Q3 2022 Adaptimmune Therapeutics PLC Earnings Call
[music].
Hello, and welcome to adopt <unk> third quarter call and business update.
I will now turn the call over to Juli Miller Julie. Please go ahead.
Good morning, and welcome to adopt Indians conference call to discuss our third quarter 2022 financial results and business update.
I would ask you to review the full text of our forward looking statements from this morning's press releases, we anticipate making projections during this call and actual results could differ materially due to several factors, including those outlined in our latest filings with the SEC Adrian rock with our Chief Executive Officer is here with me for it.
The prepared portion of the call and other members of our management team will be available for Q&A with that I'll turn the call over to Adrian Balsa Adrian.
Thank you Julie.
Thank you for joining us today.
As evident in the data press release, we issued this morning.
Pulse trial with our next generation spear T cells targeting MAGE <unk> continues to produce compelling response data across ovarian bladder and head and neck cancers, with increasing durability and a new complete response in bladder cancer.
In addition, the recent pre BLA meeting and the updated data from the spearhead one trial that we will be presenting setose continues to demonstrate the value of a fan myself, a first generation MAGE a pool of cell therapy.
The people with synovial sarcoma.
Earlier this month, we announced we'll have full control of our prime program going forward.
And with ownership of affinity and hub spare T cells against MAGE, a four and prime.
We are well placed to deliver high value products with two of the most broadly expressed well characterized them validated TCR T cell targets in the solid tumor failed.
Right.
These developments, while it's positive come during challenging economic times.
And it is evident that we need to focus on three key priorities.
On advancing the MAGE a full franchise on.
On the Prime program and on progressing the allogeneic platform.
Since these represent the highest value creation opportunities.
We've taken decisive action to pause stope de prioritize and limit resources, but noncore programs to concentrate our resources on these key priorities.
And we've also made the difficult.
<unk> decision to restructure the company.
Or will undergo a reduction in head count of between 25 and 30% between now and Q1 2023.
These actions taken together will extend our cash runway into early 2025.
Although these are difficult choices.
<unk> sense of purpose and our confidence in the potential for a firm of cell C. D program to transform the lives of people with cancer makes it imperative that we take these steps to sustain the company and position ourselves to successfully deliver these cell therapies.
Okay.
Now I want to give a little more detail about the focus of the company going forward.
For MAGE, a fall we will focus on the fan myself BLA for synovial sarcoma.
And the surpass trials of our second generation <unk> product.
Karen bladder and head and neck cancers.
For a fan myself, we are committed to submitting the BLA and we will commence our rolling submission later this year, we plan to complete the submission in midyear 2023.
We've had positive interactions with regulators K give us and others in the sarcoma space throughout our clinical development of our five myself.
And the need for and potential of this therapy is undeniable.
Uh huh.
For the Nexgen CD eight product targeting MAGE aiful being developed in the past trials.
The latest data from the <unk> trial across a basket of late stage solid tumor indications continues to demonstrate the value of this product with very positive trends since the ESMO data.
Yes.
The overall response rate across the entire Charlotte now 37%.
And importantly duration of response has improved it's now five months in this ongoing trial and will further evolve with patients and continuing and ongoing response.
Oh.
Within this past family of trials, we will focus on those indications, where we have seen outstanding response data, namely ovarian urothelium and head and neck cancers.
Oh all across.
Across these three tumor types is now 52%.
In the Euro Celio cat and so we are announcing a 57% of all with one new complete responder.
And we are pursuing a new cohort in the phase one trial in combination with a checkpoint inhibitor in the second line setting for these patients.
Yeah.
Based on compelling efficacy reported ESMO with three out of four responses. We will also proceed with a new cohort in head and neck cancer in combination with a checkpoint inhibitor in the first line setting.
The ovarian cancer. The O is now 43% in the phase II trial surpassed three is initiating a monotherapy and in combination with a checkpoint inhibitor.
Last Friday, we received FDA regenerative medicine advanced therapy, or AMA designation for ADP to enforce the P. Eight for the treatment of patients with platinum resistant ovarian cancer.
By granting all about the FDA agrees that the preliminary clinical evidence indicates the C. D has the potential to address unmet medical needs in platinum resistant ovarian cancer.
Oh, Mike gives us the advantage of increased opportunities to meet with the FDA as well as early meetings to discuss potential surrogates or intermediate endpoints.
It also allows for expedited path ways, such as Rolling review and priority review.
And although all matches for platinum resistant ovarian cancer. This designation will benefit the entire CBA program.
And we now have frame as a wholly owned asset with great potential as shown by data from our peers as well as our own research we aimed to have to train program and be ready by the end of 2023.
Finally, we will continue to evolve the allogeneic platform, both wholly owned and then partnerships with Genentech and Astellas.
You can refer to this mornings press release for more details with respect to our decision to delay our first allogeneic IMD until 2025 as we change satellites for a major for Allogeneic program a decision that will not impact the work that we're doing with our collaboration partners.
Simplistically anything that I've, not just outlined as a priority will be paused or stopped.
We will stop the <unk> II trial, and GE, Kansas and stopped work on the til IL seven program.
We will see further investment in additional noncore activities, including work on preclinical pipeline projects such as the hit program additional target some broader HLA coverage.
We will also delay investment in the commercialization of our fiber cell based on the BLA timelines and we'll provide further guidance on the likely commercial launch date. After the BLA has been submitted.
And until we understand the terms of the transfer from GSK and the data package, we will not invest in led to sell targeting NY ESO.
With resources focused on these key priorities and the corresponding restructuring we anticipate that our cash runway will extend early 2025.
This will enable us to deliver the following.
One a filing of the BLA and subject to regulatory discussions approval for a farmer selling synovial sarcoma, the first engineered cell therapy for solid tumor.
Two.
A complete dataset for the monotherapy arm of our ongoing phase <unk> trial.
Okay.
Three and initial data set from the <unk> phase one combination arm across late stage tumors.
For an initial data set for the new cohort in second line Urothelium cancer patients in combination with a checkpoint inhibitor.
Five initial data set for the new cohorts in first line head and neck cancer patients in combination with a checkpoint inhibitor.
Six complete recruitment of the phase II <unk> trial for people with ovarian cancer as monotherapy and in combination with checkpoint inhibitor.
Seven initiating clinical development for our Prime program and lastly continued progress on our I'll, let generic platform for our wholly owned and.
Pulp and partnered programs.
The business of developing engineered cell therapies for solid tumors is challenging and complex, but the strengthening data from a fair myself and our CD eight program demonstrate we are succeeding in something that has not been done before.
We've made the difficult decisions to focus the company prioritizing our pipeline and reducing our head count to extend our cash runway into 2025.
We will continue to make the choices necessary to adapt to mean to successfully develop cell therapies to transform the oncology landscape.
Parting with a fan myself people with synovial sarcoma, and CDI for people with ovarian urothelium and head and neck cancers.
With that I'll turn it over to the operator 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 will hear a tone acknowledging your request.
If you are using a speakerphone please pick up your handset before pressing any keys.
Sure try your question. Please press Star then.
Q.
We will pause for a moment as callers join the queue.
The first question comes from Marc Frahm Cowen <unk> company.
Please go ahead.
Hi, Thanks for taking my questions, maybe just to start in the response rates are broadly similar across the.
Three focus tumor types going forward.
Our refractory setting, but some of those tumor types are being advanced as a monotherapy and others only in combination right. Now can you just walk through kind of the strategic rationale for why some of those are moving as long as combinations and others.
As monotherapy as well.
Thanks, Mark I'll ask Elliott to.
I'll take a stab at that.
Yes, so I mean, we could probably have a lengthy discussion going through tumor type by tumor type and maybe we should find the time to do that but.
In general.
The monotherapy arm is of the.
Surpass trial is relatively mature and we're really focusing on getting additional data in combination in the phase one trial.
With respect to and I would say that in the target indications, we have not eliminated the possibility of continuing.
With monotherapy in late line indications.
We think that the.
The greatest benefit to patients with.
With this type of therapy is likely in earlier lines.
And likely in combination with checkpoint inhibitors and that's why we're pursuing the two indications in particular.
<unk> had a neck cancer and bladder cancer.
In earlier lines in combination with checkpoint inhibitor and we outlined some of that back at the call in September .
But there are several rash several reasons for considering that.
<unk>.
Okay.
Okay.
Helpful. And then maybe just on a modeling question just with the kind of organizational changes you announced but also.
Yeah. There's some of these cohorts are moving forward can you just walk through some of the pushes and pulls for next few quarters in terms of our expenses.
Should we expect them to go down short term and then rise again or are.
Are there investments in some of the trial is going to happen quickly enough that I'm kind of overwhelmed some of the organizational changes.
So I'm going to ask Guy Gavin.
CFO to talk about the puts and pulls as we go forward with the restructuring.
Gavin.
Yes, thanks Mark.
As we move into the.
The restructuring that we arranged organize to what was announced today.
We are going to have to think very carefully about the puts and pulls that he talks about I think as we think about the shapes of spend over the next two years is slightly that we can shine make those broadly similar between years, one and years to not.
Not least because we believe in the in the intervening time then the data that we're delivering we'll continue to drive value I think there are some spot heinous probably in Q1 as we get over some of the capex investments that he's making him in the U K and all other genetic facility that's nearly complete.
Finishing off the 90 yard expansion and so as we think through the shape to be able to update you in more detail.
Early in the new year.
Okay. Thank you that's helpful.
Thanks Mark.
Good luck question comes from Tony Butler with Roth Capital Partners.
Please go ahead.
Okay.
Thanks very much.
Or Elliot as you alluded to a few minutes ago.
You were April thank you.
Move into.
Western lines of therapy at Western.
Oh refract less refractory patients.
And she has especially in Europe steel wheel in head and neck.
Can you provide some information as to what comes next.
Total week.
That suggests this is where we need to be.
And we're going to continue to advance those.
Patients in those particular cancers, thanks very much.
So I think I think the strategy in both of those indications.
Is that the there are patients in both first line head and neck in second line bladder cancer for whom checkpoint inhibitors, whilst the.
Indicated Boston indicated for those patients have a relatively low response rate as.
As monotherapy.
20, 20% range, depending on depending on patients.
And the intent is that we would be able to dramatically transform that right based on the response rates that we're seeing.
And then in combination with checkpoint inhibitors as a standard of care, but also mechanistically as a way of continuing the efficacy of the T cells and both that we we are T cells and the T cells recruited to the tumor biology yourselves.
And then extend those responses to be.
To be durable.
With it ultimately.
Desire to impact not just on the sort of response rate basis, but on a time to event endpoints progression free survival and overall survival. So the strategy is to drive very high response rates in those settings, where the response rates are low and for those responses to be durable.
Yeah.
Yeah. Thanks, Adrian May I ask one more follow up and this is places with respect to head count reduction.
To the degree that you've made this public internally can you could you provide some information as to what areas it R&D or other.
Hum.
Reduction.
Production may be most felt in other words.
Provide some.
Color on the balance of the of the company post the reductions if you can't yet.
Yeah, So I think well what we can say is obviously, we're embarking on this process internally and this process is obviously subject to.
The appropriate process, both in the U S and in the United Kingdom.
And we will complete at the beginning of next year I think it would be I think an appropriate for me to go into more detail externally as we worked through the details on the structure internally.
I can say is that we anticipate.
Most areas of the company will be impacted by this.
And also in the.
At the end of it.
We will be not the 550 person company that we currently are but.
400 people company still split between the UK and the U S. We will we will still be a.
Trans Atlantic company in that regard, but but a smaller one.
I'm focused on the priorities that I outlined in my comments earlier and Nicole.
Yeah.
I appreciate the comments thank you.
Thanks Tommy.
The next question comes from Mara Goldstein with Mizuho.
Please go ahead.
Great.
Thanks for taking the question I'm not rolling submission for fan so can you speak to them.
The totality of the data that you'll be able to happen, but that's the submission.
And to the agency in terms of you know that Karen Shannon and wait to be able to submit and then I'm just curious on the allogeneic cell line.
How did you discover that comes along with the melody.
Totally so I will ask Dennis who leads our late stage development to and has been responsible for delivery of our pharma. So let's talk about the first well.
Firstly those questions and then I will ask Joe through a CSO to cover the question.
Question on Allergan I E. After that Dennis Yeah sure. So.
The clinical package that we are proposing to include in the BLA, which.
Which we discussed with the FDA at the pre BLA meeting and they are in agreement that it supports our BLA submission for that indication.
It will include a longer duration of follow up of all the patients right. So that and that reflects the data that we're gonna presented SITA.
The median duration of response by independent review is around a year.
And patients are still ongoing responses.
So that data cut is about 10 months.
More mature than what we originally.
Prepared that we took last year, and we're sort of writing up that application.
What aspect of the application now and so hopefully that answers your question about the BLA.
A lot of that data here again will be presented.
It sets US later this month, so you'll you'll have an opportunity to see what the efficacy and safety data looks like as well.
Some translational data that we're putting into that.
Presentation.
And I will hand, it over to my colleague Jo Brewer to talk about your question about the allo.
Okay.
Okay, Yeah, Thanks, a J.
As we see the Allied program, we're constantly looking at the kinetics of the line, it's something that we again because its a program were looking at what changes within the failed in what is currently best practice and say please.
We've done we've been aware of this is in an area of chromosome 20, which is very common it's a hotspot in I P. S. C line since that we've been looking at this weekend very carefully and.
And it's something we've been aware of for a while but what has changed without being on the balance of risk and that's a more recent analysis.
They it hasn't happened because if the editing methods that we're using it hasn't happened because if the expansion packaged coffee eased in the banking technology either way.
Stable changed its been there for a long time, it's just a change in how we view the risk of that particular level, let me take and slightly society.
That line.
Yeah.
Thank you very much.
Yes.
Sure.
At this point are you able to clean out any commonality.
Commonality from ovarian cancer.
By responding.
Uh huh.
So this is Dennis Williams again, I would say.
We see responses in <unk>.
And Ah.
Wide array of ovarian cancer patients.
There.
And surpassed there is some heterogeneity on the duration of their platinum free interval, there's heterogeneity in their major for expression.
There's heterogeneity in there their tumor burden, but we do see.
Our responses and across.
A large number of these attributes so.
But certainly for the phase III trial, that's in <unk>.
And surpass three which is in platinum resistant.
Ovarian cancer, we're looking to have a more homogenous patient population.
So we're really defining the platinum free interval periods.
Sorry did you have a follow up.
Oh, no I'm sorry.
Okay, Yeah, so hopefully that addresses your question.
Okay. Thank you very much.
Thanks, a lot.
Uh huh.
The next question comes from Jonathan Chang with SBB Securities.
Please go ahead.
Good morning, Thanks for taking my questions.
First question, maybe just to clarify are they new responses disclosed today are these confirmed our unconfirmed.
They're all they're all confirmed.
We we tend not to report unconfirmed responses in all response rates.
Got it and if I recall correctly at as no.
You guys mentioned there were two unconfirmed responses in euro filial melanoma have those been confirmed.
The melanoma response did not confirm the urothelium responses data.
That's why we got it.
Oh, that's a 14 year nearly all of our response rate.
Got it is that the same type of thing.
Hey, Leo patients, yes that is one of those urothelium patients as they complete responder correct yeah.
Understood.
And then just one more question for me.
Are there you guys announced the transfer of the Crane and NY ESO programs from GSK I can't provide any color on the reasons behind this and what the status and next steps for these programs are.
Yeah.
Okay.
Okay.
The on the on the reasons behind that I think you'll have to refer to gsk's statements on their portfolio prioritization. All I can say is that we are.
We are.
Lighted their strategic decision has resulted in such credible programs returning to their mother ship.
And then in terms of development I think I mentioned it earlier, we are looking forward to putting my putting the prime program into the clinic should be IND ready next year.
And we think that is a that is a very significant target and I think that there is a few of you generally held by the others in the field as well. So we're very excited about that with respect to let us sell we need to understand both the terms of the transition back from GSK and ultimately the data right.
<unk> from the trials that they have conducted in order to be able to determine next steps for led to sell.
Got it thanks for taking the questions.
Thanks Joseph.
The next question comes from Michael Schmidt with Guggenheim.
Please go ahead.
Hey, this is Paul on for Michael Thanks for taking our questions just a couple for Michael the first on the Bam itself and mission.
Provide some updates on the non clinical data BLA components that were in progress as of last quarter.
Clearly the vector in T cell P. P Q and just to clarify just starting that rolling BLA process mean, Columbia remaining sort of components will be ongoing in the next quarters or do those have to be sort of completed to begin the process.
Yes.
Yes sure. Thanks for the question so.
The vector a P. P. Q theres lots have been filled and they're in our analysis and reporting presently.
T cell PDQ those batches have been harvested and they are also in testing and analysis presently.
So to answer your question, yes, yes, some activities will be ongoing.
During the process of which the first part of the application would have gone out the door.
So there are a number of.
Additional validation studies, some of which influenced the last piece of the submission when it will go in that will be ongoing during that time.
Authoring of module three the CMC module of the quality module will be ongoing at the time of that we are you know.
The first part of the Rolling review.
Starts and that's part of the the advantage of rolling of you're right. I mean, so you could parts of the applications that are complete can go in and start.
Start up process, the FDA review process, while the additional pieces are being finalized.
But I'll just pause there and for any follow.
Good questions.
Got it that's helpful. Thanks, and then just a second question on the frame program that you recently gained full rights from GSK I'm, just wondering how that recent transition.
<unk> no you're near or midterm development plans, you know versus what was planned I guess previously maybe talk about sort of where you see the opportunity across crane expressing indications.
Particularly with you know a couple of other competing programs in the clinic right now.
So.
Right.
Stop start on that and then on the.
Then I'll hand over to Joe to talk about how we see prime going forward I'll.
I will just touch on the Prime program was being developed by us.
We had yet to hand, it over to GSK.
Although that decision was imminent.
In our consideration. So there is no there is no transferred back to us because we currently have that program in house.
So it is back as the is the future right. So we're very pleased about that that we can get going on that move that into the clinic is <unk> ready going into <unk>.
Next year, and then I'll ask Joe.
To comment about where we see the opportunity for a prime.
Therapy.
Going forward.
I think that yes, they see it as I've said, we have the data in hand, and and the team is very excited actually at being able to accelerate the program full I'd say, we were getting it to the states, where we were ready to pass that across to GSK says that maybe if he changes there's differences between.
Our manufacturing process and bad debt, we will need to tweak up.
But we are ready and we having full control of the platform means that we can get with AMC and the way. The way you stated at least previous Tcl see that same price I say, we know what we have to do for Crane, we've done it before with other TCR said, that's quite it's relatively easy for us and we didn't have to deal with it at different manufacturing processes.
What we would have had to do it if it did state with GSK and that we're just in that choice.
From that point of view, it's kind of come back into the fold and under our control.
And prime and it sounds like a really complementary target T J.
For them, it's obviously precedent in multiple places where it may take for it as well and I think we're well he is our existing clinical experience to really try and maximize the language that we have that say payment expressed in a wide range of indications and the indications that we're familiar with and already have those clinical links that's where we'll put it up.
He starts but that will be part of the process that speak I see you're getting an IND ready fully understanding the clinical path forward.
Great. Thanks for taking the question.
Yeah.
The next question comes from Peter Lawson with Barclays.
Please go ahead.
Great. Thanks for taking the questions.
Couple of questions clarifying questions.
Hey, Kevin.
Hey, just on.
How should we think about the scale of the sales force.
Hmm.
Uh huh.
That restructuring and she became the majority of these cost savings are happening.
In R&D.
So uh huh.
In terms of sales force, we were beginning to think about how you kind of stand that salesforce up towards the back end of the year and since it's been thinking quite hard about that.
As a result of.
Turning to be a nice as touched on earlier, we're going to be putting that investment so it might be we might be.
Making the hiring and the same profile as we had been anticipating.
Before this announcement in terms of the restructuring.
That will that will be across the organization. We're just at the beginning of the consultation with people that don't want to get too far ahead of our skis just at the moment.
But one would imagine with a reduction of approximately 25.
The 30% that most areas as the the organization will be impacted.
Thank you and then.
How are you thinking about.
The use of partnerships.
To finance the company.
Thoughts about what could be partner to them.
Eric.
Seek out partnerships, whether it's geographically or indication.
Yeah, I'll start and perhaps I dunno take Kaiser I mean.
We've clearly as a company of our size and scale and then geographic partnerships, perhaps outside of the U S and Europe will always be attractive and we've got a broad range of assets and.
Yeah.
Certain ones that you're very close to a hot the others as.
Well, we'd be more interested in partner and having this partnering conversations, but I'll hand over to Helena.
Discusses ofer yeah, Thanks, Kevin Ah Hi, Peter This is Helen take them out and just just I think one dimension I would emphasize is the co development co commercialization strategy that we've applied in all my small recent partnerships with Astellas and with Genentech in relation to assets that we develop and given the just the stage.
And potential value creation that we can achieve with a broad.
Patient satellite MAGE, a four we clearly have a lot on our hands in terms of development Ah demands and commercial opportunity, but we'll be thinking quite carefully about working with partners.
Wow that was a potential win win on how we think about development and co commercialization say that would clearly be part of the thinking as they continue to build the capabilities to accelerate these assets clearly we are always talking to potential partners that they've got to be an alignment on how we continue to build value in the company are in those discussions.
Great. Thanks, so much thanks for taking my questions.
Thanks, Karen.
The next question comes from Schmitt ROI with Jones trading.
Please go ahead.
Hi, everyone. Congratulations on all the progress and thank you for taking the question.
Two quick ones on ovarian cancer.
If you can provide any color on these do we know the baseline CA 125 levels of these patients as they were coming into your trials.
Yeah. This thanks for the question actually given the fact that surpass one its original design was a basket study.
We did not necessarily have detailed information that you might collect if the trial would have been a varian specifics. So CA 125, originally was not a pre specified item that we collected.
And the response criteria that we use did not incorporate CA 125 response.
I think since that time as we started seeing signals we started to collect.
CA 125 data right because the standard of care in this disease, but we don't have in that across all the patients. So I don't think we're in a position to comment but certainly for the the phase II trial that will be pre specified that is something that we'll be collecting.
I see can you characterize like where these patients the ovarian cancer patients had a higher tumor burden or they were like soon after the relapsed from the previous prior line of therapy.
Yes, it's pretty I'm wondering just wonder does that at least.
Yeah, it's pretty heterogeneous I mean, we see responses in and folks that have tumor burden of lets say you know.
34 millimeters up to like over.
Over 100 centimeters right. So I don't know that I can definitively say that responses are more likely in one group versus the other other than in general.
I'd say those with lower tumor volume tend to do have better responses and then those that have tier higher tumor volume and that that is true for a farmer selling that's known it's almost certainly true for CD eight almost certainly true for most cancer therapies.
We do see responses across.
Here again, a wide range of tumor burdens and this is not unique to ovarian cancer.
Great and then one last question do.
Do you see the level of major Forex, especially is it homogenous and Oh the levels are similar across the patients in ovarian cancer are.
Head and neck or is it widely varying.
Certainly heterogeneity in major for expression I think the interesting thing that I would say is.
Generally speaking in some of these indications if you have made J for expression you have a lot of major for expression right. So when we present data by H score or P score.
Some in some cases the value that we have for this trial is actually higher than in like we have for spearhead one where <unk> four expression is very commonplace and Sanofi Youll sarcoma. It just happens to be that in this you know there's a lot of these tumor types. If you have it you have a lot of it.
Yeah.
I see and that you see in.
Part of the patients.
Or less.
Based on the trial entry for these tumor types. So for ovarian cancer, it's about 25% for head and neck. It's around the same number and for bladder it a little bit higher than that.
Thank you really helpful.
Congrats on the progress again.
Thank you thanks Karen.
This concludes our question and answer session I would like to turn the conference back over to Adrian rock Cliff for any closing remarks.
Thank you for your time. Thank you for your questions today I look forward to further conversations in please do.
Reach out if you would like to discuss further have a great day.
This concludes today's conference call you may disconnect your lines. Thank.
Thank you for participating and have a pleasant day.
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