Q2 2019 Earnings Call
Operator: Good morning, ladies and gentlemen, and welcome to the Atara Biotherapeutics 2nd Quarter 2019 Financial Results Conference Call. At this time, all participants are in listen-only mode. Later, we will conduct a question and answer session, and instructions will follow at that time. If anyone should require assistance at any time, please press star then zero on your touchtone telephone. I would now like to turn the conference over to your host, Dr. John Craighead, Vice President of Vestal Relations and Corporate Communications. You may begin.
Biotherapeutics second quarter 2019 financial results conference call.
At this time, all participants are in listen only mode.
Later, we will conduct a question and answer session instructions will follow at that time.
If anyone should require assistance at any time please.
Sorry, then zero on your Touchtone telephone.
I would now like to turn the conference over to your host.
Dr., John <unk>, Vice President Investor Relations and corporate Communications you may begin.
Dr. John Craighead: Thank you, operator. Good morning, everyone, and welcome to the Atara second quarter 2019 financial results and corporate update conference call. Earlier this morning, we issued a press release providing an overview of the company's second quarter 2019 financial results and recent operational progress. This press release, as well as an updated investor presentation, are available in the Investor and Media section of atarabio.com. I'm joined on the call today by Dr. Pascal Touchon, President and Chief Executive Officer, Upal Kopekar, Chief Financial Officer, Dr. Chris Hack, Chief Scientific Officer, and Dr. A.J. Joshi, Chief Medical Officer.
Thank you operator, good morning, everyone and welcome to the Atari second quarter 2019 financial results and corporate update conference call.
Earlier. This morning, we issued a press release, providing an overview of the company's second quarter 2019 financial results and recent operational progress.
This press release as well as an updated investor presentation are available in the Investor and media section of a tar bio dot com.
I'm joined on the call today by Dr., Pascale to Sean President and Chief Executive Officer.
Called copy Carr, Chief Financial Officer, Dr., Chris had Chief Scientific Officer, and Dr., AJ Joshi, Chief Medical Officer.
Dr. John Craighead: We'll begin with prepared comments from Pascal and then open the call for your questions. I'd like to remind listeners that the company's management will be making forward-looking statements. Actual results could differ materially from those stated or implied by our forward-looking statements due to the risks and uncertainties associated with the company's business. These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's press release and the company's SEC filing. These statements are made as of today's date, and the company undertakes no obligation to update these statements. Now, I would like to turn the call over to Atara's President and Chief Executive Officer, Pascal Touchon. Pascal?
We'll begin with prepared comments from Pascal and then open the call for your questions.
I'd like to remind listeners that the company's management will be making forward looking statements actual results could differ materially from those stated or implied by our forward looking statements due to the risks and uncertainties associated with the company's business.
These forward looking statements are qualified in their entirety by the cautionary statements contained in today's press release and the Companys SEC filings.
These statements are made as of today's date and the company undertakes no obligation to update these statements.
Now I would like to turn the call over to retire as President and Chief Executive Officer has called to shown ASCO.
Pascal Touchon: Thank you, John, and thank you, everyone, for joining us this morning. Today is my first conference call at the Chief Executive Office of Atara Biotherapeutics. It has only been a few weeks since I joined Atara in late June, but I have already been impressed by the expertise and commitment of our teams in developing T-cell immunotherapies to transform the lives of patients with serious diseases. Indeed, I am confident that we are now in a strong position to execute on our commitment and create value for patients, physicians, and shareholders in multiple sclerosis and next-generation CAR T programs. What I would like to do today is first provide a brief overview of my background and tell you why I'm so excited about Atara's program.
Thank you John and thank you everyone for joining us this morning.
Today is my first conference call or the Chief Executive officer of antibiotics.
It has only been a few weeks since I joined I'll start by late June , but I've already been impressed by the expertise and commitment of all teams in developing T cell immunotherapies to transform the lives of patients we still use diseases.
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I'm confident that we are now in a position to execute on our commitment and create value for patients physicians and shareholders. The coastal topcell multiple levels is a next generation called <unk>.
Whether we like to do today is first provide a brief overview on my background and said you why I'm. So excited about that there was potential.
Pascal Touchon: I joined Novartis, where I served as Global Head, Cell and Gene, and member of the Oncology Executive Committee. In this role, my responsibilities included regulatory approval, pricing, and reimbursement, and the global launch of Chimraya, the first ever CAR T approved globally in two indications. I was also leading Novartis' Global CAR-T strategy, clinical development, manufacturing, and technical operations, and the financial performance of the oncology cell engine activity. Prior to that role, I was Global Head of Strategy, Business Development, and Licensing Oncology at Novartis. And, beforehand, Executive Vice President at Servier, where I initiated the partnership with Selectives and Pfizer on allogeneic cartilage.
I jumped from Novartis, where I served as global head set in gene and member of the O'connor She Executive Committee.
This whole my responsibilities included the thinking that that we approval pricing and reimbursement and global launch of Chemo Io.
The first of the call to your <unk> globally in two indications.
I was also reading about these global companies try to GE clinical development manufacturing and technical operations and the financial performance of the color. She said engine activities.
Prior to that whole <unk> global head strategy business development and licensing going quarter Gs novelty.
And people hand, executive Vice President of that Sobi, we initiated the partnership selective and Pfizer on others any color.
I believe my experience makes me uniquely suited to carry out our transmission to transform the lives of patients we still use disease.
Pascal Touchon: I believe my experience makes me uniquely suited to carry out Atara's mission to transform the lives of patients with serious disease. Having worked over the last five years in the field of autologous CAR-T, as well as first-generation gene-edited allogenic CAR-T, I believe cell therapy is the next therapeutic frontier in oncology and immunology, following its transformative impact on patients with B-cell malignancy. What excites me most about Atara is that its T-cell immunotherapy platform could have several important advantages over both autologous CAR T-therapies and gene-edited allogeneic CAR T-therapies. Indeed, allogenic T-cell therapies may be immunoprivileged.
I think work over the last five years in the feel of what sort of goes call tea as well as first innovation Gina DTA dilution he called T.
I believe so Tim Coffey is a next topic from tier clergy and immunology following its transformative impact on patients with B cell malignancies.
What excites me most about entourage that its T cell immunotherapy platform could that all important advantages over both autologous coffee to hobbies, and Gina didn't lose any call Peter hobbies. Indeed.
Well I don't see any T cell therapies may be immuno privilege, they obtain from healthy donors and do not require it should it its hands maintaining population and persistence advantageous.
Pascal Touchon: They are obtained from healthy donors and do not require HLA edits, hence maintaining proliferation and persistence advantages as they are matched for each patient for more inventory and available to patients within days. The treatment is more similar to prescribing and administering a biologic than the complex process of today's autologous CAR T-cell therapy, or Epstein-Barr virus, or EBV-specific platforms can lead to therapies directed at EBV-associated diseases, like TAP cell and ATA188, as well as allogenic artery therapies. The platform is already in clinical development for EBV-associated post-transplant lymphoproliferative disease, or PTLD, and other EBV-related diseases, including nasopharyngeal carcinoma and multiple sclerosis. We are also developing next-generation CAR-T immunotherapies for both solid tumors and hematological cancers.
As they are much for each patient for more inventory and the variable to patient we didn't days.
The treatment is more female prescribing and administering the biologic than the complex process of today's what sort of goes car T cell therapies.
Oh extend by virus or NPV specific platform can lead to TRP directed at BB associated diseases, like Topcell and 80 188.
As well as I do is any coffee to hobbies.
Our platform is already in clinical development, what would be the associated post transplant people put a few active disease or B T. L D.
And although you'd be associated disease, including that's with potential casino HMA and multiple securities.
We also developing next generation call teammates therapies for both solid tumors and Hematological cancer.
Pascal Touchon: Our main priority here is our mesothelin-targeted next-generation CAR T candidate, initially ATA2271, an autologous version, to rapidly achieve clinical proof-of-concept, followed by the halogenic version, with our unique innovative platform and our own state-of-the-art manufacturing facility, ATOM. We are creating a leadership position in T-cell immunotherapy, developing truly transformative therapies for durable treatment effects, I would now like to discuss our strategic priorities in greater detail, starting with TAPSEL.
Our main priority here is on missiles that integrated next generation coffee candidate. We've initially 88 20 271, no. Triggers addition to appeal the achieved clinical proof of concept.
Followed by the allergenic fashion.
We have a unique innovative platform and state of the art manufacturing facility at them.
We are creating a leadership position in T cell immunotherapy.
Developing truly transformative to appease for although treatment effect and I feel fortunate to lead such an innovative company.
I would like now to discuss our strategic priorities in greater detail starting with upset.
Pascal Touchon: As recently announced, based on discussions with the FDA, we now plan to initiate the first TAPSED regulatory submission for relapsed refractory EBV-positive PTLD during the second half of 2020. We're also in active discussions with the EMA to align on regulatory requirements and determine tap cell submission timing in Europe. The FDA has agreed to combine our two ongoing TAP cell clinical studies into a single study called ALEV. Both bone marrow and solid organ transplant patients are included, with target enrollment of 33 patients in each cohort. The primary endpoint remains objective responsibility.
As recently announced based on discussions with the FDA, We know plan to initiate first in the U.S. a tough set of regulatory submission for relapse could fluctuate NPV positive PTSD.
During the second half of 2020.
We also in active discussions with the me two line on the regulatory requirements and that I mean, TBSA submission timing in Europe .
The FDA has agreed to combine two ongoing subset of clinical studies into a single study called I live.
Both bone marrow and solid organ transplant patients included we stuck out on the whole month of 53 patients in each cohort.
The primary endpoint remains objective response rate.
Pascal Touchon: We also plan to conduct an interim analysis prior to initiating the BLA submission. Now, let's discuss the disease burden and market characteristics of this aggressive, often deadly cancer, affecting a limited but meaningful number of allogenic stem cell and solid organ transplant patients. There are no approved therapies for PTLD, and this disease disproportionately affects younger patients with a median age of under 40 compared to about 65 for all lymphomas.
We also plan to conduct an interim analyzes prior to initiating BLE submission.
Now, let's discuss the disease burden and look at characteristics of this aggressive often deadly cancer affecting limited, but meaningful number of allergenic stem cell and solid organ transplant patients.
There are no approved therapies will be TLD.
And this disease disproportionately affects younger patients with a median age of under 40 compared to about 65 for all lymphoma.
Pascal Touchon: Unfortunately, the expected survival after failure of the standard first-line therapy of rituximab with or without chemotherapy is between 3 to 12 months in a case of SOT. In HCT, survival after rituximab failure is about 1 month. In the U.S., we estimate that there are several hundred patients with EBV-positive PTLD who have failed Rituximab with or without care. This is a typical ultra-rare disease with significant unmet medical need.
Unfortunately, the expected survival after failure of the standard first line therapy of Rituximab with or without chemotherapy.
It's between three to 12 months in the case of SRT.
Their city, so if I'm going to turn it took him a failure is about one month.
In the U.S., we estimate that there are several hundreds patient weve NPV positive PTSD, where failed rituximab, we've all without chemo.
This is a typical detroit rare disease with significant unmet medical need.
Given the severe disease burden of his condition. We believe topcell has the opportunity to deliver a compelling value proposition to patients and health systems.
Pascal Touchon: Given the severe disease burden of this condition, we believe TAP cell has the opportunity to deliver a compelling value proposition to patients and health systems. First off, TAPCELL has demonstrated in both Phase II and EAP studies, objective response rates between 50% and 80%, and Role Survival in Responders at 2 Years of over 80% in both HCT and SOT. Secondly, in these studies, we have observed few treatment-related serious adverse events for TAP cell in PTLD patients, with no observed cytokinetic syndrome or treatment-related mortality. In addition, TAP cell has a low administration burden with no pre-treatment required, a brief IV push administration, and only 2-hour post-administration monitoring in clinical trials. Additionally, our off-the-shelf T-cell order, match, and supply management system is designed to deliver the treatment within three days.
First off the upset as demonstrated in both phase two and E. P studies that it has a high and durable treatment effect with objective response rates between 50% and 83%.
And overall survival responders or to use of over 80% in both electricity and esselte.
Secondly in these studies, we have observed few treatment related serious adverse events for topcell in P.T. or the patient.
With no observed cytokine release syndrome or treatment related mortality.
In addition, topcell as a new administration building with no pretreatment, requiring a brief Ivy Bush administration and only two hour post administration monitoring in clinical trials.
Additionally.
Well the shelf T cell older much and supply management system is designed to deliver the treatment we didn't free days.
Beyond the significant business scale can be TLD, we excited about the potential of Topcell as an ultra rare disease pipeline in a product.
Pascal Touchon: Beyond the significant business case in PTLD, we're excited about the potential of TAP cell as an ultra-rare disease pipeline in a product. TAP cell is in ongoing phase 2 clinical development for patients with platinum-pretreated metastatic nasopharyngeal carcinoma in combination with pembrolizumab. This is an EBV-associated cancer with limited overall survival and therapeutic options. Incidence is high in East Asia, but even in the US and Europe, there are hundreds of patients in need of better therapeutic options. Our third TAPSEL opportunity is based on a multi-cohort phase 2 study that we expect to start in the second half of 2020. We plan to enroll patients with other EBV-related cancers with poor prognosis, for which we have some clinical experience from previous studies.
That said it is ongoing phase two clinical development for patients with platinum pretreated metastatic Nettwophone Angelika cinema in combination with Pembrolizumab.
This is an MPV associated cancer with limited overall survival and therapeutic options.
Incidence is high in East Asia.
But even in the U.S. and you hope there are hundreds of patients in need of better topic options.
Our first upset opportunity is based on the multi called phase two study that we expect to start in the second half of 2020.
We plan to enroll patients are being older TBV related concerns with the prognosis.
And for which we have some clinical experience from previous studies.
Pascal Touchon: This study could support potential registrational opportunities. Hence, the same product may progressively treat more and more patients in multiple ultra-rare severe diseases. Turning now to the MS Program.
This study could support potential visit touched another opportunities, hence the same product may progressively tweets more and more patients in multiple the tribe LCD or disease.
Turning now to MSP program.
Pascal Touchon: We are also leveraging our innovative platform in developing the first EBV-specific T-cell immunotherapy in autoimmune diseases. The Off-the-shelf Allogeneic ATA 188 Program for Multiple Sclerosis is an ongoing phase one clinical study for patients with progressive MS. In late June, we presented the initial safety data of the first three cohorts for ATA188 at the 5th Congress of the European Academy of Neurology. We saw no dose-limiting toxicity and no treatment-related treatment emergent adverse events at grade 3 or higher. We are dosing the fourth and final plant cohort now, and expect to enroll a total of 24 to 30 patients in the study. The safety results also add to the overall profile of our allogenic T-cell platform, with favorable tolerability in non-immunocompromised MS patients, as well as immunocompromised PTLD patients. Although designed to evaluate safety and tolerability in order to determine a recommended phase two dose, the study also includes clinical, efficacy, secondary, and..., including a number of established measures of physical, neurological, and cognitive health.
We also leveraging here or innovative platform in developing the first NPV specific T cell immunotherapy in autoimmune disease.
Of the shelf Allergenic 88, 188 program for multiple sclerosis is ongoing phase one clinical study for patients with progressive Emmis.
In late June we presented the initial safety data or the first FICO score for 80 818.
The fees Congress that you open academy of neurology.
We saw no dose limiting toxicity.
And no treatment related treatment emergent adverse event at grade three or higher.
We are dosing the fourth and final plan called now and expect to end all the total of 24 to 30 patients in the study.
BB safety results also out to the overall profile of Allosure need T cell platform.
Well first of all to the ability in non immunocompromised mess patient as well as immuno compromised gtld patients.
Although design to evaluate safety and Tolerability in order to determine the recommended phase two dose. The study also includes clinical efficacy secondary endpoint, including a number of establish msrs or physical neurological and cognitive functions.
Pascal Touchon: We expect to report initial results on some of these clinical secondary endpoints at ECTRIMS in September, as well as additional safety results. On the basis of the Phase 1a data, we plan to proceed into the randomized placebo-controlled portion of the study. In parallel, we plan to initiate a randomized phase 2 study of ATA190, an autologous version of ATA188, during the second half of this year to compare the efficacy and safety profile of these two EBV-specific cell therapies. Last but not least, I would like to provide a brief overview of our next-gen CAR-T portfolio. We had a number of recent presentations at both AACR and ASCO earlier this year. What was most exciting for us were the two presentations by our MSK collaborators on a phase one clinical study with their mesothelin-targeted CAR T immunotherapy in patients with advanced mesothelioma.
We expect to report initial results on some of these clinical secondary endpoint extremes in September .
As well as additional safety results.
On the basis of the phase one eight data we plan to proceed into that undermines placebo controlled portion of the study.
In parallel we plan to initiate a randomized phase two study of AG 190, and that sort of reservation of AG. One eight during the second half of this year to compare the efficacy and safety profile of just to give you the specific cell therapies.
Last but not least I would like to provide a brief overview of full nexgen coffee portfolio.
We had a number of recent presentation that both AC all an ASCO earlier this year.
What's most exciting for us where the two presentations by your MSK Callable ages on a phase one clinical study with a mitigated in targeted car T therapy in patients with advanced missile tell you on that.
Pascal Touchon: Mesothelin is highly expressed on cells in aggressive solute tumors, including triple negative breast cancer, ovarian, pancreatic, and non-small cell lung cancer, as well as Mesothelioma. In the latest ASCO presentation, a subset of 16 patients with malignant mesothelioma followed for a minimum of three months and receiving MSK mesocorti together with anti-PD-1 and lymphodepleting chemotherapy showed a 12-month overall survival rate of 80% and an objective response rate of 63.
He's hoteling is highly expressed on sales in aggressive solid tumors.
Including people negative breast cancer, ovarian pancreatic and non small cell lung cancers as well as military on that.
The latest ASCO presentation subset of 16 patients with malignant mesothelioma, followed for a minimum of three months and receiving MSK mutual called T. Together with anti PD, one and if were depleting chemotherapy.
Sure the 12 months overall survival rate of 80%.
And an objective response rate of 63%.
Pascal Touchon: We reviewed these data as highly encouraged and have prioritized our mesothelin-targeted next-generation CAR T program, ATA2271, with a plan, in collaboration with MSK, to submit an IND for this program in 2020. Before opening the call to your questions, I would like to comment on a recent public offer. In July, we completed an underwritten public offering of $150 million for the issuance of 6.9 million shares of Commons Bank and 2.5 million pre-funded works. The successful offering transcends financial positions and funds planned operations into 2021, for key milestones next year, including initiating the TAP cell BLA submission and next generation mesothelene CAR-T INs. I would like now to turn the call back over to the operator so we can go ahead and take your questions. Operator?
We viewed these does highly encouraging and prioritize our missiles that integrated next generation car T program 88, 20, 271, we have a plan in collaboration with MSK to submit an I.N.D. for this program in 2020.
Before opening the call to your questions I would like to comment on our recent public offering.
In July we completed an underwritten public offering of $150 million for the issuance of 6.9 million shares of common stock.
And 2.9 million pre funded warrants.
Be successful offerings, Translarna financial positions and phones plant operation into 2021.
For key milestone next year.
Including initiating the Topcell BLE submission and next generation military in coffee.
I would like now to turn the call back over to the operator. So we can go ahead and take your questions operator.
Operator: Thank you. Ladies and gentlemen, if you have a question at this time, please press star then 1 on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. To prevent any background noise, we ask that you mute your line once your question has been stated. And as a reminder, ladies and gentlemen, that is star, then one for questions. And our first question comes from Anupam Rama from JP Morgan. Your line is now open. Good morning, all. This is Tessa filling in for Anupam this morning.
Thank you ladies and gentlemen, if you have a question at this time. Please press Star then one on your Touchtone telephone. If your question has been answered or you wish or leave yourself from the queue. Please press the pound key to prevent any background noise. We ask that you mute. Your line Whats. Your question has been stated.
As a reminder, ladies and gentlemen that is star then one first question.
And our first question comes from Pam Rama from JP Morgan. Your line is now open.
Good morning.
So following on on upon this morning. Thank you for taking my questions Daniel Pascal.
Tessa: Thank you for taking our questions, and it's very nice to meet you, Pascal. So my question is on MS. With first efficacy data for ATA 188 coming in extremes in the coming weeks, can you walk us through the scope of data here and what the points of differentiation are that we should be looking for in the phase one readout? Specifically, what are your expectations in the context of the disease for the key secondary endpoints that you will be outlining for us? Thanks so much, guys.
So my question is on Omar.
Well first off we could see data.
One.
How about ASP trends in the coming week.
Thank you operator and scope of data here on what's the point of differentiation are that we should be looking for nothing wine readout on specifically what are your expectations in the context of the disease for the key secondary endpoints that you will be I think you will be outlined flat. Thanks, so much guys.
Thank you very much for your question I will ask Agee your sheet to start answering that question.
Pascal Touchon: Thank you very much for your question. I will ask Eiji Yoshi to start answering that question.
Sure. Thank you Pascal.
Dr. A.J. Joshi: Sure, thank you, Pascal. So just to put things in perspective, this is, of course, a study that is focusing on the progressive MS population. And really, the focus in progressive MS is to delay deterioration. That's really the end goal.
So.
Just to put things in perspective. This is of course, a study that is focusing on the progressive emmis population and really the focus in progressive en masse eased to delay deterioration. That's really the end goal now in order to assess that particular parameter.
Dr. A.J. Joshi: Now, in order to assess that particular parameter, most parameters actually need about one to two years of assessment to really prove anything. So our challenge in setting this study up was, how do we get an earlier read than a couple of years? Because, as you know, these data are going to be around six months of data on a couple of cohorts of patients. We work with thought leaders to essentially define multiple parameters that are well-defined, clinically meaningful, and essentially assess those parameters across multiple time points. What you're looking for across those parameters is basically similar change across multiple parameters at a specific time point. And I should step back for just a second. So those parameters assess both clinical function, physical function, and cognitive function.
Most most brand was actually you need about one to two years of assessment to really prove anything so our challenge and in setting. This study up what how do we get an earlier read then a couple of years because as you know these data are going to be around six months.
Data on on a couple of cohorts of patients.
We worked with thought leaders to essentially define multiple parameters that are in a well defined clinically meaningful and.
Well and essentially assess those parameters across multiple time points, what you're looking for cross those parameters is.
Basically similar change across multiple multiple rounds at a specific time point.
And with that whatever and those per and I should step back for just a second so those parameters assessed both clinical function physical function condon function, it's a variety of MMS issues.
Dr. A.J. Joshi: It's a variety of MS issues. If you see a similar movement in multiple parameters at a specific time point, that gives you confidence that there is a real signal there at an earlier time point than that one to two years that I was talking about. So success for us here would look like movement across multiple parameters at the time point that we describe when the data are presented.
If you see a similar movement in multiple parameters a specific time point that gives you confidence that there is a real signal there at an earlier time point and that one to two years that I was talking about so success for us here would look like movement across multiple parameters at the time points that we described when the data are presented.
Pascal Touchon: And just to add that egg trims are an important step in building up evidence in terms of safety and efficacy for ATE 188. So then we can move to, at a later stage, when we have completed this Phase 1a study, into Phase 1b. We expect to present initial efficacy results from the lower-dose cohort, as well as additional safety results from the higher-dose cohort. The fourth and final planned cohort is almost fully enrolled, but we do not expect to have efficacy data available at the time for the fourth cohort. I have had extremes in September.
And just to add on that of an extreme is an important step in building up evidence in terms of safety and efficacy for AG. One a date. So then we can move to at the later stage. When we have completed this phase one study into phase one b.
We expect to present initial efficacy results from the lower dose cohort as well as additional safety result from the higher dose called the fourth and final Plendil School is almost fully enrolled but we do not expect to secrecy that are available at the time on the fourth called extremes in September .
Pascal Touchon: And this is just, as I say, a step, and we plan, of course, to progressively present additional data at future scientific congresses as data continue to mature. Other questions? Okay. No. No.
And this is just as I say, a step and we plan of course to progressively present additional data at future scientific Congress has that continued to mature.
Other questions.
No that's great. Thank you very much I appreciate the color.
Chris: No, that's great. Thank you very much. I appreciate the call. Thank you. And our next question comes from John Neumann from Kennecore, Genoa. Your line is now open. Hi, this is Chris on behalf of John.
Thank you and our next question comes from John Newman from Canaccord Genuity. Your line is now open.
Hi, This is Chris on for John Thanks for taking my question. We're just wondering.
Pascal Touchon: Thanks for taking my question. We were just wondering, do you have any incremental color for us for how fast new clinical sites can be opened? And if you have any details, additional details, on what you're doing besides that to help enrollment?
Do you have any incremental color for us.
Or how fast new clinical sites can be opened and if you have any details additional details on what you're doing besides that to help enrollment.
Pascal Touchon: Thank you for your question. I think, Eiji, you might want to start answering that question. Sure.
Thank you for your question I think AG you might want to start answering that question sure.
Dr. A.J. Joshi: So in terms of speed of getting sites up and running, for a PTLD, you're really looking at larger-scale academic centers, so you typically have a little bit of a longer lead time to open those sites. The reality for us is, though, that we've been building towards this for a while, so much of that lead time is already built in. So we're starting to really see the benefits of getting those sites coming in. Because, as you know, academic centers often take anywhere between six and nine months to really get up and running. But again, we've done a lot of that lead-in already.
So in terms of speed of.
Getting sites up and running.
For Pts Lee you're really looking at.
Larger scale academic centers. So those you typically have a little bit of a longer lead time to open those sites.
The reality for US is though that we've been building towards this for a while so much of that lead time has already built in so were starting to really see the benefits of getting those sites coming in because as you know academic centers often takes anywhere between six to nine months to really get up and running.
But again, we've done a lot of that lead lead and already so we do expect to open up several additional sites in the US later this year.
Pascal Touchon: So we do expect to open several additional sites in the US later this year. And, in addition, we are opening up additional geographies because we recently got a no objection letter from Health Canada. So we'll be opening up our first Canadian site later this year, and then looking forward to opening up European sites next year.
In addition, we are opening up additional geographies because we just got we recently got a no objection letter from health, Canada. So we'll be opening up our first Canadian site later this year.
And then looking forward to opening up the European sites next year.
In terms of any additional.
Pascal Touchon: In terms of any additional work that we're doing, much of the focus for us now is optimizing recruitment at the existing centers. And this has really been, we've been leveraging a variety of resources, including medical science liaisons and other activities that, you know, I implemented in the past, in my previous lives, in ultra-rare indications. Multiple Activities Reviewed in Elementary Education So that way... So I think, again, we've got to, let me step back. Multiple activities from ultra-rare indications that have been used in the past, including MSLs and including a variety of outreach to both the patient advocacy community as well as established physician societies.
Work that were doing much of the focus for US now is optimizing recruitment at the existing centers and this has been really we've we've been leveraging a variety of resources, including medical science liaisons and and other activities that you know I implemented in the past in previous lives in ultra rare indications and so.
Multiple factors, we felt very indications are that way.
So I think again, we've got we let me step back.
Multiple activities from her hair indications that have been used in the past, including myself and including a variety of outreach to both is the patient advocacy community as well as.
The established physician societies.
Pascal Touchon: And I have to say that one of my first priorities when I joined was to look in detail at the way clinical operations were run to make sure that we optimized our chance to accelerate recruitment in that very important study. I have been satisfied by what I've seen, and that's why I am confident regarding the guidance we've given, which is, of course, linked with recruitment in this study.
And I have to say that one of my first priority. When I joined was to look in details the way clinical operation where run to make sure that we optimize all trends to accelerate for equipment in that very important study.
I've been satisfied by what I've seen and that's why I'm confident regarding the guidance, we've given which is of course linked with the enrollment in this study.
Pascal Touchon: What we should say, as well, is that some of the challenges that we faced here are linked with the disease itself. It's an ultra-rare disease, rapidly progressing, where sometimes the patient cannot wait for the administrative burden of being recorded in a study. And that's why we use our EAP program, or SPUs as well, to be able to treat these patients. Additionally, we have to recognize that there have been a number of competitive trials, either directed at PTLD or basket protocol trials in this space, that have been started over the last few years, and I think there are about 12 clinical trials right now in that space. So that's also something to take into account when enrolling, but it also tells a lot about the attractiveness of that particular medical need in terms of new, innovative therapies.
What we should say as well that.
Some of the challenges that we faced here are linked with the disease itself. Its a notorious disease, hopefully progressing where sometimes the patient cannot wait for the administrative burden of being recruited into the study and that's why we use Ingo EAP program or SP use as well to be able to treat these patients.
Additionally, we have to recognize that they have been a number of competitive trials either directed at P.T. audio basket political trials in this space that I've been started over the last two years and I think they are about 12 clinical trials right now in that space. So that's also something to take into account into enrollment, but it also tells a lot about the attractiveness of that particular, all medical need that in terms of new innovative therapies.
Pascal Touchon: Got it. Thank you very much. That was very helpful.
Got it. Thank you very much that was very helpful.
Operator: Thank you. All the best. Thank you. And our next question comes from Salim Saeed from Mizzou. Your line is now open. Hey guys, thanks so much and welcome, Pascal.
Thank you and our net.
Thank you and our next question comes from drilling side from Mizuho. Your line is now open.
Yeah, Hey, guys. Thanks, so much and welcome Pascal.
Salveen Jaswal Richter: A few from me, if that's okay. One on the MS program. Curious how you guys are thinking about the risk that these T cells are going to be in MS patients, so they will have immune systems. So when you're looking at efficacy, how do you guys think about the risk here that you're giving enough T cells so that they last, right? I know you can compare it to PTLD, but that was an immune system knockout patient. How are you guys thinking about here that these T-cells will be able to last long enough to provide the efficacy that you're looking for? Number two, just on alloprogram versus autoprogram, 188 versus 190, if there's any theoretical risk here of one potentially getting past the blood-brain barrier more than the other, or if there's a mechanism in place that the human body essentially would reject 188 because it's not perfectly HLA-matched. And then the last question is just, can you provide more interim details on the Tab-Cell program How many patients do you need for the interim, and what would the ORR hurdle be? Thank you.
A few from me if I if that's okay. One on the on Dms program.
Curious how you guys are thinking about the risks that you V T cells.
They're going to be there going to be in MF patients to the you know they will have immune system. So when you're looking at efficacy like how do you guys think about the risk here that.
You're giving it enough T cells to the the last spring I know I know you can compare to Peafiel d., but that was in I mean, not immune system knockout patient. How do you. How are you guys thinking about here that these T cells.
We'll be able to laugh enough to provide the efficacy that you're looking for.
Number two.
Just on eight hour.
Our program versus auto program, you'd want to de versus when 90.
If there's any theoretical risk here of one potentially getting past the blood brain barrier more than the other or or if there is a mechanism in place.
That HM that's the human body, but essentially would Jack one indeed, because it's not perfectly easily matched.
And then the last question is just them can you provide more interim details on the on the types of program what how many patients do you need for the interim and what would be for our hurdle be thank you.
Thank you very much.
Dr. A.J. Joshi: Thank you very much. Eiji, do you want to start?
Hey, Jay do you want to start.
Dr. A.J. Joshi: So, in terms of the persistence question, you know, we actually have experience with EBV-directed T-cells, EBV-targeted T-cells in an immunocompetent population with a nasopharyngeal carcinoma program. And as you know, in the Phase I studies at MSK, we had about a 20 percent response rate in essentially an immunocompetent population. So, we should be very well able to apply that concept to what's happening in MS because you've got a similar scenario, an immunocompetent population using allogeneic T-cells. So, from that perspective, I think there's relative confidence that we should have enough persistence to get an efficacy signal and maintain efficacy appropriately.
Sure so in terms of.
The the persistence question.
We have actually experience with.
He be directed T cells, the V. chary the T cells in Immunocompetent population with the needs of Brinjal carcinoma program. So as you know in the phase one studies that MSK, we had about 20% response rate and essentially in Immunocompetent population. So you should we should be very well able to apply that concept to what's happening in M.S., because you've got a similar scenario imminent competent population using allogeneic T cells.
So so from that perspective, I think there is relative confidence that we should have enough persistence to get an efficacy signal and maintain efficacy properly.
You want.
Dr. A.J. Joshi: Do you want? Please, do you want?
Pascal Touchon: I want to comment on the blood brain barrier.
Chris do you want to comment on the blood brain barrier passage sure I think here. The tactile experience is also a good.
Pascal Touchon: [inaudible]
Dr. A.J. Joshi: Sure. I think here the TAB cell experience is also a good guide in that our experience is that EBV-specific T-cells have the ability to traffic. They cross the blood-brain barrier, and in our Phase II experience, we have observed several patients who've had CNS-located PTLD to have objective responses. We expect that to continue as well in the setting of MS. And in previous American Society of Hematology presentations, we've presented on the activity of the antiviral T-cell platform with essentially the same response rate observed in patients with CNS disease compared to those whose disease presented systemically.
Guide in that our experience is that the NPV specific T cells.
We have the ability to traffic they cross the blood brain barrier and in our.
Phase two experience we have observed several patients who've had CNS located p. TLD.
To have objective responses.
We expect that to continue as well in the setting of MF.
And.
In previous American Society of Hematology presentations, we presented on the activity of the antiviral T cell platform with essentially the same response rate observed in patients with CNS disease compared to those whose disease presented.
Pascal Touchon: and on the OTO and ALO programs in MS.
Systemically.
Pascal Touchon: And I pause; would you mind repeating the specific question on autoverisability?
And on the auto and auto program in M.S. agent.
And I thought you would you would you mind repeating the specific question on auto visitors.
Salveen Jaswal Richter: Oh, no; I think you answered that question. I think the last question was just about the interim details, how many patients and what the ORR hurdle would be.
Oh no. Thank you I think you answered that question.
And then last question is just around the interim Cinram detailed.
How many patients and what the or or.
Hurdle would be.
Sure. So as you might imagine within in anytime you're doing an interim analysis.
Dr. A.J. Joshi: Sure, so as you might imagine, anytime you're doing an interim analysis, and you're working on that with authorities.
And you're working on that with authorities, you're going to have to show substantial.
Dr. A.J. Joshi: The current RR, when you look at the total patient population of 33 patients, the null hypothesis is 20%, so our ORR would have to be 37% to meet the statistical hurdle. And, as you might imagine, any interim analysis that we do would have to have a higher ORR statistical hurdle to meet the requirement. OK.
Benefit and you know and it with some adequate level of certainty which is essentially our.
The.
Our current or our when you look at the total patient population 33 patients.
The now hypothesis, 20%, so our our would have to be 37% to.
To meet the statistical hurdle and as you might imagine any interim analysis that we do would have to have a higher.
Our our Texas, So statistical hurdle.
To meet the requirement.
Okay, great. Thanks, Thanks, so much guys. Thank you.
Dr. A.J. Joshi: Okay, great. Thanks so much, guys. Thank you. And our next question comes from Matt Phillips from William and Mary Linus Outlets. Thanks for taking my questions, and Pascal, welcome. It's good to have you.
Thank you and our next question comes from Matt.
From William Blair. Your line is now open.
Hi, Thanks for taking my questions and Tesco welcome good to have you.
You guys mentioned in the press release, the 34 sites are now enrolling in a pivotal to upsell trial. So wondering how many of those.
Matt Phillips: You guys mentioned in the press release that 34 sites are now enrolling in the Pivotal Tab-Cell Trials. I'm wondering how many of those can enroll both solid transplant and bone marrow transplant patients. Should have been just one or the other when it was two separate studies. There were not, I mean a lot of them; some of them were overlapping, some of them weren't.
They enroll both solid transplant and bone marrow transplant patients.
Suppose named US one of the other when it was two separate studies.
There was not I mean, a lot of them some of them are overlapping some of the words and then also just when can we get some disclosures on the enrollment of the trial.
Matt Phillips: And also, just when can we get some disclosures on the enrollment of the trial? Do we have to wait until you guys say that you've... Submitted a VLA, or, you know, will we get some info? I mean, I think disclosure on how it's going would be important given how long it's taken.
Do we have to wait until you guys say that you.
Submitted via La.
Will we get some info and then I think.
Some disclosure on how it's going well the important given the how long it's taken.
Pascal Touchon: Thank you. Thank you for your questions and for your welcome remark there. So on the number of sites, we say 34 that are unique sites. But, of course, some of them are doing both.
Thank you. Thank you for your questions and for your welcome remark there. So on the number of sites, we say 54.
That all unique sites, but of course some of them are doing both so we have about 23 sites for tier one and 27 sites for fuel to that.
Pascal Touchon: So we have about 23 sites for 301 and 27 sites for 302 that are open for enrollment right now. And I think, as we said, we are going to increase this number of sites in the US and also, with the recent good news from Canada, open by the end of the year in Canada before moving to Europe following the CTA's mission there. In terms of your questions on the communication related to the enrollment, in such an open study, we have decided not to communicate the number of patients being enrolled. And we will communicate on that at the time of the initiation of the submission when we go into that phase of the development of the product in that country. What is important to have in mind is that we want to recruit the full population in both cohorts, even though we will do the interim analysis on a smaller number of patients.
Open the open for enrollment right now and I think we as we say we are.
Moving to increase number of sites in the US and also with the recent good news from Canada open by the end of the year kind of insight before moving to you all.
Following the Cts emission debt.
In terms of the.
Your questions on the communication related to the enrollment in such an open study we have decided not to communicate on the number of patients being on hold and we will communicate on that at the time of the initiation to submission.
When we go into that phase of the development of the product. There what is important to have in mind is that we want to recruit the full population in both cohorts and even though we will do the interim analyses on a smaller number of patients.
Yes. Thank you.
Pascal Touchon: Yes, thank you.
And just two other than that I mean, the just to be clear we plan to communicate on the guidance. So when we say we will initiate a b a day submission in second half of 2020, we plan to communicate on that initiation at that time.
Pascal Touchon: And just to add to that, I mean, just to be clear, we plan to communicate our guidance. So when we say we will initiate BLA submissions in the second half of 2020, we plan to communicate that initiation at that time.
Thank you ma'am and our next question comes from Phil Nadeau from Cowen and company. Your line is now open.
Anhco Nguyen: Thank you. And our next question comes from Phil Nguyen from Cowen & Company. Your line is now open. Good morning, Pascal. Let me add my congratulations on your new role.
Good morning.
Scott, Let me add my congratulations on your new role.
Pascal Touchon: My first question is on TABSL and the European regulatory discussions. Can you give us some sense of what elements still need agreement between the company and the European regulators? Are they endpoints, enrollment criteria? Where is the debate?
First question is on ONTAP cellmate European.
Regulatory discussions can you give us some sense of what elements still need agreement between the company and the European regulators is it end points.
Enrollment criteria Where's the debate.
I mean, you know weve.
Pascal Touchon: I mean, as you know, we've adapted and amended our protocol for SOT, and we have merged two studies together, the SOT and the HCT study into one study with two cohorts. So that's something that has been based on our discussion and constructive dialogue with the FDA. Now we need to discuss these changes with the MEA about these changes and see how they react to that, and then what that means in terms of the timing. We are in a prime process, which is a very unique type of process for advanced therapies, where you can have regular interactions with the rapporteur. And then, of course, you may benefit from an accelerated review then. So we are actively engaged with the rapporteur and other members of the committees to be able now to clarify when the timing is for EMA submission of a CMA. So it's really around this change in the protocol that is linked with all this kind of DFDA that we now need to discuss with the EMA.
Adopted amended protocol for ISO tea and we have merger two studies together the city and the HCT study in one study with two cohorts, but that's something that has been based on our discussion and constructive dialogue with the FDA now we need to discuss with the EMEA.
We've got these changes and see how they react to that and then what does that mean in terms of the timing of potential submission of this year may.
We are in the pipeline process, which is a very unique type of process for advanced therapies, where you cannot figured all type of interactions weve. The hotter and then of course you may benefit for an accelerated review then so we are actively engage with auto and other members of the committees to be able now to clarify when is the timing for the may submission of a CMS.
So its really around this change in the political that's linked with all this you know the FDA that now we need to discuss with the Yemen.
Pascal Touchon: And do you have any sense of when your discussions with the EMA will conclude?
Do you have some sense when your discussions with you may will conclude.
It's moving rapidly cannot say exactly when it will be complete but what I can say that as soon as we have clarity there we will make that a spatafore public communication.
Pascal Touchon: It's moving rapidly; I cannot say exactly when it will be concluded, but what I can say is that as soon as we have clarity there, we will make that part of our public communication.
Pascal Touchon: Perfect. And then, next question on the next generation CAR-T, can you remind us what the difference is between your autologous ATA-2271 and the mesothelium CAR-T that was developed by Memorial Sloan Kettering and from which we have data?
Perfect and then.
Next question on the next generation car T can you remind us what is the difference between your autologous 80, 20 to 71 and the.
Ms feel in car T. There was.
Developed by loan Memorial Sloan, Kettering and from which we have data.
Chris Hack: Yes, Chris. Do you want to start on that one? Then I will explain our strategy there.
Yes, Chris do you want to start on that one and I will explain our strategy there.
Chris Hack: Sure. So we're very excited at the opportunity to incorporate next-generation co-stimulation, 1XX, for example, as well as T-cell intrinsic checkpoint inhibition through the use of the PD-1 dominant negative. And we'll be using the identical binding domain as has been used in the presentations given at AACR and ASCO. So we're using the clinically validated mesothelon binding domain together with the best available technologies as we advance the mesothelon CAR-T program.
Sure.
So we're very excited at the opportunity to incorporate next generation co stimulation, one X X for example, as well as the T cell intrinsic checkpoint inhibition through the use of the PD one.
Dominant negative and we will be using the identical binding domain.
As has been used in the presentations.
Given that HCR and ASCO, so we're using the clinically validated.
Music deal and binding domain together with the best available technologies as we advance the mesothelioma car T program.
Pascal Touchon: I think the key here is that the binding domain, the SCFV, is really unique, and in the sense that the data that were presented, the early initial data were presented at ASCO and ACR, clearly show a level of safety, first of all, and then efficacy that is not very common in mesothelene-targeted types of therapy. So we have that SCAV. That's something that we are learning from the first-generation CAR T development of our collaborators at MSK, and that same SCAV is being part of the construct of the next generation with the new co-stimulatory domain that is aiming at having the right balance between expansion and persistence of the CAR Ts. And then, of course, we have added the PD-1-DNR to have a really physiological way of addressing the need to target PD-L1 and make sure that we have enough activity of the cells when they have penetrated the tumor.
I think the key here is that the binding domain. The TV is really unique and in a sense that the data that were presented the early initial data were presented at the ASCO and SCR clearly show a level of.
Safety first of all and then efficacy that is not very common in middle of that in targeted type of therapies. So we add that they see a v. That's something that we are learning form from the first generation car T development for collaborators that MSK and that same as CMV is being part of the construct of the next generation. We have the new Costimulatory domain that is aiming at having the right balance between expansion and persistence off the call teas, and then of course, we have added the PD one DNR 12, really more physical nickel way of addressing the need to a target PD, one and make sure PDL, one and make sure that we have.
Enough activity of the sales one they are penetrated into the tumor.
Pascal Touchon: Perfect. And then my last question is on the earlier pipeline. Is there any update on ATA3219, the anti-CD19 CAR-T, or ATA2431, the CD19, CD20, and CD22 CAR-T?
Perfect.
And then my last question is on the earlier pipeline is there any update on 88, 32, 19 anti Cdnineteen car T or 80, 20 431, the Cdnineteen Cdtwenty Cdtwenty two party.
Yes, we are continuing this program of course, we've all collaborators. Therefore, the the one you mentioned, which is looking at free targets. There and then to that with more feet of course, and then for the Cdnineteen, which is not our development. This development is progressing well and as you know our objective here is really in a very well known type of car T targets to be able to show efficacy and safety that we all are low to prove the concept of erosion in car T. Based on MPV specific sales. So both programs are progressing we don't have any special comment to make on specific.
Pascal Touchon: Yes, we are continuing this program, of course, with our collaborators there for the one you mentioned, which is looking at three targets there. And then, of course, that's with Morphit. And then for the CD19, which is an Atara development, this development is progressing well. And as you know, the objective here is really a very well-known type of CAR-T target to be able to show efficacy and safety that will allow to prove the concept of allogeneic CAR-T based on EBV-specific cells. So both programs are progressing. We don't have any special comment to make on specific types of achievements there. But they are progressing very well.
Type of achievements, there, but they are progressing very well.
Pascal Touchon: Great. Thanks for taking my questions. Thank you. And our next question comes from Tony Butler from Roth Capital. Your line is now open. Yes, good morning. Good morning, Tesco, and welcome as well.
Great. Thanks for taking my questions.
Thank you and our next question comes from Tony Butler from Roth Capital. Your line is now open.
Yes, good morning, good morning, Tesco and welcome as well Mike. My question is around wanted to use the mouse and ACTRIMS.
Tony Butler: My question is around 188 MS and ectrums. There are three questions. Number one is... You state in the release that you're looking at progressive forms of MF, but in ClinTrials, it's actually both relapse-permitting and also progressive, so I'm curious what we get at ECTRIMS directly. Number two is, while you clearly won't have an EMR, or there will not have been enough time for patients to have been on the drug to see, probably any changes in MRI, I I would appreciate some specificity there if possible. And then, finally, did I hear correctly that there were patients, or at least a patient that had PTLD MS, that did clear? If that's true, could you tell me? Please describe clinically how that was actually determined. Thanks very much.
There are three questions number one is.
You stated in the release.
That you are looking at progressive forms of a mess but.
Building controls it's actually.
Both.
Permitting and also progressive so I'm curious what we get.
ACTRIMS directly that's number one.
Number two is.
Well do clearly will have.
Anymore or will not have been enough time for patients to have been on drug to see.
Probably any changes in the MRI.
Simply trying to understand what could you present that would at least provide enough information that.
The the T cells do have activity and more importantly are affecting the CMS directly.
Appreciate some specificity there if possible.
And then finally did I hear correctly that there.
Or patients or at least a patient that had BTL dms that did clear if that's true could you.
Please describe clinically.
How that was actually.
Department, Thanks very much.
Dr. A.J. Joshi: Sure, so this is AJ. Let me start with the third question.
Sure. So this is AJ I, let me start with the third question, so and apologies if there was any ms. Sandra miscommunication misunderstanding. There is no PTSD patient with them ask that we're describing I think what we're describing earlier is the concept that we have proof that the T cells do get into the CNS. They are able to cross the blood brain barrier and access the CNS compartment and exert function because we've had peak treated patients is PTSD cnf gtld. We've also treating patients in a slightly different setting with CMV retinitis in a variety of other CNS conditions related CMV with CMV targeted T cells. So there is very good proof that these T cells that we create varli targeted access the CNS compartment, well and exert their function. So that was approved source for why we believe all of these cells are getting into exert function for M.S.. So it's not really telling hope that answers question three it does say Jay. Thank you my apologies.
Dr. A.J. Joshi: So, and apologies if there's any miscommunication or misunderstanding. There is no PTLD patient with MS that we are describing. I think what we were describing earlier is the concept that we have proof that the T-cells do get into the CNS. They are able to cross the blood-brain barrier and access the CNS compartment and exert function. Because we've treated patients with PTLD, CNS PTLD, we've also treated patients in a slightly different setting with CMV retinitis and a variety of other CNS conditions related to CMV with CMV-targeted T-cells. So there's very good proof that these T-cells that we create virally targeted access the CNS compartment well and do their function. So that was the proof source for why we believe all of these cells are getting in to exert function for MS. So it's not really P-Telly. I hope that
Dr. A.J. Joshi: No, no worries, no worries. Getting back to the first question on progressive versus relapsing remedies. You're right; our original thought process was to take a look at both. However, as we got deeper and deeper into the understanding of the autologous ATA 190 program and what we wanted to focus in on with this program, we specifically decided to stay targeted on progressive MS. So when you mention MRIs, you're right. There are a lot of times you can get relatively early reads on active disease by tracking MRI status. But this is not an active disease.
As for misunderstanding.
No no worries no worries.
Getting back to Earth.
First question on progressive versus relapse, or if any you're right. Our original thought process was due to take a look at both as we gotten as we got deeper and deeper into the understanding of the autologous 81, 90 program and what we wanted to focus in on this program, we specifically decided they targeted on progressive Amat and also it's really a progressive Mds population that really doesn't have a lot of inflammatory disease. So when you mentioned amortize youre right. There is a lot of times you can get relatively early reads in active disease my tracking MRI status.
But this is not activities, we really want to focus in on the progressive component, which is where really most other therapies have failed to.
Dr. A.J. Joshi: We really want to focus in on the progressive component, which is where most other therapies have failed. And we think that's the differentiator here. So for us, the win is the early win. There's an early win and a later win.
Have failed and we think that's the differentiator here.
So for US the win is.
The early when Theres Ghana, there's an early win in a later when the later wins are sustained responses and very disability measures like EDSS scores in time 25 foot walk test and whole brain volume reduction, but again those are one to two year parameters. These are not six month parameters. So the six month parameters, what you're looking for or at least what we're looking for working with our thought leaders.
Dr. A.J. Joshi: The later wins are sustained responses on various disability measures, like EDSS scores, and time on the 25-foot walk test, and whole brain volume reduction. But again, those are one- to two-year parameters. These are not six-month parameters. So the six-month parameter is what you're looking for, or at least what we're looking for working with our thought leaders, is that there are about six or seven different measures of physical function, cognitive function, a variety of different things, well-established measures, and what you want to see is stability across those measures or no decline. Obviously, if you have improvement, that's fantastic, but it's way too early, quite frankly, to even assess an improvement. But if you're able to show stability and no decline in function, that is the win, because these progressive patients will decline in function. So that's really what we're looking for, is can you show stability or no decline in function across those various parameters across multiple parameters in a single patient?
Is there is about six or seven different measures of physical physical function cognitive function a variety of different things well established measures in which you want to see is stability across those measures or no decline.
Obviously, if you have improvement that's fantastic, but it's way too early quite frankly to even if that's an improvement, but if you are able to show stability.
No decline in function.
That is the win because these progressive patients will decline in function. So that's really what we're looking for is can you show stability or no declining function across those various parameters.
In multiple across multiple parameters in a single patient.
Pascal Touchon: And again, I think this study is really there to determine a phase 2 dose that we'll use, by the way, in phase 1B, and that's mainly based on safety and tolerability, but of course, all these efficacy parameters will inform the choice of the dose for the next portion of the study.
And again, having this study is really there to determine a phase two dose that will use by the way in a phase one b and that's mainly based on safety and Tolerability, but of course, all these efficacy parameters will inform of choice of the doe's.
For the next portion of the study.
Dr. A.J. Joshi: May I ask one follow-up question, and that is, in the progressive patient... will all have had, or will they still be on, and I'm sorry I did not look for the exclusion criteria, will they have had, or will they still be on, the Eau Collige map?
Maybe I'll ask one follow up and that is in the progressive patients.
We'll all have had or will they still be on im sorry that did not look for the exclusion criteria well. They have had four still be on a local issue Matt. Thank you.
Dr. A.J. Joshi: They would all need to wash out of Ocrelizumab before they enter the study, and Ocrelizumab or any other disease-modifying agent would have to be washed out before the end. Thank you, AJ. Thank you, Pascal.
Yes, they would all need to wash out of Oculus Amar before the enter the study and localism up or any other.
Any other disease modifying agent would have to be washed out before the interest.
Thank you Bridget Thank you crystal.
Sure.
Thank you and our next question comes from Yigal Nochomovitz from Citi. Your line is now open.
Samantha Lynn Semenkow: Thank you. And our next question comes from Yigal Nochomovitz from Citi. Your line is now open. Hi, thanks for taking the question. This is Samantha on behalf of Yigal.
Hi, Thanks for taking the question. This is Samantha on for your call.
Samantha Lynn Semenkow: I wanted to build on an earlier question on your next-gen CAR-T for mesothelioma, specifically in respect to your dominant negative PD-1. Can you just go through all the advantages you see with including this in your CAR-T versus just dosing with PD-1? Because the MSK data suggests that you're already getting a really high response rate with Pemberlizumab, so I'm just curious about your thoughts there.
I wanted to fill up on an earlier question on your next Gen car T for mesothelioma, specifically back to your dominant negative PD one.
Can you just.
Go through all the advantages you see with including.
Into your car T versus just dosing with a PD one because the MSK data suggests that you're already getting really high response rate with Pembrolizumab Im just curious I guess.
Chris Hack: Now, that's a great question. Thank you. Chris, do you want to start? And then I'll give you some feedback as well.
No. That's a great question. Thank you Chris do you want to start and then.
Give some feedback as well then.
Chris Hack: Sure, so the inclusion of the dominant negative for PD-1 in the preclinical models had additional anti-tumor efficacy compared to the preclinical combination of CAR T-cells plus an antibody-based checkpoint inhibitor. Specifically, a higher proportion of the animals studied had a complete response to their tumor. And, in addition, there was great durability. So we see a couple of important advantages in that way. In addition, of course, there's a factor of patient convenience, as the combination being present in the T-cell itself and able to essentially carry that checkpoint inhibitory function into the tumor in a manner like a Trojan horse allows them to then have a more convenient treatment, potentially, as development proceeds.
Sure so.
The inclusion of the dominant negative for PD one in the preclinical models had additional anti tumor efficacy compared to.
The preclinical combination of car T cells, plus an antibody based checkpoint inhibitor.
Specifically, a higher proportion of the animal studies.
Had complete response of their tumor.
And in addition, there was great durability, so we see.
We see a couple of important advantages in that way.
In addition.
Of course, there is a factor of patient convenience as the combination.
Being present in the T cell itself and able to essentially carry that checkpoint inhibitory function into the tumor.
In a manner like a Trojan horse.
Allows them to then have a more convenient treatment potentially as development proceeds.
Pascal Touchon: Yeah, and I think that the belief there is that the combined approach on the construct will really allow a more physiological way of targeting PD-1 there. And that is, as Chris has said, backed up by some animal data, but of course, we need now to go into patients and prove that this is a better approach than combining with the regular administration of a PD-1 blocker.
Yes, and I think that the belief there is that two of the.
Joint approach on the contract will really allow more physical recalled way of targeting PD, one day and that is as Chris assayed backup based on animal data, but of course, we need now to go into patients and to prove that this is a better pushed on combining with figured administration of PD one blocker.
Samantha Lynn Semenkow: Thanks for that additional detail. And then, in the MSK data at ASCO, 11 out of those 16 patients were PD-1 negative, but you still saw really great response rates in that population. I'm just curious whether you think expressing PD-L1 is important for this therapy, and do you plan to screen for your potential, to plan phase one for in 2020?
Thanks for that additional detail and then in the MSK data at ASCO 11 out of those 16 patients where PD one negative but you still saw.
Really great response rates in that population.
I'm just curious whether you think expressing PD L. One is important for this therapy and.
Do you plan to screen and your potential.
The planned phase one for 2020.
So.
Chris Hack: So, there was no correlation with PD-01 expression or status and outcome in the data presented by our MSK collaborators, Dr. Addis-Emeli and colleagues at ASCO. One thing to bear in mind is that when T cells enter the tumor environment, there's a release of cytokines that will dynamically change the expression of PD-L1. And that may be why it's so important to have the combination present. So I think baseline PD-L1 expression is generally low in mesothelioma, but that may not be the most important factor in a combination therapy that works through an immune mechanism because the cytokines would be expected to dynamically change that axis.
There was no correlation with.
PD PDL one expression.
Or status on the outcome.
In the data presented by our MSK collaborators.
Dredges million colleagues at ASCO.
One thing to bear in mind is that when T cells.
Into the tumor environment.
There is a release of cytokine that will dynamically change of the expression of PDL one.
And that.
Maybe why it's so important to have the combination present.
So I think the baseline.
PDL one expression.
Is generally low in mesothelioma, but that may not be the most important factor in a combination therapy that works through an immune mechanism because.
The cytokine would be expected to dynamically change.
Pascal Touchon: And again, having the DNR here could be an advantage because then in situ, that's what is really important about the activity of the T-cells when they are home to the tumor there, is the in-situ immunosuppressive environment that is laid by the PD-L1 expression there. And having that for the DNR makes a lot of sense.
That access.
And again being the DNR here could be an advantage because then in FY. Two that's what is really important about the activity of the T cells. One they have home to the tumor there is the in situ immuno suppressive element that is laid by the PDL one expression, there and having that for the Vietnam makes lot of sense.
Great. Thanks for taking my question.
Salveen Jaswal Richter: Great, thanks for taking our question. Thank you. And our next question comes from Salveen Richter from Golden Sacks. Your line is now open. Yes, hi. Thank you for taking the questions. Mariana Brightman for Salveen. I have a couple. One of them, following up on the Mesothelian sort of rationale for the changes, I also wanted to get a better sense for the timeline. And I also was trying to understand what the manufacturing stages that that process is in, you know, what the vectors have been made, and, you know, how far along are we basically in preparation for 2020?
Thank you and our next question comes from Salveen Richter from Goldman Sachs. Your line is now open.
Yes, hi, Thank you for taking the questions Mariana bright on for Salveen.
That's helpful.
Juan on following up on the marathon sort of rationale for the change is always wanted to get a better sense of the timeline and ultimately trying to understand what are the manufacturing stages.
But that process is in.
One of the vectors have been made and how far along would basically in preparation for the 20 twond.
Sorry, when you say the change of the timeline.
Pascal Touchon: So, when you see the change in the timeline... For the MISO... No, no. Just to understand the timeline, what is... Okay. Okay. Okay, no, no. Sorry for that.
For the Meizu I'd, just love to understand I understand the timeline what is okay sorry.
Okay, and I'm, sorry for that so we working with our collaborators at the M.S.K. to be able to be ready for the I. Nd and this is progressing very well our guidance has been that we will be.
Pascal Touchon: So we're working with our collaborators at MSK to be able to be ready for the IND, and this is progressing very well. Our guidance has been that we will be, I mean, our partners will be filing an IND in 2020 for this next generation CAR-T, and we are very confident in this guidance. Meanwhile, as you know, we are also progressing in supporting the first-generation study that is continuing. There is an important medical need. And as you can see, the efficacy and safety results are encouraging there, and we believe we are learning a lot from that study, and that learning could be applied to our first study with the next-generation mesocardia. So timelines are in line with the guidance, and things are progressing very well there for 2020. And manufacturing at this stage is to be done initially at MSK and will be transferred to our atom unit in due time.
I mean, our collaborators will be filing a 90 in 2020 on these next generation car T and we're very confident in these guidance.
Meanwhile, as you know we are also progressing in supporting the first generation study that is continuing there is an important medical need and as you can see the efficacy and safety results are encouraging there and we believe we are learning a lot from that study that and that learnings could be applied to all first study with the next generation mutual casualty. There. So timelines are in line with the guidance and things are progressing very well there.
For 2020 and manufacturing at this stage is to be done initially MSK and will be transferred idle autumn.
Unit in due time.
Pascal Touchon: Got it. Thank you. Thank you. And our next question comes from Mauree Raycroft from Jefferies. Your line is now open. I thank you for taking my questions. This is David Onfomori, and my first question is regarding TAPSIL. Can you share with us any updates on the expanded access program, such as updates on the number of patients included, the type of patients enrolling, and if you will report any new data from this program
Got it thank you.
Thank you and our next question comes from Maury Raycroft from Jefferies. Your line is now open.
Thank you for taking my questions. This is David on for Laurie.
Question regarding tap sale, just can you share with us any updates on the expanded access program such as updates on the number of patients included patients enrolling and if you.
If you will report a new data from this program.
Pascal Touchon: Thank you for your question. So we are not giving any number of patients at this stage, but the program is really recruiting a lot of patients that either cannot participate in the study itself, in the phase 3 studies, cannot be enrolled in the phase 3 studies, or are different types of patients there. So we're very pleased with the enrollment in that program, and we will communicate new data on this program at future congresses.
Thank you for your question. So we're not giving any number of patients at this stage, but the program is really very cutting a lot of patients.
That either cannot participate to the study.
Except for the phase three studies cannot be enrolling the phase three studies or a different type of patients. There. So we're very pleased with the enrollment in that program and we will communicate at future Congresses, New data on this program.
Pascal Touchon: Got it. That's very helpful.
Got it that's very helpful and the second question is for the top so can you talk about the status of your line is a fringe youre carcinoma trial.
Pascal Touchon: And the second question is, for the TAPSIL, can you talk about the status of your...
Pascal Touchon: of your anesopharyngeal carcinoma trial. How's enrollment currently going, and what's the sort of plan for disclosure?
Housing Roman currently going and what's the plan for disclosure.
Dr. A.J. Joshi: Thank you for your question. Eiji, do you want to answer that one?
Thank you for your question agent you want to answer that sure. So.
Dr. A.J. Joshi: Sure. So, you know, the NPC study, as you know, is ongoing. We're in the first phase of the program where we're looking to enroll, you know, anywhere between 12 and 24 patients in the study. As you know, it's the first time we've ever really combined cell therapy with PD-1 inhibition from, when I say cell therapy, the first time we've combined TAP cells with PD-1 inhibitor. So, you know, the major focus for us here is going to be really assessing the safety of the combination initially. From a timing of data point of view, we're not expecting to present data this year on that program just yet.
The MPC studies in as you know is a is ongoing we're in the.
First phase of the program, where we're looking to enroll anywhere between 12 and 24 patients in the study as you know it's the first time, we've ever really combined cell therapy with PD one inhibitor in ambition from when I say cell therapy. The first time with combined taps out with PD one inhibitor.
So the major focus for us here is going to be really assessing the safety. The combination is initially.
From a timing of data, we're not expecting present data this year.
On that program just yet.
Dr. A.J. Joshi: Got it. That's very helpful. And then the last question is on the anti-misleading CAR-T. Can you share with us any political thoughts around your potential child design for the CAR-T program in 2020?
Got it that's very helpful. And then last question is on the.
The anti feeling car T is can you just share with us any Plymouth thoughts around your potential trial design for the car T program in 2020.
So again, the I. NDS planned for filing in 2020.
Pascal Touchon: So again, the IND is planned for filing in 2020. We are not giving any details on the protocol right now because we are discussing it right now. And we will give details on that protocol in due time. Again, it is important that we take into account all the learnings from the first generation and what we're doing there. And I think that's an important aspect to optimize the IND and the first human study for this next generation CAR-T. We're very confident that we will be able to start that in 2020 as planned with an appropriate protocol that will really allow us to have proof of concept of the clinical efficacy and safety of this next generation CAR-T as rapidly as possible.
We are now twice now, giving any details on the protocol because we are discussing gets tighter and that we will.
Give details on that protocol in due time again that it is important that we will take into account all the learnings from the first generation and what we're doing there and I think thats an important aspect to optimize.
Hi, Andy and the first in human study for these next generation Carty. We are very confident that we will be able to start out in 2020 as plan. We have an appropriate protocol that will really allow us to have.
Proof of concept of the clinical efficacy and safety of this next generation car T.
As rapidly as possible.
Got it thank you for taking my question.
Pascal Touchon: Thank you. And our last question comes from Ben Burnett from Staple. Your line is now open.
Thank you and our not last question comes from Ben Bernanke from Stifel. Your line is now open.
Ben Burnett: Hey, great. Thanks so much for taking my questions. And Pascal, great to see you on board, and congratulations. Two questions for me.
Hey, great. Thanks, so much for taking my questions.
And Pascal great to see onboard and congrats.
Two questions from me just one first just to clarify on on 81 88.
Ben Burnett: Just one first, just to clarify on ATA 188. What cohorts or dose levels specifically will we see efficacy data for at ECTRIMS? And then also, have patients so far in the Phase 1 made it to the point where they can enroll in the Open Label Extension? And if they have, I guess, what's sort of been the enrollment rate or retention rate into that study?
What cohorts or dose levels, specifically, where we see efficacy data for at ACTRIMS.
And then also have patient so far in the phase one progress or are made it to the point, where they can enroll in the open label extension and if they have I guess, what's sort of been the NIM.
Enrollment rate or retention rate into that study.
Thank you again for your question Angie.
Dr. A.J. Joshi: Thank you, Ben, for your question, Eiji.
Dr. A.J. Joshi: Sure, and I may ask for a clarification on part two of the question. So in terms of the cohorts, we'll be presenting data on two cohorts out to, the first two cohorts, out to about six months' worth of data. We may have a little bit more on one of the initial cohorts, but again, it's really just a timing issue in terms of how long the patients have been in the study at this point. In terms of the enrollment into expansion, I apologize, but can you clarify that because what we have right now just as a plan is... As we finish this fourth dose-giving cohort, and we're close to finishing the fourth cohort now, we'll make kind of a database decision as to what the dosing will be for the randomized portion of this study. And is that what you're talking about as an extension?
Sure and I may ask for clarification on part to your question.
So in terms of the cohort the.
We will be presenting data on two cohorts out to the first two cohorts.
After about six months worth of data, we may have a little bit more on on on one of the initial cohorts, but again, it's really just a timing issue in terms of how long the patients have been in study at this point.
In terms of the enrollment into extension I apologize can you clarify that because it's a for what we have right now just as a plan is.
As we finish this fourth dosing cohort and we're close to finishing the fourth cohort now we'll make kind of a database decision as to what the what the dosing will be for the randomized portion of the study and is that what you're talking about an extension.
Dr. A.J. Joshi: Well, I'm referring to a study schema that you guys presented at EAN wherein it looks like cohorts 1, 2, 3, and 4 have the opportunity to go into an open-label extension after one year of treatment. I guess I was asking if anyone's made it to that point yet and what the sort of retention rates have been into that section.
Well I'm, referring to a study skin.
That you guys presented at EEI and.
Were and it looks like cohorts 123, and four have the opportunity to.
Go into an open label extension after one year of treatment.
I guess I was asking if anyone's made it to that point, yet and what the sort of retention rate spend into that section.
Dr. A.J. Joshi: That's okay; now I applaud that. Thank you for the clarification. Yes, so we do have a few patients from the first cohort that have gotten out past a year and are going into the extension. I'm not really going to be able to comment on percentages or anything like that because it's a little bit too early, but we do have patients who have gotten out to that time point.
That's okay now I apologize thank you for the clarity.
Yes. So we do have we do have a few patients in from the first cohort that have gotten out past year and are going into the extension I am never going to be able to comment on percentages or anything like that because it's a little bit too early but we do have patients who have gotten out to that that time point.
Dr. A.J. Joshi: Okay, understood. Thank you for that. And then just one last one on TAP cell and PTLD.
Okay.
Okay understood. Thank you for that.
And then just one last one on on top selling P. TLD.
Ben Burnett: I guess, can you just talk in a little more detail about the logistics of getting patients enrolled into this study? I guess, really, why has it been so challenging to forecast enrollment rates? And, I guess, what gives you the confidence now that enrollment can be accurately forecast going forward?
I guess can you just talk and a little more detail about the logistics of getting patients enrolled into the study.
I guess really why has it been so challenging to forecast enrollment rates and I guess, what gives you the confidence now than enrollment can be accurately forecast.
Yes going forward.
Dr. A.J. Joshi: Sure, it's a great question. So one of the prime difficulties, you know this is an ultra-rare disease, so clearly, it presents challenges. And this is a different challenge than some of the other ultra-rare diseases out there because this is one where the patients really do come up randomly. There are not major centers of excellence where you're gonna have a high concentration of patients. So that's step one. Step two is the timing, because when you look at this, you're really looking at patients, catching them right as they fail therapy. Now normally that's not that big of a problem, but here these patients progress so rapidly to death that there's a short window of opportunity to really help. So catching them at exactly that window is a second.
Sure so great questions one of the probably the prime perfectly you know this is an ultra rare disease. So clearly ultra rare presents challenges and this is a different challenge than some of the deals or other ultra rare diseases out there because this is one where the patients really do come up in randomly there is not a major centers of excellence, where you can have a high concentration pace. That's up step two is the timing because when you look at this you are really looking at patients catching them right as they fail therapy.
Normally that's not that big of a problem, but here. These patients progress. So rapidly today. There is a there is a short window of opportunity to really help them.
So.
You still catching them it exactly that window is part is a second job.
Dr. A.J. Joshi: We've done really well, actually. In terms of the operational efficiencies we've created to make sure we can catch these patients, that has actually gone extremely well. And we've gotten a lot better over the course of the study at achieving that. So that gives us a bit more confidence that we'll be able to enroll correctly, or at least at the pace that we're targeting. The third thing, just to keep in mind, and I'm going to roll this back into the EAP program a little bit.
We've done really well actually lever in terms of the operational financial efficiencies, we created to make sure. We can catch these patients that actually has gone extremely well and we've gotten a lot better over the course of that for the study in achieving that so that's what gives us a bit more confident that we'll be able to enroll correctly are at least on the pace that we're targeting.
The.
The third thing just to keep in mind and I'm going to roll this back into the program a little bit.
Dr. A.J. Joshi: Part of the challenges that you have is, as I mentioned, these patients kind of come up everywhere. When we find a patient who, for example, is not at a clinical trial site, we'll actually move them over to wherever the clinical trial site is, irrespective of where that is in the country. But you also have to remember that these patients are often so sick that you can't actually transfer them. Or they're able to be transferred medically, but they have a specific issue that actually prevents the transfer process. And in those cases, those are patients that get onto our Expanded Access Program, which is what Pascal had alluded to, where we actually have a fair number of patients on our Expanded Access Program, both for PTLD and for other EBV conditions. But those are the major factors why I think enrollment has been a little bit difficult to work through. But since we have focused on existing centers, we've created these operational efficiencies to make sure that that timing component, which is really critical, is not as much of a factor as it has been in the past.
Part of the challenges that you have is as I mentioned these patients kind of come up everywhere.
And.
When we find a patient who for example is not of the clinical trial site will will actually move them over to wherever the clinical trial site is irrespective of where that is in the country. But you also have to remember that these patients are often so sick that you can't actually transfer them or they have a medical need they're not they're able to be transferred medically, but they have a specific issue that actually prevent that transfer process.
And in those cases, those are patients going onto our expanded access program, which is what.
Pascal alluded to where we actually have a fair number of patients on expanded access program, both for futility and for other NPV conditions.
But those are the major factors into why I think the enrollment has been a little bit difficult to work through but since we have focused in on existing centers. We've created these operational efficiencies to make sure that that timing component, which is really critical is not as much of a factor is evident.
Pascal Touchon: And to build on that, I think our confidence in the guidance is linked to the fact that we've learned so much from this study that we're now confident that we can deliver what we've said regarding the initiation of BLA submissions in the second half of 2020. Also, keep in mind that, in a commercial setting, it would be vastly different there, because we'll have the product available within three days to any site, any physician that is in need of that product for his patients across the country. And in the US, which is a very attractive market for this type of triary disease, that means that this possibility to treat the patient extremely rapidly, offered by our TAP cell as an allergenic T cell that is available within three days, is going to be immensely useful for patients and physicians.
And to build on the other thing our confidence in the guidance is linked with the fact that we've learned so much onto the study. That's now we are confident that we can deliver what we say regarding the initiation of a BLE submissions are going downstairs and 20.
Also taken I have in mind that in a commercial setting would be vastly different there because we love the product available within three days to any side any physician that is in need of that product for these patients across the country and in the US which is a very attractive market for this type of travel disease that means that this possibility to treat the patient extremely rapidly offered by our top sellers and the notion IEC T cell that is available within three days is going to be immensely useful for patients and physicians.
Okay, great. Thanks, so much for the additional color there and Anna Congrats again Pascal. Thank you.
Pascal Touchon: Okay, great. Thanks so much for the additional color there, and congrats again, Pascal. Thank you.
Pascal Touchon: Thank you very much for that.
Thank you very much.
Pascal Touchon: Thank you, and I'm not showing any further questions at this time. I will now like to turn the call back to Pascal Touchon, President and CEO, for any further remarks.
Thank you and I'm not showing any further questions. At this time I would now like to turn the call back to Pascal Tucson, President and CEO for any further remarks.
Pascal Touchon: Thank you very much, and thank you everybody for having joined that call. I really want to thank you for taking the time to join us today. We look forward to providing updates for the remainder of the year on a regular basis as we continue to advance our position as a leader in off-the-shelf allogenic T-cell immunotherapy. Thank you very much.
Thank you very much and thank you everybody for having joined that call I want to thank really you for taking the time to join US today, we look forward to providing a date for the remainder of the year on a regular basis as we continue to advance our position as a leader in the off the shelf allogeneic T cell immunotherapy. Thank you very much.
Operator: Ladies and gentlemen, thank you for your participation in today's conference. This does conclude today's program. You may all disconnect. Everyone have a great day.
Ladies and gentlemen, thank you for your participation in today's conference. This does conclude todays program you may all disconnect everyone have a great.