Welcome everybody to our conference, and we have the pleasure of hosting Atara Biotherapeutics today. In attendance is Pascal Touchon, President and CEO of the company. Pascal, welcome. Thanks so much for spending time with us. Before we get into the specifics of the question, maybe for a few minutes, give a brief update on the company, where it stands post the MS trial failure, and how you're pivoting to a new chapter in the company's history. Thanks.
Certainly. Good morning, everyone, and thank you for inviting us.
Sure
... to this conference there. So Atara is really into a transition right now. We are clearly the leader in the field of allogeneic T-cell therapy, as we are the only company having an approved product. Tab-cel, or EBVALLO in Europe, has been approved at the end of 2022. It's been transferred now, the approval, to our partner there, Pierra Fabre, which is launching the product right now, and very successfully indeed, in Europe. And at the same time, we have moved over the last few weeks into very new situations, where we have also partnered with Pierra Fabre for global rights of tab-cel.
So now Pierra Fabre, once the deal is closed by the end of December, will be the one really controlling the asset from the point of view of commercialization of tab-cel across the world, with a particular focus on, of course, the U.S. commercialization, the U.S. being by far the biggest market there. Now, this deal is very important in the sense that it allows us not only to have a very committed commercial partner in the U.S., and more about that in a moment, but at the same time to have a cash runway that has been extended to Q3 2025, with that particular deal, and more details in a moment. So we have cash into Q3 2025.
We have a very committed partner to successfully launch tab-cel in the US once we get through the BLA submission, which is planned for Q2 2024, and hopefully then BLA approval. And then we are also actively opening investigational sites for our first clinical study with our first allogeneic CAR T, ATA3219, which has the potential to be best in class. So we're expecting to have first clinical result in the second half of 2024 with that product. And at the same time, we are now following the disappointing results of the EMBOLD study that we communicated and disclosed a few weeks ago. We are now stopping activities on ATA188.
At the same time, discussing with some pharma companies that were interested in that particular aspect of a new approach to the treatment of multiple sclerosis, particularly progressive multiple sclerosis, but also relapsing-remitting MS, in discussing with these companies, the potential for them to be interested to pursue further development of ATA188, or the vaccine that we have right now in preclinical stage.
Got it. Got it now. Lots to unpack here. Just one question on ATA188. Like, as you said, although you're not going to develop it further, other pharma companies may step in and carry the ball further. What's the likelihood of that happening? And if that does happen, what would the economics to Atara look like in that situation?
So we know that a number of large pharma company are interested in the EBV assumptions, as EBV being supported by a lot of scientific data to be the trigger and possibly the driver of disease in MS. And these companies might be interested to test ATA188 in earlier stage of the disease or in RMS, and that's certainly a study that we'll be happy to support ourself with the inventory we have of the product-
Sure
... and the knowledge and data that we have about the product. We are right now busy analyzing all the details of the EMBOLD study to be able to present that as a package to these companies and see whether there is some interest to further develop the product. In that case, it would be a situation where we just are licensing out,
Sure
... this type of development. We'll not conduct activities ourselves, and we'll have inventory that is ready for use in clinical trials of ATA188. Now, this being said, at the same time, we have this very exciting preclinical candidate as a vaccine.
This vaccine. Right. Right.
As you know, a number of companies like Moderna, like Merck, have been going into that field of developing an EBV vaccine, a vaccine against Epstein-Barr virus, with the aim to be either prophylactic in terms of preventing the disease, the glandular fever, or the consequence of the infection, such as some cancer and some autoimmune disease.
But also the possibility to go into a therapeutic vaccine, in the sense that if you intervene very early in some of the autoimmune disease or even some cancer that exist, that are caused by EBV, you may be able to stimulate enough the immune system through a vaccine that is really stimulating not only the B-cell immunity, but the T-cell immunity, to be able to create sloan response against the EBV infection, and more particularly, the impact of the EBV infection on the disease. So that's really what we are developing with our collaborators in Brisbane, Australia, QIMR, and that preclinical vaccine is very differentiated in the sense it has a coverage of more than 20 epitopes, covering all the, not only lytic phase, but also the latent phase of infections.
We have already some preclinical data, some of them has been published, that shows that there is very good stimulation of T-cell immunity following the vaccine in, of course, animal models there. So very exciting, and we think that the-
The modality of this vaccine?
It's a typical peptide vaccine, polypeptide vaccine with adjuvant.
Got it.
But it could be, of course, adapted to different type of modalities depending on what technology has the vaccine company. And we know that some vaccine company... We started some discussion with some vaccine company already on that, candidate, and we hope that might also create some opportunities of some value for MS program through partnering.
Got it. I know it's early, but on this vaccine, when can we expect data to be presented? And, second question is, when could we expect an IND to be filed, or is it still too early to tell?
On the data, preclinical data, part of it has already been published in a Nature-
Okay
... publication, and we can, of course, make that available. And then we have some additional data that are in-house right now with a different adjuvant. And then in terms of IND, we are not at this stage ourself actively working to the IND. It's ready to go. We are doing a lot of research to optimize different aspect of the vaccine, but it will be reasonable timeframe if a partner wants to go to IND, I would say less than two years.
Got it. Got it. John, any more questions on this before we move on? Let's move on to tab-cel.
Mm-hmm.
Obviously, you recently announced the completion of that out license to Pierre Fabre. I'm curious about the choice of partner for the U.S. collaboration.
Yeah.
Obviously, they're much better known in Europe, where they've already been commercializing, but they're somewhat less known here in the U.S. Why choose PF for the U.S. out license as well?
I think it's a very good question. We had a very comprehensive process with our advisors there. We had a large number of term sheets on the table, and some of them were coming from companies that have strong U.S. presence. But we thought that from a company point of view, if you think about the corporate strategy of Atara, we had some benefit in having one global partner instead of having two partners, one in the U.S., one in Europe and some other countries, and to be the middleman in between.
The reason is as follows: having now Pierre Fabre as a partner, we have a partner that is going to take over progressively all expenses and cash burn related to tab-cel, and then we can be in a situation once we hopefully obtain the BLA and then transfer the BLA to them and transfer all activities on tab-cel to Pierre Fabre. We are in a situation where we don't have any more cash burn on tab-cel, and we receive royalties and sales milestone according to the progress in launching the product in the U.S. and globally beyond the U.S., in other market as well. Having one partner allows us to have this transfer of activity, this transfer of cash burn to our global partner.
Second is, I've been doing a lot of deals over many, many years, and the best deal I've ever seen is a deal when your partner is really, really committed.
Mm.
Because sometimes you make a deal, and then six months later or a year later, you have a change of management and a change of priorities, and suddenly you find out for a commercial deal that you don't have support for your product because they have other priorities. The good thing with Pierre Fabre is, A, they don't change management rapidly. You know, as you know, they are a very, very specific company from that, which is good in that situation-
Mm
... because the managers that are signing the deal are going to be the one that are going to pursue that. Second, they are really truly committed to patients. In fact, they have this true commitment to patient, which is very important when you want to launch a therapy that is potentially as transformative as tab-cel could be. And third, and very importantly, they're going to commit to it because that's their way of entering the U.S. market. So they cannot fail.
Mm.
They don't have the possibility to fail because that's too much importance for them to be successful in the U.S., because they're going to develop their U.S. activity on the back of tab-cel launch. So they are, I can tell you, fully committed. And the fourth aspect, that has nothing to do with Pierre Fabre, is to be able to support their effort. We've done a lot of work ourselves to prepare for the future launch of the product. You may remember that just a year ago, we were supposed to launch our tab-cel.
Mm-hmm.
So the awareness is very high. The product is already in the NCCN guidelines. The product is already listed in the DRG 018, which is the Medicare diagnostic-related group related to cell therapy, even though it's not yet approved in the U.S. So you have awareness, you have guidelines, you have the preparation for the coverage of the product. All that are going to be very important in a successful launch of the product in the U.S., once hopefully it gets approved as early as possible. We have a BTD status, so I think a filing in Q2 2024 means that one can reasonably-
Right
... hope to have a potential BLA approval in early 2025 or maybe, earlier. So there is about a year for Pierre Fabre to be ready, and I can tell you, they are already very active, preparing for that. Of course, we have to wait for the deal to close by the end of December for them to go full speed on that, but they're already very well prepared, and they know the product.
Mm.
So it's not like-
Sure
... you have a partner that has to discover the product, the disease, and how to manage a successful launch. They know it. They've done it already in Europe very successfully. So they're going to apply these success factors to the U.S. launch, and we're going to support them.
Well, maybe to that comment about their successful launch in Europe, do you have any expectation about when they might start reporting EU sales themselves? Do you have expectations about their transparency of the market, about the commercialization efforts they're doing, and how that would obviously relate to-
Yeah
... Atara's
There is already an important information out there about Europe, which is the listed price.
Mm-hmm.
Listed price today is the equivalent of EUR 585,000 per patient, which is roughly about $640,000 per patient, which is a very significant price that is fully aligned with the value that the product, tab-cel and value, is bringing to patient and healthcare system.
That means that the price in the U.S. will also be, we believe, in their strategy at Pierre Fabre, aligned with the value that the product is bringing to U.S. patient and to the healthcare system, with, of course, a difference in the potential for high price in the U.S., especially for such an ultra-rare disease, where it's not the number of patients that counts, it's the ability to make sure that these patients are being treated efficiently with such a product, and that the price reflects the value of the product for the patient, as per the clinical trial that have been published and presented already on that product.
So, pricing is already an information that is available for Europe, and that does impact on how one can evaluate what could be the price potential in the US. In terms of number of patients treated and, level of reimbursement and so on, Pierra Fabre is a private company. They are not communicating on that. But one might expect that progressively there will be more and more information, but I cannot, speak on their behalf, and they will have to decide what they want to communicate and when.
I suppose we'll see, we'll see royalty line on Atara's reporting before we see their full break.
That might be a possibility.
Got it. Just one question on the BLA submission. First of all, congrats on getting alignment. And I think back in September, again, you announced that you got an alignment with the FDA in terms of analytical comparability. And this essentially allows you to kind of pool the clinical trial data from different process versions. Did the FDA simply agree to allow this if additional ALLELE data were added, which presumably contains more patients on commercial version product? Or... And if so, how come the FDA didn't come to this agreement sooner?
The fact they didn't come sooner is, of course, something that we were not expecting, and we were disappointed.
Right.
As you know, it took some time to get to that point.
Sure.
I mean, we are a pioneer. We are bringing first-in-kind type of product, and we were the first one to come to the agency with an allogeneic T-cell therapy. So it took some time for them, and it's interesting and frustrating at the same time that they came out with a guidance for comparability of manufacturing process version for cell therapy in July of this year. And what is in the guidance is exactly what we've been telling them for many years. But anyway, it is what it is, and now we're moving forward in a very constructive way with the agency there.
This alignment on comparability between the clinical manufacturing process version and the commercial, intended commercial one, allows us to pull the data from the ALLELE study, and that's what we're doing right now because we needed to do a new data cut. So that allows us to have new data on that study based on this alignment on comparability. That will be the basis, hopefully, of the BLA submission. So we'll go the typical way for once we have the full data, go pre-BLA and then BLA, that we expect to be in Q2 of 2024.
It also allows us to look at all the supportive data in a different way, because we have a lot of patients have been treated in other type of studies, be it some EAP, Expanded Access Program, some compassionate use, and so on, with both the intended commercial product but also this particular clinical process version. So that's also going to be important because the level of supportive data is very significant for the product.
Let's make sure we spend some time talking about the deeper pipeline in CAR-T, where obviously those programs have been a little slower to develop while your focus has been on MS. Now that 188 isn't the focus anymore, remind us, where do you stand on the downstream CAR-T platform with the 1XX costimulatory domain and the other programs that had been maybe not paused, but developing a little more slowly?
Now, we're going full speed on this program. In 3219, which is our first allogeneic CAR-T, which is a CD19 CAR-T, that is, in fact, going to the clinic. We have already an IND cleared. We are opening site as we speak, so we expect to enroll patients very soon and then to have some early clinical data in the second half of 2024. So in just about a year time, or less, we should have the first clinical data. And these clinical data are very important because they are the one that hopefully will allow us to show how the potential of that particular, drug candidate to be best in class in that crowded space is going to deliver.
And what we've done is really to optimize the construct of this particular allogeneic CAR-T, to put together in one product three elements that each individually have been shown to be better than autologous CD19 CAR-T right now. One being the EBV-T cell as the backbone of the allogeneic CAR-Ts. We know how to manufacture, how to deliver allogeneic EBV-T cells, and we just inserted a CD19 chimeric antigen receptor on this backbone. And the level of scale-up, the level of expertise, the database we have, having treated more than 500 patients with this type of platform, is going to support us. But very importantly, this particular type of allogeneic CAR-T has already been tested by an academic team, and they have some new data that are coming at us from that team.
We have about 12 patients that have been treated with an allogeneic EBV CD19 CAR-T, and that is kind of proof of principle type of idea of what we're doing there. These data are showing, and the abstract is limited in terms of data, but in the abstract you can see that at 3 years, in these 12 patients treated with various B-cell malignancies, you have a survival of 85% at 3 years, which is quite significant.
Yeah.
And we believe it's linked with the ability of the EBV-T cells to be a good backbone for an allogeneic CAR-T, because you maintain the TCR, you don't gene edit the TCR, and that allows to have more functional persistence of the cells. So that one aspect, EBV-T cells. Second aspect, we have a new costimulatory domain called 1XX, invented by Michel Sadelain at Sloan Kettering, and that particular costimulatory domain has already been proven in the clinic, and that was data presented at ASH 2022, to lead to very high level of response and remission that are durable, good safety, with very limited number of cells, only 25 million cells used in that study that was supported by-...
done by a strong 1XX in an autologous CAR T, and that led to, which is about 10 times less than the number of cells that you have in an autologous CAR T. So an autologous CAR T has already proven that this particular costimulatory domain is by itself enabling lower dose, longer persistence of the cells and longer remission obtained in patients with the LBCL. Then the third aspect that we have optimized our manufacturing process to have more memory cells in the final product, which again has been proven independently by data coming from Novartis with YTB-323, showing at December 2022 ASH that you have, with very low dose, good safety, high level of response and durable remission.
So we're putting all of these elements, memory phenotype, 1XX, and EBV T-cells as part of the features of ATA3219. That's why we are very excited that we have potentially a compound, a drug candidate that could be best in class in bringing a higher level of response, longer durability of remission, excellent safety. That could really be a great progress in the field of lymphoma on top of going in autoimmune disease.
Now, you mentioned the MSKCC abstract coming at ASH, and I wanted to make sure we clarify. That's an EBV-directed T-cell, an allo CD19. What's the difference between that product and your ATA3219 product, which hasn't had its IND accepted yet?
It has a more traditional type of costimulatory domain, which is CD28, CD3 zeta, so it doesn't have the optimized one, 1XX, and it's not an optimized manufacturing process to have more memory cells.
More academic.
Yeah.
Got it. Well, Pascal, I think we're out of time, but before we— But before we totally wrap up here, I do want to give you the chance, Pascal, to just go through two more things that I wanted to get clarity on the timeline for. First, you announced expanding your CD19 program into autoimmune indications recently.
Mm-hmm.
Now that MS isn't on the table, are you still committed to autoimmune space, and do you have any more clarity on your path forward into that?
Oh, yes. We're working actively towards a potential IND next year on that product. And the reason we are very excited about that is we believe that the same rationale for being a potential best-in-class in lymphoma could very well apply to autoimmune disease. So we'll give-
Obviously, it's a very crowded space in lupus right now, but-
Yeah, but you don't have so many allogeneic-
No
... out there, and certainly I'm not aware yet of an IND for an allogeneic CD19 CAR T-
Mm-hmm
In that particular space of autoimmune disease. And we think that we have the potential to be really, up for the race, and at the same time we have a potential best-in-class on all the elements I was mentioning that will apply. On top of that, we are the only one with that experience in autoimmune disease. We have 125 patients treated with ATA188, so same type of allogeneic EBV T-cells without the CAR in that case, and with very good safety profile. We did not have any safety issues. So we have the, most extended safety database of any company in the field of autoimmune disease with, ATA188, and that's a silver lining of the EMBOLD study, that we can really leverage that to make sure that we have very safe product.
Safety is going to be very important in autoimmune disease on top of efficacy.
You've also got an ASH poster on a bispecific CAR-
Yes
- CD19 and CD20 at the same time. Obviously, we've seen an increase in the number of bispecific CARs or CARs, more, non-traditional architectures. What should we be looking for in that poster, to set you apart from the broader CD19 field?
The ability to have not only an activity on CD19 and CD20 type of target, independently, so it's a true dual CAR T that works on both. At the same time, we've compared that to an autologous benchmark, and we see better preclinical data, in animal models than the autologous benchmark. So we think again, that that has a potential to be best in class, and we think there is a lot of interest, especially in lymphoma, for addressing the antigen escape on CD19 CAR T to have an even better product with a very, very potent CD19, 20, dual CAR T.
Well, we look forward to seeing it. Excellent. Once again, thank you, Pascal. Very informative, and we'll wish you luck in your future path.
Thank you. Thank you very much.
Take care.