Q4 2019 Earnings Call
[music].
Welcome to the fate Therapeutics fourth quarter 2019 financial results Conference call.
At this time all participants are in the listen only mode.
This call is being webcast live on the Investor and media section of fates website at <unk> fate Therapeutics Dot com.
Today's call is being recorded I would not likes introduced Scott Wolchko, President and CEO of fate therapeutics.
Thank you good afternoon, and thanks, everyone for joining us for the fate Therapeutics fourth quarter 2019 financial results call. Shortly after four PM Eastern time today, we issued a press release with these results, which can be found on the investors immediate section of our web site under press releases in it.
And our form 10-K for the year ended December 31, 2019 was filed shortly thereafter and can be found on the investors and media section of our web site 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.
We see the forward looking statement disclaimer on the Companys earnings press release issued after the close of market today as well as the risk factors in the company's SCC filings included in our form 10-K for the year ended December 31, 2019 that was filed with the FCC 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 for sure.
From stances.
Joining me on today's call, our Dr., Dan Shoemaker, our Chief Scientific Officer, and Dr. Wayne Chu, our senior Vice President of clinical development.
Today I will comment on key milestones, we achieved during the fourth quarter 2019.
I will discuss our outlook for 2020 in bringing off the shelf IP has thrived cellular immunotherapy is to patients.
Fate Therapeutics has successfully pioneered the clinical investigation of IP, yes derived cell based cancer immunotherapy.
We believe our unique therapeutic approach using master engineered I P. S. C lines as a renewable source for manufacturing cell therapy products, which are well defined in uniform and composition can be mass produced at significant scale in a cost effective manner and can be delivered off the shelf for broad.
Haitian accessibility.
Is highly differentiated from patient and donor derived approaches cell therapy.
Which require batch to batch sourcing and engineering of millions of primary cells.
Similar to monoclonal antibody therapy in the 19 nineties, we believe I PS derived cell therapy is a highly disruptive therapeutic paradigm that can transform the treatment of cancer. We're excited to be at the forefront of this emerging field.
We are encouraged by the initial clinical data reported in December from the dose escalation stage of our phase one study of F. HTI 500, the Companys first off the shelf I P. S derived NK cell product candidate.
Our F. HTI 500 phase one study is the first ever clinical trial in the United States of an I.P.S. derived cell product.
Additionally, it is one of the first ever clinical trials of a cell therapy to evaluate our novel multi dose treatment course, consisting of outpatient lymphoma conditioning, followed by three once weekly doses of F. HTI 500 over up to 30 day treatments.
Cycles.
In the first 12 patients administered have HTI 500 for the treatment of advanced solid tumors.
I live in November 28, 2019 data cut off.
There were no reported dose limiting toxicities no f. HTI 500 related grade three or greater adverse events were serious adverse events and no incidence of cytokine release syndrome, neurotoxicity or graft versus host disease.
Additionally, based one and assess assessments of the patients T cell and anti body repertoire.
No anti product immune responses against F. T 500 were evident over the multi dose treatment course.
In total.
62 doses of the F. HTI 500 were administered to these 12 patients in a safe and well tolerated manner.
These initial clinical data provides strong evidence that multiple doses of IP, yes derived NK cells can be delivered off the shelf without patient matching.
We believe this is a clinically significant first step for the field the by PS derived cell based cancer immunotherapy.
We continue to be excited about the rapid advancement of our engineered I P. S derived NK cell programs into clinical development and the therapeutic potential of our pipeline of engineered I.P.S. derived NK cells for the treatment if not a large malignancies in solid tumors.
In December we report on the first two patients treated in the open label multi dose phase one clinical trial of F. T. Five six team.
The company's off the shelf NK cell cancer immunotherapy derived from a clone all master I P. S. C line engineered to express a novel high affinity non cleavable CD Sixteena FC receptor, which has been modified to augment antibody dependent cellular cytotoxicity.
F T fysixteen as the second product candidate emerging from our IP FC product platform and is the first engineered I P. S derived cell therapy in the world to undergo clinical investigation.
Each patient one administered F T fysixteen as a monotherapy for the treatment of relapse refractory AML and want administered F. T 516 in combination with were tux amount for the treatment of diffuse large b cell lymphoma had received a first treatment cycle consisting of an outpatient Lynn.
So conditioning.
Three once weekly doses of F. T five six team and ill to better promote NK cell activity.
Once again initial clinical data indicated that the multi dose treatment course was safe and well tolerated.
Additionally, in the first patient administered F. T. Five six team for the treatment of relapse refractory AML, there was evidenced of product consumerism in the bone marrow and a bone marrow biopsy obtained a day 42 showed no morphological evidence of leukemia with evidence of hematopoietic recovery.
Providing initial clinical evidence that engineered IP, yes derived NK cells may confer antitumor activity.
In December the FDA allowed our second my Indiana location for F. T. Fysixteen and we are now expanding its clinical investigation to solid tumors in combination with monoclonal antibody therapy.
At the American Society Hematology meeting in December our R&D, enabling preclinical data of the F. T. 596 was selected for presentation at the organization's car T M beyond crush program, which highlighted for promising next generation.
It's or immunotherapy programs with the potential to overcome the E limitations of current generation car T cell therapies.
T 596 is the company's off the shelf multi antigen targeted car NK cell product candidate derived from a clone old Master engineered IP FC line and is the first ever cellular mentor therapy engineered with three active anti tumor components to be cleared.
For clinical investigation by the FDA.
In addition to a proprietary car targeting cdnineteen.
50, 596 expresses our novel high affinity non cleavable CD Sixteena FC receptor.
Enabling dual targeting of Cdnineteen and additional tumor associated antigens, such as CD 20.
50, 596 also expressed as a novel I O 15 receptor fusion.
Potent cytokine complex that promote survival proliferation, and trans activation of NK cells and T cells without the need for systemic cytokine support.
New in vivo preclinical does that data presented at ash showed that in a humanized mouse models of lymphoma and leukemia.
T 596 administered as a monotherapy was comparable to primary car T cells in promoting tumor clearance and extending survival.
Additionally, when combined with Rituximab F. T 596 showed enhanced killing of lymphoma cells in vivo as compared to Rituximab alone.
These data validate the unique multi antigen targeted functionality of F. T 596, and its potential to effectively overcome CD 19 antigen escape.
And provide support that Ft, 596 has best in class potential for the off the shelf treatment of B cell malignancies.
We're pleased to announce that the open label Phase one study of the F. T 596 is now open to patient enrollment.
We're also pleased with the launch of our in House GMP manufacturing facility at our headquarters in San Diego, California that is custom designed to use clone on master IPO see lines as a renewable self source for the consistent and scaled manufacture of off the shelf NK cell in car T cell.
Products.
With the facilities launch in September we successfully completed the production of hundreds of Cryopreserved infusion ready doses of clinical product at low cost per dose.
At this time.
Each of our three clinical stage programs have HTI 500 F. T 516, and F. T 596, hundreds of Cryopreserved infusion ready doses have been qualified released and stored in inventory and or immediately available for use in our clinical.
Studies.
With our full control of GMP production combined with our proven ability to genetically engineer IP, Fcs and create and qualify colonial masters lines for clinical use we believe we have established operational capabilities and redundancies unique to the industry for the consistent cost effective manufacturing clinical.
Will supply of off the shelf sell products to patients.
As we exited 2019 with strong clinical momentum, we expect to achieve significant clinical milestones and generate decisive clinical data during 2020 across our IP, yes derived cell based cancer immunotherapy programs.
We have now amended the clinical protocol of our multi dose F. HTI 500 phase one study in advanced solid tumors to include aisle to cytokine support.
We are initiating dose expansion at 300 million cells per dose and patients were refractory to have relapse following checkpoint inhibitor therapy.
We will focus enrollment on patients with non small cell lung cancer, a tumor type amenable to NK cell trafficking and targeting.
We're up to 40% of patients with resistance to checkpoint inhibitor therapy exhibit partial or complete loss of MHC class one expression.
Making these cancer cells highly susceptible to NK cell recognition and killing.
The FCC 500 Phase one study is currently enrolling at three clinical sites in the U.S. and we plan to report dose expansion data in the second half of 2020.
We're continuing to enroll the dose escalation stage of our multi dose phase one study of ft Fivesix team as a monotherapy for the treatment of AML and in combination with Rituximab for the treatment of B cell malignancies.
Third exist clinical proof of concept for donor derived NK cell therapy for these indications and we believe there are established clinical benchmarks against which we can initially assess the safety and efficacy of F. T 516.
In the setting of relapse refractory AML donor derived NK cell therapy has shown anti leukemia activity and complete response rates ranging from 20% to 35% have been reported an investigator initiated studies.
In the setting of relapse refractory B cell lymphoma single agent activity of monoclonal antibody therapy is modest with complete response rates of approximately 10% having been reported.
We currently plan to report dose escalation data in the second half of 2020.
In addition to combination with Rituximab in B cell malignancies Orion de application for the clinical investigation of Ft. Fysixteen in combination with PDL, one PD, one EG fr and her to targeting monoclonal antibody therapy is across a broad range of solid tumor.
Ours has now been allowed by the FDA.
We initially intend to prioritize the combination of F. T 516, and the PDL, one targeting monoclonal antibody volume.
In patients with advanced solid tumors, who refractory to or have relapsed. Following at least one line of anti PDL, one monoclonal antibody therapy.
A value Matt is an 80 CCGT competent checkpoint inhibitor approved for the treatment of Merkel cell carcinoma, having a single agent complete response rate of only 10% and for the advance and for advanced Urothelial carcinoma, having a single agent overall response rate of approach.
Fortunately, 15%.
We expect to initiate enrollment of F. T 516 in combination with the volume AD in mid 2020.
We're particularly excited about our F. T 596 clinical trial, which I'm pleased to announce is now open for patient enrollment, we believe that T 596, which incorporates three acted anti tumor modalities and is uniquely designed to target multiple tumor associate.
<unk> antigens expressed on cancerous b cells has best in class potential.
Our confidence in F. 30, 596 is bolstered by the initial clinical data from a donor derived car 19, NK cell program undergoing clinical investigation at MD Anderson.
Their initial clinical results recently published in the New England Journal of Medicine showed a 73% overall response rate in patients with relapsed refractory non hodgkin's lymphoma, and chronic lymphocytic leukemia with no major toxicities.
Operator: Welcome to the Fate Therapeutics fourth quarter 2019 financial results conference call. At this time, all participants are in a listen-only mode. This call is being webcast live on the Investor 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 Walsh, Co., President and CEO of Fate Therapeutics.
While these data are early these clinical results demonstrate that car NK cells can potentially confer a high level of efficacy without the significant toxicities that are commonly associated with current generation car T cell therapies.
Scott Walsh: Thank you. Good afternoon, and thanks, everyone, for joining us for the Fate Therapeutics fourth quarter 2019 financial results call. Shortly after 4 p.m. Eastern time today, we issued a press release with these results, which can be found on the investors and media section of our website under press release. In addition, our Form 10-K for the year ended December 31, 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 studies.
Scott Walsh: Please see the forward-looking statement disclaimer in 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, 2019, that was filed with the SEC. 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 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, and Dr. Wayne Chu, our Senior Vice President of Clinical Development. Today I will comment on key milestones we achieved during the fourth quarter of 2019.
We believe F. T 596 has the potential to supplant patient specific and allogeneic car 19 T cell immunotherapies that recognized only one antigen fail to address the risk of relapse due to antigen escape and have significant toxicities we.
Currently plan to report initial dose escalation data at the 2020 Ash annual meeting.
Scott Walsh: And I will discuss our outlook for 2020 in bringing off-the-shelf, IPS-derived, cellular immunotherapies to patients. Fate Therapeutics has successfully pioneered the clinical investigation of IPS-derived cell-based cancer immunotherapy. We believe our unique therapeutic approach, using master-engineered IPSC lines as a renewable source for manufacturing cell therapy products that are well-defined and uniform in composition, can be mass-produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for broad patient accessibility, is highly differentiated from patient and donor-derived approaches to self-therapy, which require batch-to-batch sourcing and engineering of millions of primary cells And we are excited to be at the forefront of this emerging field.
We also expect to file a 90 application in the next 60 days for F. T 538.
Scott Walsh: We are encouraged by the initial clinical data reported in December from the dose escalation stage of our Phase 1 study of FT500, the company's first off-the-shelf, IPS-derived, NK-cell product candidate. Our FT500 Phase I study 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 of a cell therapy to evaluate a novel multi-dose treatment, consisting of outpatient lymphoconditioning, followed by three once-weekly doses of FT500 over up to two 30-day treatment cycles. In the first 12 patients administered FT500 for the treatment of advanced solid tumors, As of a November 28, 2019 data cutoff, there were no reported dose-limiting toxicities.
Our off the shelf CRISPR edited by PS derived NK cell product candidate.
50, 538 is the right from a colonial Master IP S. C line engineered with three functional elements.
Our novel high affinity non cleavable CD Sixteena FC receptor our novel I'll 15 receptor fusion and a complete knock out of Cdthirty eight.
F. T 538 is designed to synergize with anti Cdthirty eight monoclonal antibody therapy.
Promote enhanced antibody dependent cellular cytotoxicity.
We intend to initiate clinical investigation of F. T 538 in combination with Dar tumor.
For the treatment of multiple myeloma in the second half of 2020.
Importantly, we believe the engineered functionality of 50 538 may have very broad therapeutic applicability beyond multiple myeloma.
Scott Walsh: No FT-500 related grade 3 or greater adverse events or serious adverse events, and no incidents of cytokine release syndrome, neurotoxicity, or graft-versus-host disease. Additionally, based on assessments of the patient's T cell and antibody repertoire. No anti-product immune responses against FT500 were evident during the multi-dose treatment. In total, 62 doses of FT500 were administered to these 12 patients in a safe and well-tolerated manner. These initial clinical data provide strong evidence that multiple doses of IPS-derived NK cells can be delivered off the shelf without patient matching. We believe this is a clinically significant first step for the field of IPS-derived cell-based cancer immunotherapy. We continue to be excited about the rapid advancement of our engineered IPS-derived NK cell programs into clinical development and the Therapeutic Potential of our Pipeline of Engineered IPS-Derived NK Cells for the Treatment of Hematologic Malignancies in Solid Tumors. In December, we reported on the first two patients treated in the open-label, multi-dose Phase 1 clinical trial of FT516.
As we presented at Ash elimination of Cdthirty eight expression enhances NK cell potency and persistence in preclinical studies.
Additionally, as the field of adoptive cell therapy explores non toxic strategies to reduce or replace chemotherapy based lymphoma conditioning. It is well documented that anti cdthirty eight monoclonal antibody therapy significantly depletes a patients activate.
Scott Walsh: The company's off-the-shelf NK cell cancer immunotherapy, derived from a clonal master IPFC line engineered to express a novel, high-affinity, non-cleavable CD16FC receptor, which has been modified to augment antibody-dependent cellular cytotoxicity. FT516 is the second product candidate emerging from our iPSC product platform and is the first engineered iPS-derived cell therapy in the world to undergo clinical investigation. Each patient, one administered FT-516 as a monotherapy for the treatment of relapsed refractory AML, and one administered FT-516 in combination with rituximab for the treatment of dibuse-large B-cell lymphoma, had received a first treatment cycle consisting of outpatient lymphoconditioning, three once-weekly doses of FT-516 and IL-2 to better promote Once again, initial clinical data indicated that the multi-dose treatment course was safe and well-tolerated.
Scott Walsh: Additionally, in the first patient administered FT516 for the treatment of relapsed refractory AML, there was evidence of product chimerism in the bone marrow, and a bone marrow biopsy obtained at day 42 showed no morphologic evidence of leukemia, with evidence of hematopoietic recovery, providing initial clinical evidence that engineered iPS-derived NK cells may confer antitumor activity. And we are now expanding its clinical investigation to solid tumors in combination with monoclonal antibody therapy. At the American Society of Hematology meeting in December, our IND-enabling preclinical data for FT596 was selected for presentation at the organization's CAR-T and beyond press program, which highlighted four promising next-generation cancer immunotherapy programs with the potential to overcome the key limitations of current-generation CAR T-cell therapy.
Scott Walsh: FT-596 is the company's off-the-shelf, multi-antigen-targeted CAR and K-cell product candidate derived from a clonal master-engineered iPSC line, and is the first ever cellular immunotherapy engineered with three active anti-tumor components to be cleared for clinical investigation by the FDA, in addition to a proprietary car targeting CD19. FT-596 expresses FT-596 also expresses a novel IL-15 receptor fusion, a potent cytokine complex that promotes survival, proliferation, and transactivation of NK cells and T cells without the need for systemic cytokine support.
Did the immune system without adversely affecting the patients hematopoietic stem cell compartment.
Since 50, 538 has been engineered to resist CD 38 mediated depletion.
We believe ft, 538 may be combined with anti Cdthirty, eight monoclonal antibody and effectively administered without the use of toxic conditioning agents, including indications beyond multiple myeloma.
Scott Walsh: New in vivo preclinical visit data presented at ASH showed that in humanized mouse models of lymphoma and leukemia, FT-596 administered as a monotherapy was comparable to primary CAR T in Promoting Tumor Clearance and Extending Survival. Additionally, when combined with rituximab, FT-596 showed enhanced killing of lymphoma cells in vivo as compared to rituxim These data validate the unique multi-antigen-targeted functionality of FT596 and its potential to effectively overcome CD19 antigen escape, and provides support that FT596 has best-in-class potential for the treatment of B-cell malignancies. We are pleased to announce that the open-label Phase 1 study of FT596 is now open to patient enrollment. We are also pleased with the launch of our in-house GMP manufacturing facility at our headquarters in San Diego, California, that is custom-designed to use ClonalMaster IPSC lines as a renewable self-source for the consistent and scaled manufacture of off-the-shelf NK-cell and CAR T-cell products. With the facility's launch in September, we successfully completed the production of hundreds of cryo-preserved, infusion- At this time, for each of our three clinical stage programs, FT-500, FT-516, and FT-596.
Consequently, we are using the colonial master engineered IP has seen line for F. T 538, as a foundational back though for the building of our future IP us derived NK cell product candidates.
Scott Walsh: Hundreds of cryo-preserved, infusion-ready doses have been qualified, released, and stored in inventory, and are immediately available for use in our. With our full control of GMP production, combined with our proven ability to genetically engineer iPSCs and create and qualify clonal master lines for clinical use, we believe we have established operational capabilities and redundancies unique to the industry for the consistent cost-effective manufacturing of clinical supply of As we exited 2019 with strong clinical momentum... We expect to achieve significant clinical milestones and generate decisive clinical data during 2020 across our IPS-derived cell-based cancer immunotherapy program. For example, we have now amended the clinical protocol of our multi-dose FT500 Phase I study in advanced solid tumors to include IL-2 cytokine support. We are initiating dose expansion at 300 million cells per dose in patients who are refractory to or have relapse following checkpoint inhibitor therapy. We will focus enrollment on patients with non-small cell lung cancer.
Scott Walsh: A tumor type amenable to NK cell trafficking and targeting, where up to 40% of patients with resistance to checkpoint inhibitor therapy exhibit partial or complete loss of MHC class 1 expression, making these cancer cells highly susceptible to NK cell recognition and killing. The FT500 Phase I study is currently enrolling at three clinical sites in the U.S., and we plan to report dose expansion data in the second half of 2020. We are continuing to enroll the dose escalation stage of our multi-dose phase 1 study of FT-516 as monotherapy for the treatment of AML and in combination with rituximab for the treatment of B-cell malignancy. There exists clinical proof of concept for donor-derived NK cell therapy for these indications, and we believe there are established clinical benchmarks against which we can initially assess the safety and efficacy of FT-5 In the setting of relapsed refractory AML, donor-derived NK cell therapy has shown anti-leukemia activity, and complete response rates ranging from 20% to 35% have been reported in investigator-initiated studies.
Finally in 2020, we strive to be the first group in the world to bring off the shelf IP EPS derive car T cell therapy to patients.
Scott Walsh: In the setting of relapsed refractory B-cell lymphoma, single-agent activity of monoclonal antibody therapy is modeled, with complete response rates of approximately 10% having been reported. We currently plan to report dose escalation data in the second half of 2020. In addition to combination with rituximab and B-cell malignancy, our IND application for the clinical investigation of FT-516 in combination with PD-L1, PD-1, EGFR, and HER2-targeting monoclonal antibody therapy across a broad range of solid tumors has now been allowed by the FDA. We initially intend to prioritize the combination of FT-516, and the PD-L1-T Avelumab is an 80cc-competent checkpoint inhibitor approved for the treatment of Merkel cell carcinoma, having a single-agent complete response rate of only 10%, and for advanced urothelial carcinoma, having a single-agent overall response rate of approximately 15%.
Scott Walsh: We expect to initiate enrollment of FT516 in combination with Velumab in mid-2020. We are particularly excited about our FT-596 clinical trial, which I am pleased to announce is now open for patient enrollment. We believe FT596, which incorporates three active anti-tumor modalities and is uniquely designed to target multiple tumor-associated antigens expressed on cancerous B cells, has best-in-class potential. Our confidence in FT596 is bolstered by the initial clinical data from a donor-derived CAR-19 NK cell program undergoing clinical investigation at MD Anderson, where initial clinical results recently published in the New England Journal of Medicine showed a 73% overall response rate in patients with relapsed refractory non-Hodgkin's lymphoma and chronic lymphocytic leukemia with no major toxicity. While these data are early,
50, 819, as the Companys first off the shelf IP FC derived car T cell product candidate.
Scott Walsh: These clinical results demonstrate that CAR and K cells can potentially confer a high level of efficacy without the significant toxicities that are commonly associated with current generation CAR T cell therapy. We believe FT596 has the potential to supplant patient-specific and allogeneic CAR-19 T-cell immunotherapies that recognize only one ant, fail to address the risk of relapse due to antigen escape, and have significant toxicity. We currently plan to report initial dose escalation data at the 2020 ASH annual meeting.
And is derived from a clone master engineered IP FC line engineered with a novel one Xx car targeting cdnineteen.
Scott Walsh: We also expect to file an IND application in the next 60 days for FT-538. Our off-the-shelf, CRISPR-edited, IPS-derived, NK-cell product can, FT538 is derived from a clonal master iPSC line engineered with three functional elements, our novel high-affinity non-cleavable CD16FC receptor, our novel IL-15 receptor FT538 is designed to synergize with anti-CD38 monoclonal antibody therapy and promote enhanced antibody-dependent cellular cytotoxicity. We intend to initiate clinical investigation of FT538 in combination with daratumumab for the treatment of multiple myeloma in the second half of 2020.
Inserted into the T cell receptor alpha constant Lucas and edited for complete elimination of T cell receptor expression to mitigate any risk of graft versus host disease.
Scott Walsh: We believe the engineered functionality of FT-538 may have very broad therapeutic applicability beyond multiple myeloma, and as we presented it at.
Scott Walsh: Elimination of CD38 expression enhances NK cell potency and persistence in preclinical studies. Additionally, as the field of adoptive cell therapy explores non-toxic strategies to reduce or replace chemotherapy-based lymphoconditioning. It is well-documented that anti-CD38 monoclonal antibody therapy significantly depletes a patient's activated immune system without adversely affecting the patient's hematopoietic stem cell compartment. Since FT538 has been engineered to resist CD38-mediated depletion... We believe FT538 may be combined with anti-CD38 monoclonal antibody and effectively administered without the use of toxic conditioning agents, including in indications beyond multiple myeloma.
Scott Walsh: Consequently, we're using the Clonal Master-Engineered IPSC line for FT538 as a foundational backbone for the building of our future IPS-derived NK cell product line. Finally, in 2020, we strive to be the first group in the world to bring off-the-shelf IPS-derived CAR T-cell therapy to patients. FT-819 is the company's first off-the-shelf, IPSC-derived CAR T-cell product candidate and is derived from a clonal master-engineered IPSC line engineered with a novel 1XX car targeting CD19, inserted into the T cell receptor alpha constant lobe, and edited for complete elimination of T-cell receptor expression to mitigate any risk of graft-versus-hostility. At ASH, we presented new in vivo preclinical data from our collaboration with Memorial Sloan-Kettering Cancer Center led by Dr. Michelle Sattelon, demonstrating that in a xenograph model of lymphoblastic leukemia.
Scott Walsh: FT-819 enhanced tumor clearance and extended survival in a manner comparable to primary CAR-19 treatment. At this time, we have generated and characterized the master-engineered IPSC line for FT-819, and we intend to submit an IND application to the FDA for clinical investigation of FT-819 in the second quarter of 2020. Turning to our financial results, revenue was $2.8 million for the fourth quarter of 2019, compared to $1.7 million for the same period last year. Revenue in the current quarter was derived from the company's IPS-derived CAR T-cell collaboration with Ono Pharmaceutical. Research and development expenses for the fourth quarter of 2019 were $25.2 million, compared to $14.1 million for the same period last year. The increase in our R&D expenses was attributable primarily to an increase in employee compensation, including share-based compensation associated with the growth in headcount to support the advancement of the company's product pipeline.
Scott Walsh: Internal and third-party expenses associated with the clinical development and manufacture of the company's product candidates and expenses associated with the conduct of research activities, including in our collaboration with Ono Pharmaceuticals. G&A expenses for the fourth quarter of 2019 were $6.7 million compared to $4.3 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 $27.3 million for the fourth quarter of 2019, net of non-cash stock-based compensation expense of approximately $4.6 million. In November, the company repaid its $15 million term loan, retiring in full all of its debt obligations. Including such repayment, the company ended the fourth quarter of 2019 with $261 million of cash, cash equivalents, and investments. Common stock outstanding was 75.7 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. And with that, I'd like to open the call to any questions.
Operator: Thank you. As a reminder, to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound key. Please stand by while we compile the Q&A roster. Ashiq, our first question comes from Mara Goldstein from Mississippi. Please go ahead.
Mara Goldstein: Great, thank you. Can you hear me okay?
At Ash, we presented new Invivo preclinical data from our collaboration with Memorial Sloan Kettering Cancer Center led by Dr. Michel satellite demonstrating that in a xenograft model of lymphoblastic leukemia.
Scott Walsh: Yes, we can hear you.
Ft 819 enhance tumor clearance.
And extended survival in a manner comparable two primary core 19 T cells.
At this time, we have generated and characterize the master engineered IP Sq line for Ft 819.
And we intend to submit an eye Indianapolis location to the FDA for clinical investigation of Ft 819 in the second quarter of 2020.
Turning to our financial results revenue was $2.8 million for the fourth quarter 2019, compared to $1.7 million for the same period last year revenue in the current quarter was derived from the company's IP us derive car T cell collaboration with Ono pharmaceutical.
Research and development expenses for the fourth quarter of 2019 or $25.2 million compared to $14.1 million for the same period last year.
The increase in our R&D expenses was attributable primarily to an increase in employee compensation, including share based compensation associated with the growth in headcount to support the advancement of the company's product pipeline.
Internal and third party expenses associated with the clinical development and manufacture of the company's product candidates.
And expenses associated with the conduct of research activities, including under our collaboration with Ono pharmaceutical.
Mara Goldstein: Great, thank you. So, I have just a couple of questions. And the first question is, other than those first two initial patients treated for hematological conditions with FT-516, will there be any others in that cohort? And then, I'm just curious if you can speak to where FT-538 would fit into the multiple myeloma world in a sort of anti-BCMA landscape. And also, given the fees from ONO this quarter, maybe you could just update us as to what's going on there.
Gina expenses for the fourth quarter of 2019 were $6.7 million compared to $4.3 million for the same period last year. The increase in our Gina expenses was attributable primarily to an increase in employee compensation, including share based compensation.
Wayne Chu: Sure, I'll let Wayne answer the first two questions.
Total operating expenses were $27.3 million for the fourth quarter 2019, net of noncash stock based compensation expense of approximately $4.6 million.
Wayne Chu: So, regarding the FT-516...
In November the company repaid its 15 million dollar term loan retiring in full all of its debt obligations.
Wayne Chu: study. We continue to dose escalate in patients with acute myeloid leukemia treated with FT-516 monotherapy. And we continue dose escalation with patients with B-cell lymphomas who are treated with FT-516 in combination with rituximab. So both arms are continuing dose escalation in accordance with a standard 3 plus 3 dose escalation scheme, and then myeloma with FT530. Yeah, then with respect to FT530 and myeloma, the thing is still evolving, but certainly, in combination with daratumumab and other anti-CD38 monoclonal antibodies, as we know, it's a clinically validated target. We believe that we do have a place where FT538 can fit in the context of a myeloma landscape, even with BCMA targeting agents. We know, for example, that there are examples where BCMA, similar to CD19 in lymphomas, is subject to antigen loss and alteration, which may render BCMA targeting therapy less effective. And this is where agents like FT538 in combination with anti-CD38 monoclonal antibodies or any other monoclonal antibodies for the treatment of myeloma may have a place in the treatment landscape.
Dan Shoemaker: Hi, this is Dan. So the Ono collaboration, again, is a four-year, two-product deal. We're one and a half years into the collaboration, and again, one of the products is going to be built off the 819 backbone, where we'll put additional additions to just further improve that product to get a best-in-class heme malignancy product. And then the second product, Ono, has provided a binder for a novel solid tumor target. And again, we're inserting that into our CAR-T backbone and now adding additional edits to enhance the trafficking, the persistence, the recruitment, and the tumor microenvironment. And again, that product is – they're both in development. The heme malignancy product is about a year ahead. And then the solid tumor, because it will require additional edits, will take a little bit longer. But the collaboration is going great, and we're making good progress along those lines.
Including such repayment. The company ended the fourth quarter of 2019 with $261 million of cash cash equivalents and investments common stock outstanding was 75.7 million shares and preferred convertible stock outstanding was 2.8 million shares each of which.
Mara Goldstein: Alright, thank you.
Operator: Thank you. Our next question comes from Alethea Young from Cantor Fitzgerald. Please go ahead.
As convertible into five shares of common stock under certain conditions.
And with that I'd like to open the call up to any questions.
Thank you as a reminder to ask a question you would need to press star one on your telephone.
Your your question press the pound key please standby, while we compile the acuity roster.
I show our first question comes from Barrick Gold fan from Mizuho. Please go ahead.
Great. Thank you can you hear me.
Yes, we can area.
Great. Thanks.
A couple of questions and the first.
Initial patients.
Haematological conditions with Ft, Fysixteen will there be any others and that cohort and then I'm. Just curious if you can speak to where FC 558 would fit into that multiple myeloma world in a sort of anti M&A landscape.
Andrea R. Tan: Hey guys, thanks for taking my questions. I guess there are two for me.
Andrea R. Tan: One, can you just talk about potential partnerships and collaborations and how you think about that in 2020? I guess, you know, just kind of specifically, would you consider things outside of your current assets that are in the clinic? And how do you think about structuring that? And then I just kind of wanted to get your perspective on FT-819 and just some of the puts and takes around developing a CAR-T cell product. I mean, it's certainly not trivial science going on here, so I just wanted you to just kind of walk us through as we head into the second quarter for follow-up.
Scott Walsh: Sure, sure. I'll take both those questions, and Wayne and Dan should feel free to jump in. With respect to partnerships, I mean, we've discussed this before, you know; our intent certainly is to think about partnerships that have the potential to expand Fate's pipeline. We are not prioritizing, for instance, the partnering of existing product candidates. We think we have the potential to partner up with companies, large pharmaceutical companies that are absolutely experts in discovering, identifying, and validating novel targets, including in the space of solid tumors. And we would certainly be excited about partnering with those folks and incorporating their binding domains against novel targets into some of our more advanced IPS-derived backbones. So, for instance, an example could be, you know, somebody has a novel target or a binding domain that they have validated against target X, and we could build a CAR construct and drop that CAR construct into the FT-538 backbone. That would be something, you know; we're absolutely interested in exploring those types of partnerships where we have the potential to exploit our platform, bringing that together with novel content and building product candidates together.
Scott Walsh: With respect to FT-819, yes, FT-819 has been an ongoing journey and has been a collaboration that has been in existence with Memorial Sloan Kettering since the middle of 2016. And as you've suggested, the development of an off-the-shelf IPS-derived CAR T cell is certainly more complex than developing an IPS-derived NK cell for a variety of reasons. But one reason in particular is if you truly wanna have a universal off-the-shelf CAR T-cell therapy, obviously, the TCR that is inherent within a T-cell is alloreactive and can cause very significant GVHD. And so in developing 819 and our off-the-shelf IPS-derived CAR T-cell platform, we were very interested in it. It was a requirement, from our perspective, to knock out the T-cell receptor, and we had originally worked with Memorial Sloan Kettering and Dr.
And also given the Oh fees from our biggest quarter, maybe you could just update us as to what's going on there.
Scott Walsh: protocols, at least initially as proof of concept, where the T cell receptor was present. When we knocked out the T-cell receptor, challenges emerged initially in developing highly effective IPS-derived CAR T-cells. Over the past 18 months, there's been substantial breakthroughs in solving that problem.
Scott Walsh: For instance, Michelle and Dr. Satterlein discovered a 1XX CAR construct. We've been able to drop that 1XX CAR construct in place of the T-cell. T-Cell Receptor, so effectively, we've now knocked out the T-Cell Receptor, we've replaced it with a car, and we're using that car to drive differentiation and maturation of T-Cells. And so that culminated essentially in the presentation that we made at ASH, both at our investor event, as well as a poster presentation, where we believe we are now developing highly efficacious And we've been benchmarking them over the past year against patient primary-derived CAR T-Cells, and doing that in the model systems that Dr. Satterlein has been using over the past four, five, six years in developing primary CAR T-Cell therapy. So we feel very confident.
Scott Walsh: And just one additional thing is having the car driven by the endogenous PCR promoter drive the more natural expression pattern that results in more persistent and robust CAR-T cells. And so certainly, Michelle described that beautifully in a Nature paper a year and a half ago now, but we've been able to replicate a lot of those observations in our iPS-derived CAR-T platform. So we think that's a really important step
Sure I'll, let Wayne answer the first two questions and then Dan can talk about Arnaud.
Andrea R. Tan: Thanks, guys.
Okay ordering b F T five when sick.
Operator: Thank you.
Yigal Dov Nochomovitz: Thank you. Our next question comes from Yigal Nochomovitz from TIDI. Please go ahead.
Samantha: Hi, this is Samantha on behalf of Yigal. Thanks very much for taking our questions.
Phase one study, we continue to dose escalate in patients with acute myeloid leukemia.
Samantha: I had a couple of questions on FT-516, specifically about solid tumors. First, could you just elaborate more on what's driving your decision to first test it in combination with LUMAB? And second, how should we think about which solid tumors you'll be enrolling? Is there going to be, or should we expect any overlap with the solid tumors you're currently targeting with FT-500?
Wayne Chu: So I can answer that question. As mentioned, our FT516 Phase I study in solid tumors will initially focus on combinations with FT516 plus a value map. The reason why we selected a value map was the unique properties of this monoclonal antibody, not only with respect to its abilities as a checkpoint inhibitor, similar to other anti-PD-L1 molecules like atezolizumab, but also because it differs from those molecules because it does have ADCC activity. And so, by combining a value map with FT516, it is possible to exploit both the checkpoint inhibitor mechanism of action of a value map through its PD-L1 inhibition, as well as through its combination with NK cells in terms of targeting NK cells to tumors. And so the way that the study is designed allows for patients who have PD-L1 positive tumors; those patients would all be eligible for the combination of FT516 plus a value map. And then, depending on the activity that's seen with FT516 plus a value map, that will, in part, drive the decision to open up other combinations of FT516 with monoclonal antibodies as already written in the protocol, for example, with trastuzumab and with cetuximab to target tumors that express both HER2 and EGFR.
Samantha: Thank you for that. And just a clarifying question, can these patients also have failed PD-1 therapy, or is it just PD-L1 prior therapy?
Treated with few 506 monotherapy and we continued dose escalation with patients with B cell lymphoma were treated with up to 506 in combination with Rituximab. So both both arms are continuing dose escalation in accordance to a standard three plus three dose escalation scheme.
And then myeloma with up to 500, yet with respect to keep Fivethirty multilingual and mild myeloma.
It is I think you still evolving but certainly in combination with dollar tumor mabin other anti cdthirty eight monoclonal antibodies.
As we know as a clinically validated target we believe that we do have a place where week, where few pottery a can fit in the context of a myeloma landscape even would be CCMA.
Targeting agents. We know for example that are examples where PCM, a similar to Cdnineteen and lymphomas.
Subject to antigen launching alteration it's may.
Vendor.
May targeted therapy active and this is where agents like F. 35, 38 in combination with anti Cdthirty eight monoclonal antibodies or any other animals monoclonal antibodies for the treatment of myeloma may have a place in the treatment landscape.
Hi, This is Dan.
Okay moderation in the for year two product.
Deal were a one and a half years into the collaboration.
Again, one of the.
Is it can be built off the.
819, backbone, where we'll put additional that's there too.
This further improve that product could get a best in class.
See malignancy product and then the second product owner provided a binder to a novel solid tumor target and again were inserting that into our car T backbone and now adding additional edit to enhance the traffic in the persistence or recruitment in the tumor microenvironment and and again that product is they're both into.
And that's the heme malignancies products, it's about a year ahead and.
And then a solid tumor because it will require additional added.
Take a little bit longer, but the collaboration going great games.
Good progress.
Along those lines.
All right. Thank you.
Thank you.
Next question comes from Lithia Young from Cantor Fitzgerald. Please go ahead.
Hey, guys. Thanks for taking my questions I guess two from May one can you just talk about potential partnerships and collaborations.
And how you think about over 2020, I guess, just kind of specifically would you consider things outside of your current like method there in the clinic and how do you think about structuring that and then I just kind of wanted to get your perspective on F. T. A 19 and just some of that puts and takes around developing a car T cell product I mean, it's certainly not.
Trivial science going on here, if I just wanted to just kind of walk us through as we head into the second quarter for about and as I Andy. Thanks.
Sure sure I I think both those questions and Wayne and Dan should feel free to jump in with respect with respect to partnerships we've discussed as before.
Our intent certainly is to think about partnerships that have the potential to expand.
Fades pipeline.
We're not prioritizing for instance, the partnering of existing product candidates. We think we have the potential to partner up with companies.
Wayne Chu: No, they can fail either PD-1 or anti-PD-L1 directed therapy.
Large format for large pharmaceutical companies that are absolutely experts.
Samantha: Got it, understood. And then, just thinking...
Wayne Chu: Just to clarify, they will have to have failed at least one line of PD-L1 therapy.
In discovering identifying and validating novel targets, including in the space of solid tumors.
And we would certainly be excited about partnering with those folks and incorporating their binding domains against novel targets into some of our more advanced I PS derived backbones. So foreign Cynics. An example could be if somebody has a novel target or a binding domain, which they have valid.
Wayne Chu: Okay, so they could have failed a prior PD-1 and a PD-L1, but they need that PD-L1 failure as well. Okay, I understand. Yes. Thank you for that clarification. And then, just thinking a little bit further, would you ever consider, for FT-516 or even 596, selecting for patients with low MHC-1 expression, or is that something that's sort of FT-500 specific, given those other assets are engineered, or is it something to do with
Scott Walsh: I think this is the foundational aspect of NK biology, so I think we're going to absolutely pay attention to that as we explore our entire NK platform as one of the mechanisms. And one of the nice things about NK cells is that not only can we take advantage of the functionality we're engineering in, but certainly that sort of innate ability of these NK cells to recognize and eliminate class 1 low or null cells is something that we could always take advantage of. Um, yeah, and, um... Okay, thanks.
Samantha: Great, thanks very much for taking our questions.
Jim Birkenhoff: Thank you. Our next question comes from Jim Birkenhoff from Wells Fargo. Please go ahead.
Jim Birkenhoff: Hi guys, and congratulations on all the progress. A few questions. I guess first on 596 there was reference, and you guys have mentioned the stringent release criteria. Could you maybe talk about the measures of potency and CD19 expression, and I guess what gives you confidence?
Scott Walsh: https://thevenusproject.com
Again against target acts and we could build a car construct and drop that car construct into the F. T 538 backbone that would be something we're absolutely interested in exploring those types of partnerships, where we have the potential to exploit our platform.
Bringing that together with novel content and build product candidates together.
With respect to Ft 819, yes ft 819 has been an ongoing journey and has been a collaboration.
Operator: Dr. Michael Yigal Nochomovitz, Peter Lawson, Michael Yee, Andrea Tan, William Maughan
Scott Walsh: Sure. Absolutely, when we look at the features and functionality of the released product, one criteria that we look at is the expression levels, for instance, of both CD16 as well as CAR-19. And those expression levels, while I won't disclose what the thresholds are, those expression levels are both very high.
Jim Birkenhoff: Great. And then, Scott, maybe on... On 819, could you maybe talk about the process of tech transfer from Memorial Sloan Kettering, when that will happen, and I guess what's left to do before filing an IND there?
Scott Walsh: Sure, so... THE END. I wouldn't necessarily describe what we've done to date necessarily as a tech transfer with Memorial Sloan Kettering. We've been working hand-in-hand on this collaboration, really in replicating labs for the past three years. Most of the process development has been done at Fate Therapeutics. The initial pilot manufacturing runs have been done at Fate Therapeutics, and we fully expect that the GMP production run will also initially take place at Fate Therapeutics. And so at this point in time, we are completing pilot manufacturing, and then obviously GMP manufacturing to support the IND filing. But I think at this point in time, given that we've fully generated and qualified the master cell line, it's a pretty straightforward path, and it's an IND that we have confidence in, given our experience with INDs in the past. I think it's a pretty straight line to file the IND from this point, and, to be clear, to manufacture products. Graydon
That there has been in existence with memorial Sloan Kettering since middle of 2016, and as you've suggested the development of an off the shelf IPO stride car T cell is certainly more complex than developing a and Kate IP us derived NK cell phone.
For a variety of reasons for one of one reasons in particular is if you truly want to have a universal off the shelf car T cell therapy, obviously, the TCR that is inherent within a T cell is alley reactive and can cause is very significant gvhd.
And so in developing 819, and our off the shelf IP EPS derive car T cell platform. We were very interested in it was a requirement from our perspective to knock out the T cell receptor.
And we had originally worked with memorial Sloan Kettering and Dr. satellite in depth in developing differentiation protocols at least initially as proof of concept, where the where the T cell receptor was present.
When we knocked out the T cell receptor.
Challenges emerged originally in developing highly effective IP is derived car T cells over the past 18 months theres been substantial breakthroughs in solving that problem for instance, Michelle has dr. sideline has discovered a one xx car construct we've been able to Doug.
Drop that one X X car construct in place of the T. T cell receptor. So effectively we've now knocked out the T cell receptor. We've replaced it by a car and we're using that car to drive differentiation and maturation of T cells and so that culminated essentially in the presentation that we made at all.
Cash both at our Investor event as well as a poster presentation, where we believe we are now developing I'm highly efficacious IP EPS derived car T cells, and we've been benchmarking them over the past year.
Against patient primary derived car T cells and doing that in the model systems that Dr. satellite has been using over the past 456 years in developing.
Primary car T cell therapy. So we feel very confident about the model systems were using and the data we're generating with respect to 819.
And just one additional thing.
As having the car driven by the end Dodson STR promoter tried to more natural expression pattern that results in more persistent and robust.
Jim Birkenhoff: And just one final one, just back on FT-596. Have you identified the first patient to treat? When do you expect you'll treat that first patient? And from what you've learned from FT-500 and 516, do you think the two-weekly dose is adequate to give full coverage?
Car T cells and.
So certainly michel describe that beautifully in a major paper.
Wayne Chu: So I can answer that. We anticipate that the first patient to be treated with FT-596 will be enrolled probably within the next several weeks. The study, as mentioned, is open for enrollment. There are potential patients that have been identified. They're currently going through their screening processes, so we should know within the next week or two whether or not that first patient will come on board.
Your and a half ago now, but we've been able to replicate a lot of those observations in our IPO thrive car T platform. So we think thats a really important step forward.
Scott Walsh: I would say one of the things that we're interested in, and we talked about this on our last call, is FT-596, and obviously, our platform allows for multiple doses. And in these first patients, we are giving one dose over a 30-day period. However, the FDA has provided us with an opportunity to approach them patient by patient to repeat doses, and that's something that we fully expect to take advantage of, beginning with the first patient. And so very likely. When we provide a data update, certain numbers of our patients will absolutely be redosed. That's something that's a paradigm we're absolutely interested in exploring, and we think we have a unique platform to allow for that. Well, thank you.
Thanks, guys.
Thank you.
Thank you next question comes from you go out come over from Citi. Please go ahead.
Jim Birkenhoff: Great. Well, thanks for all the detail.
Operator: Thank you. Our next question comes from Robin Kronauskas from SunTrust Robinson. Please go ahead.
Kirpan: Hey guys, this is Kirpan for Robin. Thank you so much for taking the time to answer my question and congratulations on all the progress. So one of the questions I had was, you mentioned that we can expect to see multiple data readouts later this year. I was hoping that you could maybe help set expectations about how many patients we can see from the FT500 trial, from the FT516, how many monotherapies, how many, and it may be hard to give you bookends on how many patients data we might see and whether it would be closer to the front end of the second half or maybe Any color would be helpful.
Hi, This is Smith on for your call. Thanks, very much for taking my question.
Scott Walsh: Yeah, absolutely. I think it's too early to say and get into specific patient numbers based on specific products. Obviously, we think ASH is going to be a big conference again for the company. Just given the cadence of enrollment in the studies and the timing of initiating the FT-596 study, ASH obviously lines up to be a big conference for us. CITSE is probably another conference that we are going to target, especially with respect to FT-500, given it's focused on solid tumors. I know that answer may be somewhat unsatisfactory. I will say that we will try and provide as much transparency and provide as many updates as we can with respect to where and when we intend to present data as we get closer to the conferences.
Scott Walsh: Super, that's very helpful. One small follow-up question. What sort of data can we expect, or can we expect any preclinical data at AACR? Can you give us some clarity on that?
Scott Walsh: Yes. So at AACR. I'm actually not sure if the abstracts are published or I can even say this, but at AACR, yes, we will have preclinical data presented at AACR across multiple different product candidates. At AACR, we will very likely announce a new product candidate as well, which will be a car focused on a novel target.
Kirpan: Great, thank you so much. I appreciate it. Thank you.
A couple on FTC piano us specifically in solid tumors first could you just elaborate more on what's driving your decision to first test in combination with all that Matt and second how should we think about which solid tumors there'll be enrolling is that going to be or should we expect any overlap with a solid tumors you're currently targeting with.
Operator: Thank you. Our next question comes from Ted Tenshoff of Piper Sandler. Please go ahead.
Ted Tenshoff: Excellent
Ted Tenshoff: Great. Thank you very much, guys, and just a fantastic execution here.
Scott Walsh: I'm really getting excited about the pipeline. I'm trying to get a sense for scale at the new facility in San Diego. Will you be able to really produce all clinical supply for these planned studies from that facility? And then how should we look longer term in terms of capacity? Thanks.
Scott Walsh: Sure, so the existing facility and, you know, I've talked about our manufacturing process. It's a relatively small footprint, but you have to think of our manufacturing process very differently than I think you think about or folks think about most cell therapy manufacturing. I mean, in a single GMP suite in a 45-day period, we can manufacture hundreds of doses of product. And we're already sitting on hundreds of doses of product for FT500, FT516, and FT596. So we feel really confident in our ability to supply out of our existing facility what I'll call early-stage clinical supply across our pipeline. That said, in either late 2019 or early 2020, we did announce that we are planning to move our corporate headquarters within the San Diego area and launch a new facility in mid-2020. 2021 Sorry mid 2021, and that new facility will actually include 40,000 square feet of GMP capability. And so, we certainly feel very comfortable in our ability to supply over the next 18 months, and we're certainly planning for long-term registrational and potential commercial supply out of a facility that we expect to launch in the next 18 months.
By SK 500.
So I can answer that question so.
As was mentioned are few five when six phase one study in solid tumors will.
Operator: Excellent. Thanks so much for that. Sure.
Ben Burnett: Thank you. Our next question comes from Ben Burnett from Stiefel. Please go ahead.
Well initially focus on combinations with.
506 plus of value map.
And the reason why we selected a value map was the interest there was unique properties of this monoclonal antibody not only with respect to its abilities as a checkpoint inhibitor similar to other anti PDL one molecules like it has Elizabeth.
But also because it does it differentiates us from those molecules because it does have ADCC activity.
So by combining a value map with few 516. It is a possible to exploit both the checkpoint inhibitor mechanism of action of valley Mab through its PDL, one inhibition as well as through its combination with NK cells in terms of targeting NK cells.
Scott Walsh: Great, thanks so much. I was wondering about FT576 and the steps to move that into the clinic. And I guess really what I'm trying to get at is would you want to wait and see some clinical data for FT538 before making any decisions on 576?
To tumors and so the way that the study is designed.
Allows for patients who have.
Scott Walsh: Sure, it's a great question. We are, I would say, not waiting at all. We're aggressively building FT-576, and while I don't think I mentioned it on the call, we intend to file an IND for FT-576 in the second half of 2020. So that will be our third IND for the year. And so FT-576, similar to FT-596, just in terms of how you think about it philosophically, dual antigen-targeted, certainly can hit BCMA, can hit CD38, and can combine with a monoclonal antibody. And so we think we're building a multi-antigen-targeted best-in-class product candidate for myeloma, and we're aggressively moving forward with that development, and we do not plan on waiting for any type of clinical results for FT-538 to move FT-576 into clinical development.
PDL one positive tumors those patients would all be eligible for the combination of EPS U 506, plus a value map and then depending on the activity that's seen.
Dan Shoemaker: And as Scott mentioned earlier, 576 is actually being built on the 538 backbone, and so I think this is an interesting and powerful example of how we could leverage one master cell bank to make additional products that again will have, you know, four edits, which I think shows you the direction that we're headed with this platform. Okay, great. That's really helpful.
Ben Burnett: If I could just ask one more question, just really about the design of the 516 study. Just remind me, after patients receive a second course of therapy, is there an extension study that they can enroll in? And if there is, I guess, have any patients enrolled in it yet?
Wayne Chu: So for FT516, there is a long-term follow-up extension study. It's termed FT004. It's for patients who have progressed while receiving FT516, but require continued follow-up, largely as based on requirements from FDA regarding long-term safety follow-up, as well as ongoing safety follow-up.
Ben Burnett: Got it. Okay, you're not disclosing at this point whether or not anyone is enrolled in that.
A few five when six plus the value Mab Dell and part drive the decision to open up other combinations of ft, five onesix with monoclonal antibodies as already written in the protocol for example, with trust Tusa Mab and with some tabalumab.
Wayne Chu: No. I mean, we have long-term follow-ups for all our studies. It's an FDA requirement.
Ben Burnett: Oh.
To target tumors to where it that express both her two on each CFR.
Thank you for that and just a clarifying question can these patients also failed PD one.
Operator: Fair enough.
Ben Burnett: Okay, thanks very much. I appreciate it.
Operator: Thank you. Our next question comes from Michael Schmitz from Guggenheim Securities. Please go ahead.
Or is it just PDL one prior therapy.
No they can fail either PD, one or anti PD, one directed therapy.
Got it understood and then just thinking they will have to have it.
Just to clarify they will have to have failed at least one line of PDL one therapy.
Okay. So they could have failed prior PD, one and PDL, one, but they need that PDL one failure as well.
Understood. Thank you for clarification.
And then just digging a little bit further would you ever consider for F. T five onesix or even fivenine selecting for patients with low. It makes me want expression or is that something that's sort of S&P 500 effect given those other assets are engineered or is it something to do with more about the tumor types you're targeting.
I think it was is the foundational aspect of MK biology, So I think we're going to absolutely pay attention to that as we explore our entire NK platform is one of the mechanisms and one of those things about NK cells is not only do we can we take advantage of the functionality were engineering in but certainly that sort of.
And they innate ability of these NK cells to recognize and eliminate class one low or no cells is something that we could always take advantage of.
Yes.
Okay. Thanks.
Great. Thanks, very much for taking my question.
Thank you.
Next question comes from Jim Birchenough <unk> from Wells Fargo. Please go ahead.
Hi, guys. Congratulations on all the progress a few questions I guess first on 5006, there was reference and you guys have mentioned the stringent release criteria could you maybe talk about the measures of potency and Cdnineteen expression and I guess, what gives you confidence that those right release criteria will be predictive of a highly effective.
Michael Schmitz: Hi, this is Kelsey on behalf of Michael. Thanks for taking our questions. 2020 is shaping out to be a big year for the 596 and the 819 programs. Maybe could you just help us understand how you view advancing both an anti-CD19 CAR-NK cell asset and also an anti-CD19 CAR-T cell asset? And then maybe more broadly, how do you see both the NK franchise and the CAR-T cell franchise kind of fitting into and synergizing with your longer term corporate strategy? Thank you.
Scott Walsh: So I think it's a great question. I think it's, quite honestly, a very important question.
Scott Walsh: I think it's a question that I don't think we're going to get into publicly yet at this point with respect to our long-term clinical development strategy with respect to FT-596 versus FT819. That said, I would say, generally speaking, we don't know, and I mean we in the field do not yet know the full potential, for instance, of CAR NK cell therapies. And so we are super excited about understanding the initial clinical results for FT596. I would say, while it's only a small number of patients, the 11 patients from MD Anderson at least seem to indicate that CAR-NK cell therapy has similar types of efficacy as CAR-T cell therapy, but the toxicity profile, at least in the 11 patients, seems to be differentiated in favor of the NK cell.
Scott Walsh: It is early, don't get me wrong, but I do like the fact that we are developing both CAR-NK and CAR-T, and I think we are exquisitely positioned to answer some of these really important questions with respect to the differences between an NK cell and a T cell, and importantly, how an NK cell and a T cell may synergize together to drive curable outcomes. And I do think we are a company, and we are pursuing preclinical, and you should not be surprised if you see some interesting preclinical data from Fate Therapeutics this year that delves into the synergies between NK cells and T cells.
Cell therapy, and I have a few follow ups.
Sure.
The absolutely when we look at that features and functionality of the released product.
A criteria that we look at is absolutely the expression levels for instance of both Cdsixteen as well as car 19.
Michael Schmitz: Okay, great. Thank you so much.
Operator: Thank you. Our next question comes from Byron Ammon from Jefferies. Please go ahead.
And those expression levels, while I won't disclose what the threshold var. Those expression levels are both very high.
Great and then then Scott maybe on.
On eight Onenine could you maybe talk about the process of tech transfer from Memorial Sloan Kettering, What will happen then I guess whats left to do before filing Ryan the there.
Sure so.
The I wouldn't I wouldnt describe what we've done to date necessarily as tech transfer with Memorial Sloan Kettering.
We've been working hand in hand on this collaboration.
Byron Ammon: Yeah, hi guys. Thanks for taking my questions. Maybe I'll start with 596. You know, the M.D. Anderson paper came out in the New England Journal of Medicine. When we look at it, it seems to allow the use of transplants in two of the patients after they receive CAR-NK cells, and I think another three patients receive subsequent pharmacotherapy. Are these therapies allowed in the 596 studies?
Really almost in replicating labs for the past three years.
Most of the process development.
Has been done at fate therapeutics. The initial pilot manufacturing runs have been done at fate therapeutics and we fully expect that the GMP production. Ron will also initially take place at fate therapeutics.
And so at this point in time, we're completing pilot manufacturing.
And obviously GM, then GMP manufacture to support the high in the filing.
But I think at this point in time given that Weve.
Fully generated in qualified the master cell line.
As a pretty straight forward path and say I in D. that we have confidence given our experience with high in these in the past.
I think it's a pretty straight line to file the R&D from this point.
And to and to be clear and to manufacture product.
Great and just just one final one just back on EFI Fivenine six have you identified the first patient to treat when do you expect feel treat that first patient and from what you've learned from 505.6 do you think the Q weekly dose is adequate to give full coverage.
So I can answer that so we anticipate that the first patient to be treated with ft 596 will be enrolled probably within the next several weeks.
The.
The study has as mentioned is open for enrollment there are potential patients that by that have been identified there are currently going through those screening process. So we should know within the next week or two whether or not that first patient will will come on to study.
I would say one of the things that we're interested in and we talked about this on our last call is ft Fivenine six and obviously our platform allows for multiple dosing and these first patients we are giving one dose in a 30 day period. However, the FDA provided us an opportunity to approach them patient by patient to.
Byron Ammon: Oh, sorry. Could you repeat the last part of your question?
Byron Ammon: So, I was wondering, you know, with MD Anderson, after the patients received the CAR-NK cells, two patients received transplants, another three had received, I think one received LEN, Rituxan, and another therapy. So, I was just wondering if this was allowed in your 596 studies.
Wayne Chu: So in general, yes, they are. I mean, especially now when we're in the early stages when our dosing schedules are limited to single-dose administration. As we get additional experience with multiple dosing of FT-596, you know, our intention is to treat patients with multiple doses, but if patients, if the investigators choose to do so, patients would be allowed to receive some of these post-treatment therapies.
Scott Walsh: I think, you know, at least as we think about it, I mean, this is... very early dose escalation. And if a patient and a physician want to make a decision to go on to another maintenance therapy, or if a potentially curative transplant is available, that is permitted under the protocol. And I think, you know, for an early stage dose escalation study, it might be asking too much to restrict patients from exploring other therapies.
Wayne Chu: But I would also add that as we get additional experience from the study, if there is evidence that we're not only achieving deep responses with FT-596 but also getting durable responses with FT-596, you can imagine that discussions with the investigators would involve whether or not to continue following these patients even after receiving multiple doses of FT-596 rather than instinctively going on to other therapies.
To repeat dose and that's something that we fully expect to take advantage of beginning with the first patient.
And so like very likely.
When we provided data update certain numbers of our patients will absolutely be reduced thats something thats a paradigm were absolutely interesting exploring and we think we have a unique platform to allow for that.
Byron Ammon: So, I guess, when is that conversation going to happen? Because I guess you've got a dose range in the 596 trial from 30 million cell doses to 900 million cell doses.
Operator: ...
Matthew Cornell Biegler: I was going to say, I think that conversation, to a certain extent, is going to happen with the first patient because we are interested in exploring redosing FT-596. The FDA has provided us with a window to have that conversation, and it's certainly a conversation we're excited to have.
Scott Walsh: Okay, and then on the 8th, sorry, go ahead.
Matthew Cornell Biegler: I would just add that that, you know, would probably, you know, would probably be dealt with on a patient by patient basis and discussed with the individual investigator as well.
Operator: Okay, and then on 819, with the IND going in, do you expect any concerns from FDA on manufacturing, or should we expect that the agency is going to use similar criteria for 819 compared to 596?
Scott Walsh: I don't necessarily want to predict what the FDA may or may not choose to do. I would just say, generally, I think we have a really good handle, historically, on qualifying master iPS cell lines. That step, if you will, that stage of qualifying a master iPS cell line is independent of whether you're intending to make an NK cell or a T cell. But I would say that the manufacturing process of making an NK cell or a T cell from a master cell line is similar. It's not exactly the same by any stretch, but the first 15 days where you go from that master cell line to a CD34, that discrete stage of manufacture is actually the same whether you make an NK cell or a T cell.
Great well, thanks for all the detail.
Scott Walsh: From there, it differs. When you go from a CD34 to an NK or a CD34 to a T cell, that step of manufacture is different. But in many respects, I mean, there are a lot of similarities, and we do think we will get a lot of leverage over what we've done historically in developing and clearing the IND for FT-596, which is obviously a car NKVD.
Thanks.
Thank you. My next question comes from Robyn Karnauskas from Suntrust Robinson. Please go ahead.
Hey, guys. This is coupon for Robin. Thank you so much for taking my question Congrats on all the progress.
So one of the questions I had was you've mentioned that we can expect to see multiple data readout. Later this year I was hoping that you can maybe help set expectations about how many patients. We can see from the 3500 trial from that FIFA 16, how many monotherapy, how many and maybe how.
Byron Ammon: Great, thank you.
Operator: Thank you. Our next question comes from Matt Biegler from Oppenheimer. Please go ahead.
Matthew Cornell Biegler: Hey guys, thanks for squeezing me in. Scott, I had a quick question on the first FC516 patient. Is it fair to classify this patient at this point as a complete response, or what's the best response considered a morphological leukemia free state?
Scott Walsh: Yeah, so when we talked about the patient, and we talked about the patient and Ash, I mean, we went to great lengths to not qualify a response. The protocol has a formal assessment that is conducted at the end of the second treatment cycle. And so what we have said is that both patients went on to receive a second treatment cycle, and we simply made an observational note that we had seen persistence of FT516 in the patient's bone marrow and that at day 42, through a bone marrow biopsy, at the end of cycle one, there was a morphologic leukemia-free state.
Matthew Cornell Biegler: Got it. That's helpful. And then turning to 596, your starting dose of 30 million cells, it's around an order of magnitude lower than traditional CAR-T. But I'm just wondering if that's a fair comparison for us to make on a dose-to-dose basis, since obviously, you should have a much more homogenous final product. And then, if there's any way that you can kind of quantify what you think your dose would be relative to a CAR-T, that would be helpful. Thanks.
Scott Walsh: Yeah, I think I think it's.
Scott Walsh: I think it's too early for us to speculate on what we ultimately think is going to be sort of the MTD with respect to 596. You know, I'll note that the initial dose used in the MD Anderson product was effectively 10 million cells per dose. It was weighted, adjusted per KG, but it was effectively 10 million cells per dose. And we're starting at 30 million cells per dose. But I agree with you, 30 million cells per dose relative to what's been used in the CAR-T cell space is a low dose. Clearly, though, we believe we have a more homogeneous product. We think we have very high levels of expression of CAR, and we're excited and anxious to see how this plays out. I will say, I mean, obviously, the protocol that we submitted, though, has dose levels that escalate from 30 million cells to 90 million cells to 300 million cells to 900 million cells. And so we certainly have a protocol that encompasses what we think are more traditional doses and dose levels that are seen with CAR T-cell therapy.
To do but any sort of.
Ill.
Bookends on how many patients data, we might see and would it be closer to the front end of the second half or maybe later is there any.
Conferences that we should be thinking.
Thinking about.
Any color would be helpful.
Yeah, absolutely I think it's too early to say and get into specific patient numbers based on specific products.
Obviously, we think ash is going to be a big conference again for the company.
Just given the cadence of enrollment in the studies and the timing of initiating the F 30 596 study.
Ash, obviously lines up to be a big conference for us.
Let's see is probably another conference that we're going to target, especially with respect to F. T 500, given its focused on solid tumors.
I know that answer may be somewhat unsatisfying I will say that we will try and give as much transparency and provide as much updates as we can with respect to where and when we intend to present data as we get closer to the conferences.
So if I say houses when my follow up question.
What sort of data can we expect our can we expect any preclinical data at HCR can you give us some saturday on that.
Uh huh.
Yes, so at a CR.
Scott Walsh: Got it, thanks.
I'm actually not sure abstracts are publisher I can even say this but at HCR, yes, we will have a preclinical data presented at a CR.
Across multiple different product candidates.
At a CR, we will very likely announce a new product candidate as well.
Which will be a car focused on a novel target.
Great. Thank you so much I appreciate it.
Thank you.
Thank you.
Thank you next question comes from 10 tough from 5%. Please go ahead.
Great. Thank you very much Carlson.
Fantastic cruising here, we're going a little quicker than the credit card.
So the sense for scale of the new facility will hold Diego will you be able to Lily produce all clinical supply for these plans studies.
Operator: And our last question comes from Amanda Murphy from BTIG. Please go ahead.
From that facility and then.
So we look longer term in terms of capacity. Thanks.
Sure so.
The existing facility and I've talked about our manufacturing process. It's a relatively small footprint, but you have to think of our manufacturing process very differently than I think you think about or folks think about most cell therapy manufacturer I mean in a single GMP suite in a 45 day period.
Amanda Murphy: Hi, thanks. I just have one on, Ashiq, too.
Amanda Murphy: First, on cryopreservation for NK cells. So obviously, you've spent a lot of time working on that, and if I recall, Dr. Razvani's product is still fresh, not frozen per se. So I just wanted to get a sense of, you know, as you're adding more edits into the products, is that what the gating factor is, where I'm trying to understand the limiting factors around cryopreservation and kind of how much more you can ramp up and edit without, you know, having to...
Operator: [inaudible]
We can manufacture hundreds of doses of product and we're already sitting on hundreds of doses of product for F. T 550, 516, NFP Fivenine six so we feel really confident in our ability to supply out of our existing facility what I'll call early stage clinical.
Dan Shoemaker: Hi Amanda, this is Dan.
Dan Shoemaker: So certainly, this is one of the aspects of manufacturing that we've spent a lot of time understanding and optimizing. And one of the things I think about in IPS-derived MK cells is that they seem to just be inherently resilient to the cryopreservation process. That was a good starting point that then went into a high degree of optimization in an infusion-ready media. Interestingly, as we've gone through the different product forms, whether it's 5.16 and 5.96, we haven't seen a major difference in performance in viability and potency. And so the base cryoprocess that we established for the platform really seems to be scaling well as we add additional edits. And then I will say that T cells, just in general, are easier and more resilient to cryopreservation. So that's something that is less challenging compared to the MK side. But to answer your question, this sort of the base platform that we've established seems to really be adapting well to these editable product forms with additional edits.
Supply across our pipeline that said in either late 2019 or early 2020, we did announce that we are planning to move our corporate headquarters within the San Diego area, but.
Amanda Murphy: Okay, got it. And then my last one is probably impossible to answer, but I'll try to ask it anyway.
In and launching a new facility in mid.
20, 2021, sorry, mid 2021 and that new facility will actually include 40000 square feet of GMP capability.
And so we certainly feel very comfortable in our ability to supply over the next 18 months and we're certainly a planning for.
Long term.
Registrational and potential commercial supply out of the facility that we expect to launch in the next 18 months.
Excellent Thanks Scott.
Sure.
Thank you.
Our next question comes from Ben for and that from Stifel. Please go ahead.
Great. Thanks, so much.
I was wondering if you could talk about at T 576 in the steps to move that into the clinic.
Yes, really what I'm trying to get at is would you want to wait and see some clinical data for Aktiv factor do you before making any decisions on on 576.
Sure. It's great question, and we are I would say not waiting at all.
Amanda Murphy: I mean, there's been a lot of competitive movement in the space around IPSCs in general, and one of the things that you talk a lot about is IP and, you know, the IP that you've generated in licenses, et cetera. So just trying to sort through that all in my mind or our minds as, you know, you get, I think there is a lot of interest in IPSC-derived therapies, e Not sure if you can talk specifically about your IP strategy or whatnot, but just trying to understand, like, do you think you have blocked IP? You know, how might you approach that?
Scott Walsh: So, I'll just say this: we have over 250 patents and 150 open applications that cover iPS cell technology, including iPS-derived NK cells and T cells, and engineered features and functionality that you would embed within those cell products.
Scott Walsh: That's one of the advantages of having been doing this for 10 or 12 years.
We're aggressively building F T 576, and while I don't think I mentioned that on the call we intend to file and I. Indeed for F. T 576 in the second half of 2020, so that'll be our third R&D for the year and so ft 576, similar to Aktiv 596, just in terms of.
Amanda Murphy: Right, exactly. Thank you all.
Scott Walsh: Thank you. If there are no further questions in the queue, at this time, I'd like to turn the call over to Scott Walchko, President and CEO, for closing remarks.
Operator: Thank you all for your participation in today's call and your continued support of FATE. Certainly, there is an exciting year ahead for the field of allogeneic cell-based cancer immunotherapy, and we look forward to achieving significant clinical milestones and generating decisive clinical data across multiple programs this year.
Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.
Operator: ??? ??? ???
How you think about it philosophically dual antigen targeted certainly can hit Bcm may can hit Cdthirty eight in combined with a monoclonal antibody and so we think we're building a multi antigen targeted best in class product candidate for myeloma and were agreed.
Yes, hopefully moving forward with that development and we do not plan on waiting for any type of clinical results for F. T 538 to.
To move Ft, 576 into clinical development.
And as Scott mentioned earlier 576 is actually being built on the Fivethirty backbone and so I think that the interesting and powerful example of how we could leverage.
One master cell back to make additional products.
That again, we'll have four which I think shows you a the what the direction that we're headed with this platform.
Okay, Great Thats really helpful.
If I could just ask one more just really but the design of the 516 study.
Just remind me after patients receive a second course of therapy is there an extension study that they can enroll onto and if there is I guess has anyone enrolled onto it yet.
So for Ft 516, there is a there is a long term follow up extension study its termed FTD zero zero for its for patients who.
I have progressed, while receiving up to 506, and but we continued but require continued follow up largely.
As based on requirements from FDA regarding long term safety follow up as well as long term safety follow up.
Got it okay, you're not disclosing at this point.
As to whether or not anyone is enrolled onto that.
No I mean.
We have long term, we have long term follow ups for all our studies, yes, it's an FDA okay.
Fair enough.
Okay. Thanks, very much I appreciate it.
Thank you Hi next question comes from Michael Schmidt from Guggenheim Securities. Please go ahead.
Hi, this is currency on for Mike. Thanks for taking my question and 2020 is shaping up to be big year for the five thank six and 819 program maybe could you just help us understand how you view advancing both anti Cdnineteen car NK cell assets and also an anti CD.
I think T cell assets and then maybe more broadly how you see both NK franchise and the car T cells franchise kind of fitting into in Synergizing in your longer term corporate strategy. Thank you.
So I think it's I think it's a great question I think I think it's quite honestly a very important question I think as a question that I don't I don't think we're going to get into publicly yet at this point with respect to our long term clinical development strategy with respect to ft 596 verses ft 890.
I mean.
That said I would say generally speaking, we don't know and I mean, we the field does not know yet the full potential for instance of car NK cell therapies, and so we're super excited and understanding.
The initial clinical results for F T 596.
I would say, while it's only a small number of patients the 11 patients from MD Anderson.
Leased seem to indicate.
That car NK cell therapy has similar types of efficacy as car T cell therapy, but the toxicity profile at least in the 11 patients seems to be differentiated in favor of NK cells.
It is early don't get me wrong, but I do like the fact that we are developing both core and K.. We are developing both car T and I think we are exquisitely positioned to answer some of these really important questions with respect to the differences between and NK cell a T cell and.
And importantly, how and NK cell and a T cell may synergize together to drive curable outcomes.
And I do think we are a company and I, we are pursuing preclinically and you should not be surprised if you see some interesting preclinical data from fate therapeutics. This year that delves into the synergies between NK cells in T cells.
Okay, great. Thank you so much.
Sure.
Thank you. Our next question comes from Byron Admin from Jefferies. Please go ahead.
Yeah, Hi, guys. Thanks for taking my questions, maybe I'll start with five nine fix you know the MD Anderson paper came out.
And the newly of internal medicine.
And when we look at it it seems to allow the use of transplants and a two two of the patients after they receive car NK cells.
And I think another three patients.
Received subsequent pharmacotherapy are these therapies allowed in the Fivenine fix studies.
Okay.
Oh, sorry could you repeat last part of your question sorry, So I was wondering.
With MD Anderson after the patients receive the car NK cells to patients receive transplant. Another three had received I think one or Steve land Rover Tuxpan at another therapy.
So just wondering if this was allowed in your 596 studies.
So in general yes, they are on large, especially now we're in early stages. When our dosing schedules are limited to single dose administration as we get additional experience with multiple dosing of ft. Fivenine six of our intention is to treat with multiple doses, but.
If patients.
If they have investigators choose to do so patients would be allowed to receive some of these post treatment therapies as you described.
Thanks.
At least as we think about it I mean this is.
Very early dose escalation and if the patient and physician want to make a decision to go on to a now their maintenance therapy or if they potentially curative transplant is available.
That is permitted under the protocol and I think from early stage dose escalation study I think you might be asking too much to restrict patients from exploring other therapies.
But I would also add that as we get additional experience from the study. If there is evidence that we're not only achieving deep responses with 50 596, but getting durable responses to 596, you can imagine that discussions with the investigators would involve whether or not to.
Continue following these patients even after receiving multiple doses of ft, 596, rather than instinctively going onto other therapies.
So I guess when does that one is that conversation.
Kind of happening because I guess you've got.
Dose range in the Fivenine fixed trial from 30 million sell doses to 900 million felt those.
Yes.
I was going to say I think that conversation to a certain extends going to happen with the first patient because we are interested in exploring reducing other 50 596. The FDA has provided us a window to have that conversation and that certainly.
Conversation, we're excited to have.
And then on the sorry I.
I would just add that.
I.
Would probably would probably be dealt with on a patient by patient basis and discussing with the individual investigator as well.
Okay.
And then on any one nine.
I'd going in.
Do you expect any concerns from FDIC on manufacturing or should we expect that the agency is going to use similar criteria for 819 compared to five nine fix.
You know I don't necessarily want to predict what the FDIC may or may not choose to do I would just say generally I think we have a really good handle historically on qualifying master IPO cell lines.
That's step if you will that stage of qualifying a master IPO cell line is independent of whether you're intending to make an NK cell or a T cell.
I would say that the manufacturing process.
Making in NK cell or T cell from a master cell line.
Is similar it's it's not exactly the same by any stretch.
But the first 15 days, where you go from that Master cell line to a CD 34 that discrete stage of manufacturer is actually the same also whether you make an NK cell or T cell from narrative. It differs when you go from a CD 34 to an end care Cdthirty four to T T cell that many thats.
Up of manufacturer is different.
But in many respects I mean is there a lot of similarities and we do think we will get a lot of leverage over what we've done historically in developing and clearing the R&D for F. T 596, which is obviously a car NK cells.
Great. Thank you.
Okay.
Thank you.
Next question comes from Matt Taylor from Oppenheimer. Please go ahead.
Hi, guys. Thanks for squeezing me in Scott had a quick one on the first FC Fysixteen patient.
Fair to classify this patient at this point as a complete response or what's the best response considered morphological leukemia free state.
Yes, so when we talked about the patient and we talked about the patient at Ash I mean, we went to lengths to not qualify a response.
The protocol has a formal assessment that is conducted at the end of the second treatment cycle and so what we have said is that both patients went on to receive a second treatment cycle and we simply made an observation on note that.
At that we had seen persistence of F. T 516 in the patients bone marrow.
And that a day 42 through a bone marrow biopsy at the end of cycle. One there was a morphological leukemia free state.
Got it that's helpful.
And then turning to 596, you're starting dose at 30 million sells into its around to an order of magnitude lower than traditional car T. But I'm just wondering if that's a fair comparison for us to make on a dose to those spaces sense. Obviously, you should have a much more homogenous final product and then if theres any way that you can kind of quantify.
What you think your dose would be relative to a car T.
That'd be helpful. Thanks.
Yeah, I think I think it's too early for us to speculate on what we ultimately think is going to be sort of the the MTD with respect to 596 I'll note that the initial dose used in the MD Anderson product was effectively 10 million cell.
Sales per dose it was was weighted pretty adjusted per keurig, but it was effectively 10 million cells per dose and we're starting at 30 million cells per dose.
But I I agree with you.
30 million cells per dose relative to what's been used in the car T cell space.
It is a low dose.
Clearly, though we have we believe we have a more homogeneous product. We think we have very high levels of expression of car.
And we will more we're excited and anxious to see how this plays out I will say I mean, obviously are the protocol that we submitted though has dose levels that escalate from 30 million cells to 90 million cells to 300 million cells to 900 million cells and so we serve.
We have a protocol that encompasses what we think or more traditional doses dose levels that are seen with car T cell therapy.
Got it thanks.
Thank you.
And our last question comes from Amanda Murphy from BTG. Please go ahead.
Hi, Thanks.
It's all going on to on first on cryopreservation or NK cells.
It's obviously you've spent a lot of time working on that if I recall and sector as Bonnie.
Products, it's still its crash snack nuts resin per se. So I just wanted to get a sense of ads are adding more added into the into the products is that what the gating factor is where.
And I understand it's a limiting factors around cryopreservation and I'm kind of how much more you can ramp up in added.
Without having to do.
Yes, Hi, Amanda this is Dan.
So certainly this is one of the aspects of manufacturing that we've spent a lot of time understanding and optimizing.
And.
One of the things I think about an IPO thrive NK cells, they seem to see inherently resilient to the crowd preservation process that with a good starting point that then went into a high degree of optimization in an infusion ready media interestingly as we've gone through the different product forms of whether its 516 in fivenine.
We've not seen a major differences in performance on viability and potency and so that the base optimism the base crowd process that we established for.
The platform really seems to be scaling well as we add additional at it and.
And then I will say that T cells. This in general are are generally easier and more resilient the crowd preservation. So thats something that is less challenging compared to the NK side, but the answer your question. This sort of the based platform that we've established seems to really be adapting well to these edit product forms with additional at it.
Yeah.
Okay got it and then my last one is probably impossible to answer, but I'll try to basket anyway, I mean, theres a spend a lot of competitive movement in the space or an IP has even general and.
One of the things that you talk a lot about its IP and and now that you've generated since then et cetera.
It is trying to sort through that all my mind.
You guys I think there is a lot of interesting IP drive therapies et cetera.
I'm not sure if you could talk specifically about your IP strategy or whatnot, but I'm just trying to understand like deal do you think you have blocking IP on how many your price that.
So I'll just say this week, we have over 250 patents and 150 open applications.
That cover IPO cell technology, including IP us derived NK cells and T cells.
And including engineered features and functionality that you would embedded within those sell products.
That's one of the advantage that is having done than doing this for 10 or 12 years.
Right exactly okay.
Thank you all.
Thank you actually no further questions in the queue at this time I'd like to turn the call over to Scott Wolchko, President and CEO for closing remarks.
Thank you all for your participation in today's call and your continued support they certainly there is an exciting year ahead for the field of allogeneic cell based cancer immunotherapy, and we look forward to achieving significant clinical milestones and generating decisive clinical data across multiple programs. This year. Thank you.
Ladies and gentlemen, this concludes today's conference call. Thank you for participating you may now disconnect.
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