On February 28, 2022 Atara Biotherapeutics, Inc. (Nasdaq: ATRA), a leader in T-cell immunotherapy, leveraging its novel allogeneic EBV T-cell platform to develop transformative therapies for patients with cancer and autoimmune diseases, reported financial results for the fourth quarter and full year 2021, recent business highlights and key upcoming catalysts for 2022 (Press release, Atara Biotherapeutics, FEB 28, 2022, View Source [SID1234609107]).
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"With our EMA filing for tab-cel and a strategic commercial collaboration with Pierre Fabre, ATA188’s FDA Fast Track designations and new data reinforcing its potential to reverse or halt disability in progressive multiple sclerosis, 2021 provided strong validation for Atara and our industry-leading allogeneic T-cell pipeline," said Pascal Touchon, President and Chief Executive Officer of Atara.
"2022, which has already delivered two landmark publications confirming EBV as the leading cause of MS in advance of our interim analysis from our ATA188 Phase 2 study, and a long-term strategic manufacturing partnership with Fujifilm, will be a critical year as we progress our strategic priorities. Although further engagement and alignment is required with FDA to determine the path forward for a BLA submission in the U.S., we anticipate a groundbreaking EU approval this year that will position tab-cel as the first ever allogeneic off-the-shelf T-cell therapy available for patients."
Tabelecleucel (tab-cel) for Post-Transplant Lymphoproliferative Disease (PTLD)
Atara has performed extensive studies demonstrating analytical comparability between the tab-cel manufacturing process versions used for the pivotal study and that intended for commercialization
Comprehensive comparability analyses included all 74 available product lots manufactured by Atara and covered 21 key attributes associated with potency, purity, and alloreactivity. Atara believes analytic comparability between tab-cel process versions has been demonstrated based on well-established statistical methodology and application of ICH1 guidelines and is further supported by significant and consistent clinical experience
These comparability data analyses were submitted to the European Medicines Agency (EMA) through our MAA filing in November 2021 and the review, under Accelerated Assessment, is progressing as planned following receipt of EMA day 80 Critical Assessment report, with anticipated approval in Q4 2022
A Type B CMC meeting was conducted in late February 2022 with the U.S. Food & Drug Administration (FDA) review team to discuss and potentially align on comparability between commercial and pivotal clinical trial products
The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use
Preliminary meeting responses and discussion did not result in alignment on comparability and the FDA has initially recommended Atara conduct a clinical study with commercial product as they do not agree that comparability has been demonstrated
Atara has responded with additional questions to clarify the FDA’s view and has suggested several alternative approaches to progress to a BLA submission given tab-cel is a BTD product that addresses an urgent medical need and has the potential to save the lives of patients with an ultra-rare, often fatal disease with no approved therapeutic options
Additional interactions with the Agency are expected, including receipt of final Type B CMC meeting minutes. However, based on the preliminary feedback received from the FDA, Atara does not currently expect to file a BLA in Q2 2022.
Atara expects further engagement with FDA on potential pathways to a BLA submission for tab-cel and plans to provide a further update during its next quarterly call
After entering an exclusive commercialization collaboration in Q4 2021, Atara is working with Pierre Fabre to prepare for the launch of tab-cel in Europe while adapting its U.S. commercialization preparation to account for possible delays in submission and potential approval of a BLA in the U.S.
Tab-cel for Potential Additional Indications
The multi-cohort Phase 2 study evaluating tab-cel in six additional patient populations for EBV+ immunodeficiency-associated lymphoproliferative diseases (IA-LPDs) and other EBV-driven diseases is currently enrolling in the U.S. and EU
First data from the multi-cohort study is on track for presentation in 2023
ATA188 for Progressive Multiple Sclerosis (MS)
Recent landmark studies further validate Atara’s approach and EBV-targeted platform. Publications in Science and Nature provide compelling new epidemiological evidence that EBV is the leading cause of MS and mechanistic evidence showing how EBV infection can initiate and propagate the autoimmune attack on the brain in MS
The FDA granted Fast Track designation to ATA188 for non-active primary progressive multiple sclerosis (PPMS) and non-active secondary progressive multiple sclerosis (SPMS), two populations with high unmet medical need and limited treatment options
Encouraging data presented at ECTRIMS 2021 from the ongoing Phase 1 open-label extension study of ATA188 with up to 39 months follow-up demonstrated that 20 out of 24 patients had sustained disability improvement or stabilization of disease on expanded disability status scale (EDSS)
Patients who achieved sustained EDSS improvement at any time showed significant increase in Magnetization Transfer Ratio (MTR) in non-enhancing T2 lesions at 12 months compared to baseline, suggestive of remyelination
Atara continues to advance enrollment in the Phase 2 EMBOLD study, with target enrollment of 80 patients expected soon after a planned formal interim analysis (IA) in Q2 2022
The IA will include efficacy, safety, and biomarker data to inform adjustments to sample size, if needed, to optimize likelihood of Phase 2 success, and confirm the Company’s current development strategy moving forward
A key data point at the time of the IA will be EDSS improvement at six months for applicable patients. In the Phase 1 study, EDSS improvement at six months was >85 percent predictive of achieving sustained EDSS improvement at 12 months, the primary endpoint of EMBOLD
Following the IA, Atara plans to communicate next steps for the program, including rationale, while still maintaining the integrity of the study. Atara also plans to interact with the FDA following the IA to discuss potential development pathways for ATA188
Prior to conducting the IA in Q2 2022, the Company will host a public webcast, Atara MS Day, for the investor community on March 22nd to review the key drivers generating excitement around our potentially transformative ATA188 MS program. The Company will also communicate new areas of development, including exploratory work on a differentiated EBV vaccine with encouraging pre-clinical data
CAR T Programs
Atara is building an innovative next-generation CAR T platform, which includes key features needed for efficacy and persistence, such as the use of PD-1 dominant negative receptor (DNR) and 1XX CAR co-stimulatory signaling domain technologies
The CAR T platform retains the endogenous T-cell receptor (TCR), shown to be essential for T cell persistence and survival
ATA2271/ATA3271 (Solid Tumors Over-Expressing Mesothelin)
The global strategic collaboration for autologous ATA2271 and allogeneic ATA3271 with Bayer continues to progress
Encouraging early safety and persistence of ATA2271 from lower dose cohorts of the ongoing Phase 1 dose-escalation trial in patients with advanced mesothelioma was presented at the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress in December 2021
Memorial Sloan Kettering Cancer Center (MSK) notified the FDA of a fatal serious adverse event (SAE) associated with a patient treated in the third, higher dose cohort in the ongoing Phase 1, MSK-conducted dose-escalation clinical study of autologous mesothelin CAR T, ATA2271
MSK has voluntarily paused enrollment of new patients in the ATA2271 study on a temporary basis while additional information regarding the case is gathered and reviewed. The FDA notified MSK of its agreement with this approach
Subject to the outcome of this review and resumption of enrollment of new patients in this study we expect to provide a data update from this Phase 1 study in 2022
The single case involved a patient with a history of multiple malignancies and other comorbidities undergoing treatment for advanced recurrent mesothelioma
The temporary pause in ATA2271 study enrollment does not impact the IND-enabling work currently underway to advance ATA3271, a separate off-the-shelf, allogeneic CAR-T therapy targeting mesothelin using next-generation PD-1 DNR and 1XX CAR technologies for patients with advanced mesothelioma, with an expected IND filing in Q4 2022
Atara’s pipeline programs, including ATA3271, ATA3219, tab-cel, and ATA188 all utilize the Company’s allogeneic EBV T-cell platform, the safety and tolerability of which has been demonstrated by clinical studies and experience in approximately 400 patients in various disease areas with no SAEs, including cytokine release syndrome (CRS), observed to date
ATA3219 (B-cell Malignancies)
Atara is progressing ATA3219, our potential best-in-class, allogeneic CAR T for B cell malignancies expressing CD19, and expects to submit an IND in Q4 2022
ATA3219 is an optimized approach to address high unmet medical need, leveraging our next-generation 1XX CAR co-stimulatory signaling domain and allogeneic EBV T-cell platform and does not require TCR or human leukocyte antigen (HLA) gene editing
Allogeneic T-Cell Platform Development and Operations
Atara entered a strategic manufacturing partnership in January 2022 with FUJIFILM Diosynth Biotechnologies (FDB), a subsidiary of FUJIFILM Corporation (Fujifilm), under which Fujifilm will acquire Atara’s T-cell Operations and Manufacturing (ATOM) facility for USD 100 million upfront, retaining current manufacturing and quality staff at the site. Closing of the transaction is expected to occur in April
As part of the long-term supply agreement, which could extend to 10 years following anticipated completion of the transaction, FDB will also provide Atara with flexible capacity and specific capability needed to manufacture and support the Company’s maturing and promising pipeline
Atara continues to leverage its recently established and now fully operational Thousand Oaks-based Atara Research Center (ARC), which houses the Company’s Pre-Clinical, Translational Sciences, Manufacturing Process Sciences, and Analytical Development Teams to further drive innovation
Fourth Quarter and Full Year 2021 Financial Results
Cash, cash equivalents and short-term investments as of December 31, 2021 totaled $371.1 million, as compared to $500.7 million as of December 31, 2020
The December 31, 2021 cash balance includes $47.7 million of net proceeds from the sale of 2,836,062 shares of common stock through the Company’s ATM facilities in the fourth quarter, and a $45.0 million upfront payment received under the Pierre Fabre Commercialization Agreement, partially offset by operating cash outflows
Atara believes that its cash as of December 31, 2021, together with the anticipated $100.0 million payable to Atara upon closing of the strategic transaction with FDB, will be sufficient to fund the Company’s planned operations into the fourth quarter of 2023
Net cash used in operating activities was $34.3 million and $220.5 million for the fourth quarter and fiscal year 2021, respectively, as compared to $4.1 million and $180.8 million for the same periods in 2020; the increase in operating cash usage in 2021 was primarily due to a $33.5 million increase in net loss and increased usage of net working capital, partially offset by $45.0 million received under the Pierre Fabre Commercialization Agreement
Atara reported net losses of $93.3 million, or $0.96 per share, and $340.1 million, or $3.63 per share, for the fourth quarter and fiscal year 2021, respectively, as compared to $81.3 million, or $0.95 per share, and $306.6 million, or $4.15 per share, for the same periods in 2020
Total operating expenses include non-cash expenses of $16.5 million and $63.0 million for the fourth quarter and fiscal year 2021, respectively, as compared to $13.6 million and $59.4 million for the same periods in 2020
Research and development expenses were $79.1 million and $282.0 million for the fourth quarter and fiscal year 2021, respectively, as compared to $65.6 million and $244.7 million for the same periods in 2020
The increases in the fourth quarter and fiscal year 2021 were primarily due to higher employee-related and overhead costs from increased headcount, higher facility-related costs in support of continuing expansion of research and development activities and increased spending on research, development and clinical trial costs to further advance ATA188 and CAR T programs
Research and development expenses include $8.4 million and $32.1 million of non-cash stock-based compensation expenses for the fourth quarter and fiscal year 2021, respectively, as compared to $7.2 million and $31.5 million for the same periods in 2020
General and administrative expenses were $21.8 million and $78.8 million for the fourth quarter and fiscal year 2021, respectively, as compared to $16.1 million and $64.4 million for the same periods in 2020
The increases in the fourth quarter and fiscal year 2021 were primarily due to higher compensation-related costs from increased headcount and activities to support an anticipated tab-cel launch
General and administrative expenses include $5.6 million and $21.8 million of non-cash stock-based compensation expenses for the fourth quarter and fiscal year 2021, respectively, as compared to $4.3 million and $19.8 million for the same periods in 2020
Conference Call and Webcast Details
Atara will host a live conference call and webcast today, Monday, February 28, 2022, at 4:30 p.m. EST to discuss the Company’s financial results and recent operational highlights. Analysts and investors can participate in the conference call by dialing 877-407-8291 for domestic callers and 201-689-8345 for international callers, using the conference ID 13725930. 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.