Cellectis SA (CLLS) 2020 Q4 法說會逐字稿

Greetings. Welcome to Cellectis Fourth Quarter and Full Year 2020 Earnings Call. (Operator Instructions) Please note, this conference is being recorded.

At this time, I'll turn the conference over to Simon Harnest, Chief Investment Officer. Simon, you may begin.

Thank you, and welcome, everyone, to Cellectis' Fourth Quarter and Full Year Corporate Update and Financial Results Conference Call for the 2020 fiscal year. Joining me on the call today with prepared remarks are Dr. André Choulika, our Chief Executive Officer; Dr. Carrie Brownstein, our Chief Medical Officer; and Eric Dutang, our Chief Financial Officer.

Yesterday evening, Cellectis filed its annual report and issued a press release reporting our financial results for the fourth quarter and year ending December 31, 2020. These reports and press releases are available on our website at cellectis.com.

As a reminder, we will make forward-looking statements regarding Cellectis financial outlook in addition to its regulatory and product development plans. These statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. A description of these risks can be found in our most recent Form 20-F filed with the SEC and the financial report, including the management report, for the year ending on December 31, 2020, and subsequent filings Cellectis makes with the SEC from time to time.

I would now like to turn the call over to André. André, please go ahead.

Thank you, Simon. Good morning, and thank you, everyone, for joining us today. 2020 has been focused on advancing our company objectives. Despite the challenges the world is facing, Cellectis has achieved key milestones, and we are incredibly grateful and proud for all the hard work achieved by our team, our partners and our stakeholders during this challenging year. Based on the progress we've made in 2020, we're moving into 2021 determined on our commitment to a cure. We are thrilled to share with you over the next half an hour this progress and our vision on an exciting future for Cellectis. In 2020, we fully entered into clinical development of our first 3 wholly-controlled clinical programs.

With our pioneering allogenic UCART cell programs in ALL, AML and multiple myeloma, we're developing alternative targets to the overcrowded CD19 and BCMA landscape. We have already shared early data on our ALL program, BALLI-01 at ASH this past December. All 3 programs are currently enrolling patients in Phase I dose escalation trial. And we are investigating differently for depletion regimens.

While 2020 was an extremely challenging year with a significant impact on logistics, Cellectis successfully completed the construction of our in-house manufacturing facilities on time in Raleigh, North Carolina, and in Paris, France. Both facilities are now up and running with the tech transfer between Paris and Raleigh happening in the first half of this year in order for Raleigh to start manufacturing GMP UCART cell batches in the second half of this year.

Successful product development is highly dependent upon manufacturing from stable clinical supplies to drive the execution of our clinical plans to ensuring consistent quality and meeting regulatory expectations. Our facilities in Raleigh and Paris will allow us to achieve a large degree of manufacturing independence, which is one of the most important value driver for any cell and gene therapy company. We expect to achieve this by year-end and believe this step will propel Cellectis further ahead as we continue to lead this class of cell therapy companies.

Our clinical execution strongly accelerated during 2020 as we established a world-class team of clinical experts from the CAR-T cell and the hematology/oncology space around our Chief Medical Officer, Dr. Carrie Brownstein, who joined us from Celgene. Carrie and her team have been instrumental in establishing a broad clinical presence for Cellectis within 7 of the top U.S. hospitals, giving us an unprecedented access to large patient population from which to enroll into our clinical trials.

In addition to expanding our general management and global manufacturing team with top talent, we appointed Mr. Jean-Pierre Garnier as the Chairman of the Board of Directors in November 2020. Jean-Pierre is a seasoned leader, with decades of experience within the global biopharma industry, most notably as the previous CEO of GlaxoSmithKline.

From gene editing to CAR-T cells, Cellectis has always been a strong scientific leader in this space. As an example, Nature magazine recently ranked top organizations in terms of number of patents filed and owned in the CAR-T cell space. In this ranking, Cellectis became the 4th institution worldwide just behind UPENN, BMS and Novartis. In the same publication, among the top 20 CAR-T cell inventors, 6, so close to 1/3, are from Cellectis. This is a great achievement overall. We're also listed as the #1 biotech company in the study. And this is just for CAR-T, and I'm not talking about gene editing. Yes, we are a leader in this field, and we have plenty of followers.

On the business development front, we're pleased about our recent agreement with Cytovia Therapeutics, which we announced last month. This partnership leads us to expand our TALEN gene editing platform into iPSC-derived natural killer cells, and chimeric antigen receptor, so CAR-NK cells, for a series of different tumor types. We will be responsible to develop custom TALEN, which will be used by Cytovia to edit iPSCs to be differentiated into NK cells, addressing multiple gene targets for therapeutic use in several cancer indications.

Cytovia will be -- will conduct the development of the mutually agreed upon therapeutic candidates, and we will be eligible for up to $760 million of development, regulatory and sales milestone as well as a single-digit royalty payment on net sales. We will also receive an equity stake of $15 million in Cytovia's stock as well as an option to invest in future financing round, which will allow us to be part of Cytovia as a growing value driver.

Together, with the research collaboration and exclusive worldwide license agreement with Iovance on gene-edited tumor-infiltrating lymphocytes, we announced last year, this partnership shows the growing attraction and relevance of our TALEN platform as the gene editing solution of choice for cell therapy. We're looking forward to see these next-generation gene-edited cell therapy programs become a reality for cancer patients.

Our partnerships with Allogene and Servier are also gaining momentum and further establishing our growing allogenic CAR-T platform value. Allogene presented initial data from the ALLO-715 program in relapsed/refractory multiple myeloma at ASH in December 2020, the first dataset ever presented on an allogeneic cell therapy targeting BCMA. In this initial data readout, 31 patients treated with ALLO-715 were evaluable for safety and 26 patients were evaluable for initial efficacy. Allogene is now moving into the next steps in this study, namely optimizing cell doses and lymphodepletion and plan to provide an update on ALLO-715 later this year.

Allogene also initiated a cohort exploring ALLO-715 in combination with the gamma secretase inhibitor, nirogacestat, with their partner, SpringWorks Therapeutics, and is on track to submit an IND for ALLO-605, the first TurboCAR targeting BCMA for multiple myeloma in the first half of this year.

Regarding CD19, Allogene presented initial data on 22 NHL patients treated with ALLO-501, of which 19 were evaluable for efficacy at ASCO 2020. In parallel to ALPHA, Allogene ALLO-501A ALPHA-2 trial, is designed to enroll a homogeneous patient population focused on relapsed/refractory LBCL and was recently granted Fast Track Designation for the treatment of this population. The ALPHA-2 trial is designed to potentially move into pivotal Phase II trial, should the data support it, which would make us eligible for milestone payment. ALLO will be assessing the best course of action for pivotal trial in second half of this year, setting this product into a trajectory to potentially become the first-ever approved allogenic CAR-T cell candidate in the world.

Finally, we're excited about the third target license to Allogene, CD70, entering the clinic this year with the TRAVERSE trial evaluating ALLO-316 in clear cell renal cell carcinoma. This is our first licensed allogeneic CAR-T targeting solid tumors, and we're eligible for a milestone payment for the first patient dosed.

In addition to further derisking our allogenic CAR-T platform, our alliance with Servier and Allogene are major value drivers to Cellectis. Agreement on CD19 was amended last year, and now makes us eligible to up to $410 million in development and sales milestone plus low-double-digit royalty on sales. And the licensing agreement with Allogene on 15 additional allogenic CAR-T targets makes us eligible to over $2.8 billion in potential future milestones payments plus royalty on sales.

With that, I would like to hand the call over to Dr. Carrie Brownstein, our Chief Medical Officer, for an overview for proprietary clinical programs. Carrie, please go ahead.

Thank you, André. I would like to start with our first proprietary product, UCART22, our CD22-directed TALEN gene-edited allogeneic, off-the-shelf, CAR-T cell product candidates currently being evaluated in patients with relapsed and refractory B-cell acute lymphoblastic leukemia, or BALL. We presented preliminary data from patients enrolled in the first 2 dose levels of our Phase I dose escalation trial, BALLI-01 at the American Society of Hematology Annual Meeting in December. This is the first publicly released data from Cellectis' BALLI-01 clinical trial.

As of the November 2, 2020 data cutoff, 7 patients were enrolled and 5 patients received UCART22 following lymphodepletion with fludarabine and cyclophosphamide, or FC preconditioning. One patient failed screening and 1 patient was discontinued prior to the administration of UCART22 due to an adverse event related to the lymphodepletion regimen.

Importantly, no patient experienced dose-limiting toxicity, immune cell associated-neurotoxicity syndrome, graft-versus-host disease, adverse events of special interest nor grade 3 or higher adverse events or serious adverse events related to UCART22. No patient discontinued treatment due to UCART22-related treatment-emergent adverse events. Two patients in dose level 1 achieved an objective response of complete remission with incomplete count recovery, or CRI, at day 28, 1 of which attained a complete remission, or CR, at day 42, and proceeded to hematopoietic stem cell transplant after subsequent therapy with inotuzumab. One patient in dose level 2 achieved a noteworthy reduction in bone marrow blasts of 60% at screening to 13% at day 28 after treatment with UCART22 and subsequently progressed.

Host lymphocyte reconstitution was observed in all patients within the DLT period and correlative analysis of UCART cell expansion and persistence remains ongoing. We are encouraged that UCART22 demonstrated preliminary signs of activity at low dose levels with FC lymphodepletion without unexpected nor significant treatment-related toxicity. Our next step is to evaluate and optimize the cell dose and lymphodepletion in order to augment these early responses.

We have added an arm to the trial in which we explore the addition of alemtuzumab, an anti-CD52 antibody, added to the FC lymphodepletion regimen, which we call FCA, which is expected to result in a deeper and more sustained T-cell depletion, and thereby promote expansion and persistence of UCART22 cells. We are currently enrolling patients in dose level 2 with FCA, and we plan to give an interim clinical data update on this cohort in the second half of this year.

Coming to UCART CS1, our CS1-directed TALEN gene-edited, allogeneic CAR-T cell product candidate, being evaluated in patients with relapsed or refractory multiple myeloma. We collected preliminary translational data from the first group of patients enrolled last year, and we plan to share an early look at this data in the first half of this year. Similar to BCMA, CS1 is a widely and consistently expressed target on the plasma cells of multiple myeloma.

Interestingly, CS1 is also expressed on other immune cells, including T-cells and NK cells. Cellectis is uniquely positioned to leverage this important myeloma target because through the use of our gene-editing technology, we are able to knockout CS1 from the T-cells prior to inserting the CS1-directed CAR, which avoids T-cell fracture site during manufacturing.

An additional differentiating factor is that our UCARTCS1 cells self-generate lymphodepletion through targeting CS1-expressing lymphocytes, and, thus, do not require additional preconditioning with a CD52-directed antibody. While the FDA had placed a clinical hold on this program last year following a patient death in dose level 2, which occurred toward the end of the 28-day observation period, this hold has been since lifted with updates to the protocol, and the study has resumed.

Next is UCART123, our CD123-directed, TALEN gene-edited allogeneic CAR-T cell product candidates, being evaluated in patients with relapsed and refractory acute myelogenous leukemia. This program is addressing one of the highest unmet medical need population and a successful CAR-T cell program in relapsed and refractory AML could be a significant paradigm shift for patients.

Our current clinical product is an enhanced version of UCART123, which includes updates to the manufacturing process and incorporates the CD52 knockout to allow the use of an FCA lymphodepletion regimen. We are currently enrolling in our Phase I dose escalation trial with 2 study arms, 1 with FC and 1 with FCA lymphodepletion. Enrollment in both arms is ongoing and the data obtained will give us great insight into the CAR-T cell kinetics and host lymphocyte recovery using both strategies. We are looking forward to sharing this data from the program when available.

Building on the technology platform of our current proprietary clinical programs, I would like to add that we plan to submit INDs and initiate new clinical trials this year for novel proprietary product candidates targeting additional oncology indications as well as genetic disease settings. We look forward to sharing additional information in the near future.

Our licensed allogeneic CAR-T cell development programs are making great progress as well. As André mentioned before, this year, we are expecting rich clinical data flow from Allogene and Servier from our licensed CD19 programs in relapsed/refractory NHL, and from Allogene for the BCMA program in multiple myeloma, at various medical meetings, further validating the allogeneic CAR-T cell approach, which we invented and pioneered.

With that, I would like to hand the call over to Eric, our Chief Financial Officer, for a more detailed overview of our business development activity. Eric, please go ahead.

Thank you, Carrie, and good morning. Before I provide a brief overview of our financials for the quarter and year-end, I'd like to spend a few minutes on some of our business development activities in 2020 and in early 2021. In particular, at the beginning of 2021, we announced our alliance with Cytovia, which includes up to $760 million of development, regulatory and sales milestones, and we will also receive single-digit royalty payment on the net sales of all partnered products commercialized by Cytovia. We will also receive an equity stake of $15 million in Cytovia's stock or an upfront cash payment of $15 million if certain conditions are not met by December 31, 2021, as well as an option to invest in future financing rounds.

In 2020, we announced our collaboration with Iovance and gene-edited TILs with significant undisclosed development and sales milestones plus royalties on sales along with an amendment of our partnership agreement with Servier with up to $410 million in development and sales milestones plus low double-digit royalties on sales. For the latter, we will potentially receive, in 2021, a milestone payment from the first pivotal trial of ALLO-501A in large B-cell lymphomas.

Finally, as a reminder, we are also eligible to receive up to $2.8 billion in development and sales milestones plus high-single-digit royalties on sales from Allogene related to 15 targets. We will potentially receive, in 2021, a milestone payment from the launch of the TRAVERSE trial of ALLO-316 in renal cell carcinoma.

Now on to our financials. The cash, cash equivalents, current financial assets and restricted cash position of Cellectis excluding Calyxt as of December 31, 2020 was $244 million compared to $304 million as of December 31, 2019. This difference mainly reflects $28 million of proceeds received from Servier in the first quarter of 2020 and the receipt of $21 million set guaranteed loans, which were offset by $102 million of other net cash flows used in operating, investing and lease financing activities. This cash position is expected to be sufficient to fund Cellectis stand-alone operations into late 2022. This runway discounts any future milestone payments.

The consolidated cash, cash equivalents, current financial assets and restricted cash position of Cellectis, including Calyxt, was $274 million as of December 31, 2020, compared to $364 million as of December 31, 2019. The net cash flow used in operating capital expenditure and leases were $86 million at Cellectis and $44 million at Calyxt in the full year of 2020.

The net loss attributable to shareholders of Cellectis, excluding Calyxt, was $54 million in the full year '20 compared to a net loss of $75 million in 2019. This $21 million increase in the net results between 2020 and 2019 was primarily driven by a significant increase in revenues and other income of $44 million, which was partially offset by an increase in SG&A expenses of $5 million and a decrease in financial gains of $19 million.

The consolidated net loss attributable to shareholders of Cellectis, including Calyxt, was $81 million or $1.91 per share in the full year of 2020 compared to $102 million or $2.41 per share in 2019. The consolidated adjusted net loss attributable to shareholders of Cellectis, excluding noncash stock-based compensation expenses, was $67 million or $1.77 per share in the full year of 2020 compared to $79 million or $1.86 per share in 2019.

We are laser-focused to spend our cash on developing our deep pipeline of wholly-owned product candidates in the clinic and operating our set of the art manufacturing facilities in Paris and in Raleigh. On the other hand, our focus on maintaining an efficient corporate infrastructure should enable more limited growth in G&A spend.

With that, I would like to hand the call back over to André for concluding remarks. André, please go ahead.

Thank you, Eric. Again, we're very proud of the organization and team that we have built over the past years. We started treating the first patient in pediatric ALL in 2015 under compassionate use protocol, with the first ever gene-edited allogeneic CAR-T cell therapy. Those babies are now young kids in school and continue to be tumor-free. This is what motivates us, our entire team to get to work every day with the mission to save the lives and offer a treatment option to those cancer patients that have exhausted all other treatment options.

Fast forward from 2015 to today, we now are fully integrated gene-editing biotech company, with 7 therapeutic development programs in clinical trials, including 3 wholly-controlled targets based on our appropriate TALEN gene-editing technology. To further expand our current clinical pipeline, we are in the middle of finalizing preclinical work on a series of new allogenic CAR-T cell targets and other product candidates.

We strongly believe that our proprietary cell and gene therapy platform combined with our in-house manufacturing facility and our broad clinical pipeline will lead to a paradigm shift in the cancer therapeutics and cell therapies in general, positioning us at the forefront of this promising scientific field.

With that, I would like to open the call for Q&A.

(Operator Instructions) And our first question is from the line of Michael Schmidt with Guggenheim.

I actually had a question around your investment into the CAR-NK space as part of the Cytovia collaboration. I was just curious if you could share maybe how the Cytovia technology and approach together with your TALEN approach, how that might differ or compare to what others are doing in the CAR-NK space? And longer term, how you think CAR-NK cell products might be positioned relative to CAR-T products within oncology indications?

Thanks, Michael. I appreciate the question, and thanks for joining us this morning. This is Simon. Very good question. We make very selective business development deals with very high-quality technology partners. We want to be very selective, as I said, because there is just such a wealth of new technologies coming into the market. And we think Cytovia is one of the best partners in the iPSC-derived NK cell space. So that's obviously a space that captures a lot of momentum currently, and we can make a significant difference here by adding our TALEN gene edit. And this collaboration is also positioned more as an investment for Cellectis due to the fact that we actually have an equity stake in the company rather than an upfront cash payment. So we are very encouraged by the progress of the company so far, and we're continuing to be very excited about the growth that can come out of this collaboration.

As we said, we have, obviously, over $700 million in development milestones, regulatory milestones, some sales milestones. But for us, it's much more interesting to actually make a significant change to improve with gene editing what is a very wonderful scientific platform on the iPSC-derived NK cell front. So for us, it's a foray into this space. This will include some solid tumor targets as well, but without taking the focus and resources away from us to focus on our off-the-shelf CAR-T cell treatments, which we think have the best shots on goal for the targets that we're pursuing.

And André, feel free to add anything.

Well, it's, in fact, something that is important for us because there is a lot of selection among all the gene-editing technologies, and we see more and more people that are focusing on TALEN interest because of the performance of the technology and the quality of the cell that comes out, plus Cellectis is one-stop-shop in the field of gene editing. It means we have the electroporation technologies. We have the TALEN technologies. We have other gene-editing technologies, and we have a huge amount of experience in handling cells and editing them.

On the fact of between NK, T-cells, et cetera, Cellectis is focusing on T-cells. Cytovia is focusing on NK. We cannot be on all fronts, and we believe very strongly that the focus that we have on primary T-cells is very promising and very straightforward currently because of the successes that we are starting to see in this field. The NK, we believe in them. We think Cytovia is the best partner to do it, but we don't think that Cellectis should spread itself into all directions.

Why in the T-cell space we like primary cells, for the simple reason that T-cells are more of a cocktail than NK cells. There is, of course, like different type of NK cells, but in the space of T-cells, it's CD8, CD4s, gamma delta, T-central memory, et cetera. So it's a cocktail that is part of the knowhow of Cellectis and how to extract this from a leukopak of healthy donor and that's also not within the reach of -- immediate reach of filing product on something that would be a sophisticated product in there. Now we believe in the iPSC and the stem cell differentiation and something that we are very excited. While the technology of Cytovia that comes out from very prestigious labs on the West Coast, we think that it's going to deliver very strong results at the end.

Our next question comes from the line of Gena Wang with Barclays.

I also have 1 question regarding Cytovia partnership. Just wondering the -- is there any color you can share with the initial targets? And also will Cytovia or Cellectis be responsible for any manufacturing? And second question is regarding the CS1, UCARTCS1. I know your clinical hold lift was much faster or earlier than expected. Can you give a little bit more color what FDA was looking for? And then what was the modification of the protocol going forward for the program?

Gena, thank you so much for the wonderful questions. Maybe I can take the first part of the question, and then I'll direct it over to Carrie, who is our Chief Medical Officer, who can answer a little bit of the background on the CS1 program.

So for Cytovia, they will be responsible for the manufacturing of their NK cell programs. We provide the technology for them needed to make the gene editing part, which is a pretty straightforward system that we have perfected in-house, which we have already provided for, for example, Iovance's TIL program for the gene editing approaches there. So it's a similar setup. We haven't given too much color around the targets. Obviously, the company is still a private company and has the benefit to move forward without disclosing those targets too early, but it's a mix of solid and liquid tumor targets. And Carrie, maybe you can talk a little bit about CS1.

Yes. Gena, nice to hear you. So yes, we were really pleased with the lifting of the hold back in the fall. And as we had previously disclosed to everyone that the hold initially was due to a patient death at dose level 2 during the dose-limiting toxicity window. We are planning on sharing data, hopefully, very soon from these first group of patients from last year prior to the hold. And with that, we will be providing additional details on what we were -- what we've done to reopen the study.

Our next question is from the line of Salveen Richter with Goldman Sachs.

I was just wondering if you could provide us with some time lines for the program -- the new programs moving into the clinic, be it genetic diseases, as you mentioned, or you're looking to file INDs or these natural killer iPSC cell programs?

Salveen, so first of all, the time lines for our new INDs that Carrie mentioned briefly on the call, this is something we will talk much more about this year as we're progressing towards IND filings. What we do want to show is that we have been quiet for the last couple of years on our preclinical development and our gene editing platform, while, at the same time, actually making a lot of progress on that front. And we would really like to show the Street what is under the surface at Cellectis because we are a world-leading gene editing company, with a platform in T-cells.

Internally, we have partnerships with leading companies in NK cells and TILs. And we have a gene therapy program that we would like to really put front and center as a new pillar of value for the company. But for us, the biggest focus and time lines this year is it's getting very exciting with our clinical development of our current proprietary CAR-T programs. We are advancing this to the dose escalation phases that we mentioned.

So we expect some very interesting data flow out of our current clinical programs, and then we expect new IND filings within 12 months. So bear with us just a little longer. I think we'll give more information in the second and third quarter of this year as we're getting really close to these IND filings.

Our next question is from the line of Hartaj Singh with Oppenheimer.

Just one question. You know (technical difficulty) companies and out in the field of problems locating things as simple as pipettes, also plasmids, mRNA, et cetera. A lot of it seems to be vacuumed up into the COVID-19 space. How -- André, how are you positioned with your Paris and your Raleigh facility in this regards also being autonomous by the end of this year? And then I just have a quick follow-up after that.

Thank you very much, Hartaj, for the question. I think it's an important question. And we took the decision in 2018 to start constructing our manufacturing plan. And we took a decision, was to split in order to go fast on the first phase and -- because the second phase would be longer. So the first phase was essentially to build up a manufacturing plant fully GMP to manufacture DNA, plasmids, mRNA for the TALEN, and vectors to bring the CARs inside the cells. And that's operational since 2020 and start producing.

Imagine, in 2020, with the COVID crisis, trying to order an mRNA with what's happening in there, even a plasmin, et cetera, it's becoming a real complication. And when I'm saying that Cellectis' full integration is kind of one-stop-shop. It goes like from the ID at the bench and so we can manufacture everything. All the raw materials to make a CAR-T, like plasmids internally, we can immediately have them. We have all the quality system around this. We have all the vectors, or the mRNA, everything is shipped to Raleigh. Raleigh is going to go operational this year. And the cell and gene therapy is becoming a more and more intense market and the fact that we can build everything internally, including sometimes the buffer, but the electroporation technologies are ours. So we can tune up all the little details around this. I believe today, in 2021, it's one of the biggest strengths and it differentiates the company very strongly.

Great, great, André. And then just a quick question on UCART123. I think last year, with the new IND you had mentioned that you'd be looking at patients with maybe a better performance status, maybe a slightly younger group of patients. And there might be a little bit more of a window between doses. Has that changed? Are you still sort of going through those initial phases of that escalation protocol?

Hartaj, maybe I can take it, and I can hand it over to Carrie. So we're currently dosing patients at dose level 2 at the arm of addition of alemtuzumab to the preconditioning cycle. So we actually do 2 arms of the study in parallel, 1 with Flu/Cy and 1 with Flu/Cy plus alemtuzumab. And Carrie, maybe you take over here for the patient population we're treating and the dose escalation plan forward?

Yes. So thanks for the question. So as Simon pointed out, we have 2 arms now open in that trial, and we're evaluating using alemtuzumab or not using alemtuzumab in this patient population. And I think it's important to point out, and you make that clear. Patients with AML are somewhat, I don't know, if unstable is the right word, but it's a tough group of patients to crack. They tend to be older, they tend to have poor performance status, et cetera. So it's really critically important to look at preconditioning using alemtuzumab or not because alemtuzumab can sometimes add its own issues, so we want to be sure.

That said, in terms of their performance status, the protocol, if anything, allows people with relapsed/refractory disease, we have some eligibility built in to ensure that patients -- we're enrolling patients that should be able to tolerate any side effects that we would expect like cytokine release, et cetera. But that said, as patients with AML tend to be unpredictable, what I'm very comfortable with and proud of is we have a really strong medical team, particularly in the leukemia space that I've been building since I joined early last year. And we're very close with our investigators. We're very close and speak with them regularly and discuss the patients and go over all of their criteria to ensure that we all think that this is the appropriate study for those patients. So I feel confident that we're enrolling patients that can tolerate our products so we can get some answers in this very difficult-to-treat patient population.

Our next question is from the line of Yigal Nochomovitz with Citigroup.

I just had 1 on UCART22. Could you clarify what you mean by the correlative analysis of cell expansion and persistence? Do you mean correlation of cell expansion persistence with response? And will this analysis determine whether you need to adjust the lymphodepletion regimen? And then a separate financial question. Could you just comment where you stand with respect to your stake in Calyxt? Is that something you would consider selling to further finance the company?

Yes. Thanks, Yigal. Maybe first question for Carrie, and I can start with the second question really quick. So for Calyxt, we're over 50% shareholder in the company. We love what the company is doing. They actually have what we believe is a very strong period of growth ahead of them. So please monitor their earnings call as well that just happened last night or yesterday. It's a wonderful company with a scarcity value because it's the only publicly-traded gene-editing company in the agriculture space currently, with a full focus on sustainability and improving crops in the ag space for consumer consumption. It's, again, something that we don't expect to divest any time soon. Carrie, if you want to answer the question on 22?

Yes. Sure. Thanks so much. So correlative analyses are basically all of our translational work, where we're going to be looking at the lymphocyte recovery, the subset T, NK, B-cell subsets as they come back, and correlating that with our expansion data on the cells -- on the UCART cells as well as efficacy. And we're looking at that very closely to help us understand what our best foot forward will be, whether or not we need to make any additional adjustments to the preconditioning, et cetera, so we can give the UCART cells the best chance of success.

Our next question is from the line of Wangzhi Li with Ladenburg.

I have 2 questions, too. The first 1 is regarding the new programs you expect to file R&D this year. And Carrie mentioned also there's a new direction for genetic disease. So my question is, can you provide more color in terms of the number of new INDs this year? Is this one program or other programs? And for the genetic disease, can you provide any more color on what kind of direction or space, assuming that ex vivo will approach for genetic disease? Any color would be helpful.

And then the last question is on the CAR-NK partnership. Can you provide some high-level color on the target. Is it going to -- will it be not -- will it happen with your CAR-T targets? Or is it allowed to -- for some same targets?

Thanks, Wangzhi. Very good questions. I will have to say short answer for the first question. We will provide more color on our programs that are previously undisclosed in the second quarter of this year. So we will give you all the details then. And just rest assured, it's a very exciting program where we think we have a huge differentiating technology for. So it's something that currently cannot be done with any other technology. For the second question on NK cells, André, do you want to give a little more color on the target? I don't believe we have given that color.

Well, Wangzhi, we haven't disclosed the targets because it's more on the Cytovia side to say this. And like we're -- everyone's copying on everyone in this space and more -- especially everyone copying on Cellectis in this space. So if you want to hear about what we're doing, then like I could fuel the market a new ID, and we'll definitely do this, but like to prepare ourselves as much as possible to try to like move forward very rapidly. But on the Cytovia side, I think that nothing of this was disclosed. We're super excited by the IDs we've been growing together. And it's no -- there is no information we can unfortunately air on this outside the fact of maybe waiting for the second half -- like second quarter this year to effectively give you an update on the pipeline, the preclinical pipeline we have.

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

Maybe on the myeloma program, given the clinical hold was lifted in mid-November, when do you expect to start redosing patients in that trial?

Yes. Carrie, would you like to take that one? Biren, good question.

Sure. Absolutely. So once the hold was lifted, we started all of the downstream activities that would allow us to start redosing. And we have already begun opening our sites and should be planning on first patients with redosing, hopefully very soon.

Okay. And then, I guess, with any of these 3 programs, do you anticipate that you'll have sufficient clinical data by end of this year where you can make a decision to go into a pivotal cohort next year?

So our plans as of now are, as we have the data available, to give a good package of data, as I said before, that is meaningful. As I think we've previously stated, I think UCART22 is moving forward the most quickly. And that could be something that potentially we could consider, but we will have to depend on what we see with our data and how things move forward.

Next question is from the line of Nick Abbott with Wells Fargo.

First one is on UCART22. Have you demonstrated direct evidence of host immunity targeting UCART22? There's correlation between T-cell reconstitution and disappearance of UCART22. But have you actually identified, which host cells are targeting the UCART22 cells?

Yes. No, at this point. We haven't -- go ahead, sorry.

No, no, I wanted to direct this to you.

So we're doing all of that work. We're really looking to see -- to me, more important -- well, both things are very important. Any of the cell recovery as well as which cells are actually targeting the allogeneic CAR-Ts to be rejected. So we are looking at all that data. We don't have that data available to share. That said, I do think the key is really ensuring that we are able to keep the count recovery long enough for the UCART cells to expand and do their business. And I think that the addition of alemtuzumab and ensuring that we find the best way of including it for both safety and efficacy is really key for this year in terms of our goals. And we will be looking at all that data to help inform the best plan for moving forward, whether it be in a pivotal situation or otherwise.

And that's a great segue to my second question, which is on alemtuzumab. Currently, you're looking at 20 milligrams consecutively for 3 days. So how long do you expect that to be effective at dampening down this host immune recovery? How much variability do you expect to see? And how long do you want to keep that host immune recovery down?

Yes, that's a great question. Again, I think this all goes to the data. So we know from earlier data with allogeneic transplant that the use of alemtuzumab can -- is used in preconditioning for transplant. And typically, you would expect the lymphodepletion to be 6 weeks or so. It can be for quite a long time because it's a monoclonal antibody, obviously, with a very long half-life. So finding that balance where we're keeping the host immune system at bay long enough for the cells to ablate the leukemia, but not too long that you end up with other issues is a critically important piece of this puzzle. And as we gather data, I want to be making data-driven decisions on how we do that. So to answer the question, I can't exactly answer how long because it's going to depend on what we see with the data.

Next question is from the line of Raju Prasad with William Blair.

This is Sami, on for Raj. Congrats on the progress. Based on your data and the data from Allogene to date, how are you guys thinking about redosing across your trials? And then also, could you remind us if you plan on enrolling patients refractory to BCMA therapies in your CS1 trial for multiple myeloma?

Absolutely. Carrie. You go ahead.

Right. So the second part of the question is faster, so I'll start with that. So in all of our trials, whether it's BCMA or CD19 or other AUTO or ALLO or CAR-Ts for that matter. We don't exclude them. So our programs, which I think makes them unique and exciting, is that we're able to enroll patients and potentially see a signal in a patient who's already failed one of these therapies and would not be able to go on to, let's say, if they had an AUTO-BCMA, they may not go on to an ALLO-BCMA, for example. So it does give us more shots on goal because they're alternative targets, and we're really the only people pursuing them in the ALLO space in a large way. So I think that's a really important unique property of our program. So the short answer is, yes, they can come on the study.

In regards to redosing, absolutely, one of the key, most important and exciting pieces of allogeneic CAR-Ts is the fact that we can redose, and so we are exploring that in these studies. And we will be -- when we have data to share, we'll be exciting to share that with you all.

Next question is from the line of [Ingrid Benzinga with Kankan].

I acknowledge it made difficult for you to speak for your partners. To the best of your knowledge, when would you be expecting to hear something more from Servier and Allogene about their plans for UCART19 ALLO?

Thank you so much for the question. It's a very important point because it's obviously a strong value driver for us, not just from an economics perspective and milestone revenue, but also from the platform validation perspective. So UCART19 was the first product that Cellectis brought into the clinic in 2015, and that has since been renamed ALLO-501. And ALLO-501 is equal to UCART19. However, there has been a new version of UCART19 that omits built in off switch, which is activated by rituximab, and that program is called ALLO-501A. So in short, it's just an easier to produce product that allows to use UCART19 or ALLO-501 with patients that have been treated with rituximab, which is part of the standard of care approach in NHL patients.

So Allogene and Servier are now moving forward in a unified fashion the ALLO-501A. And that all ALLO-501A program, as Allogene has recently mentioned, is slated for an update in the second quarter of this year at a medical meeting. So this is just a few months down the line now, where we will have an update on patients treated with ALLO-501 and ALLO-501A. And both companies have said that they would like to join forces to initiate a Phase II study by the end of this year for this program, which could be potentially the pivotal registration trial for this program.

So it's a very exciting time for us at Cellectis because we think the first program that we brought into the clinic as a trailblazer of the allogeneic gene-edited off-the-shelf CAR-T cell space is now actually on track towards potentially first product approval over the next 18 months or 24 months. So look out for news on that front from Servier and Allogene. There will be data on this program mid this year and potentially initiation of a Phase II trial by the end of this year.

Our next question is from the line of Jack Allen with Baird.

I wanted to ask about your thoughts with regards to timing of getting the TALEN based products into the clinic in solid tumors. I know you mentioned that ALLO-316 is expected to enter the clinic in the coming months. But I was also wondering if you could touch on the timing with respect to advancing clinical products with respect to the Iovance and Cytovia partnerships as well.

Jack, yes, it's a wonderful question. We think solid tumor approaches are really the next frontier for cell therapy as this pertains to our partnership as well as to our proprietary programs that we're aiming to move into the clinic. So we mentioned this in the past that new INDs will also address solid tumor targets from Cellectis. So proprietary targets to Cellectis, I think, will make an interesting development case here, but as you said, also on the TILs and NK cell platform. So we wanted to derisk our technology first in liquid tumors, where we've seen really great responses with our CAR-T cell approaches. And now we're expanding that beyond liquid tumors into solid tumors.

Next question is from the line of Soumit Roy with JonesTrading.

Sticking with the -- in line with the prior question, could you give us some broad stroke thought process on tackling solid tumor like -- especially looking through the lens of Cytovia deal? Are you picking winning strategies here with iPSC NK cell line? Or how do you pick between gamma-delta or alpha-beta? Are you looking into tissue penetration of cell type or T cell modification? What do you think will crack the solid tumor nut?

Carrie, maybe you want to provide some comment on that first. Thank you, Soumit, for that question. Carrie, go ahead.

Yes, sorry, I was on mute. I'm not 100% clear on the question, to be honest with you. So just in terms of which targets or I'm not -- sorry.

Like the cell type, like are you still thinking alpha-beta T cell is the right cell type to tackle the solid tumor or with Cytovia deal you are indicating maybe iPSC NK cells are a better candidate for tissue penetration in the solid tumor versus liquid tumors?

Yes. So I think that's a good question that we just don't all know -- we don't know the answer to. And I also would turn to André for more color on that, but I do think what I think is critical here for us as Cellectis is that we have the gene editing platform, so we can do all of these different approaches to whether it be a liquid tumor or solid tumor or other diseases. And I think that applying this platform to different -- to all these different platforms, whether it be iPSCs or gamma-delta, alpha-beta what have you are important clinical and research questions that need to be answered because I don't think there's an answer.

And so I think it's -- what's important that we're doing here at Cellectis is we have our feet or toes or fingers in all these different potential options that will help patients in need. And that's why I think being here is so exciting because we can make a difference in all these different ways. And we will figure out what is actually the best strategy, whether it be for liquid tumor, solid tumor or other diseases.

Yes. I cannot agree more with Carrie. The limitation that Cellectis has is not technical. We can do everything technically. Our gene editing technology is extremely powerful, and there is more and more papers that are coming, showing that the access of pairing to any kind of DNA and the precision of this technology and it's accuracy and its simplicity and the ability to promote DNA recombination, replacement, correction, et cetera, is unprecedented in this arena, plus we have like electroporation, et cetera. The limitations are not technical for Cellectis. The problem is more of focus of the company and also was, for the past years, on the manufacturing, but we just unplugged this blockage that we have. The manufacturing is internalized bit by bit, and this year, 2021, will have no limit in term of what we can manufacture for clinical supplies, but also for commercial supplies.

And also Carrie is building a huge and awesome clinical team around her from cleanups to translational, et cetera. And that's like the limit is more people and what we can do and, of course, the finances of the company that have to follow on this. But we cannot spread ourselves on a thin layer. The problem is certainly not technology-wise because we own it all. The problem is on the focus of the company, and I think we're really laser-focused on what we're doing currently.

Thank you. At this time, we've reached the end of our question-and-answer session. And now I'll hand the floor back over to Simon Harnest for closing remarks.

Thank you so much. And again, thank you all for joining us. We'll have a couple of follow-up calls after this, feel free to always reach out to me. And again, I'm very excited about this year because I think there's going to be a lot of clinical data coming that we're all very much eagerly waiting. So thank you again for joining us, and we'll speak to you soon.

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