Intermediate-Size Expanded Access Trial of Autologous Hybrid TREG/Th2 Cell Therapy (RAPA-501) of Amyotrophic Lateral Sclerosis

ALS is a lethal neurodegenerative disease accelerated by neuroinflammation. Current FDA-approved
therapies have modest benefits and do not address inflammation. To address this, RAPA Therapeutics, LLC
(RAPA) has developed an autologous T cell therapy (RAPA-501) that reduces inflammation, with the goal of
reducing ALS morbidity and mortality. RAPA-501 are manufactured ex vivo to attain dual TREG/Th2 anti-
inflammatory activity and a T-stem phenotype that permits T cell therapy without conditioning chemotherapy. In
an ongoing clinical trial of RAPA-501 in people with ALS (pwALS) (NCT04220190), RAPA-501 cells were found
to be safe (no product-related adverse events), biologically active (diverse anti-inflammatory effects in pwALS),
and showed early trends toward stabilizing pulmonary function decline. A phase 2/3 expansion cohort was added
to the trial to assess whether RAPA-501 is efficacious in standard-risk pwALS.
We will extend RAPA-501 therapy to pwALS not eligible for this ongoing phase 2/3 trial or other ALS trials,
which nearly universally require that participants have a slow vital capacity (SVC) value of ≥50% of predicted
normal. The proposed EAP will enroll pwALS who have SVC values <50%. This population of pwALS is
considered “high risk” (~50% chance of respiratory failure or death within 180 days) and thus particularly suitable
for experimental immune therapies such as RAPA-501. In addition, the RAPA-501-EAP will not exclude pwALS
who have a prolonged time from ALS-related symptoms or low ALSFRS-R scores. Participants will receive four
RAPA-501 IV infusions (every 42-days at established safe dose, 80 x 106 cells/infusion). This RAPA-501-EAP
will further evaluate the safety of this therapy, expand an understanding of the RAPA-501 therapeutic mechanism
of action, and evaluate signals of efficacy in this real-world population of pwALS using standard methods and
Origent Data Sciences machine learning ALS prediction algorithms.
The RAPA-501 EAP will be led by investigators at Mass General Hospital (MGH; Drs. Berry, Babu, and
Paganoni) and sponsored by RAPA, which is responsible for RAPA-501 manufacturing and FDA regulatory
filings under existing IND 019480 (Dr. Fowler, Sponsor). Clinical trial site investigators have experience with
RAPA-501 therapy (MGH; Hackensack University Medical Center; and Mayo Clinic Arizona) or other cells
therapies. Sites are geographically diverse and likely to accrue a significant number of underserved pwALS (U
of Iowa; U of Idaho; Providence Hospital, Portland, Oregon; UC-Irvine; Columbia, NYC). In addition, several
research collaborations will emanate from the intensive study of the clinically-annotated, valuable research
samples obtained from the RAPA-501 EAP.

Grant Number: 5U01NS136020-03
NIH Institute/Center: NIH
Principal Investigator: James Berry