Cellectis Inc.

Good morning everyone and welcome to Selective's fourth quarter 2021 and year end conference call. At this time all participants are in a listen only mode. Later we will conduct a question and answer session. Instructions will follow at that time. Please be aware that today's conference call is being recorded. I would now like to introduce the first speaker, Arthur Shrill, Chief Business Officer. You may begin.

Good morning and welcome everyone to SELECTIS Fourth Quarter 2021 Year-End Corporate Update and Financial Results Conference Call. 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 our new Chief Financial Officer, Dr. Bing Wang. Yesterday evening, Selective filed its annual report and issued a press release reporting its financial results for the fourth quarter and year ended December 31st, 2021. The report and press release are available on our website at selective.com. As a reminder, we will make statements regarding Selective's financial outlook in addition to its manufacturing, regulatory, and product development plans. These forward-looking statements, which are based on our management's current expectations and assumptions, and on information currently available to management, including information provided or otherwise publicly reported by our licensed partners, 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 31st, 2021, and subsequent filings Selectus makes with the Securities Exchange Commission from time to time. I would now like to turn the call over to Andre.

Thank you, Arthur. Good morning, and thank you, everyone, for joining us today. 2021 was a productive year for Selectus. We are proud of the progress we've made as it relates to our corporate milestones as we evolve to become full end-to-end cell and gene therapy by a pharmaceutical company. We have progressed on the clinical front with escalating doses of our product candidates. We completed our manufacturing plans, and that gives us control of product's quality and supply line. We continue to innovate. We have been working on our first dual-targeted UCART product. your CAR T20 by 22, and plan to bring it to the clinic in 2022. We have been able to leverage our valuable talent platform to provide selectives with business opportunities in the future cell therapy field outside of our core allogenic CAR T area. Regulatory issues that had posed some of our partner programs have been resolved, It is clear that none of these issues are due to select this Palin technology. And our financial position is secure. Based on our current plans, our cash takes us not just through 2023, but to early 2024. First, I will touch on some of the clinical progress. Kerry Brownstein, our Chief Medical Officer We'll give additional details later. We have trials running in three different forms of hematological cancers. At the annual meeting of the American Society of Hematology held in December 2021, we released encouraging preliminary efficacy and safety data from our BALI-01 trial evaluating UCAR-T22 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. These patients received fludarabine, cyclophosphamide, and alemtuzumab as lymphodepletion regimen and provides us strong confidence that we are moving into the right direction. These results showed that our preconditioning regimen that includes alemtuzumab was well tolerated. and promoted the expansion of clinical activity of our UCAR-T22 in patients with relapsed or refractory B-cell lymphoblastic leukemia. Currently, in the BALI-01 trial, we are enrolling patients at the highest dose so far, dose level three. We also added alimtuzumab to the preconditioning regimen in another blood cancer clinical trial Amelie 01 in acute myeloid leukemia. So in the clinic, we're moving into 2022, confident in our ability to execute our ambitious new program focused on product development and patient recruitment into our three ongoing multicenter dose escalation clinical trial, Valley 01, Amelie 01, and Melanie 01. We also plan to file a new IND for our new product candidate, UCAR T20 by 22, for patients with relapsed refractory, not Hodgkin's lymphoma. With this roadmap, our cash runway takes us into Q1 2024. Let's turn now to the progress we have made in manufacturing. In 2021, Selectus made a meaningfully powered becoming one of the few end-to-end cell and gene therapy companies. Back in 2018, Selectis made the decision to internalize the manufacturing of its therapeutics product candidates, providing the company with independence and a stronghold over its cell and gene therapy processes. We are thrilled to say that this goal has been achieved in 2021. Our two manufacturing sites in Raleigh, North Carolina, and Paris, France, are both now fully operational. We produce our own cell libraries, our own plasmid DNA, our own messenger RNA. We produce two types of vectors, AAVs and recombinant lentiviruses. We are set up to produce our own clinical-grade allogenic CAR-T cell product. In fact, In the second half of 2022, we plan to initiate dosing patients in the Bally 01 trial with clinical supplies of UCAR T22 manufactured in-house in Raleigh and UCAR T20 by 22 in non-Hodgkin-linked format trial. We're becoming self-sufficient in clinical supplies. This reduces our dependence on outside suppliers. These de-risk suppliers our path to the market. This removes bumps into the road Selectus is positioned to capitalize on clinical and commercial success of its product candidates. I already mentioned our plan to file an IND of a new product candidate, Trucar T20x22, in Mount Hodgkin's lymphoma. This is a very exciting product for at least two reasons. First, UCAR-T 20 by 22 will potentially be our first dual allogenic CAR-T to enter clinical trial. It is designed to hit two validated targets in B-cell malignancy. The product candidate is also the first product candidate Selectus has designed in-house, developed in-house, and manufactured in-house. In addition, the power of UCAR-T 20 by 22 is that it goes beyond overcrowded CD19 antigen on B cells. We believe it's a real allogenic CAR-T alternative to the crowded CD19 targeting protocol. I want to say a word now about our partner product pipeline, which remains important to selectives as a validation of our technology-based source of future revenues. In January this year, Allogene announced that the United States Food and Drug Administration has removed the clinical hold on all of the Allogene's clinical trials, which was announced on October the 7th, 2021. Allogene reported that after investigation, it was determined that the chromosomal abnormality detected in some UCAR cells of a single patient treated with allo501A was unrelated to talon gene editing in these cells. Allogene has announced that it has resumed clinical studies activities on talon gene edited product candidate allo715 and allo605 targeting BCMA for relapsed or refractory multiple myeloma. Allogene has resumed clinical studies activities on tail and gene-edited Allo316 targeting CD70 for advanced or metastatic clear cell renal cell carcinoma and began enrolling patients earlier this month. Allogene also announced that it and its partner, Servier, will resume their clinical activities on CD19, During the 2021 annual meeting of the American Society of Hematology in December 2021, Allogene, in collaboration with Servia, reported that the results from Alpha and Alpha-2 clinical data continue to support the promises Allo 501 and Allo 501a to be safe and durable alternatives to approved autologous CAR-T therapy in patients with relapse or refractory not Hodgkin's lymphoma. Allogene announced its intent to initiate a Phase II pivotal trial on Allo501A in relapsed or refractory large B-cell lymphoma is on track to commence mid-year 2022 pending FDA discussion. On the business development front, The utility of Selectus Taillin gene editing system continued to provide the company with expanded opportunity. In February 2021, we entered into strategic research and development collaboration with Cytovia Therapeutics to develop Taillin gene-edited products in new type of cells, IPSNK and CAR-TNK, for a series of different types of tumors. In November 2021, That collaboration with Cytovia expanded to include a new car target and development in China by Cytovia's joint venture entity, CytoLynx Therapeutics. Financial terms include either cash payment and or equity stake totaling $20 million, depending on the satisfaction of certain conditions by December the 31st, 2021. Delictus is in discussion with Cytovia regarding a potential extension of the deadline for such conditions to be met. The agreement also provides us up to $805 million of development, regulatory, and sales milestone, and a single-digit royalty payment on the net sales of all partner products commercialized by Cytovia. After Allogene and IOVENT's biotherapeutics, partnerships that we have signed. The collaboration with Cytovia in another cell therapy modality highlights TALEN as a gene editing technology of choice for cell therapy application. We have also expanded our general management team and board committee with top talent. Firstly, Selectus recently appointed Dr. Beng Wang, our new chief financial officers. I would like to take this moment to welcome Bing to our executive committee and to select this. Bing is a highly accomplished executive who brings extensive global finance experience in the biotechnology industry, including a background with global public companies in corporate finance. He comes to us from Refuge Biotechnologies, a cell therapy immunology biotechnology company leveraging synthetic biology and gene engineering, where he was co-founder and the chief executive officer. Bing's extensive experience in financing clinical stage biotech companies will be critical as we enter our next stage of development of our clinical trials. Welcome to Selectus team, Bing. Secondly, Selectus appointed Dr. Donald Bergstrom, as an observer on the company's board of director in November 2021. Dr. Bergstrom brings with him 15 years of experience in the biopharmaceutical and medical industry and serves as head of research and development at Relay Therapeutics, the clinical stage precision medicine company. They join a team executive clear plan to transform opportunities in cellular biology to the production of multiple focus clinical candidates. We already have a place of many of the elements that select these needs as if products prove themselves. We have invested in the future, and we have the resources to continue to push forward that future. Now, I would like to turn the call over to Dr. Carrie Brownstein, our Chief Medical Officer, to give an overview of our three sponsored clinical trials and pre-clinic product pipeline. Carrie, please go ahead.

Thank you, Andre. As Andre mentioned, 2021 has been a productive year for Selectus with our proprietary clinical programs making substantial progress. I would like to start with UCAR22, our CD22-directed, Talen gene-edited, allogeneic, off-the-shelf CAR T-cell product candidate currently being evaluated in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. We presented preliminary data at the 63rd Annual Meeting of the American Society of Hematology in December 2021. The presentation included data from patients who received UCAR22 after lymphodepletion with fludarabine, cyclophosphamide, and alamtuzumab. Alamtuzumab was added to the fludarabine and cyclophosphamide to deepen and sustain host lymphocyte suppression, thereby promoting UCAR22 expansion and persistence. As of the clinical cutoff date of October 1st, 2021, 12 patients had received lymphodepletion, 11 were administered UCAR22, of which six received UCAR22 and budarabine cyclophosphamide allamtuzumab. Three patients at the dose level 2 and three patients at dose level 2 intermediate. UCAR22, after FCA, lymphodepletion was well tolerated. No patients experienced protocol-defined dose-limiting toxicities immune effector cell-associated neurotoxicity syndrome, nor UCAR22-related severe treatment emergent adverse events. Three patients experienced mild to moderate cytokine release syndrome. One patient reported grade 2 GDHD of the skin in the setting of prior allogeneic transplant donor stem cell reactivation. Encouraging anti-leukemic activity was observed in two patients in the FCA cohort, both patients, one at dose level 2 and one at dose level 2 intermediate. achieved last reductions to less than 5%, 0.4% and 0% respectively, by day 28, accompanied by measurable UCAR22 expansion and changes in relevant inflammatory markers. Overall, UCAR22, after fludarabine, cyclophosphamide, and alimthuzumab lymphodepletion, demonstrated promising signs of antileukemic activity without unexpected or significant treatment-related toxicity. The addition of alimthuzumab to fludarabine and cyclophosphamide was well-tolerated, improved host lymphocyte suppression, and promoted UCART22 expansion, which was associated with anti-leukemic activity. These data are encouraging and support the further development of UCART22 for patients with relapsed or refractory BALL, who remain in dire need of additional treatment options, particularly those who have failed CD19 therapy. BALI01 is currently enrolling patients at dose level 3 with FCA lymphodepletion. Next, I'll move on to UCARTCS1, Our CS1-directed, TALEN gene-edited allogeneic CAR T-cell product candidate being evaluated in patients with relapse or refractory multiple myeloma. Early preliminary data from the first patients enrolled in the MELANIE-01 trial was presented at the American Society of Gene and Cell Therapy 24th Annual Meeting. These data validate CS1 as a target for allogeneic CAR T-cells in multiple myeloma, as UCART CS1 expansion and persistence was observed and correlated with changes in relevant serum cytokines and with anti-myeloma activity. Selectors are currently enrolling patients at dose level 1 with FC lymphodepletion. Lastly, I will speak to UCART 123. Our CD123-directed, TALEN gene-edited allogeneic CAR T-cell product candidate being evaluated in patients with relapsed or refractory acute myeloid leukemia. This trial addresses a patient population with severe unmet medical needs, where a successful CAR T-cell product candidate could be a major breakthrough. We are currently enrolling in our phase one dose escalation trial with FCA lymphodepletion. Enrollment at dose level two is ongoing. We look forward to sharing data from this program when it becomes available. Building on the technology platform of our current proprietary clinical programs, I'm excited to report that we plan to submit an IND for UCART 20 by 22, our first allogeneic dual CAR T-cell product candidate for patients with B-cell non-Hodgkin's lymphoma in the second half of 2022. CD20 and CD22 are both well-validated targets in B-cell malignancies and represent a therapeutic alternative to CD19-directed therapies. Targeting two antigens has important advantages. Firstly, it has the potential to increase efficacy by strengthening the contact of the CAR T cells with the tumor cells for more effective killing. Secondly, it increases the breadth of antigen targeting and therefore may increase the addressable patient population. And lastly, it provides potential to overcome antigen escape. Preclinical data supports moving UCAR 20 by 22 into the clinic, and I'm very excited to start the clinical trial for patients with relapsed refractory NHL. With that, I would like to hand the call over to Bing Wang, Selectus' Chief Financial Officer, for an overview of our financials. Bing, please go ahead.

Thank you, Keri, and good morning, everyone. I'm pleased to be here and thank everyone for the warm welcome. I will provide a brief overview of our financials. for the fourth quarter and the full year of 2021. I would like to highlight that the cash, cash equivalent, current financial assets, and restricted cash position, I'll set it like this, excluding CALEX, as of December 31, 2021, was $177 million compared to $244 million as of December 31, 2020. This difference mainly reflects $116 million of net cash flows used in operating, investing, and lease financing activities, which were partially offset by $45 million of equity proceeds raised from the sales under the Companies at the Market program established in April 2021 and $10 million proceeds from stock auction exercises. This cash position is expected to be sufficient to fund selected standalone operations into early 2024. The net loss attributable to shareholders of Selectus, excluding Calix, was $97 million in the full year of 2021 compared to a loss of $54 million in 2020. This $43 million increase in the net loss between 2021 and 2020 was primarily driven by a decrease in revenues and other income of $21 million and by an increase in operating expense of $40 million, partially offset by $18 million increase in net financial gain. The consolidated net loss attributable to shareholders of selectives, including colleagues, was $114 million or $2.55 per share in the full year of 2021 compared to a loss of $81 million or $1.91 per share in 2020. The consolidated adjusted net loss attributable to shareholders of Selectus excluding non-cash stock-based compensation expense was $102 million or $2.27 per share in the full year of 2021 compared to a loss of $67 million or $1.57 per share in 2020. In 2022, we are focused on spending our cash on developing our core programs. This allows us to extend our cash runway, excluding our subsidiary, Calix Inc., into early 2024.

Thank you, Bing. To close this call, I would like to reiterate how excited and proud we are of what Selectus has accomplished in 2021 and how the success propels us forward into 2022. More than 170 patients with relapse or refractory malignancies have been administered with Thalin-edited allogenic CAR T-cell product candidate built on Selectus technologies. In trial, sponsored by Selectus and its licensed partner with a promising safety profile, making the largest and the most robust disclosed clinical data set of any gene editing technology in the world. Our products in clinical development with the diversity of targets and indications as well as our allogenic UCAR platform positions us at the forefront of developing novel CAR T therapeutics that ushers in the next generation of cancer therapy. We continue to leverage our expertise in gene editing and clinical development to transform the lives of patients with cancer and rare genetic diseases. And we look forward to accelerating this momentum in 2022 and beyond. At Selectus, we strongly believe that our product candidates, our technologies, and our in-house manufacturing capabilities will lead us to a paradigm shift for patients with hard to treat cancers positioning us at the forefront of this promising medical and scientific field. With that, I would like to open the call for Q&As.

Thank you. We will now be conducting a question and answer session. If you would like to ask a question, please press star one on your telephone keypad. A confirmation tone will indicate your line is in the question queue. You may press star two if you would like to remove your question from the queue. And for participants using speaker equipment, it may be necessary to pick up your handset before pressing the star key. Our first question comes from Jaigo Nacimovic with Citibank. Please proceed.

Hi, guys. Thanks for taking the questions. On UCART 22, you're moving from the CRO product to the in-house product in the second half of the year. Could you just talk a little bit about the comparability between those two products, whether the FDA has signed off on the comparability, and presumably you will need an IND amendment to start the studies with the in-house version? Thanks.

Thank you, Yigal. This is Arthur. Andrea or David, you want to take this one?

Yes, I will. Thank you, Arthur. So we have already started the conversation with the agency as for how we will compare the P2 product, the one made in Raleigh, and the one that we've been using so far that was originally made at our CMO, Cell4Cure. So this is an ongoing conversation, and we're very confident we'll come to the definition of an appropriate means to do that swiftly.

Okay. Thank you. And then regarding the three phase one data sets that you're working on, at this point, are you able to give any more granularity on which of those we might see data for in 2022?

So we're definitely in the process as announced by Kerry, this is Arthur, to go through the various escalation data sets of these trials. We're not committing in particular to giving data on one specific program as we would want to get a meaningful data set, a meaningful clinical data set prior to sharing at a conference as we have done for UCAR22 at ASH last year. But what is safe to say is that we would definitely provide an update on at least one of these programs in the course of the year, if not more, depending on how data matures over the course of the year.

Okay. And last question. Obviously, the CD20x22 is a very, very interesting product. Can you talk at all about what other combo cars you might be contemplating beyond 2022? Sure.

No, actually, if someone wants to answer, this is Andre answering the question. So, listen, I think the strategy that Selectus is in today, I think it's going to go into a very interesting payoff. Probably people have been criticizing us on the fact that we're on an unvalidated target, even if we don't consider that these targets are unvalidated, such as 22, 123, CS1 or 20 by 22, but we have a very interesting positioning to develop and commercialize these products. They're not 19. They're not BCMA. This is a great positioning because we don't have to face, for example, a product such as BCMA products competition or 19 competition that is already commercial, and we have a different type of angle. So disclosing the next product we're going to develop is probably going to tip our competition, and this is not something I think would be wise on our side to disclose. I would like to have all your attention on 2022 and the data releases that is going to happen this year, as Arthur has said, because we believe that we're in a very good place concerning the development of these type of products so far. So, this is the thing that excites us, but disclosing what's going to happen in the future for dual targets that we believe is a very interesting approach for numbers of reasons. First, for potentially loss of targets, but also for enhancing the tumor-associated antigen density and the formation of synapse so to have a better killing of these products is something that would be crucial and potentially also increase the safety and the performance of these products in general got it thanks thanks andre our next question is from gina wang with barclays please proceed thank you for taking my questions i have two

The first one is regarding UCAR22 in-house manufacturing. Can you lay out the steps you need to complete in order to start dosing in-house product? My second question is regarding UCAR20 by 22. Just wondering any updated thoughts on initial doses based on the UCAR22 data?

Thank you so much, Gina. I think the first question may be for Steve, and the second question for Kerry.

Sure. This is Steve in Raleigh. In terms of the UCAR22 produced in-house here in Raleigh, we've already done so. The clinical materials have been produced, and analytical testing is ongoing, as well as preparations for an I&D amendment. So we're well on track to be using that material in the second half of the year.

Yes, sorry, and what's the second question again? Was the doses for 20 by 22?

That's correct. Any updated thoughts on initial doses?

Yeah, I'm not going to provide details on what the clinical trial design is going to look like when we start the trial, and it's in clinicaltrials.gov, you'll see, but we have lots of data from both internal and external data to help support where we start, and hopefully, given that it's a very well understood patient population and space in terms of CAR T cells with NHL. We have a lot of data to help support where our starting dose will be and potentially could help expedite the trial.

Thank you.

Our next question is from Kelly. She with Jefferies. Please proceed.

Hi, this is Dave on for Kelly Sheehy at Jefferies. My first question is on CAR T20 by 22. Just wondering, in your clinical trial design, are you thinking of enrolling both CD19 naive and relapsed patients?

Yeah, I can take that. We're thinking about enrolling a broad patient population to start because that always helps expedite clinical trials. And then based on what we see, we would make decisions on how we would expedite moving things forward in one or more specific subset.

Got it. And another one is on your solid tumor program. Do we expect any update during the course of this year?

So I can start.

This is Arthur. So basically what we've announced this year is a focus on... Actually, it's a good question.

As we announced it, given the hyper-focus of the company today on our three clinical trials and 20 by 22 IND and start of the development, there will be probably some... scientific conferences with the development of certain solid tumor products that are currently still in R&D and shelf, but the fact is that the strategy of the company is trying to push as hard as we can to get these products rapidly into expansion, pivotal trial before product that we're considering, and we'll see how The market evolves and the global situation evolves, all the pressure that we have, that external pressure and international situation and the market conditions for cell and gene therapy space before we can reconsider pushing these type of products into clinical trial. We're extremely excited by these candidate products that we have. Very, very excited, but we have to choose our fights, and we think that the most mature product that we have has all of them, huge potential, and I think it's in the interest of our shareholders and the company and, of course, the patients to put all our power into developing these heme-on product that we have.

Got it. Thank you.

Our next question is from Raju Prasad with William Blair. Please proceed.

Thanks for taking the question. I just had a quick question on the CD52 condition regimen. I know Allogene has to run a trial to show the impact of CD52 on engraftment. Is that something that you anticipate having to do? Have you had any discussions with the agency on on any conditioning trials you may have to run.

Thank you.

Sorry, I could start if anyone else wants to chime in. I think that, you know, Oh, okay. Sorry. It looks like the folks in Paris got disconnected. I can take this. So, you know, it's a little bit different. I think I'm not going to speculate here what we may or may not need to do for our BLA filings. But remember, the Allogene program is using a different anti-CD52 antibody, which is their own proprietary Allo 647, which is not a product that's ever had a marketing authorization anywhere. So it's a little bit of a different situation. But obviously, as we move forward with development, we'd have these discussions and see what we would need. But I think what we're doing right now is we've already looked at in all of our trials with and that we're using the alimtuzumab in with and without the antibody. And I think there's, you know, as we showed at ASH in December, there's strong data to support that we're not seeing expansion and persistent without it. And personally, I would find it unethical to continue dosing without it. But that would be something we'd have to discuss as we move forward with our development plans.

Great, thanks. And just curious, you know, as you get data from the 2022 product, you know, kind of in concert with the 22 product, how are you thinking about making decisions on federal trial and how to move forward? Are you planning right now to kind of move both products forward, or would there be kind of a decision point at some point maybe next year or the following year? Thanks.

Yeah, I think that's a really interesting question because obviously given what we're talking about with 20 by 22, 22, it could potentially also be work in not just NHL but in, for example, ALL. But I think as it is right now, given we have UCAR 22 and we're moving it forward in ALL, we would likely continue to move that forward for this niche patient population that's as high in medical need as a separate product. But again, those are conversations and discussions we would have as we move forward with both programs.

Great, thank you.

Our next question is from Jack Allen with Baird. Please proceed.

Great, thank you so much for taking the questions. I have two quick ones here. I guess first on the clinical side of things, I was hoping that you could provide a bit more color around your progress with the CS1 candidate. It sounds like you've moved into dose level one, but I'm curious as to how many patients maybe you've dosed in dose level one, and I guess maybe any color you can provide around the totality of that cohort, and your plans to move on to dose level two. And then on the financial side, I was hoping you could just lay out a little bit around the timing of potential milestone payments that we could see in the coming year. I think ALO 615 just moved into the clinic, and then they do have that ambition to initiate a pivotal study in the middle of next year. So I'd love to hear any color on those milestone payments, and then any comments on milestone payments from the other collaborators as well at Iovance and Cytovia. Thank you so much for taking the questions.

It's Carrie here. I could start with the questions about the CS1 program. So we are moving ahead with the UCARD CS1 program in myeloma, and we have disclosed that we're in dose level one. I'm not going to speak to how many patients and when we're planning on getting into the next sets of data. I think suffice it to say we have extremely excited investigators. They're still high on medical needs. As you know, we did come off a clinical hold and we had previously disclosed that there's some long waiting periods in between patients and things that were required by FDA. And so we're moving through it as quickly and expeditiously and safely as we can and hope to provide a data set for external disclosure when we have a reasonable data set worth sharing and probably at a pivot point for when we would potentially be starting to move more quickly, like in an expansion of some sort. And I will now pass it on to Arthur and Bing for the financial questions.

Yeah, so Jack, for the milestone payments, so basically, first of all, on the survey Allogene collaboration on CD19, we're definitely eligible for a milestone payment upon the initiation of the pivotal trial, which Allogene has guided for mid this year. And we haven't disclosed the size of the milestone payment, but there will definitely be one. To the other partnerships, again, we haven't disclosed either the terms of the Iovance collaboration. But for Cytovia, this is going to be, with the recent amendment, up to 805 million of milestones, and we're also getting an equity stake of 20 million into Cytovia stock. And so we expect that as Cytovia progresses these products in the coming months, we will start seeing some economics.

Great. Thank you so much.

Our next question is from Hartaj Singh with Oppo Dimer and Company. Please proceed.

Great. Thank you for the two questions, and thanks for all the updates. Just a quick question on the manufacturing, just going back to that. I think you had highlighted previously you might have to, you know, do an IND for 22 from the Raleigh facility. Will that then set you sort of, you know, as you go through clinical trials and hopefully get ready to file a BLA, will you be set sort of on the clinical manufacturing side of a potential BLA at that point, you know, after doing this IND? And then secondly, in that same vein, will you have to, assuming you convert CS1 and 123 and get materials from the Raleigh Manufacturing Facility, might you have to do future INDs there if you were to convert using the Raleigh Manufacturing Facility? And I just got a quick follow-up.

Steve, you want to take this one?

Sure. In terms of UCAR 22 being produced from Raleigh, that's going to be an amendment to the existing IND because it's considered a major change in the manufacturing when you move from one location, namely a CDMO to internal manufacturing, so there will be an IND amendment. And BLA is a future state, of course, depending upon where we are in the clinical trials and how well they progress. But yes, we are very hopeful this would progress us at some point to a BLA. But for 22 at the moment, the focus is on submitting an I&D amendment to enroll Raleigh as the manufacturing site.

And then just on CS1 and 123, would you ever consider moving those, producing them in the Raleigh facility?

Yes, we're planning to do this, of course.

And then just last question. They're next in line, both of them. Okay, great. And your dual targeting cars, do you see those in the future with 2022 and then others kind of, you know, sort of being more competitive against the current CAR-T, so that would be sort of a second generation kind of approach with CAR-T with the dual CAR-Ts, or do you see it as sort of moving a little bit more, you know, further along and, you know, kind of going up against the bispecifics, which some, you know, people believe might be a bridge to CAR-T? I mean, I know all this has to play up, but just any thoughts there? Thank you.

Hi, Hartaj, from a development perspective, I'm happy to take it. I mean, I think that, again, a lot of where we're going to end up positioning these programs and these products in the market space is going to be dependent on the data. I think what's extremely important to recognize when we're talking about allogeneic CAR T cells versus the current autologous space is that, I don't know if competition is the right word, But again, given their easy accessibility, the fact that they're in the clinic already, they're in the freezer, you don't need to wait for manufacturing between patients, it changes the entire paradigm of treatment for CAR-T versus the autologous phase. So while the autologous phase has been great and has been more of kind of a second line or after, as you said, the bispecifics, I think provided these data are strong enough, I think that you know, we don't need the specialized centers on and, and, and, and, and even this data isn't as strong, let's say as, which I think it will be, but let's say it's not as strong as autologous 19 or something. I don't think that's going to matter. I think that the fact that physicians can get their hands on it and give it to patients quickly is going to be huge and really change how the treatment paradigm is set up from standard of care purposes, so to speak, from all of the key players who are treating patients. So I think, again, it'll depend on the data. If the data obviously aren't as strong, then maybe it would come after. But I think our positioning is going to be as strong as possible based on the data. And we have to also remember when we're looking at data and comparing that It's actually more helpful to almost compare against bispecifics versus the CAR-Ts, because remember, when you look at the data in the labels for all of these autologous therapies that have been approved, their denominators are based only on patients who've received cells, and they throw out all of the patients who either they had a manufacturing failure or it was an out-of-spect product or that the patient progressed prior to getting treated. And so if you actually redo a lot of those numbers, the response rates and PFS and everything is just much, much, much lower than what's in the label. And so we need to be extremely careful when we're comparing. And that's part of the reason those CAR T-cell therapies look so much better than bispecifics as well. So, yeah, so I think we could be clearly in any position, which is what makes this so exciting.

Thank you, Carrie. Thanks for all the updates and the wood that you're chopping on the manufactured side.

As a reminder, it is Star 1 on your telephone keypad if you would like to ask a question. Our next question is from David Da with SMBC. Please proceed.

Hi. Thanks for taking my questions and congrats on the progress. I have a question on UCAR T123. We know that UCAR T123 is an updated product with a new construct and a new manufacturing process. Could you just share some additional color on the changes on the construct and also the manufacturing process? I also have a follow-up after that.

So maybe I can start.

David's taking it. Arthur, David is taking it.

Go ahead, Arthur.

Hi, this is David. So we did evolve UCAP-123 to incorporate the CD52 knockout, and that allows us to explore lymphodepletion, including alantizumab, which is what we have disclosed. And that was a major change in terms of molecular constructs. We also evolved the process itself, taking into account all the teachings that we had gained from working with UCAR 22 and UCAR CS1. And, well, in a nutshell, we are basically producing a much better product, and we think it's much more robust and reproducible so far. So I won't get into the details of the process evolution, but those are the elements that we can share at this stage.

Got it. That's really helpful. Just as a follow-up, and then could you provide some quick update on the in vivo programs?

Maybe share some additional color on the timing of potential IMD filings for those in vivo programs.

I'm not sure what you're saying about the in vivo programs, because we definitely have plans in this space. But I'm going to reiterate the fact that in the current situation and the roadmap that we have currently, we're putting 100% of our focus on the four assets. We have UCAR T22, UCAR T123, UCAR TCS1, and UCAR T20x22 that we believe have a huge traction, are exciting and mature product. are extremely excited and interested also in in vivo approaches using Tailin or Tailin base editors also potentially for different type of applications because we have a fantastic technology concern on base editing because it's a split activity between the two arms of Tailin that have a very high accuracy and we're excited about that but today in the current situation and the current market conditions, et cetera, all the focus of the company is on these four trials. When the situation will improve, resume, et cetera, of course, we'll put the pedal on the metal on these in vivo programs, and today they're essentially developed at the R&D stage that is perfecting and polishing and finessing all of these programs.

God, that's really helpful. Thank you for the color.

Our final question is from Sylvain Sokrian with JMP Securities. Please proceed.

Good morning and thank you for taking my questions and welcome Bing to the team. I just had two quick questions. I don't know if you can comment on this, but on UCART 123, I believe the last comment was that you are looking to enroll in DOS Level 2. Could you just give us some color on where you're at in terms of dosing on that program?

Then I have a quick follow-up.

Sure. It's Carrie. I can speak to that. I mean, we're not, again, we are not disclosing exactly where we are in terms of number of patients and which dose levels. Other than that, you know, with the beginning of this year, we've been starting at dose level two. We've been working on filling out that cohort and we'll continue to move forward as the time goes on and as we, when we have a reasonable data set to share and we're ready for the next stage, we'll be sharing data.

Great, thank you. And on UCAR 22, I think that there was going to be an additional data cut this year. And is there any chance that this could have some of the new material from the Rayleigh facility in the data, or do you think that's premature at this point?

Yeah, so we have not, as Arthur spoke to earlier in the call, we actually haven't disclosed per se exactly which data set we would be sharing this year. We will share data on at least one of the programs, but we did not specifically speak to it being 22 or not. As I've said with all of the programs, I think it's really important that we share and disclose data sets when there's a meaningful data set that's giving us the support to move to the next stage and not just be giving dribs and drabs over time because we fill the cohort. So that's not something that I want to do. So we will be figuring out which will make the most sense based on where we are and what the meaningfulness is of the set at the time.

Great. Thank you very much.

We have reached the end of our question and answer session. I would like to turn the call back over to management for closing comments.

Well, thank you very much. And thank you for all the attendees for our earnings call this year. We're extremely excited. We're excited by 2021, which was a very productive year for Selectus because we've been pushing on our three clinical trials. And also one thing that is transformative for the company, it's a different company in 22. We're now producing our own IMP from A to Z. And this is convertible to producing Pivotal product and convertible commercial in the future. And this is a huge change for Selectus. You know the history of the company, how much difficulties we had in the past with certain products that were produced at CMOs. But today, it's a different type of selectors that you have. We're entering into a very interesting phase into all our clinical trials. And 2022, I cannot be more excited about what's going on in the company. And for this year, I hope that we will be sharing information very exciting and interesting data in the coming future. And passing this step, you know, select this is unstoppable. With that, I would like you to thank you all and wish you a great day.

Thank you. This does conclude today's conference.

You may disconnect your lines at this time and thank you for your participation.