to present the final data at. I understand the interim data is being presented at ESMO, but just wanted to get a sense of timing of the presentation of final data.

Sure. Hi, Ram. It's Greg. I can take that one. You know, as you know, Ram, as we continue to be in dose escalation, it's always difficult to predict what your recommended Phase 2 dose in your MTD is going to be when you, once again, when you see such a clean safety profile. That's why we've made decisions to escalate from 150 to 200. So when you think about it, it takes a couple of months to get a cohort enrolled, treated, and completed with data. So we won't make a decision on the MTD, which is really the driver of the final data for the phase one, until we establish the recommended phase two dose and MTD. So we're a few months away from that for sure. That's why we're saying it's later in the fall. And then within a few months of that, we'll initiate our phase two. Regarding, you know, with the timing of the conference around the final data, I don't think we'll have final data in time for ASH for sure. So it would be a conference later in the winter or early spring for the final data. But we may release that as a press release even before that, a top-level press release.

What I would add, just to expand on that, just for those who don't really understand it, is MTD is an important milestone for the company, and it's a good thing. When you're not hitting MTD, that means your product's still working, and you may have more effectiveness as you climb that ladder.

Great. And also, I wanted to ask about where in the treatment continuum you see 3550 potentially being most likely to be deployed within the context of AML specifically?

Yeah, that's a great question, Ram. It's something we think about every day, obviously. So, our current study is monotherapy, and that's still our base case plans is to You know, hopefully in phase two, if we see a compelling efficacy signal, and what I mean by that is a significant number of durable CRs, not just blast cell reductions, but durable CRs, we would obviously pursue an accelerated strategy because these are patients, as you know, that don't have any effective or even approved options. We're talking about relapsed refractory AML and high-grade MDS. Yes? So, that's our monotherapy approach. And by the way, we're including, I think as you know, minimal residual disease cohort in our phase two, because that's a population of patients who have a high MND, virtually all of them will relapse, and we're essentially treating lower volume leukemia. So, the MRD cohort is very important to us. I believe that the drug could be moved up in combination with standard of care chemotherapy. And we will, while we're continuing our monotherapy expansion cohorts in phase two, we will initiate a combination trial, most likely with venetoclax and azacitidine, which is the most commonly used regimen in the relapse setting. It's also, as you know, used in frontline setting. There is a lot of published data that NK cells and hypomethylating agents, including both azacitabine and dacitabine, are synergistic and work together in AML models, ex vivo. There's also a lot of evidence that venetoclax, as well as the hypomethylating agents, are not toxic to NK cells. So it makes a lot of sense to combine, you know, the engager with a standard of care chemotherapy, and probably the perfect regimen would be venetoclax azacitabine. So that will be done in the future as well.

Great, very helpful color. I wanted to switch gears now to talk about your B7H3 targeted trike and ask if you can provide any additional color around the preclinical data previously announced, as well as give us a sense of when it might be presented at a medical conference. And also, if you have any thoughts on the current B7H3 competitive landscape, especially in terms of how that compares to other kind of canonical targets that have emerged as being of interest in the context of oncology. Thank you.

Martin, you want to handle that one?

Or Greg, either one. Greg, why don't you go ahead and then I can chime in.

No, I was just going to say Martin's done all the work on it, Ram, so I'll have Martin present it because it's really been his project.

Yeah, I mean, well, actually, the B7H3 trike that we are matriculating through preclinical studies was developed by Jeff Miller and his colleagues at the University of Minnesota. And Jeff and colleagues have published on this product candidate already. B7H3, as you know, is ubiquitously expressed on a number of tumor targets. Macrogenics has been working on B7H3-targeted. compounds for a number of years. We see, with our preclinical data for trich, we see using NK cells as a viable therapeutic modality to very specifically target and kill B7H3-expressing cancers. To date, we've looked at ovarian cancer, breast cancer, and prostate cancer, to name a few, and we've seen a good killing in vitro cell assays in our animal models. Positioning-wise, I think that it does provide an additional therapeutic agent for physicians to consider as they move forward with the comprehensive treatment plan for their patients. So I think

Yeah, that sums it up.

Great. And then just lastly, I was wondering if you could comment at all on potential combinatorial regimens that you view as most ideal for any and all of your other earlier stage investigational tri-candidates. Thank you.

Well, when you talk combinational therapies, it certainly comes to mind the... to protect T cells. But that being said, we are developing dual targeting trikes. And the idea there is to assist in cutting off immune escape. So we have dual targeting trikes that target CD138, which is present on cancer stem cells. We have ones that go after EGFR. and VEGFR3 for example PDL1 combination trike. So the platform is very versatile and that allows us to utilize multiple targeting domains with a single trike. We could for example we have for example a CD19 trike and we could co-administer that with CD33 with our GTV3550 could be done but it's I think, more efficient to make a dual targeting CD19, CD33 trike. So it's really the dual targeting strategy that I think to a large extent we're focused on more than trying to determine which trike we should pair with which other standard of care therapy.

I just want to add to that, Martin, that, you know, it's a reasonable question because Generally, historically in oncology, it's always been about combinations. We're obviously going to pursue seeking a signal as monotherapy because it's a much less challenging regulatory path if it's used as a single agent. However, we're going to go where the science tells us to go, and there's a lot of strong rationale scientifically to combine. trikes with, as Martin mentioned, checkpoint inhibitors as well as standard of care chemotherapy. I do think, you know, we need to initiate combination studies very early into development, literally after we have a couple of cohorts of single agent safety data. So, you know, we're going to start doing this with AML, with Veneza, as I mentioned, because the science is really telling us to go there, and we'll look at every possible solid tumor combination as well with our solid tumor tracts and be guided by the science as well as making sure there's a clear registration pathway for that combination.

Thank you very much.

Our next question comes from Tony Butler from Roth Capital. Please go ahead with your question.

Yes, thanks very much. Two questions, if I may. The first is maybe for Greg or Martin. In clinicaltrials.org, it actually states the Phase 1-2 study for 3550 is enrolling, obviously, at Masonic Cancer Center, University of Minnesota. But there's also Wisconsin that is listed as well, but not recruiting. And I'm just curious, will you open that site for 3550 or wait for the Phase 2? That's question one. Question two is, we spent a little bit of time, Martin and Greg, talking about other trikes, but I think at least what was new to us is this notion of sort of second generation trikes, which have demonstrated greater potency, greater activity, greater cytotoxicity, and I just wondered if you would just spend a minute on those, and in fact, I think the B7H3 trike, for example, is one that has been created based upon, you know, those second generation attributes. And while you don't have to spend a lot of time on it, but I just thought it was important that you may mention it because I think these things, it's just not a, you know, one size fits all. platform, it seems that the flexibility, a word that you have already used, but also the flexibility actually leads to potentially greater cytotoxicity, but that may be target dependent. I appreciate any commentary around that. Thanks very much.

Sure. I can quickly answer the question about the sites and then hand it over to Martin for the discussion on the newer generation trial. Regarding sites and what's posted on clinicaltrials.gov is we have pre-initiated and initiated Wisconsin, and we've gone through the process also with Oregon. You know, at the time we started the process of initiating sites, frankly, we thought we would be wrapping up phase one now. We didn't think we would get to this high of a dose, and it made sense for us to put a hold on those sites until we initiated, you know, have them come in at phase two. They're for sure coming in at phase two, but they may very well come in at the tail end of phase one now. But they are ready to go. And we, by the way, are bringing on multiple new sites for the anticipated phase two. And, you know, we'll have up to eight, you know, eight sites, eight to ten total sites. And we've received a tremendous amount of interest from, you know, many of the KOLs and AML who want to participate in Phase 2. So those initiations are starting already. I'll hand it over to you. I'm sorry.

Yeah, so thanks, Tony, for the insightful question. Yes, our platform is very versatile, and our second-generation trikes, which we're implementing across all of our portfolio. What we've learned about how trich interacts with the NK cell and the target cell has led to this second generation platform. And the key thoughts are we wanted to improve the steric interaction between the various binding domains of the trich molecule and the NK cell and the target cell. So in that regard, we moved away from single chain variable fragments to nanobodies. And in that case, we have seen dramatic improvement in the potency of the drug, of our drug candidates. In some cases, 20-fold better improvement just because we've improved the steric interaction between the trich molecule and the NK cell. And we've done the same investigation with respect to how the NK cell binds to the target cell. And there, in the case of the B7H3 tripe that you mentioned, it's a double nanobody construct with IL-15 in the middle. So we have been optimizing the platform to accentuate the positive elements of tripe therapy, and we'll continue to do so, obviously, as we grow and mature the platform.

Thanks, Greg and Morten. Appreciate it.

And ladies and gentlemen, at this time we've exhausted the audio questions. I'd like to turn the floor back over for any offline questions.

and we're showing no offline questions.

So at this point, I'd like to close the question and answer session, and I'd like to turn the floor back over to Tony Cataldo for any closing remarks.

All right, thank you, and thanks, everybody. I know all of you would have liked to have gotten an update on patients 10, 11, and 12, and as Greg was articulating, we actually have been selected to do an oral presentation at the ESMO conference in September, and because of that, We're under an embargo prohibiting us to release this kind of data. This is actually good news for GT. Results presented at a major conference like this receive much more coverage than the typical press release. I want to thank everyone for listening to our second quarter 2021 corporate update call and for the continued support of our shareholders. We additionally appreciate the courageous participation of the patients in our clinical trials and the dedication of all of those trial investigators. We look forward to sharing future data readouts from our preclinical and our clinical activities as they progress. Again, thank you, everyone, and have a great weekend.

Ladies and gentlemen, with that, we'll conclude today's conference call. We do thank you for attending. You may now disconnect your line.