Good afternoon. This is Scott Walshko, President and CEO of Fate Therapeutics, and thank you all for joining us. We are excited to share with you today interim Phase one clinical data for FT516 and FT596 off the shelf iPS derived NK cell programs in relapsedrefractory B cell lymphoma. Please note, as we discuss our FT516 and FT596 programs today, Our comments will include forward looking statements that involve risks and uncertainties. These risks and uncertainties are detailed in our SEC filings, and I refer you to our most recent Form 10 Q filed with the SEC for full disclosure of these factors.
Note that 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. Joining me on today's call are Doctor. Wayne Hsu, our Senior Vice President of Clinical Development Doctor. Sarah Cooley, our Senior Vice President of Clinical Translation and Doctor. Bob Valemir, our Chief Research and Development Officer.
During our discussion, we will review interim clinical data from our ongoing FT516 study in relapsedrefractory B cell lymphoma, including sharing a first look at durability of response. Additionally, we will review interim clinical data from our ongoing FT596 study in relapsedrefractory B cell lymphoma, including sharing response rates after a single dose treatment cycle. Finally, we will review selected translational observations that differentiate our off the shelf iPS derived NK cell franchise and demonstrate its unique potential to change the field of cell based cancer immunotherapy. Ed Dulock, our Chief Financial Officer, will be monitoring for questions that we will address at the conclusion of the prepared presentation.
FT516 is
our off the shelf NK cell product candidate derived from a clonal master induced pluripotent stem cell line engineered with a novel high affinity non cleavable CD16 Fc receptor. CD16 is an activating receptor that is naturally expressed on NK cells and mediates antibody dependent cellular cytotoxicity or ADCC, a potent antitumor mechanism by which NK cells can recognize, bind and kill antibody coated cancer cells. Our proprietary hnCD16 Fc receptor has been specifically modified to maximize ADCC by preventing CD16 down regulation and by binding more effectively to tumor targeting antibodies for enhanced anti tumor activity. FT596 is our first multiplexed engineered iPSC derived CAR NK cell product candidate. FT596 builds upon FT516 and incorporates both the hnCD16 Fc receptor and a novel CD19 targeted chimeric antigen receptor, which has been specifically optimized for NK cell biology.
These two receptors enable multi antigen targeting of tumor cells, a differentiated approach that is intended to uniquely address tumor heterogeneity and overcome antigen escape. We believe multi antigen targeting has the potential to drive deeper, more durable responses for patients, including in patients that might not effectively be treated with single antigen targeting modalities, such as monoclonal antibodies, bispecific engagers and CAR T cell therapies. FT596 is also our first product candidate to incorporate our novel IL-fifteen receptor fusion, which is designed to promote NK cell survival and antitumor activity. Both FT516 and FT596 are available off the shelf and both product candidates are designed to be delivered to patients in the outpatient setting. As we review clinical data today from our studies, it is important to note though some key differences in the current FT516 and FT596 treatment regimens.
First off, dosing. With FT516, three doses are administered within a twenty eight day treatment cycle. These three doses are administered on days one, eight and fifteen. In contrast with FT596, only a single dose is administered on day one. Secondly, cytokine support.
Each dose of FT516 is administered with low dose IL-two to promote NK cell activity. FT596 is not aided by co administration of IL-two and relies on its IL-fifteen receptor fusion to drive activity. Thirdly, cycles. FT516 is administered over two cycles, while FT596 is administered over one cycle. So up to six doses of FT516 compared to only one dose of FT9596 are delivered to patients.
Patients who derive clinical benefit from the first FT596 cycle may receive a second single dose cycle with FDA consent. Finally, rituximab. While FT516 is combined with rituximab to exploit its HNCE16 receptor enhanced ADCC, the FT596 study has two treatment regimens: a monotherapy arm that evaluates the single antigen targeting activity of the product candidate's novel CD19 targeted CAR receptor and a combination arm that combines FT596 with rituximab to exploit the product candidate's multi antigen targeting functionality. Shown here is the total cell dose of FT516 and FT596 delivered in one twenty eight day treatment cycle. As we think about today's FT596 clinical data, we look to the monotherapy arm to assess the potential of our novel CD19 targeted CAR construct to drive responses, particularly in those patients that are naive to autologous CD19 CAR T cell therapy.
As we consider the combination arm, it is important to recall that dose dependency observations from our FT516 study, where the activity of the hnCD16 construct was first observed at 90,000,000 cells per dose delivered as three weekly doses. In other words, a total cell dose of two seventy million FT516 cells. Based on these observations, we would not expect the hnCD16 construct to be a major contributor to efficacy at single dose levels of 30,000,090 FT596 cells. As such, we also consider the first 10 patients treated with the combination arm to primarily be a test of the CAR construct's activity rather than a rigorous assessment of the multi antigen targeting functionality of FT596. Here's our first look at FT516 durability.
At the ASCO Annual Meeting in June, we presented positive interim clinical data for 11 patients treated in the second and third FT516 dose cohorts of 90,000,000 cells per dose and 300,000,000 cells per dose respectively. Eight of eleven patients or seventy three percent achieved an objective response, including six patients who achieved a complete response on day twenty nine, following the second FT516 treatment cycle. Notably, two of four patients previously treated with autologous CD19 targeted CAR T cell therapy achieved a complete response. We are pleased to share today that at three months from the first infusion, all eight responders maintained their response without further therapeutic intervention. And as of the data cutoff date of 07/07/2021, five of eleven patients or forty five percent continued in ongoing response without further therapeutic intervention.
This includes four patients that remain in complete response at four point six to nine point five months and one patient that remain in partial response at six point one months. The favorable safety profile, high response rates and durability of response of FT516, including in patients that have progressed through multiple CD20 targeted regimens, demonstrate the unique therapeutic value of our proprietary HMCD16 receptor and in combining FT516 with rituximab. I'm also pleased to share today early clinical data from our FT596 clinical trial. As of 06/25/2021 data cutoff, 10 patients in the monotherapy arm and 10 patients in the combination arm, so 20 patients total, were evaluable for safety and efficacy in the first, second and third single dose cohorts of 30,000,000, 90,000,300 cells respectively. In the second and third single dose cohorts comprising a total of 14 patients, ten of fourteen patients or seventy one percent achieved an objective response, including seven patients or fifty percent that achieved a complete response as assessed on day twenty nine following FT596 infusion.
Eight of 10 patients or eighty percent that had not previously received CD19 targeted CAR T cell therapy achieved an objective response, including five patients that achieved complete response. Two of four patients that previously received CD19 targeted CAR T cell therapy achieved a complete response, both of whom were treated in the combination arm, once again underscoring the potential therapeutic value of multi antigen targeting to overcome antigen escape. Notably, of the six patients in dose cohort one across both arms, only one of six patients achieved an objective response. In contrast, six patients in dose cohort three across both arms, five of those six or eighty three percent achieved an objective response, suggesting a dose response relationship for FT596. The observed safety profile of FT596 was favorable and potentially differentiated from that of T cell modalities.
We believe these early FT596 clinical data are exciting. Again, I want to emphasize that this is a CAR T cell like treatment paradigm, CyFlu followed by a single dose of FT596 with initial response assessment conducted at one month following infusion. As a whole, the interim clinical data from our FT516 and five ninety six studies are compelling and demonstrate a safety profile, response rate and durability of response that support the disruptive potential of our engineered off the shelf iPS derived NK cell programs for patients with relapsedrefractory lymphoma. I will now turn it over to Wayne for a more detailed review of our clinical data.
Thanks, Scott. Beginning with a quick reminder on the FT516 study design. As Scott mentioned, FT516 is administered in up to two treatment cycles. Each cycle consists of three consecutive days of flu site conditioning, a single dose of rituximab and three weekly doses of FT516. IL-two cytokine support is administered with each FT516 dose.
Of note, there is no requirement for mandatory hospitalization during the treatment period. All treatments may be administered in the outpatient setting. Baseline characteristics are summarized here for the 13 patients treated in the first three dose cohorts. These characteristics are typical of a patient population with advanced relapsedrefractory lymphoma where treatment options are extremely limited. In this regard, several disease specific characteristics to note here as we consider response rates and durability of response.
First, ten patients had aggressive histology, including diffuse large B cell lymphoma, high grade B cell lymphoma and transformed indolent lymphoma. Three patients had double hit or triple hit lymphoma that are known to be associated with particularly poor clinical outcome. Six patients were refractory, meaning no response to their most recent prior treatment. And five patients received prior CD19 targeted CAR T cell therapy. And finally, most patients had advanced stage disease with substantial tumor burden.
Here, we show individual patient histories and response rates for the 11 patients treated in the second and third dose cohorts of 90,000,000 cells per dose and 300,000,000 cells per dose, respectively. As I mentioned, six patients were refractory to their most recent prior therapy. And for nearly all of the five patients that responded to their most recent prior therapy, the duration of response was very short. In fact, of the 11 patients treated with FT516 in the second and third dose cohorts, only two responded to their most recent prior therapy with a duration of response exceeding two months. FT516 response assessments conducted after Cycle two show that eight of the 11 patients had an objective response as assessed by Lugano twenty fourteen criteria.
Of note, six of these objective responses were complete responses, demonstrating the ability of FT516 to drive clinically meaningful responses. Also of note, two of four patients that had received prior CD19 targeted CAR T cell therapy achieved an objective response, both of which were complete responses. Updated safety data for FT516 is summarized in this slide, which overall continue to support a highly favorable safety and tolerability profile and one that is differentiated from T cell based modalities. There were no cases of any grade of CRS, ICANS, which is immune cell associated neurotoxicity syndrome or GVHD. And there were no FT516 related serious adverse events and no FT516 related grade three or greater adverse events.
Overall, the data support administration of FT516 in the outpatient setting. And in fact, over eighty five percent of FT516 doses to date were administered in the outpatient setting. FT516 durability of response is illustrated in the swim lane plot of the 11 patients treated in the second and third dose cohorts. Of the eight patients that responded to FT516, all eight patients maintained their response at three months from first infusion. This indicates a seventy three percent overall response rate and a fifty five percent complete response rate at month three, which is shown by the vertical dotted line.
As of the 07/07/2021 data cutoff, five patients continue an ongoing response ranging from four point six to nine point five months, four of whom continue incomplete response. This includes three patients with aggressive lymphomas, subjects two thousand and eleven, two thousand and thirteen and two thousand and fifteen, all three of whom were refractory to their most recent prior therapy and one of whom, subject two thousand and fifteen, had previously been treated with a CD19 directed CAR T cell therapy. The ability of FT516 to provide profound clinical benefit in extremely difficult to treat lymphoma patients is exemplified in this case study of patient two thousand and fifteen, who was featured in our ASCO presentation. This patient had an aggressive refractory high grade triple hit B cell lymphoma characterized by bulky disease, which was refractory to all prior therapies with the exception of autologous CD19 CAR T cell therapy for which the duration of response was extremely short. Upon treatment with FT516, the patient achieved a complete response, and the patient continues incomplete response at almost five months.
As of the most recent follow-up, the patient was assessed as being MRD negative by local testing with the clonoSEQ assay, suggestive of a very deep response with the potential for long term durability. Overall, we remain highly encouraged by the data with FT516. The safety profile, response rate and durability of response demonstrate that FT516 can be effectively combined with CD20 targeted monoclonal antibody to drive meaningful therapeutic benefits in difficult to treat patients, including those with aggressive lymphomas, with refractory disease and with disease progression following autologous CD19 targeted CAR T cell therapy. And with that, I will now turn it over to Bob to review the biologic features and preclinical data of FT596.
Thanks, Wayne. As described earlier by Scott, FT596 is an off the shelf multi antigen targeted iPSC derived NK cell that incorporates three novel anti tumor modalities. First, a novel high affinity non cleavable CD16 Fc receptor to maximize ADCC in combination with various therapeutic antibodies. Second, a unique IL-fifteen, IL-fifteen receptor fusion to promote NK cell survival, proliferation and antitumor activity, avoiding the need for exogenous cytokine support. And three, a novel optimized for NK cell activity that targets CD19.
Next slide, because FT596 is manufactured from a clonal master engineered iPSC line, the FT596 drug product is a pure population of NK cells that uniformly express es its three engineered modalities. The manufacturing process is robust, over 1,000,000,000,000 iPSC derived NK cells can be produced from a single vial of bank starting material. Note that these yields are based on our small scale manufacturing process and we are currently working to implement larger scale processes as we launch our new GMP manufacturing facility. As seen here in this in vitro demonstration of multi antigen targeting functionality of FT596 in eliminating the heterogeneous population of lymphoma cells. Isogenic lymphoma lines were generated to either express both CD19 and CD20 as seen in red or to only express CD20 as seen in green.
These lines were combined in a fiftyfifty ratio and then co culture with no effector cells, a CAR NK cell targeting only CD19 or with FT596, which can leverage both its CAR and its HNCD16 Fc receptor to target CD19 and CD20. As illustrated, both CAR NK cells and FT596 clearly target the CD19 positive lymphoma compartment of the cold culture. Although you can see that IL-fifteen receptor fusion of FT596 further enhances killing to drive complete elimination of CD19 positive lymphoma cells. Now with the addition of rituximab, FT596 uniquely recognizes and kills CD20 positive lymphoma cell as evidenced by the elimination of the CD19 negative CD20 positive green population. Turning to Slide 21, the antitumor activity of FT596 is highlighted here in various in vivo xenograft models of leukemia and lymphoma.
On the left, effective CAR mediated cytotoxicity is demonstrated as non sick cells in red are eliminated by FT596 in green and this disseminated xenograft model of leukemia. And on the right, the HNCD16 mediated cytotoxicity is shown using the aggressive Raji lymphoma xenograft model. Rituximab alone in blue fails to provide durable inhibition of tumor growth, whereas the combination of FT596 and rituximab in purple effectively clears all mice with a tumor burden. As these data demonstrate, we believe best in class cell products will have multi antigen targeting functionality to address tumor heterogeneity and overcome antigen escape, driving deep and durable responses for patients. And now back to Wayne to discuss the FT596 study design and clinical results.
Thanks, Bob. Turning now to our clinical data with FT596. The FT596 study has a monotherapy arm and a combination arm with rituximab. As Scott mentioned, there are some key differences in treatment with FT596 as compared to FT516. While FT516 is administered three times in a cycle with IL-two cytokine support, Only a single dose of FT596 is administered, and it is administered without any exogenous cytokine support.
Similar to FT516, there is no requirement for mandatory hospitalization during the FT596 treatment period, and all treatments may be administered in the outpatient setting. Today, we will describe clinical data from a total of 20 patients, 10 treated in the monotherapy arm and 10 treated in the combination arm at single dose levels ranging from 30,000,000 cells to 300,000,000 cells. Patient baseline characteristics are summarized here. Similar to what was previously presented for the FT516 study, these characteristics are typical of a patient population with advanced relapsed and refractory disease. Several things to note here as we consider response rates with FT596.
Patients received a median of four prior lines of therapy, and seven of the twenty patients received prior CD19 directed CAR T cell therapy. A full fifty percent of patients were refractory. As a reminder, these are patients that had no response to their last prior treatment. And in comparing baseline characteristics between the monotherapy arm and the combination arm, it does appear, although data is early, that patients in the combination arm had more difficult to treat disease as evidenced by the higher percentage of patients with aggressive histology, refractory disease, higher stage disease and greater tumor burden. Individual patient histories and response rates for the seven patients treated in the second and third dose cohorts of the monotherapy arm are presented here with a data cutoff date of 06/25/2021.
Only two of these seven patients had documented response to last prior therapy. Response assessments conducted after a single dose of FT596 showed that six of seven patients had an objective response as assessed by Lucano twenty fourteen criteria, including three complete responses. At this point, it is important to underscore that this response assessment is conducted at the end of the first cycle. This does not capture any potential benefit from retreatment with FT596. In other words, this is the patient derived CAR T cell like treatment paradigm, one dose only.
Of note, the one patient that failed to respond was previously treated with autologous CD19 targeted CAR T cell therapy. So for the six patients who are naive to CD19 targeted CAR T cell therapy, the response rate was one hundred percent, demonstrating the robust clinical activity of the product candidate CAR construct. Safety data for the 10 patients treated in the monotherapy arm is summarized in this slide, which again supports a highly favorable safety and tolerability profile that is differentiated from T cell modalities, including T cell engagers as well as CAR T cell therapies. With respect to adverse events of interest, there were no cases of any grade of CRS, ICANS or GVHD. Additionally, there were no FT596 related serious adverse events, and there were no FT596 related grade three or greater adverse events of interest.
Of note, the events of infection were not attributed to FT596 by investigators and were generally reflective of the underlying disease and effects of conditioning chemotherapy. Individual patient histories and response rates for the seven patients treated in the second and third dose cohorts of the combination arm are presented here with a data cutoff date of 06/25/2021. Only two of these seven patients had documented response to last prior therapy, one of which had very short duration of response of less than two months, again, indicative of a very difficult to treat patient population. Response assessments conducted after a single dose of FT596 combined with rituximab showed that four of the seven patients had a complete response as assessed by Lugano twenty fourteen criteria. Notably, three patients that achieved a complete response were refractory to their most recent prior therapy.
And as we observed with FT516 in combination with rituximab, FT596 was also effective in driving complete responses in patients previously treated with CD19 targeted CAR T cell therapy. In the combination arm, three of the seven patients were previously treated with CD19 targeted CAR T cell therapy with two of these three patients achieving a complete response. The ability of FT596 to provide clinical benefit extremely difficult to treat lymphoma patients is exemplified in this case study of patient two thousand and sixteen. The patient had refractory diffuse large B cell lymphoma and was treated with six prior therapies, including multiple CD20 targeted regimens as well as autologous CD19 targeted CAR T cell therapy. The patient tolerated FT596 well with no events of any grade CRS, bicans or GVHD, with grade three or greater treatment emergent toxicities limited to hematologic cytopenia.
Upon treatment with a single dose of FT596 combined with a single dose of rituximab, the patient achieved a complete response, exemplifying the activity of FT596 in patients who failed multiple standard therapies, including autologous CD19 directed CAR T cell therapy. Safety data for the 10 patients treated in the combination arm is summarized in this slide, which similar to the safety data for FT596 monotherapy suggests a highly favorable safety and tolerability profile differentiated from T cell based modalities. The data also indicate that the safety and tolerability profile of FT596 is not adversely affected by the addition of rituximab. With respect to adverse events of interest, there were no cases of any grade of ICANS or GVHD. Additionally, the events of infection were not attributed to FT596 and again were generally reflective of the underlying disease and effects of conditioning chemotherapy.
There were two cases of low grade CRS reported, one grade one and one grade two, both of which resolved within twenty four hours. Digging into these two CRS events a bit further. In the case of patient two thousand and five, grade one CRS was reported following administration of 30,000,000 characterized only by fever that resolved in the absence of any CRS directed therapy on the same day of its onset. Of note, this patient had multiple concurrent factors that could potentially have contributed to the fever of presentation, including a history of lymphoma related fever and disease associated pleural effusion necessitating placement of an indwelling pleural catheter. In the case of patient twenty eleven, Grade two CRS was reported following administration of ninety million FT596 cells and characterized by fever and hypotension.
In this case, tocilizumab was empirically administered as CRS directed therapy. Additionally, antibiotics were empirically administered for infection, which is known to have a similar clinical presentation at CRS. In this regard, the patient was subsequently confirmed to have a pneumonia by CT scan, and notably, the fever and hypotension resolved on the same day as onset. This slide summarizes the clinical activity of emphasizing that these responses reflect a single dose of FT596 and do not capture the potential benefit of retreatment. In total, in dose cohorts two and three at 90,000,000 cells and 300,000,000 cells respectively, ten of fourteen patients or seventy one percent had an objective response with seven patients, fifty percent achieving a complete response.
And among the ten patients who are CD19 CAR T cell naive, eight or eighty percent had an objective response with five, fifty percent achieving a complete response. Finally, among the four patients who received prior CD19 CAR T cell therapy, two or fifty percent had an objective response, both of which were complete responses. Of note, there is strong indication of dose dependent activity. Specifically, at the thirty million cell dose, only one of six patients achieved an objective response, while at the three hundred million cell dose, five of six patients, eighty three percent achieved an objective response. While it's easy to focus on the patients whose disease responded to FT596 treatment, it is important to understand the underlying disease and clinical characteristics of those patients who did not respond to FT596.
In this regard, observations from the four patients who did not respond when treated with 90,000,000 FT596 cells or higher are summarized here. Notable observations include the following: In the monotherapy arm, which is reliant on CD19 targeted CAR construct and is not aided by the product candidate's HMCD16 receptor, the one non responding patient had previously been treated with autologous CD19 targeted CAR T cell therapy. In the combination arm, of the three patients that did not respond, one patient had previously been treated with both autologous CD19 CAR T cell therapy and an investigational CD20 targeted CAR T cell therapy, while the other two patients had aggressive lymphomas that were refractory or had extremely short durations of response to frontline therapy. We are further assessing non responders and certainly believe the learnings will be critical as we seek to deliver clinically meaningful responses for all patients. As we have mentioned multiple times in this presentation, the FT596 clinical data presented thus far reflect activity following a single dose of FT596.
However, we believe our iPSC product platform provides a unique opportunity to maximize the therapeutic potential of cancer based cell based cancer immunotherapies, and we are actively exploring additional levers of opportunity for FT596. First, we are continuing dose escalation to increase the cell dose in a single dose treatment cycle. Second, we are introducing a multi dose treatment cycle with FT596 administered on day one and day fifteen of the treatment cycle. And third, similar to the paradigm established with FT516, we are assessing administration of a second treatment cycle. Let's discuss this second treatment cycle a bit more.
Under the current protocol for FT596, a second single dose treatment cycle may be administered to a patient with FDA consent. All requests for retreatment that we submitted were approved by the FDA. And as of the data cutoff date, eight patients in dose cohorts two and three have been retreated with single with a second single dose treatment cycle. The clinical course of patients receiving the second single dose cycle notable for the following. First, the second FT596 cycle was well tolerated and that there were no events of any grade of CRS, ICANS or GVHD.
Second, the clinical activity of the first FT596 was maintained. Four patients with a complete response after cycle one were retreated and maintained complete response after cycle two. Response assessments for the other four patients were pending as of the data cutoff date. Based on the data submitted to the FDA to date, the FDA has recommended that they amend the clinical protocol to allow retreatment with a second FT596 treatment cycle without requiring FDA consent. And now I will turn it over to Sarah to review key translational findings from our FT516 and FT596 studies.
Thank you, Wayne. I'd like to briefly discuss some key data and observations from our translational investigations. First, I will address the potential of host immune cell rejection of FT516 and FT596. The mechanisms by which allogeneic cell products may be rejected are not fully understood, and approaches to overcome rejection are not well established in the clinic for allogeneic cell products. That said, the importance of lympho conditioning is well recognized across the field of cell therapy, including for the success of autologous CAR T therapy.
In addition to inducing homeostatic cytokines, lympho conditioning depletes potentially alloreactive host T and NK cells, creating a window of opportunity for allogeneic cell products to induce durable antitumor activity. In our clinical studies, we are closely investigating key determinants that define this window of opportunity for our cell products. As part of our investigations, we use a modified mixed lymphocyte reaction, or MLR assay, as shown in the cartoon on the left, to assess the reactivity of patient lymphocytes against product cells at various time points during the course of FT516 or FT596 treatment. Reactivity of patient lymphocytes is measured based on interferon gamma production by EliSpA and is compared against an alloreactive control that has been established using peripheral blood mononuclear cells primed to recognize and kill our product cells. Shown on the right are the median and interquartile range of interferon gamma producing patient lymphocytes sampled at the end of Cycle one or Cycle two of FT516 and FT596 treatment after co culture with our product cells.
All groups demonstrated less than 10 positive counts, comparable to that of the negative control and significantly lower than the alloreactive control, which gave greater than three hundred positive counts. Of note, we can also correlate the interferon gamma score to our companion in vitro cytotoxicity functional assay, where we have determined that the measurable cellular cytotoxicity is not observed until well above the range of 100 positive counts. Thus, for both FT516 and FT596, our data demonstrate minimal product specific recognition after two cycles of treatment, and there is no evidence of functional cytotoxicity by patient lymphocytes against the cell products. Similar to our previous observations, we also looked for and were unable to detect the development antibodies specific to the cell products. Our inability to detect host immune cell rejection of FT516 and FT596 is consistent with the peripheral blood PK data shown here for FT516.
PK is assessed at multiple time points after infusion using a digital droplet PCR assay that measures the HNCD16 transgene. Shown here are the HNCD16 transgene copies detected in patients at cell doses of 90,000,000 in green and 300,000,000 in red. The dots represent individual patients with the mean of each dose cohort represented by the bars. As shown, FT516 is detected after each of the three weekly infusions, supporting our findings that FT516 is not being rejected. For each dose, FT516 copy number decreases over a seven day period, which is not unexpected as NK cells have a short half life.
Notably, the second and third doses of FT516 do peak at lower amplitudes compared to the first dose, and this may be due to numerous factors evolving during the treatment cycle, including a decrease in FT516 survival resulting from a decrease in cytokine availability, decrease in antigen driven FT516 proliferation resulting from a decrease in tumor burden, and or differential trafficking of FT516 out of the blood and into other tissues based on Homing cues. We're also keenly interested in differences that we might observe between FT516 and FT596, which again incorporates the CD19 CAR construct as well as the IL-fifteen receptor fusion for cytokine support. Here, we are comparing the peripheral blood PK of the first dose of FT516 in red with that of a single dose of FT596 in blue. Again, individual patients are represented by dots and the median values are shown as the bars. Remember, FT516 is administered with IL-two, while FT596 is administered without any exogenous cytokine support.
We find that a single dose of FT596 administered without IL-two persists at a higher frequency and for a longer duration compared to the first dose of FT516. We believe that this differential profile of FT596 reflects the ability of its engineered IL-fifteen receptor fusion modality to provide autonomy from homeostatic cytokines induced by the lympho conditioning regimen. This is exciting as the experimental conditions are identical, the same patient eligibility, the same CyFlu regimen, the same cell dose. This certainly validates the potential to effectively administer FT596 without the requirement for exogenous cytokine support. That said, it is important to emphasize that while these peripheral blood PK data demonstrate differences between FT516 and FT596, we have not seen a correlation between peripheral blood PK and response.
It is important to recognize that NK cells are not T cells and surrogates of activity for the CAR T cell field may not apply to NK cells. More work is ongoing here to determine the best surrogates to correlate And lastly, I'd like to share a case study from a patient treated on the monotherapy arm of the FT596 study, which demonstrates the ability of the CD19 directed CAR to overcome CD20 antigen escape. This 78 year old patient had received four prior therapies, including three CD20 targeted regimens. Her baseline tumor biopsy demonstrated high expression of CD19 and complete loss of CD20.
She was treated with a single dose of FT596 at 90,000,000 cells as monotherapy. Peripheral blood samples taken throughout her treatment course demonstrate the kinetics of clearance of the CD19 positive malignant population and recovery of the phenotypically normal B cell population. At day minus five prior to treatment, both normal CD19 plus CD20 plus B cells and malignant CD19 plus CD20 negative lymphoma cells are present. At day four, immediately after the FT596 dosing, the normal cells have been ablated, while the malignant cells show resistance to the CyFlu lympho conditioning. By day twenty nine, the normal B cell population is recovering, while the CD20 negative lymphoma cell population continues to decrease.
After one cycle, she achieved a complete response with complete resolution of all metabolically active disease, a 92% reduction in tumor size, and the clearance of the lymphoma from her bone marrow that had been present at baseline. And by day one hundred and four, without the benefit of second FT596 treatment cycle and with no further intervening therapy, a robust recovery of normal B cell population was observed with complete elimination of the malignant cells. This example highlights the value of multi antigen targeting to overcome antigen escape, a common mechanism of resistance to standard CD19 or CD20 targeted therapy, and to drive a durable complete response. At this point, I will turn it back to Scott for some final comments.
Thanks, Sarah. Our mission at Fate Therapeutics is about changing the game in cell therapy. While cell therapies hold extraordinary potential, the business of making and delivering a cell therapy is massively complex, very often personalized and far too limited with respect to patient reach. Our vision is to develop and deliver cell therapies in a manner similar to monoclonal antibody therapy. Our renewable cell line is used for manufacture, product is mass produced in a cost effective manner, the product is conveniently administered in a thaw and infused manner and many patients have access to and receive the product with the urgency needed to treat cancer.
We believe our iPSC product platform is uniquely delivering on this promise. And while we believe our iPSC product platform confers unparalleled advantages paired to patient and donor derived cell therapy approaches, our focus is on bringing best in class cell products to patients. To that end, I want to summarize a couple of key observations from today. With respect to product efficacy, early clinical data from our FT516 and five ninety six programs in difficult to treat patients demonstrate compelling response rates and the maturing durability of response data from our FT516 program indicate that the clinical benefit can be lasting. We have shown that our proprietary hnCD16 Fc receptor can uniquely synergize with and enhance the mechanism of action of tumor targeted antibodies and that both FT516 and FT596 can be effectively deployed in combination with CD20 targeted monoclonal antibody therapy to enhance patient outcomes.
The clinical benefit mediated by our hnCD16 Fc receptor has been shown to be deep and early data suggest the potential for significant durability of response. Additionally, we have demonstrated the activity of our novel CAR construct incorporated into FT596 and its potential to drive high response rates with a single dose treatment schedule in heavily pretreated patients. Together, the integration of these two elements into FT596 enable multi antigen targeting and a potential best in class therapeutic profile with the ability to attack tumors through multiple mechanisms of action to effectively address tumor heterogeneity and to uniquely overcome antigen escape. With respect to product delivery, we have shown that FT516 and FT596 are available on demand at the time of patient need. We have demonstrated the ability to serve patients in the outpatient setting with over eighty five percent of FT516 doses administered outpatient.
We have also demonstrated the ability to deliver multiple doses without eliciting host T or B cell mediated rejection, a treatment paradigm that may drive deeper and more durable responses. Finally, with respect to safety and tolerability, we have continued to show that our iPS derived NK cell product candidates are well tolerated and have a profile that is differentiated. We believe this favorable profile will facilitate combination with other therapies, including those used as standard of care in earlier lines, and will allow patient reach into the community setting. Where do we go from here? With respect to FT516, we're currently planning to initiate multiple dose expansion cohorts to further assess its efficacy.
These cohorts include third line diffuse large B cell lymphoma and third line follicular lymphoma, both in patients that are naive for autologous CD19 CAR T cell therapy. Additionally, since we have observed complete responses in two of four patients in dose cohorts two and three whose disease progressed following autologous CD19 CAR T cell therapy, we plan to initiate a dose expansion cohort in patients with aggressive B cell lymphomas that have been previously treated with autologous CD19 CAR T cell therapy. We believe this dose expansion cohort in particular addresses a growing market segment with a significant unmet need and may offer a potential fast to market development path. Finally, since FT516 may be administered in the outpatient setting given its favorable safety profile, we plan to initiate a dose expansion cohort of FT516 in combination with bendamustine and rituximab and without tyFlu chemotherapy conditioning to explore its use with standard of care CD20 targeted regimens and earlier line therapy. In these dose expansion cohorts, we intend to include sites that serve patients in the community setting.
With respect to FT596, we are currently enrolling the single dose treatment schedule at 900,000,000 cells in both the monotherapy and combination arms. We are initiating enrollment in the two dose treatment schedule beginning at 300,000,000 cells in both the monotherapy and combination arms and expect to dose escalate the two dose treatment schedule to 900,000,000 cells. Based on observed safety and efficacy, we expect to select either the single dose or two dose treatment schedule for conduct of dose expansion. As a reminder, based on the FDA's recommendation to amend the FT596 clinical protocol, retreatment with a second FT596 treatment cycle without requiring FDA consent will now be permitted. And finally, we are poised to expand clinical investigation of our off the shelf multiplex engineered iPS derived NK cell franchise to multiple myeloma.
Similar to our approach in lymphoma, we are beginning clinical investigation by leveraging our HNCD16 receptor, combining FT538 with the CD38 targeted monoclonal antibody daratumumab to maximize ADCC. We're also advancing FT576, our off the shelf iPS derived CAR NK cell product candidate designed to target multiple antigens through its hMCD16 receptor and its high avidity BCMA targeted CAR. We are poised to begin clinical study of both FT538 and FT576 in multiple myeloma and look forward to bringing patients these potentially best in class therapies. Thank you for your time today. I would now like to open the call up to any questions and Ed will moderate those.
Great. Thank you, Scott. We've had a number of questions come in during the presentation. But as a reminder, you can ask a question by utilizing the questions and answers functionality within the webcast presentation. First question is about dose response, specifically related to FT596.
There's an observation that there's clearly an effect from 30,000,000 to 90,000,000 cells, but an observation of this leveling off potentially from 90,000,000 to 900,000,000 or 300,000,000 cells. So have we reached an optimal dose at ninety million or just general comments about dose response for FT596?
Sure. Wayne, do you want to comment on that?
Think so I think it's very clear that with respect to five ninety six, there's clear evidence of dose dependency just given by the fact that at 30,000,000 cells, we see only one out of six responses. And certainly, as we get to the 300,000,000 cell dose level, we see six out of seven. Whether or not that whether or not the trend of that dose response is maintained, I think it's just going to require more data. Because I think that, as everyone can appreciate, these patients are highly heterogeneous. There may be other factors that contribute to that dose response.
And as we further optimize our dose and schedule, I think we'll have definitely have that opportunity to determine what that dose response relationship is, not only with respect to the number of cells per dose, but the cells that are delivered over multiple doses.
Thanks, Wayne. Second question, multipart questions, we'll take this in pieces. Talking about FT516 and the durability responses, what can we see at this point versus allogeneic CAR T?
I mean, I'll take that. I mean, I think it's too early to know ultimately what the long term durability of FT516 is and how that compares to CAR T cell therapy. I think we're encouraged to date that the three month durability of response, I think is similar to CAR T cell therapy. I think we noted it was 73 OR and 55% CR, which I think is in line with even autologous CAR T cell therapy. And I think we're very encouraged by the durability that we're seeing as we continue to follow these patients.
Four of the eleven patients remain in CR. Several of those were, I think we alluded to, were refractory to prior therapy. And in fact, one of those was previously treated with CAR T cell therapy and continues in CR.
And then a follow on question about bringing FT596 into the equation, moving to multiple doses per month, the potential for higher CR rates, thus potential benefit in terms of durability, any thoughts on five ninety six versus five sixteen?
Yes. I mean, I think five ninety six we continue to believe is a best in class product candidate, absolutely. And I do believe that patients can be aided by additional therapy. We've certainly reported that in the past for five sixteen and we have reported that for five ninety six. I think it's important to note that as we have retreated patients, we've continued to see maintenance of response and in some cases deepening of response.
So I do think there's a benefit to continue to add a second cycle as long as it's well tolerated and that that second cycle can drive deeper and more durable responses.
Thanks, Scott. The next question, again, 05/16 and 596. Have we learned anything about the second or third dose in a cycle of FT516 versus what we're moving to with five ninety six in terms of going from a one dose to a multi dose paradigm and what we expect the read through might be for FT596?
I'll start and then I'll allow Sarah to jump in. Look, think what we have seen and we've seen with the PK data, and again, the blood may be a poor proxy ultimately for measuring NK cells. But I think we have seen that certainly with FT516, we've been able to safely deliver three different doses that those three doses are detected. And we've seen that actually the second cycle with FT516 can add patient benefit. We've seen certainly deepening of responses after from the first cycle to the second cycle with FT516.
With respect to FT596, I think the data that Sarah presented has clearly shown that the first dose of FT596 is at least again using the blood as the proxy, which may be a poor proxy, but it's certainly outperforming FT516 with respect to its presence in the blood and its persistence. And so I do think as we look at, for instance, five being administered in a three dose treatment schedule, we are confident based on what we're seeing with FT596, including the response rates, as well as the PK, that a two dose schedule for five 96 in cycle is the right schedule. Don't know, Sarah, if you have anything to add to that.
No, I agree with how you characterized it. And I guess I would just add that clearly this is not an apples to apples experimental design to understand multidosing versus single dosing. And the protocol amendments that Wayne spoke of will give us more opportunity to look at how FT596 behaves in a multiple dose per cycle schedule.
Thank you, Sarah. Next question is around durability for FT516 and how do we think about this in the context of approved CD19 autologous CAR T cell therapies? And specifically, this six month rule as it relates to CR rates that relevant in the context of NK cells and FT516 specifically?
Yes. I mean, I think, look, the reality is there are multiple autologous CAR T cell therapies that are approved. And I think, if I'm going to get this right, and Ed, you're an expert in this, so you can correct me. But the six month CR rate for the autologous CAR T cell therapies ranges anywhere between say thirty percent to thirty five percent, something in that range with respect to the six month CR rate. If I look at our data today, we're right in that range with FT516.
We are four of eleven patients remain in CR anywhere between four point six out to nine point five months. A fifth patient is in continuing PR. So I feel really good about where we are with respect to FT516, which keep in mind doesn't have a CAR, and its ability to synergize with Rituxan and drive responses. I think the one of the things we're trying to accomplish with FT516 and we're excited about is the potential to look at its ability to be used down line of CAR T cell therapy, where we've clearly been able to show that patients that have progressed after CAR T cell therapy are able to respond. And they are responding with degrees of durability, which is exciting to see.
And then in addition, going to the other end of the patient spectrum, I do think we have a differentiated safety profile. And clearly, we've administered, I think Wayne mentioned, about eighty five percent of the doses in the outpatient setting. So I think we have the ability to move to earlier lines of therapy essentially become an add on to a rituximab regimen that is used standard of care in earlier line. I think CAR T cell therapy will have a very difficult time moving into that outpatient paradigm.
Thanks, Scott. The only thing I would add is those CR and response rates typically in autologous CAR T are done on a modified intent to treat population, whereas ours is obviously an ITT population. The next question, straightforward one related to FT596, And do we have any thoughts on the value potentially adding IL-two, the treatment regimen for FT596?
I mean at this point in time,
we don't plan on adding IL-two to the treatment regimen. We're pretty excited about what we're seeing with the IL-fifteen receptor fusion that is engineered into the product candidate. And clearly, we are seeing, at least again, peripheral blood as a proxy, we're seeing FT596 outperform, if you will, FT516, which is aided by IL-two, but does not have the benefit of the IL-fifteen receptor fusion.
Thank you, Scott. Next question related to FT596 and about repeat or second cycle dosing. So for all the patients that receive a second cycle of FT596, were those all patients who had an initial response to the first cycle? And then the second part of the question is, do we have any data suggesting retreating someone in the first cycle who did not respond and whether or not there's a benefit of that subsequent FT596 cycle?
So I believe Wayne can jump in, but I believe all the patients that were retreated with FT596 had a response at the end of the first cycle. And that response was either maintained or deepened with the second cycle. We do not yet, to my knowledge, and Wayne jump in, we don't have any experience yet with treating a patient that has not responded following the first cycle. But Wayne, you may confirm that.
Yes. No, that's indeed true. As Scott mentioned, all patients who were retreated had at least a partial response after the first cycle. And also as Scott mentioned, we do have cases where we have evidence of a deepening response after the second cycle of treatment. And then in patients who achieved a complete response after the first cycle, as we've stated in the presentation, those patients were able to maintain that complete response.
Thanks, Wayne. Number of questions around the expectations for ASH as it relates to the durability update we should expect for both FT516 and FT596?
Yes, think we do plan on providing additional updates to both the five sixteen and five ninety six programs at ASH. And I expect we'll get our first look at durability with respect to FT596, certainly in the single dose treatment paradigm.
Great. We have a number of questions about next steps. Think we addressed some of this in the presentation. But questions around have we determined what the recommended Phase two dose is, is the first part of the question. There's a couple of follow ups as well.
I don't think we've determined yet what the recommended Phase two dose is. I think with respect to both FT516 and FT596, we're at the top end of what we think is dose escalation at this point, at 900,000,000 cells as the dose level. And so we'll generate that dataset, look at the data and then obviously proceed with what we think is the right dose for the expansion.
Okay. And then for FT516 specifically, any more details around the plans for engaging with regulatory authorities? And are we able to give any loose timelines with respect to potential BLA filings with the earliest date for 05/16?
Yes, I think it's too early to make a comment on BLA filings, but I will comment on sort of regulatory engagement. As we complete dose escalation for FT516, which should wrap up in the next couple of weeks, we do plan on submitting an RMAT application to the FDA to begin to engage in a more formal way with respect to a pivotal path for FT516. I think our initial sense is that the a potential fast path to market is treating patients that have progressed or failed autologous CAR T cell therapy, where we've certainly seen responses with both FT516 as well as FT596.
Thanks, Scott. There are a number of questions about an interest in learning more about the expansion as it relates to bendamustine Rituxan combination. Any other additional comments around design or timing for that expansion or plans beyond that would be useful.
Sure. Wayne, do you want to comment on that?
Sure. So regarding rituximab and bendamustine, that is a combination that will be initiated very soon with FT516. And as was mentioned in the presentation, the concept around combining FT516 with something like rBenda takes advantage of arbenda's properties, both with respect to the anti lymphoma activity, as well as the ability of agents such as bendamustine to act as a conditioning agent to support FT516 pharmacokinetics. So that piece of FT516 is already included in the most recent protocol amendment, and we expect to enroll patients testing that combination very soon.
Thank you, Wayne. Question related to FT596, we've mentioned multi antigen targeting on a number of occasions. Question specifically is around, is this referring to CD19 and CD20 only? Are there other antigens that we're considering as well?
Certainly. I think with the Fc receptor, this HNCD16 Fc receptor, we feel there's the ability to engage multiple different monoclonal antibodies, for instance, and target a variety of antigens where there is a monoclonal antibody that is available for targeting. And so, for instance, we are leveraging that receptor clearly in combination with rituximab. We will leverage that receptor in combination with abituzumab, both in the lymphoma setting. We're leveraging the CD16 receptor in combination, for instance, with daratumumab, both in AML and lymphoma.
And certainly as we think about solid tumors as well, we look forward to leveraging the HNCD16 receptor combination with monoclonal antibodies that are used early and often in treating solid tumors.
Thanks, Scott. Question generally about chemotherapy induction and the necessity for this for our NK cells, including FT596 that has IL-fifteen receptor fusion?
Yes. I mean, I can Sarah can comment on that. I think it's one of the reasons we're interesting in combining with our bendamustine. And I'll hand it over to Sarah.
Yes. I mean across the field, lympho conditioning traditionally with CyFlu is utilized. And as I mentioned, understanding the specific elements in terms of inducing IL-fifteen and other homeostatic cytokines versus clearing space versus eliminating potentially alloreactive cells all play a role. And it's our hope to dissect out for our products in specific which of these elements are necessary. So for example, the data with five ninety six demonstrates that perhaps the need to induce IL-fifteen from the patient is not there if we've engineered that element into the cell.
So we're actively investigating opportunities to use less intense conditioning, specifically with the bendamustine arm that will be opening soon that Wayne mentioned and other paths to look what is the minimal necessary lympho conditioning that we need to add to allow that window of opportunity for the cells to proliferate and achieve the antitumor effect sufficient for durability.
Thank you, Sarah. Next question about patients who had previously exposed to autologous CD19 CAR T therapy, do you have any reason to believe that FT596 or FT516 in combination with rituximab would reactivate or reinvigorate CD19 CAR T cell therapy? Have we looked at this in any of the responses that we've seen in relapsedrefractory patients?
I'll take that. It's an intriguing question and we're very interested to understand if we can resuscitate either autologous CAR T cells or just plain autologous T cells in the patient. And so we're doing extensive immune profiling to understand characteristics of the reconstituting T cell compartment to look for interactions between our product and the patient T cells. I'll add it's a little it's slightly difficult to evaluate other parts to pick out the CAR T cells of patients who've undergone prior therapy with the approved products, but it's something that we're actively looking at.
I would just also add that in those patients who've received prior autologous CD19 CAR T therapy and were treated with either FT516 or FT596, As we kind of alluded to in the presentation, we don't see anything, at least from a safety perspective, that suggests, you know, a profile of either cytokine release syndrome or ICANS that strongly indicates a pattern of reactivation of CAR T cells, knowing that, at least anecdotally, that some of the patients who received prior CAR T did have some level of CRS when they received CAR T that was not replicated with the administration of our INK cell products.
Okay. Thanks, Sarah. Thanks, Leen. Question relates to five ninety six and the moving towards multiple doses and potentially up to two cycles. We have is this more in the context of driving greater durability?
And do we have a clear understanding looking at immune response, what that rate frequency of dose and schedule are for FT596 to drive durability similar to CAR T response?
Yes. I think it's too early for us to answer that question. I think clearly with FT516, we've been able to demonstrate we can safely administer three doses in two cycles. I think with the PK data and the response rates that we're already seeing with FT596, We certainly believe that we can drive significant responses off a single dose in a single cycle, yet we strive to deliver the best product candidate to the patient. Our platform allows for dosing flexibility and we believe that that's worth exploring here in at higher doses as part of dose escalation before we move into an expansion.
Thanks, Scott. The next question I think we've addressed at some level in the presentation. As it relates to five ninety six and responses of monotherapy patients versus the combination, Is the more difficult to treat set of patients in the combination are sort of explain the lower response rates observed in that combination with Rituxan?
Yes. I think it's hard to make generalization on relatively speaking small numbers of patients. But yes, I think as Wayne alluded to in the presentation, I think the patients in the combination arm were more difficult to treat. A higher percentage of them had had CAR T cell therapy previously, had had refractory disease, had greater tumor burden. Yet, I would note the CR rate was in fact higher in the combination arm.
Thanks, Scott. The next question also related to five ninety six. Maybe, Wayne, this is a question for you if we cut the data. We are looking for response rate and CR rates in aggressive versus indolent lymphoma histologies for five ninety six?
Yes. So yes, for five ninety six, so based on the information that we presented, you know, with the individual patient data and then presentation, if you just by the hand count, For diffuse large B cell lymphoma, and I would actually include the one case of Grade 3b follicular lymphoma in that category because for all in terms of clinical outcomes, are similar. There are a total of seven patients with DLBCL and the one case of Grade 3b follicular lymphoma. Four of those seven had an objective response, three of which are which were complete responses. And then for follicular lymphoma, which is grade one, two, three, a follicular lymphoma, there are a total of four patients.
Three of them had a response and all three of them were complete responders. And then just for completeness sake, the remaining three patients had other types of lymphomas. All three had responses and one of them with a complete response. I should point out that these numbers, a total N N14 reflect those patients treated at a cell dose level of 90,000,000 FT596 cells or higher.
Thank you. Next question, again FT596, translationally do we look for cell expansion and durability, either PCR or flow cytometry to understand the expansion and durability of five ninety six cells post infusion? This is more of question a about the functionality and validating the functionality of the IL-fifteen receptor fusion.
Yes. So the data I shared comparing FT516 and FT596, you can see the PK profile and kinetics of the five ninety six product after infusion. We, when possible, collect the cells from the peripheral blood if they're there in sufficient numbers to evaluate the function of the product cells over time in vivo after being exposed to tumor. And I don't have specific details that I can share with you now about changes in the function compared to infusion and after in vivo exposure, but that's something that we're characterizing closely.
Thank you. Follow-up question, just generally, guess, 16 or five ninety six about evading endogenous immune clearance. Do you have any engineered cells, anything about stealth of our capability there, whether they're required and whether or not they're engineered or thought about for a five sixteen or five ninety six?
Can I just make one comment? The data that we showed today so far for five sixteen and five ninety six that the doses infused, we're not seeing evidence that there's immediate host rejection. So today, it's not a problem that we're seeing. However, in the future, it could develop. So I'll let Bob
comment. Sure. No, I agree with Sarah completely. Right now we're seeing for the first two months no recognition. And if we were to see that, I think we have multiple programs that we'll be updating you at ASH on unique strategies that I think are best in class and look forward to sharing that with you guys, Ben.
Thanks, Bob. Question on five sixteen, the lower Cmax, the three dose schedule of five sixteen plus rituximab, are we considering any modifications to the schedule as we think about expansion cohorts or studies beyond Phase one development? No.
I think at this point, we're really pleased with what we're seeing with respect to FT516. I mean, we're seeing clearly that three doses can be well tolerated in the first cycle. We've seen evidence that in certain patients that the second cycle is clearly adding to a deepening of response. So at this point in time, based on the response rates that we're seeing and the durability of response, including down line of CAR T cell therapy, I think we're very comfortable in filing our RMAT submission and engaging with the FDA to plan for a pivotal study, which again most likely with FT516 will be focused on patients that are down line of CAR T cell therapy or in patients that we plan to treat earlier line with a standard of care rituximab regimen.
You, Scott. Wayne, maybe back to you, a question around FT596. Think I we addressed this in the presentation, there are talk about the wide spectrum of histologies within our Phase one study. How do these patients compare to a more traditional third line DLBCL population in terms of aggressiveness of disease?
Yes. So as it relates to a late line relapsedrefractory population with aggressive disease, I would say that based on the characteristics that we presented with respect to prior therapies, degree of refractoriness, the advanced stage of disease and overall tumor burden, I think it's at some level, it is very comparable to what one would expect in this particular patient population, particularly with respect to the number of prior therapies. And I think that the advanced stage and the significant tumor burden that we see in these patients are just reflective of the fact that, for patients who don't get cured with initial treatment, treatment options are extremely limited. And despite multiple efforts, a patient's underlying aggressive lymphoma continues to grow.
Thank you, Wayne. In terms of five sixteen or five ninety six, do we see a correlation with Cmax and tumor burden programs?
Yes. We've looked for multiple things that could predict Cmax or response or PK, and we have not been able to correlate tumor burden or tumor histology with the PK profile at this point.
Maybe one or two more questions. The next question talks little bit about from a regulatory perspective in patients with prior CAR T. Do we have a sense of what the bar would be in terms of clinical benefit and durability specifically?
I think it's too early to comment on that.
Next question about product specific or lack of product specific anti HLA antibodies is the same after issuing subsequent cycles of 5516 or May?
Yes, that's a good question. I touched on that too briefly. So we look for the development of anti product HLA Class one and Class two antibodies. And we haven't seen in the patients on 05/16 or May any development of any anti product antibodies after Cycle I or Cycle II to date.
Last question? Yes, last question. With respect to May and where we are in dose escalation at 900,000,000 cells, just clarification on where we expect to be at ASH in December?
At ASH in December, I think we will continue to backfill in the single dose cohort. We will continue to backfill at the 300,000,000 dose. We will continue to escalate now at 900,000,000 cells, which we will also likely backfill. So we are probably between now and ASH, we're looking to backfill 300, complete 900 with up to six patients. And in addition now, begin to treat patients at 300,000,000 cells with the two dose treatment schedule.
And so I think we'll have a pretty fulsome update with FT596 at ASH, including on durability of the responses that we're seeing.
Great. Scott, back to you. Thank you. Thank you. Thank you.
And thank you everyone for participating in today's call. Be well.