Celyad Oncology SA
Q2 2019 Earnings Call Transcript

Published: 23 Aug 2019

[Operator:]

Ladies and gentlemen, thank you for standing by and welcome to Celyad's Second Quarter 2019 Financial and Business Update. At this time, all participants are in a listen-only mode. There will be prepared remarks by Celyad's Management, followed by a question-and-answer session. I must advise you all that the conference is being recorded.And with that, I'd like to turn over the call to Dr. Anne Moore, Celyad's Vice President of Corporate Strategy. Please go ahead, madam.

[Anne Moore:]

Thank you, operator. And thank you, everyone, for joining us for our first half 2019 results call today. Joining me today is Filippo Petti, our CEO and Interim CFO; Dr. David Gilham, Vice President of Research & Development; and Dr. Frédéric Lehmann, Vice President of Global Clinical Development and Medical Affairs.We will start the call with the business and clinical update, followed by an overview of the financials. And then we will open the line for your questions.With that, I'd like to turn over the call to Filippo Petti. Please go ahead, Filippo.

[Filippo Petti:]

Thank you, Anne. And thank you, everyone, for joining us today. We have had a steady flow of news over the past few months, and the momentum in our business has been building steadily since the beginning of the year.I am pleased to say that Celyad team has continued to execute on the development strategy for our NKG2D-based autologous CAR-T candidates, CYAD-01 and CYAD-02; as well as our allogeneic NKG2D-based candidates, CYAD-101 and our shRNA based allogeneic CYAD-200 series of pre-clinical candidates.In addition to advancing our pipeline, we have also made strategic enhancements to our platform, including the introduction of a proprietary OptimAb manufacturing process. T cells continued to be a promising area of oncology therapeutic development, and we believe that Celyad is increasingly helping to advance the landscape.In the past few months, we announced promising data from our ongoing Phase 1 clinical trials, both for the treatment of hematological malignancies and solid tumors. In June, we presented an update to our autologous relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome program at the European Hematology Association, or EHA meeting, in Amsterdam, Netherlands; shortly followed by the presentation of preliminary data and our refractory metastatic colorectal cancer program at the European Society of Medical Oncology World Gastrointestinal Congress or ESMO GI in Barcelona, Spain, in early July.We continue to be pleased with the preliminary data generated to date, for both our autologous and allogeneic NKG2D-based CAR-T product candidates, CYAD-01 and CYAD-101 respectively, and look forward to future updates for the program in the months to come.Importantly, in June, we also introduced our updated manufacturing process, OptimAb; which brings together the best attributes from previous manufacturing processes that we have – well, that we have a high level of manufacturing reliability with, in line with our clinical development strategy needs for our autologous program, CYAD-01 and CYAD-02.With that as an intro, I will turn the call over to Dr. David Gilham, to discuss our updates on the Food and Drug Administration's clearance of the investigational new drug application or IND, for our next generation NKG2D-based CAR-T therapy, CYAD-02; and to provide our additional thoughts on our manufacturing process, OptimAb.We will then turn the call over to Dr. Frédéric Lehmann, to highlight details around our clinical updates that we provided during the quarter, including the preliminary data presented at EHA Congress in June for the THINK and DEPLETHINK Phase 1 trials, evaluating CYAD-01 in the treatment of relapsed/refractory acute myeloid leukemia myelodysplastic syndrome, as well as the preliminary data announced from the SHRINK and alloSHRINK trial for CYAD-01 and CYAD-101 respectively in the treatment of metastatic colorectal cancer.I will then provide the financial overview for the first half of the year and walk through the next milestones for Celyad, before we open the call for questions.I will now turn the call over to David, the floor is yours.

[David Gilham:]

Thank you, Filippo. And thank you, everybody, again, for joining us today. As Filippo mentioned earlier, our programs and the work we are focused on, strategically positions Celyad at the front of the pack in terms of the advancements we're making in T cell therapies. And this is truly an exciting period for us.Our vision is to help enhance our autologous NKG2D-based CAR-T cell therapy programs, to potentially deepen the breadth, the frequency and the duration of the clinical response in these refractory, highly rapidly progressing patient populations.Over the past year, we have been working towards increasing the potency of CYAD-01 through different means. In June, we were excited to announce our new manufacturing process called OptimAb, which brings together the best attributes from previous manufacturing processes being worked on Celyad.This includes an eight-day culture period, which is two days shorter than the previous antibody based manufacturing process, the incorporation of an NKG2D blocking antibody, and the inclusion of a selective PI3 kinase inhibitor that helps us to enrich T cells with a memory-like phenotype.The OptimAb process is being developed in response to the increased understanding of the role of memory-like cells in CAR-T cell therapy, and center around in-house expertise in cell therapy, R&D and manufacturing.Based on research data from out in vivo experiments, the OptimAb manufacturing process led to an improved antitumor activity in a highly aggressive AML model, compared to our standard antibody manufacturing process.CMC amendments relating to OptimAb were recently accepted by regulators in both the United States and Belgium, and are now in effect under the current IND application for CYAD-01. Looking ahead, we will be treating all future patients in our autologous relapsed/refractory AML and MDS program with an OptimAb manufactured product.With the recent introduction of the OptimAb manufacturing process, we are continuing to tap into our deep expertise and knowledge in cell therapy manufacturing, which is providing tremendous flexibility in our platform and the ability to produce autologous novel CAR-T cell therapies with a memory-like phenotype for increased persistence and CAR-T potency.We're excited by the opportunity to initially assess out new OptimAb manufacturing process, CYAD-01 in the DEPLETHINK trial, under the current IND application for CYAD-01. Following additional assessment of our relapsed/refractory AML and MDS program for CYAD-01, we now plan to treat the first patients using the OptimAb manufacturing process, the CYAD-01 in Cohort 3 of the trial, which will evaluate 300 billion cells of CYAD-01 following preconditioning.We expect to treat the first patient with CYAD-01 using the OptimAb manufacturing process by the end of September.In addition to optimizing the manufacturing process, we have focused our efforts to optimize the persistence of our NKG2D-based autologous program by using short hairpin RNA or shRNA, to modulate the expression of the NKG2D ligands. This brings me to our novel next generation NKG2D-based CAR-T cell therapy, CYAD-02, which we announced at our R&D day earlier this year.CYAD-02 and CYAD-01 are very similar in terms of being NKG2D-based therapies. The key difference is that CYAD-02 benefits from Horizon Discovery's shRNA SMARTvector technology, which is designed to deliver efficient knockdown with high specificity for NKG2D ligands MICA/MICB.We believe these similarities and the preclinical work we have performed to-date, comparing CYAD-01 and CYAD-02, have positioned 02 to benefit from both the preclinical and clinical work we are already performing for CYAD-01 with respect to safety and dosing.In addition, CYAD-02 has the potential to further enhance the antitumor activity beyond with CYAD-01 where both the manufacturers are using the OptimAb manufacturing process.Regarding next steps for CYAD-02, the FDA has cleared the IND application for CYAD-02 for the treatment of relapsed/refractory AML and MDS. We are currently planning to move ahead with Phase I trial, to evaluate the safety and clinical activity of CYAD-02 with preconditioning chemotherapy of cyclophosphamide and fludarabine, or CyFlu, in the United States and in Europe in early 2020.We believe that this will be the first example of the clinical testing of a single shRNA, targeting the expression of two independent genes, that provide some insight into the opportunities afforded by this technology.With that, I would now like to turn over the call to Frédéric, Celyad's VP of Clinical Development. Frédéric?Frédéric LehmannThank you, David. I will start with the clinical update for our lead product candidate, CYAD-01 autologous NKG2D-based CAR-T in the THINK and DEPLETHINK trials for the treatment of relapsed/refractory AML and MDS patients. Then I will review the clinical data presented at ESMO World GI Congress for CYAD-01 in the SHRINK and CYAD-101 in the alloSHRINK trial for the treatment of refractory metastatic colorectal cancer patients, which continues to see encouraging clinical activity.Starting with the Phase 1, THINK trial, evaluating multiple injections of CYAD-01 without any preconditioning chemotherapy, we announced in June at the AHA conference, preliminary data from the Cohort 10, assessing a more frequent schedule of CYAD-01 at 1 billion of cells that was generally reported to be well tolerated and showed better cell engraftment compared to biweekly injections of CYAD-01 without preconditioning.We are currently enrolling patient Cohort 11 of the THINK trial, which is evaluating a more frequent dose schedule of 3 billion of cells of CYAD-01.Important to note, both of these cohorts use CYAD-01 cell generate with the antibody as called mAb manufacturing process. We expect preliminary results from Cohort 11 in the fourth quarter of 2019.In addition, we are also investigating CYAD-01, following preconditioning chemotherapy regimen, cyclophosphamide and fludarabine, for the treatment of relapsed/refractory AML and MDS in the dose escalation depleting trial.Initial safety data from the first dose level of 100 million of cells of CYAD-01 have shown the regimen to be well tolerated and lead to a better cell engraftments of 01 cells, compared to the dose escalation segment of the THINK trial, evaluating the cycle of three infusions of CYAD-01 without preconditioning chemotherapy.As David highlighted earlier, we plan to move the OptimAb manufacturing process for CYAD-01, seamless into depleting trial and expect to have the results from the Cohort 3, evaluating 300 million of cells following CyFlu, by the year end 2019.I would now like to turn to the recent data from the SHRINK and alloSHRINK trials, which were recently presented at ESMO World GI Congress, in July by Professor Van Cutsem. As a reminder, these two trials are similar to Phase 1 dose escalation study design that are evaluating the safety, the clinical activity and the CAR-T cell kinetics of the CYAD-01 and it's sister, CYAD-101 respectively for the treatment of refractory metastatic colorectal cancer patients.The SHRINK study is an open label Phase 1 trial, evaluating multiple dose of the autologous CAR-T, CYAD-01, administered concurrently with the standard FOLFOX chemotherapy, while the sister study, the alloSHRINK trial, it's also an open label Phase 1 trial assisting multiple dose of the allogeneic CAR-T, CYAD-101 administered also concurrently with the FOLFOX chemotherapy.Looking at the primary endpoint of these two trials, we have observed both regimens appear very well tolerated. Importantly, in the alloSHRINK trial, CYAD-101 show no clinical evidence of graft versus host disease across the patients treated to-date, which is important that it support the ability of our novel inhibitory peptide TIM or T cells inhibitory molecules to reduce signaling of the TCR complex in allogeneic cells.With respect to the alloSHRINK trial, we continue to observe encouraging preliminary antitumor activity, as reported at ESMO GI in Barcelona in July, including one patient's experience partial critical response and treat patients with stable disease, out of the six patients that have been heavily pretreated relapsed/refractory colorectal cancer patients.Of note, all patients in the alloSHRINK trial have previously received the FOLFOX chemotherapy. As previously announced, we have decided to enroll additional patients at the 1 billion cell dose per injections in the alloSHRINK trial, and now anticipated up to nine patients in this cohort. We anticipate to announce the additional data for the dose escalation of alloSHRINK trial by the year end 2019.I think it's also worth mentioning that, to our knowledge, the alloSHRINK trial is a very first study with an allogeneic CAR-T cell therapy from the treatment of a solid cancer indications.With that, let me now turn the call back to Filippo. Filippo?

[Filippo Petti:]

Thank you, Frédéric. Turning to the financials. I'd just like to remind you all that our full financial details are available on the Celyad website in both French and English. For the first half of 2019, research and development expenses totaled €12.7 million, compared to €11.1 million for the same period in the previous year.The increase in 2019 expense reflects the organic growth of the Company's operations for both preclinical and clinical activities, driven primarily by increased spending related to our key clinical studies for CYAD-01 and CYAD-101, as well as increased spending associated with the development of our shRNA allogeneic platform and CYAD-200 series.General and administrative expenses totaled €4.5 million in the first half of 2019, compared to €5.5 million for the same period of 2018. For the first half of 2019, the Company's other income and other expense, mainly include non-expense, cash expenses related to liability assessment required by International Financial Reporting Standards or IFRS, related to the advancement of the Company's NKG2D-based CAR-T candidates.Overall, the Company has posted €0.4 million in net income for the first half of 2019, against a €3.9 million net loss for the first half of 2018.Net operational cash burn, which excludes non-cash events, was €16.0 million in the first half of 2019, compared to €13.9 million for the same period of 2018. The Company's loss for the first half of 2019 amounts to €16.0 million versus a net loss of €18.5 million for the same period of 2018.The Company ended the first half of 2019 with a treasury position of €33.7 million, compared to €62.4 million as of December 31, 2018. Celyad confirms it previous position, and its treasury position based on the current scope of activities should be sufficient to fund operating expenses and capital expenditure requirements until mid-2020.In closing, the start of 2019 has the Celyad team very exciting. We look forward to achieving additional milestones over the next several months, including the treatment of the first patient with the CYAD-01 OptimAb process at 300 million produced with the OptimAb manufacturing process and the DEPLETHINK Phase 1 trial, which is expected by the end of September.Also we expect results from the Cohort 11 of the THINK Phase1 trial and Cohort 3 of the DEPLETHINK trial, availing CYAD-01 produced with the manufacturing process for the treatment of relapsed refractory AML and MDS by the end of the year as well. Additional results from the dose escalation Phase 1 alloSHRINK trial, evaluating CYAD-101 for the treatment of metastatic colorectal cancer are anticipated by year end 2019.Looking into 2020, we plan to announce the initiation of the Phase 1 dose escalation trial, availing CYAD-02, following preconditioning chemotherapy for the treatment of relapsed refractory AML and MDS which is expected in early 2020 as well as the submission of the IND application for CYAD-211, our shRNA based allogeneic BCMA CAR-T candidate for the treatment of patients with multiple myeloma, which is expected during the first half of 2020.And with that, I'll now turn the call over to your questions. Operator?

[Operator:]

[Operator Instructions] We will now take our first question. Please go ahead. Your line is now open.

[Raju Prasad:]

Hey, it's Raju Prasad from William Blair. Thanks for taking the question. Just a couple for me. Just how you think about how you are going to take CYAD-101 forward and potentially hemalignancies and given your producing next generation autologus NKGD2mica/micb. How are you thinking about potentially using CYAD-02 construct in the allo platform moving forward? Thanks.

[Filippo Petti:]

Very good. I think they're great questions and once that we've been discussing over the last few months in terms of how maybe 101 could continue to be evaluating an additional malignancies perhaps and hematological malignancies or other solid tumors. I think we've seen encouraging data so far from the 101 program that Fredrick described as ESMO GI in the alloSHRINK trial we'll have an additional update at the end of the year for that trail.I think based on that assessment we will look to see how we could pivot that and is it something we could look at in AML, is it something we should further investigate into colorectal cancer what might be the right approach in colorectal cancer, I think we'll let the data set kind of dictate that. But I do believe there is an opportunity for us to leverage CYAD-101 and based on the data that we've seen so far, what that will entail what indications that will to your point also would be led little bit by the initial OptimAb data that will have for 01 and perhaps the 02 program.So I think, as you know it's never just a single data point that will lead you in a specific direction. We'll take the -- look at the totality of the data and strategically how that resolve for us to think about next steps but 101 is top of mind for us and making sure that we fully evaluate that and look at its true prospects as a potential of shelf NKG2D- CAR-T.

[Raju Prasad:]

It seems although you guys have obviously executed pretty well in regulatory filings, that was very pretty quick responses from the agencies. As you are thinking about moving in Phase 2 or kind of more of a registrational focus data set, when do you plan engagement latency on the data that you're producing from kind of all these different durations, would you plan on kind of moving over to Phase 2 first and then to Phase 2 meeting or plan to data to them before kind of initiating a Phase 2 study next year? Thanks.

[Filippo Petti:]

Yes, that's a good question. I think the way we think about it is we're – I think first for us is to let's kick into the DEPLETHINK trial begin to enroll that first patient with the OptimAb process, and that makes its way through the channel we begin to collect the patients there.I think we will base our next step into a Phase 2 based on let's say 12 to 15 patients on that OptimAb product to make an assessment as to how we move the forward with the program. And I think on that and that data set, as we kick into maybe perhaps the Phase 2, we will go out to the agency and speak to them and thinking about how we could leverage that initial data set and that how that can move towards not only in initial Phase 2 but then eventually registrational as well.So I think for us, what we're looking for and the ideas not only from the OptimAb process and DEPLETHINK, but in general, I think we want to get through a 12 to 15 patient data set for us to say its full speed ahead and let's have a discussion with the agency in thinking about what exactly needs to be in process, and next steps for us to get through registration. Maybe I'll just turn it over to Fred, to provide some additional thoughts as well.

[Frédéric Lehmann:]

Just an additional thoughts, the way to interact with authorities will be obviously depending of the data that we will generate and so as mentioned by Filippo, the objective response rate and the duration of the response rate with OptimAb out of those 12, 14 patient, 14 patient will be OptimAb and as you know when we talk about registration study, we have to knock on the door and the authority is not asking about advice only but to come with some proposal, and therefore the registration study design will depending obviously of the rate of the objective response and the processes of those.Do we have for example for United States, do we have a breakthrough type designation, do we have to go for randomization versus best supportive, etcetera. So all about that to say that we need to first generate data and therefore accordingly we will know how to approach and what will be our tactic to discuss with the to the folks.

[Filippo Petti:]

And I would, the last thing I would add to that Raj, for us by the end of the year we will have on the monotherapy approach and using the schedule authorization on top of the THINK dose escalation, somewhere between 15 to 20 patients worth of data. We'll look to have a similar size in terms of the initial dose cohorts and DEPLETHINK as well as some additional incremental data from OptimAB and we'll have somewhere between 15 to 20 patients there as well.We'll have a more wholesome data set for the OptimAB in the first half of 2020 but I would just say to note the way that DEPLETHINK and THINK are set up is that they are seamless in design and that they can go from a Phase 1 into a Phase 2 for allow us to pursue the signal before really having to go out to the agencies and having a discussion with full data. We can quickly move through and collect as much data if we're seeing the right signals.

[Operator:]

We will take our next question, caller please go ahead. Your line is now open.

[Jim Birchenough:]

Its Jim Birchenough from Wells Fargo. Hi, Phil. Thanks for the call and all the detail, so what sounds like you know pretty broad plans for development and continued efforts to pursue next generation candidates here, how do you think about ending the cash runway and perhaps you could talk to non-dilutive means to give more space with the cash runway and if you might be able to elaborate some of your TCR, IP and allogeneic T-Cell IP?

[Filippo Petti:]

Yes, great question, Jim. You know as we announced it in the press release and in the prepared remarks, our cash run way to goes to mid-2020. We're obviously looking at various opportunities to how to extend that as we kick into 2020 and we'll see data throughout the year.I think to your point, can we get credit for the data we've generated so far from the AML program. That is certainly top of mind and thinking that maybe areas you know, we would unlikely go out and commercialize maybe territories such as Asia. I think top of mind is also we have - we had a collaboration and an agreement with a previous pharma company around 101, and can build on the data that we have now and continue to pursue that as well as an opportunity to bring in some non-dilutive business development cash.And I think to your last point around the IP, I think for us, we're certainly encouraged by the activity we're seeing in the allogeneic space. I think we want more of that because we do believe that we're sitting on a patent, a state that could be very helpful in terms of us bringing in non-dilutive cash from potential strategic partners similar to what we did in May of 2017 with Novartis around the two targets that we provided access to.So I think we're looking at multiple avenues. We recognize that we have lofty plans and we need to fund that. And we're looking at different instruments that can get us there.

[Jim Birchenough:]

And then just maybe on the technology side, can you just speak or maybe quantify the benefit of knocking out MICA/MICB in terms of reducing fratricide potentially. and how you think that's impacted prior results and how you think could be improved with that second generation effort when you reduce the potential for fratricide?

[David Gilham:]

I think that's a pretty complicated question to ask, I'm afraid. Because the question of fratricide that we see in vitro, there is a real question of whether this actually applies in vivo. And of course, our clinical trials were helped define that over time.But aside from fratricide, one of the – I think, potential advantage is knocking down MICA/MICB may have is that they may also reduce the sensitivity of these cells to being targeted themselves by other natural killer cells resident in the patient.So while we can see in vitro that there is certainly an effect on fratricide in terms of the fact that there is a protection against that in vitro phenomena. And what happens in the patient, I'm afraid, we'll really have to depend on whether fratricide is an important or not. And we really have very little evidence to say that fratricide is important in the patients.But I think there's also other added benefits knocking down MICA/MICB could have that go beyond that straight forward - that phenomenon. So without being able to really give you a hard quantification, we're expecting to see some potentially different impacts.And, of course, one of the broader things is whether the impact of MICA/MICB expression on T cells may be applicable beyond just the NKG2D approach.

[Jim Birchenough:]

And then just one final question just on cost of goods, it's becoming an important consideration. And maybe you could speak in general terms on the OptimAb process, how competitive your cost of goods are with – what we know about existing CAR-T's that are out there on the market?

[David Gilham:]

It's very hard to quantify at the moment, because we're still in the Phase 1 stage of our clinical trials. And what I can say at least from our own experience is that we've not seen a particular impact of the OptimAb process as compared to our mAb process. Mainly, because there were maybe an additional small cost of a reagent, we're culturing the cells for a shorter period of time.But I just really can't provide you with hard quantifiable data at the moment, because we're just at such an early stage and continuing to develop these. And we're also not sure what our recommended dose will be for the future. And so, I don't think we can really make a fair comparison as yet to what's really being discussed in the - particularly with respect to licensed products at the moment.

[Filippo Petti:]

Yes, the only thing I would add to that, Jim, is obviously I think we're well hedged. Obviously, our targets in 01 and 02 are our lead programs. But we are looking at non-gene edited allogeneic approaches and led by CYAD-101 and certainly the focus to drive forward our shRNA platform in the CYAD-200 series. As we look to the future of that, we do believe that an allogeneic product specifically for treating patients with perhaps solid tumors may have to be allogeneic.So I think we're well positioned both across autologous and allogeneic, and certainly keeping top of mind the cost benefit to patients and to the system here.

[David Gilham:]

Sorry, Jim, can I just add one further caveat to that as well. And the fact that you have manufacturing costs, and cost of goods are really related to manufacturing success rates. And the reason why we work through the iterations of our manufacturing process, and particularly the moment to the mAb and Ab building on the mAb has really been around improving our manufacturing success rate, which I think is very high, particularly for where we are and the patients we're treating.And so that, and that we will have a beneficial effect and the cost of goods in the end. So when we're thinking about this as we go through these modifications, one of the things that are top of mind really is to ensure that we maintain that manufacturing success rate. So we're not looking to generate cells that are particularly free not tight but then compromising in our manufacturing success. And so I think that's an important thing to remember.

[Operator:]

Thank you. We will take our next question. Please go ahead. Your line is now open.

[Unidentified Analyst:]

Thanks for the update. I was wondering if you could clarify again. I understand that you would have about 12 to 14 patients in the Cohort 3 by mid-2020 and about 15 to 20 in Cohort 11 around the same timing, how many patients would you be able to given up an update by 4Q 2019 for the hemato arm.For the alloSHRINK trial, so I understood that to date you have not seen any [indiscernible] this to date, so after the ESMO meeting reporting, with regard to the reporting 2019 do you plan to again present the data on conferences like ASH or SITC or do you have another timing for reporting and then a very final last questions on the R&D spending going forward, if you could give us roughly a great on the existing or the ongoing clinical programs hemato and CYAD-01, solid CYAD-101 and then the next generation programs. Thanks.

[Filippo Petti:]

Yes, so I would say from the hematological standpoint we're on target for let's say the monotherapy the THINK combined with the THINK schedule optimization cohorts to have somewhere between 15 to 18 patients work to data by the end of the year. So that's the first one.And again remember those are based on the MAB antibody, they are the MAB manufacturing process. For the DEPLETHINK trial, we provided an update on six patients so far in the first dose cohort, we are going to three issue now we've treated going through, ongoing through the MAB 300 Cohort 3 process where we'll look to have an additional three patients there and then layering the OptimAB manufacturing CYAD-01 product to somewhere in three additional patients report perhaps thinking about dose escalating up. So I think from an overall perspective and that we think we'll have somewhere maybe between 12 patients or so 10 to 12 patients by year end.Now the comment around the OptimAB, I think what we're trying to strive is they think for us to make a fair assessment on OptimAB. We would like to have somewhere between 12 and 15 patients to make kind of go, no go decision on that approach to using 01.You know, based on what we would see for the program on folding over the next several months and recruitment rates, we think by maybe mid-next year could we get to, it's probably going to be less than that but our goal is to get to maybe nine patients or so or a little bit more from that process. But I would say, the overall goal for OptimAB is 12 to 15. Where that falls exactly in the timelines will be remain to be seen depending on how we look at the program, see the initial data from 300 and if it's necessary for us to access grade up to 1 billion dose level. So its kind of a moving target at this point but I think overall the picture is we won't have a dozen patients from the OptimAB process from us to make a decision.Now as we kick into 02, 02 study will kick in early next year, that's a dose escalation three plus three study design, that data set is most likely probably a year end 2020 update in terms of the AML program. And so I think that's kind of how that fold for how we think about AML over the next several quarters.With respect to the CYAD-101 data, as you saw we did have the updated ESMO GI. We are recruiting as Frederic said at that high dose level an additional up to nine patients there and we will hope to have update by year end 2019 and we are focused on a potential medical conference to present that data. And may not be for the full data set that we're looking for the dose level but we hope to have a more meaningful update to build upon what was presented at ESMO GI at Barcelona.

[Unidentified Analyst:]

And with regard to some of the R&D spending, breakdown for the second half of 2019 on the ongoing clinical trials versus next generation program, if its possible to give us some indication there?

[Filippo Petti:]

Yes, it's a good question. I don't think we can provide the full granularity but I think we continued to have cash runway as we set to mid-2020. As we think about the programs, the larger set of the burn is sitting with the 01 program. As you can imagine because that's already up in running.Now obviously on the 02 we are working on some planning of that which is certainly taking a bite into the R&D spend as well as the work that David and the team are focused on with respect to getting the CYAD-220 series and particular, CYAD-211 our BCMA candidate filed for IND by middle of next year. So it's a fair balance, you know between clinical and preclinical but those are really the major levers for us in terms of how we think about the programs over the next several quarters.

[Operator:]

We will now take the next question. Caller please go ahead. Your line is now open. We can hear you please go ahead.

[Unidentified Analyst:]

Hi. This is Ming Wong on for Peter Lawson, at Suntrust. Thank you so much for taking our questions. Lets really quick talking about OptimAB, it sounds like you guys are now planning on to Cohort 3 after additional effects can you talk a little bit more about what you saw in this assessment that made you say Cohort 3 as oppose I think previously you guys mentioned in Cohort 4 and also the timing can you certain push back little from August end of September?

[Filippo Petti:]

So I think with respect to the OptimAB and obviously we provided an update in late June following the clearance of the amendment from the FDI with respect to using OptimAB manufactured product in the CYAD-01 program. So really I would say there's a few reasons as to why we move to Cohort 3 of the DEPLETHINK trial.I think overall we were looking at the CYAD 01 program broadly and since we've in the process of treating three patients at the 300 million dose level in Cohort 3 of DEPLETHINK, it provides us an opportunity to evaluate OptimAB at that dose level and allows us for a reasonable comparison between the patients with the MAB or antibody manufacturing process compared to the OptimAB manufacturing process both from a safety and a translational readout perspective. So I think that's really the first element.I would say the second one is based on, we are, from the OptimAB manufacturing process producing in rich memory like phenotype cells and the profile for CYAD-01 cells produced with this process. At 300 million dose level it may offer us the opportunity to evaluate what maybe the recommended dose level and then thirdly I think as I touched upon before is the idea that starting at 300 allows us also to think about dose escalating up to the 1 billion dose level, if necessary.If we stick with the 300 we could provide some additional patients and quickly go through that but I think first and foremost it's the ability of we'll have three patients from 300 from the MAB process and we'll get an obviously an opportunity to compare that to what a OptimAB manufacture process looks like translational for those three patients as well.

[Unidentified Analyst:]

I guess, then moving forward hopefully you'll be looking for, I think you had mentioned about looking for things for moving on to dose escalation or Cohort 4 maybe dependent on some readout from presumably Cohort 3 you are looking at, what would you be looking for data readout there?

[Filippo Petti:]

Yes, I think well its going to be -- its we will look to and have three patients before making a decision. What are some of the initial clinical act -- perhaps clinical activity obviously we're making sure that safety is in check as well some of the translational work and that's why we really did go one of the reasons why we decided to go with the 300 is that we'll get a better assessment between the two processes.I think, what does that look like compared to the mAb process and then thinking about, do we need to dose escalate upper [indiscernible] with continuing enrollment. Really, the goal of the DEPLETHINK trial is for us to find the recommended dose. And we felt that it was necessary to evaluate OptimAb at 300 before making the decision to just quickly start at the 1 billion dose level.

[Unidentified Analyst:]

I guess last question from us. With the cash runaway being mid-2020 and everything going on, it seems like you may possibly get meaningful data beyond 2020; so is it going to be that you guys will keep all the trials running and then possibly - or how are you thinking about focusing on certain trials over others around the timing around your cash runway?

[Filippo Petti:]

It's a good question. I think the way we think about the program right now, strategically, we have the funding to go through what we have in plan for 01, and obviously some of preclinical activities for the 02 process, bringing on some additional resources. It's certainly top of mind for us, as we talked about earlier and with one of the other questions, looking at all avenues.And I think one of the things we can pursue there is non-dilutive financing that we can help to extend out the cash runway in a partnership or perhaps other means and instruments that we can think about.Overall, we have a kind of excitement across both what's in the clinic now, what will soon be in the clinic, as well as what we plan to have in the clinic. And as you know, as a biotech company, we need to continue to think about where we can source funds to continue to drive the investigation of our programs and our pipeline.

[Operator:]

Thank you. [Operator Instructions] There are no further questions at this time. Please continue.

[Filippo Petti:]

Great, thank you, operator. So that will bring our call to a close. To briefly recap, we are very excited with the progress made in the first half of 2019, which as you've heard, include some significant advances in our clinical development programs, particularly around our lead candidates CYAD-01, as well as our non-gene edited allogeneic clinical candidate CYAD-101 across a number of different trials.Thank you everyone for joining the call, and we look forward to speaking with you all again soon.

[Operator:]

Ladies and gentlemen, this does conclude your conference for today. Thank you very much for participating. You may now all disconnect.