Cellectis SA (CLLS) 2017 Q4 法說會逐字稿

Greetings, and welcome to the Cellectis Full Year 2017 Financial Results Conference Call. (Operator Instructions) As a reminder, this conference is being recorded.

It is now my pleasure to introduce your host, Mr. Simon Harnest, Vice President of Corporate Strategies and Finance. Thank you. You may begin.

Thank you, and welcome everyone to Cellectis' Fiscal Year and Fourth Quarter 2017 Financial Results Conference Call. Joining me on the call today with prepared remarks are André Choulika, our Chairman and Chief Executive Officer; and Eric Dutang, our Chief Financial Officer.

Yesterday evening, Cellectis issued a press release reporting our financial results for the fourth quarter and year ended December 31, 2017. This press release is available on our website at www.cellectis.com.

As a quick reminder, we will make forward-looking statements regarding financial outlook in addition to 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 on most recent form 20-F on file with the SEC.

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

Well, thank you, very much Simon, and good morning, everyone. 2017 was a great year and is of tremendous advancement for the CAR-T field as a whole and for Cellectis, in particular, as we brought our first wholly-owned program into the clinic.

We are, more than ever, very excited about the potential of CAR-T for the treatment of cancer. Cellectis is the company of 2 revolutionary concepts, gene editing on one side and CAR T-cells on the other side. By combining these 2 technologies, we have set the trajectory of the concept of gene-edited allogeneic CAR-T's to become a revolutionary therapy in the field of oncology and beyond.

At Cellectis, we're combining the cutting edge of proprietary gene-editing technology with the latest generation of CAR-T constructs, resulting in an unparalleled proprietary knowledge of cGMP-grade cell manufacturing.

We are taking the first step in transforming cell therapy into a genuine pharmaceutical product. Since 2014, we have been producing, through a series of manufacturing campaigns, large-scale gene-edited allogeneic CAR-T cell batches under internationally recognized cGMP standards, which led to the first-ever clinical application of an allogeneic CAR-T product candidate, UCART19 for compassionate use back in June and November 2015.

These first patients treated with UCART19 for an aggressive ALL are still in complete remission and cancer-free today, and our partner, Servier, continued to advance this next-generation product candidate through clinical trials.

The driving force behind allogeneic off-the-shelf CAR-T platform is our desire to make this groundbreaking treatment modality more accessible to patients and clinicians worldwide and to remove some of their uncertainties associated with CAR-T regarding cell quality, yields or manufacturing uncertainties, as well as the time lag between (inaudible) and injection.

And to enable a cost treatment below the cost of individualized autologous CAR-T therapy. In one word, to this revolutionary therapy, CAR-T, we plan to bring market access.

At the recent American Society of Hematology annual meeting, or ASH, in December 2017, our corporate partner, Servier, along with our clinical partner, UCL and King's College London, presented the first set of adult and pediatric CD19 positive ALL patients treated with UCART19 from their ongoing Phase I dose escalation trial.

Only patients who have exhausted all available treatment options, including the ones that failed the enrollment into an autologous CAR-T therapy were eligible to be enrolled in this trial. All in all, 5 out of 5 pediatric patients were completely tumor free, defined as MRD negative, at the day 28 post UCART19 administration, dose at 4 million cells per kilo.

5 out of 7 adult patients were completely tumor free, MRD negative, a day 28 post UCART administration dosed with 100,000 cells per kilo. We're also pleased with the safety profile of UCART19 to date with no serious adverse events related to GvHD and only 2 cases of cytokine release syndrome gathered than -- greater than grade 3 in 14 patients treated today with no neurotoxicity.

We are looking forward to more presentations this year by our partner on UCART19 that will include longer-term follow-up of these initial patients as well as data from higher dose's cohorts.

These data demonstrate that allogeneic CAR-T's are not a hypothetical future for patients. At Cellectis, we made it happen and it's happening right now, today, in hospitals in the United States and in Europe.

Over the past 3 years, in addition to the production of UCART19, we have manufactured another wholly-owned allogeneic CAR-T product candidate, UCART123, which is currently in Phase I trial in AML and BPDCN in the United States. After a hold by the FDA in September 2017, UCART123 is back in trial at the dose at 62,000 cells per kilo as the new start dose for the dose escalation -- for the escalation phase.

Currently, we are manufacturing our third product, UCART22, which is set to enter clinical trial in the second half of this year in ALL and non-Hodgkin lymphoma.

In 2018, we will build up on the clinical proof of concept of the selected UCART platform, started almost 3 years ago with UCART19, by advancing our wholly-owned product candidates, UCART123 and UCART22, through clinical trials.

Cellectis is currently running 2 dose escalation trial with UCART123, the AML trial, which is lead Dr. Gail Roboz at Weill Cornell Medical School in New York City, and the BPDCN trial is by Dr. Naveen Pemmaraju at MD Anderson Cancer Center in Texas.

While we already have a series of patients waiting to be enrolled in these trials, there is one significant aspect to be considered for patient safety. It's an FDA requirement for all allogeneic donor-derived CAR-T cell programs to go through a dose-escalation phase, where the dose-limiting toxicity and the maximum tolerated dose are defined.

This is one of the differentiating factors to autologous CAR-T cell programs. The requirement enabled us to empirically establish the relationship between CAR T-cell dosing and the antitumor effect of our CAR T-cells.

We expect to complete this dose-escalation phase for UCART123 within the next 12 months before moving into the expansion phase in 2019, where we plan to enroll up to 150 ML and BPDCN patients. This is where the true advantage of allogeneic CAR-T cell manufacturing process kicks in as we have already produced enough vials of UCART123 up front to treat patients simultaneously through the expansion phase of these studies.

AML is a particularly difficult-to-treat disease. The current standard of care leaves a huge gap in unmet medical need. We believe UCART123 has the potential to significantly impact the tumor burden in patients. Our goal is to move through the dose-escalation phases of these trial through 2018 to enable us to open expansion cohorts in 2019. We expect to report an initial clinical data by the end of this year that details the initial safety and antitumor activity observed in the dose-escalation trial.

Following in the steps of 19 is UCART22, an interesting target for the treatment of ALL and NHL in patients who either express CD22 from the onset or have relapsed CD19 negative following CD19 directed CAR-T treatment and for expressive CD22.

We're currently in the final stage of cGMP manufacturing, and we plan to submit an IND for UCART22 in the second quarter of this year to treat ALL and non-Hodgkin lymphoma patients with clinical trial -- trials in the U.S. to start shortly after.

While we are in the first stage of manufacturing -- final stage, excuse me, we're in the final stage of manufacturing UCART22, we're already running multiple production runs and process developments for UCARTCS1 in multiple myeloma.

UCARTCS1 is the first time that CAR-T cell therapy will go after this target. The trick is, you need to knock out CS1 or SLAMf7 from the surface of CAR-T cells first, using gene editing, before integrating a CAR-T that targets CS1. We believe that UCARTCS1 represents a promising therapy for multiple myeloma patients built on one hand on the validation of the target by -- produced by the use of elotuzumab as a monoclonal antibody, and on the other hand, by the promising results producing by autologous BCMA CAR-T approach for multiple myeloma.

CS1 has a potentially adventurous safety profile as CS1 is not expressed on healthy tissues as BCMA is. UCARTCS1 will follow UCART22 with an IND filing planned in 1 year. As a platform behind our clinical progress, Cellectis is housing one of the strongest R&D departments in our space. One highlight was our recent presentation of our proprietary TALEN gene-editing technology at the Keystone conference in February.

We presented a poster on an [engining] CAR-T cell with a TCR alpha and TCR beta knock out, beta-2 microglobulin knock out, a CAR-T knocking and an NK inhibitory knocking. While our single-gene knock-out efficiencies are close to 100%, this multiplex gene-editing platform, including the use of multi-gene targeting by DNA break-induced homologous recombination with an overall efficiency up 68% showcased the power of our technology and knowledge.

We have shown that TALEN are capable of achieving simultaneous double knock-out and double -- double knock-in and double knock-out efficiency over 68%. This is the highest efficiency to date achieved in such a multiplexed knock-out and knock in T-cell with any gene-editing technology by a factor close of 2x. And this is just a glimpse at our capacity.

In the past, we have shown that we could achieve at the R&D level could robustly translate into cGMP production for clinical supply. This is our strength. Therefore, this represents the next step in our manufacturing platform. Starting in 2019, we are planning to manufacture CAR-T product candidates on the basis of targeted gene insertion of CAR-T replacing the traditional antiviral vector approach.

Another very important key aspect is yields. Achieving high-performance gene editing is great, but Cellectis' goal is producing pharmaceuticals, therefore yield through all the manufacturing process is key.

In 2010, we have acquired an asset of CytoPulse -- the assets of Cyto Pulse, an electroporation company based in Maryland, and we have heavily invested to develop the technology until today to achieve very high level of cell transduction and viability post T-cell transduction.

We have perfected our proprietary electroporation technology to handle large quantities of cells like gently transducing cells with TALEN. This results in very high transduction rate of cells in CNG -- cGMP conditions, but most excitingly, the cell survival, post electroporation, is also huge.

This translate into high yields and, of course, low COGS. This is key. A large distinguishing factor for Cellectis in the gene-editing space is our IP. Our proprietary patent portfolio that encompasses a large -- and a large umbrella patent in gene editing, starting by a basic licensed homologous recombination patent, no nuclease needed, to the nuclease-based gene-editing space, using homologous recombination as well as nonhomologous end joining, together with the specific patent families as they're related to TALEN or meganucleases.

We have recently also announced the issuance of a specific patent related to the editing of T-cells using CRISPR. However, due to the secure efficiency and plasticity as well as safety, we're using TALEN for the manufacturing of all of our therapeutic CAR-T cell programs.

Turning now to our partner programs, we have been extremely impressed with the progress made by our partner. Servier recently announced the expansion of UCART19 in multiple centers in the U.S. and the EU.

Once the dose-escalation phase is completed, UCART19 will move into expansion phase in 2019, which could be followed rapidly by a registration trial. We're looking forward to hear more updates this year.

Pfizer has shown very exciting results on the first off-the-shelf BCMA CAR-T program for multiple myeloma and also the first allogeneic solid tumor CAR-T targeting EGFRvIII for gliblastoma.

We strongly believe that the successes of CAR-Ts in solid tumors will lead through allogeneic CAR-T and gene editing. We strongly believe in the superior potential of the CAR-T programs of our partners, Pfizer and Servier, both in terms of potential and span, with (inaudible), today, the leading team of the allo CAR-T space by far.

With the competition walking up -- waking up on this huge opportunity, our intention is to accelerate.

With that, I would like to turn the call over to Eric Dutang, our Chief Financial Officer, for a discussion of financial results. Eric, please go ahead.

Thank you, Andre. As of December 31, 2017, Cellectis had $297 million in cash, cash equivalents and current financial assets compared to $291 million as of December 31, 2016. The $6 million increase over the 12 months period was notably explained by the following elements: $38 million proceeds received as part of Calyxt IPO, $7 million proceeds from the sale and leaseback transaction at Calyxt, $15 million of positive Forex impact on cash flows, which were partially offset by $52 million net cash flows used by operating activity.

The team continues to execute a strategy with financial discipline. We expect that the cash, cash equivalents and current financial asset position of $297 million as of December 31, 2017, will be sufficient to fund current operations into 2020.

Revenues were $34 million for the 12-month period ended December 31, 2017, compared to $56 million in 2016. Collaboration revenues decreased by $19 million, which was notably explained by $8 million in onetime milestone revenues recorded in the second quarter of 2016 in connection with UCART19, $6 million decrease in revenue recognition of upfront payments and a $5 million decrease in revenue of research development services and supply of UCART19 products.

Operating expenses were $126 million for the 12-month period ended December 31, 2017, compared to $124 million in 2016. Excluding noncash stock-based compensation expenses of $49 million in 2017 and $59 million in 2016 adjusted operating expenses increased by $12 million from $65 million in 2016 to $77 million in 2017.

For the 12-month period, R&D expenses remained stable at $79 million. Excluding noncash stock-based compensation expenses, adjusted R&D expenses increased by $9 million from $46 million in 2016 to $55 million in 2017.

This increase in adjusted R&D expenses was notably related to UCART123, UCARTCS1, UCART22 and other product candidate development, including payments to third parties and costs related to clinical trials, strategies of biological materials and expenses associated with the use of laboratories and other facilities.

For the 12-month period, we recorded $45 million and $43 million of SG&A expenses in 2017 and 2016 respectively.

Excluding noncash stock-based compensation expenses, adjusted SG&A expenses remained stable at $18 million between both periods.

Net loss attributable to shareholders of Cellectis was $99 million for the 12-months period in 2017 or $2.78 per share compared to a net loss of $67 million in 2016 or $1.91 per share.

Excluding noncash stock-based compensation expenses adjusted loss attributable to shareholders of Cellectis for the 12-month period ended December 31, 2017, was $50 million or $1.41 per share compared to $9 million in 2016 or $0.24 per share.

I'll now turn the presentation back over to André for closing remarks.

Well, thank you, very much, Eric. I would like to highlight again what remarkable progress we've made in 2017 by transforming the off-the-shelf CAR-T cell concept into reality.

Today, everyone knows that the future of CAR-Ts is in gene editing. It's a fact. We made it a reality. I believe we can say, without a doubt, that we have only just scratched the surface of what a powerful treatment gene-edited CAR-T cell therapy represents.

In 2018, Cellectis will be building up on the foundation fed during the past 5 years and will reach a turning point in 2019, reaching expansion phase and extending our lead into the allogeneic CAR-T cell field together with our partners.

By the end of this year, 3 off-the-shelf CAR-T product candidates will be in the clinic with our wholly-owned UCART123 and UCART22 programs as well as partner UCART19.

Looking ahead into 2019, we'll have 2 different oncology programs, ALL, AML, in an expansion phase and expect to advance additional UCART product candidates into clinical development with UCARTCS1 and UCART CLL1.

This year and next, we will continue the robust development of the best-in-class manufacturing process of our next-generation CAR-T therapeutics, including implementing our proprietary gene-targeted gene-insertion technology into our pipeline of product candidates.

To support this progress, we will significantly expand our clinical leadership team and footprint in the U.S., and we will invest significantly in proprietary assets, such as in-house manufacturing of commercial supplies with a state-of-the-art industrial process and large-scale multiplex gene editing.

At Cellectis, we think big and with the proof of concept in hand, we're pushing forward full force with our partners to bring allogeneic CAR-T cell programs into the clinic and to the patients worldwide.

We also plan to file an IND for a program built on our TALEN gene-editing platform outside of the field of oncology in the future, extending our lead in gene editing in the gene-editing space.

We look forward to sharing more about our exciting work in this area at the medical meetings throughout 2018 and 2019.

With that, I want to thank you very much for your attention, and I'd like to open the call for questions.

Joining me for the Q&A will be Eric Dutang and Simon Harnest. Operator, please go ahead.

(Operator Instructions) Our first question comes from the line of Christopher Marai with Nomura Instinet.

First, I was wondering if you could further elaborate on your UCART123 studies and the type of data we might see year-end. You had discussed, obviously, the requirement to have dose escalation for the allogeneic CAR-T approaches, and I was just wondering is it your expectation to have the recommended Phase II dose sort of declared in the year-end update for that program? And then secondarily, with respect to the expansion phase, how should we think about that? It's about 150 patients. That looks to be about the size of some of the registrational trials. And now, obviously, I guess you're selecting for patients with CD123 or that's relatively also heavily expressed in AML anyway. Can you maybe we walk us through that approach with respect to registration?

Well, thank you, Chris for these very good questions, and good morning, by the way. It should be quite early for you. Yes, actually the dose escalation we, of course, plan by like within 1 year to have the right dose. We think that the start dose we've targeted with last year at 6.25x10^5, which led to the clinical hold after the injection of the BPDCN patients with a Grade 4 CRS was probably a good dose. But we're now like at -- like 62,000 cells per kilo, like 62,500 cells per kg, which is a very low dose, so we still think we're below the optimal dose, and we have to move forward into the dose escalation. It's a 3 plus 3 dose escalation. Potentially, we can maybe, just for confirmation, have 3 more patients. There is a lot of enthusiasm around the product, and we would like to -- you will probably see that Cellectis is trying to accelerate this in the future, so we'd like to push forward into a speed-up process, and we're working with our Chief Medical Officer, Stéphane Dépil, and our Chief Regulatory officer to try to speed up this process to try to reach the time where we have defined this best dose.

But the dose finding is a critical step in oncology. If you go too fast in there and you miss the right dose, it might also hamper the potential of the product. So we are doing this extremely seriously. Now for the second part of -- we're doing this seriously, and we expect probably to complete this within a year. On the expansion phase, I said 150 -- up to 150 patients for AML and BPDCN, it's like both trials. We will, of course, be extremely open and trying to dialogue with the FDA to try to see what is the threshold to go for registration. But whenever we have convincing results and meeting the endpoints, we'll, of course, like run into registration. This is why also we're starting to think about what should be a commercial supply manufacturing plan. So we should get started from now.

Great, thank you. And then with respect to the UCART22 program, if you'd maybe elaborate on some of the patient populations you may go into, would those be CAR-T naïve patients or would you go into patients who have previously -- who have progressed having previously received CD19-based CAR-Ts?

The trial is -- like in the trial, we would like to be totally agnostic and like concerning patients that relapsed CD19 negative, CD22 positive. The only criteria we're looking at is the presence of CD22 on the surface of the B-cell malignancy. One of the thing, also, is like the CD22, the gene is -- has more wobbling than CD19, so the stability of expression on the cells and the variegation cell expression from patient to patient could be quite different. So what we will be focusing on is, of course, the presence of the tumor (inaudible) antiandrogen on the tumor surface. We expect potentially to have maybe less of potential compared to UCART19 to go directly in patient untreated with CAR-T or maybe we will have the potential to go with patients that have not been treated with CAR-T, but definitely you have a series of patients that do relapse CD19 negative and are CD22 positive, or potentially you could use this in combo. So it could be also a definitely very interesting way to be able to treat patients like with a shot of 19 followed by a shot of 22. So the potential of off-the-shelf CAR-Ts and the potential of repeat dosing and combo therapy is unexplored for now, and we definitely have the intention to do this. So it's like really a start. Like we're not like hampering ourselves of any -- like preventing ourselves to go in like any direction for now. We're open.

Our next question comes from Pete Lawson with SunTrust Robinson Humphrey.

Just -- I apologize, I joined late. So if I -- if you already mentioned this, just on 123 reopening, how many patients have you enrolled since in November?

I did not [said] it. How many patients were enrolled but like the trial has restarted like since end of 2017, but it's not a number we communicated on.

Okay. And you don't want to talk about like how many are already in or just what the pipeline is like for patients?

No, not in this call. We'll probably talk about this later. But for an earnings call, I think that it's pretty -- too early to speak about this. Like the trial has really resume since the end of 2017. It may be early to start giving numbers on this. We're -- you'll probably see some information concerning this in the coming months.

Got you. But it sounds like there's pent-up demand. And I wonder if you could also talk through additional sites that you would be opening for the 123 trial and...

Yes, currently it's essentially at MD Anderson and Cornell for both trials, and like the expansion will come up in the future. There's probably 2 new sites that will open in the U.S. and potentially more sites outside the U.S. during the year. So the real intention of the company to try to speed up the patient enrollment and make -- like expand the potential different type of protocols and therapies and trying to tune this up, but we will -- our intention is to put the pedal on the metal.

Our next question comes from Hartaj Singh with Oppenheimer & Co.

My part, you know on UCART22, it's getting really interesting that you're also now mentioning B-cell NHL, André, as an area that you're focused on, the relapse setting there. What's the -- can you just tell us a little bit about what percentage of the NHL population is C22 positive in this relapse setting. ALL, I imagine, is a lot smaller than going into NHL. And then I've got a quick question on also GVHD. We were at the BMT Tandem Meetings out in Salt Lake City and it's interesting in bone marrow transplantation, they regularly see about 7% to 10% of GvHD, docs that are pretty used to dealing with it, but sometimes we get pushback from investors on the low percentage point GvHD that you see. Can you just put that in context? What you're seeing versus what the BMT community used to dealing with?

Hi, Hartaj, well, thank you very much for these questions. So concerning GvHD -- I'm starting or I will start by the question on GvHD. Concerning GvHD we've been dosing a series of patients for now between UCART19 and UCART123 and the process of manufacturing is fully similar because there is 2 editing in 19 and 1 editing in 123. We can consider, today, as the problem of GvHD as irrelevant in our process. The worst-case scenario that we had was, I think, the first patient and was like probably one of the first batches we ever made clinically -- like for clinical supplies was -- for UCART19 was the first patient that we dosed had suspected grade 2 GvHD. And even though we're not 100% sure that this was related to our cells and more like the analysis of the skin GvHD that was detected, there was a grade 2 that disappeared in 48 hours after using topical cream, seemed to be the result of the previous bone marrow transplant that happened that failed. But currently, for example, for adults, we don't have -- like for 123, have seen no signs for GvHD for adults, for the 19, we see no signs of GvHD and few skin rashes that could be attributed to grade 1 GvHD in 2 cases, I think. So I -- it cannot be compared with like an allo bone marrow transplant for now. And with the performance of cell filtration and the process of gene editing that we have, and I consider this problem as, of course, something that has to be a real concern during the manufacturing, of course, and on the safety of the product. But the QC and all the details that we are dealing with can definitely lead with products that are super high quality and don't lead to GvHD, so it's not a problem anymore. And I think that's part of the past up to now. Now on -- the first part of the question was?

What part of NHL is CD22, percentage-wise?

Yes, okay, okay, I remember the question. So like 22, the expression of 22 on B cells, it's present on all B cells unless there is a mutation that leads to the disappearance of 22. It's not that much of a problem. It's more the variegation in the expression of like CD22 on the surface of cells. So you see there is a wobble in the expression. So certain patients are high expressors, and this is fine. Some other patients are low expressors or you an intergenic population. And we don't know exactly how much you can wipe out down to a threshold of suboptimal expression of CD22 on the surface. Now I guess that once you're starting using the CD22 as a target, you'd probably fall into maybe a category of like pressure over the tumor where you might have CD22 negative, but we know the 22 is always expressed on B cells up to now. It's like CD19, it's very like much a copycat with this instability in the expression that makes it maybe a target that could be very valuable and used in combo with 19 for all the B-cell leukemia in general.

So we like this product. We think it's a very good product for B-cell leukemia. It's a kind of copycat of CD19 (inaudible) CAR-T 19, but we believe that also the rationale beside the portfolio and the combination of CAR-T or using it like a standalone CAR-T brings huge potential. Now in NHL or ALL or CLL you always can find these populations, and our intention is not to -- without regard to any other option that I cited, is trying to push down UCART22 in all the potential indications where it could be useful, always in trying to get the patients that have the best expressor -- expression for CD22, of course. But the logic is developing a portfolio.

Our next question comes from Wangzhi Li with Ladenburg Thalmann.

So just a few. Maybe start with UCART19. Are you -- the Servier is going to present the data at the upcoming EBMT meeting on March 21. Can you maybe provide a little bit more color in terms of whether we should expect the data. You mentioned a [long before] lab, do we also could expect more patients or how many more patients -- additional patients? Any additional color there?

Wangzhi, hi, how are you? Like do you want me to have like problem with Servier if I say a word on this? They will not be very happy about me speaking about what they're going to present. So I will not -- I cannot say this, because I very much respect my partners and I'm not allowed to speak about their programs. And second, I think it would be really a pity to start to disclose the results before like the physicians have the occasion to present the data by themselves. So I'm sorry, I'm not going to be able to answer this question, but it's a good question. Thank you very much.

Okay, no problem. Okay, so maybe you cannot answer the second question, too. So I just wondered maybe your thinking in terms of you mentioned that the UCART19 we'll have the expansion phase in 2019 followed with the registration trial, which I assume is in ALL. I just -- what's you're thinking or your partner's thinking right now on expanding UCART19 with DLBCL?

I think our partners have the plan to develop UCART19 in all indications, not with -- everything that -- like every tumor that could be the target to -- targeted with like UCART19 will have a potential development. But of course, it started with ALL pediatric and adult, but you will very soon see how much effort we're putting on this and how much acceleration our intention is in the future. Yes, DLBCL will be part of it but non-Hodgkin lymphoma, in general, and all other tumors that have CD19 on the surface. The results we have obtained in ALL are very convincing to try to expand this in a lot of different type of indications, and I think that there is absolutely no restriction behind this. No, this product is not meant to become only a bridge to transplant. No, this product is not to become only for ALL. This product is going to become a major product for all B-cell leukemia as much as they express CD19. And as I said it, it could also be potential synergies with other products targeting B cells such as UCART22.

Got it. And I'm sure you can answer this one. At the -- I just want to -- if there are any updates on the 2 compassionate use patients because, by now, they should have been followed up for a long time, right? Are they still in remission?

Yes, these 2 patients are still in complete remission. We're close to 3 years for the first patient. Like in June, it will be the case, and we're up to 2.5 years for the second patient that was dosed in November in 2015. This is spectacular, seriously, because like they received 1 dose of UCART19 and this is it. These patients failed all other therapies, including bone marrow transfer, blinatumomab, everything. It's like it was really the first demonstration. And, of course, everyone was expecting these patients to relapse, which is, I think, not cool for patients in general. And we -- we're extremely pleased to see that like we do have long-term remission.

Great to learn. Maybe last question is, as you mentioned earlier in your call, the gene-editing space is getting very active, so I just -- maybe share some color in terms of selected thinking or plan to go on the business development front for this year or next year.

Well, yes, actually there is like -- everyone is becoming agitated about using gene editing in CAR T-cells these days. And suddenly, hey, like it's becoming the main idea and we've been talking and advocating this since several years, and I know that most of you have been following Cellectis on this lead. There is a strong conversation between a lot of gene-editing companies, including Cellectis and other players in this field. The future of CAR-T -- the future of cell therapy, if cells are becoming a therapy, then the future lies in the ability to program the DNA of these cells to make them better products, either for the strong tissues such as CAR T-cells, like ablation of tissues such as cancer or reconstructing tissues or repairing tissues and healing and all these things. So gene editing is part of the future of medicine and is becoming a reality since 3 years, since Cellectis is pushing this forward.

And are we pushing forward to make more deals in this field? Cellectis has the intention today to bring our portfolio of products and beyond the products you already know to commercialization. This is my goal. This is the goal of Cellectis. It is becoming a commercial company in the future and being able to commercialize very important products for the patients and promote the high standard products. Is business development part of the strategy potentially to bring in new technologies, but our goal, as we are today, it's essentially to try to bring 123 in -- to commercial, to bring 22 commercial, CS1, CLL1, et cetera, and develop the wholly-owned portfolio of products either for CAR-T, but also behind -- beyond CAR-T.

Now yes, there is a lot of like business development interest all around our space today. And I think that 2018 is going to be a huge year for CAR-Ts and gene editing, in general, when I look all the announcements of our partners around because there is potential a lot of INDs a new patients that are going to be dosed. So I think it's going to be a real turning point in the industry in general. Well, with the past deals from like Gilead with Sangamo Biosciences that shows the interest that's -- it's exactly the same type of deal we signed with Pfizer in like 2014, 4 years ago, like almost 4 years ago, so we're excited to see that suddenly other companies are starting to say, while the future of autologous CAR-T is allogeneic CAR-T, we're not alone anymore.

Our final question comes from Biren Amin with Jefferies.

Just for the 123 trial, given other AML studies allow for bridge-to-transplant in patients that achieve complete remission. Is this something that you're allowing for the UCART123 study in AML?

Of course. Biren, this is -- making a single shot in a patient did make sense back 5 or 6 years ago when CAR-T started to spring because whatever you can get from like T-cells from a patient, then you can do dose and a yield of like lentiviral transduction, then finally, you inject everything you had and like you see what's happening. With the potential of having off-the-shelf products and with the potential of the ability to develop a therapy and not just like a therapeutic procedure, there is a span of potential that is illimited.

Today, we still have to find the right dose. What is the number of cells, with the potency they have, injected to the patient, confronting to this tumor mass will give that much of activity or tumor melting at the end? We have to know exactly this: robustness in manufacturing, what is the activity of cells to melt down tumor cells -- how many tumor cells they can melt. And once you get all these data, then the potential of developing this different type of administration mode is illimited. And we have a strong conviction at Cellectis, in order to reduce potentially the initial CRS that we have, for example, for the AML and the BPDCN patient last year, in the summer, is potentially to go with lower doses at start and expand the number of CAR T-cells with repeat dosing for the potential issues. But first of all, we have to go through the dose escalation with the potential to redose afterwards, and you will see that the protocol that will be applied by Cellectis will expand this potential in the future in different type of protocol settings. But we're strong believers by this type of approach. Not only this, but what I said in the -- like during this call, you can go after a tumor that have, for example, multiple types of tumor associated antigens, tackle the tumor with CD123, then re-tackle the tumor with potentially another product, let's say, CLL1, et cetera, to be sure that you cleaned up all the cells with a repeat dosing, one after the other and trying to reduce slowly the tumor for the comfort of the patient and his safety, but also to be able to totally clean up, on long term, the patient even if the potential to redose maybe 6 months after. I think nothing can be ruled out at the stage of today with the potential of opening a freezer and pull out a vial, whatever this vial is and analyzing the tumor and how the tumor reacts. I think that this is a key component to the CAR-T therapy in the next decade and probably in the 21st century.

Thank you. There are no further questions at this time. I would like to turn the call back over to Mr. Harnest for any closing remarks.

Thank you, everyone, for the great questions and for, obviously, tuning into our year-end financial call. We really appreciate the interest in the company and look forward to seeing you at future conferences. Thank you so much.

Thank you. This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation, and have a wonderful day.