Q4 2021 Atara Biotherapeutics Inc Earnings Call

Operator: Good afternoon everyone, thank you for standing by and welcome to the Atara Biotherapeutics fourth quarter and full year 2021 financial results conference call. At this time, all participants are in a listen only mode; a question and answer session will follow. No one should require, Please be advised that today's call is being recorded.

Good afternoon, everyone and thank you for standing by and welcome to the <unk> Biotherapeutics fourth quarter and full year 2021 financial results Conference call. At this time all participants are in a listen only mode. A question and answer session will follow the formal presentation.

One should require operator assistance during todays conference. Please press star zero on your telephone keypad. Please be advised that today's call is being recorded I would now like to hand, the call over to Mr. Eric Highland Grant Vice President of Investor Relations and finance at <unk> Biotherapeutics. Please go ahead Sir.

Eric: Thank you, operator. Good afternoon, everyone, and welcome to Atara's fourth quarter and full year 2021 results conference. Earlier today, we issued a press release announcing our fourth quarter and full year financial results and operational progress. This press release and an updated slide deck are available in the investors and media section at atarabio.com. On today's call, members of the Atara executive team will provide an update on our financial results and operational progress and also review our upcoming key milestones and objectives.

Thank you operator.

Good afternoon, everyone and welcome to <unk> fourth quarter and full year 2021 results conference call.

Earlier today, we issued a press release announcing our fourth quarter and full year financial results and operational progress. This press release and an updated slide deck are available in the investors and media section at <unk> Dot com.

Today's call members from the entire executive team, who will provide an update on our financial results and operational progress and also review our upcoming key milestones and objectives joining.

Eric: Joining me on today's call are Dr. Pascal Touchon, President and Chief Executive Officer, Dr. Jacob DuPont, Executive Vice President and Global Head of Research and Development, Upal Kopekar, Chief Financial Officer, Dr. A.J. Joshi, Chief Medical Officer, and Dr. Kristen Urema, Chief Commercial Officer.

Joining me on today's call are Dr. Pascal <unk>, President and Chief Executive Officer, Dr. Jakob Dupont Executive Vice President and global head of research and development.

Paul Copay card Chief Financial Officer.

Dr AJ Joshi, Chief Medical Officer.

Dr Christian <unk>, Chief commercial officer.

Eric: We will begin with prepared comments from Pascal and Jacob, then open up the call to your questions. We would like to remind listeners that during the call, the company's management will be making forward-looking statements. However, actual results could differ materially from those stated or implied by our forward-looking statements due to risks and uncertainties associated with the company's business.

We will begin with prepared comments from Pascal and Jacob then open up the call for your questions.

We would like to remind listeners that during the call. The Companys management will be making forward looking statements actual results could differ materially from those stated or implied by our forward looking statements due to risks and uncertainties associated with the Companys business.

Eric: These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's press release and the company's SEC filings. These statements are made as of today's date, and the company undertakes no obligation to update these statements. Now, I'd like to turn the call over to Pascal. Pascal?

These forward looking statements are qualified in their entirety by the cautionary statements contained in today's press release and the company's SEC filings.

These statements are made as of today's date and the company undertakes no obligation to update these statements.

Now I'd like to turn the call over to Pascal Pascal.

Pascal Touchon: Thank you, Eric, and thank you all for joining us this afternoon. The fourth quarter, and in 2021. Atara made important progress because of three strategic priorities, TAP cell 8188 in multiple sclerosis, and our next generation allogeneic RT progress. I would like to start off with, provide an update on the MAA review in Europe and our plan for BLA submission in the UK. First, some background on TAP cell CMC development and comparability. As you know, over the last few years, we had to make minor changes in terms of the manufacturing process between the pivotal study and intended commercial products. Scallop and complied with CGN.

Thank you Eric and thank you all for joining us this afternoon.

In the fourth quarter and in 2021.

<unk> made important progress at causal strategic priority upsell 80, 188 in multiple sclerosis, and next generation Allogeneic car T programs.

I'd like to start off with stop sale and provide an update on the MAA review in your hope and our plan for BLA submission.

First some background on tab cel CMC development and compatibility.

As you know.

Over the last few years, we had to make minor changes in terms of manufacturing process between the pivotal study and intended commercial product to scan and complied with cgmp.

Pascal Touchon: In order to file for regulatory approval through FDA and EMA, we have performed comprehensive studies showing analytical comparability between the pivotal study and the commercial manufacturing process version. This comparability analysis included all 74 available product lots manufactured by Atara and covered 21 key attributes for potency, purity, and alloreactivity for each key attribute. However, there is some inherent variability.

In order to file for regulatory approval.

In EMEA, we outperformed comparable sheep studies showing analytical compatibility.

Between the pivotal study and commercial manufacturing process vessels.

These comparability analyses included all 74 available product loss, mainly affected by at all.

And covered 21 key attributes for potency purity and although the activity.

For each key attribute there is.

Viability.

Pascal Touchon: Even with a well-controlled and robust manufacturing process, as seen already with all approved cell therapies, in the absence of specific guidance for such a first-in-class allogeneic cell therapy, we have determined an acceptable range of variability for the Values of Key Attributes, based on the extensive and favorable clinical efficacy and safety data for TAP2. He then applied...

We have a well control and the whole best manufacturing process at.

<unk> seen already with <unk>.

All our pool sales.

These.

In the absence of specific guidance for such a first in class allogeneic cell therapy.

We are determined and acceptable range of viability for the values of key attributes.

Based on the extensive and thoughtful of both clinical efficacy and safety data for Factset.

We then applied a specific and well established statistical methodology.

Pascal Touchon: Specific and well-established statistical methodology demonstrated comparability between process versions for each key attribute. Minor differences on a few specific attributes were justified according to ICH guidelines, demonstrating the absence of clinical impact, based on our significant and consistent clinical experience across process versions. Following our analytical comparability studies, we believe that the tap cell, pivotal, and commercial product versions are indeed comparable. These comparatability data were discussed in a pre-submission meeting with EMA and submitted as part of our MAA filing in November 2021.

Demonstrate comparability between process visions for each key attributes.

Mono differences on a few specific attributes were justified according to <unk> guidelines and demonstrating the absence of clinical impact.

Based on the significant and consistent clinical experience the cough ported version.

Hello, Ingo analytical comparability studies, we believe that tab cel pivotal and commercial product vision are indeed compatible.

This compatibility desktop we have discussed in the pre submission meeting with EMA.

And submitted as part of a filing in November 2021.

Pascal Touchon: The review and the accelerated assessment are progressing as planned, following receipt of the EMA Day 80 Critical Assessment Report with anticipated approval on June 4, 2021. Pre-launch preparations are progressing well in collaboration with our partner Pierre Fabre in the U.S. We conducted a type B CMC meeting in late February with the FDA to discuss and potentially align on the topic of comparability of pivotal clinical trials to commercial products. As previously noted, we believe this alignment will facilitate a BLS emission by the end of Q2 2022 as planned. However, preliminary meeting response, and discussion, did not result in alignment, and unexpected.

The review and the accelerated assessment is progressing as planned.

Are we in receipt of EMEA AP critical assessment report with an anticipated approval in Q4 2022.

Preparations are progressing well.

Collaboration with Boston up yes hub.

In the U S. We conducted very recently.

B CMC meeting in late February with the FDA to discuss and potentially align on the topic of comparability of pivotal clinical trial to commercial Pollock.

As previously noted we believe this alignment will facilitate the BLA submission by the end of Q2 2022.

Preliminary meeting responses and discussion.

Not result in alignment.

And unexpectedly.

Pascal Touchon: The FDA initially recommended Atara conduct a clinical study with the commercial product as they do not agree that comparability has been demonstrated. Atara has responded with additional questions to the FDA in order to clarify the FDA's view and has suggested several alternative approaches. Progress to a BLS Mischief Given the unique nature of TAP cells, having BTD status with the potential to address an urgent unmet medical need in an ultra-rare disease for patients with limited life expectancy and no approved therapy, as additional background.

FDA initially recommended I thought I'll conduct a clinical study with a commercial product.

Do not agree that compatibility has been demonstrated.

It all has responded with additional questions to FDA.

To clarify as you.

<unk> said whole alternative approaches to progress towards BLA submission.

Given the unique nature of tab cel, having PPD studies with the potential to address an adjunct unmet medical need.

And they'll try rare disease for patients with limited life expectancy and no approved therapy.

As additional background.

Pascal Touchon: We also filed an IND amendment in Q4 2021 with the FDA in order to use commercial products for clinical trials so that we can cover patients with appropriate HLA masks using or existing inventory of commercial products instead of needing to manufacture new lots of clinical materials for the ongoing study. Following submission and review of this IND amendment by the FDA, We have started treating patients into fall 2021 with a commercial tap cell product in our clinical trials and the expanded access program.

We also filed an IND amendment in Q4 2021 with the FDA.

In order to use commercial product for clinical trials.

As we can cobalt patients with appropriate HLA much using our existing inventory of commercial products instead of needing to manufacture of new laws of clinical material for the ongoing studies.

Following submission and review of.

The amendment by the FDA.

We started treating patients in Q4 2021 with commercial subset Pollock.

Clinical trials and the expanded access program.

Pascal Touchon: This means that we are already gathering clinical data with a commercial product, and we will be able to provide such data to the FDA. Additional interactions with the Agency are therefore expected, including receipt of the final Type B CMC meeting minutes.

This means that we are already gathering clinical data with a commercial product.

And we will be able to provide such data to the FDA.

Additionally, interaction with the agency are therefore expected in.

Including receipt of the final type D CMC meeting minutes.

Pascal Touchon: However, as a result of such preliminary feedback we see from the FDA, Atara does not currently expect to file a BLA for TAP cells in Q2 2021, although it is disappointed by the FDA's unexpected preliminary response on comparability. We will continue to engage with determination and confidence with the FDA on potential pathways to a BLA submission for TAP cells, and we plan to provide a further update during our next quarterly. Why are we confused?

But whether as a result of such preliminary feedback we received from the FDA.

<unk> does not currently expect to file a BLA for tab cel in Q2 2022.

While disappointed by the unexpected preliminary response on comparability.

We will continue to engage with determination and confidence with the FDA on potential pathways to a BLA submission for tab cel and.

And we plan to provide a further update during our next quarterly call.

Why are we confident.

Pascal Touchon: TAPCEL is a first-in-class breakthrough therapy-designated product that addresses urgent and met needs. Patients in second line PTSD have no approved therapy and a very limited media life expectancy of just a few weeks to a few months. TAPSEL is also a particularly unique case, as its development over many years has led to the need for minor changes in the manufacturing process to achieve GNP compliance and, Weather have said clinical experience of over 300, including more than 180 with EBV-positive PKG, establishes, we believe, very clearly, the Safe and Effective Branch of Key Product Attributes Values, enabling determination of acceptable commercial product specifications.

That said is the first in class Blake food TRP designated public debt.

Addresses urgent unmet need.

Patients in second line PTSD.

No approved therapies.

And the very limited median life expectancy of just a few weeks to a few months.

Upsell is also particularly unique case.

Its development over many years has led to the need for minor changes in our manufacturing processes to achieve GMP compliance in Quebec.

Whether that said clinical expense of over 300 patients, including more than 180 with EBV positive <unk>.

As publishers, we believe very clearly.

With an effective branch of key product attributes values, enabling determination of acceptable commercial product specifications.

Pascal Touchon: We are Pioneering Initial Therapy. Darcelle has the potential to be the first of its kind, which may require a unique approach to approval, similar to what was achieved with Otoroguzka. So the collaboration with the FDA could allow us to align on a reasonable path to submission and approval so as to allow U.S. patients in serious need to access this potentially life-saving therapy. I know from personal experience that bringing transformative therapeutic innovation to patients is not always straightforward, but I feel confident that we will find a constructive way to get TAPSEL filed and approved in the United States. Now moving to the rest of our pipeline.

We have plenty of in cell therapy, and <unk> has the potential to be the first look at Scott, which may require a unique approach to approval excuse me at all to what was achieved by Orthos coffee.

So the collaboration with the FDA could go to is to align on a reasonable path to submission and approval. So as to allow U S patients until you need to access these potentially life saving therapy.

I know from personal experience that bringing a transformative therapeutic innovation to patients is not always trade fault.

But I feel confident that we will find a cost effective way to get upsell filed and approved in the U S.

Now moving to the rest of our pipeline is important first to mentioned that we believe the current compatibility regulatory topic on tab cel.

Pascal Touchon: It is important first to mention that we believe the current comparatability regulatory topic on TAP cells is specific to this product development. Therefore, this unique situation with stem cells does not apply to ATA188 or our allogeneic CAR T program.

Pacific two with product development.

Indeed, this unique situation with upsell does not apply to <unk> or our allogeneic car T programs.

Pascal Touchon: It is also worth noting that as a result of our CMC development history and regulatory interactions with that field, we have already incorporated several learnings and have adjusted our approach going forward to optimize success with regulatory agencies for other pipeline products and our platform. Turning now to 8188, our logenic MS program, momentum continues to build for this potentially game-changing product within both the medical and investor communities. Recently, two separate non-marked publications.

It is also worth noting that as a result of our CMC development easterly and regulatory interactions with stop sale.

We have already incorporated several buildings and have adjusted our Portugal fault to optimize success with regulatory agencies for OLED pipeline product and our platform.

Turning now to 80, 188, allogeneic and Thats part one.

Momentum continues to build for this potentially game changing product.

Within both the medical and Investor community.

Recently, two separate non mass publication in science and nature.

Pascal Touchon: Science and Nut Parakeet presented what we believe is compelling new epidemiologic evidence that EBV is the leading cause of MS, and Mechanistic Evidence, showing how EBV infections can initiate and propagate the autoimmune attack on the brain in a. As a result of the excitement generated by these publications, we are seeing increasing injuries from patients, MS experts, and potential partners. Furthermore, building on this increase in momentum, we are also pleased to announce that we will be hosting an Atara EBV and MSD meeting with investors and analysts in late March, prior to conducting the interim analysis in Q2 of this year.

Presented what we believe is compelling new epidemiological evidence that <unk> is the leading cause of blindness.

And mechanistic evidence showing how EBV infection can initiate and propagate the autoimmune attack on the blending limits.

The result of the excitement generated by this dedication we are seeing increasing interest from patients and thats experts and potential partners.

Further building on this increasing momentum. We are also pleased to announce that we will be hosting and other EBV and MSA with investors in earnest in late March.

Prior to conducting the interim analyses in Q2 of this year.

Pascal Touchon: The Atara EBV and MS Day will cover all aspects of the causal association between MS and EBV, the rationale for addressing this disease as its root cause through precision therapy like 80188, and current data and development plans for 80188. We hope this event will continue to further build excitement and understanding around the potential of our approach to create significant value for patients, for Atara, and for shareholders prior to conducting the IA in Q2.

Yeah, Hi, Vivien NSA will cover all aspect of the causal association between the mezzanine BD.

The rationale of addressing this disease, whose kohl's, who precision therapy like 80% and 88 in Q1 that are in development plans for <unk>.

We hope this event will continue to further build excitement and understanding around the potential for our approach to create significant value for.

Ah patients.

And for shareholders prior to conducting the IEA in Q2.

Pascal Touchon: As we communicated in January, EVA granted first-track designation in both non-active SPMS and non-active PPMS populations, and we are continuing to make good progress with enrolling the face to randomize double-blind, flexible control and both studies. Evaluating the efficacy and safety of H1-AGA in patients with progressive amaz- ing, patient number 80 expected to be enrolled soon after the planned interim analysis.

As we communicated in January FDA granted fast track designation.

And both non active espns and <unk> populations and we are continuing to make good progress with an all in the phase II randomized double blind placebo control in both studies.

Evaluating the efficacy and safety of <unk> in patients with progressive Ms with patient number 80 expected to be in the whole soon after the plant in Germany.

Yes.

Pascal Touchon: With respect to the interim analyses for the 80 and 88 and both studies, we are on track to conduct the IA in Q2 of this year so as to optimize the likelihood of success in phase two and to confirm our development strategy going forward. After the IAEA is conducted, we plan to communicate our decision on next steps for the program, including rationale for adapting or not the study samples. We also plan to continue our productive dialogue with the FDA following the IA, and first, we will likely communicate our decision on next steps for the program before we formally discuss the IA data with the FDA.

With respect to the interim analysis for the ACO and 88 in Boston, we are on track to conduct the IAA in Q2 of this year.

To optimize the likelihood of success in phase III and to confirm our development strategy going forward.

After the Iea's conducted we plan to communicate our decision on next steps for the program, including rationale for adapting or not the study sample size.

We also plan to continue our productive dialog with the FDA following the IAA and first we will likely communicate a decision on next steps for the program before we formally discussed yet that would give you.

Pascal Touchon: Planned discussions with the FDA following the IA will include next steps in the development pathway and potentially other accelerated pathway applications such as ARMA. We will communicate any relevant updates as appropriate following this discussion. Additionally, we continue to have strong interest from large pharma companies in potential partnering opportunities with AQ&A, and we would continue those discussions following the I. And we would continue those discussions following the I. OMS Prodigy, focused upon AQ&A, but it also includes developing an EBV vaccine, leveraging our unique knowledge of the link between EBV and autoimmune diseases like MS. To this end, we are pleased to announce that preclinical work is progressing on Atara's very own EBV vaccine.

Our planned discussions with the FDA. Following the Ie would include next step on the development pathway and potentially other accelerated by for applications such as Ahmad.

We will communicate any relevant updates as appropriate following these discussions.

Additionally, we continue to have strong interest from large pharma companies.

Potential partnering opportunities with 80 188, and we will continue this discussion following the IAA.

Our next strategy is focused upon a Q&A.

But it also includes developing an EBV vaccine.

Leveraging our unique knowledge of the link between EBV and autoimmune disease like cabinets Division. We are pleased to announce that preclinical work is progressing.

On a thought there is an EBV vaccine.

Pascal Touchon: For some time, we've been collaborating with our vaccine expert, QIMR, on encouraging preclinical studies, and we are currently advancing into IND-enabling. We will have more to say about this program at our upcoming Atara IBV and MSB. Last month, we were also pleased to announce our strategic partnership with Fujifilm Biotechnologies to acquire our atom manufacturing facility in Phazan-Ox for $100 million, which is on track for an uncipated clause in April. Both of the trans-art- We will enter into a long-term supply agreement with Fujifilm, which will provide Atara with access to expert cell therapy manufacturing staff. Flexible Capacity, Specific Capabilities to Support the Pipeline. Additionally, we expect to benefit from reduced operating expenses going forward over time.

For some time, we've been collaborating with our vaccine expert <unk> mall with oncology preclinical studies and we are currently advancing into IND, enabling studies.

We will have more to say about this program at our upcoming at the IBD and a mistake.

Last month, we were also pleased to announce our strategic partnership with Fujifilm <unk> Biotechnologies.

Biotechnology to acquire or auto manufacturing facility in thousand Oaks for $100 million apart.

Which is on track for an anticipated close in April .

That's part of the transaction, we will enter into long term supply agreement with Fuji.

Which will provide at the heart with access to experts cell therapy manufacturing stuff.

Flexible capacity and speed.

Specific capability to support our pipeline.

Recently, we expect to benefit from reduced operating expenses going forward over time.

Pascal Touchon: IMPORTANT IMPORTANT, After the close of the deal, we retained a talented technical operations team, including process science, quality assurance, and supply chain logistics, and we'll also continue to invest in our research, product design, manufacturing, and asset development for early stage and scale-up phases. We are excited to work closely with Fuji going forward. I would also like to highlight that any possible delays in TAPSEL US approval will not impact this partnership, as we have built in the necessary flexibility in terms of our supply needs. Moving now to a financial- With regard to our cash position, in our own way, we entered the fourth quarter of 2021 with 371 million in cash.

Importantly, after the close of the deal we retain talented technical operation team, including process science quality assurance and supply chain logistics.

And we'll also continue to invest in our research product design manufacturing and assay development for early stage and scaling phases.

We are excited to work closely with Fuji going forward.

I would like also to highlight that any possible delays in subset U S approval will not impact this partnership as we built in the necessary flexibility in terms of our supply needs.

Jacob Dupont: This includes 48 million from the sale of shares of common stock to go fund the ATM facility in the quarter, and a 45 million upfront payment in a pair-fabre commercialization agreement. We believe we will have cash as of December 31, 2021. Together with the uncipated 100 million payable to Atara Bon on the Closing of the Strategic Transaction with Fuji, we'll be sufficient to fund the company plan operation into the fourth quarter. I will now turn the call over to Jacob to give you more details on ATA-188 development and our CAR-T program.

Moving now to our financials with regard to our cash position and one way we ended the fourth quarter of 2021 with $371 million in cash.

This includes $48 million from the sale of shares of common stock ATM facility in the quarter.

And $45 million upfront payment received in the Pierre Fabre commercialization agreements.

We believe cash as of December 31, 2021, together with the anticipated 100 million payable to us.

Closing of the strategic transaction with Fuji will be sufficient to fund the company planned operations into the fourth quarter of 2020.

I would now turn the call over to Jacob to give you more details.

When AK development and our coffee program Jacob.

Jacob Dupont: Thank you, Pascal. With regard to ATA-188, our product candidate for multiple sclerosis, recently there were landmark publications in the journals Science and Nature which presented what we believe is undeniable evidence that EBB is a leading cause of multiple sclerosis and a required trigger for the disease. Specifically, MS may be mediated by B cells and plasma cells that are infected with EBV. In the science paper, it was shown that the risk of MS increased 32-fold after infection with EBV but was unchanged after infection with other viruses. Serum levels of neurofilament light chain, a biomarker of neuroaxonal degeneration, increased only after Epstein-Barr virus seroconversion.

Thank you Pascal.

With regard to <unk> 88, a product candidate for multiple sclerosis recently, there were landmark publications in the journal Science and nature, which presented what we believe is undeniable evidence that <unk> is a leading cause of multiple sclerosis, and a required trigger for.

The disease, specifically EMS may be mediated by b cells and plasma cells that are infected with EBV.

And the science paper it was shown that the risk of MFS increased 32 fold after infection with EBV, but was unchanged after infection with other viruses serum levels of nerve filament light chain, a biomarker of Neuro example, degeneration increased only <unk>.

After Epstein Barr virus share conversion.

Jacob Dupont: Adding to the EBV-MS epidemiological connection, scientists detail the nature of how EBV shares or mimics certain peptide sequences with a healthy brain protein called gliocam. The damage occurs when the immune system B cells that have been infected by EBV produce antibodies that target EBV. And unfortunately, these antibodies also attack the self-brain protein. In basic terms, it's a case of mistaken identity.

Adding to the EBV EMS epidemiological connection scientists detailed in nature, how EBV shares or mimics certain peptide sequences with a healthy brain protein called glia Cam.

The damage occurs when the immune system b cells that have been infected by EBV produce antibodies that target EBV and Unfortunately. These antibodies also attack the self brain proteins in basic terms, it's a case of mistaken identity. The antibody is produced.

Jacob Dupont: The antibodies produced target both EBV and central nervous system proteins leading to barren inflammation, demyelination, and axon destruction, which are all hallmark features of multiple sclerosis. We are very excited about these findings, which were widely publicized, including in the popular press as well as among the neuroscience community, and viewed as further validation of our approach for ATA-188 to target EBV in MS patients to improve their outcomes. As Pascal noted, after these studies were published, there has been an uptake in inquiries by MS investigators and patients, as well as potential ATA 188 partners.

Produce target boats, EBV and central nervous system proteins, leading to a barren inflammation demyelination and axon destruction, which are all hallmark features of multiple sclerosis. We are very excited about these findings which were widely publicized including in the popular press is.

Well, it's among the neuroscience community and viewed as further validation of our approach for <unk> 188 target EBV and MF patients to improve their outcome.

As Pascal noted after these studies were published there has been an uptake in inquiries by M. S investigators and patients as was potential 88 188 partners at our upcoming MSA in late March we look forward to diving deeper into these studies and the implications of what it might mean.

Jacob Dupont: At our upcoming MS Day in late March, we look forward to diving deeper into these studies and the implications of what they might mean in the context of treatment with ATA-188. As we look forward to the results of the randomized placebo control phase 2 and bold study, I want to first remind everyone of the encouraging data we've seen thus far in phase 1. Recall, in our phase one data, an open label extension of 24 patients, we saw seven patients demonstrate sustained EDSS improvement, with 13 showing stability through the participation of the study. Remarkably, 20 of 24 patients either improved their EDSS or were stable, which is contrary to the expected decline over the natural course of this disease.

<unk> in the context of treatment with <unk> 188.

As we look forward to the results of the randomized placebo controlled phase II Embowed study I want to first remind everyone of the encouraging data we've seen thus far in phase one.

Recall in our phase one data in open label extension of 24 patients. We saw seven patients demonstrates sustained E. DSS improvement with 13, showing stability through the participation of the study remarkably 20 of 24 patients either improve their EDI SaaS.

Or were stable, which is contrary to the expected decline over the natural course of this disease also as a reminder, we have agreed with the FDA that the primary endpoint of the phase II and both study will be sustained Etfs improvement at 12 months.

Jacob Dupont: Also, as a reminder, we have agreed with the FDA that the primary endpoint of the Phase II studies in both studies will be sustained EDSS improvement at 12 months. To this end, the key data point we will analyze at the interim analysis will be sustained EDSS improvement at six months. As patients continue to enroll at different times in the study, there will be a range of treatment durations at the time of the IA. For example, some patients will have been on treatment for more than six months. Some will have been in school for less than six months.

To this end the key data point, we will analyze at the interim analysis will be sustained Etfs improvement at six months as patients continue to enroll at different times. In this study there will be a range of treatment durations at the time of the IAA. Some patients will have more than six months some will have.

Less than six months, we will take a look at all of these data when making our decision.

Jacob Dupont: We will take a look at all these data when making our decisions. We have confidence that the six-month time point for sustained EDSS improvement is meaningful. Based on our phase one data, patients achieving sustained EDSS improvement at six months are over 85% predictive of achieving sustained EDSS improvement at 12 months. As a reminder, we showed 33% sustained EDSS improvement at six months in the two high-dose cohorts in the Phase I study. The results of the IA will support determining the sample size necessary to achieve target conditional power at the end of the study, and it will inform our phase 3 design and planning.

We have confidence that six month time point for sustained Etfs improvement is meaningful based on our phase one data of patients achieving sustained etfs improvement at six months.

Is over 85% predictive of achieving sustained Etfs improvement at 12 months as a reminder, we showed 33% sustained etfs improvement at six months and two high dose cohorts in the phase one study.

The results of the IAA will support determining the sample size necessary to achieve a target conditional power at the end of the study and then we will inform our phase III design and planning.

Jacob Dupont: After the end of phase two, we plan to conduct pivotal phase three studies in both non-active SPMS and PPMS populations. One study will focus on non-active SPMS where there are no approved therapies in the U.S. or E.U., and a separate study will focus on non-active PPMS where there are very few treatment options of limited efficacy. Now, turning to our CAR T programs.

After the end of phase two we plan to conduct pivotal phase III studies in both non active S. Pms and P. Pms populations. One study will focus on non active S. Pms, where there is no approved therapies in the U S or EU and a separate study will focus on non active P. P.

S where there are very few treatment options of limited efficacy.

Now turning to our car T programs recently, we announced that our partner for autologous HCA $22 71, namely Memorial Sloan Kettering notified the FDA of a fatal serious adverse event associated with the patients treated in the ongoing phase one Ms Kate <unk>.

Jacob Dupont: Recently, we announced that our partner for autologous ATA 2271, namely Memorial Sloan Kettering, notified the FDA of a fatal serious adverse event associated with a patient treated in the ongoing phase one. MSK conducted dose escalation studies. As noted, MSK voluntarily paused enrollment of new patients in the study on a temporary basis. This is a complex case, and MSK is in the process of further evaluating the occurrence. We anticipate providing an update in the next several weeks following further investigation and discussion with MSK.

The dose escalation study.

As was noted M. S K voluntarily paused enrollment of new patients in this study on a temporary basis. This is a complex case and M. S. K is in the process of further evaluating the occurrence we anticipate providing an update in the next several weeks following further investigation and <unk>.

Discussion with MS. Kay our thoughts are of course with the patient and their family.

The temporary pause of HCA 22, 71 study enrollment does not impact the IND, enabling work currently underway to advance 80, $832 71, a separate off the shelf allogeneic car T therapy targeting mesothelin using next generation PD, one DNR and one <unk>.

Car technologies for patients with advanced mesothelioma for which we anticipate an IND filing in the fourth quarter of this year.

Now $832 71, <unk> hundred 32, 19 tab cel and <unk> 188, all utilize a taurus allogeneic EBV T cell platform the.

Jacob Dupont: The safety and tolerability of which have been validated by clinical studies and experiences in approximately 400 patients in various disease areas, particularly with no observed cytokine release syndrome to date. Hence, there's no impact of this ATA-2271 event whatsoever on our clinical studies with Tabsell or ATA-188. As a reminder, our approach to CAR T does not require TCR or HLA gene editing and presents a differentiator approach that retains the endogenous T cell receptor.

The safety and Tolerability for which has been validated by clinical studies and the experiences and approximately 400 patients in various disease areas, particularly with no observed cytokine release syndrome to date, hence there is no impact of this <unk> $22 71 event whatsoever on our clinical studies with.

Tab cel or <unk> 188.

As a reminder, our approach to car T does not require TCR or HLA gene editing and presents a differentiated approach that retains the endogenous and.

Endogenous T cell receptor. This has been shown in academic studies to increase persistence durability and trafficking of the cells <unk>.

Jacob Dupont: Additionally, I'd like to highlight that today is Rare Disease Day, a day in which we raise awareness of patients living with rare diseases and the urgency with which patients need life-saving therapies. Today, on Rare Disease Day, we recognize how vital the efforts are to find new transformational therapies for patients with PTLD and other rare diseases. In closing, I'd like to extend my gratitude to the Atara staff, our collaborators, and the patients involved in our studies.

Additionally, I'd like to highlight that today is rare disease day.

<unk>, which we raised awareness of patients living with rare disease, and the urgency with which patients need lifesaving therapies today on rare disease day, we recognize how vital the efforts are to find new transformational therapies for patients with <unk> and other rare diseases.

In closing I'd like to extend my gratitude to the entire staff our collaborators and the patients involved in our studies, we are working together as a team with purpose and with hope as we chart new territory for Allogeneic T cell therapies, we acknowledge the challenges yet are committed to bringing transformational new <unk>.

Jacob Dupont: We're working together as a team with purpose and with hope as we chart new territory for allogeneic T-cell therapies. We acknowledge the challenges, yet are committed to bringing transformational new therapies to patients in need. Now, I'd like to turn the call back over to Pascal. Thank you, Jacob.

<unk> to patients in need now I'd like to turn the call back over to Pascal. Thank you Jacob and thank you all again for joining US. This afternoon, we've covered a lot of ground on today's call and before we get into Q&A I want to take a few minutes to summarize what we've discussed with regard to tab cel in the U S.

Pascal Touchon: And thank you all again for joining us this afternoon. We've covered a lot of ground on today's call. And before we get into Q&A, I want to take a few minutes to summarize what we've discussed with regard to the sale of tapas in the US. At this time, the FDS recommendation is pretty minor (inaudible), and we are currently exploring several alternative pathways with FDA to enable the filing of a BLA based on data from the ongoing Aliil Pivotal study. TAP-Cell is a novel product and has the potential to save the lives of patients with an otherwise subtle disease.

At least on the Fda's recommendation is preliminary.

And we are currently exploring several alternative pathways with EBITDA to enable the filing of the BLA based on data from the ongoing <unk> pivotal study.

<unk> is a novel product and has the potential to save the lives of patients with another wide sort of disease.

Operator: We are confident that we can find a reasonable pathway in collaboration with the FDA to give U.S. patients access to these potentially transformative therapies. And now, I turn the call back to the operator to begin the Q&A portion of the call. Operator?

We are confident that we can find reasonable pathway in collaboration with the FDA to give us patients access to this potentially transformative therapy.

I'll now turn the call back to the operator to begin the Q&A portion of the call operator.

Operator: With this time, we will be conducting a question and answer session. If you would like to ask a question, please press star 1 on your. For more information, tell them what indicates your line is in the question. You might press star 2 if you would like to remove your... Speaker Equipment, it may be necessary for you to pick up your handset before pressing the start button.

At this time, we will be conducting a question and answer session. If you would like to ask a question. Please press star one on your telephone keypad.

Tom will indicate your line is in the question queue you might press star two if you would like to remove your question from the queue for participants using speaker equipment. It may be necessary for you to pick up your handset before pressing the star keys, one moment, while we poll for questions.

Salim Syed: One moment while we pull for questions. Your first question comes from Salim Syed with Mizuho. You may proceed with your question. Great. Good afternoon, guys. And thanks for all the color.

First question comes from the line of selling side with Mizuho. You May proceed with your question.

Pascal Touchon: Two for me, if I can, one on AT88 and one on an additional indication that I think you were alluding to in the press release, but I just wanted to confirm. So, Pascal or Jacob, AJ, one of the bare cases right now on the stock, obviously, is that the interim analysis is not going to be something that investors can really understand what this data is looking like because the communication will just be qualitative. So I just wanted to tick through, if I could, just a few points here.

Great. Good afternoon, guys and thanks for all the color two for me if I can.

One 888, and one on an additional indication thank.

Thank you were alluding to in the press release I just wanted to confirm.

So pascal or Jacob J.

One of the bear cases, right now on the stock obviously is that the interim analysis.

It is not going to be something that investors can really.

Understand what this data is looking like because the communication will just be qualitative. So I just wanted to tick through if I could just a few points here.

Pascal Touchon: If you're going to, if these are at least in the cards of how you're thinking about communicating this data, so A, are you, is it possible that you're going to use some sort of cross- trial comparison or reference to the phase one treatment data, or some cross- trial comparison of placebo? B, could, could we expect? Is it in the cards that a pharma partnership is going to come simultaneously with the IA communication?

If these are at least in the cards of how youre thinking about communicating this data so a are.

Is it possible that youre going to use some sort of cross trial comparison, a reference to the phase one treatment data or some cross trial comparison placebo b.

Could could we expect.

Is it in the cards, but a pharma partnership is going to come simultaneously with the IV communication and then.

Pascal Touchon: And then C, is an rRMS trial start something that you're also considering simultaneously with the IA announcement? And then the second question is just about a recent publication in Cell talking about EBV reactivation for long COVID. And I'm just wondering if that's an indication that you are looking at long COVID given your EBV platform. Thank you. Thank you, Salim.

<unk>.

It is in our RMS trial start something that you're also considering.

Simultaneously with the <unk>.

<unk> announcement.

And then just the second question is.

Is this on a recent publication in cell talking about EBV reactivation for long Covid and I'm just wondering if that's an indication that you are looking at long COVID-19 .

Given your EV platform. Thank you.

Thank you Sally and so I'll start on your first question then Jacob will under the second one.

Pascal Touchon: So I'll start with your first question, then Jacob will answer the second one. In terms of the IA, what we say is that we'll be communicating a decision related to the study sample size and the rationale for that. We have not given any more specifics in the sense that the specifics will depend very much on the type of data that we have access to and the consequence of the readout of these data.

In terms of the IAA, what we say that we'll be communicating or decision related to the.

The study sample size.

And the rationale of that we have not given any more specifics in a sense that the specifics will depend very much on the type of data that we have access to and the consequence of the readout of this data.

Pascal Touchon: But we understand the questions from the investors' community, and we'll make sure that we are as clear as possible in our communication at the time of the IA. Now, you asked about formal partnering. Our current plan, and I think that's what we try to express in the prepared remark, is that there will be time for the IA and the communication following these interim analyses based on our internal decision following access to some specific data. That kind of first time of communication.

But we understand the questions from the investors community and we will make sure that we are off clear as possible.

Our communication at the time of the I.

Pascal Touchon: Then there will be, in parallel, discussions with potential partners that will have access under the CDA to some type of data to be able to move forward in partnering discussions. And as we said, we have a number of very interested parties right now that we're discussing with. But they will only have access only after the IANO decision and only to part of the data.

Now you asked about some are partnering of current plan and I think that's what we tried to express in the prepared remark is that there will be the time of the IAA and communications. Following these interim analyses based on the internal decision.

Following access to some specific data.

That kind of first time of communication.

Then they will be in parallel discussion with potential partners that will have access under CDA to some type of data to be able to move forward in partnering discussions and as we said we have a number of very interested parties right now that we are discussing with but they will have access on the after.

The INR decision and only two part of the data.

Pascal Touchon: And then, in parallel, we will also engage with the FDA to be able to work with them on the next steps of development and a potential additional accelerated path such as ARMA. So the best way to look at that, Salim, is to say communication after the IAEA, once a decision is being taken about the decision and the rationale, then some update at some stage on interaction with the FDA. And at some stage, hopefully, a discussion on partnership and an update on that.

And then in parallel we will also engage with the EBITDA to be able to work with them on the next steps of development and potential additional accelerated paths such as almond.

So the best way to look at that study is to say communication. After the <unk>. Once a decision has been taken about the decision and the rationale then some update at some stage on interaction with the FDA and at some stage hopefully a discussion on partnering and an update on.

Pascal Touchon: But as you know, this type of update is only at the time the deal is being executed, which always takes a few months following a particular issue. So that's what you should expect from that kind of... Now, on the RMS study, maybe, AJ, you want to say a few words about that. Sure, excuse me.

But as you know these type of data is only at the time of the deal is being executed which always takes a few months. Following a particular event. So that's what you should expect from that point of view.

Now on the Artemis study, maybe AJ do you want to say a few words about that.

Sure.

A.J. Joshi: Sure, I think from the RMS perspective, that's something we've been contemplating for a while. As you know, we would expect ATA188 to work really across any type of multiple sclerosis. And we actively kind of assess the right type of RMS study design. And that is something we are contemplating fairly actively right now. And then, regarding the EBV possible opportunity for additional treatment, Jacob. Yeah, absolutely.

Excuse me sure.

As you see them I think you know from the RMS perspective, that's something we've been contemplating for a while as you know we would expect 18 188 to work really across any type of multiple sclerosis.

We are actively.

Assessing the right type of arm study design and that is something we are contemplating a fairly.

Accurately right now.

And then regarding the EBV placebo opportunity for additional treatment Jacob.

Yeah, absolutely so celine thank you for raising this issue.

Jacob Dupont: So Salveen, thank you for raising this issue of long COVID and the potential role of EBV here. So we've been following this story with a lot of interest as well. And, as we know with the pandemic, up to 30% to 70% of COVID patients will suffer from long COVID.

Long COVID-19 and the role potential role of EBV here. So we've been following the story with a lot of interest as well and so as we know with the pandemic up to 30 to 70.

Set of Covid patients will suffer for long Covid. So this is becoming.

Jacob Dupont: So this is becoming a really emerging health issue in the population. And there have been some really high-profile publications of late. And Salim, as you mentioned, there was the Cell publication in January of this year by Su and colleagues. And it was really interesting.

Are really emerging health issue in the population and.

And there had been some really high profile publications of blade and Selim as you mentioned there is the cell publication in January of this year by Sue and colleagues and it was really interesting they looked at 309 patients.

Jacob Dupont: They looked at 309 patients and looked for various underlying causes of long COVID or PASC. And they actually found that one of the four risk factors for developing PASC was actually reactivation of latent EBV. And it's pretty interesting when you consider some of the symptomatology of long COVID where you have memory lapses, you have fatigue, which are not unlike some of the things that you see in MS where, again, EBV is the driver.

And looking for various underlying causes for for long COVID-19 or task and they actually found that one of the four.

Risk factors for developing Pascal was actually reactivation of Leighton EBV, so and it's pretty interesting when you consider some of the symptomatology of long Covid, where you have memory lapses you have fatigue, which are not unlike some of the things that you see with with an M. S.

We're again.

<unk> is a driver and then there is another publication of note by gold and colleagues and pathogen to described in this small study, but two thirds of patients.

Jacob Dupont: And then there is another publication of note by Gold and colleagues in pathogens that describe the pathogens that were described in this small study, but 2 thirds of patients with long COVID had EBV reactivation, which compared to only 10% of control patients. So it looks like there certainly is a risk there of developing COVID with EBV reactivation. And that's certainly where a product like Tab-Cell could come in. As regards your further query, we have been in discussions with leading academic institutions regarding this topic. And This has been going on for several months.

With long Covid had EBV reactivation, which compared to only 10% of control patients. So it looks like long Covid certainly.

There is a risk there.

<unk> long COVID-19 with EBV reactivation that certainly where a product like tab cel could come in so to your further query we have been in discussions with leading academic institutions regarding this topic and this has been going on for several months. So we're not in the <unk>.

Jacob Dupont: So we're not in the position now to announce any active studies of this sort, but we're certainly exploring this possibility and think that this could be quite interesting to explore further with academic groups. Very helpful. Thanks so much, guys. Our next question comes from the line of Tessa Romero with JP Morgan. Hey guys,

<unk> now to <unk>.

Ounce any active studies of this short, but we're certainly exploring this possibility and think that.

This could be quite interesting.

To explore further with academic groups.

Very helpful. Thanks, so much guys.

Our next question comes from the line of Tessa Romero with J P. Morgan you May proceed with your question.

Hey, guys.

One is doing well thanks for taking our questions.

Tessa Romero: Hope everyone is doing well. Thanks for taking our questions. The first one is on TAPSAL.

The first one is on tab cel to confirm has the Eni agreed that dependent on commercial materials are comparable.

Tessa Romero: To confirm, has the EMA agreed that the pivotal and commercial materials are comparable? And then, for the FDA, based on recent interactions here, do you know exactly why they don't see any comparability between the two products? Are there specific attributes that they disagree with?

And then for the FDA based on recent interactions here do you know exactly why they don't see comparability between the two products are there specific attributes that they disagree with and then I have a follow up if I could.

Thank you first question, maybe Jacob and I'll take the second one absolutely. So thanks for the question Tessa and.

Tessa Romero: And then I have a follow-up question, if I could. Thank you, Tess. First question: maybe Jacob, and I'll take the second one.

Jacob Dupont: Absolutely. So thanks for the question, Tessa. And as Pascal has described, we performed extensive studies showing analytical comparability between the TABSOL process versions between the pivotal and the intended commercial one. We shared all of this comparability data with EMA through the MAA filing that we submitted in November of last year. And this filing is currently under review through the accelerated assessment mechanism in Europe and is proceeding according to plan.

As Pascal has described we performed extensive studies.

Showing analytical comparability between tabs our process versions between the pivotal and the intended commercial one we've shared all of this comparability data with the EMA through the MAA filing that we submitted in November of last year and this filing is currently under.

Review through the accelerated assessment mechanism in Europe and is proceeding. According to plan that we did receive as Pascal mentioned, the EMA day 80 critical assessment.

Jacob Dupont: Now, we did receive, as Pascal mentioned, the EMA day 80 critical assessment, and we are looking at an anticipated approval in Q4 of this year. But the preliminary report in that day 80 critical assessment indicates acceptance of comparability between process versions in that EMA assessment.

We are looking at and anticipating anticipated approval in Q4 of this year, but the preliminary report front in that day 80 critical assessment indicates acceptance of comparability between process versions.

In that assessment.

Jacob Dupont: And to your second question, I think, as we mentioned, there is some inherent viability in all cell therapies, including those approved. And we are confident that, in the absence of specific guidance, we have determined the range of variability for the values of key attributes based on this extensive and favorable clinical efficacy and safety data that we have available for TAF cell and that we've presented and published across different forums. Now, what we've done is applied specific and well-established statistical methodology to demonstrate comparability between process versions for each attribute. And there have been minor differences on a few specific attributes.

And to your second question, Ted I think the as.

What we mentioned there is some variability even with well controlled and robust manufacturing process for all cell therapies, including user pool.

Jacob Dupont: And what we did with the FDA and the EMA is that we justified these minor differences according to ICH guidelines to demonstrate that there is no clinical impact, whether on safety or efficacy, of these minor differences between some key attributes between process versions. And we have consistent clinical experience across process versions. So the discussion with the FDA is really related to these aspects. Does this answer your question? Yeah, that's really helpful.

And we are confident that in the absence of specific guidance, we update them in the range of viability for the values of key attributes based on this extensive and favorable clinical efficacy and safety data that we have available for tab cel in that we presented and published called the control now what we've done is that we've applied space.

If we can well established statistical methodology to demonstrate comparability between positive mentioned for each attributes and they have been minor differences on a few specific attributes and what we did with the NDA may that we justified this minor differences. According to <unk> guidelines to demonstrate that there is no clinical.

Talks with over 50 of the efficacy of this minor differences between some on some key attributes between pulses version and we had consistent clinical experience across process fashion. So the discussion with the FDA is really related to visa aspect does it answer your question.

Tessa Romero: And just thinking just quickly on the MS program here, as a follow-up to the prior question, I guess, will we have a directional sense for how the data is trending at the time of the IA or not? Is that a question that you're willing to answer at this time, or not? That would certainly be nice to have, to be able to communicate, more than to have; we'll have it, but to be able to communicate at the time.

Yeah that's.

Really helpful.

And just thinking just quickly on the MS program here.

As a follow up to the prior question.

I guess.

Well, we have a directional sense for how that data is trending at the time of DIY.

Is that.

Is that a question that youre willing to answer at this time right now.

That will certainly be nice to us to be able to communicate more than 12, we love.

To be able to communicate at the time, what we say that it's too early to exactly this very specific about what we would be able to communicate as we said in the past we still want to preserve the integrity of that study, especially for discussion with the agency with the FDA. So at this stage, we cannot give any more specific but the gain in tons will be.

Tessa Romero: What we say is that it's too early to be very specific about what we will be able to communicate. As we said in the past, we still want to preserve the integrity of that study, especially for discussion with the agency and the FDA. So at this stage, we cannot give any more specifics, but again, our intent will be to be as specific as possible, as clear as possible, within the context at the time of our communication on our next step following the IEP. Okay. Thanks so much, guys. Thank you, Tessa.

To be as specific as possible us clear placebo within the context at the time of our communication on a next step following the idea.

Okay got it.

Thanks, so much guys.

Okay.

Operator: Our next question comes from the line of John Neumann with Canada. Hi guys, thanks for taking the question. A few questions here.

Our next question comes from the line of John Newman with Canaccord. You May proceed with your question.

Hi, guys. Thanks for taking the question.

Two questions here.

John Neumann: The first one is, Regarding the interim analysis for ATA, I'm assuming based on prior experience that at least internal staff will be able to assess and EDSS at six months, but you will also have A certain number of patients have moved beyond six months, for example, to nine or 12.

First one is.

Regarding the interim analysis for HCA 180.

I'm, assuming based on prior comments.

And at least internally.

We'll be able to.

Yes.

Sustained etfs improvement.

Six months, but you will also have a certain number of patients.

Booth beyond six months.

For example to nine or 12 months.

John Neumann: I was wondering if those data, at least, will be able to be shared currently with partners. FTA, Second question I have on tab, so. Do you believe that there are differences in the analytical comparability method that could still be adjusted, or are you now at a point where you may be considering just giving the FDA additional... Okay, I'll answer the first question, which is more about communication, and Jacob, you will take the second one, I guess.

I'm just wondering if those data at least we'll be able to be shared.

Internally with partners.

And the FDA.

Second question I have on tap so.

Do you believe that there are.

Differences.

<unk> analytical comparability method.

It's still be adjusted or are you now at a point, where you may have.

Be considering just giving the FDA additional clinical data with me.

Thanks.

Okay I'll answer the first question is more about communication and Jacob you will take the second one I guess the first question the intent is indeed.

Pascal Touchon: So, on the first question, the intent is indeed, John, to communicate, under a confidentiality agreement, to the selection of potential partners, as well as to the FDA, data from the interim analysis. And you're right to say that even though the main criteria for determining the conditional power of the study is going to be the EDSS improvement at six months, because it's 85% predictive of the ultimate endpoint at 12 months, we will have a number of patients with 9, 12, even up to 18, or whatever, months.

John to communicate under confidential agreement to selection of potential partners as well as to the EBITDA.

Data from the interim analyses and you're right to say that even though the main criteria for determining the conditional power of the study.

The DSS improvement at six months, because it's 85% predictive of the ultimate endpoint at 12 months, we will have in adult patients with 912, even at 2018.

What are the malls and I think that was something that will be important in terms of the overall perspective on the study now we will also have access to data.

Pascal Touchon: And I think that is something that will be important in terms of the overall perspective on the study. Now, we will also have access to data on MRI and NPR, as well as some biological markers. And all that will help us to put together a particular package of data to be communicated to potential partners and to the FDA with different objectives, with these two different groups of that organization that would get access to part of the data and the... Now, on the second question, Pascal, maybe, Jacob, you could elaborate a bit on our plan for alternative paths with the FDA. Yeah, absolutely.

Hi, and MTR as well as some biologics market and all that will help us to put together a particular package of data to be communicated to potential partner and to the FDA with different objectives.

With these two different groups of.

Organization organization that could get access to part of the data under CDA.

Now on the second question on tab cel, maybe Jacob you can elaborate a bit on our plan for alternative path with the FDA.

Yeah, absolutely so John Thanks for the question so.

Jacob Dupont: So John, thanks for the question. So what we're doing, after the type B meeting that we recently had with the agency, we asked a series of additional questions for clarification on the FDA position. And we will get those final minutes within due time here.

What we're doing.

After the type B meeting that we recently had with the agency we ask a series of additional questions for clarification on the FDA position and we will get those final minutes within due time here.

Jacob Dupont: And that will be very interesting. We've also made additional proposals to the agency where we believe that there are other ways to answer the questions that the FDA has rather than embarking upon a new clinical trial. So we think that we have a range of options. We are in active dialogue with the FDA. And again, we'll get those official minutes.

And that would be very interesting. We've also made additional proposals to the agency, where we believe that there are other ways.

Two.

To answer the questions that the FDA have rather than <unk>.

Embarking upon a new clinical trials. So we think that we have a range of options. We are in active dialogue with the FDA and again, we will get those official minutes, but we've also made a series of other proposals to the FDA that we think could resolve this issue.

Jacob Dupont: But we've also made a series of other proposals to the FDA that we think could resolve this issue. And more particularly, I think, to come back to your question, John, here, we think that there are different aspects that are worth discussing. One is that we have, as we said, established a safe and effective acceptable range of values for each other. So we have ways to establish the specification of a commercial product that will support a safe and effective product, and we want to discuss how to establish a range of specification based on the clinical experience with different values of Kiyat.

And more particularly I think.

I'll come back to your question John Here, we think that there are different aspects that are worth discussing in data. One is that we have as we said establish.

Safe and effective acceptable range of values for each attributes. So we have ways to establish the specification of a commercial product that will support a safe and effective product.

And we want to discuss how to establish rental specification based on the clinical experience with different values of key attributes. We also of the data that we have started to generate by already adding promotional products and are cleaning treating patients, which is a great way to generate clinical data and of course.

Jacob Dupont: We also have the data that we have started to generate by already having commercial products in a clinic treating patients, which is a great way to generate clinical data. And, of course, we are also proposing to do some continuous monitoring in a post-marketing setting, which may be another way to address some questions about having further clinical data about the commercial product. Does that answer your question? Yes, thank you. Our next question comes from the line of Phil Medjugorje. Hi, this is Ernie Rodriguez for Phil.

We also are proposing to do some continuous monitoring in a post marketing setting which may be another way to address some questions about adding further clinical data of the commercial product.

Does it answer your question.

Yes.

Yes. Thank you.

Our next question comes from the line of Phil.

Phil Nadeau with Cowen and co. You May proceed with your question.

Hi, This is Daniel Rodriguez for Phil Thank you for taking my call.

Ernie Rodriguez: Thank you for taking our call or question. I guess, first I have a clarification question: did this decision change the mind from the FDA, or was this a reaction to the new analysis? So, in fact, it was, as I said, unexpected. We were surprised by that preliminary recommendation to say that they do not agree with the comparatibility and suggest a clinical trial with a commercial product. We are very surprised by that.

A question.

I guess first I have a.

Clarification Pete.

This decision.

That has changed in mind from the FDA what is the reaction to the new analysis.

So in fact, it was as I say unexpected we were surprised by that.

Preliminary.

The recommendation to say that they do not agree with comparability, suggesting a clinical trial with a commercial product. We are very surprised by that because as you know hook out the past few quarters with given regularly during our quarterly calls are very trust fund update of <unk>.

Pascal Touchon: Because, as you know, throughout the past two quarters, we've given regularly during our quarterly call a very transparent update of our progress on this aspect of comparability between pivotal and commercial products with the FDA. We explained that initially, we had submitted data on 50 nodes for each partial version with statistical power with a 95% confidence interval to demonstrate equivalence. Then the FDA said that they wanted to see more. And they wanted, in fact, to see all the manufacturing batches. So then we presented, and we had a CMC type B meeting in October. With data on all 74 loads, that represented the vast majority of the total loads produced.

Rs on this aspect of comparability between people with our lead commercial product with the FDA. We've explained that initially we had submitted that around 50 nodes for each partial vision with a statistical power revenue was 95% confidence interval to demonstrate equivalence than the FDA said that they wanted to see more and they want it in fact to see.

All the manufacturing batches. So we then we presented and we add a CMC diabetes in October with data on all 74 loss.

That's why we limited the vast majority of the total loss produced and then.

Pascal Touchon: And then the FDA asked for additional questions. We provided the answers to these additional questions in an IND amendment at the end of the year. And then we had another type B briefing book for the very recent type B meeting, where we put together not only all these statistical analyses, not only all these analytical comparability data, but also put that in perspective with the clinical data according to ICH guidance. So the debate has been going on for some time, but we always thought that we had provided the FDA with the answers to their questions and the amount of data that we have to demonstrate comparability is quite impressive in terms of both And more than 180 with EBV positive PTSD, which I remind you is a natural disease.

Ask for additional questions, we provided at the onset with additional questions.

The amendment at the end of the year and then we had another type B briefing book for the very recent <unk> meeting where here, we put together not only all the statistical analyses not only all these analytical comparability data, but also putting that in perspective of the clinics.

According to <unk> guidelines. So the debate that's been going on for some time, but we always felt that we were provided the FDA with the answers to their questions and the amount of debt that we ought to demonstrate comparability is quite impressive in terms of both the analytical data and the <unk>.

Correlation and linked with the clinical data and very consistent clinical that are in terms of efficacy and safety across doses veterans across more than 300 patients treated and more than 180.

EBV positive PTSD, which I remind you is an ultra rare disease. So it's quite impressive to see the amount of data that we provided and we that's why we were very surprised of the preliminary acquisition.

And how is that decision that the rationale behind our decision different under their agreement to allow you to use the commercial product for the current studies, because you're treating patients with that commercial product.

Different there.

It's a different process, but you're right to point that out as something interesting, but it's a different process I mean, when you when we asked them to be able to use a commercial product to treat patients that has been <unk>. The amendment, so with providing data for now you had the amendment and as usual when the review is that.

Pascal Touchon: It's a different process, but you're right to point that out as something interesting, but it's a different process. I mean, when we ask them to be able to use a commercial product to treat patients, that has gone through an IND amendment. So we've provided data for an IND amendment, and as usual, when they review this data, if they don't react within a certain period of time, you can start to treat patients, and we've started to treat patients, including in single patient use, that they approve patient per patient.

They don't react within a certain period of time, you can start to treat patients and we started to treat patients including in single patient use that they approved patient per patient. So that has been one process and in parallel there is this process of demonstrating comparability for the BLA filing which is of course a different process.

Pascal Touchon: So that has been one process, and in parallel, there is this process of demonstrating comparability for the BLA finding, which is, of course, a different process, having different types of questions from the FDA. On the one hand, they have allowed us to treat patients with a commercial product, and I think that's very important, because we are accumulating data in terms of efficacy and safety of that commercial product.

As of ink.

<unk> type of questions.

Questions from the FDA, so on one hand.

Pascal Touchon: On the other hand, they have not agreed on the comparability between commercial and pivotal at this point. And just one final quick one, they mentioned; they recommended a clinical study. Did they give you any details about what that study may require?

<unk> us to be able to treat patients with a commercial product and I think that's very important because we are accumulating data in terms of efficacy and safety of that commercial product on the other hand.

Not agreed on comparability between commercial and pivotal at this stage.

Okay.

One final quick one.

Sure. They recommended a clinical study to give you any details about what that study may require.

Pascal Touchon: And I guess how confident are you that that decision, that preliminary recommendation, can be swayed? Yeah, no; they are proposing to have a dialogue with us on that. But, as we said, we have proposed alternative paths to the BLS submission because we think that there are other ways to answer FDA questions. And that's what we are discussing in an active dialogue with them now, this alternative path to the BLS submission that will rely upon the clinical data from the allele pivotal study, as well as all the other elements I mentioned earlier related to how you establish the specification for such a commercial product based on the range of acceptable values It's an active dialogue, and we look forward to further collaboration with the FDA to find a solution. Our next question line is Ben Burnett with Stiefel.

And I guess, how confident are you that that decision that preliminary recommendation can be sweet.

Yeah, no they're proposing to have a dialogue with us on that but as we said we have proposed alternative paths to the BLA submission because we think that there are other ways to answer the questions and that's what we are discussing in an active dialogue with them. Now is this alternative path to a BLA submission that will rely upon the clinic.

Data from the <unk> pivotal study as well as all the other elements I mentioned earlier on related to how the USW specification for such a conventional product based on the range of acceptable values of the key attributes as well.

This new clinical data that we're accumulating on the commercial product in the <unk> clinical trials and expanded access program.

Alright, thank you.

These items selective dialogue and we look forward for further collaboration with the FDA to find a solution.

Thank you.

Yeah.

Our next question comes from the line of Ben Burnett with Stifel. You May proceed with your question.

Carolina Ibanez: You may proceed with your question. Hi, this is Carolina Ibanez on behalf of Ben Burnett. Thank you for taking our question. If I understood you well in your prepared remarks, you stated that you plan to provide an update in the next few weeks on your investigation into the fatal serious adverse event that occurred in the phase one study of APA 2271. Can you share, at this point, the level of cell expansion observed in the treated patient who died? And in the context of this fatal event, could you please review the rationale behind the use of the 1XX co-stimulatory domain over a more validated construct such as CD28? Thank you. Thank you, Carolina.

Hi, This is candidly neither Nissan for bamboo, Matt. Thank you for taking our question is.

If I understood you well in your prepared remarks, you stated that they do plan to provide an update in the next few weeks Ungird investigation into the Paypal serious adverse event that occurred in the phase one study of 88% to staple line.

And you can just share at this point the level of an expansion observed in <unk> treated patients who died.

And then in the <unk>.

Context of these state only band could you could you review the rationale behind deem the use of one X X College stimulatory domain and I'm, sorry, I'm more bodies at it comes through <unk> 28.

Thank you.

Thank you, Kevin and Articulately you want to address these questions yeah, absolutely so.

Jacob Dupont: Jacob, do you want to address these questions? Absolutely. So we are communicating, obviously, with Memorial Sloan Kettering on this particular patient, and we will be getting more information on the work-up that Memorial is doing for this patient over the course of the coming weeks. So we will have further updates for you in this regard. As we mentioned, FDA or the... Sloan Kettering did their duty, and obviously, they put a temporary hold on enrollment here, and then they shared the information with the FDA and with us, and the FDA supported the decision there.

We are.

Communicating obviously with memorial Sloan Kettering on this particular patient.

And we.

We'll be getting more information on the workup that memorial is doing for this patient over the course of the coming weeks. So we will have further updates for you.

In this regard.

As we mentioned the FDA or the.

Sloan Kettering did their duty and they obviously they.

Put a temporary hold on enrollment here and then they shared the information with the FDA and with US and the FDA has supported that decision. There now we are getting data in on things like cytokine profiles and cell expansion and so forth as well, but we will be able.

Jacob Dupont: Now, we are getting data in on things like cytokine profiles and cell expansion and so forth as well, but we'll be able to provide more detail on this particular patient over the course of the coming weeks.

To provide more detail.

On this particular patient over the course of the coming weeks.

Jacob Dupont: And related to the 1xx domain, that's something, as you know, that we've been using at this stage in different constructs of our allogeneic RT program, as well as in the case of 2271, the autologous mesothelin-RT. And this is a costimulator domain that has already been used in a clinic, I mean, because it was not licensed exclusively to Atara.

And related to the <unk> domain.

That's something as you know that we've been using.

Using.

At this stage in different construct for allogeneic car T program as well.

<unk> thousand 70, <unk> Mesothelin car T.

This is christina towards domain that has already been used in the clinic I mean, because this was not licensed exclusively to at Aha.

Jacob Dupont: You probably know that this domain has also been licensed to Takeda, to FATE, in addition to Atara. And there are other programs in the clinic. And so far, we've not heard about any safety aspect of this program, of safety issue with this program in the clinic. Again, the case of this unfortunate case with a patient with 2271 requires some further investigation because it's a very complex case with many confounding factors. So we need to do that in a very good way and deep way with our partners at MSK. And we will communicate in proper time when we have a better understanding.

You probably know that this domain has also been licensed to Takeda to fate. In addition to Ottawa and there are other program in the clinic and so far we have not heard about any safety aspect of this program a safety issue with this program in the clinic.

Again, the case of this.

Fortinet case with a patient with 22 71 requires some further investigation because it's a very complex case with mainly confounding factors. So we need to do that.

In a very good way and deep way with our partners at <unk>, and we will communicate and pull the time when we have a better understanding it's a very complex case a lot of confidence factor is a very advanced patient in fourth line of treatment and we need to have a better understanding of these different aspect before.

Jacob Dupont: It's a very complex case, a lot of concerning factors, a very advanced patient who has undergone four lines of treatment. And we need to have a better understanding of these different aspects before MSK can make a conclusion, and we can communicate about that conclusion about the potential cause of this particular unfortunate case. And just one other comment regarding 1XX. We do believe that that construct, which is really a next-generation co-stimulatory domain, has advantages over CD28, CD3, Zeta, or 4-1BB per se, where the behavior of this co-stim domain in terms of the persistence of cells in vivo expansion, some of the phenotypic aspects of the CAR T cells are really favorable relative to the first generation.

<unk> M. S. K can make a conclusion that we can communicate about that confusion about the potential of calls.

This particular unfortunate events.

And just one other comment regarding one Xx, we do believe that that construct which is really a next generation co stimulatory domain has advantages over <unk> 2008, <unk> or.

<unk> BB per se, where.

The behavior of this co stim domain in terms of persistence of cells.

Vivo expansion some of the phenotypic aspects of the car T cells are really favorable relative to the first generation. So we think that this particular design from Dr. Michelle Sandlin at Memorial Sloan Kettering really does have some advantages over the first generation.

Jacob Dupont: So we think that this particular design from Dr. Michelle Sadelein at Memorial Sloan Kettering really does have some advantages over the first generation construct. Understood. Yes, perfect. Thank you again.

Constructs.

And there is another question.

Yes, Thank you again.

Thank you.

Tony Butler: Thank you. Our last question comes from the line of Tony Butler with Rothkapp. Thanks very much, Pascal. The notion of the FDA not agreeing with the comparability of Tab-Cell didn't therefore imply that there would be a difference in safety and efficacy of the product. I assume that would be true. That's part A.

Our last question comes from the line of Tony Butler with Roth Capital You May proceed with your question.

Thanks, very much for scale.

Oh.

The notion of the FTA not agree with comparability on tab cel.

It Didnt, therefore imply that there would be a difference in safety and efficacy of the product I assume that would be true that's part a and part B is.

Tony Butler: And part B is, it strikes me, though, I guess I'd have to ask how rapidly the expansion cohort in which the newer product, the commercializable product, is being utilized. Wouldn't that be sufficient, at least at some patient level, to solve the questions at the age of, That's question one.

It strikes me, though.

Tony Butler: And then question two is, what gives you confidence that 188, for example, would not be affected in any way, either as this progresses and or gets solved or just comes to a standstill or just takes a longer time? Thanks very much. Thank you, Tony. I suggest, Jacob, you take the first question. I'll take the last one.

Yeah, I guess I'd have to ask how rapidly is the expansion cohort in which the commercial launch.

The newer product to commercialize a bold product.

Is being utilized.

Wouldn't that be sufficient at least at some patient level to solve.

The questions.

The agency that's question one and then.

Question. Two is what gives you confidence that 188 for example would not be affected in any way.

As this progresses and door.

Salt or just comes to a standstill or just takes longer time, thanks very much. Thank.

Thank you Tony Jacob you take the first question. Please the last one absolutely. So thank you Tony.

Jacob Dupont: Absolutely. So, thank you, Tony. I will say that we now have a lot of clinical experience. You know, Pascal mentioned this, where we've treated over 300 patients through the Academic and the Atara programs, over 180 patients with EBV-positive PTLD. There's a very robust clinical data set there, and the safety is really quite good.

I will say that.

We now have a lot of clinical experience Pascal mentioned this where.

We're we've treated over 300 patients through.

Through the academic and the entire program over 180 patients with EBV positive <unk>, it's a very robust clinical data set there.

Safety is really quite good we don't see or Oregon rejection, we don't see graft versus host disease.

Jacob Dupont: We don't see organ rejection. We don't see graft-versus-host disease beyond the background. We don't see cytokine release syndrome.

Beyond background, we don't see cytokine release syndrome, and this has really been true across the various process versions and as you saw at Ash. The safety profile is really quite good and that comes with really outstanding efficacy, where once again, if you look at the pivotal a lille data at Ash, we see high.

Jacob Dupont: And this has really been true across the various process versions. And as you saw at ASH, the safety profile is really quite good. And that comes with really outstanding efficacy, where, once again, if you look at the pivotal allele data at ASH, we see high response rates, 50%, you know, for these patients that have no other treatment options. And that's a durable response.

High response rates, 50% for these patients that have no other treatment options and Thats a durable response, we believe that some of these patients treated years ago at Memorial Sloan Kettering are actually cured of this fatal disease and so we know what the specifications are for the various process.

Jacob Dupont: We believe that some of these patients treated years ago at Memorial Sloan-Kettering are actually cured of this fatal disease. And so we know what the specifications are for the various process versions there. And there is great consistency in that clinical data. So we believe it's a very reassuring data set. We also, as mentioned, have submitted this data to EMA as well. And they have preliminarily come to the conclusion of comparability.

Versions, there and and there is great consistency in that clinical data. So we believe it's a very reassuring data set.

We also as mentioned have submitted this data to EMA as well and they have preliminarily come to the conclusion of comparability. So again. This is an active dialogue with the FDA, we do think that focusing on the clinical data in this very high unmet need population and BTT.

Jacob Dupont: So again, this is an active dialogue with the FDA. We do think that focusing on the clinical data in this very high unmet need population for a BTD therapy is really important. And we believe it's quite consistent as well. And so in terms of... you mentioned this expansion of the cohort of patients with the commercial product. We think it's very exciting.

<unk> therapy is.

<unk> is really important and we believe it's consistent quite consistent as well.

And so in terms of you mentioned this expansion of the cohort of patients with the commercial product. We think it's very exciting we are in the clinic with a commercial product and as mentioned we did have that ironed that went through the FDA here in December of last year.

Jacob Dupont: We're in the clinic with the commercial product, and as mentioned, we did have that IND that went through the FDA here in December of last year. And we are actively treating patients on expanded access, as Pascal mentioned, also on alleles, also on the 205 studies. So we think that this is reassuring that we'll be able to provide this data as well. And again, these are the types of alternative proposals that we are making to the FDA as we continue our negotiations.

And we are actively treating patients on expanded access as Pascal mentioned also on the Lille also on the 205 studies. So we think that this is reassuring that we'll be able to provide this data as well and again. These are the types of alternative proposals that we are making.

To the FDA as we continue our negotiations again. This is a very active area of discussion and I will let Tony that top offer being accumulating now clinical data with the commercial product we.

Jacob Dupont: Again, this is a very active area of discussion. And I will add, Tony, that on top of having, and accumulating now, clinical data with the commercial product, we already have significant clinical data with different values of the key attributes that are part of the commercial product. That's something that is important to have in mind that among the 300 patients, more than 300 patients have been treated with TAP cell therapy, and among the 180-plus patients who have been treated with TAP cell therapy for EPV-positive PTSD, there have been different levels of values for key attributes.

<unk> already significant clinical data with the different values of the key attributes that are part of the commercial product.

That's something that is important to have in mind that among the 300 patients of more than 300 patients into the reception among the 180 plus patients of interested we substitute for EBV positive <unk>.

There have been different level of values for key attributes. So we have that tranche and a commercial product is within that range.

Jacob Dupont: So we have that range, and the commercial product is within that range. So we have clinical experience already with different process versions but of a specific value. That's what makes us extremely confident that we'll find a way forward. Now, your questions on 8188 are, and why do we think there is no particular impact on this development? First of all, the TAP cell, again, is a very special case. It's been developed over many, many years, with different process versions, and there have been these minor chances across those versions.

So we have clinical experience already with different positive vessels, but of the specific value of key attributes that shows efficacy and safety. That's what makes us extremely confident that we'll find a way for Walt.

No.

Questions on ATM and HCA is and why do we think there is no particular impact on this development.

First of all top set again is a very special case has been developed over many many years different process veterans.

And they have been this minor transfers of cost plus vision. If you think about it if we had the same process vision between pivotal in commercial we won't have that debate about comparability between the two.

Jacob Dupont: If you think about it, if we had the same process version between pivotal and commercial, we wouldn't have that debate about comparability between the two. So that's what is part of our plan for 81-88, to have that possibility to have the same process and material used in phase 3 as in commercial supply. The other aspect that we've learned a lot from this interaction with the FDA, and we know better now how to, moving forward, address some of the potential questions they may have in the future for new products.

So that's what is part of our plan for it when that is.

Is that.

Thats, possibly towards the same process and Matteo to use in phase III and commercial supply. The other effect that we've learned a lot of this interaction with the FDA and we know better now how to moving forward how to address some of the potential question. They may have in the future for new product. So I think this learning.

Jacob Dupont: So I think this learning and this ability to have phase 3 and commercial supply the same process version makes us also extremely confident that this particular debate on comparability we are having right now on TAP cell, which is again a very specific case with the FDA, should not be an issue for 81-88 and the rest of the pipeline.

And this ability through our phase III and commercial supply with a sample size version makes US also extremely confident that this particular debate on comparability. We are seeing right now on tab cel, which is again, a very specific case with the FDA should not be an issue for <unk> and the rest of the pipeline.

Pascal Touchon: Does it answer your question, Tony? Yes, sir, Pascal, thanks very much. Thank you, Jacob. Thank you. That concludes our questions- Atara Biotherapeutics Fourth Quarter and Full Year 2021 Financial Results Conference Call. You may disconnect your lines at this time. Thank you for your participation and enjoy the rest of your day.

Does it answer your question please.

Yes, sure <unk>, thanks, very much thank you Jacob.

Thank you.

That concludes our question and answer session for today. Thank you for joining the <unk> biotherapeutics fourth quarter and full year 2021 financial results Conference call. You may disconnect. Your lines at this time. Thank you for your participation and enjoy the rest of your day.

Okay.

Okay.

Yeah.

[music].

Yeah.

[music].

Jacob Dupont: Our thoughts are, of course, with the patient and their families. The temporary pause of ATA-2271 study enrollment does not impact the IND-enabling work currently underway to advance ATA-3271, a separate, off-the-shelf allogeneic CAR-T therapy targeting mesothelioma using next-generation PD-1-DNR and 1xx CAR technologies for patients with advanced mesotheliom Now, ATA3271, ATA3219, TAB cell, and the ATA188 all utilize Atara's allergenic EBVT cell platform.

Pascal Touchon: So it's quite impressive to see the amount of data that we provided them with. That's why we were very surprised by their preliminary position. And how is that decision, the rationale behind that decision, different than their agreement to allow you to use the commercial product for the current studies? Because you're treating patients with that commercial product. So what's different there?