Benzinga | Sep 11, 2020 08:01AM EDT

Atara Biotherapeutics Reports All Progressive Multiple Sclerosis Patients with Sustained Disability Improvement at Six Months Confirmed Improvement at 12 Months in the Phase 1a Study of ATA188

Atara Biotherapeutics, Inc. (NASDAQ:ATRA), a pioneer in T-cell immunotherapy leveraging its novel allogeneic EBV T-cell platform to develop treatments for patients with severe diseases, including solid tumors, hematologic cancers and autoimmune disease, today announced the presentation of data from the first part of the ongoing Phase 1 study of ATA188 for the treatment of progressive forms of multiple sclerosis (MS). ATA188 is an off-the-shelf, allogeneic EBV-specific T-cell immunotherapy. These data demonstrate that ATA188 was well-tolerated across all four dose cohorts; patients who achieved sustained disability improvements at any timepoint maintained it at all future timepoints and a higher proportion of patients showed sustained disability improvements (SDI) with increasing dose. The results are featured in an e-poster at MSVirtual2020: 8th Joint ACTRIMS-ECTRIMS Meeting, held September 11-13, 2020.

"It is very encouraging to see that patients receiving ATA188 who achieved sustained disability improvement at any time point maintained it at all future time points and tended to also show improvements in fatigue and physical function at 12 months," said Jakob Dupont, Global Head, Research and Development. "These results together with a favorable safety profile highlight the potential of ATA188 for patients with progressive MS and reinforce our excitement around advancing the randomized placebo-controlled portion of the study which is currently enrolling."

This Phase 1a multicenter, open-label study of ATA188 in patients with progressive forms of MS was designed to establish safety and tolerability, to select the recommended dose for the randomized placebo-controlled Phase 1b study, which is currently actively recruiting, and to assess potential efficacy. Patients were treated across four dose-escalating cohorts (5 x 106, 1 x 107, 2 x 107 and 4 x 107 cells), with six patients each in cohorts 1-3 and seven patients in cohort 4.

The e-poster presented at ACTRIMS-ECTRIMS assesses safety as well as sustained disability improvement (SDI), defined as improvement in Expanded Disability Status Scale (EDSS) or Timed 25-Foot Walk (T25W) at ?2 consecutive time points. Other measures evaluated include Fatigue Severity Score (FSS), 12-item Multiple Sclerosis Walking Scale (MSWS-12), Multiple Sclerosis Impact Scale (MSIS-29), and whole brain volume (via magnetic resonance imaging, MRI).

All patients in cohorts 1-4 of this Phase 1 study showing SDI at six months, maintained improvement through 12 months. Additionally, a dose-related increase in the number of patients with SDI at 12 months was observed (42 percent in Cohorts 3 and 4 vs 17 percent in Cohorts 1 and 2) and EDSS was the main driver of SDI (vs T25FW) in five of the seven patients who achieved an SDI response at 12 months. These patients also showed a trend toward improvement in Fatigue Severity Scale, MS Impact Scale measuring physical function and the MS Walking Scale.

Data from the open-label extension (OLE) with redosing at 12 months show that all three patients that achieved SDI at 12 months maintained SDI at 15 months with the patient evaluated at 18 months maintaining SDI at that time point as well. A fourth patient achieved SDI during the OLE at 24 months.

The study found that across the four dose cohorts, ATA188 was well-tolerated in patients with progressive forms of MS. No dose-limiting toxicities and no fatal adverse events (AEs) have been reported. The safety profile has remained consistent with previously reported data.

A poster featured at ACTRIMS-ECTRIMS also details the Phase 1b double-blind randomized placebo-controlled study, which is actively recruiting. In addition to measuring disability progression, the study will evaluate other facets of disease, including: cognition and outpatient ambulatory activity; fatigue, and biological end points in blood and cerebrospinal fluid/CSF (IgG, synthesis and index, OCBs, product kinetics); and MRI imaging. This study will be amended and expanded to allow for SDI to become the primary end point.

In addition to the clinical data reported, Atara also presented at ACTRIMS-ECTRIMS preclinical translational data that further support the proposed mechanism of action of ATA188 targeting EBV-infected B cells. These combined analyses of T cells comprising ATA188 are consistent with its proposed mechanism of targeting EBV-infected B cells by recognizing MS-relevant EBV antigens on these cells via defined T-cell receptors (TCRs).

"Our innovative approach of targeting EBV-infected B cells has led to very encouraging clinical results as we see sustained disability improvement consistently over time throughout this first study with ATA188," said Pascal Touchon, President and Chief Executive Officer of Atara. "Although some treatments may delay disability progression in progressive MS, there are currently no treatment options in progressive MS that reverse the progression of disease. Therapies that improve disability would be very meaningful for patients with this progressive, debilitating, and life-altering disease. We are investing further in this valuable program in optimizing the protocol of our Randomized Control Trial, running new translational studies to further elucidate the Mode of Action and implementing novel process improvements using stirred-tank bioreactors to scale up manufacturing."

Atara Conference Call and Webcast Information

Atara will hold a conference call at 8:30 a.m. ET for analysts and investors to review the Phase 1a data and Atara's continued plans for the ATA188 program and provide an additional corporate update. The call will include:

* Pascal Touchon, President and Chief Executive Officer, Atara Biotherapeutics

* Jakob Dupont, MD, Executive Vice President, Global Head of Research and Development, Atara Biotherapeutics

* AJ Joshi, MD, Senior Vice President and Chief Medical Officer, Atara Biotherapeutics

Analysts and investors can participate in the conference call by dialing (888) 540-6216 for domestic callers and (734) 385-2715 for international callers, using the conference ID 6694633. 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.

Details of the MSVirtual2020 e-Poster Presentations:

Title: Phase I study of ATA188, an off-the-shelf, allogeneic Epstein-Barr virus-targeted T-cell immunotherapy for progressive forms of multiple sclerosis

Poster #: P0226

Abstract #: 1635

Title: Phase I, multicenter, two-part study of ATA188, an open-label, dose-escalation and double-blind, placebo-controlled dose-expansion study

Poster #: P0227

Abstract #: 1691

Title: Gene expression profiling and TCR diversity of ATA188, an off-the-shelf, allogeneic EBV-targeted T-cell immunotherapy for progressive MS (encore from AAN 2020)

Poster #: P0084

Abstract #: 1770