Cellectis S.A. (NASDAQ:CLLS) Q3 2023 Earnings Call Transcript

Cellectis S.A. (NASDAQ:CLLS) Q3 2023 Earnings Call Transcript November 7, 2023

Operator: Good morning, everyone, and welcome to the Cellectis Third Quarter 2023 Earnings Calls. [Operator Instructions]. I’d now like to introduce the first speaker Arthur Stril, Chief Business Officer. You may begin.

Arthur Stril: Good morning, and welcome, everyone, to Cellectis third quarter 2023 corporate update and financial results conference call. Joining me on the call today with prepared remarks are Dr.Andre Choulika , our Chief Executive Officer; Dr. Bing Wang, our Chief Financial Officer; and Dr.Mark Frattini our Chief Medical Officer. Yesterday evening, Cellectis issued a press release reporting a corporate and business update for the third quarter 2023 and its financial results for the nine- month period ended September 30, 2023. As a reminder, we will make statements regarding Celectis financial outlook, including the sufficiency of cash from operations in addition to its manufacturing, regulatory and product development status and plan and product development of its license partners.

A biochemist observing cell cultures under a microscope, representing the groundbreaking research of the biotechnology company.

These forward statements, which are based on management’s current expectations, and assumption and on information currently available to management, including information provided or otherwise publicly reported by our license 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 20F filed with the Securities and Exchange Commission SEC and the financial report including the management report for the ended on December 31, 2022, and subsequent filing Cellectis makes with the SEC from time to time. I would now like to turn the call over to Andre.

Andre Choulika: Thank you, Arthur, and good morning, and thank you, everyone, for joining us today. Last week, we announced a strategic collaboration and investment agreement with AstraZeneca. We are very proud to initiate this partnership with one of the top leaders in the pharma space, pairing our strong commitment and ambition cell and gene therapy, AstraZeneca, because we have been very much impressed by the long term strategy in this space. Backed by a strong commitment and development already made paving the way powered by top leadership in this arena. We strongly believe that together since AstraZeneca, that next generation of genomic medicine will be developed under our collaboration will revolutionize medicine across a number of therapeutic areas in the years to come.

Part of our agreement, AstraZeneca has agreed to make an initial payment of $105 million to select composed of $80 million equity investment in exchange of $16 million ordinary shares at $5 per share. $25 million upfront payment under the research collaboration agreement. Cellectis is also eligible to receive an additional $140 million equity investment in exchange for $28 million convertible preferred shares at $5 per share, subject to Cellectis shareholders’ approval and several other condition of closing. Now some words about the research collaboration. It’s a very ambitious proposal to develop novel cell and gene therapies across oncology, immunology and rare diseases. We have exclusively reserved 25 genetic targets for AstraZeneca from which up to 10 novel candidate product could be explored for development.

The beauty of this agreement is that our clinical stage assets UCART22, UCART123, and UCART20x22 remain under our own ownership and control. And you should expect regular updates in the advancement of this program for us. Within the collaboration, we will leverage our cutting edge innovation and best-in-class manufacturing capability. Develop new disruptive product candidate and AstraZeneca will have an option for a worldwide exclusive license on 10 of the candidate products exercise before IND filings Our research costs under the collaboration will be funded by AstraZeneca and we’re eligible to receive an IND option key and development, regulatory and sales- related milestone payments ranging from $70 million and up to $220 million, per each of the 10 candidate products, plus tiered royalties.

We’re very excited to get to work with AstraZeneca to leverage our capabilities and build the next-generation of genomic medicines to address areas of high unmet patient need together. During this past third quarter Cellectis innovation key excelled in releasing disruptive preclinical data on gene editing of stem cell gene therapy for an immunological disease. Later, on our proprietary power base editing technology and multi armored allogenic CAR-T cell targeting MUC1 for triple negative breast cancer, demonstrating one more time to spend and the power of our gene-editing platform and to develop next-generation cell and gene therapies for patients with unmet medical need. In addition, our clinical team will be presenting update of results for the Phase 1, BALLI-01 trial of UCART22 and preliminary results of the NATHALI-01 trial evaluating UCART20x22 in relapsed or refractory B-Cell Non-Hodgkin’s Lymphoma at the American Association, the Hematology Annual Meeting.

But I will let Mark in a couple of minutes talk about these abstracts. However one thing I would like to highlight in what Mark is going to present after, is the importance of the know-how in manufacturing. In cell therapeutics nothing is more important but the fitness of the cell that will be injected to patients. The quality, the reproducibility of manufacturing is one of the game changer in the success of these therapies, which is why we have fully internalized manufacturing. Now this work is totally completed and this is why it’s going to make a difference. So like this will continue to control strictly cash burn within these difficult market environment. And we will continue to focus our efforts and expenses on advancing our core clinical trial BALLI-01 evaluating UCART22.

NATHALI-01 evaluating UCART20x22, and AMELI-01 evaluating UCART123 With that, I would like to turn the call over to Dr.Mark Frattini our Chief Medical Officer, who will give an overview of these clinical trials. Mark, please go ahead.

Mark Frattini: Thank you, Andre, we will be presenting updated results of the Phase 1, BALLI-01 trial of UCART22 in relapsed or refractory acute leukemia. And preliminary results for the NATHALI-01 trial evaluating UCART20x22 in relapsed or refractory B-Cell Non-Hodgkin’s Lymphoma at the American Association of Hematology 65th annual meeting in December. As Andre just mention regarding our clinical trial, BALLI-01 evaluating UCART22 and relapsed or refractory B-cell ALL. We have a comparison between a product manufactured at a CDMO, this is process 1. And the same product manufactured in house here at Cellectis, this is process 2. In vitro comparability studies suggested that UCART22, process 2 manufactured by Cellectis biologics is is more potent than UCART22 process 1 manufactured by an outside CDMO.

In June at the EHA Congress, we showed you data of patients enrolled at dose level three with 5 million cells per kilogram with UCART22 using process 1. Since then and as of July 1, 2023, three patients were enrolled into the first UCART22, P2 cohort at dose level 2 at 1 million cells per kilogram. UCART22, P2 was administered after fludarabine, cyclophosphamide, and alemtuzumab (FCA) lymphodepletion and was well tolerated. No dose-limiting toxicities or immune effector cell associated neurotoxicity was observed. And CRS observed was Grade 1 or 2. There was a higher preliminary response rate, 67% at dose level 2 with 1 million cells per kilogram with with UCART22 P2 compared to 50% response rate with a dose 5 times higher at dose level 3 of UCART22, P1 that was manufactured by outside CDMO.

UCART22 expansion was observed in the responding patients and correlated with increases in serum cytokines and inflammatory markers. The study continues to enroll patients at dose level 2i 2.5 million cells per kilograms with UCART22, P2. We will also be presenting preliminary results of NATHALI-01 study, evaluating UCART20x22, the first in a dual CAR T-cell product in patients with relapse refractory B-cell non-Hodgkin lymphoma at the ASH meeting in December. In this case UCART20x22 has been fully manufactured in-house by selective, at our raleigh manufacturing plants. As of July 1, 2023, three patients were enrolled and treated at dose level 1. Here, we are using a flat dose of 50 million cells for patients over 50 kilograms. Cytokine release syndrome,Grade 1 or 2 occurred in all patients, and all CRS resolved with treatment.

No immune effector cell associated neurotoxicity or graft versus host disease was observed. There were no UCART20x22 dose limiting toxicities and there was 1 CLLS52 or alemtuzumab. All patients responded at day 28, with 1 partial metabolic response and 2 complete metabolic responses in patients who had failed prior autologous CD19 CAR T-cell therapies. UCART20x22 expansion correlated with increases in serum cytokine and inflammatory marker levels as well as with Cytokine release syndrome. These initial data with the 100% responses at the initial dose of 50 million cells per per patient support the continued study of UCART20x22 in relapsed refractory B-cell NHL and the study continues to enroll. Lastly, our AMELI-01 study evaluating UCART123 in patients with relapsed or refractory acute myeloid leukemia continues to progress and enroll patients in the FCA 2 dose regimen are.

With that, I would like to hand the call over to Dr. Bing Wang, Celectis’s Chief Financial Officer for an overview of our financials for the third quarter of 2023. Bing, please go ahead.

Bing Wang: Thank you, Mark. I would like to highlight that in our financials, the cash, cash equivalents, restricted cash position of Cellectis, excluding Caelyx, as of September 30, 2023, was $72 million compared to $95 million as of December 31, 2022. This $23 million difference mainly reflects from the $79 million of cash-out, which includes $23 million for R&D, $12 million for SG&A $32 million for staff cost, $8 million for rent and taxes, $4 million of reimbursement of the PGE loan, and $2 million unfavorable impact on foreign exchange partially offset by a $23 million net cash inflow from the capital raise closed in February. And a $21 million net cash inflow from the European Investment Bank loan from a $6 million of net cash received from the research tax credit refinancing, a $1 million cash outflow related to the grant, a refundable advances from BPI, $3 millions of financial investments’ capital gain and interests, a $1 million reimbursement of social charges paid on stock options, and a $2 million net cash inflow from licenses and other cash receipts.

With cash and cash equivalents of $67.4 million as of September 30, 2023, and a $105 million from the AstraZeneca agreement. The company believes that we have sufficient resources to continue operating for at least 12 months following the consolidated financial statements’ publication. Additionally, the MOU contemplates that AstraZeneca will make a potential further equity investment in Cellectis of $140 million by subscribing for two newly created classes of convertible preferred shares of Cellectis. If confirmed the closing of the additional investment will remain subject to Cellectis shareholder approval with a two-thirds majority of the votes cast by voting shareholders and a clearance of such investments from the French Ministry of Economy according to the foreign direct investment, French regulations and other customary closing conditions.

So the current with these additional $140 million in our anticipated borrowing of EUR15 million under the Tranche B of the EUR40 million finance contract with a European Investment Bank, the company believes that we would extend this cash runway into 2026. The closing of the proposed Calyxt Merger was finalized on May 31, 2023. Consequently, Calyxt was de-consolidated and presented as discontinued operation in the financial statements only until May 31, 2023. The net loss attributable to shareholders of Cellectis was $58 million were $1.7 per share. For the nine months of 2023, of which $53.2 million was attributed to Cellectis continuing operation compared to $79 million or $1.74 per share. For the nine months ended September 30, 2022, of which $73 million was attributed to Cellectis continuing operations.

The $21 million decrease in net loss between the first nine months of 2023 and 2022 was primarily driven by a $14 million decrease from R & D expenses and a $4 million decrease of SG&A expenses, and also increased $4 million or the financial gain due to the de-consolidation of Caelyx compensated in part, but the decrease of fair value Cytovia’s note receivable and decrease of $2.2 million loss from discontinued operations attributable to the shareholders of Cellectis. These downward impacts on the net loss were partially offset by a decrease of $1.2 million of revenues and other income. The adjusted net loss attributable to shareholders of Cellectis, which excludes non-cash stock based compensation expenses, was $57 million, were $1.05 per share in the first nine month period of 2023 compared to a loss of $72 million or $1.58 per share in the first nine months of 2022.

We are laser focused on spending our cash on developing our clinical candidates and operating our state-of-the-art manufacturing facility in Paris and Raleigh. In addition, our focus on maintaining an efficient corporate infrastructure should also enable more limited growth in G&A expense. At this point, I’d like to hand it back to Andre for closing remarks.

Andre Choulika: Thank you, Bing. Post out this call, I would like to reiterate how excited we are about a strategic collaboration with AstraZeneca and how much confident we are about the continued progress of our three ongoing clinical trials in as well as our continued development of our pre-clinical program. At Cellectis, we strongly believe that our product candidates, our technologies and our in-house manufacturing capabilities will lead us and our partners to a paradigm shift for patient with hard to treat cancer, positioning us at the forefront of this promising medical and scientific field. With that I would like to open the call for question and answers.

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Q&A Session

Operator: [Operator Instructions]. Our first question is from Kelly Shi with Jefferies.

Dev Prasad: Hi, this is Dev prasad on for Kelly Shi. Thank you for taking our question and congratulations on the updates. I have one question on UCART20x22 you showed a great result, DL 1. So my question is, do you plan to increase the enrollment sites and and how many dose level do you anticipate to study before finalizing the RP2D?

Arthur Stril: Dev thank you so much for this first question which will go to Mark

Mark Frattini: Hi thanks for the question. And yes, we will — we anticipate doing an escalation obviously, and the data from the subsequent escalation will obviously determine, where we stop and calling RP2D. So right now, it’s right now it’s to be determined with the clinical data.

Dev Prasad: Thank you.

Operator: Our next question is from the line of Gena Wang with Barclays.

Unidentified Analyst : This is [indiscernible]. So we have two questions on your clinical programs, one is that you previously guided UCART123 I believe it by end of 2023, May I ask like the timeline for now would it be a late breaker for ASH? And another question is the next step for UCART22 you mentioned about potential to advance to pivotal study without further dose escalation is that still the plan? Thank you.

Arthur Stril: Great. Thank you very much for both questions. That will be for Mark.

Mark Frattini: So for UCART123, we began at ASH last year, we announced how we were or remodeling the treatment program to include the two dose regimen. And we are continuing on in that two dose regimen in dose escalation. So we anticipate that we will really be clinical data at some point next year. And in terms of UCART22 study, I guess we in fact, we’ve pointed out in the abstract for ASH that we have dose escalated to 2.5 million cells per kilo with the products. So we will see where that data bears this out and as we move ahead.

Operator: Gena, do you have any questions?

Unidentified Analyst : Thank you so much for taking our questions. Maybe one last follow up question on the AstraZeneca deal. Is there a time line that they have to select certain lead targets? And would you only give it as hold like early hold if they turn it down?

Arthur Stril: Sorry, I’m not sure I understood the –. This is Edison Arthur. I’m not sure I understood the end of the question. But definitely so as part of the agreement Astrazeneca will have to choose up to 10 candidate products from a pool of 25. And then once the 10 products are selected, the remaining non-selective targets will come back to us.

Unidentified Analyst : Okay, got it. Thank you.

Operator: Our next question is from the line of Yigal Nochomovitz with Citi.

Unidentified Analyst : I think this is Carly on for you guys. Thanks for taking our questions. I had two from us. First on your UCART22 and UCART20x22. Just wanted to clarify if we should expect data on additional patients at ASH to relative to the abstract? Or will the ASH data before focused on longer-term follow-up from the patients or just the patient included in the abstract? And then the second question is on that potential additional $140 million equity investment from AstraZeneca. Just wondering if you can clarify if there is a specific trigger for that from AstraZeneca side and what’s the potential timing might be? Thank you.

Arthur Stril: Great. So I’ll hand it over to Mark for the first business question, and I’ll take the question on the AstraZeneca deal. Thank you. Yes, for in terms of the two abstracts that we will be presenting, we will be presenting some follow up on the patient’s described in the abstract.

Mark Frattini: Yes, on the $40 million. So this is subject to a few closing conditions, including approval of our shareholder that are to certain majority of the votes cast and clearance for according to a foreign direct investment french regulation, and a couple of unless other customary closing conditions. We’re working expeditiously to finalize these.

Unidentified Analyst : Okay, got it. Thank you.

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

Hartaj Singh: Great. Thank you, and thanks for the update. And I got two questions. One is you’re starting to show some complete responses in BALLI-01 and NATHALI-01. I was wondering what would you view as sort of like a durability from a durability perspective? How many months of follow-up would you like to see? When you do when you could classify these as being very durable responses, especially on the CR side? And my second question is yes, specific to UCART123. Have you switched over to the commercial product there also? And if not, what’s the timing on that? Thank you.+

Arthur Stril: Thanks for those questions. And Mark, over to you.

Mark Frattini: Thanks, Hartaj, for the questions. So I’ll start with the UCART123 first and further UCART123 . We are still currently using the CDMO made product for UCART123 and that’s where we are with that right now. In terms of your first question, yes, we are definitely seeing CRs, as you pointed out in the two studies. I think importantly, the stress for the UCART20x22 studies at the initial dose level, we did see two metabolic CRs is were in patients that failed prior CD19 CAR -T in addition to several other therapies. So I think in the setting of 19 failures on having two CRs, is great is great news at this dose level. I think in terms of your question for durability, I think that remains to be seen given the the line of therapy that we’re in and giving the extensive therapies that these patients have been relapse and refractory from I think at some point looking into three to six month range is not unreasonable.

It’s interesting to look for good duration of response in these patients.

Hartaj Singh: Great. Thank you, Mark. Thanks for all the questions.

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

Jack Allen: Thanks for taking the questions and congratulations on the team on the progress. My question is also as it relates to the ASH abstracts really impressive results UCART20x22 program. As a first dose level here, as I was wondering, and I see if the team had any comments about the need to escalate dose are you satisfied with the but the early results you are seeing here? Love to hear about that.

Arthur Stril: Yeah Jack, thanks for the question. And yes, I’m as you point out, three out of three responders at the initial dose level. And as also you can see the safety quite good at this dose level as well. And I think given given both of those facts, we will be we will in fact, be escalating those study just, you know, to see where we can get at it, the next higher dose level. So stay tuned for that.

Jack Allen: And then just one brief follow-up on as it relates to longer follow-up on these patients on, can you provide some context around when the data was taken for ASH and what you expect to present at the conference? And then just to clarify on, we should be primarily focused on additional data from the first three patients rather than a second dose cohort as well.

Arthur Stril: Yes. So we’ll we’ll be focusing on the first three patients for the poster presentation.

Jack Allen: Any thoughts on additional kind of follow up there or what kind of thought we could expect from those three patients at the conference?

Arthur Stril: So well, we’ll give some further follow up that we have on them. So please come by and visit us at the poster.

Jack Allen: Great. Thanks so much.

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

Whitney Watson: Hi, this is Whitney on for Salveen. Thanks, much for taking your question. Could you just remind us of the strategy for UCART20x22 in terms of the targeted patient population given positive data at ASH?

Arthur Stril: Thank you very much for the question that would be for Mark.

Mark Frattini: Hi. Yes, thank you for the question. So you know, we are — is in third-line or greater that we’re using this, and this is prior CD19 failures are also included in this study. So that’s where we’re continuing.

Operator: Our next question is from the line of Silvan Tuerkcan with JMP Securities

Silvan Tuerkcan: Good morning and congrats and thanks for taking my question. My first question is now that you have human data with UCART22 with product 1 and product 2. Do we do we know what why products to so much more potent? You have any metrics reflects a two times or more [Technical Difficulty]. And then a second question is, are there any more near term milestones associated with our schemes, anti CD-70, the or programmes? You could be getting. Thank you so much.

Arthur Stril: Great. Thank you very much for both questions. I’ll hand it over to Andre for the first one.

Andre Choulika: Yes, hi, nice events that and thank you very much for the nice question because I think that the manufacturing that tottaly makes a huge difference. And as Mark described this presentation, there is process one the process that was used at the CMO initially, and the one we’ve implemented after internally this process two. So there’s few that have changed. We know exactly why. One day someone asked me a question in about how we do it, how we can do cells that have so much potency. And let me tell I’m going to share this quick review here online. So I see all the faces around me. Andre don’t do this I’m going to do it. Well, we’ve done close to 10,000 batches internally in the process development. We’ve done and crushed and crushed and crushed cells and tweaked every parameter and there are hundreds of parameter.

This is called experience. We are the ones that have invented the concept of allogenic CAR-T. I can tell you that like the post that didn’t came out like this slide from from the ground, it took a long time before we go to the point where we are. And today, I think that will probably, the best on the planet to do allogenic CAR-T, as Mark said, come at our poster session at at ASH, watch the expansion of the cells, even a super low doses. You will see what it means that such type of experience and experience cannot be invented in a day. It can be transmitted, but we don’t know transmit the 10 years of crushing batch after batch of small, midsize to large size, batch in GMP conditions, et cetera. Up to the time we have tweaked all parameter to perfection.

That’s the answer. And for the Allogene?

Arthur Stril: Thanks, André. And on the Allogene questions. So we definitely have a significant vested interest Allogene success, just remembering upto to $410 million in development and sales milestones for CD- 19 through our agreement with the survey and up to $2.8 billion in development and sales milestones. We haven’t disclosed the granularity of the milestones, but we’ll invest in if you communicate that in when Allogene hit those milestones and we get at the amounts in our back.

Silvan Tuerkcan: Great.Thanks for revealing the secret sauce.

Operator: Our next question is from the line of Yanan Zhu with Wells Fargo

Unidentified Analyst : This is Kwan Kim for Yunnan. So my question is on the new CAR-T 22. So can you give us more detail about the grade by AE now was revealed in the abstract and how that may affect the further study contact? Thank you.

Arthur Stril: Thank you for the question, and this will be for Mark.+

Mark Frattini: So as you know, as we rebuild in the abstract, this grade five events happened after long after several couple of weeks after the day 28 assessment in this patient who had a morphologic leukemia-free state. So as bacterial infection that the investigator related, related to everything, which is why it’s there. So it’s really not affecting anything as we move move ahead.

Unidentified Analyst : Got it. Is there a way to quantify how much of that was contributed by the UCART22 itself or the Thank you.

Mark Frattini: Yes. So there’s some, , has will show on the poster. There’s a level of expansion that was seen with the cells by flow . At the time point of this event happen, we don’t believe there were any UCART22 cells record remaining. So we think that the likelihood it was less related to UCART22. This was a patient who was again, as outlined in the abstract, was super heavily pretreated, they failed alo transplant, they failed prior octalagus CAR-T. They failed multi-agent chemo in and they also failed blinatumomab or inotuzumab and venetoclax. So the cumulative dose in the prior chemo that they made and going into this study very high both cellular explained some of the issues that are developed.

Unidentified Analyst : That’s super helpful. Thank you so much.

Operator: Thank you. As there are no further questions, I would now hand the conference over to Andre Choulika, CEO for closing comments.

Andre Choulika: Well, first of all, I would like to thank the team for helping in doing the call here. It’s been a pleasure to prepare this together, and I would like very warmly thank all the analysts that have been following the covenants supporting in watching what we’re doing is very valuable. And I would like to make a special word of so to our long-term shareholders that has been continuously supporting the company over the past years. And I hope that to the company is going to have like a very strong end of ’23 and ’24 and ’25 and ’26. So we’ll come up very soon for an update on the progress. Thank you very much.

Operator: Thank you. The conference of Cellectis has now concluded. Thank you for your participation. You may now disconnect your lines.