The Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital has been awarded a three-year grant to support Rapa Therapeutics’ intermediate size Expanded Access Protocol (EAP) in Amyotrophic Lateral Sclerosis (ALS) from the National Institute of Neurological Disorders and Stroke (NINDS) at the National Institutes of Health (NIH).  The grant is supported by the ACT for ALS (Accelerating Access to Critical Therapies for ALS Act). This EAP will evaluate the benefits of Rapa Therapeutics’ (Rapa) investigational product RAPA-501, an Epigenetically Reprogrammed Autologous Hybrid TREG/Th2 T-Stem Cell Therapy, in people living with ALS (PALS). The project will be led by Healey & AMG Center faculty, Drs. Suma Babu, MBBS, MPH James Berry, MD, MPH and Sabrina Paganoni, MD, PhD in conjunction with Rapa.

“The funding from the NIH to support this important program will allow us to learn more about the biological effects of RAPA-501 and its safety in a broad population of people living with ALS,” said the study PIs, Drs. Babu, Berry and Paganoni.

“We are appreciative of NIH’s support to increase the availability of RAPA-501’s novel therapy. At Rapa, we are committed to bringing our reprogrammed T cell therapy to this underserved ALS patient population,” said Brian Radecki, Rapa’s Chief Executive Officer. “This trial will help facilitate realization of the ultimate goal of improving respiratory function and survival in this particularly high-risk ALS patient population that has essentially no other treatment options,” said Dr. Daniel Fowler, Rapa’s Chief Medical Officer.

This EAP will provide access to RAPA-501 for pwALS who have reduced pulmonary function and are otherwise not eligible for ALS trials. The RAPA-501 trial will provide important safety, biomarker and efficacy data in this high-risk population, which has an estimated 50% rate of respiratory failure or death within 6-months of study entry. The RAPA-501 EAP, will be conducted at up to 10 enrolling centers across the US, treat patients in an outpatient setting and will not use a placebo arm but will alternatively employ machine learning/Artificial Intelligence (A.I.) to investigate the effect of RAPA-501 compared to “virtual controls” (collaboration with Dr. David Ennist, CEO at Origent Data Sciences). Furthermore, the RAPA-501 EAP seeks to enroll a diverse population of pwALS and incorporates state-of-the-art remote monitoring during trial implementation (collaboration with Indu Navar, CEO at the citizen-driven research organization, EverythingALS).

Expanded Access, also referred to as Compassionate Use, is an FDA-regulated pathway that allows people with a serious and life-threatening disease to access an investigational drug that is not yet approved by the FDA. RAPA-501 is an autologous T-cell therapy (personalized drug product for each trial participant) that expresses a hybrid, induced regulatory T (iTREG) and Th2 phenotype designed to reduce inflammation, with the goal of slowing, stopping or reversing ALS disease progression. RAPA-501 cells are manufactured using automated closed system procedures at Rapa’s state-of-the-art GMP facility in Rockville, MD by a proprietary, patent pending process. After isolation of immune blood cells using an intravenous (IV) approach (apheresis), Rapa epigenetically reprograms the patient’s cells through incubation in culture conditions that incorporate mTORC1/mTORC2 inhibition and polarizing cytokines, and then returns the cryopreserved RAPA-501 product to the clinical trial site for up to four subsequent IV infusions to trial participants in an outpatient setting. In an ongoing clinical trial of RAPA-501 in pwALS (NCT04220190), RAPA-501 cells were safe (no product-related adverse events), biologically active (diverse anti-inflammatory effects), and showed early trends toward possibly slowing pulmonary function decline. The Phase 2/3 component of this continuous, adaptively designed trial is ongoing.

The researchers at the Healey & AMG Center for ALS are optimistic that this study will continue to pave the way for patient-centric and scientifically relevant EAPs to be conducted across the US. Such EAPs are implemented in parallel to late phase randomized controlled clinical trials and contribute research data to supplement clinical development programs of investigational products in ALS.

Background on ALS
Amyotrophic lateral sclerosis, ALS, is the most prevalent adult-onset progressive motor neuron disease, affecting approximately 30,000 people in the U.S. and an estimated 500,000 people worldwide. ALS causes the progressive degeneration of motor neurons, resulting in progressive muscle weakness and atrophy. There are currently few FDA therapies approved for treating ALS—riluzole, edaravone (IV and oral formulation), sodium phenylbutyrate/taurursodiol , and tofersen. Dextromethorphan/quinidine is also used for the symptomatic treatment of pseudobulbar affect (PBA) in people with ALS.

 About the Sean M. Healey & AMG Center for ALS at Mass General
At the Sean M. Healey & AMG Center for ALS at Mass General, we are on a quest to discover life-saving therapies for all individuals affected by ALS. Launched in November 2018, the Healey Center leverages a global network of scientists, physicians, nurses, caregivers, people with ALS and families working together to accelerate the pace of ALS therapy discovery and development.

Under the leadership of Merit Cudkowicz, MD and a Science Advisory Council of international experts, we are reimagining how to develop and test the most effective therapies to treat the disease, identify cures and, ultimately, prevent it. The key to our success is our tightly integrated research and clinical efforts, encouraging opportunities to bring the challenges our patients face every day into our laboratories, focusing investigations on finding solutions that will make a meaningful difference to our patients without delay. Our collaborative efforts are designing more efficient and effective clinical trials while broadening access to these trials for people with ALS.

About Rapa Therapeutics

Rapa Therapeutics is a clinical-stage T cell immunotherapy company located in Rockville, MD that has developed a Next-Generation Cell Therapy Platform focusing on innovative adoptive T cell products that harness the power of the immune system to create safe, cost-effective, curative T cell therapies. Rapa inhibits the mechanistic target of rapamycin (mTOR) pathway to epigenetically reprogram autologous polyclonal RAPA-201 Th1/Tc1 cell therapy for end-stage cancer (focused on solid tumors) and hybrid RAPA-501 induced TREG/Th2 T-stem cell therapy for the treatment of autoimmune and neurodegenerative diseases (initially, ALS). Rapa’s unwavering mission is to address the high unmet public health needs in these end-stage diseases and to extend the lives of patients so that they can spend more time with their families. Rapa’s clinical trial efforts using RAPA-501 have been partially supported by an award from the ALS Association.