Fate Therapeutics Inc Q1 FY2020 Earnings Call

Welcome to the Fate Therapeutics' First Quarter 2020 Financial Results Conference Call. At this time, all participants are in a listen-only mode. This call is being webcast live on the Investors and Media section of Fate's website at fatetherapeutics.com. As a reminder, today's call is being recorded. I would now like to introduce Scott Wolchko, President and CEO of Fate Therapeutics.

Thank you. Good afternoon and thanks everyone for joining us for the Fate Therapeutics first quarter 2020 financial results call. Shortly after 4:00 P.M. Eastern Time today we issued a press release with these results which can be found on the Investors and Media section of our website under press releases. In addition, our Form 10-Q for the quarter ended March 31, 2020 was filed shortly thereafter and can be found on the Investors and Media section of our website under Financial Information. Before we begin, I would like to remind everyone that except for statements of historical facts, the statements made by management and responses to questions on this conference call are forward-looking statements under the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that could cause actual results to differ materially from those in such forward-looking statements. Please see the forward-looking statement disclaimer on the company's earnings press release issued after the market closed today as well as the risk factors in the company's SEC filings included in our Form 10-Q for the quarter ended March 31, 2020 that was filed with the SEC today. Undue reliance should not be placed on forward-looking statements which speak only as of the date they are made as facts and circumstances underlying these forward-looking statements may change. Except as required by law, Fate Therapeutics disclaims any obligation to update these forward-looking statements to reflect future information events or circumstances. Joining me on today's call are Dr. Dan Shoemaker our Chief Scientific Officer; Dr. Bob Valamehr, our Chief Development Officer; and Dr. Wayne Chu our Senior Vice President of Clinical Development. Today, I will comment on the impact of the COVID-19 pandemic on our business, highlight key milestones we achieved during the past several months, and discuss the transformative collaboration we recently entered into with Janssen. The global COVID-19 pandemic has significantly impacted our daily lives and we have been compelled to change our day-to-day operations to confront these unprecedented times. We have taken numerous measures to protect the health and safety of our employees, their families, and the extended community, while continuing to operate our business. Shortly after the JPMorgan Conference, we reassessed our preparedness for a potential pandemic and began implementing changes to our operations. We confirm that our master iPSC lines and our manufactured clinical products were inventoried in redundant locations and we stocked clinical sites with our clinical products to enable off-the-shelf administration to patients. We also worked with our suppliers to accelerate the sourcing of key materials to support the conduct of our planned in-house GMP manufacturing campaigns. We implemented a work-from-home policy and restricted on-site personnel to those conducting essential laboratory and manufacturing activities. We worked closely with our clinical trial sites and investigators to promote the safety and continued care of study participants, implemented remote site activation and patient monitoring, and preserved data integrity. We believe we have established operational capabilities including full control of GMP manufacture that will allow us to operate with resolve and advance our business objectives. The commitment, resourcefulness, and resilience of our employees have carried us through these challenging weeks. We have been disrupted by the COVID-19 pandemic, though as the cadence of new clinical trial site initiation and patient enrollment has slowed. While we remain committed to our clinical programs and development plans, these disruptions have introduced some uncertainty regarding our projected timelines for enrollment and data readouts across our clinical trials. Nevertheless, we have maintained significant business momentum across our three clinical programs, all of which have continued to enroll patients. For each of our programs, we have manufactured hundreds of cryopreserved infusion-ready doses that have been tested, released, and stored in inventory and are immediately available for use in our clinical studies. With respect to our FT500 program, we have now treated three patients with FT500 at the 300-million cell dose level in combination with checkpoint inhibitor therapy and successfully completed enrollment in the dose escalation stage of the FT500 Phase I clinical trial in advanced solid tumors. We believe this is a significant clinical milestone as our FT500 Phase I study is the first-ever clinical trial in the United States of an iPSC-derived cell product. Additionally, it is one of the first-ever clinical trials of a cell therapy to evaluate a novel multi-dose treatment course, consisting of outpatient lympho-conditioning followed by three once-weekly doses of FT500 over up to two 30-day treatment cycles. I'm pleased to report that consistent with our prior clinical observations in the dose escalation stage of the FT500 Phase 1 study, there were no dose-limiting toxicities, no FT500-related Grade ≥3 adverse events or serious adverse events, and no incidence of cytokine release syndrome, neurotoxicity, or graft-versus-host disease reported by investigators in these three patients. Enrollment in the dose expansion stage of the FT500 Phase 1 study is proceeding at three clinical sites in patients with non-small cell lung cancer, where up to 40% of patients with resistance to checkpoint inhibitor therapy exhibit partial or complete loss of MHC Class 1 expression making these cancers highly susceptible to NK cell recognition and killing. We expect to treat up to 15 patients in the outpatient setting in the dose expansion stage, administering three once-weekly doses of FT500 at 300-million cells per dose over up to two 30-day cycles along with IL-2 cytokine support and with the checkpoint inhibitor on which the patient failed or progressed. FT516 is the second program emerging from our iPSC product platform and the first engineered iPSC-derived cell therapy in the world to undergo clinical investigation. We continue to conduct the dose escalation stage of the FT516 Phase 1 clinical trial as a monotherapy for AML and in combination with rituximab for advanced B-cell lymphoma. We have successfully activated two additional sites for a total of three active sites and we are currently working with two additional sites on remote activation. In addition, we successfully expanded the clinical scope of our FT516 program to advanced solid tumors. In January, the FDA allowed our second IND application for FT516 enabling clinical investigation in combination with PD-L1, PD-1, and EGFR and HER2-targeted monoclonal antibody therapies across a broad range of solid tumors. We intend to initially evaluate FT516 in combination with avelumab, an ADCC component anti-PD-L1 immune checkpoint inhibitor in patients with advanced solid tumors who are refractory to or have relapsed following at least one line of anti-PD-L1 therapy. With respect to our FT596 program, we treated the first patient in the dose escalation stage of the FT596 Phase 1 clinical trial for advanced B-cell malignancies and chronic lymphocytic leukemia. We are particularly excited about this clinical milestone. FT596 is the first-ever cellular immunotherapy engineered with three active anti-tumor components to be evaluated in patients and is uniquely designed to target multiple tumor-associated antigens expressed on cancerous B cells for best-in-class potential. In addition to a proprietary CAR targeting CD19, FT596 expresses our novel high affinity non-cleavable CD16 Fc receptor enabling multiple antigen targeting of CD19 and additional tumor-associated antigens such as CD20. FT596 also expresses a novel IL-15 receptor fusion, a potent cytokine complex that promotes survival, proliferation, and transactivation of NK cells and CD8 T cells without the need for systemic cytokine support. One site is currently active, and we are currently working with three additional sites on remote activation. In addition, I'm also pleased to announce that we have successfully expanded the clinical scope of our FT596 program as the FDA allowed a second IND application for FT596, sponsored by investigators from the Masonic Cancer Center, University of Minnesota. This new Phase 1 clinical study is intended to assess the potential of FT596 to prevent relapse in patients undergoing autologous hematopoietic stem cell transplant for the treatment of non-Hodgkin lymphoma. The clinical trial is expected to enroll up to 18 patients considered high-risk for early relapse based on failure to achieve complete or partial remission on or relapse within 12 months of prior therapy. Up to three dose levels of FT596 will be administered in combination with rituximab 30 days following transplant. We also continue to be excited about our rate of preclinical innovation including our ability to add on additional engineered features and functionality, rapidly build next-generation product candidates and advance our pipeline of engineered iPSC-derived NK cell product candidates into clinical development. I'm pleased to announce that we have recently submitted an IND application to the FDA for FT538, the first CRISPR-edited, iPSC-derived cell therapy. FT538 is derived from a clonal iPSC line engineered with hnCD16 and our IL-15 receptor fusion and edited for elimination of CD38 expression to mitigate anti-CD38 antibody-mediated fracture side. We intend to clinically investigate FT538 in combination with anti-CD38 monoclonal antibody therapy for the treatment of multiple myeloma. In addition to FT538 as a clinical candidate, we believe the clonal master engineered iPSC line for FT538 may serve as a foundational cellular backbone for the building of future iPSC-derived NK cell product candidates. For example, at this week's American Society of Gene and Cell Therapy Virtual Annual Meeting, we will highlight the creation of a master engineered iPSC line for FT576, our off-the-shelf iPSC-derived CAR-BCMA, NK cell product candidate, using an existing master engineered iPSC line from the FT538 program as starting material. Similarly at ASGCT, we will also present preclinical data for our recently announced CAR-MICA/B program, targeting pan-tumor associated stress proteins where the initial product candidate forms have been developed using existing master engineered iPSC line from the FT538 program. As many of you know, about five years ago when we set out on this journey to bring iPSC-derived cell-based cancer immunotherapy to patients, our mission included both NK cells and T cells, as the delivery of both cell types may ultimately play a critical role in curing cancer. We formed a foundational collaboration in 2016 with Memorial Sloan Kettering, led by Dr. Michel Sadelain to guide our path in developing off-the-shelf iPSC-derived CAR-T cell therapy. Over the years, we've followed the science and the clinical learnings emerging from the autologous CAR-T cell field and continued to innovate to include state-of-the-art features and functionality in our iPSC-derived CAR-T cell programs. We pioneered the creation of a clonal master iPSC line engineered with a CAR inserted into the TRAC locus to regulate CAR expression, optimize cytotoxic activity and eliminate T cell receptor expression for mitigation of graft-versus-host disease risk. We refined our differentiation protocol with the goal of making potent alpha-beta T cells that closely match their naturally occurring counterparts. And we raised our iPSC-derived CAR-T cell product candidates against primary CAR-T cells in the most stringent preclinical models under our collaboration with the founder of CAR-T cell therapy. I'm pleased to announce that we remain on track to submit our IND application to the FDA in the second quarter for FT819, the world's first off-the-shelf iPSC-derived CAR-T cell therapy. FT819 is derived from a clonal master iPSC line engineered with a novel 1XX CAR targeting CD19 inserted into the TRAC locus and edited for elimination of TCR expression. We continue to strive to bring FT819 to the first patient in 2020. Finally, I'd like to make a few comments about our newly formed collaboration with Janssen. The partnership is transformative for us, and I believe it significantly increases our ability to invest in innovation, build commercial-scale iPSC manufacturing operations, bring best-in-class iPSC-derived cell-based cancer immunotherapies to patients, and deliver value to shareholders. The collaboration brings together Janssen's scientific leadership in deep domain expertise in oncology and our industry-leading iPSC product platform. Our mutual objective is to research, develop and commercialize novel off-the-shelf iPSC-derived CAR NK and CAR-T cell products. With respect to the collaboration scope, the collaboration is antigen-targeted-based and includes both CAR NK and CAR-T cell candidates directed to up to four tumor-associated antigens. The binding domains directed to the four antigen targets are proprietary to and are being contributed by Janssen for the construction of the CAR constructs. The cancers we are seeking to treat include both hematologic malignancies and solid tumors. Note that this is a deep collaboration and that it is not limited to a specific number of collaboration candidates. In fact, we can continue to innovate and develop next-generation collaboration candidates together against those four specific antigen targets. Under the collaboration, we will drive and conduct innovation, preclinical development, and conduct IND-enabling activities for each iPSC-derived CAR NK and CAR-T cell collaboration candidate. Importantly, all these activities are entirely funded by Janssen. And we will receive full funding for all innovation, preclinical development and the IND-enabling activities that we perform under the collaboration. Upon the completion of activities sufficient to allow for submission of an IND, Janssen will have the right to exercise an exclusive option and obtain an exclusive license for the clinical development and commercialization of the collaboration candidate. Janssen will be solely responsible for worldwide clinical development and commercialization, and we will be primarily responsible for the manufacture, at Janssen's cost, of the collaboration candidate. For each collaboration candidate upon Janssen's attainment of clinical proof of concept, we have the right to elect to co-commercialize and share equally in the profits and losses in the United States, subject to sharing in certain development costs. I'd like to emphasize that the collaboration candidates, under the Janssen collaboration, do not include any product candidates that are currently under clinical or preclinical development by us or otherwise part of our current product pipeline. We will continue to independently innovate and exploit our deep pipeline of wholly owned product candidates. With respect to the collaboration economics, we received $100 million in April, of which $50 million was an upfront cash payment and $50 million was in the form of an equity investment at $31 per share. For the first antigen target, we are eligible to receive up to $898 million upon the achievement of specified development, regulatory and sales milestones for the first collaboration candidate. And up to $460 million of milestone payments for each additional collaboration candidate. For each of the second, third and fourth antigen targets, we are eligible to receive up to $706 million in milestone payments for each of the first collaboration candidates and up to $340 million in milestone payments for each additional collaboration candidate. In total, assuming only one collaboration candidate, across each of the four antigen targets we are eligible to receive payments of up to $1.8 billion upon the achievement of development and regulatory milestones and up to $1.2 billion upon the achievement of commercial milestones. In the event we elect to co-commercialize a particular collaboration candidate, with the benefit of sharing equally in the profits and losses in the United States, these milestone payments are subject to reduction. In addition, we are eligible to receive double-digit royalties ranging up to the mid-teens on net sales of collaboration products that are commercialized by Janssen. With respect to the collaboration's strategic value, I would highlight several key points. First, we have partnered with one of the strongest oncology teams in the entire industry, one, with outstanding scientific, clinical development and commercialization expertise. We will be building collaboration candidates using proprietary binding domains identified and optimized by Janssen, creating the opportunity to develop highly differentiated products. Second, Janssen has committed substantial dollars to the collaboration's work plan. And we will be receiving significant annual research and development payments to drive innovation, including for the research and development of next-generation features and functionality, and for the scaling of our GMP manufacturing processes to support commercial-scale operations. Importantly, we retained rights to this innovation for use across our iPSC product platform. Furthermore, the collaboration represents an opportunity for us to leverage our industry-leading iPSC product platform and expand our product pipeline. We have not encumbered our existing product pipeline in any way whatsoever. For each collaboration candidate, we retained significant economic interest, with the rights to opt in to co-commercialization and equal share of profits and losses in the U.S. Lastly, I would highlight that we retained responsibility for the manufacture of collaboration products. Under the collaboration, we have formed a joint manufacturing committee, where Janssen can provide advice and support for our activities in building and scaling a world-class cell therapy manufacturing operation. I would like to thank the Janssen oncology team. These are uncertain times, and we're all facing new challenges during this COVID-19 pandemic. Janssen was unwavering in their commitment to this partnership. And I'm really appreciative and sincerely grateful for the significant time and effort that Janssen dedicated to finalizing this collaboration in the midst of the pandemic and at the trust that the Janssen team has placed in our team. I'm really excited to lead Fate Therapeutics as we begin this transformative collaboration together and dedicate ourselves to building novel off-the-shelf CAR NK and CAR-T cell cancer immunotherapies and bring life-changing medicines to patients. Turning to our financial results. Revenue was $2.5 million for the first quarter of 2020 compared to $2.6 million for the same period last year. Revenue in the current quarter was derived from the company's iPSC-derived CAR-T cell collaboration with Ono Pharmaceutical. Research and development expenses for the first quarter of 2020 were $29.3 million compared to $17.7 million for the same period last year. The increase in our R&D expenses was attributable primarily to an increase in employee compensation, including share-based compensation and expenses associated with the clinical development and manufacture of our product candidates, the conduct of research activities including under our collaboration with Ono and the facility lease for our new corporate headquarters. General and administrative expenses for the first quarter of 2020 were $7.7 million compared to $5.4 million for the same period last year. The increase in our G&A expenses was attributable primarily to an increase in employee compensation, including share-based compensation, and in legal and accounting fees. Total operating expenses for the first quarter of 2020 were $30.1 million, net of non-cash share-based compensation expense of $6.9 million. The company ended the first quarter of 2020 with $219 million of cash, cash equivalents and investments, which excludes $100 million received in April in connection with the Janssen collaboration. Common stock outstanding was 76 million shares and preferred convertible stock outstanding was 2.8 million shares, each of which is convertible into five shares of common stock under certain conditions. Common stock outstanding excludes the issuance of 1.6 million shares in April in connection with the Janssen collaboration. The global pandemic has shaken all our lives and many of us are experiencing first-time challenges and significant instability. I want to thank our employees for their passion, commitment, and resiliency. I'm proud that we have demonstrated our ability to act swiftly to changing times and remained unwavering in our commitment to bring our pipeline of engineered iPSC-derived NK cells and T-Cell cancer immunotherapies to patients during these unprecedented times. I sincerely hope that all of you and your family members are well and staying safe. And I'd now like to open up the call to questions. Thank you.

Your first question comes from Ted Tenthoff with Piper Sandler.

Great. Thank you, guys. Congrats on all of the update across the pipeline, it's really exciting. Trying to get a sense for sort of where you see the applicability for 819 vis-à-vis the other products in development and out there currently. Really excited to see that one advance into the clinic and do think we would most likely get data sometime next year. But just want to get a little bit more color on 819. Thanks.

Sure. Wayne is currently located in San Francisco. Wayne, do you want to answer that – take that question from Ted?

Sure. So yes, we're very excited about FT819 entering the clinic. And I think it raises some very intriguing development questions and possibilities given the fact that we also have a product in FT596, where based on what we know we should also expect to see activity. And I think that the challenge from a clinical development perspective is finding indications that are most appropriate for the risk-benefit profile of each of the products as we gain clinical data in our Phase I studies. And so I think that the answer to your question will largely be dictated by what we see in terms of efficacy and more importantly safety and tolerability because that will then define what are the most appropriate indications within B-cell leukemia and lymphomas in which to more fully develop these products.

Great. Thank you very much.

Your next question comes from the line of Robyn Karnauskas with SunTrust Robinson.

Hi, everyone. Thank you for taking my question. I have two parts. First, regarding the impact of COVID, could you clarify how the timelines of the 516 and 510 trials were affected or if FT500 enrollment faced any disruptions? Specifically, how many patients were enrolled during that period and were there any skipped visits? Secondly, congratulations on the recent deal. How do you view potential future deals, and does this agreement impose any restrictions on pursuing them? Thank you.

Sure. I'll do those in reverse order. So there's nothing in the Janssen deal that prevents us from doing future deals, other than we are mutually exclusive with Janssen on the four antigen targets. So those four specific antigen targets, which are named to be clear, we're working exclusively with Janssen on those four targets. So obviously, if you think of the space of cancer immunotherapy, there are countless targets that you could potentially pursue and more emerging each and every day. And so yes, we absolutely have the opportunity to continue to do partnerships as we think about continuing to build our pipeline and leverage our platform. I think one of the exciting things that I mentioned, for instance, on this call is that we are continuing to evolve our pipeline and our platform where we are creating multiplexed engineered product candidates. For instance, FT538 already has three engineered pieces of functionality in that cell product. We can use that now as a backbone essentially to create new product candidates starting with that as the starting material. So I think our ability to develop highly multiplexed engineered product candidates is really exciting and is one of the things that we think and I think partners think is very attractive about our platform, as we look at how to for instance attack solid tumors as an example, where I think it's going to take potentially highly engineered and edited solutions. Regarding the trials, there is some debate about when COVID impacted us. However, in the FT500 program, we were in the process of completing the 300-million cell dose in the dose escalation phase, which we successfully finished. To my knowledge, there were no missed visits during the completion of the dose escalation at 300 million cells per dose. I discussed the results during the call, and we are very excited to see strong safety and tolerability, particularly as patients moved into the second cycle after receiving all six doses. For FT516, it's still early days. We treated the first patients in the dose escalation phase around late October, and we are currently progressing through this phase in the FT516 program.

Got it.

I would also just add that as Scott mentioned, we were in the midst of dose escalation in all of our active trials when the COVID-19 situation became such that there were rules at the institutional level to restrict patients coming on to Phase I trials. And so we've been monitoring the institutional guidelines very closely and have been in very constant communication with investigators to ensure that patients who are on the trials are being monitored appropriately. And for the most part, despite the COVID-19 situation patients are still adhering to their schedules with respect to monitoring even to the point of still continuing to come into the clinic to have physical exams and lab draws and things like that. But cognizant of the impact of COVID-19, we have worked actively with clinical sites to ensure the possibility of remote monitoring and other contingencies in cases where patients are unable to come to the clinic.

Your next question comes from the line of Jim Birchenough with Wells Fargo.

Hi, guys. Congrats on all the progress, a lot to cover. So a couple of questions. I guess number one, could you just talk about how your platform allows you to be opportunistic as sites reopen for patient dosing? Have you been able to ship all those doses that you mentioned to different sites? And maybe compare how you're able to be opportunistic as sites open versus other cell therapies.

Yes, I believe one of our unique advantages is our iPSC cell platform, which allows us to have an off-the-shelf product model similar to monoclonal antibody therapy. We have a significant supply of manufactured doses that are already cryopreserved, with redundancies in where they are stored. Some of these doses are kept at our distributor, while others are available at our clinical sites, ensuring they are stocked on-site. We are also promoting an outpatient approach to treat patients. As we navigate out of the COVID-19 pandemic, I think we are in a particularly advantageous position to accelerate our progress more quickly than we would in traditional cell-based therapies, where sourcing patient or donor cells is necessary for each manufacturing run.

And then maybe just Scott following up on the Janssen deal, and congrats on that deal. For the individual targets that get selected, is there anything that prevents Janssen from pursuing ADCs or bispecific antibodies or naked antibodies for the same target? And if they do, is there some provision where they make your iPSC-derived cell therapy a priority? Just we've seen that in other instances, where the CAR-T as an example is the leader and then it's followed very quickly by a bispecific or an ADC. Is there anything to protect against that in the collaboration?

There's nothing to necessarily protect against that in the collaboration. The reverse might be true in this collaboration where they may already have a bispecific which we are creating a CAR NK or CAR-T cell product out of it using a binding domain that may actually already be in late-stage preclinical or clinically validated.

Just one final one Scott on the deal. You mentioned that there's no overlap with anything you're working on internally at Fate. Do they have access though to the FT538 master cell bank? Could they make use of that to kind of accelerate the development of the partner assets?

So to be clear, they don't have access to it. But certainly, we can use it. They – Janssen to be clear is handing us the binding domains. And we are building the CAR constructs. And so I think the direction you're headed in where we might see first-generation product candidates under the collaboration that arise using FT538 as a backbone? Yes, that's a distinct possibility.

Great. Well, thanks for taking the question. Congrats on all the progress.

Thank you.

Your next question comes from Alethia Young with Cantor.

Hey, guys. Thanks for taking my question or two. Congrats on the progress. One, I was just kind of curious about how you're thinking about clinical trial sites like expanding them. I noticed you referenced maybe some potential additional sites. So I just wonder, how much of a strategy will that play? And it also seems like an interesting move long term? And then when you look at the Janssen collaboration, I guess, what's the one piece you think that really is that big secret sauce? Is it the manufacturing capability? Or is it just a natural synergy that you have? Like, what do you really think is like the value add? I'm sure there was a lot of interest in people doing a deal with you guys. Thanks.

Sure. I would say, with respect to clinical sites, yeah, I mean, we're going to be aggressive in adding clinical sites. I think one of the unique opportunities that we have having a potentially outpatient therapy and having product that's available off-the-shelf is that we can move away from the centers of excellence like for instance Memorial Sloan Kettering or an MD Anderson, which have obviously pioneered CAR-T cell therapy. There's a tremendous amount of competition obviously at those centers of excellence with respect to delivering product. I think we have the opportunity to broaden the number of clinical sites that we potentially go to given the off-the-shelf nature of our product candidate. With respect to the Janssen collaboration, I think there's – I mean, I think there's multiple points of value that we see in our product pipeline and – we see in our platform and that we hope others also see in this platform. I think one of the distinguishing features of what we do and I sort of just alluded to it with the response to Jim was this notion that I think folks do believe as we move forward in the next two, three, five years in order to really address solid tumors, we will have multiplexed engineered functionality embedded into cell therapies. And I think that's very challenging to do three, four, five edits batch by batch at a cell population level. And so, being able to, for instance, engineer a single cell characterize a single cell with three, four, five edits and use that in a renewable fashion as a starting material I think just provides some really, really powerful advantages as you think about cell therapy going forward. I think that's one of the really distinguishing features of what we do being able to collapse all the engineering into literally a one-time event.

Great. Thank you very much.

Your next question comes from Yigal Nochomovitz with Citi.

Hi. This is Carly on for Yigal. Thanks very much for taking our question. First question we had was for the FT516 ongoing trial. Can you just give us a sense for where you are in the dose escalation and then what you see as kind of the key learnings from the next data update in the context of your longer-term strategy for this program?

For FT516? Yeah for FT516, we're still early in dose escalation, when obviously the COVID pandemic hit. We're continuing to add sites to the FT516 program. I think FT516 if you look at it, it is the first engineered IPS-derived cell therapy. The CD16 receptor, we think is really novel and powerful, because we can use it to hit multiple antigen targets. And so getting that first glimpse of using, for instance, FT516 in combination with monoclonal antibody therapy in this case Rituxan, I think, is going to be really interesting to us. I'd also say that the setting for FT516 as a monotherapy is AML. And there's a lot of historical precedent with respect to the use of donor-derived NK cells in the AML setting. And so being able to, for instance, benchmark over time a product candidate like FT516 or FT538 in the setting of AML, I think could be really interesting and potentially is a really powerful therapeutic given the precedent that exists with respect to NK cells and antileukemic activity in the AML setting.

Got it. That's helpful. And then just building on some of the prior questions around the Janssen deal and potential future partnering opportunities, can you talk about the process and kind of the timelines associated with developing an iPSC-derived product candidate once a partner comes to you with a desired target?

It really depends on the contributions from the partner at the start of the collaboration. For instance, in the case of Janssen, they are providing some validated binding domains that they are enthusiastic about. If a partner were to deliver us a validated binding domain and we create a CAR construct using the FT538 backbone, we could potentially have an IND candidate ready in about 18 months. However, this is contingent on the partner's confidence in providing a validated binding domain that we could utilize to develop a CAR NK or CAR-T cell product.

Great, that’s really helpful. Thanks for taking the question.

Your next question comes from Daina Graybosch with SVB Leerink.

Hi. Thanks for the questions. A couple. The first one is if you could just help us understand when we might see some clinical data for FT596, primarily but also 516, 500, and ProTmune, which I think maybe you had initially thought we'd see data in the second half.

Sure. I’ll address them one at a time, starting with ProTmune. I believe we announced that the ProTmune study was fully enrolled in November 2019. There are two key data sets for ProTmune. The first is day-100 data, where we assess the cumulative incidents of grade two through four GVHD. Our patients have completed that day-100 endpoint. The second key data set is a secondary endpoint that reflects the overall outcome of hematopoietic stem cell transplants. This composite endpoint, known as GRFS, includes moderate-to-severe chronic GVHD, relapse, and survival, with a readout at day-365. The study is currently blinded and will remain so through the evaluations at both day 100 and day 365. Therefore, we expect to see ProTmune data in the first half of 2021, assuming my calculations are correct. With respect to the iPSC-derived programs, FT500, FT516, FT596, we're not going to go patient-by-patient with respect to data so we will not do that. We will wait until we have essentially an informative group of patients through dose escalation and then provide that type of data. Obviously, we have been delayed, and we think there's going to be some delays with respect to new site initiation and patient enrollment because of the COVID pandemic. And so, we will provide more transparency as we approach the enrollment and the disclosure dates for the clinical data.

Awesome, and then my second question is on a different topic. For this new pan-tumor mic AB target, I don't think you mentioned whether it's a CAR NK or CAR-T. I wonder if you can clarify that. Also, how close is it to the Celyad CAR-T program, and what have you learned from that program as you advance yours into the clinic?

Sure. I will provide a high-level overview since we are about to reveal this information at ASGCT. At ASGCT, you can expect to see data regarding CAR MICA MICB in both NK cells and T cells. We will present some initial findings related to CAR MICA MICB for both types of cells. In terms of other programs, we have extensively researched NKG2D, which serves as a crucial activating receptor on NK cells. The targets of NKG2D, such as MICA MICB, can shed. A significant aspect of this program is our growing understanding of mechanisms related to T cell escape, and now evidence suggests that NK cell tumor escape also occurs. Shedding of stress ligands on tumor cells may be a key mechanism of tumor escape, particularly in solid tumors. This is what excites us about this program, as we believe that targeting MICA MICB, specifically the alpha 3 domain of the ligand, allows us to address the shedding issue and improve NK cell effectiveness against tumors.

All right. Thanks. Appreciate it.

The next question comes from the line of Ben Burnett with Stifel.

Good afternoon. Thanks so much for taking my question. I guess, first, can you just talk about the 516 study for COVID-19? Specifically, what exactly are sites role here? I'm just curious if you can talk to the researchers that you'd be responsible for that program. And then just as a quick follow-up how does this impact 516 inventories as it relates to the company-sponsored trials? Thanks so much.

Sure. So your second part of your question first. I mean it's not a significant drain on our inventory with respect to the inventory we have on hand with respect to FT516. You should assume that we've done more than one manufacturing, run for FT516 and we have hundreds of doses that are in fact available. With respect to how this all came about, we did – we actually did not initiate the discussions here. The infectious disease team at the University of Minnesota approached us, wanted to know if we'd be willing to supply FT516 to support a UMN-sponsored study. Obviously, the University of Minnesota has been a terrific partner of Fate Therapeutics for years. And so we were happy to agree to supply product to them. And if we can provide another tool in the arsenal to try and fight COVID-19, we're more than happy to do that. I think there is actually some strong rationale potentially for using NK cells, obviously to fight infectious disease. I think one of the things that was appealing to us as we looked at the clinical design that the University of – the folks the infectious disease team at the University of Minnesota were putting forth is again continuing to reinforce this idea of being able to give patients multiple doses. So patients in the study are actually receiving multiple doses over a week. And it's actually a very interesting study from a clinical translation learnings perspective for us that may benefit us actually on our oncology programs because the intra-patient dose escalation starts at 90 million cells, goes to 300 million cells, goes to 900 million cells all in the course of a week. So there's administration of day one, day four, day seven where you go very quickly from 90 million to 100 million cells all the way to 900 million cells. And so we will be able to – from a clinical translation perspective, we will be able to get an interesting read on what is a very high dose level in a relatively short period of time.

Okay. That's great. That's great context. And maybe just a quick follow-up to sort of the Janssen collaboration discussions that we've had. I guess I just wanted to ask about your appetite, specifically for maintaining ownership of your current clinical candidates. I guess is there a scenario where they could be on the table too?

Yes. I mean I'm not going to rule anything out. I mean anything is a possibility. I think we think that we both with respect to for instance, let's just pick 596 as well as $576 million, obviously there if you think of CD19 and if you think of BCMA, these are targets specifically in the CAR-T cell world that has been largely derisked. And we do think we have a very disruptive approach to going after the CD19 as well as the BCMA market with an off-the-shelf paradigm. And so as we look at it today and again the world can change but as we look at today, we're more than prepared to go after and pursue those opportunities on our own.

Okay. That’s fantastic. Thanks so much.

Sure.

Your next question comes from Matthew Biegler with Oppenheimer.

This is Kalpit on for Matt. Thanks for taking the question. First for the relapse prevention program for 596, are the investigators planning to include patients who received prior CAR T therapies? Or is it just going to be prior chemo-treated patients?

It's most likely prior chemo only. And so these patients are for instance they will have to have failed only one line of therapy, are eligible for autologous hematopoietic stem cell transplant and are at high-risk for relapse. So they may have only for instance received one line; have qualified for transplant but are deemed at high-risk for relapse. And I think Wayne touched on it. The rate of relapse in these high-risk patients is high and they do relapse quickly. So if you treat patients on the study and you find that a fair proportion of these are having event-free survival in excess of that, then there will be opportunities to expand the study to get a more precise read on that.

Got it. Thank you.

Your next question comes from Biren Amin with Jefferies.

Yes. Hi, guys. Thanks for taking my questions. Maybe on FT500. You've announced that you've dosed three patients with 300 million cells in combination with checkpoints. Can you just talk about how many cell doses the patients received? And I guess, can you maybe talk about the background of the patient in terms of tumor type? In particular, did you have any patients with non-small cell lung cancer, which led you to expand into that setting?

Yes, this is Scott. We have completed the treatment of the last three patients in the dose escalation phase of the study. All three patients were qualified for the second cycle, and at least some of them received all six doses. The initial hypothesis of the Phase 1 study was to analyze safety and tolerability, whether through monotherapy or in combination with checkpoint inhibitors. We did not specifically focus on non-small cell lung cancer patients during the dose escalation phase. For the expansion, we are making an informed decision based on existing literature regarding checkpoint inhibitors and non-small cell lung cancer. This includes insights into mutations that result in the down-regulation of MHC Class 1, where we believe NK cells may have a distinct advantage in targeting these tumors. Therefore, our hypothesis for pursuing non-small cell lung cancer stems more from gathered knowledge, including discussions with key opinion leaders in the checkpoint inhibitor field, rather than purely from the clinical data observed during the dose escalation.

And Scott for the non-small cell lung cancer study, what type of IL-2 support will patients be required to have? Can you just maybe provide additional color on that? As well as are you enrolling patients with certain PD-L1 baseline TMB or CD3 counts?

Yes. We are not specifically selecting based on MHC Class 1 levels at this time; instead, we are requiring a pretreatment tumor biopsy. This is essential for enrollment, and we will have the ability to classify MHC Class 1 expression levels as we bring patients on board. This information will be valuable. Regarding IL-2 support, we are enthusiastic about incorporating it since we believe it is crucial for effectively activating the NK cells. We will administer a sub-therapeutic dose with each dose of FT500.

Okay. Great. Thank you.

Sure.

Your next question comes from Mara Goldstein with Mizuho.

Hi. Can you hear me?

Yes.

Thank you. I have two questions. First, regarding MICA and MICA B, I understand they are not the only stress ligands. Can you quantify the losses in tumors relative to what would typically be considered normal, especially in comparison to the broader group of stress ligands affected by this process? I’m curious about this perspective. Secondly, concerning CAR BCMA, could you share what preclinical data might highlight the differentiation between your approach and the current field?

Sure. With respect to CAR BCMA, I'd sort of ask you to hold your question for about two days because the FT576 poster is going to be presented at ASGCT as well, I think on Wednesday or Thursday of this week. And so you will see sort of some of the differentiating features of FT576, which again includes and we are big believers in this the ability to attack multiple antigens at the same time. And so we think that's one of the unique advantages with the product candidate not that it's just off-the-shelf, but we will be able to do multi antigen targeting, for instance, in combination with an anti-CD38 mAb as an example not just the CAR BCMA. And so we're excited about that. With respect to MICA MICB, I mean, it's early totally agree that there are multiple stress ligands that can be expressed by tumor cells. And obviously NK cells can interact with those types of stress ligands. It's one of the reasons we're excited about NK cells is because NK cells have a sort of an array of activating receptors that can interact with these stress ligands. I would say if you look at certain solid tumors and I'm happy to send you some papers on this, MICA MICB as a ligand is predominantly expressed on certain solid tumors as the stress ligand. And so we think it is a very significant target for which to go after. It is a target as we mentioned that is absolutely subject to shedding though. And I think it's one of the challenges that's emerging in the setting of solid tumors is that these tumors are very smart and crafty. And they have mechanisms to escape T-cell recognition as well as NK-cell recognition. And so targeting these stress ligands in a way where you can access the solid tumor, engage the solid tumor and overcome these escape mechanisms is something we're super excited about.

All right. Thanks. Appreciate it.

The next question comes from the line of Peter Lawson with Barclays.

Thanks, Scott. Thanks for taking the questions. So just as we kind of think about the trials you've got started and starting and there's a lot of options around the platform itself and what indication of construct do you think you could get to a pivotal trial fastest?

I believe FT596 is a product candidate that is well-positioned for rapid development. We need to demonstrate safety and efficacy, but I believe it's a candidate worth considering. CD19 is a risk-mitigated target. We feel we have a highly differentiated strategy by offering an off-the-shelf approach that allows for potentially multiple doses and targeting various tumor-associated antigens. Thus, I view FT596 as a de-risked target, and I think we have a distinctly innovative product in this context. Regarding FT500, we are gaining valuable insights. However, to effectively target solid tumors, as I mentioned in this call, it will likely require several engineered components to achieve lasting responses.

Great. Thank you. Regarding your comment about using these in an outpatient setting, what percentage of your trial sites are located outside areas of excellence, and is there potential to operate beyond those areas?

We initially started at some of the top centers of excellence, and our clinical trial sites are publicly listed on clinicaltrials.gov. However, we are now activating some trial sites remotely that are not typically considered top centers, like Memorial Sloan Kettering or MD Anderson. For example, while San Diego is known for cancer research, we are working with Moores Cancer Center at UCSD, which is more community-based compared to MD Anderson.

Great. Thank you. And then on the expansion in non-small cell lung cancer, the FT500, when can we see data? And then how should we think about I guess teasing out any effects that IL-2 or PD-L1 potentially adds?

Yes. Regarding IL-2, we are administering subtherapeutic doses, which is quite common. Consider what we've observed in programs like TIL therapy, where subtherapeutic doses of IL-2 are also utilized. Regarding the contribution of PD-L1 and the checkpoint inhibitor, it's important to note that these patients had received the same inhibitor they previously progressed or failed on. However, it's been shown that patients can indeed be resensitized with a checkpoint inhibitor. We will be able to determine how response rates compare to the checkpoint inhibitor alone in patients who have already failed that therapy.

Great. Thanks so much. Thanks for taking the questions.

I am showing no further questions at this time. I would now like to turn the conference back to Mr. Scott Wolchko.

Thank you. Thank you everyone for participating in today's call. We look forward to talking to you in the near future. Be well.

Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.