REMIT (Rescue Mitochondrial Therapeutics): Unlocking Broad-Spectrum Mitochondrial Rescuers

Perlara, Pbc, Alameda CA

Investigators

Abstract

Project Summary Founded in 2014, Perlara PBC was the first biotech company established as a Public Benefit Corporation (PBC). Over the past decade, the company has pioneered the use of invertebrate model organisms—such as yeast, worms, and flies—for drug repurposing to address rare genetic diseases. Since 2022, Perlara has shifted its primary focus to the budding yeast Saccharomyces cerevisiae. This model organism offers unmatched speed, cost-efficiency, and suitability for studying inherited metabolic disorders, including congenital disorders of glycosylation (CDGs) and mitochondrial diseases like Leigh Syndrome. Within just two years, Perlara has developed a pipeline of 17 yeast-driven drug repurposing programs, each funded by affected families and resulting, in most cases, in the identification of clinically actionable compounds. Notably, the company’s flagship PMM2-CDG program has progressed from a yeast-based discovery to a fully enrolled Phase III pivotal study (NCT04925960) in under five years and with less than $5 million in funding. This program was advanced in collaboration with Maggie’s Pearl, LLC, a family-led organization (https://www.maggiespearl.com/). Building on the success of its yeast platform and targeting mitochondrial diseases, Perlara now plans to screen 8,400 repurposable drugs and nutraceuticals using Yarrowia lipolytica, an obligate aerobic yeast. By inhibiting specific complexes of the electron transport chain with pharmacological agents, this novel screening approach will uncover therapeutic candidates capable of restoring mitochondrial function. Promising compounds identified through these screens will undergo validation in human fibroblast models, utilizing assays such as Seahorse for mitochondrial function and RNA sequencing for transcriptomic profiling to inform clinical outcomes. The company’s commercialization strategy aims to combine clinical development pathways for FDA approval with partnerships involving nutraceutical manufacturers and compounding pharmacies. This approach will enable the direct-to-consumer availability of proprietary combination therapies. Over time, the model anticipates cost reimbursement from insurers, healthcare systems, and government programs, driven by the potential for system-wide savings. Additionally, these therapies are expected to create broader economic benefits by allowing caregivers to rejoin the workforce and empowering patients to lead more fulfilling and productive lives.