Celyad Oncology SA
Q1 2020 Earnings Call Transcript

Published: 8 Aug 2020

[Operator:]

Greetings. Welcome to the Celyad Oncology First Half 2020 Earnings Call. At this time, all participants are in a listen-only mode. A brief question-and-answer session will follow the formal presentation. [Operator Instructions] Please note that this conference is being recorded. At this time, I will now turn the call over to Filippo Petti, CEO. Filippo, you may begin.

[Filippo Petti:]

Great, thank you operator. Thank you everyone for joining us today on our first half 2020 financial results call. Joining me from the management team is Dr. David Gilham, Chief Scientific Officer; and Dr. Stephen Rubino, Chief Business Officer. We will start today's call with an operational and clinical update followed by an overview of the financials and outline the expected key milestones for the company over the next several months. We will then open the line for your questions. I would like to start today's call by drawing your attention to the fantastic effort our team has put forth over the past several quarters in generating a steady stream of data and updates from our clinical and preclinical programs. Most recently, we announced the advancement of our allogeneic programs, including the recent data we provided from the alloSHRINK Phase 1 trial evaluating CYAD-101 for the treatment of advanced metastatic colorectal cancer, as well as the updates from our next generation non-gene edited CYAD-200 series of the CAR T candidates, led by CYAD-211, for the treatment of multiple myeloma. I believe the team's combined efforts to develop and further advance these programs proved that we are looking to strengthen our leading position in the industry with these allogeneic programs. For example, the CYAD-101 alloSHRINK trial is the first study to evaluate a non-gene edited allogeneic CAR T cell therapy candidate for the treatment of a solid cancer indication. We are proud of this fact and we continue to drive our leadership position within the segment of the allogeneic space. Well some of these programs were underway ahead of my joining the company. We have enhanced our position in the allogeneic space by placing strategic focus behind our differentiated assets and technology platforms. We started out the year by taking a closer look at the company as a whole and considered the concentration of our resources in oncology, as well as the significant progress we're making with our next generation CAR T programs. This self-evaluation led us to a step to a more accurately emphasized our commitment to cancer patients. And in June, we announced the rebranding of the company to Celyad Oncology. As part of this effort, we have introduced a new logo and launched a new corporate website. Looking at the path ahead, the progress we made in the first half of 2020 positions us with a balanced pipeline of clinical and preclinical CAR T candidates, as well as a robust patent estate related to both NKG2D receptor and allogeneic CAR Ts. We are excited by this traction and have several milestones on the horizon for the second half of 2020, which we'll get to in a moment. With that as an intro, I will turn the call over to Dr. David Gilham to highlight details around the scientific and clinical updates that we provided during the quarter. I will then provide the financial overview for the quarter ended June 30, 2020, and walk through the next set of milestones for the company before we open up to question – the call for questions. I will now turn the call over to David. David?

[David Gilham:]

Thank you, Filippo, and thank you everyone again for joining us today. As Filippo mentioned, Celyad Oncology continues to make strides as an innovator in the CAR T space. Together, our team has set the goal to advance the clinical potential for each candidate in our pipeline in order to improve patient care by following the science. At last year's R&D Day, we highlighted our shRNA platform, pipeline of next generation NKG2D based and our off-the-shelf non-gene edited CAR-T candidates, as well as our proprietary OptimAb manufacturing process. Throughout the course of 2020, we executed a rather novel science described at last year's R&D day and we look forward to further discussing our pipeline of clinical and preclinical programs as well as our shRNA technology platform in greater detail during our upcoming R&D Day in September. Quickly turning to our pipeline updates, I'll start with the clinical updates for our lead allogeneic candidate CYAD-101 and reviewed the data from the alloSHRINK Phase 1 trial, evaluating the TIM-based non-gene edited off-the-shelf NKG2D CAR T candidate for the treatment of refractory metastatic colorectal cancer. Next, I will review recent updates from our novel shRNA based allogeneic next generation CAR T platform, including our lead shRNA based candidate CYAD-211, our anti BCMA CAR T for the treatments of relapsed/refractory multiple myeloma. Finally, I will provide an update from our autologous NKG2D CAR T programs for the treatment of relapsed and refractory acute myeloid leukemia and myelodysplastic syndromes, including our CYAD-01 and CYAD-02 candidates. As many of you know, our leading off-the-shelf allogeneic candidates, CYAD-01, co-express the NKG2D receptor and the novel inhibitory peptide referred to as TIM. CYAD-101 continues to advance in the alloSHRINK Phase 1 trial for the treatment of advanced metastatic colorectal cancer and recently at the ASCO virtual scientific program, the company presented data from the first 15 patients enrolled in the ongoing alloSHRINK trial, assessing safety and clinical activity as CYAD-101 administered following FOLFOX chemotherapy in refractory patients with advanced metastatic colorectal cancer with microsatellite stable or MSS disease. Result from the study showed that treatment with CYAD-101 was well tolerated. With no clinical evidence of Graft-versus-Host Disease, or GvHD, observed. In addition, anti-tumor activity was observed in the trial with two patients who achieved a confirmed partial response, according to RECIST 1.1 criteria, and nine patients who achieved stable disease, including two of the nine patients showing stable disease of greater than six months. Our recent analysis of the dose-escalation segment of the alloSHRINK trial showed the median progression free survival was 3.9 months for all 15 patients treated with CYAD-101 following FOLFOX chemotherapy. Also and importantly, we did not observed the correlation between clinical responses and the degree of human leukocyte antigen or HLA matching between patients and CYAD-101 donor cells, indicating that the CYAD-101 can be used in a broad patient population regardless of the HLA haplotype. As we have discussed previously, we have decided to move ahead with the expansion cohort of the alloSHRINK trial that will evaluate CYAD-101 following FOLFIRI preconditioning chemotherapy in refractory metastatic colorectal cancer patients with microsatellite stable disease, at the recommended dose of one billion cells per infusion. We are progressing towards the filing of the CMC amendments for the program following a tech transfer of the manufacturing process into our Belgium facility and enrollment in the expansion cohort is expected to begin during the fourth quarter of 2020. Turning to our first-in-class shRNA-based allogeneic CAR T candidates, and second non-gene edited off-the-shelf program, CYAD-211. We recently announced that our investigational new drug or IND application for CYAD-211 is in effect with the U.S. FDA. As a quick reminder, CYAD-211 is our lead allogeneic candidate from the next generation CYAD-200 series. CYAD 211 targets B-cell maturation antigen, or BCMA, for the treatment of relapsed/refractory multiple myeloma. CYAD-211 is engineered to co-express a BCMA-targeting chimeric antigen receptor and a single shRNA, which interferes with the expression of the CD3 beta component of the T-cell receptor complex. Proceeding will go ahead on the IND, put CYAD 211 on track to enter the dose escalation Phase I IMMUNICITY trial by year end, positioning the program to be one of the first off-the-shelf BCMA approaches to enter the clinic. We are very pleased to have the IND go into effect, which is a major milestone for the CYAD-211 program, as well as the broader shRNA platform and CYAD 200 series and demonstrates our ability to advance in parallel multiple off-the-shelf product candidates based on differentiated non-gene edited allogeneic technologies into the clinic. Again, I am extremely proud of the team and their ability to continue to execute on our strategy, even in the current COVID-19 environment. The preclinical in vivo data, we have generated for the 200 series has demonstrated that targeting CD3ζ not only protects against Graft-versus-Host Disease or GVHD, but interestingly also leads to increased persistence of T cells with the shRNA knockdown as compared to allogeneic T cells generated with gene editing the CD3ζ component. Let me now discuss our autologous relapsed/refractory, acute myeloid leukemia and myelodysplastic programs. Looking at CYAD-01, our first-in-class NKG2D CAR T clinical candidate, we announced yesterday the THINK Phase 1 trial continues to advance in the dose expansion segment of the trial, evaluating the 300 million dose level of CYAD-01 without the prior preconditioning chemotherapy in relapsed/refractory AML and MDS patients. We also announced that the DEPLETHINK Phase 1 trial evaluating CYAD-01 following preconditioning chemotherapy has been deprioritized within the relapsed/refractory AML and MDS program. The strategic decision to stop enrollment in the study was probably based on data that has emerged from the dose escalation DEPLETHINK trial over the past few months, coupled with preliminary data observed to date from the dose escalated CYAD-02 CYCLE-1 trial. As such, we will continue to evaluate the next generation NKG2D candidates CYAD-02 following preconditioning chemotherapy in the dose escalation CYCLE-1 Phase 1 trial. In July, we began the enrollment in the third dose cohort of the CYCLE-1 trial evaluating CYAD-02 for the treatment of relapsed/refractory AML and MDS. As a brief reminder, the study is assessing the safety and clinical activity of a single infusion of CYAD-02 produced with the OptimAb manufacturing process following preconditioning chemotherapy with cyclophosphamide and fludarabine. Overall, we continue to expect additional data from the autologous relapsed/ refractory AML and MDS programs, including the latest clinical results from all three Phase 1 studies by year end 2020. With that, let me now turn the call back to Filippo.

[Filippo Petti:]

Thank you, David. Turning to the financials. I'd like to remind you that all our full financial details are available on the Celyad Oncology website in both English and in French. Our research and development expenses for the quarter were €11.1 million for the first half of 2020, compared to €12.7 million for the first half of 2019. The €1.6 million decrease was primarily driven by lower preclinical and process development expenses and decreased clinical costs associated with the autologous relapsed/refractory AML and MDS franchise. General and administrative expenses were €4.8 million for the first half of 2020, compared to €4.5 million for the first half of 2019. The difference of €0.3 million was primarily due to increased insurance costs for the period. Our net other income and expenses for the first half of 2020, mainly include non-cash expenses related to contingent consideration liability reassessment required by International Financial Reporting Standards or IFRS, with the liability mainly associated with the advancement in the company’s NKG2D CAR T candidates. Overall, we posted a €0.6 million in net other expenses for the first half of 2020 compared to a net other income of €1.3 million for the first half of 2019. The net other expenses for the first half of 2020 is primarily due to the fair value adjustment up €2.4 million expense on the contingent consideration liability which is partially compensated by additional grant income from the Walloon Region of €1.6 million during the period. Net loss was €16.6 million, or €1.19 per share, for the first half of 2020 compared to a net loss of €16.0 million, or €1.34 per share, for the same period of 2019. The increase in net loss between periods was primarily due to the decrease in net other income. Net cash used in the operations, which excludes non-cash effects, was €14.6 million for the first half of 2020, compared to €16.1 million for the first half 2019. The difference was primarily driven by a decrease in spend associated with research and development as described earlier. As of June 30, 2020, we reported had a treasury position of approximately €26.7 million. We expect the existing treasury position will be sufficient, based on the current scope of activities, to fund operating expenses and capital expenditures requirements into the third quarter of 2021. We're also excited to announce in yesterday's press release that in July 2020, the company was awarded €3.3 million in non-dilutive funding in the form of recoverable cash advances by the Walloon Region associated with company’s lead allogenic CAR T candidate CYAD-101. The regional funding will help support the development of CYAD-101 for the treatment of metastatic colorectal cancer, including the launch of the expansion segment of the ongoing alloSHRINK trial. In closing throughout the most of the first half of 2020, I was proud of the way in which the Celyad Oncology team faced challenges associated with COVID-19, while keeping the development of our programs advancing. We look forward to achieving additional milestones over the next several months, which we expect to include

[Operator:]

Thank you. At this time, we'll be conducting a question-and-answer session. [Operator Instructions] Thank you. Our first question today comes from the line of Raju Prasad with William Blair. Please proceed with your question.

[Raju Prasad:]

Thanks for taking the question and congrats on the progress. Let me just first start with the data expectations for the second half of the year. It seems like you're going to have some data from CYAD-01 as well as CYAD-02. Maybe just put into context strategically, how you're sticking it out, the different types of data you're going to get, the different modalities you're using and how we should be thinking about the program going into 2021 with a lot of the shift toward the allo programs, mCRC and multiple myeloma. And then I will follow-up. Thanks.

[Filippo Petti:]

Sure. Thanks Raju. I appreciate the question. You're right. I think that really the goal for us is to continue to provide data and clinical results for the CYAD-01 and CYAD-02 program. As you know, we're looking at both the monotherapy approach with the THINK trial for CYAD-01, and as we've heard today, we'll continue to push forward with CYAD-02 in the preconditioning approach. But all three, Phase 1 data sets where we're pushing to have that as an update, we'll look to perhaps the medical conference at year end. As we think about really how things evolve for – just taking a step back, the THINK trial, which the expansion segment we kicked off in the beginning of this year. We're enrolling up to 10 patients following the CYAD-01 with multiple infusions there with no prior preconditioning that is ongoing. We've continued to enroll patients throughout the course of the last few months and after kicking that off. And as we talked about a little bit of a delay with regards to kind of COVID-19 in the spring. But that is, it's ongoing, continue to see traction there. And then as we think about the CYAD-02 candidates as we highlighted in today's comments, we're now entering, in July, we entered into the third dose cohort there. For us it's important to continue to evaluate as we dose escalate up to CYAD-02 program following preconditioning of cyclophosphamide and fludarabine. And I think we'll have a fully, the totality of the data I think will come in by year end and allow us to make a decision. I think the benchmark has been consistent for us in terms of how we've been describing this. And it's really seeing 25% complete response rate in those patients. They were enrolling in and going out at least three, four months duration of response. And that continues to be the criteria for us now. As we think about and as you point out, we have been spending more of our time around the allogeneic side of lane and I think that continues to be a very strategic focus for the company. And we'll look to see how the data emerges on the AML franchise and then look to find a potential partner. So, we check the box there. And we continue to have high prospects for the program, but I think giving where the autologous field has moved and CAR T knowing that we would need additional resources. So I think we continue to think about that the best path forward there is to find a potential partner for us to move those into further development, but we'll wait to see how the data matures and we'll take it from there.

[Raju Prasad:]

Great. Thanks for that color. Obviously, the multiple myeloma program will be kicking off later this year. Just wanted to kind of hear the hopes for number of sites and will it be the U.S. and EU trial or will it be primarily U.S. sites that are used in the study? And then David, you mentioned the tech transfer process. I didn't catch all the details on that. Can you just give a little more color on what needs to be tech transferred and for what program? Thanks.

[Filippo Petti:]

Yes, so maybe just quickly, and I'll turn it over to David, he can give you some answers on 211. But we will be providing some additional data around the IMMUNICITY Phase 1, IMMUNICITY study for CYAD-211 as we kicked that study off. But Raju to your point, we are looking at both the U.S. and Belgium sites for that study, but we will give more details as that gets closer to beginning enrollment. David?

[David Gilham:]

Hi, Raju. The tech transfer question relates to CYAD-101 actually. So for the alloSHRINK trial to date, we actually outsourced [indiscernible] CYAD-101, primarily due to laws that were in place at the time in Belgium, which hindered us using donors from outside of certain specific sites within Belgium, that law has now been repealed, which means that we can now actually bring in and generate the allogeneic product in-house. So the tech transfer has been to actually bring the technology, the process back in-house, and to allow us to compete regulatory submissions and approval to generate our batches in-house rather than through an external CDMO. And so, that's basically CYAD-101 and a change in national laws in Belgium now and analysis to actually generate their own cells which we're in the processes of working through the regulatory framework, so we can generate the next clinical batches.

[Raju Prasad:]

Great. Thanks for the questions and congrats on the quarter.

[David Gilham:]

Thank you, Raju.

[Filippo Petti:]

Thanks, Raju.

[Operator:]

Our next question is from the line of Jim Birchenough with Wells Fargo. Please proceed with your question.

[Jim Birchenough:]

Hi guys, congrats on all the progress. Two questions from me, just put us on the alloSHRINK study, for the two patients that had PRs and the nine patients with stable disease. Are there certain factors you could describe for their prior course or patient factors that would make it unlikely for them to have that kind of response to FOLFOX alone? And then I've got a follow up.

[Filippo Petti:]

Jim, thanks for the question. Yes, I do and then I'll turn it over to David. We haven't seen anything that allow us to think about how those patients if there's any background there or specific reasons as to why we saw related to partial responses versus some of the others, David can highlight maybe some of the early cell kinetic data perhaps that may be attributing to that in terms of the infusions of the 101 of how that was consistent perhaps throughout three – all three infusions as compared to maybe some of the other patients, who only have got stable disease, but I’ll maybe turn it over to David to provide some additional thoughts.

[David Gilham:]

Yes, thanks, Filippo, and hi, Jim. In terms of the patients themselves for entry into the trial, the patients have to already have seen a full course of FOLFOX chemotherapy, which is six doses. In some situations, patients may undergo a first round of FOLFOX and because of the toxicity failed to achieve all six doses at which point there's certainly some precedents where those patients are then retreated with FOLFOX can show responses. And this is largely due to the fact that they're not seen a full length of six doses beforehand. Each of the patients that we've treated in this trial today has actually received a full dose range of six FOLFOX beforehand. And in that situation, their anticipation to respond to further FOLFOX is really considered to be extremely low at best in the literature very low percentage, but according to PIs and KOLs that really is the extreme high level in terms of the response rates. So, we think given the background and the fact that these patients have all undergone six rounds of FOLFOX that would argue against them responding significantly to further oxaliplatin treatments. And indeed the patient with the longest partial response that we have actually had to have a delay in the third infusion of T cells and FOLFOX because of oxaliplatin toxicity, which highlights one of the issues for using oxaliplatin response rate and the rationale why we're moving towards using FOLFIRI as the backbone in our future expansion study. In terms of kinetics and what we understand at the moment that there's no obvious HLA dependency that's associated with responses for instance. We are not seeing any evidence of differences in terms of cytokine responses, the only difference there may have been and this is very small and the numbers are very low, so it's hard to put too much based on this. So the patients, who have the two partial responses maintained a slightly higher engraftment, but the third dose of FOLFOX as compared to the patients, who achieved stable disease, now that may be – it could be, I think a logical response developing against the T cells, but it may also [indiscernible] those patients are becoming more and more resistant to the effects of FOLFOX because they've effectively seen around nine doses of FOLFOX up into that point. So a long answer short, there's nothing obvious in the background that suggests of these patients would be typically suited to have a further response against oxaliplatin and we’re still working to try and understand whether there's some characteristics of the cells and characteristics of the patients that had the more durable responses, whether there's a particular condition relating to the cell engraftment that may correlate to that increase response, but it's very early days and very hard to put hard and definite note on that Jim.

[Jim Birchenough:]

Got it. That’s very helpful. And maybe just a follow up on 211, can you maybe, at a high level, remind us of the advantage of a non-gene edited approach over a more permanent gene-edited approach and the durability of the TCR science then you get from the shRNA. And then on 211 specifically, could you talk about your considerations for preconditioning and at some point would be considered as CD52 knockout and a TCR conditioning. Thanks.

[Filippo Petti:]

David, would you like to answer the questions on 211?

[David Gilham:]

Yes, of course. So one of the key advantages, and certainly what drew my eye to this technology, Jim, was the work that Horizon Discovery had done in terms of the microRNA framework. And so because the shRNA expression is intrinsically linked, some expressions of the chimeric receptor, basically if CAR is there, the shRNA is there – and if the shRNA is there, then the T cell knockdown is maintained. And what we saw in our pre-clinical multiples is that there was maintenance of T cell receptor knocked down during the periods of engraftment in the animals through 60 days or so. And so clearly, the CAR has been expressed here within this period of time as well as the shRNA and of course that correlates them with a lack of induction of Graft-versus-Host Disease. In our clinical trial, we plan, of course, to be using a cyclophosphamide and fludarabine preconditioning as our initial approach. And we fully expect ourselves and engrafted as would typically be expected around two to three weeks. So if we extrapolate from the NSG mice, where we saw long-term knockdown through 60 to 70 days plus, so actually sort of lengthy experiments in those animals. We were fully confident that the shRNA expression that we maintain through the two to three weeks that we would expect these cells to engraft within patients after cyclophosphamide and fludarabine preconditioning. Now, in terms of the preconditioning, which is your second point really, Jim, so the combination of CD52 knockdown and then using that Alemtuzumab or a similar approach to increasing this, is certainly showing some interest. And you may be aware that in our ASCO presentation earlier this year, we showed that we can now multiplex and express multiple shRNA and we have shown a preclinical proof of principles that we knockdown CD52 efficient in using our shRNA. And what we did show in that that publication is the fact that those cells also resisted then to Alemtuzumab and they're not killed as far as we can kill in our in vitro assays. So it's certainly possible. I think the question really comes down to dealing with the potential toxicities of using a CD52 depleting antibody in these patients and the benefit of having that longer-term lymphodepletion. So for us it's a stepwise approach and we're using basically a standard type of approach. You may be aware that that many of our colleagues in the space are using the hands more aggressive lymphodepletion, where we're using effectively, if there is a standard, we're using a standard dose of Cy/Flu as an entry level for our initial allogeneic approach. And then really to see how the engraftment the activity we see, and then determining whether there's some increased aggressiveness of lymphodepletion is required for allogeneic approach. So we certainly see it as a step wise approach, Jim.

[Jim Birchenough:]

That’s great. Thanks for all the detail David and Filippo and congrats again on the progress.

[David Gilham:]

Thanks, Jim.

[Filippo Petti:]

You’re welcome, Jim.

[Operator:]

Our next question is from the line of Ed White with H.C. Wainwright. Please proceed with your question.

[Ed White:]

Hi, good morning. So just a couple of questions Filippo, a couple of financial and then strategic questions. On the financial question, R&D was down half over versus last half – last year, but you're increasing, it seems like the number of trials that you're doing, although the preclinical work might be down. I just want to get your thoughts on R&D spend for the rest of the year. And then also, is there a possibility of – for the grant from the Walloon Region, have you – maybe you can go through the process there and how the grant [indiscernible]. I'll follow up with other questions. Thanks.

[Filippo Petti:]

Sure, thanks. Thanks for the questions, Ed. [Indiscernible] number, I think a lot of these as we had last year where we were getting for in terms of really the process development around OptimAb, getting things in place for the studies, in particular, the DEPLETHINK study. We also had at that point some additional THINK, dosing scheduling the cohorts 10 and 11. So there has been a little bit of – maybe it's less – more studies on this side, but I think there were more patients associated with the THINK program last – in the first half of last year, which is contributing a little bit in terms of the difference in the R&D spend. And as we think about going out and I think this level, in terms of how we think about first half, second half, I will try to mirror that. I think we're going to, as we pointed out, cash flow might goes into third quarter of next year, and you can see a steady rate in terms of the spend on the R&D side and with things across, in terms of, G&A being pretty consistent. With regards to perhaps additional Walloon Region perhaps as you see we announced the Walloon Region non-dilutive funding today around the 101 program, I think just continues to help us out in terms of pushing out on the programs, allowing us to really put resources where we truly think there's a benefit for allowance. So we continue to maintain a nice cash runway. So we're excited about that. So there are opportunities for other grants, I think there may be – I don't want to speak too early about that. We were continuing to evaluate if there's potential opportunities there for us to go back to the Walloon Region for additional non-dilutive funding. But it's, I think, too early to say if there'd be anything else we would put into the pipeline associated with that yet.

[Ed White:]

Okay…

[Filippo Petti:]

Between – yes, between the 3.3 that we received this year, roughly the 10, I mean, it's been a fantastic partnership that we've had with the Walloon Region. And now they see funding our sciences and especially around the allogeneic CAR T space.

[Ed White:]

Great. Thanks. And just strategically, we had been talking in the past about through the thing between DEPLETHINK and THINK going forward by the end of this year, it seems like you've made your decision on 201 for DEPLETHINK. I just want to circle back and think about is this indicate that you'll be moving forward with DEPLETHINK over THINK or 201 versus 101, or will we learn more about that with the data reveal in the fourth quarter? Thanks.

[Filippo Petti:]

Yes, with today's update, I think, we – you know, we’ve seen and as you know the DEPLETHINK trial using OptimAb manufacturing process for the CYAD-01 candidate, we kicked that off last September. That was a little bit entered, let's say, the shoot a little bit earlier than the THINK expansion as well as the CYCLE-1 study for CYAD-02, which kicked off the January Q1 timeframe. So for us it had some additional time around that. We've seen as we've kind of dose escalated into the 300 and the 1 billion dose and compared that to – initial very preliminary data out of the 02 trial, the CYAD-02 CYCLE-1 trial that we were running two candidates on following preconditioning chemotherapy. We've had the three opportunities, the three shots on goal over the past year. And I think we were just beginning to better understand which asset is best positioned to move forward. As you know, the CYCLE – the CYAD-02 candidate has differentiated versus the first generation CYAD-01 and some of the data that we've included with the shRNA targeting MICA and MICB, translates into encouraging increased in vitro proliferation and B bone graft and antitumor activity. So there's certainly differentiation between 02 and 01. And since, we were evaluating both on the preconditioning, the data is still early and it's emerging, but we decided to put our strategic focus on the 02 candidate under those conditions. And we continue to have high prospects for both the CYAD-01 THINK trial and the CYAD-02 trial, CYCLE-1 as it continues to progress here over the course of the second half of this year.

[Ed White:]

Thanks, Filippo. So I'm just trying to get an idea for 2021. Do you think by the end of this year, you're going to be able to make a decision whether to go forward with DEPLETHINK with the preconditioning or focus on no preconditioning for THINK?

[Filippo Petti:]

Yes, so, I think, with 01 we'll focus on the THINK trial and no prior preconditioning to further evaluate the prospects there. On the preconditioning side, we'll focus our attention with CYAD-02. We'll have a dataset for 03. I think the goals to us to provide a clinical dataset for 03 by year end. But I think as we think about strategically how we would move the assets forward at least at this point based on the ongoing clinical trials, it's – 01 is more without preconditioning and the 02 continues to evaluate the preconditioning approach.

[Ed White:]

Okay.

[Filippo Petti:]

So for 20 – yes, for 2021, we'll look to see how the totality of the data ends up. And again, as we said, we'll provide an update by year-end on all three trials and then make a decision on how – again, if they achieve the benchmark that we set for all three studies. And as you can imagine now, it's really just the two studies we're looking for to get a better understanding on. And then take that into consideration in terms of how that would move forward. And I think we've talked about – there's a chance if we hit the right dataset that we would look to find a potential partner that opposite as well depending on how we’re going to purchase.

[Ed White:]

Great, thank you.

[Filippo Petti:]

Thanks for your question Ed.

[Operator:]

The next question is from the line of Sandra Cauwenberghs with KBC Securities.

[Sandra Cauwenberghs:]

Yes, hi. I actually had a question around the same line of the previous analyst with regards to CYAD-02 on the combination with chemo or the preconditioning when you plan on initiating that, so to get an idea of timelines next year. But yes, what I pick up is that it's difficult to say today. Maybe some clarity, do you think you could start that type of a trial in the second half of next year? Would that be feasible?

[Filippo Petti:]

Sandra, hi. Thanks for the question. Just to confirm you're referring to the AML program, correct?

[Sandra Cauwenberghs:]

Yes, correct – yes with the OptimAb with a new protocol, basically.

[Filippo Petti:]

Yes. So, right now, I think, we are full steam ahead to continue to enroll patients in the 02 CYCLE-1 study as we talked about we've entered the third dose cohort there. As you know, it's a three plus three design. We're evaluating the safety and efficacy there. We enrolled 9 to 12 patients. So there's an opportunity maybe to extend out on that higher dose level. But there's also flexibility to add some additional patients throughout. So, really, I think we'll look to build a dataset for us in the broader AML context. Take a step back and then decide how we could potentially move forward. The CYCLE-1 study is flexible where we can add. And I think it’s a number and David maybe – you may recall the number of patients we can expand out to enroll the cohort at the high dose levels actually as well as at the middle dose level to an extended number of patients. So, I think, if we continue to see the – if we see a signal that we want to continue to explore, we will continue to push forward on enrollment. At this point it really is, you know, we're just entering the high dose level. I think it's preliminary, but I think we are encourage in terms of the differentiation we're seeing their versus maybe the 01 candidate following preconditioning. David, I'll turn it to you to see if there's anything you'd like to.

[David Gilham:]

Yes. I think perhaps a confirmation is really required to Sandra. So 02 candidates, we competed dose level one and dose level two. We’re currently recruiting in dose level three. And we expect to share certainly the initial data from the whole dose-escalation by end of year. We will be sharing all the information we have from the DEPLETHINK-01 CYCLE trial at the end of the year. And we'll also be sharing the data that we have from the expansion of the 01 THINK trial as well by the end of the year. And so, we're really looking to make data driven decisions by the end of the year looking at the overall activity of all of our autologous activity across all three trials. So basically a data-driven decision that leads us into 2021 as I was just mentioning.

[Sandra Cauwenberghs:]

And when you talk about a different profile of 02 versus 01, what's exactly the clinical evidence that you have to date in terms of that – the differentiation between the two products, not only preclinical or in vitro, but really clinical evidence.

[Filippo Petti:]

Yes. As David pointed out, the data still emerge and it’s very early days with regards to the clinical experience we've had so far. We'll look to provide an update on the full Phase 1 trial at the end of the year. But, I think, we can – begin to see that there is potential some of – some signs there that there is differentiation between the first next generation candidates for NKG2D, but it's still small numbers, Sandra. So I think, we're – it's tough to make a kind of a statistical decision on this, but I think that's what we're seeing as the data is emerging. That gives us a view that there is some differentiation there, but hard to really speak about the numbers at this point as the data is pretty – it's preliminary in nature.

[Sandra Cauwenberghs:]

Okay. Thanks.

[Filippo Petti:]

Thank you, Sandra.

[Operator:]

Our next question is from the line of Olga Smolentseva with Bryan, Garnier & Company. Please proceed with your question.

[Olga Smolentseva:]

[Technical Difficulty]

[Filippo Petti:]

Hi, Olga. I think we’re having a tough time hearing you.

[Olga Smolentseva:]

Sorry, is that better?

[Filippo Petti:]

Yes.

[Olga Smolentseva:]

[Technical Difficulty]

[Filippo Petti:]

We’re still having a tough time. I think your question was a little bit…

[Stephen Rubino:]

I think she was asking about PFS and potential for OS data.

[Olga Smolentseva:]

Yes, that's correct.

[Filippo Petti:]

Thank you. Thanks, Stephen. As we highlighted in yesterday's press release, PFS is now coming in for the 15 patients that we had in the dose escalation were encouraged by the 3.9 number. Especially if you compare that to somebody's historical numbers for third, fourth line agents that have been approved, the regorafenib and TAS-102, 3.9 compared to maybe a 2.5 month median PFS. And as we think about OS, that data is still maturing. I think we'll look to provide an update here in the near-term, tough to say exactly when as many of those patients are still with either stable disease or moved down to an additional therapy there. So as that data matures, we'll be sure to provide an update. And I think we're certainly encouraged about the PFS and hopefully how that could potentially translate to the overall survival number. Again, with the caveat, Olga, as we all know, these are – it's still 15 patients worth of data. But I think we're seeing the right signals there for us to continue to warrant us putting additional resources, again moving towards the expansion phase of the trial as soon as possible.

[Olga Smolentseva:]

Great, thanks. And my second question would be on CYAD-211, considering recent approval of – how should we think about design of the upcoming study, I think that would be anti-BCMA naïve population?

[Filippo Petti:]

We're going to be looking at a – and we'll talk more about the trial. I think what we have talked about publicly for the 211 programs that we will look at relapsed/refractory multiple myeloma patients as we kick off the study design and get closer to entering the clinical, provide some of that background. As David highlighted, we'll be looking at a cyclophosphamide fludarabine preconditioning. We will be looking to have sites across both the U.S. and Belgium there, and we'll provide some additional details. But as you can imagine, from a perspective of where we would evaluate that, I think as you look across the landscape, it would be similar to somewhere our other peers are sitting with the allogeneic CAR T assets as well for BCMA so similar type of patient population there.

[Olga Smolentseva:]

Thank you.

[Filippo Petti:]

David, if you would like to highlight that maybe beyond what was touched upon.

[David Gilham:]

No, I think that's exactly the case. We clearly need to treat the similar population as our peers, because we need to understand the relative activity of the BCMA CAR. But really for the company, as important as the BCMA activity is the shRNA activity. And so we will certainly – we're looking forward to probably the first three to six patients were controlled the GvHD in those patients over the period of time of that trial. Really will be an important checkpoint for our shRNA platform, and then will give us real momentum in terms of developing that platform for next-generation candidates.

[Olga Smolentseva:]

Sure. Yes, thanks. That's clear.

[David Gilham:]

Thank you, Olga.

[Filippo Petti:]

Thank you, Olga.

[Operator:]

Thank you. At this time, we've come to the end of our question-and-answer session. Now I'll turn the call over to Filippo Petti for his closing remarks.

[Filippo Petti:]

Thank you, operator. If there are no more questions, then we'll bring the call to a close. We'd like to thank everyone for joining our first half 2020 call. And we look forward to speaking to you all again soon. Have a great summer and catch up soon. Thank you.

[Operator:]

Thank you. This will conclude today's conference. You may disconnect your lines at this time. Thank you for your participation.