Alaunos Therapeutics, Inc. (TCRT) Q4 2018 Earnings Report, Transcript and Summary

Good day, ladies and gentlemen, and welcome to the Ziopharm Fourth Quarter 2018 Earnings Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will be given at that time. [Operator Instructions] As a reminder, today's program may be recorded. I would now like to introduce your host for today's program, David Connolly, Vice President of Corporate Communications and Investor Relations. Please go ahead.

Hi, thank you. We're starting a few minutes late this afternoon as there was a last minute rush of callers. We wanted to give a few minutes to let folks actually get engaged on the call. And earlier today, we issued a press release with our financial results for the fourth quarter and the year end of 2018 and that press release is available on our website, www.ziopharm.com. We'll discuss these results today and Company highlights during this call, and representatives of the Company will make a number of forward-looking statements that are -- including statements regarding the potential therapeutic candidates in our development pipeline. Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described in our 10-K -- SEC filings. And moving to slide 3, there is one housekeeping item for today's call before we begin. For those of you following along online, you are now in control of advancing the slides, not us and the folks on this side of the phone call. And speaking on today's call are Dr. Laurence Cooper, CEO and Director for Ziopharm Oncology and Dr. David Mauney, our Company President. After their remarks, we'll open the call to take any questions you may have. And with that, I'll turn the call over to Dr. Mauney.

Thank you, David, and thanks everybody for joining us on the call today. We'll start on slide 5 and we'll touch on it briefly. However, we ended 2018 with a very strong quarter, a quarter that truly transformed our Company's ability to achieve immediate and longer-term success. As a quick reminder, we secured a new licensing agreement, we eliminated $157 million in convertible preferred stock, we raised $50 million, and established two new partnerships and collaborations. We are in our strongest position ever to execute in 2019, and have already demonstrated success in most of these efforts. We have noticed considerable change across the organization now that we have full operational and clinical control over our platforms. From a qualitative view point, I can tell you that we have increased our operating efficiency in just about every category. We have seen dramatic increase in interest from a recruiting perspective, and with regards to outreach to potential partners, analysts and investors, we have seen a considerable change in posture, and in some cases, noticeable surprise and renewed interest in our story. We will obviously push this trend as strongly as we can going forward. We have also made considerable progress in adding and promoting within our organization, and we continue to build a world-class team in every area, with particular focus and active external recruiting efforts to expand our C-suite and manufacturing capacity in Houston. In addition, we now enjoy an almost entirely revamped Board of Directors, having changed four of the six occupied seats and naming a new Lead Director. We have one open seat remaining and a very active outside search is ongoing to fill it with a seasoned leader who will bring valuable and unique skills to our table. With demonstrable success seen in multiple areas over the last quarter and a half, we believe this is an excellent time to be a shareholder in Ziopharm. We are tightly focused on continuing this strong momentum in turn bringing more value to our investors, and most importantly, bringing much needed therapy to patients. Now to slide 6. We are fortunate to enjoy world-class partners, and with each existing partner, we are expanding those efforts. First, we believe Regeneron represents a best-in-class entrepreneurial partner for our Controlled IL-12 platform, and we could not be happier with their commitment to our efforts. Our teams are thoroughly engaged across multiple levels, and we are excited for our efforts to bear more fruit throughout 2019 and beyond. Second, we enjoy a meaningful relationship with MD Anderson Cancer Center and have over $27 million in pre-funded capital to put to work there. While the initial work has been focused on CD19, we now are actively working with senior administrators and an expanded group of physician leaders there, to broaden this relationship for the years to come. Our CAR-T based relationships also extend to James Huang and the teams at Panacea Healthcare Venture, TriArm Therapeutics and Eden BioCell and up to $35 million in financial commitments they made to our CD19 CAR programs in China. James spent years looking for best-in-class technology to solve clinical and commercial needs of the China CAR-T marketplace, and we cannot be more delighted and appreciative of his intellectual and financial commitment to us. Lastly, Dr. Steve Rosenberg and his team at the NCI have committed tireless work in bringing some of our most important technology towards the clinic. We are pleased to announce today that we have extended the CRADA, the Collaboration Research and Development Agreement with the NCI for two more years, a sign that both parties are committed to, and excited to be developing Sleeping Beauty TCR-T cell therapies to treat solid tumors. We are delighted to continue our work for the years to come with Dr. Rosenberg and his team. Importantly, we affirm today that our Sleeping Beauty TCR-T cell therapy will be in the clinic in mid-2019. It should be noted that all facets of the regulatory work to allow us to be in the clinic is done entirely by Dr. Rosenberg's group at the NCI. Historically, the NCI does not issue press releases or make public notifications to highlight regulatory submissions to the benefit of companies like ours. However, since we reaffirm that we will be in the clinic in the middle of 2019, and we remind you this guidance is in conjunction with, and supported by the teams at Ziopharm and the NCI, we remain on track with our 2019 timelines. As a publicly traded company, of course, we look forward to being able to share with you material progress related to the trial as appropriate. The NCI's process to assemble the IND involves many steps, which we understand have all now been achieved. Let me provide some granularity and assurance, surrounding some of the critical work the NCI has done thus far. They have shown, for example, that the Sleeping Beauty system can express high levels of TCRs, targeting more than one neoantigen, that these T-cells can be grown to numbers needed in prior trials infusing TIL for solid tumors; and that the produced T-cells meet anticipated release criteria. The standard operating procedures, the documents that govern the production of the Sleeping Beauty modified T-cells have all been written. All this material has passed the internal scrutiny of the NCI, and is the basis of the IND application to the FDA. As we said before, the NCI is responsible for this process, and we are very confident in their abilities as we move to the clinic. As we also said in November, our use of Sleeping Beauty is a first of its kind for TCRs, and with a non-viral means to gene transfer could be a key to targeting solid tumors of all types, and most importantly could enable truly personalized autologous therapies with multiple targets per patient. We see this path as nearly impossible to commercialize with today's viral-based manufacturing process. The team at the NCI has reported back that the Sleeping Beauty system could be a terrific solution for this complex process, and rest assured, Ziopharm and the NCI are both poised to enter the clinic with a high degree of confidence in this approach. Slide 7, please. Ziopharm enjoys very significant markets for each of the three pillar programs. TCRs, for example, have the ability to target solid tumors. Let me remind you how significant of a market this is. According to the latest statistics from the American Cancer Center, there are 1,762,450 new cancer cases every year in the United States and 606,000 cancer deaths. We now know that the vast majority of these deaths are caused by metastatic, epithelial or solid tissue cancers. Said another way, the solid tumor market represents billions of dollars of potential opportunity even at very modest penetration rates. For CD19 lymphomas and leukemias, there are approximately 130,000 new cases each year, and we know well that companies with CAR-T therapies have seen multi-billion dollar valuations, even with the prospect of modest commercial penetration. And Controlled IL-12 has a clear market for recurrent glioblastoma with more than 11,000 cases in the United States each year, and more than 13,000 in Europe. In fact, the global glioblastoma multiforme or GBM market is estimated to reach $1.15 billion by 2024, fueled by the increasing occurrence of cancer in the central nervous system, among the aging population. We have seen past precedent that even with modest improvements in survival, extremely large valuations on drug approval for this indication alone can follow. Ziopharm does -- has an immense chance to make a huge difference in the lives of so many people suffering from liquid and solid cancers, and the summary is, we now have a clear and independent path forward and we have three amazing pillars to build upon with our technologies in TCR, CD19 CAR and IL-12. Slide 8, now to update you on our current financial status. As we detailed in our press release this afternoon, we have approximately 61.7 million in cash at Ziopharm as of December 31, 2018. This is the primary source of cash for our Controlled IL-12 platform, the work with the NCI, as well our G&A, which is primarily in Boston. And this cash takes us into the second quarter of next year. In addition, there is $27.8 million at MD Anderson pre-paid to cover our clinical and preclinical development work done there. These resources cover all of our existing CD19 work planned at MD Anderson well into 2020, as well other important initiatives we are exploring now in partnership with them. As we now turn a new leaf and execute in 2019, we are filled with confidence as the changes in our ability to execute and build are absolutely tangible, and we are on the cusp of having all of our technologies in the clinic this year. Indeed, we believe now is an excellent time to be a shareholder in our Company. And with that, I'd like to turn over the call to Laurence and slide 9. Thank you.

That's right, and well said, David. Thank you. We are a different company from years past. After we restructured the license agreements in October of 2018, we gained autonomy and operational independence, which allows us to go in a direction that is beneficial to us and to our shareholders, and as David detailed, we are well on our way in that direction. We have continued support from our investors, mutually beneficial relationships with partners of the highest caliber, and we are enhancing and expanding these relationships. We are building and expanding our in-house capabilities and expect to have manufacturing and laboratory facilities as well as infrastructure and programs developed in Houston. This will enable us to broaden the number of patients who can benefit from our programs. Slide 10. We are on the cusp of treating patients with solid tumors with our neoantigen specific TCR-T cell, a therapy designed to be unique to each patient. This is a long sought-after goal by many, and it is Ziopharm that will be in the clinic with this mid-year. This is a huge milestone for our Company. In addition, we expect to be off-hold and in the clinic in the second half of this year with a very rapid manufacturing of genetically modified CAR-T cells to produce patient-derived CD19 specific CAR-T in two days or less. We've made significant strides in our engineering work for improved cell viability for this third-generation Sleeping Beauty trial. Furthermore, having recently come back from China, I can tell you our partners at TriArm are already fast at work to bring our CD19 therapy into the clinic as soon as possible. Lastly, we are seeing excitement with our Controlled IL-12 program as we expand our clinical footprint in the treatment of glioblastoma over the last quarter or so. Our immunotherapy for this brain tumor has captured the interests of clinicians, potential partners, and patients alike, as there is optimism about our data which is showing improved survival. With that overview, let us dive into each of our two platforms, Sleeping Beauty and Controlled IL-12. So moving to slide 11. Let me begin with our Sleeping Beauty platform and an update on our TCR-T program, and specifically the timing of the launch of the first-in-human trial using a non-viral gene transfer event for TCR therapies targeting neoantigens in solid tumors. This work is being undertaken in collaboration with the best in the field, Dr. Steven Rosenberg, and his continued enthusiasm to get this started is a huge validation of our efforts. As we said before, Dr. Rosenberg and his team have two approaches to genetically modification of T-cells to express neoantigen specific TCRs. We understand that this process at the NCI from identifying the antigens, to selecting the TCRs targeting these antigens is similar for Gilead and Ziopharm. However, the important primary difference is the gene transfer event itself to integrate the introduced TCR is where we diverge because Ziopharm has a non-viral process. We use the Sleeping Beauty system and Gilead uses retrovirus. We feel our non-viral approach is a better pathway to commercialization of TCR-T targeting solid tumors. We know that to cure solid tumors, one must infuse T-cells against multiple neoantigens. This places added burden on programs that have decided to use virus to reprogram T-cells, as one needs, not just one retrovirus to express one TCR per patient, but multiple retroviruses per patient depending on the number of targets. To us, this is not commercially feasible. Simply put, DNA plasmids from the Sleeping Beauty system are advantageous in that they are scalable to meet the needs of targeting multiple patients and multiple neoantigens within a single patient. We note the investment community reacted with applause late last year, when it was revealed that the first two patients have been dosed at the NCI based on expression of TCRs using retrovirus. We anticipate having the same success enrolling and treating patients at the NCI using Sleeping Beauty, and look forward to announcing similar news mid-year. Slide 12. Moving onto the CAR-T program, also built on the Sleeping Beauty platform, is our work to very rapidly manufacture CD19 specific T-cells. This is now advancing on two continents, in Greater China and in the United States. There are international markets for low-cost less-complex CAR-T therapies targeting CD19 expressing leukemias and lymphomas. CAR-T therapy that costs $300,000 to $400,000 or more per patient, just for the drug, and not including the ancillary costs is unsustainable, and we are seeing that reality play out. We believe using the body itself to propagate the infused effect of cells is the best solution to the problems plaguing the CAR-T space. Our system is centered on DNA plasmids from the Sleeping Beauty system. This enables us to genetically modify resting T-cells from the blood, without the need to propagate them with the associated expense and time of placing them for lengthy periods in tissue culture. With our proprietary membrane-bound IL-15 for CD19 specific CAR, we have a built-in go signal into the T-cells, enabling them to sustain growth after infusion. Indeed, this may one day also take away the need for lymphodepleting chemotherapy. Furthermore, we expect to be able to infuse far fewer T-cells compared to competing CAR-T therapies, which we believe can benefit patients with reduced risks of cytokine release syndrome. We remain confident that we will be in the clinic in the second half of this year as we've been working to improve cell viability levels. This required an engineering solution with improvements in cell processing, efforts for which we have made great progress. As you recall, this effort in the United States will be initially performed at MD Anderson and their clinical team is primed to move this forward, and we look forward to updating you when we are off hold. We also expect to advance the same very rapid manufacturing of CD19 specific CAR-T therapy into the clinic with Eden BioCell in Greater China. The teams have met multiple times, both in the United States and in China. Together with TriArm, we'll have the infrastructure and personnel to undertake this approach to CAR-T and are thrilled with this relationship. Under the joint venture structure with Eden BioCell, we will have the flexibility to build our own enterprise with its own operating and clinical plans, and look forward to updating the market as future plans take shape. Slide 13. Turning from Sleeping Beauty to our second platform which is Controlled IL-12. We have witnessed a dramatic increase in clinical interest in the programs, with brisk enrollment of patients with recurrent GBM. Regarding our expansion sub-study, we recently announced that we exceeded our planned total of 25 patients by enrolling 36 patients in less than six months. We attribute this to the compelling data on overall survival, particularly in patients who received 20 milligrams of veledimex and low-dose steroids. As a reminder, we showed data at the Society of Neuro-Oncology last November where the median overall survival for that subset of six patients reached 17.8 months, which is quite remarkable compared to historical controls of 7 to almost 10 months. We now have more than 50 patients in the 20 milligrams of veledimex cohort with the expansion study completed, and we expect approximately half of those will be treated with low-dose steroids. We look forward to providing an update this year. Our decision to focus on combining IL-12 with PD-1 inhibition is supported by other studies that recently reported a potential survival benefit to PD-1 blockade in patients with recurrent GBM. Recent studies have shown immune checkpoint inhibitors can have a positive impact on brain cancers in select patients. Investigators in a multi-center study published data in Nature Medicine last month, demonstrating the subset of those patients with recurrent GBM, who received PD-1 inhibitor pembrolizumab or KEYTRUDA when administered before tumor resection, achieved a median overall survival of approximately 13.2 months. The reason that PD-1 inhibition appeared to work is activation of the immune system, and the associated production of gamma interferon in the tumor microenvironment. As a reminder, our IL-12 monotherapy data in a subset of patients demonstrated 17.8 months of median overall survival, and our biopsy data, which we've talked about before revealed production of interferon gamma. Thus, we remain optimistic about survival of patients that received both controlled IL-12 and PD-1 inhibitors. Slide 14. We are now combining our Controlled IL-12 platform with immune checkpoint inhibitors enrolling patients with recurrent GBM. We had two combination trials with PD-1 inhibitors. In our Phase 1, dose-escalating trial in combination with OPDIVO or nivo, which began dosing in June of 2018, we have commenced a third cohort combining OPDIVO with IL-12. We expect to complete enrollment in that trial in the second quarter, and then, we will open the Phase 2 trial to evaluate Ad-RTS, IL-12 + veledimex in combination with Regeneron's Libtayo or cemiplimab also in the second quarter of 2019. Regarding the combination with cemiplimab, since this is a Phase 2 trial without the constraints or pauses in enrollment due to multiple cohorts, we expect this checkpoint combination trial to accrue quite rapidly. Slide 15. In summary, we have multiple shots on goal with each program in the clinic this year. For our Sleeping Beauty platform, we stand poised to treat patients with solid tumors with a first-in-class non-viral TCR-T therapy that can be scaled to target individual antigens in solid tumors. In CAR-T, we are advancing the very rapid manufacturing of CD19-specific therapy in the United States and in China, bringing a solution to the cost and complexity issues that are standing in the way of commercial success for approved CAR-T. For our Controlled IL-12 platform, we have expanded our monotherapy and combination data with PD-1 inhibitors, and we are set to begin a Phase 2 trial with Regeneron. We have multiple opportunities for the investor at Ziopharm, and we see tangible changes inside and outside of our Company. We have done much to improve during these last several months and we are excited for the year ahead. With that, we thank you for your support and return the call to the operator for our questions.

[Operator Instructions] Our first question comes from the line of Reni Benjamin from Raymond James.

Maybe, just to start off with the NCI, Laurence, can you talk a little bit about what this Phase 1 trial could look like? I assume it will be an all-comers, but any sort of color regarding what sort of tumor types you'll be going after, the vein-to-vein time, as it exists right now, and do you ever see a point of care product potentially coming into play in the TCR setting or is that just not something that could work out in the near future?

Sure. So, thank you, Reni. Those are very helpful questions to us. So the NCI, and indeed Ziopharm, as the trial opens for enrollment, we'll give further details and clarifications on the trial design. And just to kind of give you some of my excitement about the types of learnings that I think we will find, the first is that the patients on this trial, as is typical for the referral pattern to Dr. Rosenberg's program, will have advanced solid tumors, metastatic solid tumors. These are some of our nation's sickest patients, and obviously highly motivated to find new treatments. In some ways, these are sort of the toughest of the tough, but we fully expect to be able to treat those patients. The second is, there's really going to be a multiple of opportunities here and I won't go into exactly what tumor types are going to be addressed, but to give you a sense, the technology that we're in partnership with the NCI, is designed, by nature, to be in some ways agnostic of the solid tumor type. We can go after really multiple solid tumors because we're going after the neoantigens, in other words, those genetic mutations that gave rise to the tumor. So I think what you'll see as we get into the details later this year, is that there is really an opportunity for across the solid tumor spectrum. The vein-to-vein time, obviously, is important, but it actually is perhaps a little less pressured than when you're treating fast-growing liquid cancers like leukemias and lymphomas. There, it really is a foot race between the ability to get the product made and the patient to be medically stable to receive those cells. In solid tumors, there's a win-to-win, really, of opportunity and a little bit longer, if you would, for the cells to be made. So that's probably as far as I can take it there, Ren, on that part. And then, the last one is a really interesting question, and that is, explain a little bit more about a point of care, if you would, or very rapid manufacturing in the TCR space. And so, I think for you, Ren, and for the investors alike, Ziopharm at the moment has carefully calibrated its programs to give you three enticing lines of investment, our TCR program, our CAR program and our IL-12 program, but rest assured, in my mind, as I map essentially the future of Ziopharm, these programs will all essentially have opportunities to synergize together, and to build a cohesive story that is actually the summation -- more than the summation of its parts. And more importantly still, we have rights to all of those three programs, and you'll see essentially us building upon that in the months to come.

And just kind of sticking with the TCR program and thinking about multiple antigens, I think, during the prepared remarks, you mentioned that the NCI is already kind of established and has gone through utilizing multiple antigens utilizing the Sleeping Beauty system. How do you control for, I guess, the equivalent expression of multiple antigens in this process, and how do you decide from patient to patient, how many antigens to use?

Yeah, again sophisticated questions here. So in terms of the relative pattern of expression at the antigens, so here, the T-cells actually act in your favor in this respect, and the dialog of the T-cell receptor for instance against antigen A that's very highly expressed versus the dialog the T-cell receptor against antigen B that has a reduced level of expression, the T-cells will respond to that level of threat. The A antigen specific T-cells will expand the number and can recycle their effectual function to knock out the more dominant A expressing cells, and the B one, essentially by analogy here, will have less of that drive, less of essentially need, if you would, to propagate within the tumor microenvironment because the B antigen load is less. So there is a built-in mechanism in the T-cells to essentially solve some of the heterogeneity of antigen level of expression. But your second question is also very important, and that is what is the answer to the heterogeneity of antigens that are more than one. In other words, how is that, that you're going to target more than one antigen, and this is really where the Sleeping Beauty system will separate itself from the pack because it's just simply not feasible to be able to make product and make more than one product per patient when one's using a viral-based approach. The only way I know to be able to do this is using a non-viral system because it's the plasmids. It's really the simplicity of using plasmids and the cost reduction of using plasmids that allows you to make multiple products per patient. Picking those products, picking those antigens then is the next step, and here, we partner with the best in the business. We already know for Dr. Rosenberg's work that the -- essentially the picking process, if you would, the identification of the neoantigens and the selection of the right T-cell receptor has put patients into remission using non-genetically modified T-cells, using TIL, if you would, TILs that have grown up and expanded input into patients. The issue there, of course, is that those TIL, while when they work, work with a real sense of wonder and excitement, it's just simply not scalable or reproducible because the TIL themselves, the effector function of those T-cells, they run out of gas. So you have to graft the T-cell receptor into these fresh, young T-cells, and the Sleeping Beauty system, with essentially its scalability, can do that.

And, I guess, just one final one for me, just regarding Eden BioCell, I know you mentioned multiple trips to China. Can you talk a little bit about, maybe an estimate as to when we might see the studies to begin or when the manufacturing might be complete, any sort of color? Thanks.

Yeah. Yeah, and that will all come really through the remainder of the year here. Let me just say that, that going to China and witnessing essentially the progress since we have started this joint venture to basically to today, it is remarkable how much progress can be made in such a short timeframe. People have been hired, people have been training, infrastructure is going into place, GMP's coming online, all basically within a blink of an eye. And so, if that momentum keeps going, I think Eden BioCell and its partners with TriArm, will be well positioned to attest a point of care, sooner rather than later.

Our next question comes from the line of Eric Joseph from J.P. Morgan.

Just a couple on the IL-12 program. I guess with the monotherapy expansion study fully accrued, I'm just wondering if you can elaborate a little bit more on the rationale design, what feedback you got from docs on -- what's the latest feedback was from docs on the use of a low-dose or steroid-free regimen, and maybe if you can just sort of set the stage a little bit in terms of number of valuable patients and duration of follow-up when we see preliminary data later this year, and sort of how that [indiscernible] next steps particularly in relation to the ongoing PD-1 combo studies.

Yeah. Thanks, Eric. So just taking that the questions in order here, in terms of the steroid-free or low-dose steroids, this is something we are very anxious to test with our clinician partners because as you know and I think the investors know, we had six patients or -- that have had low dose steroids with the 20 milligram of veledimex and those patients really tell a very interesting story that living 17.8 months now at last check, and that gave us essentially a playbook for what we think is the magic recipe, 20 milligrams of veledimex, the activator ligand, and low-dose steroids. So when we guided the -- and collaborated with the physicians, we were anxious to share that 17 month survival story, and we were anxious to share with the physicians that we think the magic recipe is, as I've said, the low-dose steroids. That met with a lot of head nodding and acceptance. And we're really just delighted, Eric, because the patients that are now on the trial in the sub-study, at least half of them, have low-dose steroids. So this is completely feasible now for patients to undergo neurosurgery, to have a direct injection of the adenovirus into their brain, to have received 20 milligrams of veledimex, and to essentially receive low-dose steroids, and we're very optimistic for those patients. In terms of the reporting of the data, we started that study -- that sub -- expansion sub-study basically last quarter, September or so of last year, and it's already accrued, and if you would, Eric, the clock is now ticking on those patients. So that bolus of patients now are marching through this year and we'll get to update the investors on essentially the overall survival of those patients towards the end of this year. In terms of the PD-1 data sets, those data sets are also essentially are in hand. As you heard on our call, we have two cohorts now treated in the Phase-1 trial with nivo and that data started accumulating in, I think, June of last year. So for some of those patients, the data is actually maturing quite nicely and we just opened the third cohort -- dosing cohort for that. Again, that data set will mature in terms of their overall survival, and we look forward to updating the Street also this year as we begin to look at the overall survival of those patients.

Yes, I'll just add one comment, Eric, this is David. I mean, I think when you're looking for qualitative feedback from physicians and hospitals, I mean, one thing you just have to look at to get a quantitative answer is look at our enrollment rates. I mean if you look where we were a little more than a year ago, when I started at Ziopharm, the biology was a bit unknown. It was a bit untested. We were just into the 20 milligrams of veledimex. Since then, we've gotten some biology, some biopsy data. We've gotten more information on the low-dose steroids, and as a result, it's not by accident that our enrollment rates have gone up dramatically, and with that, obviously, comes inbound interest for the technology, and for what we're going to do this year. So I think if you just look at the momentum we have across all three programs, it should be pretty telling.

I guess, I'm just curious to understand whether you -- I guess, given the interest that you have on the monotherapy expansion cohort, how much more information you -- whether you might wait, whether in fact you might still need to wait for the PD-1 combination data before moving forward with a potential registration study or is it -- is there actually a kind of a waiting consideration here do you kind of move forward with both approaches potentially?

Yeah, I mean, that's a great question. The way I think about it is that we have two shots on goal for registration. We have monotherapy, and if the data holds around the 17 plus months of survival with this expanded dataset, that will give a lot of enthusiasm for a monotherapy registration trial. But to double down on that, we have this compelling rationale to combine IL-12 with PD-1. And so, as that data plays out, and it will come roughly around the same time, we'll start to essentially see both sets of data coming out. We'll have essentially that second look if you would, that second opportunity in the design of the registration study.

Our next question comes from the line of Sean Lee from H. C. Wainwright.

I just have a quick one on the IL-12 program, for the upcoming Phase 2 study with Libtayo, could you compare and contrast that a little bit with the ongoing studies with OPDIVO in terms of patient populations, treatment regimen, and how do you expect those two to play out?

Yeah. Thank you, Sean. So, the Phase 1 data with nivo is very important to us because the first time that folks have been able to put a PD-1 inhibitor with IL-12, and by guiding the Street now that were in the third dosing cohort really gives reassurance that this is a safe combination. You can put these two powerful immunotherapies together, and to do so in patients with recurrent GBM. That data directly feeds into now the Phase 2 trial with cemiplimab and that learning, essentially, of the dosing of the IL-12, the dosing of the PD-1 inhibitor, the ability to treat basically all-comers with recurrent GBM who then have a surgery, that allows us to essentially have a direct line of sight to how the Phase 2 trial is built, and so it's going to look in terms of the patient population very similar, but it will be accelerated in terms of its accrual pattern because basically we figured out all of the -- if you would, the mechanics of how to put these two drugs together on the Phase 1 study.

I see. Would we see some information regarding the different dosing in that from the OPDIVO study this year?

Yeah, I think that's fair to say. We will give an update on that this year in terms of the cohort dosing, and the safety data and begin to give some initial data on the OPDIVO study in terms of overall survival in this year.

Thank you. And this does conclude the question-and-answer session as well as today's program. We thank you, ladies and gentlemen, for your participation. Everyone, have a great day.