Fate Therapeutics Inc (FATE) Q4 2020 Earnings Call Transcript

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Fate Therapeutics Inc (FATE -3.08%)
Q4 2020 Earnings Call
Feb 24, 2021, 5:00 p.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Welcome to the Fate Therapeutics Fourth 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 on 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. The floor is yours.

Scott Wolchko -- President and Chief Executive Officer

Thank you. Good afternoon, and thanks everyone for joining us for the Fate Therapeutics fourth 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 Investor section of our website under Press Releases. In addition, our Form 10-K for the year ended December 31, 2020 was filed shortly thereafter and can be found on the Investor section of our website under Financial Information.

Before we begin, I'd 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 can 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 close of market today as well as the risk factors in the company's SEC filings included in our Form 10-K for the year ended December 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 the 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. Wayne Chu, our Senior Vice President of Clinical development; Ed Dulac, our Chief Financial Officer; Dr. Dan Shoemaker, our Chief Scientific Officer; and Dr. Bob Valamehr, our Chief Development Officer.

Today we will review some of the clinical data for FT516 and FT596 programs that we shared at the Ash Conference in December, highlight our clinical progress and plans for each of our disease franchises and discuss our advancement toward clinical development of our next wave of Multiplexed Engineered IPS derived cell product candidates for solid tumors.

Over the past several years, Fate Therapeutics has pioneered an unprecedented vision for cell therapy, one where the significant limitations of patient and donor derived cell therapies are overcome through induced Pluripotent Stem Cell Technology, Clonal Master Engineered iPSC lines and off the shelf multiplex engineered cell products. Within the past several months, we have made great strides in delivering on this vision for the benefit of patients with cancer. We have demonstrated that iPSC derived NK cells can be mass produced, cryopreserved and administered off the shelf to patients in the outpatient setting.

We have demonstrated the clinical safety and the therapeutic activity of engineered iPSC derived NK cells having shown that our off the shelf cell product candidates can drive patient responses, including complete responses in patients with relapsed refractory disease. We have demonstrated that treatment schedules consisting of multiple doses and multiple cycles of IPS derived NK cells can be well tolerated without evidence of host rejection and that patient responses can deepen through additional dosing. We have demonstrated that our proprietary high affinity non-cleavable CD16 Fc receptor, a poor functional component used in our IPS derived NK cell product platform can effectively synergize with and enhance the mechanism of action of tumor targeted antibodies. And we have demonstrated that our IPS derived NK cell product candidates can be engineered with multiple components of synthetic biology to attack cancer and that we can successfully work with the FDA to bring these first of kind multiplexed engineered cell products to patients. We are very encouraged by the clinical progress we have made across our disease areas and we look forward to a promising year ahead.

In the disease area of B cell malignancies, we are encouraged by the interim data we reported in December from our Phase 1 study of FT516 in combination with Rituximab for patients with relapsed refractory B cell lymphoma. As of November 16, 2020, data cut off three or four efficacy of valuable patients in dose cohorts two and three achieved an objective response with two patients achieving a complete response. We believe these clinical data are compelling on multiple fronts. All four patients had been treated previously with at least two lines of Rituximab containing regimens, including one patient with diffuse large B cell lymphoma, who was most recently refractory to Rituximab containing regimen and achieve the complete response following treatment with FT516.

The outpatient treatment schedule, consisting of two cycles of three weekly doses of FT516 was well tolerated. And there was clinical evidence to suggest that the second FT516 treatment cycle conferred clinical benefit. One patient who has achieved a partial response on an interim assessment following the first FT516 treatments cycle achieved a complete response following the second FT516 treatment cycle. There were no events of any grade of CRS, neurotox or GvHD and there were no evidence of Tier B cell mediated host rejection. Collectively, early clinical activity of FT516 suggests that the product candidates' high affinity non-cleavable CD16 receptor can effectively synergize with Rituximab to drive complete responses in patients that have relapsed following or are refractory to Rituximab containing regimens. And the safety profile of FT516 suggests that multiple doses and multiple cycles can be administered in the outpatient setting.

Dose escalation with FT516 is currently ongoing at 900 million cells per dose and we are preparing to initiate dose expansion in relapsed refractory B cell lymphoma upon clearance of this dose cohort. In addition, given the safety activity and mechanism of action of FT516, we're currently considering earlier line opportunities for clinical investigation of FT516 in B cell lymphoma, where CD20 targeted monoclonal antibody therapy regimens are used as standard of care.

At Ash we're also pleased to share a clinical vignette of the second patient treated in our Phase 1 study of FT596. The case study described a heavily pre-treated patient with diffuse large B cell lymphoma, who had previously received seven prior treatment regimens and was most recently refractory to an experimental NK cell regimen consisting of Cy/Flu lympho conditioning, followed by ex vivo expanded donor derived NK cells, IL-2 plus Rituximab. The patient was administered a single dose cycle of 30 million cells of FT596s monotherapy and achieved a partial response at day 30 following administration. Notably, upon review of the patient's clinical course, the FDA consented to administration of a second single dose cycle of FT596, which was administered on day 47 and resulted in a deepening response as evidenced by further decreases in both tumor size and metabolic activity. No DLPs, no FT596 related SAEs and no events of any grade of CRS, ICANs or GvHD were reported by the investigator.

We believe this patient case study is significant on a few fronts. Since FT596 was administered as a monotherapy, this provides a first clinical demonstration that our proprietary car construct optimized for NK cell biology, which contains an NK G to D transmembrane domain, 2B4 co-stimulatory domain and a CD3-zeta signaling domain is active. Additionally, the patient achieved a partial response without any events of any grade of CRS, ICANs or GvHD suggesting that CAR NK cells may have a differentiated safety profile as compared to CAR T cells. And the patient's response deepened with a second single dose cycle of FT596. Once again underscoring that follow on doses and cycles of IPS derived NK cells can be safely administered and confer clinical benefit.

On this last point, we are encouraged by the patient's partial response at day 30. However, we continue to believe that relapse refractory patients with aggressive cancers will be best served by administration of multiple doses during the first weeks of treatment. It is well documented that adoptively transferred NK cells persist for short duration that adoptively transferred cells, including CAR T cells can undergo significant changes in phenotype and function in the days and weeks following administration, and that the critical period for maximal anti-tumor activity is during the first days and weeks following administration. To this end, we plan to submit a protocol amendment to the FDA in the coming weeks to enable multi-dosing of FT596 within the first 30-day treatment cycle.

Under the current clinical protocol, dose escalation with FT596 for the treatment of B cell lymphoma is ongoing in the second dose cohorts of 90 million cells as monotherapy and in combination with rituximab for multi-antigen targeting. Additionally, the first patients with chronic lymphocytic leukemia have been treated in the first dose cohort of 30 million cells as monotherapy. And we plan to begin enrollment in combination with Obinutuzumab for multi-antigen targeting upon clearance of the first monotherapy dose cohort. We also continue to make great progress in pioneering the clinical development of IPS derived CAR T cells for cancer. Last year, we successfully worked with the FDA to clear the first ever IND application for an IPS derived CAR T cell product candidate and we are now preparing to initiate a multi-center Phase 1 clinical trial for FT819 across three types of B cell malignancies, chronic lymphocytic leukemia, acute lymphoblastic leukemia and B cell lymphoma.

Notably, each disease type will enroll independently and each indication will evaluate three treatment regimens single dose of FT819, single dose of FT819 plus IL-2 cytokine support and three fractionated doses of FT819. In preparation for study initiation, we've completed our first GMP manufacturing run and continue to conduct as a validation and product release testing for FT819. We also continued to innovate and optimize our manufacturing process, including under our collaborations with ONO and Janssen and we have initiated a second GMP manufacturing run of FT819 to implement certain improvements. We expect to treat the first patients with FT819 in the middle of 2021.

AML is our second disease area of interest and one where there is strong clinical precedent for donor derived NK cell therapy. Most clinical studies in the donor derived NK cell field, however, have been conducted as single site investigator initiated studies, as patient eligibility has been significantly limited by the requirement to use NK cells that are matched to the patient that are manufactured solely for that patient and that are delivered fresh as a single dose therapy. We believe there is a significant therapeutic opportunity for off the shelf NK cell therapy for patients with relapsed refractory AML, one where multiple doses of a cryopreserved NK cell product can be thought and infused to significantly reduce or eliminate leukemic burden, enabling patients to qualify for the potentially curative procedure of allogeneic stem cell transplant.

In 2020, we made strong progress with our FT516 and FT538 programs for the treatment of relapsed refractory AML. Dose escalation with three weekly doses of FT516 is currently ongoing at 900 million cells per dose. Additionally, we successfully worked with the FDA to clear our IND application for FT538, the first ever CRISPR-edited IPS derived cell product to advance the clinical investigation in the U.S. FT538 is our third generation product candidate designed to innate immunity and is derived from a Clonal Master iPSC line uniformly engineered with three functional components, our high affinity non-cleavable CD16 FC receptor and IL-15 receptor fusion that augments NK cell activity and the deletion of the CD38 gene, which confers resistance to oxidative stress and prevents fratricide when combined with CD38 targeted monoclonal antibody therapy. Dose escalation with three weekly doses of FT538 is currently ongoing at 100 million cells per dose for the treatment of relapsed refractory AML.

At the European hematology meeting in 2020, a presentation caught our attention that highlighted the potential therapeutic role of CD38 targeted monoclonal antibody therapy in treating elderly patients with AML. An assessment of bone marrow samples from newly diagnosed elderly AML patients showed CD38 expression on leukemic blasts in 239 out of 241 samples tested, strongly indicating the potential of CD38 as a therapeutic target for AML. To exploit this potential and to promote NK cell mediated ADCC, we are assessing FT538 in combination with daratumumab and FDA approved CD38 targeted monoclonal antibody therapy.

The Phase 1 clinical trial which is sponsored and managed by investigators from the Masonic Cancer Center University of Minnesota is designed to assess three weekly doses of FT538 in combination with daratumumab and patient with relapsed refractory AML. We expect this trial to initiate in mid-2021.

Our third disease area of interest is multiple myeloma and we are very excited about our potential to generate compelling clinical data over the next 12 months with both our FT538 and FT576 programs. In December the FDA allowed our IND application for FT576, the first ever cell therapy to incorporate four functional anti-tumor components, including a CAR targeting B cell maturation antigen. Importantly, our BCMA binding domain is novel. And in preclinical studies, it has shown greater killing of target cells with low expression levels of BCMA in comparison to other BCMA binding domains.

The clinical protocol for Phase 1 clinical trials FT576 includes dose escalation, both as a monotherapy and in combination with daratumumab to enable dual antigen targeting of BCMA and CD38 for myeloma cells and approach that we believe is highly differentiated and holds best-in-class potential. Additionally, the protocol includes an assessment of both single dose and multi dose treatment regimens to maximize the therapeutic index during the first 30 days following infusion. Similar to our approach in lymphoma, we're beginning clinical investigation of multiple myeloma by leveraging our high affinity non-cleavable CD16 receptor and we are combining FT538 with daratumumab to maximize ADCC. While daratumumab effectively targets CD38 expressed on multiple myeloma cells and induces cell death. It also induces NK cell fratricide, which may impair the effectiveness of ADCC.

In addition, NK cell function is often impaired in patients with multiple myeloma, further reducing the potential therapeutic activity of daratumumab. Collectively, preclinical and clinical observations suggest a potential therapeutic benefit of maintaining NK cell numbers and function. In the second quarter, we expect to initiate enrollment of FT538 in combination with daratumumab and the first dose cohort of three weekly doses of 100 million cells for patients with relapsed refractory multiple myeloma who have failed at least two lines of therapy.

Over the next 12 months, we plan to substantially increase our clinical investigation in the area of solid tumors. We're certainly enthusiastic about the therapeutic potential of NK cells to address significant unmet needs across a wide range of solid tumors. And we are pursuing multiple avenues of investigation for clinical benefit. Since NK cells have the innate ability to recognize and directly kill cancer cells that lack MHC class 1 antigen presentation, we believe NK cells may play a unique role in attacking tumors that have evaded T cells and are resistant to checkpoint inhibitor therapy.

We're currently enrolling the dose expansion stage of the FT500 Phase 1 clinical trial for patients with non-small cell lung cancer or classical Hodgkin's lymphoma, who are refractory to or who have relapsed on checkpoint inhibitor therapy. We intend to treat up to 15 patients, administering up to six doses of FT500 at 300 million cells per dose, each with IL-2 cytokine support in combination with the checkpoint inhibitor on which the patient failed or relapsed. Additionally, we are leveraging our high affinity non-cleavable CD16 receptor in combination with FDA approved monoclonal antibodies to promote ADC for solid tumors. We are currently enrolling patients in the second dose cohort of our Phase 1 study of FT516 in combination with Avelumab, an ADCC competent, anti-PD-L1 checkpoint inhibitor therapy. We are also actively considering additional settings to exploit the broad potential of ADCC, including with FT538 and other tumor targeting antibodies in solid tumors.

And finally, we believe our iPSC product platform represents the ideal framework for designing and developing multiplex engineered CAR NK cell product candidates. And we currently have four novel IPS derived CAR NK cell programs for solid tumors undergoing preclinical development. These programs include three wholly owned programs and one program under our collaboration with Janssen. During 2021, we expect to submit an IND for FT536, our proprietary CAR NK cell program targeting the Alpha 3 domain of the pan-tumor associated stress antigens MICA/B, as well as for FT562, our first CAR NK cell program targeting an undisclosed antigen under our collaboration with Janssen.

And finally, I want to take a moment to note that data on the primary and secondary endpoints in our randomized controlled and double blinded Phase 2 protect clinical trial of ProTmune are scheduled to be available in the second quarter of 2021. ProTmune is our investigational next generation donor derived cell graft for patients with hematologic malignancies, undergoing allogeneic mobilized peripheral blood transplant. The primary efficacy endpoint of PROTECT is cumulative incidence of grades two through four acute GvHD by day 100, where clinical studies have shown that up to 60% of patients undergoing matched unrelated donor transplant experience grade two through four acute GvHD.

The second efficacy endpoint of PROTECT is the proportion of subjects alive without relapse and without moderate or severe chronic GvHD, or GRFS by day 365 where clinical studies have shown that only about 20% of patients successfully achieved GvHD free, relapse free survival at one year. That statistical analysis plan is designed to independently assess both primary and secondary endpoints.

I would now like to turn the call over to Ed to highlight our fourth quarter financial results.

Ed Dulac -- Chief Financial Officer

Thank you, Scott. Turning to our financial results, revenue was $15.9 million for the fourth quarter of 2020 compared to $2.8 million for the same period last year. Revenue in the current quarter was derived from our collaborations with Janssen and ONO pharmaceutical.

In December, we shared with ONO, a preclinical data package for an iPSC derived CAR T cell product candidate incorporating ONOs proprietary antigen binding domain targeting a cancer specific antigen expressed on certain solid tumors. Based on these data ONO elected to continue preclinical development of the product candidate under the collaboration and we received a $10 million milestone fee from ONO. As a reminder, ONO maintains an option to develop and commercialize the iPSC derived CAR T cell product candidate in all territories of the world. And we retain the right to co-develop and co-commercialize the product candidate in United States and Europe under a joint arrangement where we are eligible to share at least 50% of the profits and losses. In the fourth quarter, we recognized $6.1 million of the $10 million milestone payment received from ONO.

Research and development expenses for the fourth quarter of 2020 were $39 million compared to $25.2 million for the same period last year. The increase in R&D expenses was attributable primarily to an increase in employee headcount and compensation, including share based compensation and expenses associated with the facility lease for our new corporate headquarters. General and administrative expenses for the fourth quarter of 2020 were $10.3 million compared to $6.7 million for the same period last year. The increase in our G&A expenses was attributable primarily to an increase in headcount and employee compensation, including share based compensation. Total operating expenses for the fourth quarter of 2020 were $40.5 million net of $8.8 million in non-cash share based compensation expense.

In the fourth quarter, we recorded a non-cash $20.1 million non-operating expense associated with the fair value of contingent milestone payments under iPSC derived CAR T cell collaboration with Memorial Sloan Kettering. In the event a certain clinical milestone is achieved with an iPSC derived CAR T cell product candidate, up to three milestone payments may be owed to MSK based on subsequent trading values of the company's common stock ranging from $50 to $150 per share. These milestone payments in the aggregate total up to $75 million and no amounts have been paid or are currently owed to MSK. We will remeasure this liability currently valued in the aggregate at $47.7 million on a quarterly basis and changes in the fair value will be recorded in our earnings as a non-operating income or expense.

The company ended the fourth quarter of 2020 with $483 million of cash, cash equivalents and investments. This does not include the aggregate net proceeds of approximately $432 million received from our January 2021 public equity offering. Common stock outstanding was 88 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. The common stock balance does not include the 5.1 million common shares issued as part of our January 2021 public equity offering.

I would now like to open the call to questions.

Questions and Answers:

Operator

[Operator Instructions] Your first question comes from the line of Robyn Karnauskas from Truist Securities.

Srikripa Devarakonda -- Truist Securities -- Analyst

Hey guys, this is Kripa for Robyn. Thank you so much for taking my call and congratulations in all the progress. One question I had was in addition to your partnerships that with ONO and Janssen, what is your strategy and bandwidth for any additional potential partnerships? And especially if those that include your wholly owned products?

Scott Wolchko -- President and Chief Executive Officer

Sure, happy to answer that. I think we absolutely have a platform that is amenable and we have bandwidth to do additional partnerships as well as increase the existing partnerships if we chose to do so.

Srikripa Devarakonda -- Truist Securities -- Analyst

Great. And then, you have you plan to start initiate an AML program with FT538, would you need to see data from the monotherapy trial before you initiate the combo? Or can they be run in parallel? And also, it seems like you're continuing to enroll patients in the FT516 trial for AML, can you maybe talk about your overall strategy in AML?

Scott Wolchko -- President and Chief Executive Officer

Sure. So I'll start long-term vision, long-term vision in AML. I think at the end of the day, we're very interested in targeted strategies for AML. Certainly, historically, non-engineered donor derived NK cells have shown activity, I think in about 20% to 25% of patients donor derived NK cells, again, not engineered, not targeted, in any express way, have been able to drive responses. But I do think there's significant room for improvement, just like we've seen in other hematologic malignancies. And so the long-term strategy in AML, I think would be to absolutely have a targeted approach. It was one of the reasons we were really intrigued by the data that we saw at EHA with respect to CD38 expression on leukemic blasts and potentially, which we're now doing combining FT538 with daratumumab in AML, as a first means of looking at a targeted strategy.

Operator

Your next question comes from the line of Alethia Young from Cantor.

Alethia Young -- Cantor -- Analyst

And certainly it's been an exciting past three or four months. I just wanted to kind of go back to the notion of r dosing and the conditioning regimen review. I've got a couple questions I think recently around how viable it might be to use a conditioning regimen kind of if you had to do it -- you've had to deal with couple of times. And maybe the second part of that question is, are you considering maybe a lighter version of a conditioning regimen? I mean, so far, the profile has seemed pretty benign as far as the drug itself? Thanks.

Scott Wolchko -- President and Chief Executive Officer

Wayne and I are not in the same room. Wayne, are you there? You want to address?

Wayne Chu -- Senior Vice President, Clinical Development

That's a great question. Thank you for asking. I think that one of the fundamental questions, for our clinical programs and I don't speak just for the Fate portfolio, but I would say all sponsors are developing the cellular therapies, is really defining the nature of the conditioning regimen. We currently are utilizing the combinations of fludarabine and cyclophosphamide across our trials. I should note that there are some differences with respect to the schedule and the doses that we're using, depending on the indication being tested. So I think one of the things that we're trying to understand, with our current slate of trials, is directly addressing the question you raised around what is the tolerability of a patient to receive potentially multiple rounds of condition that's consistent fludarabine and cyclophosphamide. And I think it's probably worth mentioning the fact that the combination of Flu/Cy does have clinical precedent. For example, in patients who are newly diagnosed with chronic lymphocytic leukemia, one of the more common immuno-chemotherapy regimens is the combination of Rituximab with Flu and Cy. And so there is some clinical precedence to the idea of being able to give multiple rounds of Flu/Cy containing regimen.

But I think an important question which we plan to address as part of our ongoing studies is to see whether or not things like dose adjustment to the fludarabine and cyclophosphamide dose are feasible, not only from a patient safety and tolerability perspective, but also with respect to their ability to support with pharmacokinetic profile of our product candidates. We are also very interested in understanding whether or not other combinations of therapies can be used as conditioning such that we're not necessarily wed to a paradigm that involves fludarabine and cyclophosphamide conditioning. And those ideas are all being on the table and we hope to include initial clinical experiments to address that question in the not too distant future as part of our current study.

Operator

Your next question comes from the line of Michael Schmidt from Guggenheim.

Michael Schmidt -- Guggenheim -- Analyst

I had two actually, one bigger picture question around pipelines strategy, obviously, your engineered NK cell pipeline is much more expensive than your CAR T program at this point. I was just wondering longer term how you think the Fate portfolio may evolve? And will it be maybe more NK cell-centric as opposed to CAR T focus? So that's my first question. And I have a follow up.

Scott Wolchko -- President and Chief Executive Officer

Sure. I can start with that. Obviously, you're well aware of the history of the company. And we certainly got a head start with NK cells as compared to T cells. There's a long history of using IPS cell technology to derive T cells, which quite honestly started with our collaborator, Memorial Sloan Kettering, Michel Sadelain. And initially, he was able to develop gamma delta T cells and published on that, I want to say probably around 2015. Our collaboration with him was expressly around making alpha beta T cells. And we think, we've actually nailed that quite well and are really excited about advancing 819 into clinical development this year. I would sort of underscore, yes, we are absolutely more advanced on NK cells. And we are pushing very hard with respect to the NK cell side of our pipeline and are quite honestly super excited about what we're seeing. But let's also acknowledge that there's been some really exciting results and patient responses that have been generated with T cells. And our collaborations including our ONO collaboration and our Janssen collaboration do involve the development of IPS derived CAR T cell candidates. So I would say that while for instance, our NK cell pipeline is more mature, I would not take that as an indication that we are significantly betting on an NK cell approach over a T cell approach. We're absolutely developing both cell types aggressively.

Michael Schmidt -- Guggenheim -- Analyst

Great, thanks. And then, a question on 516, specifically, you did mention that you're now planning the first expansion cohort on DLBCL. And I was just wondering around the dosing paradigm, I know you've talked about giving multiple doses over time et cetera. At the same time, you have seen already deep and good responses after only giving one or two cycle and the dose escalation. So I was just wondering how you thinking about the dosing paradigm in this expansion cohort? Will this be a fixed cycle or fixed time duration, dosing paradigm? Or will it be a chronic regimen more akin to an monoclonal antibody therapy?

Scott Wolchko -- President and Chief Executive Officer

Yes. So, great question. I think what you will see us do as part of dose expansion is continue with where we have seen success. So we will likely kick off a dose expansion that includes the existing treatment paradigm with FT516. At the same time, you should not be surprised if we also experiment with other treatments cycles with FT516, which may involve for instance, we were just discussing Cy/Flu, it may involve less Cy/Flu, it may involve a conditioning regimen that is not Cy/Flu and it may involve longer duration of dosing of FT516. But there will at least be a core arm of dose expansion that involves the existing treatment paradigm where we are seeing and are excited by the responses.

Operator

Next is from Yigal Nochomovitz from Citi.

Yigal Nochomovitz -- Citi -- Analyst

I had a broad on your myeloma franchise strategy, obviously, there are two programs for myeloma and combo with daratumumab with [indecipherable] FT576. So can you talk about the development strategy there? Are you prepared to advance both combo regimens into later stage trials? Or is your objective to settle on one data combo after you're done with Phase 1?

Scott Wolchko -- President and Chief Executive Officer

Yes, it's a great question. I think it's too early for us to say what our long-term strategy is necessarily. I mean, we have to see sort of what the profiles of both product candidates are. Obviously, we are really encouraged by, if you go to the lymphoma side, we're super encouraged what we're seeing with FT516 and we're pushing FT516 aggressively forward even though we have FT596. And we're excited by FT596, there may be opportunities for both programs in different lines of treatment, absolutely. And I think we're approaching myeloma, from that same perspective, that we're very open minded, we're going to let the data guide us, the clinical data guide us as to the potential for the product candidates. Generally, I will still continue to say, I mean, I do think multi-antigen targeting offers best-in-class potential, but obviously that needs to play out in the clinic and there's very few multi-targeted programs in clinical development of any kind whether IPS derived or patient or donor derived.

I would say today, I mean, certainly our confidence has been significantly bolstered in our proprietary CD16 receptor and its ability to promote ADCC with monoclonal antibody therapy.

Yigal Nochomovitz -- Citi -- Analyst

Okay, thanks. And then turning to AML, the EHA data that you mentioned, the 239 and the 241 expressing CD38 is obviously very interesting. Is that a fair assumption, therefore, that for this combo study, that you've announced the 538 cluster, that you're not going to do any screening for CD38? You're just going to take AML patients?

Scott Wolchko -- President and Chief Executive Officer

That's correct. We're not screening for CD38 in advance, but obviously, in getting bone marrow biopsies we'll be able to assess for them.

Yigal Nochomovitz -- Citi -- Analyst

Okay. And then just one question on your preclinical program, on the CAR B7H3, is that the correct expectation that the multiplex engineering is going to include the high affinity non-cleavable, CD16 and the IL-15 receptor fusion? And are there other functionalities beyond those two that you might be developing for this program?

Scott Wolchko -- President and Chief Executive Officer

Sure, I'll let Bob answer that question. But before I turn it over to Bob, because I know Bob will talk about all the unique features we are putting into the product candidate. Let's keep it to what we've publicly disclosed.

Bob Valamehr -- Chief Development Officer

Sure, thanks, Scott. And obviously, we're very excited about the ability to put multiple things and we are going to add a couple of more components. And we'll be talking about those things later this year at this conferences in the second half of the year, but expect some added bells and whistles to CAR B7H3 program beyond what we have today to add further attributes for the purpose of going to solid tumor settings.

Yigal Nochomovitz -- Citi -- Analyst

Okay. Thank you very much.

Scott Wolchko -- President and Chief Executive Officer

I would say generally, therefore, where we're starting in solid tumors, is building off of the FT538 backbone, which already has three edits and includes the CD16 receptor.

Operator

Your next question comes from the line of Mara Goldstein from Mizuho.

Mara Goldstein -- Mizuho -- Analyst

A question on the BCMA program in multiple myeloma and I'm just wondering how you view what will ultimately be the true competitive landscape for the programs on the NK side that you're working on relative to what we see currently in the clinical marketplace today.

Scott Wolchko -- President and Chief Executive Officer

I think that's going to continue to be a significant amount of innovation in the myeloma space. And obviously, we are partnered with Janssen, who is a company that has arguably the leading franchise in myeloma and has probably at least today a best-in-class CAR BCMA product candidate, if that is patient derived. So I do think the landscape in myeloma, given the very nature of that disease is going to lend itself to off the shelf treatment. I think it's going to lend itself to duration of therapies. And I do think it will lend itself today, given there are relapse rates that are still meaningful and significant to a multi-pronged approach to the disease, including embedding multiple mechanisms of action within the cell therapy. I mean, if you look at today, myeloma, it's littered with combination therapies, which bring multiple mechanisms actions to attack the plasma cells. I think long-term as you think about how you attack myeloma and potentially try and cure it, it's going to take multiple mechanisms of action. And so that's one of the things we're super excited about -- with a cell therapy approach, especially IPS derived. You can embed those multiple mechanisms of action within a single modality, the cell therapy.

Mara Goldstein -- Mizuho -- Analyst

Okay. I'd like to just ask what you're thinking for this year in terms of your approach to releases data, exiting last year, you had said that you would wait till you have, sort of critical mass and cohorts. So how are you guys thinking about it this year?

Scott Wolchko -- President and Chief Executive Officer

Sure, I'll let Ed tackle that.

Ed Dulac -- Chief Financial Officer

Yes. We're trying to consolidate things into a more manageable digestible format of disease areas. And so similar to what we did at ASH this year around CD16 biology, I think you'll see us do a disease oriented approach. And I think there is four major milestones to look forward to in 2021. The first one is likely to be around AML where we get into late spring or early summer we have both FT516 and FT538 now dosing patients in AML. So we'll have some updates from those programs, call it by middle of the year. Shortly thereafter, we'll probably revisit lymphoma where we have both FT516 in combination with Rituximab, as well as the ongoing monotherapy in combination with Rituximab for FT596. The third major milestone will probably come in the third quarter and it'll be emphasizing solid tumors where we have FT500 ongoing in an expansion. And we're making good progress there, as well as what Scott mentioned in his prepared remarks around FT516 in combination with Avelumab. We also may have an opportunity to talk about the IND filings that we also referenced around FT536, our MICA and MICB program, as well as the progress we're making with Janssen and again in Amgen, it's not been disclosed, but we'll plan to file an IND. So we have quite a bit going on clinically, but also preclinically in terms of new innovation around solid tumors that we'll talk about in the third quarter.

And then lastly, and fourthly around ASH, we'd like to have a good presence in multiple myeloma with FT538 in combination with daratumumab and then a small but hopefully good number of patients in FT576, for which we clear the IND at the end of last year and will begin to those patients as we get into the second half of this year. So quite a bit going on clinically focused on disease areas. And as we get into the fourth quarter with ASH specifically, we could use it as an opportunity to revisit lymphoma, or additional data as well. So, lots of clinical data set for 2021 around 14 times [Phonetic] of the year beginning mid-year with AML.

Scott Wolchko -- President and Chief Executive Officer

As well as AML at ASH potentially too.

Operator

Next question is from Matt Biegler from Oppenheimer.

Matt Biegler -- Oppenheimer -- Analyst

So, maybe I missed this but if you could just maybe walk me through 596s planned protocol amendment in terms of dosing? Is there going to be the same dose you have now divided out over several infusions? So I know you're on 90 million. Now, would it be like, let's say 30 million over three doses and I guess what you're doing with 516 and 538 or just any color you can give there might be helpful.

Scott Wolchko -- President and Chief Executive Officer

Yes. I think our plan would be to the dose level where currently cleared on, we would begin multi-dosing that clear dose. So if we're cleared, for instance, let's just pick 90 million cells. Let's say we're cleared 90 million cells as a single dose, we may have a protocol where it's three doses of 90 million cells each.

Matt Biegler -- Oppenheimer -- Analyst

Oh, OK. Interesting. That's great. Cool.

Scott Wolchko -- President and Chief Executive Officer

I mean, if you go back, I mean, the analogy is, if you look at the 819 protocols that we have, where the 819 protocol has single dose and multi dosing, as well as the 576 protocol that has single dose and multi dosing, you essentially clear a single dose level of say, pick it 100 million cells. Once you clear that single dose level of 100 million cells, you can begin multi dosing with that cleared dose level. So you could do 2 100 million cell doses.

Matt Biegler -- Oppenheimer -- Analyst

Got it, that make sense. Then I had maybe more of a subjective question. But have you noticed any uptick in patient recruitment or investigator interest in your trials following the ASH data set? Obviously, a lot of the indications are going after are pretty competitive in terms of investigational therapies. So just, any type of subjective insight you have would be helpful?

Scott Wolchko -- President and Chief Executive Officer

Yes. I definitely think we've seen a lot of interest and there has historically been a lot of interest in our IPS derived cell therapy programs. Part of the challenge that we deal with today is, we are in dose escalation. So we're gated right by how fast we can potentially move. So, today we're focused on a core number of sites that we think can help us manage through dose escalation in efficient way, but obviously, once we get to dose expansion play for instance, like with FT516, we have the potential to open up that -- to open that up much more broadly. And yes, we think there's significant interest there.

Operator

Next question is from Ben Burnett from Stifel.

Carolina Ibanez Ventoso -- Stifel -- Analyst

This is Carolina Ibanez Ventoso on for Ben Burnett, thank you for taking our questions. I was wondering, can you provide any color on the type of high risk patients been enrolled into the University of Minnesota relapsed prevention study? And when might we get a look at clinical data there?

Scott Wolchko -- President and Chief Executive Officer

Sure. Wayne, do you want to take that? I mean, with respect to clinical data? I mean, I'll jump on that. Obviously, it's an investigator initiated study. So we'll work with the University of Minnesota with respect to clinical data. I would not expect clinical data before ASH, though on that program at the earliest given that the study is a relapse prevention study. But go ahead Wayne.

Wayne Chu -- Senior Vice President, Clinical Development

Yes. With respect to the study design, the way it goes is that patients with high risk B cell lymphoma and these are patients that have relapsed or there are refractory from their initial therapy. And then these are patients who otherwise would undergo high dose chemotherapy, followed by autologous stem cell transplant. And so the design of the study is essentially to take that high dose chemotherapy followed by autologous stem cell transplant and then add the combination of FT596 plus rituximab following transplant. And so that's where the relapse prevention comes from because we know historically that patients who undergo autologous stem cell transplant, at least half of them will still have relapsed disease following transplant. And so one of the primary endpoints for the study is essentially relapse free survival to see whether or not we can increase the percentage of patients who are relapse free, after following autologous transplant.

Carolina Ibanez Ventoso -- Stifel -- Analyst

Okay, got it. And then, we haven't seen much evidence of CRS or neurotoxicity with regarding NK cells of lymphoma, do you take a similar result with current NK in the multiple myeloma setting?

Scott Wolchko -- President and Chief Executive Officer

This is pure speculation. Go ahead, Wayne.

Wayne Chu -- Senior Vice President, Clinical Development

It's pure speculation, of course, but I think that we have been encouraged by what we have seen with other NK cell product candidates, particularly those in lymphoma, where in contrast, to CAR T therapies that are targeting the same antigen and CD19. We certainly don't see the frequency nor the severity of cytokine release syndrome or neurotoxicity have been observed with CAR T. And as Scott mentioned, in our FT516, and FT596 dated today, we haven't seen any grade CRS or neurotoxicity. So, for what it's worth, we're encouraged by that and we hope to see the same pattern in our myeloma programs.

Operator

Next question is from Biren Amin from Jefferies.

Biren Amin -- Jefferies -- Analyst

Maybe on 538. With a combination with dara and multiple myeloma, I think you stated that first dose at 100 million cells in patients who have failed at least two lines of therapy. Can you just talk about, I guess, prior lines of therapy because typically, I guess, in, with the BCMA CARs, we're seeing a median of about five or six lines of therapy. Are you expecting patients at third line in that trial? Or would you expect more refractory patients, and this is just simply like the inclusion criteria?

Scott Wolchko -- President and Chief Executive Officer

Sure. Go ahead, Wayne.

Wayne Chu -- Senior Vice President, Clinical Development

Yes. So, I mean, it's a fair question. From an eligibility standpoint we say that patients, have to have received two prior lines of therapy not just with respect to standard myeloma agents, such as a proteasome inhibitor and so on and so forth. But I think realistically, as we begin to enroll patients on this trial, at least initially, we would expect to see patients who received more than just two prior lines of therapy and we'll probably be seeing a patient population akin to -- but what has been enrolled with respect to the BCMA directed CAR T therapies.

Biren Amin -- Jefferies -- Analyst

Okay, that's helpful. And then, you mentioned the focus on the T cells earlier, Scott. Can you maybe just give us a status update on FT819? I think the IND cleared last July, on clinicaltrials.gov, the design was up in November. I guess, what are the steps you need in order to achieve patient dosing? And then, a question off of that is, there was a paper I think last month from Takeda researchers, I think lead authors, Eric Gucci, talking about, just iPSC cell differentiation for T cells and talked about, I guess, challenges with CD4s in particular versus CD8. I'm not sure if you saw that paper but if you could maybe comment on your efforts. And what you've seen with differentiation on CD4s versus CD8s.

Scott Wolchko -- President and Chief Executive Officer

Sure. Bob is nodding his head. So I'll let Bob answer the second question. The first question is, we've completed the first manufacturing run for 819. We're currently doing product release testing on that batch that we manufactured. Obviously, getting to the point you're making and Bob will discuss, we think there's obviously continued opportunity for process improvements with respect to developing out really high quality alpha beta T cells. And we're working on some of those improvements in parallel in real-time, including under our collaborations with ONO and Janssen. And we have kicked off a second manufacturing run where we've implemented those improvements. And so we're continuing to do a little bit of work assessing the improvements and we've guided that we will enroll the first patient in the middle of this year.

Bob Valamehr -- Chief Development Officer

A follow up Scott's point, obviously referring to the nature communication study, where they took T cells and the reprogram. So there was no TCR engineering. And they had the -- even though they had challenges, they actually took a shortcut, because they had the opportunity to just have the endogenous TCR that they can take advantage of. What we've done over the past four or five years with Michel Sadelain has been basically coming up with a strategy where you don't have the TCR available, because we're going into an allogeneic setting and how to mitigate TCR signaling with a CAR. And that's where we put the CAR on the track locus, it turns on, [indecipherable] out of places and in a temporal manner gives us the signal we need for T cell selection. So it's a very complicated process.

To your question about a CD8s and CD4s, the composition of our FT819 is a CD8 product. It is a very highly effective cell population. The CD4 compartment it's always been discussed as a helper population. And that population you need for long-term persistence when you have a single dose. So here in a multi-dose manner, we feel that the CD8s are the proper dosing strategy for our first product. We are actively working on making CD4s on the side, but CD8s are the focus of FT819. So basically, that's our strategy mix CD8, carrying the CAR and make CD4s in a different timeline.

Operator

Your next question comes from the line of Peter Lawson from Barclays.

Peter Lawson -- Barclays -- Analyst

The AML data we get kind of mid-year-ish, is that going to be kind of ASCO or is it kind of like a press release? What's the plan around that?

Scott Wolchko -- President and Chief Executive Officer

We'll continue that what we've done in the past, I mean, whether it will be part of a conference agenda, or we will do it alongside the conference, like we did at FT516 at ASH. We'll do it as part of a scientific conference. We're not just going to do as part of just a one off press release. We'll announce it as part of some type of event.

Peter Lawson -- Barclays -- Analyst

What's the best buy there for 516 and 538 in AML? Is it you kind of want to be on par with the hallow kind of approaches for NK cells?

Scott Wolchko -- President and Chief Executive Officer

Historically, I think, he look, I think people have been honestly excited about some of the complete responses that have been generated in AML, and again, relapsed refractory AML. These are patients that really don't have any great options. And they're not in a position given the state of their disease where they can go on to transplant. And so, we're certainly looking at and we talked about the limitations with donor derived NK cell therapy that wasn't really scalable given some of the limitations. And so, if we can come in with an off the shelf cell therapy, achieved CR, CRI rates of 20% to 30% drive patients to leukemic free state where they can bridge the transplant with an off the shelf product candidate. I think that's a great option. And I think there's really a meaningful therapeutic impact that you can have for patients with relapsed refractory AML if we can achieve that. I do say I will stand by, the comment I made earlier, though, long-term, if you start thinking about long-term AML, yes, you will have engineered targeted strategies.

Peter Lawson -- Barclays -- Analyst

Okay. And then, just generally, as we kind of think about repeat dosing, do you think on repeat dosing, there's going to be an increased chance of graft rejection essentially?

Scott Wolchko -- President and Chief Executive Officer

It's an interesting question. I mean we look at this for every single patient that we treat across any of our programs, 500, 516,596, 538 I mean, we look for this. We have not seen Tier B cell mediated rejection arise. Now, it's a fair question, as you go out further on the curve and further out from conditioning, as you do more rounds of conditioning, will that arise? It's a fair question. And it's something as sort of Wayne alluded to, we're interested in investigating including comparing it to non Cy/Flu conditioning regimens.

Peter Lawson -- Barclays -- Analyst

And my next question, do you think we can get away from Flu/Cy conditioning?

Scott Wolchko -- President and Chief Executive Officer

I think we're going to begin investigating that in pretty short order.

Operator

Your next question comes from the line of Nick Abbott from Wells Fargo.

Nick Abbott -- Wells Fargo -- Analyst

So Scott, you probably created over 40 patients now in FT500 series of trials, can you talk a little bit about the clinical protocol logistics, I mean there's an obvious need for bridging therapy, presumably, but that would rely on the fact that everything goes well, and the cells are there and the patients get the Flu/Cy on time. And then, of any patients required hospitalization before or immediately after for treatment related AIE. I know the cells are given in the outpatient setting. But I'm just wondering about rates of hospitalization. And I have a follow up.

Scott Wolchko -- President and Chief Executive Officer

Wayne can talk about this sort of what we've seen in preparing patients, I mean, we've seen very little utilization of or need to use a sort of a bridging strategy, given the cells are there, they can be administered off the shelf. We obviously never discussed hospitalization rates, but most of our product candidates are designed for the protocol to be delivered in the outpatient setting. I will say, though, there are certain centers, when they treat the first patient, for example, or the first second patient at that center, where they do initially require hospitalization for a short period of time, just because it's the first time with respect to the therapy.

Wayne Chu -- Senior Vice President, Clinical Development

Yes. I mean, I think just to add to that in our cumulative experience to-date, we have virtually no instances where a patient received, co-bridging therapy, where the reason for administering that bridging therapy was to buy time until FT series of cells were made available. So, it was really -- in most cases, as exemplified by what we discussed earlier, patients who are refractory from their last therapy, as soon as they become eligible for the study, they come on to the study, they get their Flu/Cy and they get themselves, they've not had to have, a single agent chemotherapy as a tie over. So that is almost -- that's virtually non-existent in our experience to-date.

And then, as far as hospitalization is concerned, I think one thing that's worth reminding is that, to-date we have not seen any serious adverse events that are attributable to any of the cell products, which means that in virtually all cases, patients who require hospitalization during the treatment period, they're hospitalized for things other than effects of the cells and it's most often due to the patient's underlying disease, as well as in some cases, effects from the Flu/Cy conditioning, which are expected given what we know about the safety profile for that combination.

Nick Abbott -- Wells Fargo -- Analyst

That's helpful. And for the expansion cohorts, it sounds like at least in some of them, you're going to do some additional exploration of dose and as you mentioned, lympho conditioning. Are you going to begin to focus on specific cohorts and I'm thinking of AML, where you could have a cohort of primary induction failures, early relapse, or even non-elderly frontline patients who are ineligible for intensive induction therapy?

Scott Wolchko -- President and Chief Executive Officer

Yes, absolutely. I think that is absolutely an opportunity in AML. Certainly, given the different lines of therapy, I think, where we will absolutely start to -- you'll start to see this as with FT516 in lymphoma where today we have the most flexibility given we are at the highest dose level and give it the safety and efficacy profile we've seen to-date.

Nick Abbott -- Wells Fargo -- Analyst

Okay, thanks. And then just last one, you mentioned that there are some improvements for 819. Are you going to complete this second batch before you decide which to use in the middle of the year?

Scott Wolchko -- President and Chief Executive Officer

Yes, we probably will. I mean, we've done a lot of work on the first batch. And we're actually very comfortable with the in vivo efficacy we're seeing from the first batch. But like I said, we're always innovating. We have implemented some process of improvements on the preclinical side and preclinically they do make a difference. So we are going to take a look at the second batch.

Nick Abbott -- Wells Fargo -- Analyst

Okay. And then by extrapolation and should we assume the -- not felt the need to do that with the NK portfolio?

Scott Wolchko -- President and Chief Executive Officer

With the NK portfolio, we have definitely made process improvements over time. But this was a situation where we were making a process improvement in real-time before we had treated the first patient. There was an element of innovation that occurred prior to treating the first patient.

Operator

That is your last question presenters, you may continue.

Scott Wolchko -- President and Chief Executive Officer

Perfect. Thank you everyone for participating in today's call. Best wishes.

Operator

[Operator Closing Remarks]

Duration: 68 minutes

Call participants:

Scott Wolchko -- President and Chief Executive Officer

Ed Dulac -- Chief Financial Officer

Wayne Chu -- Senior Vice President, Clinical Development

Bob Valamehr -- Chief Development Officer

Srikripa Devarakonda -- Truist Securities -- Analyst

Alethia Young -- Cantor -- Analyst

Michael Schmidt -- Guggenheim -- Analyst

Yigal Nochomovitz -- Citi -- Analyst

Mara Goldstein -- Mizuho -- Analyst

Matt Biegler -- Oppenheimer -- Analyst

Carolina Ibanez Ventoso -- Stifel -- Analyst

Biren Amin -- Jefferies -- Analyst

Peter Lawson -- Barclays -- Analyst

Nick Abbott -- Wells Fargo -- Analyst

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