Alaunos Therapeutics, Inc. (TCRT) Q4 2020 Earnings Report, Transcript and Summary

Greetings, and welcome to the ZIOPHARM Oncology Inc Fourth Quarter and Fiscal Year 2020 Earnings Conference Call. At this time, all participants are in a listen-only mode. A question and answer session will follow the formal presentation. [Operator Instructions]. I would now like to turn the conference over to you host Adam Levy, Executive Vice President of Investor Relations and Corporate Communications. Please go ahead.

Thank you, Omar. Good afternoon and welcome to the ZIOPHARM Oncology conference call and webcast to review results for the fourth quarter and year ended December 31st, 2020. This afternoon we issued our financial results release, which is also available in the Investors section of our Web site, ziopharm.com. For informational purposes, we have also included in our webcast a set of slides to accompany today's commentary. These slides can also be found on our website. Today's press release also contains several other corporate update, which will be discuss by our speakers. During today's call, the company will make a number of forward-looking statements, including statements regarding the potential therapeutic candidates in our development pipeline, regulatory status, financial information, and business trends. Forward-looking statements are subject to numerous risks and uncertainties. You can see a summary of our forward looking statement disclosure on slide two of the materials we posted today. Joining me today to give some prepared remarks will be Dr. Laurence Cooper, Mr. James Huang, Ms. Heidi Hagen and Dr. Raffaele Baffa. Please refer to slide three for an overview of the topics we'll cover during these remarks. First, Laurence, James and Heidi will briefly share their perspectives on the leadership transition. Second, Heidi will share a business overview including our financial summary and strategic capital allocation priorities across our program. Third, Heidi will highlight some additional detail on our IND clearance announced today for our library hotspot TCR-T program. Fourth, Raffaele will provide a summary of upcoming clinical milestones and share additional details on our upcoming R&D Day. We will then open the call to your questions. Side, four, five and six feature our next three speakers. That's a lot to cover . So let's get to it. At this point, I'll turn the call over to Dr. Cooper. Laurence, please go ahead.

Thank you, Adam, and welcome everyone. This is going to be an a typical quarterly call and one that is somewhat bittersweet. As you likely saw in the release today and effective today, Heidi Hagen will be stepping into the CEO role on an interim basis. I would like to spend a few moments sharing my perspective. I joined ZIOPHARM, almost six years ago, with a vision to bring new hope to children and adults suffering from the devastating impact of cancer. As a physician, I witnessed this devastation all too frequently. And to me and others, the Sleeping Beauty technology when combined with the power of T cells offered an opportunity to develop a new type of cellular therapy, one with almost limitless possibilities. But the initial vision was just that a vision. We had to work tirelessly as a team to bring that vision to the clinic. Now that the clinical development path for our technologies appears launched, I am leaving to enable the company to pursue a path towards commercialization. In the past three months alone, we have received IND clearance to enter the clinic for both our CD19 RPM CAR-T technology in Taiwan, and our library hotspot TCR-T program in the United States. Adding to the previously cleared IND for our allogeneic RPM CAR-T utilizing healthy donors, and the IND for personalized TCR-T at the NCI. We now have a compelling suite of our key technologies in the clinic. And our controlled IL-12 is perhaps the furthest along, where we continue to seek a partner for a future development, including potential registrational work. I am thankful to have led an exceptional team under which ZIOPHARM has grown to be an independent and fully equipped clinical stage company. I leave the company in an incredibly strong position. Before I close, I want to specifically express my gratitude to all my colleagues at ZIOPHARM who came with me on this journey. We dare to dream big and those dreams are becoming reality. I wish James, Heidi, the board and this amazing company and my fellow shareholders well. You're in good hands, and I look forward to a smooth transition. Now, I would like to hand the call off to James Huang, our Executive Chairman. James?

Thank you, Laurence. On behalf of the entire board, entire organization, we thank you for your leadership and vision. We look forward to your continued guidance on the promising signs that serves as the centerpiece of our company. I would like to briefly comment on three topics today, which you can see on slide number five. First, my thoughts on the transition leadership. Second, where I see the company today. And finally, my belief on our technologies. Regarding the transition, I offer my full support to both Laurence and Heidi during the transition. I'm eager to take a more active role as the Executive Chairman, and I'm committed to help the transition to Heidi as our Interim CEO and into a full time replacement as smooth as possible. Shareholders should know that I take this role very seriously. We're going to be incredibly selective in identifying a leader who has the acumen and experience on the business and commercial side to help us realize the potential we have in front of us. I will work closely with the rest of the board to find such a leader. In the meantime, I'm so grateful to Heidi for agreeing to step in as Interim CEO. Second, I wanted to share a perspective on the company that Laurence and the team has built over the past years. In my experience as an Investor, entrepreneurial in Biotech over two plus decades. There comes a point in time when every company must transition from primarily an early-stage science company to one with multiple products in clinical trials, and increasing operational activities with an eye towards commercialization. This transition often includes greater reliance on the development of technology, and manufacturing and capability, change to success. We're now at the point at ZIOPHARM. The commercial path will be grounded in a science that will include additional challenges and complexities that the company must be ready to tackle. I will take a strategic and disciplined approach to resource and capital allocation and the continued commitment to scientific excellence. I look forward to continuing to be an active part of the leaders of the organization in this regard. Finally, I'm often asked about my views of the technology at ZIOPHARM. I'm not a scientist, but I've been in the business long enough to be able to understand and objectively assess the potential of a new technology. At ZIOPHARM, all the ingredients are in place. Specifically, the company possesses a distinctive understanding of the immunology of hematological cancer and solid tumors. And the role that re-engineered T cells, as the way we have know them today, could happen as an effective and potentially transformative therapy. The company also has demonstrated, it has a scalable technology that can leverage that knowledge in truly unique ways to bring those therapies to patients. The foundation of the Sleeping Beauty non-viral system, which Laurence helped pioneer, along with promising clinical stage programs across hematological and solid tumor cancers, taken together, is poised to deliver in the coming years for ZIOPHARM, our shareholders and the patients who will ultimately benefit. The IND clearance, Lawrence had just mentioned, offer evidence of the potential in both the CAR-T space, with our JV with TriArm therapeutics, Eden BioCell is leading the efforts in a highly capital efficient manner, as well as in the TCR space with a library hotspot TCR-T program. I look forward to sharing more in particular on our CAR-T programs in Asia, where I will deliver additional comments at our upcoming R&D Day on March 11. Despite many competitors who are exploring technologies in our space, I believe we will remain ahead of the path and continue to have an opportunity to continue to be in these areas of potential transformational science. I would like to turn the call over to Heidi Hagen now, our incoming Interim Chief Executive Officer. Heidi?

Thank you, James. Let me echo your thanks to Laurence and add a personal reflection before turning to a business overview. I have known Laurence for some years now and I'm honored to call him a colleague and friend. Laurence, I look forward to calling upon your expertise in the coming months. And I'm optimistic the company will continue to benefit from your sage wisdom for many years to come. Thank you. Turning to slide six, I would like to share a few perspectives informed by my 30 years in Biotech, of which the last 20 have been in cell and gene therapy. First, I would encourage all of us to keep in mind the tremendous patient benefits that directs everything we do. I have seen firsthand the impact of cell and gene therapies and it motivates me every day. I have been fortunate enough to be able to lead the design and establishment of cell therapy manufacturing sites in U.S., Asia and Europe, and develop an understanding of the importance of manufacturing, often the most challenging part of delivering cellular therapies to patients. The other thing I've learned is that this is a competitive business environment. One that requires making bold, operational and strategic capital allocation choices, and executing the tough decisions that sometimes come along with that. Shareholders should know that I understand they invest their capital in companies like ours because they believe in the mission and also because they think value can be created long term. I see ZIOPHARM now poised to deliver on all these fronts with a distinctive scientific base, a capital efficient infrastructure we continue to build out and a renewed strategic focus guiding our priorities and planning. More work needs to be done, but I am energized by the challenge and the opportunity as we shift the company to a multi-clinical trial operational entity. Now turning to our business overview. You see on slide seven our financial picture, including a snapshot of where we are at the end of fourth quarter 2020 on the left side of the slide. Cash and cash equivalents as of December 31, 2020, was $115.1 million.I In addition, we also had a prepayment balance of approximately $8.1 million for work to be conducted by the company at MD Anderson. Our cash runway continues to bring us into late second quarter of 2022. We are committed to identifying ways of extending this runway through better capital allocation, greater operating efficiencies, and other non dilutive approaches. My expectation as CEO is that we will be successful. More detailed financials can be found in our 10-K, which we expect to file shortly, and we'll have available on our website. But let me share a few items that we summarized on today's press release. Our research and development expenses were $14 million for the fourth quarter of 2020. That is compared to $10.2 million for the fourth quarter of year 2019 and $52.7 million for the full year as compared to $38.3 million in 2019. This increase reflects increased clinical trial preparation and operational activity. G&A expenses were $8.8 million for the fourth quarter of 2020 and $27.7 million for the full year, compared to $5.8 million and $19.5 million, respectively in the year of 2019. For the full year of 2020, we reported a net loss applicable to common shareholders of $80 million and or -- sorry, $0.38 per basic and diluted share, compared to the net loss of $117.8 million or $0.70 per share for 2019. On the right side of the slide, you see how our strategy and capital allocation priorities map against each of our three programs. As I alluded to earlier, strategy is all about making choices and we are committed to spending our time, capital and resources judiciously. First, our top priority continues to be our TCR-T programs. We are very excited with our announcement earlier today that we received IND clearance for library TCR-T program for Phase I/II clinical work across multiple solid tumors. This study will utilize our Sleeping Beauty technology to deliver non virally engineered T cells across six unique mutagenic hotspots. We are on track to begin dosing patients during the second half of the year at MD Anderson Cancer Center, our initial clinical site. Next regarding our CD19 specific CAR-T RPM autologous program being conducted in Taiwan. We continue to make great progress through our JV partner Eden BioCell. we announced our IND clearance during fourth quarter 2020 of a Phase I clinical trial to evaluate our non viral Sleeping Beauty enabled rapid personalized manufacturing or RPM technologies. This study will investigate treatment of patients with relapsed CD19 positive leukemias and lymphomas and is the first non viral CAR-T study in Taiwan. Despite several market itself-therapy, there remains tremendous challenges preventing broader use of CD19 specific CAR-T therapies. We feel our platform, which allows infusing T cells to stay after gene transfer has the potential to be important and valuable as it offers differentiated features not currently available in marketed CAR-T cell therapies. It is also important to highlight the fact that ZIOPHARM retains full ex Greater China rights to this technology, including any process improvements identified by the Eden BioCell team in Taiwan. Finally, with respect to our controlled IL-12 program, the team is workin incredibly hard to bring the program to this point. During fourth quarter 2020, we reported additional data at SNOW, illustrating the benefit of our technology that highlighted the important benefits in combination with checkpoint inhibitors and as a monotherapy. The full body of clinical data supports a consistent story of potentially meaningful clinical benefit and patients suffering from recurrent glioblastoma. We will continue to seek the right partner for this program for further development, including registrational trials and commercialization, with a focus on returning value to the company and shareholders for the promising progress to date. Turning now to our third theme of progress in cell therapy. On slide eight, you can see a schematic of our two approaches in the TCR-T space, the library and personalized programs. As we mentioned a few moments ago, our company IND for the library hotspot TCR-T trial was cleared by the FDA. This IND advances six curated TCRs from our library of over 30 into clinical trials for five cancer types. In essence, it is six INDs in one, and reflects an incredible effort by the team that worked tirelessly over the last past month, including through the holidays. Patients on this TCR-T trial will be matched with TCRs and library based on their underlying mutation to KRAS and TP53 and their HLA type. The screening for the neoantigen is based on tumor profiling, which in many cases is already available in the patient's medical record combined with HLA testing for every patient. Once matched, the TCR, which is already in a clinical grade Sleeping Beauty construct is used to reprogram the patient's T cells to target one of the two driver genes. We will not only hope to begin enrolling patients this year, but we also expect to add TCR to library trial. Six TCRs that our library should provide patients with an opportunity for a match. But the greater the number of TCRs, the greater the chance of patient can receive our TCR gene therapy. On the bottom of this panel, you will see a schematic of the personalized approach. A comment on the NCI work on the personalized approach. Work is suspended in the ongoing delay being outside of our control. And it is unrelated to ZIOPHARM technology. We understand all gene and cell therapy work is being impacted. We are fully engaged and supportive of Dr. Rosenberg and his team and we look forward to their progress when their cause of their delay is addressed. I would like to turn the call over to Raffaele now who will cover the fourth theme around our upcoming milestones and talk in more detail about our R&D event next month. Raffaele?

Thank you, Heidi. Let me start from the slide nine by highlighting the next 18 to 24 months of clinical milestones. As you can see, this year we bring many exciting milestones. Let me point out just a few. First, I would echo both James and Heidi's excitement for the clearance of the TCR-T library IND. One of the things that attracted me to ZIOPHARM was the non-viral Sleeping Beauty technology and its potential to develop transformative therapies for patients suffering from solid cancer. It's an incredible opportunity to be part of the ZIOPHARM team now, taking that potential into the clinic. This team is poised to begin enrolling and treating patients which we would expect to occur in the second half of the year. We look forward to sharing the initial clinical data on this program next year. We are also excited that in the Q4 of 2020, we received clearance on our CD19 RPM CAR-T program in Taiwan. We expect that our JV partner and Eden BioCell with those patients in the study during the first half of the year, and plan to be able to share the preliminary data during the second half of the year. As a reminder, in Asia, as we reported last month, patients have already been treated and the compassionate use and investigator initiated trials. These efforts, while not formally part of a controlled clinical trial, continue to provide encouraging early signals about the potential of the therapy. Regarding our IL-12 program, we look forward to providing updates later this year. I would like to conclude by highlighting some detail around the working agenda, our Cell Therapy Focus, R&D Day event next month. You can see these on slide 10 in the deck. This will be an important and exciting event for us. Everyone will have the opportunity to hear in greater detail information and updates about our cell therapy programs. Heidi, will kick things off for us by sharing more detail on our strategy and our vision. I will share more thoughts on our portfolio and some perspective on where we are. Now I evaluate the portfolio still as a relative newcomer to the company. Drew Deniger, our Vice President of Immunology, will follow with a review of our own TCR program and our vision for the continued evolution in the clinic. As James mentioned earlier, he will share some observation and thoughts on our work in Asia for our CD19 RMP CAR-T. Importantly, we are also very fortunate to have a world class thought leaders and research visionaries joining us on the call, as you can see on slide 11, including Dr. Steven Rosenberg, Dr. Carl June and Dr. Scott Kopetz. They will share their perspectives on the current prospects across both the CAR-T and the TCR-T space as it pertains to our program. Finally, our management team will be available to take your questions and feedback. I hope you will join me and the rest of the team for this event. Registration link was provided in the press release today and is available on our website. I will now turn the call back to the operator for questions. Operator?

At this time, we'll be conducting a question and answer session. [Operator Instructions] And our first question is from Alethia Young with Cantor Fitzgerald.

Hey, guys, thanks for taking my question. A couple questions I have here and wishing you all the best Laurence. One, just for the future of the company, obviously, this IND filing for TCR-T library, it's big. I guess, just talk a little bit about how that opens up further doors and lowers your reliance perhaps others? And also does it speed up the pace at which you can put assets into the clinic. And I'll ask the second one then I'll slate my third one. My second one is, with your IL-12 program, is it kind of moving forward a lower priority because of the GBM target itself? Or is it just that you find, kind of other technologies more promising? And then I had just one last one.

Raffaele, do you want to take the first question from Alethia on the TCR program?

Yes. So, Alethia, can you say again, because I was focusing actually on the second part of the question, but the first one, I can add to that we -- the IND clearance is a big step forward for us, right? And we are going to have patients by the end of the year, but you brought up a very important issue. So that opened the door for our programs to go into clinic in the next year. If that was the question.

Yes, basically, that was it.

I don't know.

And then, on IL-12, I think I'm happy to kick off. And Heidi, if you want to comment, but -- there is -- it's a lot of different factors in my mind contributing to the strategic choices we're making. It's not exclusively, the target or the technology. But it's a matter of making some discipline choices. And as you know, Alethia, we've talked about a lot in the past. As programs move into registrational trials, that's where the big expense is incurred and the big capital outlays occur. So the decisions are in a way dependent on the phase we're moving into. And I think that's guiding part of the thinking here. I don't know, Heidi, if you want to add anything to that?

Sure. I think that it's very -- as you stated a multifactorial decisions. And along with phase, we see the program is extremely promising, especially with the data that we brought to date and the package that we have so far. And we just see a distinct opportunity to look out into the broader industry for partners who can bring their expertise to the table in kind of the registration and commercialize -- commercialization opportunities with that. So it's really is a combination of focus, capital allocation, and really knowing what the program is and what it means for the next step. And we are a company of a certain size with multiple and great technologies. And so this is one of those difficult decisions you sometimes make in terms of focus. And so, it is many different factors that have gone into how we've done our allocation.

Okay. And this maybe my third question is just, with the management changes, I guess where kind of would you tell investors to kind of put their focus? Whether it would be on technology or kind of the path forward as far as producing clinical assets. Additionally, you have this kind of off-the-shelf library that's fully sorted out? Thanks.

James, do you want to jump in on that one?

Sure. I really think on convention perspective, everyone will be focusing on the patient data that are going to generated over the next 12 months. That's what create value. We have some early signals we said today in today's call, of Asia, but remember, that's actually in a compassionate use setting initiative by the investigators. And so, what we have been learning from those early signals is how we, in a true IND setting in Taiwan, to then to prove that the power of our platform. I really believe in the next six to 12 months, you will see powerful data coming out of our program.

Great. Thank you.

Thanks, Alethia.

And our next question is from Eric Joseph with JP Morgan.

Hi, good afternoon. This is Hannah on for Eric. Thanks for taking our question. Just a couple from us. First, on the upcoming library TCR-T trial, you had indicated earlier in this year that there was a possibility to potentially submit a amendment with IND to include more than the original six TCRs. Just wondering if that was still in mind? And if so, what would the selection criteria be for these additional TCRs? What kind of data would be informing that selection? And would they also be against the same driver mutations as the original?

Thanks, Hannah. Raffaele, do you want to talk about how we're thinking about expanding the library?

Okay. So the current IND as you said earlier includes six of the TCR. But our plan is to add additional TCR with the one amendment or more than one amendment. You ask the question about which TCR? Of course, I can't share that information. But its going to be selected based on the our preclinical data that will support the moving to the clinic for the different TCR.

Okay, great. Thank you. That's helpful. And I just have one about the Eden BioCell or just the original, the initial data coming through from the compassionate use and investigator use studies in Asia. When might we expect to see some of that data? Would you be able to present it in March? Or does that seem more like a later update from you guys?

James, do you want to talk a little bit about that?

Sure. I'll be happy to talk about that. We have already enrolled a small cohort patients. And based on the small cohort patients, we will be presenting at the R&D Day, the patients we have available information and access to that. But again, keep in mind, these are compassionate use data. And we can only obtain information that are available given to us by the investigators. I'll be happy to share a lot more details when we get there.

And Hannah, I would just add, as you know, the real validating data will come through controlled clinical trials. And that's why we pointed to the Taiwan IND is being so critical. So, we're all eager to see that get launched and we'll have more to say on that as well.

Okay. That makes sense. Great. Thank you so much.

Sure. Thanks, Hannah.

Our next question is from Chris Howerton with Jefferies.

Hey, Chris.

Hey. Thanks for taking the questions. And Laurence, I truly wish you nothing but the best. It's been great to get to know you over these last couple of years. So with respect to the questions, I guess, for the current six TCRs that you have available, do you have any way to estimate what kind of coverage or efficiency you might have in terms of the patient populations sort of overlay that to HLA that might be available in just a general population. Just trying to get a sense of coverage that you have from your library, first of all? And then the second question is that, obviously, Laurence has had a great relationship with MD Anderson. And that's an important part of the strategy moving forward. What can you do to provide comfort to investors that will maintain to be true in the future?

Yes, Raffaele, do you want to talk about the coverage in broad terms for the initial six TCRs?

Yes. So, we have estimates, of course, but we are not going to share it. Probably you're going to hear a little bit more on the R&D Day. So welcome to join us that day. And as we said earlier, answering the previous question, we are planning also to expand that, right? So the other question on the MD Anderson, we know, as Laurence said, this great relationship with MD Anderson. So we as a ZIOPHARM we still have a very strong relationship with MD Anderson. I personally have a very strong relationship. I've been working with MD Anderson for the past 10, 12 years. So that will continue. We'll continue to work with MD Anderson, absolutely. And we come from Laurence help, of course.

Sure. Okay. Well, I guess. Stay tuned for a couple weeks then.

Thank you, Chris.

And our next question is from Yale Jen with Laidlaw & Co.

Good afternoon, and thanks for taking the questions. And I end my appreciation for Laurence and welcome Heidi to the great situations.

Thank you.

My first question -- you're welcome. And my first question is that in terms of the Taiwan clinical study, was there any indication has been selected to be included in the CD19 trial? Or is that still open for many potentials?

Sorry, Yale. Was your question around which indications.

Yes. What indications for the CD19 CAR-T to be included in the Eden's trial?

Yes. I think it's -- I can let James follow on. I can just jump in. It's autologous T cell relapsed, leukemias and lymphomas. These are very sick patients.

That's correct.

Okay. And also, just for the TCR-T from Houston. Are you guys going mainly -- potentially mainly cover solid tumors, including non-small cell lung, or you might even possibly started with the myeloma, those very immune responsive tumors at the beginning?

No. We are going to -- we're focusing actually -- the current IND is focused on five indication and all of them are epithelial solid tumor. So, I can tell you that cholangiocarcinoma pancreatic cancer, non small cell lung cancer, and colorectal cancer cholangiocarcinoma. So, no myeloma, no hemato malignancies.

Okay, great. Well, thanks a lot. And again, congrats on the new directions.

Thanks Yale.

And our next and final question is from Thomas Flaten with Lake Street Capital Markets.

Great. Thanks, guys taking the question. Welcome Heidi and James. Just from a practical perspective, with respect to the ongoing programs within IL-12, will those continue to be funded through to completion? Or how are you thinking about kind of rounding out the package that you have to out license or sell?

Heidi, you want to jump in on that?

Sure. As you can imagine, with any program that is mid-step, you don't just completely shut it off. So, we will be looking at those pieces that we will perhaps wind down. Finish up pieces that are really important for partnering and making sure that we have the best and valuable package in which we can potentially partner with somebody on. So, it'll be done in a very judicious manner and something that will be appropriate for both capital allocation but also the opportunity that would present for partnering and moving that program forward, next stages with somebody who may want to do that with us.

So, with those expenses likely to wind down, but then winding up expenses on some of the other programs, can you help us think through spending over the course of 2021?

I think quite honestly, coming just straight into this position, literally in the last couple days, we're going to dive into that and really look at what's going on with each of the programs. And what can really move us forward. As we mentioned before clinical data is really important in all these programs. And that's going to be a priority for us and will be a springboard to opportunities of other potential programs as we move forward. So we will be focusing on our TCR-T program. The CAR-T program, as we've mentioned before, is being heavily carried forward in Taiwan and China. And we will look to the data there to make decisions later on that. So, most of our focus will be on TCR-T. But as I said, we'll judiciously do what we need to on IL-12 to make it a valuable program.

Okay, great. Thanks for taking the questions.

We actually have another question from David Novak with Raymond James.

Hey, David. David, are you there?

Sorry, guys, can you hear me now?

Yes. We can hear you David.

I apologize about that. Thanks very much for taking my questions. And first and foremost, Laurence, I just want to wish you the absolute best in the next chapter. And most of my questions have been answered here. However, I suppose I just have one remaining. You guys talk about maintaining the rights to any process improvements, developed by Eden BioCell ex China. Are there any such improvements you can talk about that have been developed to date, which could or maybe have already been implemented in the U.S. ALLO CAR-T trial?

Yes. Thanks, David. We don't disclose specifics around that, especially to people that call in late and start their question on mute. Just kidding, of course. But we'll be able to share a little bit more detail on the technology strategy at our R&D Day. But I think it's important just to emphasize the general principle, which is that as we talked about, the learnings from the team and Taiwan at Eden flow through and will benefit the programs in the rest of the -- across the rest of the geographies and those accrue directly to ZIOPHARM.

Got it. Thanks very much, guys. I appreciate it.

Sure, David.

Ladies and gentlemen, we've reached the end of the question and answer session. And I would like to turn the call back over to Adam Levy for closing remarks.

Thank you, Omar. And thank you, everyone for joining us today. As always, we are happy to set up additional discussions and make members of the management team available to answer any additional questions. As a reminder, we also look forward to speaking with you again very soon on our R&D Day, March 11. Thank you. Have a good afternoon.

Thank you. This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation and have a great day.