On November 4, 2021 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leader in T-cell immunotherapy, leveraging its novel allogeneic Epstein-Barr virus (EBV) T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, reported financial results for the third quarter 2021, recent business highlights and key catalysts over the next several months (Press release, Atara Biotherapeutics, NOV 4, 2021, View Source [SID1234594484]).

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"Atara continues to make meaningful progress across our strategic priorities and with positive data from our pivotal Phase 3 ALLELE study and imminent EU regulatory submission, we are now at an inflection point as we work to deliver tab-cel, a potentially transformative first-in-kind therapy, to patients in need," said Pascal Touchon, President and Chief Executive Officer of Atara. "We are equally encouraged by new data confirming our conviction for ATA188 as the first investigational therapy to reverse disability in progressive multiple sclerosis, and upcoming milestones related to our potentially best-in-class CAR T portfolio that does not require TCR or HLA gene editing."

Tabelecleucel (tab-cel) for Post-Transplant Lymphoproliferative Disease (PTLD)

First presentation of new positive data from the pivotal Phase 3 ALLELE study, reinforcing the transformative potential of tab-cel, has been accepted as an oral session at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2021
Top-line data with additional patients and extended follow up confirm a strong objective response rate (ORR) and a safety profile in line with prior results, demonstrate durability of response, and will support the imminent EU Marketing Authorization Application (MAA) submission
An ORR, as measured by independent oncologic response adjudication (IORA) assessment, of 50% (19/38, 95% CI: 33.4, 66.6) was observed, with an ORR of 50% (12/24, 95% CI: 29.1, 70.9) in PTLD following SOT and 50% (7/14, CI: 23.0, 77.0) in PTLD following HCT, with a best overall response of Complete Response (CR; n=5, SOT; n=5, HCT) or Partial Response (PR; n=7, SOT; n=2, HCT)
Overall, the median time to response (TTR) was 1.1 months (0.7-4.7). Of 19 responders, 11 had a duration of response (DOR) lasting more than six months and median DOR has not been reached yet
The one-year survival rate was 61.1% overall (57.4% for SOT, and 66.8% for HCT). Those who responded had a longer survival compared to the non-responders, with a median overall survival (OS) not evaluable (NE) (95% CI: 16.4, NE) and 1-year survival rate of 89.2% (95% CI: 63.1, 97.2)
Safety findings were consistent with previously published data, with no new signals. There were no reports of tumor flare reaction, and no confirmed evidence of graft versus host disease (GvHD), organ rejection, infusion reactions, or cytokine release syndrome (CRS) related to tab-cel
At ASH (Free ASH Whitepaper), Atara will present additional data on tab-cel through several abstracts, including a second oral presentation on long term OS from Phase 2 and multi-center Expanded Access Protocol (EAP) studies in relapsed/refractory EBV+ PTLD showing median OS of 54.6 months in all patients and OS at two years reaching over 86% in responders whether patients experienced CR or PR
Following successful interactions with the European Medicines Agency (EMA), and their recent granting of accelerated assessment to tab-cel, Atara will imminently submit a MAA for tab-cel, with an EU approval decision anticipated in H2 2022
The previously announced exclusive agreement with Pierre Fabre for the commercialization of tab-cel in Europe, the Middle East, Africa, and other select emerging markets for EBV-positive cancers has started strongly. Atara will retain full rights to tab-cel in other major markets, including North America, Asia Pacific, and Latin America
Atara has continued to make good progress through Type B meetings with the U.S. Food and Drug Administration (FDA)
After gaining clarity, alignment on key comparability methodology has been reached
Based on the requests from FDA following recent interactions, Atara will provide the Agency with additional analyses of CMC data already generated
FDA has not requested additional studies or manufacturing lots
Atara subsequently plans to have further interactions with the FDA in Q1 2022 and complete the Biologics License Application (BLA) submission for tab-cel in Q2 2022
Tab-cel for Potential Additional Indications

Atara is committed to pursuing the development of tab-cel in additional EBV-positive patient populations, with a primary focus on immunodeficiency-associated lymphoproliferative diseases (IA-LPDs)
Enrollment is continuing at sites in the Phase 2 multi-cohort study, which is evaluating six patient populations, including four within IA-LPDs and two in other EBV-driven diseases, in the U.S. and EU. Phase 2 study data is expected in 2023
ATA188 for Progressive Multiple Sclerosis

Positive momentum around the ATA188 program continues to build, with increasing awareness of and excitement for the transformative potential of ATA188 in multiple sclerosis (MS) among the medical community and industry
At the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) meeting in October, Atara presented translational data based on magnetization transfer ratio (MTR), an imaging biomarker of myelin density, and updated Phase 1 open-label extension (OLE) clinical data in patients with progressive MS treated with ATA188 for up to 39 months
Findings continue to demonstrate that patients may achieve sustained disability improvement (SDI) at a higher rate and longer duration than would be expected based on the natural history of progressive MS; the majority of SDI is driven by improvement in the expanded disability status scale (EDSS)
In seven of eight patients, SDI was maintained at all subsequent timepoints up to 33 months, with multiple patients regaining enough function that they no longer needed a walking aid and were able to walk a few hundred meters unassisted. Most patients in the OLE were progression free, which could be another significant measure of clinical benefit in people with progressive MS
Magnetic Resonance Imaging (MRI) results showed increases in MTR suggestive of remyelination. In patients treated with ATA188 who achieved sustained EDSS improvement versus those who did not, MTR for non-enhancing T2 chronic brain lesions increased at six months and this increase achieved statistical significance at 12 months; A similar trend of MTR increase was also seen in normal-appearing brain tissue
These MTR data, where the time course for increase in MTR parallels the EDSS improvements observed, provides evidence that remyelination may be the driver for clinical improvement, and supports a potential biological basis for clinical EDSS improvements observed with ATA188
Updated results from the ongoing OLE demonstrate continued safety and tolerability of ATA188 with up to three annual treatments. As of August 2021, no fatal adverse events, grade >3 events, dose-limiting toxicities, CRS, or GvHD were observed
Atara is continuing to make good progress with enrollment of the Phase 2 randomized, double-blind, placebo-controlled dose-expansion EMBOLD study evaluating the efficacy and safety of ATA188 in patients with progressive MS, across clinical sites in North America and Australia
An interim analysis to assess efficacy and safety is planned for H1 2022. The Company plans to communicate its decision on next steps for the program, including rationale, while still maintaining the integrity of the study
Atara expects to complete enrollment for EMBOLD in H1 2022
Atara will present encore data at the 29th Annual Meeting of the European Charcot Foundation in November 2021. The Company will present an overview of the methodology planned to determine the potential pharmacodynamic effect of ATA188, by quantifying a decrease of EBV infected cells following treatment with ATA188
CAR T Programs

ATA2271/ATA3271 (Solid Tumors Over-Expressing Mesothelin)

The global strategic collaboration for ATA2271 and ATA3271 with Bayer continues to progress, with work advancing across both mesothelin-partnered CAR-T immunotherapy programs
The first presentation of preclinical, clinical, and translational data from the lowest dose cohorts of the open-label, single-arm Phase 1 clinical study of ATA2271, an autologous CAR-T therapy targeting mesothelin, designed to improve efficacy, persistence, and durability of response for patients with advanced mesothelioma, will take place during a Mini Oral session at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress on December 9, 2021 (presentation #46MO)
Atara is continuing to make progress on IND-enabling studies for ATA3271, an off-the-shelf, allogeneic CAR-T therapy targeting mesothelin using next-generation PD-1 dominant negative receptor (DNR) and 1XX CAR co-stimulatory signaling domain technologies and expects an IND filing in H2 2022
Preclinical data for ATA3271 will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting, taking place November 10-14, 2021 (poster #136)
ATA3219 (B-cell Malignancies)

Atara is making good progress and expects to submit an IND for ATA3219, an off-the-shelf, allogeneic CD19 CAR T immunotherapy targeting B-cell malignancies, in Q1 2022
Leveraging our next-generation 1XX CAR co-stimulatory signaling domain and allogeneic EBV T-cell platform, ATA3219 is a potential best-in-class therapy that does not require T-cell receptor (TCR) or human leukocyte antigen (HLA) gene editing
Allogeneic T Cell Platform Development

To date, the safety and tolerability of Atara’s allogeneic EBV T-cell therapies and platform has been validated by clinical studies and experience in approximately 400 patients in various disease areas
We have established a new Atara Research Center (ARC) to house the Company’s Translational and Pre-Clinical Sciences, Process Sciences, and Analytical Development teams. New capabilities will support our product pipeline and further drive innovation by leveraging our unique and differentiated allogeneic cell therapy platform
Third Quarter 2021 Financial Results

Cash, cash equivalents and short-term investments as of September 30, 2021 totaled $357.2 million, as compared to $373.4 million as of June 30, 2021
The September 30, 2021 cash balance includes $46.4 million from the sale of 3,123,570 shares of common stock through the Company’s at-the-market (ATM) facility
Atara believes that its cash as of September 30, 2021, together with the $45.0 million upfront payment received as a result of our entry into the Pierre Fabre Commercialization Agreement, is sufficient to fund planned operations into the second quarter of 2023
License and collaboration revenue was $5.4 million for the third quarter 2021 and consisted of revenue from activities performed under the Bayer Collaboration Agreements. Atara did not recognize any license and collaboration revenue for the same period in 2020
Net cash used in operating activities was $59.0 million for the third quarter 2021, as compared to $53.0 million for the same period in 2020
Atara reported net losses of $84.7 million, or $0.90 per share, for the third quarter 2021, as compared to $74.3 million, or $0.92 per share, for the same period in 2020
Total operating expenses include non-cash expenses of $16.0 million for the third quarter 2021, as compared to $15.4 million for the same period in 2020
Research and development expenses were $70.3 million for the third quarter 2021, as compared to $59.9 million for the same period in 2020
The increase in the third quarter 2021 was primarily due increased research and clinical trial costs related to the Company’s ATA188 and CAR T programs, and higher employee-related costs from increased headcount
Research and development expenses include $7.8 million of non-cash stock-based compensation expenses for the third quarter 2021, as compared to $8.2 million for the same period in 2020
General and administrative expenses were $19.8 million for the third quarter 2021, as compared to $14.8 million for the same period in 2020
The increase was primarily driven by higher compensation-related costs from increased headcount and activities to support our anticipated tab-cel launch
General and administrative expenses include $5.9 million of non-cash stock-based compensation expenses for the second quarter 2021, as compared to $5.1 million for the same period in 2020
Conference Call and Webcast Details

Atara will host a live conference call and webcast today, Thursday, November 4, 2021, at 8:30 a.m. EDT to discuss the Company’s financial results and recent operational highlights. Analysts and investors can participate in the conference call by dialing 888-437-3179 for domestic callers and 862-298-0702 for international callers, using the conference ID 13723551. A live audio webcast can be accessed by visiting the Investors & Media – News & Events section of atarabio.com. An archived replay will be available on the Company’s website for 30 days following the live webcast.