Q3 2020 Cellectis SA Earnings Call

Dead dead dead greetings and welcome to the selective Q3 2020 earnings call at this time. All participants are in a listen-only mode a question-and-answer session will follow the formal presentation. If anyone should require operator assistance during the conference, please press star zero on your telephone keypad as a reminder. This conference is being recorded dead.

I would not like to turn the conference over to your host Simon harnessed senior vice president strategy and finance.

Thank you, and welcome everyone to selected third quarter 2020 corporate update and financial results conference call Johnny on the call today with prepared remarks are doctor and chief executive officer. Dr. Carrie Brownstein our chief medical officer and Eric detail our Chief Financial Officer yesterday evening selective issued a press release reporting our finance office for the second quarter and the September 30th 2020. The press release is available on our website at selected. Com.

as a reminder we will make

Forward-looking statements regarding Financial Outlook in addition to Regulatory and product development plan. These statements are subject to risks and uncertainties that may cause actual results to differ from the forecast 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 ended December 31st, 2019 and subsequent filing selected makes with the Securities Exchange Commission from time to time. I would now like to turn the call over to Hyundai Hyundai, please go ahead.

Thank you Simon. Good morning. And thank you everyone for joining us today yesterday select this as well as our sublicense allergy announced a series of clash updates in the form of abstract selected for all presentations at the upcoming conference. These abstracts will be the main subject of today's call and our chief medical officer. Dr. Carrie Brownstein will summarize these data in detail followed by an update on our financials from our Chief Financial Officer Eric. As a quick overview select this yesterday announced an app track on an early entry in clinical data readout of Valley zero wage study investigating. You karti twenty to one of our holy control allergenic car T-cell programs.

This data set has been selected for an old presentation at the upcoming conference in December this abstract provides and dream data on the first page to those cohorts of the Bally's 0 1 dose-escalation clinical trial a few karti 22in patient with relapsed of or refractory be same time for plastic leukemia.

Already at the first those level of a hundred thousand or a gun with a standard for their them and cyclophosphamide lymphodepletion regiment off without electricity. Two out of three patients achieved a best response of complete remission or c r and second patient off with a CR with incomplete in my in my pelagic recovery. We also announced the second abstract selected for trial in progress poster presentation of family 01 Phase 1 dose-escalation study of new car t123 in relaxed refractory ml patients.

We have cleared the to the first two dose levels and are progressing to dl3 and we are looking forward to presenting clinical update when available.

Strategy moving forward is to give regular updates on clinical milestones for our lead allergenic car. T-cell programs new car t22 in the valley Thursday, 1:30 in PLL. And you karti 123 in the Emily 01 study in Anna.

We are.

About to start those cohorts for both studies with the addition of alappuzha map to the fludarabine plus cyclophosphamide lymphodepletion regimen a patented invention a selective utilizing our Gene editing platform to knock out the CD fifty to Jean in allergenic car T cells.

Our third, holy control program new car TCS one is in its first dose cohort in patient with relapsed refractory multiple myeloma in Melanie zero one study while the study is currently on clinical hold who have responded to the questions of the FDA and are waiting for an agreement under proposed Thursday. We believe we have a straightforward plan to get this promising candidate back on track in clinical development and we will share an update any update as soon as available.

A sub-licensing allergy Therapeutics yesterday announced an asterik selected for oral presentation at Ash on the universe trial investigating a low 715 and relax refractory multiple. Myeloma patients a low 715 Xin allergenic car T-cell pro-life candidate targeting me, which is exclusively licensed from selectors to Allergy. The virtual presentation will include data on approximately 20 patients available for efficacy across a low 715 those cords and lowered those at 39 milligrams of aloe 6:47 as well as patient available for a security who are treated with higher doses of a load 715 and higher doses of six or seven.

We are impressed with the initial response rate in this first-in-class allergenic karti approach and are excited for the future of this program. The quick word on our aloneness regarding the cd19 targeted allergenic car. T-cell program allergen continues enrollment in the phase 1 Alpha and Alpha 2 trials expecting a package that data set to emerge.

Pending data allergens current plan is to initiate the potential phase two trial of a low 500 one day in 2021.

Furthermore allergen announced its plan to send me three additional applications in the coming months has expanding clinical development of targets on a life under our license agreement. This includes the first solid tumor Target with 316 targeting cd70 by the end of twenty G20 as well as the extension of the BCM a franchise 715 in combination with Nero guess that by the end of 2020 and uh, and I will 6105 a new BCM a turbo karti in multiple. Myeloma will be filed in 2021. Although the year twenty-twenty have created a challenging environment for virtually every aspect of professional and personal life. We had immediately adapter

this new environment

I'm excited to announce that our in-house manufacturing site in Europe. And in the United States are on track to start production by year 2020 and you're twenty Twenty-One years respectively. This is a major milestone for Selective in becoming an independent Gene and cell therapy manufacturing Powerhouse with that. I would like to handle over to dr. Carrie Brownstein our chief medical officer who will go into more details on the abstracts for our proprietary clinical program. Carrie, please go ahead.

Thank you Andre. I would first like to go into more detail on which is a phase one open-label dose-escalation studies designed to assess the safety off the maximum tolerated dose and preliminary anti leukemia activity for you. Karti, 22 our first proprietary program in patients with relapse refractory diesel acute lymphoblastic leukemia, which will be presented in an oral presentation at the upcoming virtual meeting in December as of July 1st, 2026 patients were enrolled on the trial took one patient discontinued prior to you karti twenty-two Administration after developing hypoxia related to the lymphodepletion and five patients received new car t22 infusions wage. Three patients were administered dose level one of 100000 cells per kilo and two patients were administered dose level two of 1 million cells per kilo.

All five patients received the standard lymphodepletion regiment the cyclophosphamide and food are being which we refer to as FC patients were heavily pretreated having received between two and four thousand lines of therapy, including one patient with prior cd19. Karti and one patient with prior cv-22 ADC therapy and all presents with high Baseline bone marrow of last month the depletion with a median or 35% We are encouraged by the initial Auntie leukemia activity observed two or three patients in dose level ones achieved an objective response black one with the best response of complete remission and a second patient with a CR with incomplete account recovery or CRI of note the patient with the CRM other one had previously been done successfully treated with Dina to the mab an antibody-drug conjugate targeting cd22 one of two patients at dose level to achieve the significant wage.

In in bone marrow black from 40% on De Minas one to 13% at day 28 22 infusion. Notably. This patient was unsuccessfully previously treated with a CD nineteen targeted car T-cell therapy. We are excited about this data as this is the first time we could show there is an allergen a car T-cell potential for patients who have previously talked out a CD nineteen or ct22 targeted therapies, including prior karti, these promising results were achieved in the lower to dose levels with standard ft lymphodepletion fire to the incorporation of Alum to the map.

new card

322 was generally well-tolerated and demonstrated. No dose-limiting toxicities unexpected toxicities Norwich treatment-related patient deaths no patients developed graft-versus-host disease affect your cell Associated neurotoxicity syndrome nor grade 3 or higher cytokine Willy's syndrome with this safety profile and activity Milestone We believe We achieved our goal of validating a cv-22 as a new allergen a a car T-cell Target as a Next Step the addition of alemtuzumab to the standard FC lymphodepletion regimen is now being explored in ongoing treatment cohorts to potential achieve a deeper and more sustained T Cell depletion and promote expansion and Persistence of you karti twenty-two patient enrollment in these cohorts is ongoing and we are excited to share further updates on this Thursday or next year.

Coming to you karti 123 our program in acute myeloid leukemia.

I believe 01 is our Phase 1 dose-escalation trial of our proprietary 123 product candidate in patients with relapsed and refractory acute myeloid leukemia and will be represented as a trials and progress poster a new format for the annual meeting AML is an area of significant unmet medical need it is the most common form of acute leukemia in adults and despite the number of products approved in the past few years. The prognosis remains poor novel therapeutic approaches are urgently needed that can be applied to a broad patient population. 8123 is a cell surface Target Express on the vast majority of a blast in most most patient segments.

2001 is a multi-center clinical trial designed to evaluate the safety tolerability and preliminary anti leukemia activity of you. Karti 123 in patients with real a factory acute myeloid leukemia in the initial cohort patients receive lymphodepletion with fludarabine and cyclophosphamide followed by administration of you. Karti 123 page receive one or four potential dose levels are evaluated for the presence of dose-limiting toxicities during a 28-day observation. And are evaluated for response at day 28 those level one and I have cleared safety review without dose-limiting toxicity and enrollment at the next dose levels are proceeding in the third quarter. We have initiated simultaneous dose-escalation cohorts evaluating the administration of your party 123 after lymphodepletion with fludarabine cyclophosphamide plus alemtuzumab after those level one enrollment in these cohorts were dead.

Is added to the FC lymphodepletion has already started and we look we are looking forward to presenting updates on this program next year when available with that. I would like to hand the call to our CFO Eric to Tom who will give an update on our financial position Eric, please go ahead.

Thank you. Carry, a third quarter 2021 driven by what kind of shows the cash cash equivalents Current financial cash position m x 2 in character as of September 30th 2020 was at $278 compared to 304 million as of December 31st 2019.

That many reflects twenty-eight million dollars, of course. He's received from Sunday in the first quarter of 2020 and 21 million dollar said guaranteed loans receipt from a bank which was offset by $17 million of other net cash flows using operating investing and Lease financing activities. This cash position is expected to be 5200 new version into twenty twenty-two.

The Consolidated Cash Cash equivalents Current financial assets and cash position of selective including Kelly was off as of September of 2020 compared to $364 as of December 31st, 2019 the net cash flow used in our perch capital expenditure this and that financing activities where twenty nine million dollar at selective and thirty 1 million dollars at Kelly of the first page of twenty-twenty the net loss attributable to shareholders of selective excluding character was twenty 1 million in the first nine months of 2020 compared to a net lot of forty-six million dollars in 2019.

These twenty-five million dollars increase in the net result between 2020 and 2019 was primarily driven by a significant increase in revenues and other information forty-four million dollars, which was partially offset by unique within the expenses of four million dollars and decrease in financial gains of 15 million dollars a month.

The cost net loss attributable to share the selective including Kelly was $42 or 98 cents per share in the first nine months of 2020 compared to five million that up or $1.52 per share in 2019.

The Consolidated adjusted net loss attributable to shareholders of selective excluding non-cash stock-based compensation expenses was Thirty million of 72-month censorship in the first nine months of 2020 compared to $48 or $1.12 per share in 2019.

Laser practice to spend our cash on developing our department wholly-owned product in the clinic and entering into production without set of manufacturing facilities in Paris in 2020. And in Wireless in 2021 with that I would like to add up the call over back to

Thank you, Eric. I'm proud of the progress. We have made in our journey over the last nine months even more over the past eight years select. This has been pioneering the allergenic car. T-cell space was it sub licensees allergy and survey we have believed clinical results in already three different targets cd19 dcma and City 22. This is just the beginning.

With more clinical results on these targets as well as our other proprietary and partner targets to come next year.

We are the first company that brought gene-editing to create allergenic car T cells. You karti nineteen, the first-ever gene edited allergenic car program entered the clinic back in 2015 further more selective was the first company in the world to bring life as the life-saving therapy to patients with unmet medical needs.

Along the way we have amassed strong intellectual property in the field of Gene editing since the early nineties using different Technologies, including magnet glazes and finger nucleases Caitlin Mega tiles and crisper one illustration of our Innovation is the earliest Lexus invention that has led to the patent covering the cd52 knock out in T cells with concurrent Administration. That's an anti cd52 antibody to pronounce the window of Persistence of our Cartier Subs.

In 2013 selected five patent applications in the use of crispr in T cells such as the removal of the TCR to suppress a low reactivity and essential step to create allergenic car T cells with crisper. This pattern has been granted in Europe in 2017 and upheld in 2019 following an opposition procedure and it was granted in in March 2020.

Furthermore R&D team has constantly published cutting-edge invasion in the car teeth of pace with the first beta 2 microglobulin knockout in car T cells presented in 2016. We have been granted on January 2020 a pattern covering The Knockout beat that 2 microglobulin together with The Knockout of the alpha using crispr in car T cells such as the one targeting cd19 off.

all these

Elements are essential tools for the successful allergenic car T-cell programs and we intend to make full use of our technological Arsenal to drive the success of our development program.

We have a trumpcast position to lead us through a series of clinical Milestone into 2022.

This cash Runway projection is conservative in its assumption regarding our expected Milestone revenue from our partner programs. And we believe the progress of artistic license program increases the likelihood of success of our expected Milestone Revenue as a reminder, we could potentially receive up to 410 million in Milestone payment from the cd19 targeted under our life lines with survey and up to $155 for each of the 15 targets directly licensed to Allergy including the bcma and the CD 70 as well as additional money on an undisclosed Milestone to come from our partnership with iovance Biotherapeutics.

Along with high single-digit or low double-digit percent royalty and further World while sales we strongly believe the combination of our Preparatory and partner clinical programs and our in-house manufacturing capacity as well as our strong intellectual property position in the cell therapy and genetic engineering will lead to Major value creation and transformation of selective over the next month with that. I would like to hand the phone over to the operator to open the Q&A operator.

Thank you, sir. At this time will 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 indicates line is in the question queue. You may press star to if you would like to remove your question from the Q4 participants using speaker equipment necessary to pick up your handset before pressing the star key.

Our first question today is from Gina Wang of Barclays. Please proceed with your question.

Thank you for taking my questions. I have a few regarding the new car 22 just wondering, you know, it seems those level one and level two. I understand a small number of patients but we didn't see very clear dose-response in terms of CRA. And the related question is why you know, the those level one seems that achieve pretty high GRE. So what is the reason to adding voltages mad? Is that because the durability from the dose level one was not very good and the asphalt presentation. Just wondering how many more pages we will see for the full presentation.

Thank you Tina. That's a very very good question. And thank you. First of all for taking the time to be on our call today, but very excited to give you the first updates on our first proprietary program. Although it being very early age. Um the question I'd like to delegate it to carry who can best answer the question from Allen to the math et cetera and dosages.

Yeah. Hi Gina. Thanks so much for the question. You're absolutely right. I mean, I think it was interesting that we saw more response into silver one than those level to walk again though. These are very early those levels and again without the incorporation volunteerism ab and therefore it's really hard to say whether you would necessarily see a dose-response at this time given the low dose levels know we're looking forward to continuing to enroll to see these cohorts with alemtuzumab as well as higher dose levels and see see where that takes us, you know, we've decided that we think the album Susan ABS important particularly given the day that we've seen with b-cell NHL as well as from from allergy and from our other partners from survey in and we think that's an important part of the puzzle to ensure that we're giving you to the patients the best Channel.

success

Okay, and how many more patients should we expect at the ash?

Yeah, I mean we're not we can't disclose what the date is going to be it until because the abstract is the only thing that's been out yet. So we'll we'll see where where that is. Okay, that's fair. And my last question is regarding the partner a low allergies b c m a l o r t just wondering like from their home data so far see seems like safety look a little bit worse than the cd19. She would get to see more infections than have a 1 grade 5 infection just any thoughts. You know why the safety profile could be so different between these two programs.

I'm sorry between which two programs are saying is in which one the allergies vs. Yeah. I mean, I don't I don't want to speak to their programs and I think there are better people to ask that but I would say that they are two very different indications. So I I think it's hard to complain. It's how I would answer, but they would know better than I given it's their program. Okay, great. Thank you.

As a reminder. If you'd like to ask a question, please press star one on your telephone keypad. Please ask one question and one follow-up question and then for additional questions, our next question is from Eagle, not your minutes of Citigroup. Please proceed with your question.

Hi.

Okay. Thank you very much for taking the question for the patient in the valley 01011 trial at this level to that had the bone marrow glass production from 40% to 13% I'm just 1 month. Is there still an opportunity for this patient to show a c r or a CRI with more time on study or is that a is that bone marrow glass production the best response that we can expect from the same station?

Thank you, though. That's a very good question. So I mean given it's leukemia and it's not NHL where patients can just sit and wait and get rescanned and things like that, which is what you would do in a month, and Leukemia because it's a much more, um, proliferative and Progressive disease, they need to move on to other therapy. Um, but you know, I think that this is the kind of patient where additional doses would make sense and that's something we're going to continue to look at as we move forward in the development plan because clearly the patient had Summers had a response had some activity and therefore would have been a good patient for for something like that and we're looking forward to getting that data together.

Okay, great. And then for the patient that has the CRI after failing to see the 22 Target at ATC could you just talk a bit about whether this patient remained cd22 age positive at enrollment? And what was your expectation for targeting patients that failed prior cd22 targeted therapies with with the expectation for Success With You Part 22 prior to seeing the CRI in this particular patient.

Yeah, so in order to get enrolled in this part of the trial the patients do require to have a significant cd22 expression. So that wasn't an issue in terms of having previous ct22 age though. I do think it's very promising and encouraging that after having a prior cd22 that didn't work out so well for the patient that we were able to show some activity.

And what was the second part of the question again? I feel like there was a wondering what your expectations were for for success with you in patients that had failed rc22 age. Yeah. I mean, I think as long as they're expressing the cv-22 we expect that there's a good chance of activity.

Okay, and then just one thing I'd like to say it's like very often some failure with T-cell engagers off and sometimes due to the fact that the T-cell of the patient are not super fit at the time of the injection and therefore the respondent the engager needs to have page after page like a toggle T cells are fit. It's the same thing like in the Target karti sell products. So when they fail doesn't mean that when you inject allergenic T cells that don't have the same signal would not respond differently and that's why we we can kind of

Okay. Thank you and just one.

On technical question. Is there is there any particular reason why in the valley 011 trial you're exploring three levels where as in Emily one? You're testing for those levels or some odd reason for that.

Yes, that's a good question. The reason is that in the new card 123 program. We are actually we were based on those escalation of three doses, but there is one place. So so to speak between the second and the third dose built into the study. That's why there's for both of them.

Got it. Okay. Thanks, Donna.

The next question is from Jim Burke know of Wells Fargo. Please proceed with your question congrats on the on the data. I guess just following up on the theme of durability lack of response and what we might expect adash. Will you have data on car persistence antigen expression and and just in terms of durability overall. Do you think it's more a function of depth of initial response or Persistence of the car? And then we're going to follow up.

good question for care

Yeah, I think Jim for the question. I mean, I think it's it's a little bit part one is in terms of what we're going to present in terms of additional data. You know, I'm not going to speak to today that said I think that the answer to a lot of the questions you're asking now are going to hold with the alemtuzumab cohorts Thursday. We're we're looking forward to collecting that data and and and showing that when we have it either so it's really

Where we are with the with that data?

And maybe you can I carry and the gym thank you so much for that information just to clarify we are in the middle of enrollment for you / 22 in Bali package and for family with 123 without the album too, but I want to the map addition and we're now starting enrollment with the LM to the map Edition for the U card 123 program. This will probably be two cohorts one with alemtuzumab and one without and for the twenty-two program because it's very similar to the nineteen program that's driven by allergies in l o v a one we're probably quitting over to the usage in the limbo depletion with Alan to the map and that's why right. Now the number of patients that were announcing is limited and we are off the next real big data update for us will be the addition with alemtuzumab and we are waiting to have a cohort completed to then show that different in the durability of response.

And maybe one thing that has to be kept in mind here like the data for example for DL one is like two patients out of birth a test.

Like see ours like that those is $100,000 per cake which is time on the sales for an adult approximately when you compare this to for example, nineteen data without knowing susah Nya without anything without these two micro level and not cetera. This is the kind of response you have this type of product which is quite interesting to assess in the condition. Would you compare for example with other data where you go? For example, 30 million cells per cake with no responses with the first time of reconditioning. It's a total different type of sets. So that's why I think it's also dead.

Interesting to analyze it through this angle and that's why we made with or without cohorts with or without the office is Matt Ford.

Or maybe just yeah, no, just maybe it's on the beta 2 microglobulin knock knock out and congrats on the IP. When does that when would you move into clinical knock out a sort of a follow-on effort hitting hitting both the TCR and then the be to em,

Well today, I'm not sure that I'm like fully convinced with the with the data we've seen with this. I think that definitely a combo between knock out and replace them with a p l e e like blocking and knt might be really interesting. It might be interesting for repeat dosing strategy. For example in the solid tumor setting but now like the strategy would only chews them up gives way more flexible the in the way we're we're going for this. So it's something that has been in the papers of the company for more than ten years now and like the this would come probably after we took the solid tumor space, which is

something where I'm visiting

and just maybe finally on cs1 any sense of when you know what the timeline timeline might be to hear back from FDA and how you communicate that to the street.

Are you want to answer this one?

Sure. So, I mean the second part I'm in can answer but how you want to communicate but at this point, you know, we've submitted everything we can we have a very straight-forward path forward with FDA to have it reopened. I think the FDA is has a lot on my plate right now. So we're just waiting to hear back. And once we have a path forward that's you know, final we're happy to walk share how we're reopening and and more information on that.

And maybe I can be able to add so see as one is an excellent product and we are so excited by the early start of the trial as we've seen patient enrollment in the beginning of this year. And there's a lot of patients that need for this product and we think the Fantastic alternative to a PCM a Target and you know, as Kerry said we've submitted everything to them already, you know, we could go and we're just waiting to hear back. We think the questions from the FDA were pretty straightforward and you know, we answered in a very clear way and we have you know a plan that we think is acceptable and you know, as soon as we hear back obviously we will let the street know cuz it's exciting for us to get this product back on track.

Thanks for taking my questions guys.

Thank you, Jim.

The next question is from Michael Schmidt of Guggenheim. Please proceed with your question.

Thanks.

Hey, is this is Kelsey on for Michael? Thanks for taking our question. I guess maybe just to start off with you twenty-two. Maybe just could you maybe help us Guide to Life? You know what the efficacy bar is that you're thinking about as we kind of assess this initial look at at Ash and then bigger picture. Did you say you would be pursuing repeat dosing for your programs? And if if so, I guess what patients would get retreatment. Thank you. Thank you. That's a good question for carry. Sorry Hi, I cannot get no problem. Thank Simon. So I'm sorry. So the first part of the question about the efficacy bar so in you know what we're looking at in particular and why I love our Target of cd22 is that it gives us multiple shots on goal for a regulatory strategy and so you can foresee wage.

That going forward a very fast to Market lower bar for an approval would be in patients who've already failed the cd19 directed treatment whether it be a uh any options whether it be a party or otherwise and so looking at prior approvals for very refractory relapse patient populations and a l l the bulb is not terribly high. So the FDA has precedent for approving on single-arm Trials see our rates that are reasonably durable with mrd. Negativity back in the thirty the 35% range, so that that's not so in that group that would be where we were looking obviously a upside for this program would be if the activities better than that, you know, we could easily move it up in the treatment Paradigm to get earlier patients. So so that's what you know, one of the important factors are for this program.

And then as far as reducing I you know, we have said before one of the main.

Improvements in a low party's over Auto is the fact that it can be treated like a pharmaceutical product and can be dosed more than once a month and we are actively pursuing how and in which patients we would potentially be redosing, you know in a l l in particular. We know that in the normal treatment. Let me treat with chemo in these patients. They typically get an induction type of therapy where you try to get them into remission and then they get another slug of high-dose therapy to consolidate that road commission. So we can Envision a treatment strategy similar to that that we could use with our product. So that's the kind of thing that we're going to be looking at as we move forward in the development.

Okay, great.

Thank you so much.

The next question is from salveen Richter of Goldman Sachs. Please proceed with your question.

Good morning. I just curious here as you look at the other players like allergy and Chris Brown Precision, you know provide data and really lay out then a V6 right on a purchase whether it's data to M knock out or knocked down or adding out and playing with you know, multi doses or you know refractory to to karti. How are you adopting that in in addition to the other leverage you're playing with into your trial design just so you can optimize one aspect before kind of moving to to the next and I'm just curious if you have any take away from what we're seeing from the landscape to date.

PayPal being the time and thank you so much for the question. Really appreciate it. So as you see the landscape come together to us is very rewarding because honestly and you can see the the Publications we were the first with all these approaches. We were the first with The Knockout we presented that at the Keystone conference in the spring of 2016. We were the first to file patents in the lounge scene editing space on these approaches where actually the first to use the album to the map approach that's attached that selected owns with the CD 50 to knock out and the concurrent administration of Ellen to the map. Um, so now it's interesting that a lot of people are acting what we pioneered and are implementing implementing that in their programs so far the city nineteen and bcma targets are the most expensive and what we're trying to show with our proprietary pipeline is that we are actually giving alternatives to these very crowded targets like cd19 or b c m a

We think from our strategy from that point of view. We have the best partner in the space with allergies and the most advanced partner to bring forward an allergen a first name off the shelf car as well as the first PCM a car that's off the shelf and we think with alemtuzumab you have a great way of actually dialing in a window of persistence because you have a modality that you can dose in different levels, which is Ellen to the map. And with the BTM knockout. You just have the knockout on the sales as if without any modality there, but it's a very interesting alternatives for sure for our trials, you know, we have learned from what we've done over the last five years in the clinic and we are optimizing the length of the policemen and we will give all those details with complete cohorts because we think it's more important to show full completed cohort than you know, make too many forward-looking statements while not having the clinical data yet. So the Ellen Susan map trials are dead.

Going with you twenty two and one two three p as one is a different mechanism of action because the knockout of Cs one in the car T-cell and targeting cs1 actually help these T cells lymph athletes on.

Their own which is very interesting as well in the setting but we're excited that you know, we show already responses and patience with 22. For example without Ellen Susan map at the lowest dose of wage. Mm output Seal program, which is pretty comparable to the early fifty nineteen approaches and we're seeing responses in patients that have been treated with a karti targeting cd19 before but that's you know, kind of showing two proofs of concept that we wanted to, you know confirm and with this data set we have with all although being very early, but carry sorry that was a long answer already. But if you want to have anything, please go ahead.

No, I think you got it all there. So I'm in thank you and I think Andre has something to say thank you very much for this great questions. I'll leave a really appreciate the position of the company is quite simple, you know, like we have two of our very important assets like a series of our important Assets in the hands of all Partners particularly the city life that I think is going to be the first one to be to file a d l a as an allergenic karti when you compare for example, an allergenic within the tolerance you see real interested in bringing an allergenic party because there are a lot of patients that are excluded of tall the therapy for numbers are freezing sometimes lack of or the poor quality of the T cells Etc. So the proof of superiority or the expansion of the market access of this type of product makes it a provable when you come with another city nineteen car you have a game

Allergenic cd19 car can you have to prove something different shows better? And I'm not sure that it's going to be that much easier when you look for example at the data from a legend on the BTN and the box is it induced by bcma or the 19th data competitors that induce that has also induced toxicity that the alternate job karti on nineteen MBC Mac shows a better index with this. We have a very strong IP that comes behind this and that can protect our assets for their commercial during their commercialization that within the hands of our partner and that's why I T is for if you have a protection during for example, all the the the the trials at this cold the Safe Harbor once you go out into commercialization, then the Safe Harbor disappears and the IP comes full-fledged now dead.

Our side we have alternatives to these two overloaded targets nineteen and bcma which is 22. Yes one or unencumbered Target such as 1 2 3 months and that's where the company has a very clear path to the registration with a strong IP behind it. And hopefully you see that the quality of the product that we produce even in hundred thousand supplicate 536 time less than others. We have better results even without any kind of partitioning or knockout Etc and give it a clear path to where the competition heading at in the coming month. Thank you.

The next question is from accessing Oppenheimer & Company. Please proceed with your question.

Great, really nice update all thank you. Just a couple of questions one is you know with the addition of the feeding regimen 2/22 and 125 your modeling and you know experience with your partner programs. Also how much of a you know, boost could you get from that? I mean trying to understand what additional Source, you know efficacy would be able to offset any safety. And you know, how are you thinking about that? If you can give us some color there secondly on manufacturing, you know, the way you're integrating your vehicle and Commercial manufacturing, I think actually something that that here competitors are doing so if you could just give us an update there and how that could help as you move your programs into made a late stage and then lastly, you actually detail for us what are some of the specific Milestones as much as possible that you could receive based on, you know, the uh, the Milestones that your partner's have disclosed over wage.

1224. Thank you.

A hard time. Thank you so much and I can take the second part of the question first and then I'll hand it over to carry for the clinical part. So in terms of Milestones, this is becoming very relevant for us because of our making a lot of progress in our collaborative targets. So for the cd19 line that's in the line just as a reminder between selected and survey for the US and European right and survey supplies and see u s right to allergen. So just to know that framework and all of those City nineteen cars if it's off of 151 et cetera are basically bundled in one Alliance and for this aligned we are entitled to receive up to $410 in outstanding Milestone payments plus a low double-digit royalty on worldwide sale and fees Milestone payments are obviously tied to whichever product makes it into the market first and in whichever indication and then Thursday.

Any further any thing would apply as well that is the cd19 aligned for the other targets. There are 15 targets that are directly licensed to allergies. So essentially dead allergy and pipeline is built up on selected licensed targets and selective is entitled to receive up to $185 million dollars per Target in developmental Milestones plus a low a plus a high single-digit royalty on worldwide sales of any products out of this Alliance. So in those targets are bcma Etc what Allergies have already and carry, sorry to the clinical part of that question.

They're still back to the yeah. So the album to the might question. I mean, I think that the the key here, there's not too much to say is that I can't quantify per month how much more efficacy we should see but see the key is that the alemtuzumab should allow for deeper and more prolonged on lymphodepletion which would only benefit the dead cells to have more time to expand and I don't you know, the point of our trials or really want to see how much additional expansion and there and how that them and correlates or translates into improved and more prolonged efficacy in these patients. So we're like you looking forward to seeing what that data looks like.

Just any updates on the manufacturing just on the clinical and Commercial and how that could help with the As you move your trial from early to mid and then too late stage in the next 12-24 months.

Do you want to take the car manufacturing, but actually the manufacturing wage tracks so we'll like the parasite constructions finished production started and that's like producing all the raw materials. We think we're on track also on the construction site and whereas probably start producing next year for all the clinical supplies, but also the commercial supply to the version is dead currently on track to be produced for the three products themselves and we have a back up with animals on with the moment n Lanza. I think the company has a tremendous amount of experience in the field of production of car keys. I think the quality of the product we produce and that's why dead

Low doses gets interesting results because of the quality of the products were producing at the end and also probably the genetic technology itself gives you more fit cells to expand the patient at the end and all they like proportion technologies that we master. So I think that this step is fully Mastered by the company and its untracked 2 a.m. To move on what I think was the key decision inside. The company is the ability to in-house manufacturer from Clinical supplies after Commercial Supplies, and we have a good view on this and I think that next year is going to be a big year with the kickoff of the production of the first Bachelor that rally at a private facility and I hope that we'll be able if we get out from all the situation to organize it visit and and see where like the the high standard of the company where we are where we have where we are at now.

Great. Thank you. Thank everyone. Thank you.

The next question is from Langley of Lautenberg, Please proceed with your question. Hey, thanks for taking my question. I notice a difference between the UK and you got the 1912s you look at it. You can in 1912 when you have you know, basically, there's not much courtesy extension and no response. But your current abstract the out of the three those one patience. You have to buy response time, I think and you may already mentioned this but I want to see if any further color on the potential reason for the difference. Do you think the average manufacturing the later manufacturer that you got a 22 has some see improvements over the issue you could be nineteen that may enable more potent expansion or advocacy. Yep.

without adding to the map

Or or any color on the Improvement in manufacturing may be related to that difference.

Anyone via Simon thank you so much for the question. Really appreciate it you dial again? So the it's a little too early to tell exactly obviously and a patient set up just three months but we have certainly always made improvements to a manufacturing. It's something that we quietly make we don't make too much of a big deal about it for competitive purposes, but we continuously improve our manufacturing jobs and we have a lot of know-how in terms of selecting the best cells into fitness sells for these trials. Um, what we do know and Carrie can elaborate a little more on this is the boss took the map Edition certainly increases the window of persistence for these cars. So it is something that is we think important for the durability of response. That's also why we're adding that to our trials right now. I'm there for you know why we're super excited about these early cars and these are indications that have been extremely difficult to treat and they have failed basically all of the therapies. We're also very excited about the significant reduction in wage.

In the patient on deal too because that was a patient that was previously treated with a city nineteen car. And so we do show that we have a very powerful product already at low Doses and it may be the only option for the stations that carry maybe talk a little bit about our vision with Alex. Isn't that going forward?

Yes, sir. Thanks. So yes to that question. I mean I can't I can't speak to why there's a difference and again as Simon clearly pointed out with life treating five patients at this point. It's very hard to draw any conclusions that said we're obviously incredibly encourage that without the album Susan have been in that dose cohort we were able to see if she responds so we're very excited about that and we think that when we add in the album to the mab it should only improve the responses that we see cuz it will give significantly more time for cell expansion that room for them to to expand and do their do their thing in the patients. So, you know, we're looking forward to continuing to enroll those cohorts and Gathering that data and presenting that in the future but you know, I I can't see necessarily to why it wasn't seen in that in those dead.

making early cohorts without now and she's not

like the manufacturer like one's the high ones be hiring. Like maybe one thing I'd like to add is like the manufacturing process has evolved, of course over the time and every month and the process of Laughlin that is becoming a real trade secret among all companies around it's like so difficult to elaborate on this and we will not however, I think I'm seriously I was surprised that like for example and then work with was Nineteen because like when you look at our data or for example other companies that don't use Alex's and although I thought of preconditioning such as like Precision biosciences data, I think it's interesting to see that there they do have also expansion and responses with their their car keys off. It's there is the ability to do this and this is not extraordinary activist. What is important is to see on the cell per keg or

Find the flat those that you give and the type of response that you get with the amount of cell that are.

Injected gives you a hint on the quality of the product at the end why that because in the violin J. There is a need to have the right cells there that will get you the extension and the right type of extension CD4 cd8 Gamma Delta cetera all the the the the the secret sauce around like the the the the number of like peace on Earth the central memory cells et cetera. Everything that is inside the vial should be sent and great in there and that's why I can also not only the way you call to culture the cell but the gene editing techniques that don't share the DNA is important but also they like portion technology in the way you deplete the cells at the end comes and all to the secrets ought to give you products that can expand very powerful even with supermodels.

Got it. Hopefully maybe even may I ask your last question is for the optimization current plan is a fixed income. But do you think do you see a feasibility to maybe personalize the Dos based on the patient conditions with a baseline Community or to my birthday or any other thoughts by markers?

Yeah, I can just do that. I think that's a really good point and it is something that we're going to be looking at it. I think the complication obviously is when we're doing the development and the way the regulator wage at it if they look at the length of the police and regimental us a dose as the treatment so we would have to you know, it becomes a little bit more challenging to do what you're saying though. I do think there is a place that not only for the LM choose a map but really for the entire regimen because there will be patients who have much more banged up bone marrow than other things where they can't tolerate as high damage is let's say if like Lacosta might or what-have-you versus patients that can and and that could be partially contributing to some of the differences we see from study to study as well and from patient patient. So I do think that is something that needs to be looked into and and explored as we move forward. But again, the straightforward plan is to have it be a stand.

Under some sort of standard dosing because that's just the way the agency and The Regulators look at it as a treatment Paradigm as a regimen not just as the the dose of cells, but that is something that's all she needs to be moved not just for us, but for the whole field in my opinion got it. Thanks a lot.

The next question is from Rogers Prasad of William Blair seems proceed with your question.

Hey, thanks for taking the question just a couple of clarifying questions one on the team that made alluded to potentially taking over the manufacturing of the city. Nineteen our product. Do you just maybe in with regards to your car 222 versus you car to nineteen? Maybe just describe a little bit more color in some of the differences in manufacture there and then um, you know, it says that in the in the press release it says that there's a dose cohort level too with alemtuzumab that's being enrolled right now. Can you bring up the dose and and how the the dose level will um change over time?

Hey Rodger, thank you so much for the question and it's very.

Important to clarify that on the manufacturing parts. So you guard nineteen or the season 19 cars have been manufactured since 2016 by our Partners 1st. That was survey and Pfizer Pfizer handed it over to Aladin and now because allogene is doing fantastic work here in the US. It seems like I think I don't know all the details about it, but it seems that Serbian allergies are consolidating their manufacturing effort. So that's really great to see but what I was saying earlier on another question is that we don't talk often about manufacturing but I think we can proudly say that we have one of the best manufacturing of car T cells in the States. This is sometimes not public information so we don't share this in detail, but we get some of the highest yields with the most potent cells per manufacturing runs off. So again what we said previously we can technically treat well over a hundred patients out of one manufacturing run. We have a very high cell yield or electroporation systems are giving close to a hundred percent wage.

Fidelity of sales or Knockouts are over $95 to 99% efficient. And this is in GMP scale. This is already in basically commercial-scale manufacturing. This is not in your lap. I think the manufacturing add selected the Top Notch and that's why we're so excited to you know, really fully make our car keys in house because that is starting next year with the completion of our manufacturing facility. And I think allergy is somewhat on the same track of finishing the build out of their own manufacturing facility as well. But it's great that the partner targets are being manufactured by our partners with our proprietary targets are manufactured by selective because that obviously it gives us the freedom to fully focus on how proprietary programs and then the second question. I think it's important for Kerry.

Sorry. Maybe you can repeat the second part of the question. Yeah, yes. It's not like it was off the personally because that goes level to talk to them that enrollment is ongoing can't disclose that dose and kind of the strategy around those finding with the aunties and lab goes off moving forward. Yeah, absolutely. So the so we we've disclosed before the dose levels. So it was a hundred thousand sells for 41122 was a million people per gig Shack the way we designed the trial was that we were starting at those level one without alemtuzumab after we cleared dose level two without we would then split the trial in two cohorts with them without that would would enroll independently so we now have, you know able to Dos escalate if we chose to without Alan Susan

Repeat those level-2 with alemtuzumab and that's where we are now and we're starting to move forward on that side of the trial and the evening.

Sure. I mean we haven't disclosed what we're using but you know, we're starting at somewhere in between where um allergy and has been so we're doing for this trial law sixty milligrams. So got it and would you would you anticipate you know, given what you've seen within potentially moving up or what what's in the protocol them? Yeah. I mean, I think we'd have to see you know, we you know, we came up with our dos based on scouring of the literature and not just their literature but the transplant literature and you know from my review page speaking with aol's and others that do you transplant and I've done transplant myself, you know, we know you needed those probably higher than 30 milligrams, but you'd want it less than a hundred. Typically you start to see significant infectious problems around a hundred milligrams. So, you know, we kind of wanted to start somewhere that seemed um in the range of what you really need to to get the depletion you need without off.

Overstepping with potential risk of infection and obviously we don't see what we want to see we could always change but I think from a prudent perspective given the patient population. I think we're starting at the right place wrong. Is that is that 60 given all split dosing up over a couple of days and we left that open because as you know, Alan Susan found something different formulations and things that we wanted to make it easy for um easy for the Physicians to um to give it that would because you know, it's not um, you know, and also some patients have issues with infusion-related reactions and things that some Physicians like to titrate up and things like that. So to us, it's really the total dose that matters not so much about how it split up.

Great. That's very helpful. Thank you.

Sure. Thank you so much for the question.

The next question is from Madrid Kumar up. There'd please proceed with your questions. Hey, thanks. I apologize. I might have missed some of these questions a bit earlier. But just what are your thoughts on employing dd22 parties in dlbcl given what you've seen so far in v a l l and then given some of the kind of noise around latent virus reactivation lock. How does that impact your thinking about either screening protocols for patients for monitoring of latent virus reactivation in kind of the limbo depletion karti regiment employer.

Either too great questions. Thank you so much. I'll have it directly over to carry. I expected that so really good questions. So yeah, so am I particularly dlbcl makes sense for ct22? Um, it's something we will think about in our clinical development plans. Um as we move forward, you know, I think there's no reason, you know, it's a it's a highly expressed in in and and b-cell NHL as well as in a l l that said and it's the same story as you would expect with as we talked about earlier that it's a a Target that there is not quite as much

Going on as much competition right now.

So it does give a opportunity for patients who have failed other things and provide potential, um fast track for approval. So it's a very good question is something that we are thinking about in terms of latent virus. Absolutely. Right? So, you know, almost everybody at some point in their life has been exposed to and has lived in them all these viruses particularly. Hhv six and seven, which is is an issue and is something that we're paying attention to unfortunately unlike some of these other viruses where there are medications that can get for prophylaxis.

There really isn't anything for you to be six and seven and it is an area of current study in the field. There's really only one medication right now that really works well for it, which is a carnivore isn't something you'd want to give patients as prophylaxis because it has all of these issues with your kidney and other problems. So it is something we have to pay attention to something we need to watch and we have to make sure the patients as they are screened and monitored closely for reactivation of these viruses and that when something does happen where you start to see some reactivation that is pounced on quickly, So it is something to pay attention to absolutely and we have incorporated into our trial monitoring and management of all these different latent virus infections as well as other opportunistic infections. If you can see in these patients with or without alemtuzumab quite frankly the to ensure that we're giving the the best monitoring and management of these these potential problems so we does not get wage.

Way of developing our product.

Okay, great. And if anyone has seen it, they've called Pennsylvania for Joe Biden and so he's been called us cuz of the United States by decision desk.

Sorry.

The next question is from Kelly. She of Geoffrey's please proceed with your question. Hi. Thank you guys for taking my questions, and I'm glad found the progress and this is Kylie fagg a variance from Japanese. I wonder if you have the information on 3022 expression level of credit patience. I know it's early and also am curious if you see the response actually correlates with the city 22 expression level. And another question is do you have anything like our lease on all probably from the biology perspective such as the stadium 22 expression level versus City nineteen exertion level that suggests 322 targeting strategies. Could it be better than sitting in nineteen targeting strategy as a single agent, Sara pee? Thank you.

Very very important question and I'll hand it over to to carry but obviously we take ct22 for a reason because we think it's very very well expressed. Very good. Yeah, I'm sorry. I'm still like reeling from the last song. Do you want to know if I can just do the the first part again and I heard the second part.

Oh, okay.

So the first question is do you see any do you see a correlation between City 22? Okay level and the response is yes. Yes when you have that? Yeah. We yeah, we haven't looked at that age. I mean we we do have a requirement of a certain level or higher to get on the first part of the study because we want to make sure that we're not throwing the baby out with the bath water so to speak so we haven't done a correlation wage because we are requiring a significant expression of cd22 at this point in the trial but it is something we will be looking at as we go in till later stages of the program. And then as far as the second part of the question, I think Simon said ct22 we believe in it. We think it's an important. It's an important Target in Linden DSL malignancies in general. I think that you know part of the reason I think cd19 ended up kind of being the number one target for peace and malignancies is just kind of because it just was similar to how ever talks about.

Happened to Justin CD twenty and that's why he became so important but also back in the you know, many years ago. There was a antibody, um effort to synopsis EP 22 that didn't really do very much I think cd22 fell out of favor a little bit, but we feel really strongly that. It's an important Target ubiquitously expressed and it really does provide a um, really exciting opportunity for patients who fail cd19 because as of right now given the city nineteen s or way ahead in development, they will be something that has given first and we know they relapse without a seating nineteen often express. So I think that you know, we think it's a really important place to be and does provide multiple shots on goal for an approval.

Okay. Thank you. Mister helpful. Thank you so much.

There are no additional questions at this time. I would now like to turn the call back over to Simon harness for closing remarks.

Yeah, thank you so much again to everyone on the call. We really appreciate your interest in selective, and we think we're really at a very unique moment for the company to start showing a lot of data on our proprietary program. So I will keep you posted and feel free to contact us if you have any further questions or would like follow up. Thank you so much.

This concludes today's conference. You may now disconnect your lines. Thank you for your participation.

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