Full Year 2022 Adaptimmune Therapeutics PLC Earnings Call
Well go to adapt them in and T. C. R squared joint webcast to discuss their strategic combination announced earlier this morning.
I will turn the call over to Julie Miller, VP of Investor Relations and corporate affairs at adapting in Julie.
Thank you operator, Hello. This morning, we issued a joint press release with TCR squared therapeutics announcing entry into an agreement for the strategic combination of our two companies and the second press release, we provided our Q4 and full year 2022 financial and business updates.
I would ask you to review the full text of the forward looking statements, we anticipate making projections. During this webcast and actual results could differ materially due to several factors, including those outlined in our latest filings with the SEC as well as our 10-K filing for the year ended 2022, which will be filed later today.
Of note, we will share slides during this webcast, which are also available on the presentations tab of our Investor Relations website, Adrian Raw Cliff, our Chief Executive Officer, and Garry Menzel, TCR squared Therapeutics, President and Chief Executive Officer are here with me for the prepared portion of the call as well as QE.
With that I'll turn the call over to Adrian Raw Cliff add.
Yes.
Thanks Julie.
We are delighted to welcome you to this webcast to discuss the strategic combination of our two companies, which creates a preeminent cell therapy company to treat solid tumors.
The details of the transaction are set out on the next slide.
This is a stock for stock transaction.
Did that to me and shareholders will own 75% and Tcl scratch, a therapeutic shareholders would own 25% of the combined company at closing.
This is anticipated to extend the runway for the combined company into 2026, following closing and the Navy link a series of catalysts, which we'll come to later.
I will be the continuing CEO and we will have a strong board with members from both adapt to me an N P C all square, including Gary.
We anticipate the transaction to close in Q2 2023 subject of course to shareholder approval.
That's the Waterboy, what we are doing however.
However, the purpose of todays call is to tell you why we are doing it.
While we are excited about this combination, particularly at this time in the evolution of cell therapy.
Here are the five compelling reasons why this strategic combination is the right thing to do.
First with two companies that have spent their entire history focused on solid tumors, the largest unaddressed opportunity for cell therapy.
Second we each have a strong clinical pipeline that has been highly focused on MAGE a pool that makes us feel it.
Has significant value, creating near term catalysts, including the filing and potential approval of the first engineered T cell therapy for a solid tumor indication.
We also have medium term preclinical pipeline focused on prime and <unk> 17.
Third together, we have an innovative next generation tool box designed to enhance the functionality of our products and the Chiba microenvironment as we aim to develop cell therapies that are both curative and mainstream.
Fourth we have end to end capabilities, because both companies have been entirely dedicated to discovering developing and delivering T cell therapies I'm, both have knowledgeable and experienced teams who have successfully advanced these therapies into late stage trials.
Finally, and critically this combination enables us to continue the focus development of a strong pipeline with an extended cash runway of approximately three years into 2026 due to significant operational advantages.
We're now going to cover each of these five points in greater detail on the following slides.
Gary and I, along with our collective management teams share the conviction the cell and gene therapy are about to have an impact on the therapeutics landscape comparable to that of monoclonal antibodies 25 years ago.
We believe these therapies will transform the treatment of cancer.
But to do that they clearly have to move out from the narrow confines of car T and Hematological malignancies, which nonetheless realized nearly $3 billion in sales in 2022.
Because a significantly larger opportunity is in the solid tumor space.
Treating solid tumors has been the life's work to the exceptional employees of the doctrine TCR square.
And the programs we have in clinical development, all amongst the leading cell therapies for solid tumors, where we have already seen robust response rates in multiple cancer indications.
These T cell therapies in the clinic and others coming behind will enable cell therapy to complete the transformation of this landscape, providing hope to people living with cancer.
At a macro level treating solid tumors with cell therapies is the ultimate value creation thesis for this industry.
This is why all companies exist.
I accessing this opportunity with a breadth of pipeline depth of runway is why this combination makes sense.
Yeah.
Although hematological malignancies, the only 10% of U S cancer deaths, the majority of cell therapies, and all approved car Ts all focused on these diseases.
90% of cancer deaths from solid tumors and this space is largely untapped by cell therapies, and we have said is living medicines able to respond to the tumor microenvironment cell therapies have distinct advantages to treat solid tumors.
I believe that our combined company will have a strong leadership position in this rapidly growing and evolving failed due to its complementary technology platforms, which Garry is going to talk about now.
Thanks, Ed as I had said this is truly an exciting time for cell therapy focused on solid tumors with many cancer patients already benefiting from treatments in clinical trials.
Together, we have complementary platforms that will allow us to address a broad universe of both intracellular and extra cellular protein targets with all speed and truck T cell therapies.
And that means proprietary spear T cell technology is based on the affinity enhancement and engineering of T cell receptors or T C ours.
Typically tolerably target peptide HLA complex is just how uniquely expressed on solid tumors.
C. R. Squareds proprietary truck T cell technology uses an antibody based binding domain used to TCR subunits to reprogram and any tax TCR complex to recognize tumor surface antigen.
Those technologies can be further leveraged in the combined company's allogeneic platform.
With spear T cells and truck T cells, we have an opportunity to increase patient access to cell therapy.
Ed.
Thanks, Gary.
With these complementary platforms, we are prioritizing and focusing on key validated targets for cell therapy in the solid tumor space.
Tom.
And a wide range of tumors.
Tells you is that we know we can address with our T cell therapies and.
And targets that are expressed in Kansas the between them kill more than 300000 people a year.
We have the opportunity to make cell therapy, a mainstream option for people with cancer through our focused pipeline against these targets.
And all technologies against these targets have enabled a deep pipeline across multiple cancer types. Our lead programs will target MAGE a for at least the feeling.
In the clinic and preclinical development will focus on Prime and C 17.
As Julie described this pipeline is available for you on the website. So I won't go into it in great detail because I want to focus on the clinical data and the catalyst that we believe are going to create near and midterm value.
We have compelling clinical efficacy from our two lead franchises.
With a pharma so we're on track to complete a BLA submission for the treatment of synovial sarcoma in mid 2023.
Which would mean a possible approval in 2020 for the first engineered TCR T cell therapy for solid tumor.
Our next generation cell therapy targeting MAGE, a for a D. P. A to enforce a D. Eight is delivering an overall response rate of 37% and a phase one signal finding supposed trial across a range of solid tumors.
And in ovarian and bladder and head and neck cancer, we see a response rate of 52% improving still further to 75% in patients with these tumor types, who have received three or fewer prior lines of therapy.
Going forward, we are initiating new cohorts in first line head and neck in second line bladder cancer in combination with parallelism up.
And the phase II trial support three which we intend to become registered Registrational for pace.
With platinum resistant ovarian cancer.
Gaba salad and the next generation therapy, TC 510 target Mesothelin, which is also expressed in a broad range of Kansas.
In the phase one dose finding trial there was cimo regression nearly every heavily pre treated patient had an overall response rate of 22%.
And in patients with ovarian cancer. The response rate was almost 30%.
Going forward, we have the potential to screen patients with ovarian cancer, both MAGE <unk> and makes us either which would significantly improve the screening success rate.
And this type of joint development is one of the distinct operational advantages of this strategic combination.
The phase II trial with <unk> is ongoing and includes options for multiple doses in combination with checkpoint inhibitors to potentially enhance response rates and persistence.
The next generation product targeting Mesothelin is Tc five Ted which incorporates a PD one CD 28 switch designed to increase potency.
The phase one trial is currently in dose escalation across a range of trimas.
Touching on safety across our combined programs well most specifics are available in the materials generally speaking, we see adverse events that are consistent with those associated with limpet depletion and the administration of cell therapies, mainly crs at various levels, which is typically manageable and reversible using.
Existing approaches.
Overall, the benefit risk profile to date has been acceptable.
On closing this transaction the combined company would have anticipated bond then into 2026.
We expect to deliver multiple value, creating catalysts from these programs within that financed window.
He is a long list of what you can expect over the next 22 months of course, we will continue to optimize the combined portfolio, making data driven resource allocation decisions and focusing on those programs that will deliver greatest value I'm going to touch on a number of these items for our pharma. So it's all about BLA submission and the potential for approval.
So the C. D. Next generation program, we have trials ongoing or initiated with the potential for Readouts This year and next.
Firstly for the combination in late line patients with a checkpoint inhibitor and then readouts from cohorts in front line head and neck cancer and second line bladder cancer.
That gave us a later this year, we anticipate the first readout from the phase two portion of the trial in platinum resistant or refractory ovarian cancer in combination devote them up.
We will also have a media readouts in mesothelioma patients who enrolled before the focus was narrowed to Iberia, which will include key translational data speaking to the impact of checkpoint inhibitors.
In 2024, we can expect additional readouts in the Gaba cell trial of TC 510, the next generation version of Gaba cell.
Trial is dose escalating and we anticipate initial safety and then potential efficacy along with dose finding was out in 2024.
A prime and TC 520, which target <unk>.
C D 70 will.
We'll be moving these to be I N D ready in 2003 and 24 with both companies have previously outlined.
Now I'd like to turn it over to Gary to explain some of our Nextgen enhancements some of which are already in use in all clinical trials.
Thanks, Ed not only do we have compelling clinical data and exciting preclinical programs. We also have a toolbox to further enhance our T cell therapies.
When we think about how best to treat solid tumors with a T cell therapy several factors come into play.
Trafficking of T cells to the solid tumor persistence in the hostile tumor microenvironment and to killing effectiveness. Once they are there.
A C D H and PD one switch next generation technologies have already made it into the clinic as autologous therapies.
We also have many others such as IL 15, and IL seven CCL 19, there can be thrown into the fight.
And one of domestic exciting aspects of our complementary technology platforms is the ability to target multiple acts of James and.
Importantly, all of these approaches can also be used in our allogeneic platforms as well.
Now suddenly it doesn't take a technology tool box. It takes a unique set of capabilities to make cell therapies work.
And with that I turn it back over to Ed.
Yeah.
Thanks, Gary.
One of the realization that both companies have had is that cell therapies are a truly unique class of medicines and to convert complex technologies into actual products that benefit patients requires a highly specialized set of capabilities that need to be tightly integrated in ways that particular to cell therapy.
All combined companies has been wholly focused on cell therapy for solid tumors since the beginning.
We have experienced teams who have a proven track record in this field.
Between us we've taken seven programs into the clinic.
Those are ongoing and the first BLA for an engineered TCR T cell therapy will be submitted this year by us.
The capabilities, we've outlined in our U S and U K facilities on the right hand side of this slide are not there by chance. They are not optional. These are the capabilities that we have deliberately built from the ground up by each of the companies as.
And as we bring together our complementary technologies teams and infrastructure there'll be significant operational advantages as we aim to transform the cell therapy landscape for solid tumors.
Now when this transaction closes we will have cash into 2026. This will enable us to finance the catalysts on the slide I showed you earlier.
As a combined company, we will continue to focus on investing our balance sheet and a data driven manner to create maximum value from the portfolio.
I'd like to return to the key differentiators that make the strategic combination of attractive.
A shared focus on solid tumors by far the largest opportunity for cell therapy.
Compelling data and clinical progress in solid tumors with our existing clinical pipeline.
A deep preclinical pipeline focused initially on prime and CD 70 backed up by expert teams specialized end to end capabilities a decade in the making.
And who made possible by our extended cash runway, we have the opportunity to deliver against our catalysts and against the ultimate goal of making transformative medicines for people with cancer.
And with that I'll open up for questions operator.
Thank you we will now begin the question and answer session to join the question queue. You May Press Star then one on your telephone keypad.
You'll hear a tone acknowledging your request.
If youre using a speakerphone please pick up your handset before pressing any keys to withdraw your question. Please press Star then two.
Once again anyone on the conference call, who wishes to ask a question May Press Star then one that now.
Our first question comes from Mark frame of T. B Cowen. Please go ahead.
Hi, Good morning. This is Tony with regards for or Mark. Thank you for taking our questions.
I'm just too high.
Two for US why don't you if you can provide more color on the on the cash runway.
Thinking that you have once the transaction closes how much gosh.
What was the cash balance I guess would be on and wildlife assumptions that that'd be W has.
No.
Thinking about all the catalysts that you weren't all that a lot of assumptions was that.
That's the assumption and the second question is about the B L. A.
Just wondering what.
What are the gating factors right now what what needs to be done in order for you guys to be able to complete it by 23. Thank you.
Okay. Thanks, Eddie so on the on the cash runway at both companies.
Pattern is to give our cash runway guidance, but not a obviously detailed cash flow guidance.
And that's compounded in this case by two things one integration planning is obviously only just starting on the back of this in two ways.
We just put out our Q4 results but.
T C. All squared have not done so so it's a bit early to be giving detailed forecast on cash utilization, but you can anticipate more information in due course I think the key thing is we are confident we.
We are confident that the the cash runway will can be extended into 2026 and can deliver on those catalyst and there's obviously a range of things that you could you could look for in terms of the advantages that come from both the operational advantages that I've talked about during the scripted.
Scripted portion of the discussion such as the ability to jointly screening with with a barbarian cancer, such as the obs potential synergies overtime associated with the manufacturing capabilities that adapt to me and has great data as we think about putting multiple products onto the market in due course.
And obviously establishment costs, we have.
Just simplistically to D&O policies for example, which we won't have going forward.
But I think we need we still need to go through the integration planning and between now and the close of the transaction.
Secondly on the affair myself BLA, we've laid out the pathway that we have agreed with the.
Agency to submit the elements of the rolling BLA and just to remind you that was the preclinical module initially which was submitted in December the clinical module, which we anticipate going in shortly.
And then the CMC module, which will be the final pace are anticipated in the mid mid 2023.
And the <unk>.
Work to composite complete those is the gating item between now and getting that I'm sorry.
Compiling the information for the clinical pieces. So as you as we go.
As we speak and we will be doing the same for the CMC piece and finalizing the work required to submit that with the information that we agreed with the agency.
Thank you that's very helpful. Thanks again.
Yeah.
Yeah.
Our next question comes from Mara Goldstein of Mizuho. Please go ahead.
Great. Thanks, so much for taking the question.
Just hoping that you could maybe review for us I bet I, perhaps even confirm that as as the deal comes together that T. R squared pipeline and the expectations for that pipeline for this year, you know that there will be consistent with what T. C. R. Squared has previously guided to and then secondarily I'm just curious about.
You know once you put the two companies getting you have greater scale you know what you think from a time perspective, I guess, where is the advantage, let's say with a T. Smith TCR scratch TC 510 program, which is in a phase one at this point and where can you bring synergies to bear there.
Yeah, I guess I'll take that one this is Gary speaking.
First of all I think the guidance is similar to what we provided before.
In the case of ovarian cancer, where we have a readout at the end of the year for that particular cohort.
510 are the same the difference I think is in the new guidance provided today is in the middle of the year, we intend to showcase the mix at the OEM of patients that we treated in the phase two trial before we narrowed the focus.
Two ovarian cancer. If you recall, we did let people know that if there was any excess manufacturing capacity, we would devote it to nisha theory on that.
Patients now intend to release some of that clinical data, including key translational data.
Speaks to the impact of checkpoint inhibitors in.
In the middle of the year. So that's in terms of guidance.
In terms of where there are synergies going forward I think because there are a number because we have.
Several overlapping clinical sites between the two companies we also have.
Some unique clinical sites.
Between the two we have an ability since both of US are focused on a very intense to co screens amaze J O N.
It makes a deal in which makes it a little more attractive to physicians, who know that they'll get a cell therapy treatment for that patient if they work with us.
So we see synergies there, which may help us as we go into next year move things along a little faster 510 is more constrained because of the design remember its dose escalating you have to move.
In a steady fashion.
Cohort by cohort as you move up each screening. So I don't think we can move that along much faster than we're doing already.
Okay. Thanks, so much.
Thanks Ross.
Our next question comes from Tony Butler of E. F. Hutton. Please go ahead.
Thanks, very much Adrian two questions. One is on the city gate program in ovarian cancer I, just wanted to well in.
The other cancers of head and neck and bladder. They were first and second line patients are these later line patients in ovarian cancer that will be treated that's question. One question two there was.
Statements about expanding the clean room space in the Navy yard.
Because of your manufacturing I assume that is not necessarily a component of what is required to complete the CMC components et cetera, as it relates to a fan myself and even though the expansion would.
Hum allow for more fans itself will be created.
I just wondered if you could provide a few words on that rationale.
Thanks. Thanks, Tony. So you are correct was the cohorts that we are initiating in the surpass trial in head and neck cancer and bladder cancer are designed to be in earlier lines of first and second line roughly.
Inc.
In conjunction with a standard of care Pembina lays them out the patients in the past three and the population where we believe we could.
Develop thought towards a registration.
Is in the platinum resistant setting at.
And again I just want to touch on that that trial has two arms to it both mono therapy with cells alone and in combination with pember Lytham mob.
Independently are designed against historic controls.
Giving us potentially sort of two shots on goal with that so I'm not that's based on and this is this is important because I think what we're doing now is we're transitioning out from and we have been for some time and in sarcoma from the proof of principle of a technology into actually developing products in specific indications.
Taking account of the treatment paradigms in those indications and that's why this makes sense and that's ovarian setting.
So that's the that's the ovarian study in the future for so Pos with respect to the manufacturing Youre correct, we built out our AR facility and the Navy yard expanded capacity.
To.
Did that over the course of the last year, hence the fairly heavy capital expenditures in the last year that won't be repeated unnecessarily going forward.
That gives us the ability to manufacture many more products it doesn't really affect the MSL.
Relevant.
The suites that we currently have open for pharma, South where incidentally, we manufactured all of the spearhead one patients where we will be launching from those suites are likely to be able to cope with the capacity.
Needs of domicile as a commercial product temple. The continued clinical trials associated with a far myself. So it's more that as we get into larger patient populations in the past that space becomes more useful with the manufacturing methods associated with the Pos.
Thank you Adrian.
Thanks Tommy.
Our next question comes from Michael Schmidt of Guggenheim. Please go ahead.
Hey, guys. Good morning, Thanks for taking my question.
Just a modeling question perhaps.
Yes, Greg.
Obviously, you did announce some cost reductions earlier this year, how should we think about the potential for additional cost synergies following the merger.
Yeah.
And then a pipeline question as well.
Okay.
So why don't I.
Start with that just at a high level and then Gary if you want to you want to comment specifically on the on the shape of TCR T. C. L square to the extent, obviously that we can see.
So I think the one of the challenges that you you guys are gonna have modeling. This is that both companies have actually gone from I, a larger cash burn in 2022.
To a much smaller cash burn in 2023 talking from the adapt to me inside.
Yeah last year, you'll see the cash burn net cash burn was.
Approaching approaching.
So that's gonna come that's come down so substantially on the basis of the decisions that we took both to focus the pipeline onto the key assets, where we've got a really strong signal all other product opportunities, but also to reduce the size and shape of the company, which we bet we executed on.
Over the course of the last few months and I know that the TCR squad team have done similar which makes it difficult to look at the 2022 numbers and project Board and that's what that's partially why we we've done some of that work in the run up to the to.
To the combination that we announce today in order to enable us to project forward into 'twenty the runway into 2026 and as we continue with the integration work between now and the close of this deal integration planning between now and the close of this deal and that obviously ultimately the integration work will be able to say more.
About that in due course.
Gary anything to add to that.
No I think you got it right D anything I'd point you to.
Michael is that in an 8-K I think we filed an updated.
Our cash position.
So there's a little bit of information, but the reality.
Not all of the impact of the changes that we made at the beginning of the year are reflected in that there were some other moving parts and then of course you layer in this.
Transactions so.
Sorry that we're not able to give you precise numbers good.
As we begin our integration planning our paths will be able to say more going forward.
Okay sounds good. Thank you and then just on the.
On the debt on the ATM program.
What else did we learn from the ongoing phase one study this year I know that phase III readout next year, but anything else, we'll learn on the phase one and 2023.
Yeah.
Thanks, Thanks, Michael So so I think that the.
The phase one program.
So Pos for C. D H, the surpass trial itself and the original cohort of that which was recruiting across a basket of tumors types, all of whom are reasonably reasonable a high MAGE <unk> expression in late stage patients with most having heavily pre treated multiple prior.
Lines of therapy, obviously.
That that that study has two part that that piece of two parts to it.
The the mono therapy arm, where we reported 43 patients.
Mono therapy in that 37% response rate last year, we anticipate completing that Tom and the guidance. We've given is that we will have ultimately 50 to 60 patients in it.
And I'm reading that out in in 2023, we also anticipate well we are also recruiting in parallel a combination again and those are.
That range of tumor types and again in late stage patients in combination with the bolt them up.
And that that.
We intend to enroll between 10 to 20 patients to give us experience using checkpoints in combination with ourselves as.
As a precursor for all the other work that we're doing further downstream and that will also read out.
Anticipate this year.
Later on this year and so.
That's what you can expect from the original I just want to make sure that everyone understands the two cohorts in first line head and neck. In first line bladder are also part of that so Pos trial, albeit that they're separate cohorts at different patient populations.
Great. Thank you.
Thanks, Michael.
Our next question comes from Jonathan Chang of SBB Securities. Please go ahead.
Hi, guys. Good morning, Thanks for taking my questions first.
First question how are you thinking about strategic priorities. Following the combination are more specifically for Gaba. So is the focus still ovarian cancer and what would you need to see in the data by year end to continue further development of the program in ovarian cancer.
And then second question I guess just for emphasis.
Following up on the prior questions can you give us more granular color on how we should be thinking about expenses on a combined company moving forward.
Trying to make the model work. Thank you.
Okay.
So maybe I'll, maybe I'll start on sort of the.
View of strategic focus and then maybe I'll ask.
Gerry to comment on the focus in ovarian cancer with with Gaba South.
Perhaps what it was what a good signal looks like there.
And then I'll.
They all come back down to come back to the cost discussion.
In terms of strategic focus one of the things that you have is you have two companies who have already gone through a very a significant.
Significant rush portfolio rationalization as part of that becoming fit for purpose for the world that we find ourselves in and so for US that was that was narrowing down I'll focus clinically to buy myself for synovial sarcoma and for C. D. Eight two the three indications.
What stages as we just talked about for.
For for full book.
It may J, Paul I'm, focusing on MAGE a pool.
And then in preclinical that was all focusing really heavily down on prime.
In the short term and moving forward to try and deal with that.
For the other.
<unk> TCR Squareds Ah that the focus is on is on is on Mesothelin focus on ovarian specifically, but Gaba Sal and then T. C 510, and dose escalating trial. So again first and second generation programs and one target essentially in the clinical labor side. So that's the narrowing of the focus of them behind it particularly.
Ted obviously.
TC 520 April .
With the vote.
The C 17, and preclinical so I think you've got a very nicely focused pipeline two clinical targets two preclinical targets within the clinical targets focused out on indications. Nonetheless, we as a company we will look to make rational data driven decisions as we go forward about how to develop this combined focused portfolio.
And and you can anticipate that not just immediately but over the course of the net of the entire financing window as well yeah, we're going to we're going to focus the resources of the company on those areas, where we fail as a combined company we have the most opportunity to create real value in products for.
Patients so that thought Gary do you want to talk a little bit about specifically.
<unk> focus and and signals there.
Yeah.
Yes, it's a good.
Question, Jonathan good to hear your voice.
Basically with Gaba. So what we have been advised is that if we can maintain the objective response rate that we showed in phase one, which if you recall was around 30%.
And demonstrate durability.
Is that is a positive outcome.
What's your ability, it's basically being able to get responses last six months or more and then feeds ultimately into overall survival since that's what patient cares about more than <unk>.
Anything else, we're obviously employing checkpoint inhibitors in order to help with that from the phase one and re dosing strategies as well as moving to earlier lines.
A therapy there'll be some translational data presented in the middle of the year.
We haven't decided exactly which conference, but we'll present that in the middle of the year AR and AR and the goal as I said is to be able to showcase that the checkpoint inhibitors are indeed, helping us with durability, but thats the readout, but we're looking for at.
At the end of the year.
And then thanks.
Thanks, Gary and then answer your last question or request for increased granularity on the on the cash flow and the short answer is we call giving increased granularity at this point in time.
I referred to previously however, maybe I could say a couple of things that might be useful.
As you think about the modeling.
I think that but the first is that both.
Both companies have have executed fairly significant downsizing. So the 2023 spend looks nothing like the 2022 spend for both companies. So that's first 0.2nd point.
The that the.
Financing the profile of financing for for adapt to me and specifically as we've talked about before is it is historically and we anticipate being in the future quite quite lumpy specifically, we tend to spend the majority of the net cash burn in the fed.
As part of the year and that.
That has been all but understand offset by both tax credits and payments from partners that we typically received in the second half of the year.
Inside of the combination of that makes makes the.
That makes the cash flow through the year quite yet.
Yeah.
Spiky so when we when we put all of this together make reasonable assumptions about.
The levels of of efficiency going forward. We believe that we are financed into 2026 with this combined portfolio delivering the catalysts that we have outlined previously.
Yeah.
Got it thank you.
Yes.
Our next question comes from Scott <unk> of Twist Securities. Please go ahead.
Hey, guys. Thanks for taking my question Alright, I got it I know what's going on here. This is a secret this merchant secret plot for the bridge to take over cell therapy isn't it.
[laughter].
Absolutely.
[laughter] okay.
Added Gary Okay. So a question I like for both if you to answer independently from a scientific standpoint, what technologies are being brought together from both your companies that you're most interested in putting into a single cell.
And then a question on on on.
He was their manufacturing capacity when do you when do you get to use the <unk>.
So when the T T R squared once a job get ya adapting our manufacturing capacity and related to that does the merger closing in the second quarter allow you to build the bulk capacity to treat lung cancer patients who had Gaba so rather approach it opportunistically how.
You outlined earlier Allah, you'll you'll get you'll treated lung cancer patient that does know ovarian cancer slots are being used.
Okay.
So why don't I take a stab at what I'm most excited about.
From a tech platform perspective, Gary I think Duffy you you could do the same.
I actually got a focus on I'm going to focus on three things that I think are a really really interesting problems from a technical perspective, I'm I'm going ahead with the first birthdays.
The combination of the <unk>.
The mental platforms is actually really interesting and we will then have access to the entire talking to universe, So and I will point out that the TCR square at all I believe the only company who have a robust efficacy signal with a mix of feeling targeting Ah talk to cell therapy.
And I think that is indicative of the potential of the truck platform for cell surface antigens in between the two of US. We then cover the entire Targa universe quite well.
Secondly.
I think the combination of the next generation approaches has has a lot of leverage associated with it.
I'm, particularly interested personally given that it's in the clinic in clinical development in the PD, one and <unk> 28 switch.
That are priced differently to most of our existing.
Next generation approaches and I think that would be really interesting to see the applicability of this. So then lastly, I think the opportunity to own and this is obviously over the longer term to take take the Florida border pipeline and put it onto a dock.
Back to millions allogeneic platform.
That matures I think is also a really key long term benefit of this combination.
Gary.
So as ticker since and has basically managed to grab all of the innovations.
Telling you about them.
I'm going to go membrane bound IL 15.
That is very true I guess I can throw that in there, but I'll tell you what I'm in some respects most excited about it's a perhaps a softer issues, but it's a really important one.
This gets to your first comment about.
Is this the beginning of consolidation within the cell therapy space on the solid tumor side.
And that is that what I've observed is the the leadership teams on the scientific side in these conversations have been excited about each of those technologies and become griffing.
Over what they might do together in the future new ideas that will emerge from the combination of the company and the <unk>.
Two companies into one combined entity I really do feel that's going to be a lot of innovation that comes out of that and this is a space where we do need continued innovation. So beyond the items that were mentioned by AD, which I fully endorse I'm really excited.
About what the teams will create together going forward.
Yes.
And then the next question was on sort of manufacturing capability and manufacturing capacity and things like that.
Access to that four they are and I think I think there's a there's an interesting balance that will need to play out over time. So one of the things that I am really excited about is most of our companies are.
Very pragmatic when it comes to developing cell therapies, I think developing cell therapies teaches us humility and it teaches you pragmatism and and so we are going to need to make pragmatic choices about the development of these on the basis of the existing platforms that we've got.
And largely our TCR square it is at a little tiny part D. G platform and largely we are on other platforms that we've developed internally to different ones, where I found myself in CVI.
Having said that.
Over time, there is obviously the opportunity to either bring them. It was tiny part D platform into a capacity or capabilities and all are as the pipelines evolve.
Move to common manufacturing processes over time, and so that's an obvious synergy and I just want to point out something that's really interesting about these these companies.
As you put the two as you think about putting the two together.
I would encourage you to think about the the fit of these companies because we are both solid tumor both engineered TCR cell therapies, we both use a number of the same.
Platforms and approaches that just pick one and lengthy viral vector transduction for two inside the genetic material into themselves there where both of them were both on common platforms. We have.
For some of this and then we have other areas, where we can over time combine them bring synergies. So there's a great deal of intellectual synergy associated with the act of developing engineered T cell therapies for solid tumors, but at the same time.
The engineering allows us to do different things because tcl squared is focused on extracellular proteins and we've been focused almost entirely on intracellular proteins and the expression on a peptide I might say complex and talk to that and so.
This very unique combination where theres a lots of intellectual platform capability advantages, but at the same time. It expands the universe of the things that we're able to to address I'm Bill. It's a company that really has heft in the solid tumor space.
Great. Thanks for taking my question guys.
Thanks, Thanks Jessica.
Our next question comes from Kelly She of Jefferies. Please go ahead.
Thank you for taking my question.
I apologize.
So how do you all along.
For the combined business.
Cool.
Across each of our acclaimed crime commercial demand.
Hum.
Energy costs.
Yeah.
Yeah.
Gary do you want do you want to have a go with that in addition to what I just said.
Yeah, I mean, I think from our side it Kelly what excites me.
Many of the things that excite me about the steel manufacturing is one of them we have.
Adopted a policy up to this point all relying on.
External agencies in order to do our manufacturing and that's worked very well for us up to this point.
Now, we don't need to build internal capabilities because those exist.
Ready to.
Adapt and so we'll be able to rely on that it's great that gives you greater control.
Your patient delivery supply chain and I'm happy about that.
So for me. This is one of the major advantages of the combination.
Thank you.
Our next question comes from Mr. Ryan of Jones Research. Please go ahead.
Good morning, everyone and congrats on all the progress one question on the <unk>.
On the maybe for the ovarian side and the Galveston are trying to understand if this is gonna be competing products are they are mutually.
Gonna be exclusive of the.
Well up to our address the patient population are.
Is there any overlap in the expression of major four in Missouri, Illinois, they're exclusively expressing different patient population set in ovarian or.
Head and neck or any of the other indications.
Yeah.
So I think I think we have most insight into probably the ovarian the ovarian space.
Maybe I can just.
I think thinking about that guide as to how to how to think about that so we're actually really excited about the opportunity for developing these in parallel I think it is in parallel because although although I'm sure. There are some patients who express both Magi for Mesothelin, we don't think that the.
No.
Likely to be completely separate populations.
Nor is the overlap likely to be.
Of the of the of the ovarian population.
So we think that there's a real opportunity to do a couple of things one is to the first one and probably in sequence first is to look at how we screen patients onto the trials.
It's obvious that if you if you could reduce the screen failure rate increase the screen success rate by having both of the trials ongoing at a particular site that would be that would that would be a fantastic opportunity to capture a larger portion of the ovarian cancer.
Patients and then the second second sort of piece of that is obviously then.
Commercial that you could offer a brew a cell therapy to a broader commercial population as well.
And then and then the other piece is I think longer term scientifically it will enable us to explore but what happens in those patients who have both they both do have overlapping expression is there the opportunity to either give the products in sequence or together to enable for that patient population than even deeper response, and I will add to that the prime.
It also has significant it's not in the majority of patients but significant expression in the.
In the ovarian cancer population. So actually long term you can think about MAGE, a four gave us out of prime all expressed in a minority of ovarian.
Ovarian cancer patients.
But to get the opportunity to offer a a cell therapy treatment to a larger population of ovarian cancer patients and to look at the patients with multiple antigens and think about whether there's the opportunity through multi antigen strategies to.
To be able to get to better outcomes for patients with multi antigen strategies long term of course, if you think about all of that on the allo platform as well.
The opportunities there. So I just think there's a real opportunity over over the long term to think about how to optimize this in the short term. However, I think what we've got is BJ for CD eight and I.
These two trials that we hope to become a resi registrational surpassed three that could become a product for us that I gave us all in a trial in combination with checkpoint inhibitors with a readout. This year, that's very pragmatically, where we need to be focused in the short term.
Yes.
Got it.
And.
On the commercialized insight, we see Cynthia Cna's, leaving so is there a reshuffling going on on the commercial team and how is this company. How are you going to combine the R&D team from these two different companies because they seem to be specialized in their own ways with their own products is that expense going to be completely additive.
Probably 25% reduction on the TCR to site and also the clinical team. It seems like everything is adding up rather than.
Having a synergy there.
Yes.
So I think we're just starting integration planning so it's not appropriate for us to talk specifically about.
Particular particular areas. However.
I think.
For Cynthia, leaving as Chief commercial Officer, Cynthia has built a great team.
Decision was associated with the reductions that we announced as an organization last year, but since he has built a great team that will enable us to continue with the commercial planning and strategy for our.
By myself.
Okay.
In due course in addition, Cynthia will continue as a consultant for us.
In particular on commercial strategy associated with that program.
That relates to the previous discussions that we've had and the decisions we made last year with respect to synergies.
Starting integration planning.
Have more we'll have more to say on that in due course, yeah. Clearly the balance is the balance of this is that.
They're all unique skill sets on both sides that we would need to preserve and leverage in order to be able to realize our ambitions for this pipeline.
Same time, it's obvious that there are things like establishment costs et cetera that are that are duplicated between the two companies.
Hum.
Hum.
Thank you for taking all the questions and good luck in 2023, it's gonna be a busy year for you guys.
Sadly as I said as much.
Our next question comes from Yanan Zhu.
Wells Fargo Securities. Please go ahead.
Oh, hi, Thanks for taking the question I just have a quick one on a timeline to durability of response data.
For the respective ovarian cancer product candidates from both companies.
Maybe if I may a floor that could if you could also comment on the I O combo.
We see a durability of response.
When might you have a sense, that's the a potential extension and scalability of fish months. Thank you.
Okay, I think I think that's right. So specifically on the MAGE <unk> because I think we've always said that on the Gaba sell side.
Because that's that's in progress at the moment.
So with respect to MAGE, a full actually you would the reason that we design the support three trial and the way that we did with an independent monotherapy and combination arm is because.
We want to assess.
Assess the potential for the <unk> program as monotherapy to actually be a registrational program. That's why we did that so it's pretty obvious we think that from that that there's a reasonable jobs that the.
Durability is is.
Is sufficient to enable and registration there otherwise we wouldn't have to design the trial and that way. However, the add on with PD, one is to drive depth and durability and the potential number of responders in that in that setting and it's just worth pointing out that in ovarian cancer checkpoint inhibitors typically do not have a significant efficacy signal in the <unk>.
So it's a real opportunity for synergy associated with.
With the with the.
The cells in.
Terms of timeline.
From that trial surpassed three because that is a registration oriented trial, we do not anticipate releasing data from that until we have fully enrolled.
The that that that trial in that cohort.
That won't happen until the sort of tail end of 2024, when we're fully enrolled that registration oriented or trial.
So I think the data from ovarian cancer will be late in combination will be related to a small number of patients. But we are we have been able to recruit will be able to recruit in the.
Phase one study.
Slightly different patient population in combination with our with devote them out.
And that we would anticipate being probably tail end of this year or into early next year before we have durability data.
In that relatively modest number of patients.
And then I think just to reaffirm on Gaba sell again in ovarian cancer Youll see clinical durability data.
The end of the year, that's what our intention is to present in the middle of the year.
Youll see some translational data.
Which hopefully will provide a pathway to that clinical data.
At the backend of the year.
Great. Thanks, Thanks, a lot and also I have another kind of a related question I think eight or afternoon.
And obviously he's.
Advancing the head and neck, and you're a female cancer studies in earlier line.
Setting I was wonder wondering if.
Yeah.
On the NASA sitting inside for the combined company.
Wood exploring earlier line also potentially be a potential a potential <unk>.
<unk> Uh huh from that side.
The combined company.
So so I think I think I'll talk maybe principal there maybe Gary you could touch on thinking on from your side on Mesothelin in earlier lines of therapy.
So in principle, we think that there are substantial advantages to moving into earlier lines for cell therapies. In addition to the normal oncology development advantages.
But you get which is healthier patients less fewer levels of pre treatment in a less advanced chuba, there's a really critical piece in cell therapy. The everything that we know says that the.
Early you can get cells from a patient the more pristine those cells are the less damaged by repeated assaults from chemotherapy or other therapeutic regimens. The early you can go back to those cells are likely to perform in this this is the ultimate starting point is that when we do work, but in patients who.
Ah patients cancer patients or healthy donors, the healthy donor cells typically.
Grow better and produce fitter T cells engineered T cells. So everything suggests that getting in earlier won't be better for cell therapies and that's why we believe that there is this opportunity in head and neck and bladder cancer to go to go in in these earlier settings and potentially.
Form those spaces with the response rates that we're seeing in very late stage patients replicated potentially improved in the early line settings.
Gary.
And I would just endorse that.
Our own dataset, we just don't have enough patients to be able to parse out.
Lines of therapy.
It is dose escalations or use of checkpoint inhibitors or re dosing.
Or other strategies, but the principle that has been shown I think in many other studies in oncology is that the earlier lines of therapy gives you a better shot at.
Treating patients if you think of Gaba sell in phase one we were treating patients who are.
Either in or going to hospice, who have other comorbidities just incredibly sick.
5678 lines of therapy.
Before them and it just makes it very difficult so having healthier patients who can tolerate therapies more.
And who sells are likely to be more robust.
Logically you would hope that that would lead to better clinical benefit.
We just didn't have the data to prove that out yet from our own studies.
Got it very helpful. Thank you.
Thanks.
Okay.
Our next question comes from Peter Lawson of Barclays. Please go ahead.
Great. Thanks, Thanks for taking the question just getting back to cash guidance. Just curious if that includes commercial product from bush.
Good afternoon, and TCR squared.
So the only product that would be launching within that timeframe would be our famous cell for the treatment of synovial sarcoma.
We've pre it doesn't include revenue from those products and do so so from that product.
Simple answer to that that would be additive to that and we've said that we will comment more on our commercial plans.
As we get through registration so it's inherently a conservative approach to what.
What we might do with aside myself.
Okay. Thank you and then.
Just a question for Gary but this was a.
That's the process how long does it take and is there any breakup fees.
So last question first yes, there a breakup fees fairly standard breakup fees I would say first of all that there'll be an S four coming out.
We will provide full details of of the dialogue what I can tell you now because you'll have to wait til then for that is at and I have known each other for a couple of decades.
So even before we were both specialized in cell therapy, we had an ongoing dialogue and of course with both feet and cell therapy.
For a number of years now not surprisingly being at the forefront of all fields we've had.
Ongoing dialogue just in terms of our thoughts.
In the field, but in terms of this particular process. The fall of last year was when we began.
To have discussions in earnest and you'll see more of that in other words. This was a thoughtful process and we're always talking to lots of people in the field.
So.
That's all I think we can say at this point.
Can you disclose the break up fees that we have to.
Wait for the filings.
You'll have to wait for the filings.
Okay and then.
Just goes back to the cash runway does that include.
Since you said the rationalization as a combined pipeline is that something you foresee doing that's something we have to wait until <unk> or is it kind of a <unk>.
Data driven thing or should.
Or should we just look at that pipeline has to go foods.
Okay.
So.
I think all of the above yes, as a data driven thing the pipeline that we've put out. There is is the is the pro forma combined pipeline of the companies and we will make we will make data driven and based on the catalysts that we've outlined to you those will be the data points. When will we will be able to make decisions about development pathways for those assets.
Perfect.
Thank you for the question Yeah.
I think at the end.
Thanks, Matt.
This concludes the question and answer session I will now turn the call back over to Adrian Rockwell for any closing remarks.
So.
Like for clothes by referring you back to the.
The five rationale for why this is a compelling transaction at this point in time, the solid tumor focus the catalyst achievable within the extended runway the deep innovative pipeline and the end to end capabilities that both companies have shown that I think between them.
The combination will make this a compelling cell therapy company for the future.
Thank you very much and look forward to catch up conversations with many of you in due course.
This concludes today's conference call you may disconnect. Your lines. Thank you for participating and have a pleasant day.
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