Q4 2021 Cellectis SA Earnings Call
Good morning, everyone and welcome to selective fourth quarter 2021 and year end conference call. At this time all participants are in a listen.
Only mode.
We will conduct a question and answer session and 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 Schram Chief Business Officer, you May begin good morning, and welcome everyone to select this fourth quarter 2021.
And corporate updates and financial results conference call.
Joining me on the call today with prepared remarks are doctor on actually got our Chief Executive Officer, Dr. Carrie Brownstein, our Chief Medical Officer, and our New Chief Financial Officer, Dr being Lane.
Yesterday evening, the electric 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 selected Dot com.
As a reminder, we will make statements regarding selected financial outlook. In addition to its manufacturing regulatory and product development plans. These.
These forward looking statements, which are based on management's current expectations and assumptions and on <unk>.
Formation 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 20-F filed with the SEC and our financial reports, including the management report for the year ending on December 31, 2021, and subsequent filings select this makes with the Securities Exchange Commission from time to time.
I would now like to turn the call over to Andre.
Thank you Arthur and good morning, and thank you everyone for joining us today.
<unk> 21 was a productive year for selective.
We are proud of the progress we've made as it relates to our corporate milestones.
As we evolve to become a full end to end cell and gene therapy biopharmaceutical company.
We have progressed on the clinical front with escalating doses of our product candidates.
We completed our manufacturing plants and that gives us control of product quality and supply line.
We continue to innovate we have been working on our first dual targeted you cart product your car T 20 by 'twenty, two and plan to bring it to the clinic in 2000.
<unk> thousand and 22.
We have been able to leverage our valuable talent platform to provide selected.
But there's opportunities in the future cell therapy field outside of our core allogeneic car T area.
Regulatory issues that had posted some of our partnered programs have been resolved.
It is clear that none of these issues argue to select it.
Palin technology.
And our financial position is secure.
Based on our current plans our cash takes us not just through 'twenty, two 'twenty three but too early 2024.
First I will touch on some of the clinical progress Carrie Brownstein, our Chief Medical Officer will give additional details later.
We have trials.
And three different forms of Hematological cancers.
Annual meeting of the American Society of Hematology held in December 2021, released encouraging preliminary efficacy and safety data from our Bali zero, one trial evaluating your cart G 22 in patients with relapsed or refractory <unk>.
B cell acute lymphoblastic leukemia.
These patients received Fludarabine cyclophosphamide and Alemtuzumab islip for depletion regimen.
It provides us.
I'm confident that we're moving into the right direction.
These result.
So that's all pre conditioning regimen that includes Alemtuzumab was well tolerated and promoted the expansion of clinical activity of our U car T 22 in patients with relapsed or refractory b cell lymphoblastic leukemia.
Currently.
And the ball easier one trial, we are enrolling patients at the highest dose so far does level three.
We also added alemtuzumab to the pre conditioning regimen and another blood cancer clinical trial amyloid zero one in acute leukemia.
Okay.
So in.
In the clinic, where we're moving into 2022 confident.
Ability to execute.
Ambitious new program focused on product development and patient recruitment into our three ongoing multicenter dose escalation clinical trial valleys zero, one and believe zero, one and melon easier one.
We also plan to file a new idea for a new product candidate <unk>.
Car T 20 by 'twenty two for patients with relapsed refractory refractory non 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 and.
2021, black dismayed meaningfully power, it's becoming.
One of the few end to end cell and gene therapy companies.
Back in 2018.
Select has made the decision to internalize the manufacturing of its therapeutic product candidates, providing the company with independents and the strong hold over at cell and gene therapy processes.
We are thrilled to say that this goal has been achieved in 2020, an hour or two manufacturing site in Raleigh, North Carolina, and Paris, France are both now fully operational.
We produce our own cell libraries, our own plasma DNA, our own messenger RNA, we produce two type of vectors av's and recombinant lengthy viruses.
We are set up to produce our own clinical grade allogeneic car T cell product in fact in the second half of 2022, we plan to initiate dosing patients in the valleys zero one trial with clinical supplies of your car T 22 manufactured in house and rally.
<unk>.
And your car T 20 by 'twenty, two and not touch skin lymphoma trial.
We're becoming self sufficient and clinical supplies.
This reduces our dependence on outside suppliers.
These de risks our path to the market. This we move them into the road selected is positioned to capitalize on clinical and commercial success.
Its product candidates.
I already mentioned our plan to file a 90 of a new product candidate to car T 20 by 'twenty, two and not Hodgkin's lymphoma.
This is a very exciting product for at least two reasons.
Your car T 20 by 'twenty, two will potentially be our first dual allogeneic car T to enter clinical trials.
It is designed to hit two validated targets in B cell malignancy.
The product candidate is also the first product candidate select this has designed in house that's locked in house and manufactured in House. In addition, the power a few car T 20 by 'twenty two is that it goes beyond the overcrowded P. D 19 antigen on B cells. We believe it is.
Real allogeneic car T alternative.
Two the crowded.
Oh C D 19 targeting protocol.
I want to say a word now about our partner product pipeline, which remains important to select us as a validation of our technology base and source of future revenues.
In January this year allergy and announced that the United States food and drug administration has removed the clinical hold on all of the all of the genes clinical trials, which was announced on October 7th 2021.
Allergy reported that after investigation.
It was determined that the chromosomal abnormality detected in some your cart cells.
A single patient treated with Allo 5018 was unrelated to tailing gene editing in these cells.
Yeah.
Allergy has announced that it has resumed clinical studies activities on Palin gene edited product candidate Allo, 715, and allo six O five targeting DCM, a for relapsed or refractory multiple myeloma.
Gene has resumed clinical studies activities on tailing gene edited Allo 316, targeting CD 70 for advanced or metastatic clear cell renal cell carcinoma.
And began enrolling patients earlier this months.
Allergan also announced.
Got it and its partner Servier will resume their clinical activities on CD 19.
During the 2021 annual meeting of the American Society of Hematology in December 2021.
<unk> in collaboration with Servier reported that the results from Alpha and Alpha to clinical data continue to support the promises.
The five O on Allo 501, eight to be safe and durable as turn it is to approve the autologous car T therapy in patients with relapsed or refractory non Hodgkin's lymphoma.
Allergy and announced its intent to initiate a phase III pivotal trial on allo, 501, a and relapsed or refractory large b cell lymphoma is on track to commands mid year 2022 pending FDA discussion.
On the business development from utility of select this tailing gene editing system continues to provide the company with expanded opportunity.
In February 2021, we entered into strategic research and development collaboration with Si told you our therapeutics to develop tailing gene edited products.
A new type of cells I P. S N K and car T and K four series of different type of tumors.
In November 2021.
That collaboration with Pfizer <unk> expanded to include a new car target and development in China by site told yes joint venture entity title links therapeutics.
Financial term include either a cash payment and or equity stake totaling $20 million, depending on the satisfaction of certain conditions by December 31 2021.
This is in discussion with tight toga 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 in a single digit royalty payment on the net sales of old partnered product commercialize by site Tobia.
After allergy and I events biotherapeutics.
Partnerships that we have signed the collaboration with Si told yacht and another cell therapy modality highlights tailing as a gene editing technology of choice for cell therapy application.
We have also expanded our general management team and Board Committee.
Top talent.
Firstly.
Select this recently appointed Doctor Bang, Wang our new Chief financial officers I would like to take this moment to welcome back to our executive Committee and to selective bidding is a highly accomplished executives.
Who brings extensive global finance experience and the bias acknowledging industry, including background with global public companies incorporate finance.
He comes to us from where future by technologies cell therapy in oncology Biotechnology company, leveraging synthetic biology and gene engineering.
Were he was co founder and Chief Executive Officer.
Being extensive experience in financing clinical stage biotech companies will be critical as we enter our next stage of development of our clinical trials well.
Well come to selected team being.
Secondly, breakfast appointed Doctor Donald Berg strength as an observer on the company's board of director and November 2021 Dr. Bergen trend brings with him 15 years of experience in the biopharmaceutical and medical industry and serves as head of research on this.
<unk> relay therapeutics, a clinical stage precision medicine company.
Did you join this team executive clear plan to transform opportunities and seller of biology to the production of multiple focus clinical candidate.
We already have that place of many of the elements that's like this needs.
Is it 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 first three sponsored clinical trials and preclinical product pipeline.
Gary Please go ahead.
Thank you Andre as Ondrej mentioned 2021 has been a productive year for selective with our proprietary clinical programs, making substantial progress I would like to start with your cart 22, our CD 22, directed Hammond 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 16th annual meeting of the American Society of Hematology in December 'twenty 'twenty. One that presentation included data from patients who received no cart 'twenty two after months of depletion with Fludarabine cyclophosphamide and Alan teaching them Alan.
Alan season that was added to this with Guardian, and cyclophosphamide, deepen and sustain host lymphocyte suppression, thereby promoting your cart twenty-two expansion and persistence.
As of the clinical cutoff date of October 1st 'twenty 'twenty 112 patients had received month of depletion 11 were administered your cart 22 of which six received your car 22, and the Dara D and cyclophosphamide Alan Cincinnati.
Three patients at that dose level, two and three patients at dose level two intermediate.
You cart 22 after FCA the depletion was well tolerated no patient experienced protocol defined dose limiting toxicities.
And in fact yourself associated Neurotoxicity syndrome, no argue cart twenty-two related severe treatment emergent adverse events.
Three patients experienced mild to moderate cytokine release syndrome, one patient reported great T. G D. H D at the skin in the setting of cryo allogeneic transplant donor stem cell reactivation.
Encouraging anti leukemic activity was observed in two patients in the FCA cohort those patients when they first of all to end one at dose level, two intermediate a cheap laughs reduction for less than 5%, 0.40% respectively.
28, accompanied by measurable your cart 22 expansion and changes in relevant inflammatory markers overall your cart 22, after the Derby cyclophosphamide and Alan She's a map lifted depletion demonstrated promising signs of anti leukemic activity without unexpected or significant treatment related toxicity.
The addition of Alemtuzumab to Fludarabine, and Cyclophosphamide was well tolerated and proved host lymphocytes depression and promoted your cart 22 expansion, which was associated with anti leukemic activity. These data are encouraging and support the further development of your cart 'twenty two for patients with relapsed or refractory B a L L who remain in dire need of additional.
All treatment options, particularly those who have failed PD 19 therapy.
But I'll leave you right. One is currently enrolling patients at dose level, three with FCA, but the depletion.
Next I'll move on to your Cart C. S. One R. C. S. One directed tammen gene edited allogeneic car T cell product candidates being evaluated in patients with relapsed or refractory multiple myeloma early and preliminary data from the first patients enrolled in the melamine zero. One trial was presented at the American Society of gene and cell therapy.
24th annual meeting these data validate the S. One as a target for allogeneic car T cells in multiple myeloma as your cart. So yes, one expansion and persistence was observed and correlated with changes in relevant cytokines and with anti myeloma activity.
Select is currently enrolling patients at dose level, one with FCA length of depletion.
Lastly, I will speak to your cart 123, or C. D 123 interactive tailing 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. We are successful car T cell product candidate could be a major breakthrough. We are currently enrolling in our phase one dose escalation trial with FCA once a depletion enrollment at dose level two with ongoing we look forward to sharing data from this program when it becomes available.
Building on the technology platform or our current proprietary clinical programs I'm excited to report that we plan to submit an <unk> for your cart 'twenty by 'twenty two our first allogeneic car T cell product candidate for patients with B cell non Hodgkin's lymphoma in the second half of 2022.
D. D 20, NCD 22 are both well validated targets in B cell malignancies, and represent a therapeutic alternative to CD 19, 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 a tumor cells for more effective killing.
Secondly, it increases the breadth of antigen targeting and therefore, it may increase the addressable patient population.
And lastly, it provides potential to overcome antigen escape.
Preclinical data supports moving your cart 'twenty by 'twenty two 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 being selected as Chief Financial Officer for an overview of our financial Bank. Please go ahead.
Thank you Gary 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 full year of 2021.
I would like to highlight that the cash cash equivalents current financial assets and restricted cash position Oh Southwark this excluding colleagues.
As of December 31, 2021 was 177 billion compared to $244 million as of December 31, 2020.
This difference mainly reflects $160 million of net cash flows used in operating investing at least financing activities, which were partially offset by 45 million of equity proceeds raised from the sales under the Companys at the market program established in April 'twenty, 'twenty, one and 10.
Proceeds from stock option exercises.
This cash position is expected to be sufficient to fund selective stand alone operations into early 2024.
The net loss attributable to shareholders of select is excluding <unk> was 97 million in the full year of 2021 compared to a loss of $54 million in 2020.
There's $43 million increase in the net loss between 2020 , one 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 selectors, excluding 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 are still like this excluding noncash 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 'twenty 'twenty four.
Thank you Bing.
To close this call I would like to reiterate how excited and proud we are of what select it says accomplished in 2021.
And how the success propels us forward into 2022 .
More than 170 patients with relapsed or refractory malignancies has been administered with steel and edited allogeneic car T cell product candidate built on select this technologies and trial sponsored by selective and it's licensed partner with a promising safety profile.
Making the largest and the most robust disclosed clinical dataset of any gene editing technology in the world.
Our product and clinical development.
With the diversity of targets and indications as well as our allogeneic you cart 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.
I selected.
We strongly believe that our product candidates arc 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.
With that I would like to open the call for Q&A.
Thank you.
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.
You May press Star two.
A question from the queue.
Since using speaker equipment it may be now.
Sorry to pick up your handset before pressing the star he.
Our first question comes from that.
Jim of Itch with Citibank. Please proceed.
Hi, guys. Thanks for taking the questions on your cart 22, you're you're moving from the C. R O product to the in house product.
The second half of the year could you just talk a little bit of 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 indie amendment to to start the studies with the in house version.
Yeah.
Yeah.
Thank you Yigal.
Andrea 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 pizza product. The one made in Raleigh, and the one that we've been using so far that was originally made a CMO cell for cure. So this is an ongoing conversation and we're very key.
And who will come to.
The definition of an appropriate means to do that too swiftly.
Okay. Thank you.
And then regarding the three phase one datasets that youre working on.
At this point are you able to give any more granularity on which of those we might see data for an <unk>.
The 2022.
Yeah.
Yes.
So we're so we're definitely in the process as announced by Kerry. This is Arthur to go through the various escalation datasets are 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 sets a meaningful clinical datasets prior to sharing.
<unk> says we have done for your Cal 'twenty two at Ash last year.
But when it is safe to say is that we would definitely provide an update on at least one of these programs are in the course of the year, if not more depending on how that data matures over the course of the year.
Okay and last question, obviously, the CD 20 by 'twenty two is a very very interesting product.
Can you talk at all about what other combo cars, you might be contemplating beyond 2022.
Yeah.
Oh, no actually [laughter], if someone wants to answer this is Andre.
So the question.
So listen it's a I think the strategy that selected us and today I think it's gonna have like what go into very interesting pay off.
Probably people are had been criticizing off on the fact that one on validated target even if we don't consider that these targets on validated such a 22 123, yes, one or 'twenty by 'twenty two.
But we have a very interesting possess.
Positioning.
To develop and commercialize these products, they're not 19 theyre not DCM. A this is a great positioning because we don't have to face for example, the product such as the DCM April box 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 we'd.
We'd like to have all your attention on 2022 and the data releases that was going to happen this year.
As Arthur 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 excited exciting.
But disclosing what's going to happen in the future for dual targets that we believe is a very interesting approach for a numbers of freezing first for potentially lots of targets, but also for enhancing the tumor associated antigen density and the formation of <unk>. So to have a better killing of these protocols.
This is something that would be crucial and potentially also increase the safety and the performance of this product syndrome.
Got it thanks, Thanks Andrea.
Our next question is from Gena Wang with Barclays. Please proceed.
Thank you for taking my questions I have two.
The first one is regarding your cartoon D to our 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 your car 20 by 'twenty two I'm just wondering any updated thoughts on initial doses based on that.
New car 22 data.
Thank you so much gena I think the first question maybe for Steve <unk> and the second question for Kerry.
Sure. This is Steve in Raleigh in terms of the <unk> 22 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 all India Amendment. So we're well on track to be using that material in the second half of the year.
Okay.
Yes, sorry, what's the second question again whats the doses for 'twenty by 'twenty two.
That's correct and your updated thoughts on initial doses.
Yeah, I'm I'm not gonna provide details on what the clinical trial design is going to look like when we start the trial and it's in clinical trial Doc up you'll see but we have lots of data from both internal and external data to help support where we start them and hopefully given that it's a very.
Well understood patient population and space in terms of car.
Car T cells with N H L.
We have a lot of data to help support where our starting dose will be and potentially could help expedite the.
The child.
Thank you.
Yeah.
Our next question is from Kelly.
Jefferies. Please proceed.
Hi, This is Dave on for Kelly. She at Jefferies. My first question is on car T. 'twenty late 'twenty two just wondering in your clinical trial design are you thinking.
Thinking of enrolling both CD 19, naive and relapsed patient.
Yeah, I can take that so where 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 a moving things forward in one or more specifics.
Right.
Got it and another one is on a on a yeah, our solid tumor program.
Do we expect any update during the course of this year.
Yeah.
So I can I can start that this is Arthur so basically what we've announced this year and just focus on actually it's a good question and I'm glad that we have.
Given the.
Hyper focus of the company today on.
Our three clinical trials and 20 by 'twenty, two I N D and start of the the development that will be probably some scientific conferences with the developing a certain solid tumor programs that are currently still in.
And in R&D and shelf, but the fact is that.
Uh huh.
The strategy of the company is trying to push as hard as we can to get these products rapidly to expansion pivotal trial before prologue that were Oh, 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 on the international situation and market conditions and market conditions for cell and gene therapy space.
Before we can reconsider pushing these type of products into the.
The clinical trial.
Clinical trials, we're extremely excited by these these candidate products that we have are very very excited but we have to choose our fights and we think that the most mature product that we have all of them huge potential and I think it's in the interest of our shareholders in the company.
And of course, the patients to put all our power into developing these him on a product that we have.
Got it thank you.
Our next question is from Rajiv Prasad with William Blair. Please proceed.
Thanks for taking the question I just had a quick question on the.
C. D 52 conditioning regimen that know allergy has to run a.
A trial to show the impact of.
Of CD 52, Hum Grafman, because that's something that you anticipate having to do have you had any discussions with the agency on.
Any conditioning trials you may have to run a thank you.
Okay.
Yeah.
Yeah.
Okay.
I'm, sorry, I can't start if anyone else wants to chime in.
Think that.
Oh, Okay, sorry, it looks like the folks in Paris got disconnected I could 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 allergy and program is using a different anti CD 52 antibody, which is their own proprietary.
Allo 647, which is not a product that's ever had to a marketing authorization anywhere. So it was 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 them, but I think hum and what we're doing right. Now is we've already looked at them in all of our child.
With that we are using the album season, I've been with and without them. 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 of 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.
Pivotal trial and how to move forward or are you planning right now to kind of move both products forward or would there be kind of a decision point.
At some point in the next year or fall here.
Okay.
Yeah, I think that's a really interesting question because obviously given what we're talking about with 20 by 'twenty to 'twenty two it could potentially also E on working not just NHL, but then for example, a O L. But I think as it is right now given we haven't quite 22, and we're moving it forward in a L. L. We would likely continue to move that forward for this.
Niche on patient population that the high unmet medical need as a separate product, but again those are conversations and discussions we would have thought with both programs.
Great. Thank you.
Our next question is from Josh Allen with Baird. Please proceed.
Great. Thank you so much for taking my questions I have two quick ones here.
First on the on the clinical side of things I was hoping that you can provide a bit more color around your progress with the C. S. One candidate it sounds like you've moved to dose level, one, but I'm curious as to how many patients may be you dose and dose level, one and I guess, maybe any color you can provide around the totality of that cohort in 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.
The timing of potential milestone payments that we could see in the coming year I think allo 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 comment on milestone payments from the other collaborators as well and I events and Tovia. Thank you so much for taking the questions.
Yeah, It's terrie here I could start with the question, but that's one of the programs and we are moving ahead with the your cart T. S. One program in myeloma, and we have disclosed that we're in dose level, one and I'm not going to speak to how many patients and when we're in the planning on getting into the next sets of data.
I think suffice it to say, where we are extremely excited investigators, there's still high unmet medical need.
As you know we did come off clinical hold and we had previously disclosed that there are some long waiting periods in between patients and things that were required by FDA.
And so we're on it we're moving through it as quickly and expeditiously and safely as we can and hope to provide a dataset external for external disclosure. When there is yeah. When we have a reasonable dataset worth sharing and probably at a pivot point for when we would.
Potentially be starting to.
To move more quickly like in an expansion of I'm sorry.
And I will now pass it on to Arthur and Bang for your financial question.
Yeah, So Jack for the milestone payments are basically first of all on the Servia allergy and collaboration on CD 19, we're definitely eligible for a milestone payment upon a D. The initiation of the pivotal trial, which are other gene has guided for mid this year and we haven't disclosed the size.
The milestone payment, but there will definitely be one.
To the other partnerships are again, we haven't disclosed either the terms of the I owe them a collaboration but for Cytori. Yeah. This is going to be with the recent amendments Oh.
Two 805 million of milestones and we're also getting an equity stake of 20 million in two sides of your stock and so we expect that as cydonia progresses. These products are in the coming months, we will start seeing some some economics.
Great. Thank you so much.
Our next question is from <unk> Singh with Oppenheimer and company. Please proceed.
Oh, great. Thank you two questions and then thanks for all the updates.
Just a quick question on the manufacturing just going back to what I.
I think you'd highlighted previously you might have to.
Doing R&D for for 'twenty, two from the Raleigh facility.
With that being said you sort of you know as you go through clinical trials.
We get ready to file a BLA would you be set sort of on the clinical manufacturing side of the potential BLA at that point you know after doing this R&D and then secondly in that same thing when you have two assuming you can really see is one and or one to three.
Get materials from the Raleigh manufacturing facilities might you have to do future R&D. There are if you were to convert a using the Raleigh manufacturing facility I just got a quick follow up.
Steve you want to take this one.
Sure in terms of all your cart 'twenty two being produced from Raleigh, that's going to be an amendment to the existing all you are indeed, because that's all considered a major change in the manufacturing when you move from one location, namely a C. D moved to a new so there to internal manufacturing. So there will be an idea then.
And B L. A as a future state of course, depending upon.
Where we are in the clinical trials and how well they progressed, but yes. We are very hopeful this would progress at some point it will be all a bug for 'twenty two at the moment. The focus is all on submitting an IND amendment to enroll Raleigh is the manufacturing site.
And then just on C. H, one N and want to treat would you ever consider moving those producers that are involved with.
Okay.
Uh huh.
Yes, we're planning to do this of course.
Okay.
Then just last question you know there are next in line and both of them.
Okay, Great and your dual targeting calls you know.
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'd be sort of a second generation kind of approach where countries have a dual car ts or do you see it.
Moving a little bit more apps.
Further along and you know kind of going up against the bi specifics with some.
People, who might be a bridge to car T. I mean, I know, it's hard to pull out but just any thoughts there. Thank you.
Yeah, Hi, heart ties from a development perspective, I'm happy to take it I mean, I think that again, a lot of where you were going to end up positioning. These programs is kind of like any product in the market space and it's going to be dependent on the data I think was extremely important to recognize when we're talking about allogeneic car T cells versus.
And 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 are in the clinical read either in the free there don't need to wait for manufacturing between patients that it changes the entire paradigm of treatment for car T versus the autologous space, while the autologous this has been going.
And has been more of a kind of a second line or after as you said the bi specifics I think.
Provided the data are strong enough that I think that you know.
We don't need the specialized centers and Dan Dan Dan Dan even the fee that isn't as strong, let's say add 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.
That in 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 and setup from standard of care at peak purposes. So to speak from all of the key players who are treating patients. So I think again it all depends on the data if the data obviously arent at.
Strong.
Then maybe it will come after but I think our positioning is going to be as strong as possible based on the data and then you have to also remember when we're looking at data and comparing its actually more helpful to almost compare against bi specifics versus the cart teens, because remember when you look at the data in the label for all of these are autologous therapies have been approved.
Their denominators are based only on patients supersede that well and they throw out all of the patients who either they have a manufacturing failure or it was that that product or that the patients progressed.
Prior to getting treated and so if you actually redo a lot of those numbers the response rates and.
PFS and everything its just a 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 that was car T cell therapy. It looks so much better than by specifics as well. So yeah. So I think we can be clearly in any position, which is what makes us so excited.
Okay, well. Thank you Karl Thanks for all the updates on the go.
It would go to a topic I don't know if off itself.
As a reminder, this star one on your telephone keypad, if he would like to ask a question. Our next question is from David.
With S. M D. C. Please proceed.
Hi, Thanks for taking my questions and congrats on the progress.
I have a question on your car T. One 'twenty three we know that your cart High Street three is the updated product with the new cost structure and your manufacturing process could you just share some additional color on the changes of the construct but also the manufacturing process. I also have a follow up after that.
Yeah.
Yeah.
So maybe I can start.
David taking it Arthur David.
Hi, This is David So we did evolve you kept 123 to incorporate a CD 52 knockout and that allows us to explore.
<unk>, including Alemtuzumab, which is what we have disclosed.
And that was the major change in terms of molecular construct we also evolve the process itself taking into account all the teachings that we had gained from working with you've got 22 and you can see this one.
And.
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.
Yeah.
Got it that's really helpful. So just as a follow up.
And then could you just provide some update on the in vivo programs maybe share some additional color on the timing of a potential IND filings for those of you who are programs.
Oh.
I'm not sure what youre, saying about the in vivo programs, because we definitely have plans in the 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.
The four assets, we have your car to your 'twenty to your cart you went to three your car T. C. S. One in Europe .
Car T 20 by 'twenty two that we believe are.
<unk> has a huge traction are.
Exciting and mature product we are extremely excited and interested also in in vivo approaches using tailing or tailing based editors also potentially for different types of applications.
Because we have a fantastic technology concern on base editing because.
It's a split the activity between the two arms of tailing that type of very high accuracy.
And we're excited about that but today.
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 the in vivo programs and today Theyre essentially they've looked at the R&D stage that is perfecting and polishing and finishing all of these programs.
Got it that's really helpful. Thank you for the color.
Yeah.
Our final question is from Savannah to King with JMP Securities. Please proceed.
Good morning, and thank you for taking my questions and I'll come back to the team.
I just had two quick questions I don't know if you can comment on this but on your cart 123, I believe the last comment was that you are looking to enroll and dose a dose level three two.
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.
Okay.
Sure, it's Terry I cannot 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 level the other than that.
Beginning of this year, but starting at that level two who've been working on them for like not that cohort and we will continue to move forward at the time goes on and as when we have I E reasonable data.
Sure and we're ready for the next stage I wont be sharing data.
Great. Thank you and on your cart 'twenty, two I think that that was going to be an additional data cut.
Here.
Is there any chance that this could have some of the new material from the rail facility.
And the data or do you think that that's.
Pretty much further.
Yeah, So we have not.
As Arthur spoke to earlier in the call, we actually haven't disclosed per say exactly what state it that wouldn't be sharing this year, we will share data on at least one of that program and so we did not specifically speak to it in 'twenty two we're not as as I've said with all the programs I think it's really a.
That we disclose share disclosed data that's 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 still have a cohort so I'm not that's.
That's not something that I wanted to do and so we will we will be figuring out which will make the most sense based on where we are in China and what the meaningful message 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 select us 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 'twenty two.
We're now producing our own iron piece from eight to Zee.
And this is convertible to a producing people product and convertible commercial in the future and this is a huge change for selected.
The history of the company how much difficulties, we had in the past with certain products that were produced at CMO.
But today, it's a different type of selected that you had were 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 very exciting and interesting.
Data in the coming future.
And passing the steps you know select this is unstoppable.
With that I would like you to thank you all and wish you a great day.
Yeah.
Yeah.
Thank you. This does conclude today's conference you may disconnect. Your lines at this time and thank you for your participation.
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Yeah.
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