Jakob Dupont, MD

"This is a first in class cell therapy in multiple sclerosis. What's so critical, going back to the Hippocratic oath that we all sign up for as physicians is, first and foremost, do no harm. So, the safety profile here is critical."

Part 2 of a study evaluating ATA188 (NCT03283826) safety/tolerability, product kinetics, and biological and clinical effect in adults with progressive forms of multiple sclerosis (MS) is now underway.

The design of part 2 of the phase 1, multicenter double-blind, placebo-controlled study was presented by Amit Bar-Or, MD, FRCP, FAAN, FANA, professor, and chief, MS Division, Perelman School of Medicine; director, Center for Neuroinflammation and Neurotherapeutics; staff neurologist, University of Pennsylvania; and research scientist, Children’s Hospital of Pennsylvania at the 

Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2021

The study will evaluate incidence of adverse events, change from baseline in cerebrospinal fluid (CSF) immunoglobulin G index, change from baseline in clinical disability on expanded disability status scale, Timed 25-Foot Walk, and/or 9-hole peg test, ambulatory activity monitoring, cervical spinal cord volume and whole brain volume on magnetic resonance imaging, the number of gadolinium-enhancing and new or enlarging T2 lesions on brain MRI scans. Other exploratory end points include assessment of potential biomarkers such as oligoclonal bands in CSF, persistence of ATA188, and cytokine profiling in blood and CSF compartments.

 spoke with Jakob Dupont, MD, MA, head of global research and executive vice president, Atara Biotherapeutics, the company that is developing ATA188, to learn more about the potential first-in-class cell therapy for MS. He also discussed the upcoming study’s design.

For more coverage of ACTRIMS Forum 2021, 

Bar-Or A, Gamelin L, Ye W, et al. Phase I, multicenter, two-part study of ATA188, an open-label, dose-escalation and double-blind, placebo-controlled dose-expansion study. Presented at ACTRIMS Annual Forum; February 25-27, 2021. Abstract P048.

Videos

The head of global research and executive vice president of Atara Biotherapeutics discussed the upcoming study evaluating ATA188. 

Developing Cell Therapy for Progressive MS: Jakob Dupont, MD, MA

“We're actually seeing physical improvement in these patients with progressive MS, which is unheard of in this patient population. By definition, progressive MS... gets worse and worse over time. So, moving the clock back and seeing physical improvement, as we are in our early clinical experience, is quite notable.”

Part 2 of a study evaluating the safety/tolerability, product kinetics and biological and clinical effect of ATA188 (NCT03283826) in adults with progressive forms of multiple sclerosis (MS) is now underway.

The design of part 2 of the phase 1, multicenter double-blind, placebo-controlled study was presented at the 

, February 25-27, by Amit Bar-Or, MD, FRCP, FAAN, FANA, professor and chief, MS Division, Perelman School of Medicine; director, Center for Neuroinflammation and Neurotherapeutics; staff neurologist, University of Pennsylvania; and research scientist, Children’s Hospital of Pennsylvania.

The study will evaluate end points including incidence of adverse events, change from baseline in cerebrospinal fluid (CSF) immunoglobulin G index, change from baseline in clinical disability on expanded disability status scale, Timed 25-Foot Walk, and/or 9-hole peg test, ambulatory activity monitoring, cervical spinal cord volume and whole brain volume on magnetic resonance imaging, the number of gadolinium-enhancing and new or enlarging T2 lesions on brain MRI scans. Other exploratory endpoints include assessment of potential biomarkers such as oligoclonal bands in CSF, persistence of ATA188, and cytokine profiling in blood and CSF compartments.

 spoke with Jakob Dupont, MD, MA, head of global research and executive vice president, Atara Biotherapeutics, the company that is developing ATA188, to learn more about the potential of the investigational therapy to treat progressive MS. He also outlined the upcoming part 2 of the study.

The head of global research and executive vice president of Atara Biotherapeutics discussed improvements seen in patients treated with the investigational therapy. 

ATA188’s Potential in Progressive MS: Jakob Dupont, MD, MA

"We're developing this therapy for progressive MS, which is the most difficult-to-treat population of patients with MS. And as such, it really represents the greatest unmet need.”

Part 2 of a phase 1, multicenter study evaluating the safety/tolerability, product kinetics and biological and clinical effect of ATA188 (NCT03283826) in adults with progressive forms of multiple sclerosis (MS) is now underway.

The study design of the double-blind, placebo-controlled study was presented at the 

, February 25-27, by Amit Bar-Or, MD, FRCP, FAAN, FANA, professor and chief, MS division, Perelman School of Medicine, and director, Center for Neuroinflammation and Neurotherapeutics, and staff neurologist, University of Pennsylvania, and research scientist, Children’s Hospital of Pennsylvania.

Researchers will evaluate endpoints including incidence of adverse events, change from baseline in cerebrospinal fluid (CSF) immunoglobulin G index, change from baseline in clinical disability on expanded disability status scale, Timed 25-Foot Walk, and/or 9-hole peg test, ambulatory activity monitoring, cervical spinal cord volume and whole brain volume on magnetic resonance imaging, the number of gadolinium-enhancing and new or enlarging T2 lesions on brain MRI scans. Other exploratory endpoints include assessment of potential biomarkers such as oligoclonal bands in CSF, persistence of ATA188, and cytokine profiling in blood and CSF compartments.

 spoke with Jakob Dupont, MD, MA, head of global research and executive vice president, Atara Biotherapeutics, the company that is developing ATA188, to learn more about part 2 of the study of its investigational therapy.

The head of global research and executive vice president of Atara Biotherapeutics discussed the trial design of part 2 of the study of ATA188. 

Evaluating ATA188 in Progressive MS: Jakob Dupont, MD, MA

“We are encouraged by what we’re seeing in the clinical trial because when we get into Cohort 3, we are seeing sustained disability improvement in these patients…this isn’t just one point in time where we’re seeing a patient doing better today.”

ATA188 is an investigational, allogeneic T-cell immunotherapy for patients with progressive multiple sclerosis (MS) being developed by Atara Biotherapeutics. Specifically, the agent targets cells infected by Epstein-Barr virus (EBV), which literature has suggested plays a role in the disease processes of MS.

The data from this first-in-human, phase 1, multicenter study (NCT03283826) were presented at 

MS Virtual 2020, the 8th joint ECTRIMS-ACTRIMS meeting, 

September 11–13, 2020. The readout included data from the first part of the trial, the open-label dose-escalation portion, and the second part—a double-blind, placebo-controlled dose-expansion study—is underway. All told, the data suggest that the agent is safe to administer and pointed to signs of positive clinical outcomes based on sustained disability improvement (SDI) measurements.

To find out more about the data that were presented and what this ATA188 could offer patients with progressive MS, 

 spoke with Jakob Dupont, MD, executive vice president, and head of global research and development, Atara Biotherapeutics. Dupont discussed the specifics of the data and offered his insight into the positive signs observed with SDI measures.

REFERENCE
Pender MP, Hodgkinson S, Broadley S, et al. Phase I study of ATA188, an off-the-shelf, allogeneic Epstein-Barr virus-targeted T-cell immunotherapy for progressive forms of multiple sclerosis. Presented at MS Virtual 2020 Joint ACTRIMS-ECTRIMS meeting; September 11–13, 2020. Abstract P0226.

The executive vice president and head of global research and development at Atara Biotherapeutics spoke to the findings of a phase 1 study of the cell therapy ATA188.

Jakob Dupont, MD

Articles

Developing Cell Therapy for Progressive MS: Jakob Dupont, MD, MA

ATA188’s Potential in Progressive MS: Jakob Dupont, MD, MA

Evaluating ATA188 in Progressive MS: Jakob Dupont, MD, MA

Jakob Dupont, MD: Phase 1 Data on Cell Therapy for Progressive MS