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Edited Transcript of FATE earnings conference call or presentation 5-Nov-19 10:00pm GMT

Q3 2019 Fate Therapeutics Inc Earnings Call

San Diego Nov 9, 2019 (Thomson StreetEvents) -- Edited Transcript of Fate Therapeutics Inc earnings conference call or presentation Tuesday, November 5, 2019 at 10:00:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Bahram Valamehr

Fate Therapeutics, Inc. - Chief Development Officer

* Daniel D. Shoemaker

Fate Therapeutics, Inc. - Chief Scientific Officer

* J. Scott Wolchko

Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director

* Wayne Chu;Vice President, Clinical Development

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Conference Call Participants

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* Alethia Rene Young

Cantor Fitzgerald & Co., Research Division - Head of Healthcare Research

* Amanda Louise Murphy

BTIG, LLC, Research Division - MD & Senior Biotechnology Equity Analyst

* Benjamin Jay Burnett

Stifel, Nicolaus & Company, Incorporated, Research Division - Associate

* Biren N. Amin

Jefferies LLC, Research Division - MD and Senior Equity Research Analyst

* Daina Michelle Graybosch

SVB Leerink LLC, Research Division - MD & Senior Research Analyst

* James William Birchenough

Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst

* Kelsey Beatrice Goodwin

Guggenheim Securities, LLC, Research Division - Associate

* Mara Goldstein

Mizuho Securities USA LLC, Research Division - MD of Equity Research Department

* Matthew Cornell Biegler

Oppenheimer & Co. Inc., Research Division - Associate

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Presentation

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Operator [1]

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Welcome to the Fate Therapeutics Third Quarter 2019 Financial Results Conference Call. (Operator Instructions) This call is being webcast live on 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.

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [2]

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Thank you. Good afternoon and thanks, everyone, for joining us for the Fate Therapeutics Third Quarter 2019 Financial Results Call. Shortly after 4:00 PM Eastern Time today, we issued a press release with these results which can be found on the Investors & Media section of our website under Press Releases.

In addition, our Form 10-Q for the quarter ended September 30, 2019, 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 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-Q for the quarter ended September 30, 2019, 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. Dan Shoemaker, our Chief Scientific Officer; Dr. Bob Valamehr, our Chief Development Officer and Dr. Wayne Chu, our Vice President of Clinical Development. Over the past 3 months, Fate Therapeutics has achieved a series of key milestones that have firmly established the company as the leading manufacturer and developer of off the shelf engineered NK-cell and T-cell cancer immunotherapy and which enabled the company to generate decisive clinical data across multiple product candidates from our iPSC product platform. These milestones include, one, treatment of the first patient with FT516. FT516 is an off-the-shelf targeted NK-cell cancer immunotherapy derived from a clonal master-induced pluripotent stem cell or iPSC line engineered to uniformly express a novel, high affinity, noncleavable, CD16 Fc receptor. FT516 is the second product candidate emerging from our iPSC product platform and it is the first ever cell product in the world derived from a genetically engineered iPSC line to be administered to a patient.

Number two, FDA clearance of our investigational new drug application for FT596. FT596 is an off-the-shelf iPSC derived Chimeric Antigen Receptor or CAR, NK-cell cancer immunotherapy that is uniquely designed to engage multiple tumor-associated antigens expressed on cancer cells for best-in-class activity. FT596 is the first-ever cell therapy cleared by the FDA for clinical investigation that is engineered to express 3 active anti-tumor functional modalities.

And 3, launch of our cGMP facility for the clinical manufacturer of IPS derived cell therapies. Our state-of-the-art facility is custom designed to use clonal master iPSC lines as a renewable cell source for the manufacture of off-the-shelf allogeneic and K-cell and T-cell products. The facility has been commissioned and qualified. The company has been issued a drug manufacturing license by the State of California, and we have begun clinical manufacture of multiple product candidates within the facility. With our full control of cGMP production combined with our proven ability to genetically engineer iPSCs and create clonal master iPSC lines qualified for clinical use, we believe we have established operational capabilities unique to the industry to ensure consistent, large scale and cost-effective manufacture of off-the-shelf cell products for on-demand delivery to patients.

Starting with FT516, FT516 is the first engineered NK-cell cancer immunotherapy emerging from our iPSC product platform. The product candidate is derived from a clonal master iPSC line engineered to express a novel high affinity noncleavable CD16 Fc receptor. CD16 is a naturally occurring activating receptor expressed on NK cells and the receptor has been shown to be the key mediator of antibody-dependent cellular cytotoxicity or ADCC which is a potent anti-tumor mechanism by which NK-cells recognize, find, and kill antibody-coated tumor cells. CD16 is most commonly found in its low-affinity variant form and its expression has been shown to undergo considerable down-regulation in the tumor microenvironment, which can significantly limit NK-cell anti-tumor activity.

In contrast, the novel CD16 Fc receptor incorporated into FT516 is comprised of 2 unique functional enhancements. It is comprised of the high-affinity variant form to enhance binding to tumor-targeting antibodies and it has been modified to prevent down-regulation which are designed to [exist] significantly augment ADCC. The FT516 clinical trial is a multidose Phase I clinical trial in which FT516 is being investigated as a monotherapy for the treatment of relapsed refractory acute myeloid leukemia and as a combination therapy with CD20 directed monoclonal antibodies for the treatment of relapsed refractory B-cell lymphoma.

The study is designed to assess the safety and activity of an outpatient treatment cycle comprised of 3 once weekly doses of FT516. Patients who are clinically stable following the first treatment cycle are eligible to receive a second treatment cycle of 3 once weekly doses of FT516. Importantly to promote FT516 anti-tumor activity, patients will receive a moderate lympho-conditioning regimen prior to each treatment cycle of FT516 as well as IL-2 cytokine support with each dose of FT516. Both arms of the FT516 clinical trial are enrolling concurrently, 3 dose levels of 90 million, 300 million and 900 million cells per dose are planned for AML with the CD20 directed monoclonal antibody combination arm starting at 30 million cells per dose to evaluate safety in a single patient. In October, the first patient received FT516 in combination with rituximab for the treatment of diffuse large B-cell lymphoma and a second patient in the clinical trial received FT516 as a monotherapy for the treatment of refractory AML. We believe there is compelling clinical proof of concept to support the potential clinical benefit of FT516 for the treatment of AML and as a combination therapy with CD20 directed monoclonal antibodies for the treatment of B-cell lymphoma and that there are well established clinical benchmarks against which we can assess safety and efficacy. Specifically in the setting of relapse/refractory AML, hundreds of patients have been treated with donor-derived NK cell therapy, notably leukemic blast in the bone marrow have been shown to be particularly susceptible to direct NK cell mediated killing and complete remission rates ranging from 20% to 35% have been reported in investigator-initiated studies of donor-derived NK-cell therapy.

In addition to bone marrow biopsies to assess clinical anti-leukemic responses to FT516, we will also collect bone marrow samples before treatment and following the third dose of FT516 in the first treatment cycle to gain an early read on FT516 homing to the bone marrow and anti-leukemic activity.

In addition to the direct NK-cell mediated killing, numerous clinical studies with FDA approved tumor-targeting monoclonal antibodies have demonstrated that ADCC is an important mechanism of action that drives the anti-tumor activity of monoclonal antibody therapy.

Importantly, these studies have demonstrated that patients homozygous for the CD16 high-affinity variant 158V have significantly improved clinical outcomes following treatment with monoclonal antibody therapy; however, only about 15% of patients are privileged with this advantaged CD16 form. In the setting of relapsed refractory B-cell lymphoma, single-agent clinical activity of monoclonal antibodies have shown modest clinical responses, for example with response rates of approximately 10% and overall response rates of approximately 30% in DLBCL. Since FT516 incorporates a novel high affinity 158 variant and since it is noncleavable which prevents down-regulation and maintains active levels of [self] expression, we believe FT516 can significantly augment ADCC resulting in higher and more durable responses. In September, we announced that the FDA-cleared our investigational new drug application for FT596, FT596 is an off-the-shelf CAR NK-cell cancer immunotherapy derived from a clonal master iPSC line engineered with 3 antitumor functional modalities. A proprietary CAR that targets B-cell antigen CD19. The novel, high-affinity, noncleavable CD16 Fc receptor that enables multiantigen targeting and an IL-15 receptor fusion protein that promotes enhanced NK-cell activity, FT596 is at the forefront of cell-based cancer immunotherapy. It is the first cell therapy cleared for clinical investigation by the FDA that is engineered with 3 active anti-tumor components. We believe FT596 is a transformative product candidate and has the potential to supplant patient specific and allogeneic CAR19 T-cell immunotherapies that recognize only one antigen and fail to address the significant risk of relapse due to antigen escape.

Clinical experience with patient-derived CAR T-cells both in the case of single antigen targeting CAR T-cells against CD19 in leukemia and lymphoma and against BCMA in myeloma have clearly demonstrated the down-regulation of the target antigen such as CD19 and BCMA is a major mechanism of resistance that accounts for failure to respond and even for those patients that initially respond, failure to achieve long-term durable remission. FT596 is uniquely designed to target multiple tumor-associated antigens and overcome CD19 antigen escape. In addition to the proprietary CAR targeting CD19, FT596 expresses the high-affinity, noncleavable CD16 Fc receptor, which enables coincident targeting of CD19 and additional tumor-associated antigens in combination with therapeutic antibodies.

FT596 also expresses the IL-15 receptor fusion, a potent cytokine complex that promotes survival, proliferation and trans-activation of endogenous immune cells without the need for systemic cytokine support. Together, these features of FT596 are intended to maximize potency and improve durability of response. The Phase I clinical trial is specifically designed to exploit the multiantigen targeting functionality of FT596 and overcome antigen escape. [Upon] establishing safety as a monotherapy in a first dose cohort of 30 million cells per dose, the clinical trial will assess the safety and activity of FT596 in combination with rituximab in patients with B-cell lymphoma at 4 planned dose levels, 30 million, 90 million, 300 million and 900 million cells per dose.

Additionally, upon establishing the maximum tolerated dose in combination with rituximab, the clinical trial will assess the safety and activity of FT596 in combination with obinutuzumab in patients with chronic lymphocytic leukemia. Each patient will receive a moderate outpatient lympho-conditioning regimen prior to the first treatment cycle of FT596, which cycle consists of a single dose of FT596. Since FT596 incorporates the IL-15 cytokine support as part of its engineered functionality, cytokine support will not be administered to the patient based on enhanced persistence of FT596 observed in our pre-clinical studies.

Importantly, each patient may be eligible for additional treatment cycles of FT596 based on evidence of clinical benefit subject to review of the patient status by the FDA.

At this time, we have finalized the clinical protocol in consultation with leading clinical investigators in the CAR T-cell field, clinical trial startup activities have begun at multiple sites and we are planning for treatment of the first patient in early 2020. We continue to be excited about the multifaceted direct and indirect roles of NK-cells that they may play in attacking solid tumors.

While remarkable responses have been achieved with checkpoint inhibitor therapy across a number of solid tumor types, these therapies are not curative and in most cases, patients either fail to respond or progress on these agents. One common mechanism of resistance to checkpoint inhibitor therapy is associated with loss of function mutations in genes critical for antigen presentation, which can result in partial or complete loss of MHC Class I expression and escape from T-cell anti-tumor activity. Compelling biological evidence continues to emerge that supports the potential for NK cells to recognize and directly kill tumors with these mutations and convert checkpoint inhibitor therapy resistant patients into clinical responders.

We believe FT500, the first off-the-shelf NK-cell product candidate emerging from our iPSC product platform represents a novel, therapeutic strategy to potentially re-sensitize patients to checkpoint inhibitor therapy and overcome disease resistance. We are currently investigating FT500 in a multidose Phase I clinical trial for the treatment of advanced solid tumors. The study is designed to assess the safety and activity of 3 once weekly doses of FT500. As a monotherapy in the salvage setting of disease and in combination with 1 of 3 FDA-approved checkpoint inhibitor therapies in patients whose tumors fail to respond or progressed following initial response with prior checkpoint inhibitor therapy. Patients who are clinically stable following the first cycle of FT500 treatment are eligible to receive the second treatment cycle of 3 additional once weekly doses of FT500 for a total of up to 6 doses at each dose level.

Importantly, the dose escalation stage of the Phase I study of FT500 is designed to assess safety and tolerability. The FT500 clinical trial is the first ever clinical trial in the United States of an IPS-derived cell product. Additionally, it is one of the first-ever clinical trials to systematically evaluate a novel treatment paradigm for cell therapy where multiple doses are administered over multiple cycles. Finally, FT500 is the first universal, off-the-shelf NK-cell product to be combined with checkpoint inhibitor therapy.

To best promote a first principles assessment of safety and tolerability of FT500. patients in dose escalation are to receive a mild outpatient lympho-conditioning regimen prior to the first treatment cycle only and no cytokines support. A key objective for the dose escalation stage is to complete a robust assessment of the patient's immunological response to FT500 including number one, measuring endogenous immune cell reconstitution and activation including CD8 cytotoxic T-cells and T-regulatory cells. Two, cytokine activity including evidence of cytokine release syndrome, neurotoxicity and GvHD and three, the occurrence of the anti-sell immunogenicity including evidence of rejection mediated by endogenous B-cells and T-cells.

We continue to be pleased with the progress and preliminary indications of clinical safety and tolerability we have observed to date in the dose-escalating stage of the FT500 Phase I clinical trial. In the monotherapy arm of the study, 3 patients have been treated at 100 million cells per dose and 5 patients have been treated at 300 million cells per dose with no reported dose-limiting toxicities or FT500-related serious adverse events. Additionally, in the combination arm of the study in patients that have failed prior checkpoint inhibitor therapy, 3 patients have been treated at 100 million cells per dose in common combination with checkpoint inhibitor therapy with no reported dose-limiting toxicities or FT500-related serious adverse events. Enrollment in the dose-escalating stage of the FT500 Phase I clinical trial is currently ongoing at 300 million cells per dose in the combination arm of the study.

Subject to establishing safety at this dose level, we plan to initiate [dosing] expansion in the combination arm of the study only with an amended clinical protocol that is specifically designed to promote FT500 anti-tumor activity. These modifications include enriching for tumors with partial or complete loss of MHC Class 1 expression based on pre-treatment biopsy, adding cytokine support to induce NK-cell activity and selecting cancers that are most amenable to NK-cell infiltration. We look forward to sharing our initial clinical insights into our first-in-human clinical experience with FT500 and our plans for the design of the dose expansion stage of the FT500 clinical trial at the upcoming 61st American Society of Hematology Annual Meeting.

As we look toward the end of 2019, we are pleased that our IPS-derived cell-based cancer immunotherapy pipeline will be featured at both the 34th Annual Meeting of the Society for Immunotherapy of Cancer as well as the 61st Annual ASH Meeting. At SITC during the Sunday plenary session entitled Innovations in Cellular Therapy for Therapeutically Targeting Advanced Malignancies, Dr. Jeff Miller of the University of Minnesota is scheduled to showcase the company's off-the-shelf IPS-derived NK-cell platform and present pre-clinical data demonstrating the cytotoxic function of FT500 as compared to donor-derived NK cells and the synergistic anti-tumor activity of FT500 in combination with checkpoint inhibitor therapy.

Additionally, I'm pleased to announce that we had 6 abstracts accepted for presentation at ASH which will be unveiled tomorrow morning and that we will be hosting our fourth annual ASH investor event on Friday evening where we will be joined by esteemed guests including Dr. Miller of the University of Minnesota, a pioneer of adoptive NK-cell therapy and our collaborator in developing IPS-derived NK-cell cancer immunotherapies; Dr. Eric Smith of Memorial Sloan-Kettering Cancer Center, an expert in cellular immunotherapy for multiple myeloma; and Dr. Michel Sadelain of Memorial Sloan-Kettering Cancer Center, a pioneer of adoptive NK cell therapy and our collaborator in developing off-the-shelf IPS derived T-cell immune therapies, including FT819, our first IPS-derived CAR T-cell product targeting B-cell malignancies.

Finally, I want to recognize recent accomplishments of the ProTmune clinical trial and manufacturing team. In October, we completed patient enrollment and treated the 80th patient in the randomized, controlled, and double-blinded Phase II protect study of ProTmune. ProTmune is the company's first-in-class, allogeneic, hematopoietic cell product candidate for the prevention of acute graft versus host disease in patients undergoing hematopoietic cell transplantation for the treatment of hematologic malignancies. GvHD is the leading cause of early morbidity and mortality following allogeneic transplant and there are currently no therapies for the prevention of acute GVHD approved by the FDA. The completion of patient enrollment is a notable operational achievement for the company and we look forward to seeing the data from this blinded study in 2020.

Turning to our financial results, revenue was $2.4 million for the third quarter of 2019 compared to $1 million from 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 third quarter of 2019 were $23.2 million compared to $13.6 million for the same period last year. The increase in our R&D expenses was attributable primarily to an increase in employee compensation, including stock-based compensation associated with growth in head count, internal and third party expenses associated with the clinical development and manufacture of the company's product candidates and expenses associated with conduct of research activities under our collaboration with Ono Pharmaceutical.

G&A expenses for the third quarter of 2019 were $6.3 million compared to $4.1 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. Total operating expenses were $25 million for the third quarter of 2019, net of noncash stock-based compensation expense of approximately $4.6 million. In September, the company completed a $100 million -- a $173 million common stock offering. Including net proceeds from the offering, the company ended the third quarter of 2019 with $303 million of cash, cash equivalents in short-term investments, common stock outstanding was 75.4 million shares.

And preferred convertible stock outstanding was $2.8 million shares, each of which is convertible into 5 shares of common stock under certain conditions. I continue to be pleased with the company's operational progress and expanding leader position in our pursuit of bringing disruptive cellular immunotherapies to patients with cancer and we are well positioned to generate decisive clinical data across multiple product candidates from our iPSC product platform. And with that I'll open the call up to questions.

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Questions and Answers

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Operator [1]

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(Operator Instructions) And our first question coming from the line of Alethia Young from Cantor Fitzgerald.

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Alethia Rene Young, Cantor Fitzgerald & Co., Research Division - Head of Healthcare Research [2]

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Congrats as we move toward closer to kind of a readout of your ASH. I got 2, one with the release from Allergan going after iPSC today with [nontherapeutic], so maybe just talk about points of differentiation that you perceive in that technology and then also you are starting to add a notable amount of patients in FT500, so I just want you to talk about what it means from the safety that you're seeing and the implications around, redosing and how we make a read through the platform.

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [3]

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Sure, so I'll talk about Allergan and sort of their initiative in iPSCs, Wayne should feel free to talk about the initial results we're seeing with FT500 which we can -- are going to talk much more about at ASH. The group that Allergan did the collaboration with is led by an investigator, Juan Carlos [Fluker] and so we are very familiar with Dr. Fluker . We've had conversations with Dr. Fluker quite frankly dating back for probably 5 years and we're very familiar with his technology.

Our read of his technology is that his technology primarily relates to maturation of T cells and maturing T cells to specific phenotypes. I, in all my conversations with Juan Carlos, interestingly enough, have never viewed him as someone who is an expert in iPS cell technology, quite frankly. So I think the technology is interesting as it relates to how you might mature a cell to a specific T-cell phenotype, but I did not, and I don't think Juan Carlos necessarily views himself as an expert in iPS cell technology.

I would say we've looked at that technology that is being used by that group and we are very comfortable with the technology we've developed under our Memorial Sloan-Kettering collaboration, the phenotype of the T-cells we're generating and we plan to highlight some very significant in vivo data at ASH, I don't know, Bob, if you have anything to add to that.

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Bahram Valamehr, Fate Therapeutics, Inc. - Chief Development Officer [4]

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No, that's exactly right. We've been talking to JC for quite some time as Scott mentioned and his technology is associated with taking him out of places down the T-cell lineage, specifically microbeads that have expressing ligands DL4 and VCAM, which has been published a couple of years ago. He is amazing in T-cell development, but when it comes to iPSC culture, I think, as Scott mentioned, there is data, we still think we have a differentiated platform that's not seen by JCs technology.

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [5]

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And then with respect to FT500. I mean I'll it over to Wayne. I mean he's obviously very closest to running the FT500 clinical study and he can comment a little bit more on safety that we're seeing with respect to the multidose paradigm but really we're looking forward to unveiling a deeper dive on what we're seeing at our ASH Investor Event.

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Wayne Chu;Vice President, Clinical Development, [6]

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Yes. What I can say about FT500, as Scott mentioned earlier that, I think one of the key objectives of FT500 is demonstrating that safety and tolerability of giving multiple doses on demand of FT500 in patients and I think one important point to remember is that all of these FT500 doses are administered on an outpatient basis, so unlike some of the other autologous CAR T products that require mandatory hospitalization for monitoring, we do not have such requirement and the patients that we have treated to-date with FT500 have all tolerated the FT500 quite well, really there has been no dose-limiting toxicities or any related serious adverse events as was mentioned before and really primarily reasons for not continuing to the full course of FT500 are really related to underlying disease rather than anything related to FT500, so it's still relatively early days, but we're very encouraged by what we've seen so far from a safety and tolerability perspective.

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Operator [7]

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And our next question coming from the line of Michael Schmidt with Guggenheim Securities.

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Kelsey Beatrice Goodwin, Guggenheim Securities, LLC, Research Division - Associate [8]

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This is Kelsey on for Michael. I guess kind of more bigger picture, now that you kind of keep adding increasingly more edits, now are up to 3 kind of in the clinic. I guess how have you seen regulators respond to this increased complexity and do you see a ceiling for the number of edits that you could make to these sales.

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [9]

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Sure. I'll touch lightly on this topic because it has to do with regulatory -- regulators view of editing. I do think -- as we talked about in the past, I do think we have a significant advantage when it comes to gene editing and that is imparted upon us based on the specific nature of our platform, we're engineering IPS cells and we're selecting a specific clone where that and the engineered properties are locked in and they are uniform just by the very nature of selecting a single clone.

And so I think that is very unique, I think in a world of patient-derived cell therapy or donor-derived cell therapy where your engineering at a batch level, I believe, in our experience has been, at least pre-clinically, it is very challenging to create a homogeneous product and that there are significant off-target effects associated with batch engineering, especially when you're trying to do 2, 3, 4, 5 edits. I mean Dan can talk a little bit about the work we're doing under Ono collaboration right now, but we certainly have not stopped at 3, certainly we didn't stop there with FT596 in the clinic. But what we're doing under the Ono Collaboration and the limits that we're seeing, I mean we were thinking about for solid tumors ultimately that we are exploring right now, 4, 5, 6 edits as part of a iPSC platform again where you have the benefit of onetime engineering, selecting a single clone and fully characterizing the elements associated with that engineering event.

And then that translates all the way to the patient, because ultimately the patient is receiving a homogeneous cell product and quite frankly that homogeneous cell product has been -- that exact product with those engineering features has been thoroughly pre-clinically tested before seeing a patient and I think -- that's I think a very -- that's another unique difference. We can do preclinical evaluation of all that editing and ensure that the patient is receiving that product and that's very different than batch engineering. I'll turn it over to Dan who will provide more insight into the Ono Collaboration.

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Daniel D. Shoemaker, Fate Therapeutics, Inc. - Chief Scientific Officer [10]

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Just a few thoughts here is we're really, as you just said, the lead products now have 3 edits that's really focused on dual targeting, persistence and just sort of a function of the base CAR T and CAR NK-cell. As we then look towards solid tumors, there is whole new realms of opportunity to make yourselves better, stronger, faster with respect to trafficking, infiltration into the tumor, overcoming the tumor microenvironment, and recruiting other immune cells into the tumor to turn cold tumors hot.

So I think the future is really going to take the shape of how are we going to build on this current generation of base products to overcome the challenge of solid tumors and I think as we sort of assess the competitive landscape of what different platforms are capable of doing, I think one of the unique strengths of our IPS clonal platform is the ability to generate these highly edited clonal IPS populations and perform extensive characterization to demonstrate all of the rigorous copy number variation and translocations and things that can happen, these are just part of our standard QC process that we think is a unique path to getting into these really extraordinary processes and this is one of the things we're most proud about.

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Operator [11]

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Our next question coming from the line of Ben Burnett with Stifel.

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Benjamin Jay Burnett, Stifel, Nicolaus & Company, Incorporated, Research Division - Associate [12]

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Great. Just two questions and thank you for laying out so explicitly the FT500 updates at SITC and ASH that we can expect, but can you provide maybe just a little bit more color as to whether any FT516 data will be disclosed by either Dr. Miller at SITC or by Fate at the company's event at ASH.

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [13]

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Sure, so at FT -- at SITC, I can absolutely confirm that Dr. Miller is not going to disclose clinical data around the FT516, his presentation at SITC is around FT500 and the pre-clinical data package around the FT500 including the value of the NK cells, synergizing with checkpoint inhibitor therapy, which he has a publication that I think is currently in review around that, so he will be discussing that at SITC. At the ASH conference, we do have an ASH event.

Obviously, I can't speak to what abstracts will be unveiled tomorrow, but we will give an update certainly on FT500. I think it's a little too early for us to say definitively whether FT516 will be part of that clinical update or not, but certainly, we're very pleased with the fact that we've dosed the first 2 patients. The first obviously being in the lymphoma arm in combination with Rituxan and the second being an AML.

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Benjamin Jay Burnett, Stifel, Nicolaus & Company, Incorporated, Research Division - Associate [14]

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Okay. Got it. That's helpful. And maybe if I could just ask beyond ASH and into this year, sort of -- with sort of the cadence of clinical updates for FT516 and I don't know if it's too early, but also FT596, that we can expect.

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [15]

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Yes. I think we will be happy to talk more about this at ASH.

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Benjamin Jay Burnett, Stifel, Nicolaus & Company, Incorporated, Research Division - Associate [16]

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Okay. Okay, and maybe if I could just squeeze one more on ProTmune then, if I recall. there was some discussion around the potential to use a day one 100 Point versus maybe waiting for data to mature and look at a longer -- think we talked about at 1 year end point which could potentially inform on survival. I guess can you just remind us to sort of the current thinking and when we can expect the Protmune trial to readout and sort of what the end points are that you're looking at.

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [17]

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Yes, the primary end point of the study, you are correct, is a day 100 end point, it's cumulative incidence of grade two through four GvHD at day one 100. We are finalizing the statistical plan right now, with respect to the primary end point. And we are looking very closely at also including a key secondary end point which is a composite around freedom from chronic GvHD relapse and death at day 365 and we've been -- we are going to discuss this more at ASH with our key investigators in the PROTECT study, but that key composite end point as we've thought about it and gotten feedback, it is important to at least consider that, as a potential secondary end point given it does represent essentially the totality of the outcome of transplant.

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Operator [18]

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Our next question coming from the line of Matt Biegler with Oppenheimer.

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Matthew Cornell Biegler, Oppenheimer & Co. Inc., Research Division - Associate [19]

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Definitely a lot of progress, a lot to digest, a quick clarification on FT596, is stage 1, is it only a single patient that will be enrolled in the monotherapy cohort and also on that Phase I, is it all (inaudible) by design or will you be excluding patients who are CA-19 negative.

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [20]

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Sure, I'll let, Wayne answer those questions.

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Wayne Chu;Vice President, Clinical Development, [21]

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Yes, so for FT596, it will initially start as a monotherapy cohort, but it will directly transition into an escalation that focuses on the combination of FT596 with the anti-CD20 antibodies, specifically rituximab. So that initial cohort. It's just -- it's a 3-patient cohort in adherence to 3 plus 3 dose escalation principle, so minimum 3 patients will need to be enrolled in that monotherapy cohort before being tested at that same dose but in combination with rituximab. And then dose escalation will proceed from there.

As far as the types of patients to be enrolled, we -- it's generally quite broad across multiple subtypes of non-Hodgkin's lymphoma with the goal of getting to the maximum tolerated dose or maximum assess dose as quickly as possible and then at the point of dose expansion, then we have the optionality of enrolling specific cohorts based on histology and other their baseline characteristics where we would then look at the overall safety, tolerability, and anti-tumor activity in greater depth.

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Matthew Cornell Biegler, Oppenheimer & Co. Inc., Research Division - Associate [22]

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Got it. That's helpful. And then I was just wondering if we should expect any updated data from the NK100 programs, I mean I do realize that these programs have been discontinued and the focus is on IPS things -- iPSCs going forward.

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [23]

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Yes. I think we are having discussions right now with the investigators that are involved in that study with respect to whether they would like to publish that data or present data at various conferences. We're very open to that and I think actually at SITC, Jeff may provide a little bit of update on the ovarian study, quite frankly, I've seen a draft of this presentation, there is a little bit of an update on the ovarian study with NK100.

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Operator [24]

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Our next question coming from the line of Amanda Murphy with BTIG.

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Amanda Louise Murphy, BTIG, LLC, Research Division - MD & Senior Biotechnology Equity Analyst [25]

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Just a question on 596. You've obviously done a good job at [500 and 516] in terms of laying out what you view to be the comparable efficacy targets, I guess, or sort of the bogeys, how do you about that from your 596 perspective. I know there's not obviously easy comparisons that are already out there other than maybe MD Anderson, slightly different but just kind of thinking about what you're looking for in both arms in response and durability in theory, for that one -- for that therapeutics?

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [26]

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So for FT596, because it has many of the features that we think are desirable to maximize efficacy against lymphoma and based on what information has been -- that has been released so far regarding NK-cell-based therapies with CD19-directed CAR, what we're expecting to see with FT596 quite frankly is a level of efficacy that approaches the level that's seen with other adoptive cell therapies, but potentially with a safety profile that is quite manageable in the sense that minimal cytokine release syndrome, minimal neurotoxicity in totality, which still enables us despite the addition of these genetic engineered elements to administer FT596 on an outpatient basis and certainly because of the flexibility with respect to multiple dosing and even flexibility with dose and schedule, one would hope that we would not only be able to achieve deep responses at a meaningful level of frequency, but also have these responses be durable.

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Amanda Louise Murphy, BTIG, LLC, Research Division - MD & Senior Biotechnology Equity Analyst [27]

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Do you have the option to tweak the lymphodepletion as well or is that pretty much set at this point, if you want…

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [28]

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I would say -- I mean Wayne can answer. I mean basically our -- I think our view is that what we've seen and the conversations we've had with the FDA, the FDA is very amenable to protocol changes that are based on clinical data.

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Wayne Chu;Vice President, Clinical Development, [29]

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Yes, I think that certainly given this is still a relatively new area, I think that the lympho-conditioning regimen that we specified for FT596, I would consider as a starting point, as we get more data regarding the persistence of FT596, maybe data around the [pharmacokinetics] of FT596, the safety, the efficacy, so and so forth, we will have the opportunity to look into the possibility of modifying lympho-conditioning, even if it means modifying lympho-conditioning with a subsequent cycle compared to the first. There are a lot of different variables that one can consider, but we would need to generate that data before we would make an informed decision on that.

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Amanda Louise Murphy, BTIG, LLC, Research Division - MD & Senior Biotechnology Equity Analyst [30]

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If i can just sneak in one about the sort of longer-term question I guess and the [answer I could] wait for ASH, so that's a fair bit. I just was curious, you've obviously made a lot of progress on the T-cell backbone side as well. When you think going forward from here, how are you thinking about prioritization of the pipeline between -- that's in the (inaudible) products you've talked about BCMA CAR, (inaudible) et cetera vis-a-vis a T-cell backbone candidate.

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [31]

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So from my perspective, we're doing both and we are completely committed to doing both. There may be -- we talked about this a little in the past, there may be situations where T cells, we think T cell are particularly advantaged, there may be tumor types -- for instance, we've talked about the solid tumor types, where MHC Class I has been down regulated where T cell are clearly not advantaged and NK cells might be advantaged and I have said this publicly before, it will not surprise me within, well, let's just give it 2 years, if a cell therapy is given that is comprised of both NK cells and T cells.

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Wayne Chu;Vice President, Clinical Development, [32]

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I could just simply add that -- I can simply add that in terms of prioritization of where to place individual products, I think it will be largely dictated by what we see in terms of the clinical data that defines the risk/benefit profile for these products and then matching them with the individual disease because as many of us know, lymphoma is a very heterogeneous disease and what works really well in one indication may not necessarily work well in another indication.

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Operator [33]

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Our next question coming from the line of Biren Amin with Jefferies. Your line is open.

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Biren N. Amin, Jefferies LLC, Research Division - MD and Senior Equity Research Analyst [34]

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Scott, on 596, what criteria would trigger redosing of patients in that trial? And then I guess how are you defining moderate lymphodepletion, if you could just further characterize that a bit more?

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [35]

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Sure. I mean we could touch on that. So I mean actually I'll let Bob -- both Bob and Wayne touch on this. One of the things with -- that is very unique to FT595 as we've discussed, it as 3 anti-tumor functionalities embedded into it. One of them is the IL-15 receptor fusion. I'll let Bob talk about some of the pre-clinical data we've seen with that IL-15 receptor fusion which has led us certainly to the conclusion that we are looking at only giving one dose per cycle, based on what we've seen pre-clinically. And then I'll let Wayne talk about the conditioning regimen specifically that we're starting out for FT596, which I think you'll be very familiar with, it's a condition regimen that is used quite frankly by multiple groups in the CAR-T cell space that are better conditioning and not depleting.

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Bahram Valamehr, Fate Therapeutics, Inc. - Chief Development Officer [36]

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Yes. So as Scott was mentioning that these modalities are tailor-made for NK-cell expansion and so for example you take the IL-15 receptor fusion, that brings in not just proliferation but also survival and growth. So these cells are autonomous, they can be cultured in the manufacturing process without the need for IL-2 and IL-15. That lack of -- that independence of cytokine support continues into the in vivo models we have and so we're very confident that the cells will persist.

A second triggering mechanism that's going to give these cells persistence and antigen-mediated expansion is the card that has been calibrated for NK biology that has been highlighted by Scott in previous discussions and so the combination of these 2 modalities really gives the cells that boost where a onetime dose will be triggering enough of the activation and expansion of the cells to have an effective clinical response.

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Wayne Chu;Vice President, Clinical Development, [37]

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And then as to the FT596 clinical trial, with -- specifically with respect to the lympho-conditioning, it's essentially the same lympho-conditioning regimen that's used for the CAR T, specifically 3 consecutive days of fludarabine and cyclophosphamide, with the fludarabine dose of being 30 milligrams/m2 per dose and cyclophosphamide being 500 milligrams/m2 per dose.

Importantly, with the FT596 Phase I, it's currently written with a single administration of FT596 and then dose escalating based on that, but in line with all of the other products, our intention and goal is to get to a point where we can give multiple doses of -- multiple cycles of FT596. So even in the protocol, it's currently constructed, as Scott mentioned, there is the opportunity to give an additional cycle of FT596 contingent on patients being clinically stable to receive a dose and that includes sufficient recovery from any treatment-emergent adverse events following cycle one and then any evidence of clinical improvement either clinically or radiographically.

And then as Scott mentioned, once that data package is reviewed with FDA, then patients potentially could get another cycle of FT596. Ultimately, once we have sufficient data from at least several patients and had that discussion with FDA, the intention is that we would amend the FT596 Phase I study such that every patient coming on would have the opportunity to receive multiple cycles of FT596 without having to -- going through a data review on an individual patient-by-patient basis with the FDA.

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Biren N. Amin, Jefferies LLC, Research Division - MD and Senior Equity Research Analyst [38]

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So just on the FDA patient review, how many patients would FDA need before they're comfortable in approving an amendment to the protocol. Have they disclosed what that number is?

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [39]

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We don't know what that number is, they've not disclosed that number to us. I do not believe it is a significant number of patients. I think the FDA was asking us to -- as I have said before, I mean this is a first for cell therapy, forget about iPSCs -- this is cell therapy that has 3 antitumor modalities engineered into it and so I think the FDA is appropriately asking us to demonstrate a little bit of safety before launching into a treatment paradigm, which is also novel, giving multiple cycles of therapy.

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Biren N. Amin, Jefferies LLC, Research Division - MD and Senior Equity Research Analyst [40]

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That's fair. And I've done a couple of follow-ups on other programs. So on 500, Scott, you mentioned that you could potentially be enriching for tumors with partial or complete loss of MHC1 expression as well as enriching for cancer is with NK-cell infiltration. So for both of these parameters, how well do they correlate in terms of, let's say lung or renal cancer?

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [41]

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Yes. So I think there is a high correlation with lung, so I think, about 40% of patients, 30% to 40% of patients that progress or fail on checkpoint inhibitor therapy, if you look at the tumor, the actual tumor, the mechanism of resistance appears to be associated with significant down-regulation of MHC Class 1 expression.

Additionally, when you administer NK cells systemically, they absolutely traffic through the lung. So based on when you look at significant areas of resistance -- areas of resistance that are associated with the loss of MHC Class 1 and potential for NK cells to traffic and infiltrate, lung rises to the top of the list.

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Biren N. Amin, Jefferies LLC, Research Division - MD and Senior Equity Research Analyst [42]

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Got it. And then I guess on -- you also mentioned that you may amend for cytokine support. So are you thinking about administering IL-2 after dosing these cells?

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [43]

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Yes, yes, I mean that's historically what has been done with donor-derived NK-cell therapy and I believe it's also done with a particular TIL therapy that everyone has sort of people's attention right now. IL-2 is commonly given with dosings, and so when we think about amending the protocol to now promote NK-cell anti-tumor activity. Yes, IL-2 would be an obvious thing to add with the dose.

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Biren N. Amin, Jefferies LLC, Research Division - MD and Senior Equity Research Analyst [44]

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Got it. And then maybe if I could get a last question in. You talked about Jeff Miller presenting at SITC, what do you think is the biggest differentiator of your platform versus donor-derived NK cells, is it the noncleavable CD16 component that you've talked about or is there some other component that your think differentiates.

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [45]

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The platform generally platform, I think there is a multitude of factors that differentiate this platform. I mean we spoke a little while ago about just the nature of engineering, I fundamentally believe cell therapy will incorporate multiple engineering elements to best promote anti-tumor activity and I believe that is going to be very hard to accomplish at scale In a predictable way and produce homogeneous product if those edits are occurring batch-by-batch as part of the manufacturing process. I think that's going to be super challenging, not to mention super expensive. That's -- so the engineering is one element, because we've collapsed all the engineering into a onetime event at a master cell line.

I do really believe in the world of cancer immunotherapy, just like oncology, there are very few agents that are given as a single administration and there is going to be plenty of data and there is plenty of data coming out with CAR T cell therapy. Talking about the challenges of single dose administration, single antigen targeting that is leading to relapses and lack of durable responses. And so to me the idea of being able to give multiple doses over multiple cycles like monoclonal antibodies are given, but doing that with a cell therapy where you can now engineer in multiple mechanisms of action. I don't know any other way to do this other than use an IPS cellular-based approach.

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Operator [46]

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Our next question coming from the line of Jim Birchenough with Wells Fargo.

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James William Birchenough, Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst [47]

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It's just one high-level question. Across FT500, FT516 and FT596, what's going to be the best opportunity to identify the efficacy of the cell therapy itself.

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [48]

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So I don't think it's a fair question, quite honestly, with respect to the product candidates. I mean FT596. I mean you're sitting here talking about 3 different functional modalities being embedded into it. So it's not a fair fight, some basic level between the 3 product candidates.

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James William Birchenough, Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst [49]

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So but given that, I guess what I'm trying to understand with 596, it sounds like we're moving into a Rituxan combo pretty quickly, is they're going to be a good opportunity to assess the monotherapy activity of the cells at a reasonable dose and benchmark it against what we've seen from the CAR NK data from MD Anderson as an example?

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [50]

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There -- may be, but that's not our objective. Our objective is our belief that multiantigen targeting is a best-in-class approach. I don't think we're alone in that belief and FT596 was designed to exploit it and that's where we are...

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James William Birchenough, Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst [51]

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And then maybe just -- just thinking about the Rituxan combinations, could you maybe speak to how many patients you need to treat or what level of response you need to see to rule out contribution from Rituxan and I get the point that you have, maybe responses in some patients as low as 10% to 20%, but you need to treat quite a few patients to rule out that level of response at the lower [lower band] of confidence intervals. Could you speak to that because I think it's -- at some point we're going to be trying to figure out the contribution of the cells and the antibody in this data going forward.

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [52]

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Well, to be clear, they will have failed Rituxan.

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James William Birchenough, Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst [53]

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And the definition of Rituxan failure?

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [54]

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So the definition of rituximab failure is quite simply is a patient who received prior rituximab-based therapy and either did not respond to that or progressed following an initial response. So just as a kind of a rough benchmark. If you look at what is our -- the monoclonal antibody clinical experience in this patient population, there are basically 2 examples, one is single agent obinutuzumab and the other is the single agent MOR208, that's the CD19 directed monoclonal antibody from MorphoSys, both molecules have been tested as a single agent in a patient population of failed rituximab and it has been fairly consistent in diffuse large B-cell lymphoma, the complete response rates for both his ranges are approximately 10% best, overall response is about 30% to 35%. Those numbers are a little bit higher and some of the more indolent lymphomas. So as we do our initial assessment of FT516 and FT596, those are the rough benchmarks that we used to see whether or not there is additional activity that is has confirmed by the cell product.

But to your point, in order to rigorously rule that out, we would have to do it at an expansion cohort with a requisite number of patients to rule out that lower bound. I would also just reiterate to be clear, as Wayne discussed, the target product profile for FT596 is we are looking for -- I would say similar response rates that have been achieved with CAR T cell therapy.

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Operator [55]

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Our next question coming from the line of Mara Goldstein with Mizuho.

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Mara Goldstein, Mizuho Securities USA LLC, Research Division - MD of Equity Research Department [56]

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So I have a couple of questions, one on the FT500 program. What's the highest number of doses that an individual has received so far in the trial or is that something that you're going to disclose at ASH. And then I'm curious if you could characterize for us in a 516 program, what mild cytokine support means. And thirdly, just a question from a -- I guess regulatory question and that has to deal with, in your interaction with FDA and sort of discussion in characterizing iPSC derived cell products, is the focus on sort of the phenotypically and functionality correctness versus safety and what does that access look like.

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [57]

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So I'll sort of go in reverse. There is a tremendous amount that goes into the regulatory discussions with respect to clearing an investigational new drug application for clinical study. There are multiple elements that are important I will tell you that characterizing the engineering events is absolutely -- characterizing the effect of engineering, the integrity of engineering is absolutely important. Safety is absolutely important, and there's a whole host of factors that go into putting together the regulatory package and demonstrating to the FDA that we have a product that we believe is safe to justify clinical study.

Engineering is certainly one of those elements and looking at the engineered features, yes, and being able to characterize the product with respect to those features I think is really important and as I think it's one of the areas where we're aided by the fact that ultimately we can trace the final product back to a single clone, which ensures uniformity of those engineered features.

I'll let Wayne talk about the clinical experiences with FT516. FT500, the clinical protocol with FT500 initially -- in its initial form was written to allow for up to 6 doses. So 3 doses in the first cycle, 3 doses in the second cycle, that is how it was originally written for the first part of dose escalation.

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Wayne Chu;Vice President, Clinical Development, [58]

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And then with respect of FT516, the dosing schedule of FT516 is similar in the sense that it is 3 weekly doses per treatment cycle given on day 1, day 8 and date 15 of each treatment cycle and then patients would be eligible to receive up to 2 treatment cycles. So that would mean 6 total doses of FT516. And then your specific question around cytokine support, it would be IL-2 given at a dose of 6 million IU, given subcutaneously with each dose of FT516. So there'll be a total of up to 6 doses of IL-2 support for the FT516 clinical trial.

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Operator [59]

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Our next question coming from the line of Daina Graybosch from SVB Leerink.

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Daina Michelle Graybosch, SVB Leerink LLC, Research Division - MD & Senior Research Analyst [60]

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Great. Good discussion thus far. One more question from me, maybe taking it back to the very first question. With more and more competitors coming in, I think as a testament to your approach and the value that you've been talking so much about, how do you think we should start comparing the data as it comes out from these competitors. What things in particular do you think are most interesting and helpful to compare pre-clinically, both for the iPSCs as well as the CAR NK competitors that start to come.

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [61]

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So we've discussed, just to be clear discussing pre-clinical data because I don't think people will be discussing clinical data from a competitor for probably…

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Daina Michelle Graybosch, SVB Leerink LLC, Research Division - MD & Senior Research Analyst [62]

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Exactly. No, agreed. We're going to be stuck with pre-clinical data. So how should we judge that in your perspective and compare it to your programs pre-clinically?

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [63]

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Sure. I mean I'll let Bob answer that question because Bob has sort of the greatest purview of what people are trying, I'll use that we're trying, to do in the iPSC field. One thing I'll say before turning it over to Bob, as much as people have talked about iPS-cell technology, I mean we have spoken a lot about the value of selecting a single clone and we believe there is a lot of value to that. I still have not seen anyone talk about being able to select a single clone and make a master cell bank, I still have not seen that from one person. So when you see that, let me know. But I'll let Bob go.

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Bahram Valamehr, Fate Therapeutics, Inc. - Chief Development Officer [64]

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So that's a great question and Scott kind of started it up and we've been talking about it the whole time. I mean I think you could think about it in 4 stages. The first stage is exactly what Scott said, when you make that master cell bank and then master cell banks [in general] from a single cell, what the integrity of your master cell bank, how well have you characterized it and do you have genomic stability, athletic massive expansion.

So first stage one, generation of the master cell bank that contains your [modalities] in a uniform manner that is well characterized, the second stage is -- may need specific differentiation, how well can you take that vial that you've created in the master cell bank and then guide it through differentiation to make your cell -- the final cell product a fully mature T or NK cell that has the ability to do exactly what you told it or you engineered it to do, so that's the second stage to your manufacturing process to create homogeneous process -- product every time that is of desired attributes. The third stage of that is now the distribution of that off the shelf product, can you directly [thaw and infuse], can you make the bags, can you ship to the hospitals and can you go through all that stability, all the things that the regulatory challenges, the manufacturing operations, the clinical logistics, so that's the off the shelf stage.

And then finally is the product itself. I think one of the things that we have been very proud of, it's not just manufacturing of iPSCs, but the intelligence that goes behind product development is still a targeting approach, it's something that working with Michel Sadelain, Jeff Miller and other collaborators, Dan Kaufman, Kalle Malmberg, we've been able to put together and I think as the next year rolls out, you'll see more exciting products that are entry points of the solid tumor, for example, so the actual modalities you put in, and it's also going to be part of it, so if you look at those 4 unique stages, I don't think anybody today can say we've get it all covered and the only reason we're here saying that we think we got all covered is because we've been doing this for 12 years now.

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [65]

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The other thing that I would add from just a more practical regulatory perspective, I mean one of the things I was asked about and I actually didn't touch on this, you have an IPS cell, right, that iPS cell has the potential to walk down arguably 200 different paths of life. The purity of your final product is going to be critical and we've discussed our purity levels and then as Bob sort of touched on the potency post [thaw], if you have an -- truly have an off-the-shelf product is also going to be critical.

So when people -- we can talk about pre-clinical data in mice and all that kind of good stuff, but when you have a scalable manufacturing process that starts with a genomically stable master cell line that's clonal and when you have a final product candidate that is almost pure coming out of manufacture with high potency post thaw, let me know, I'm a bit curious to look at that data.

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Operator [66]

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I'm not showing any further questions at this time, I would now like to send the conference call back over to Mr. Scott Wolchko for closing remarks.

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J. Scott Wolchko, Fate Therapeutics, Inc. - Founder, CEO, CFO, President, Treasurer, Secretary & Director [67]

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Great. Thank you, everyone, for participating in today's call and we look forward to seeing you in the next couple of weeks including at SITC and our ASH Investor event. Thank you.

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Operator [68]

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Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may all disconnect. Have a good day.