GEMMABio Awarded ARPA-H Funding to Pursue Innovative Base-editing Strategy for Rare Liver Diseases

- The goals of this project will be enabled through a partnership with Profluent Bio who will deploy its frontier AI models and its scalable base editor platform

- GEMMABio will utilize a nonviral approach, encapsulating mRNA coding for Profluent's base-editing machinery into lipid nanoparticles to target hepatocytes

- The award will support research & development that should lead to new personalized medicines for founder mutations that cause homozygous familial hypercholesterolemia and maple syrup urine disease

PHILADELPHIA, July 9, 2026 /PRNewswire/ -- Gemma Biotherapeutics ("GEMMABio"), a clinical-stage, global, genetic medicines company, today announced that it has been awarded funding by the Advanced Research Projects Agency for Health (ARPA-H). The project includes a partnership with Profluent Bio ("Profluent"), the frontier AI lab for biology. This award is made under ARPA-H's Treating Hereditary Rare diseases with In Vivo precision genetic mEdicines (THRIVE) program, and it will support the Regional-bAsed Personalized medIcines Development (RAPID) project to test new AI-designed base-editing systems. THRIVE is led by ARPA-H Program Manager Daria Fedyukina, Ph.D.

GEMMABio will work with Profluent to develop four distinct, lipid nanoparticle (LNP)-delivered, mRNA-encoded base-editing products targeting four founder-type mutations across two rare, life-threatening, monogenic liver diseases: homozygous familial hypercholesterolemia (HoFH), caused by mutations in the low-density lipoprotein receptor (LDLR) gene, and maple syrup urine disease (MSUD), caused by mutations in the branched chain keto acid dehydrogenase E1 subunit beta (BCKDHB) gene. As part of the collaboration, Profluent will deploy its catalogue of base editors generated using its protein language models. These base editors have been designed to correct any transition mutation with exceptional activity and specificity.

Founder mutations have resulted in geographic concentration of patients experiencing severe disease with limited treatment options. Focusing on specific, disease-prevalent variants will enable GEMMABio and Profluent scientists to establish a critical proof-of-concept for this flexible base-editing approach that will maximize patient-to-product ratio, ultimately reducing cost and increasing clinical impact.

"GEMMABio was founded to develop transformative genetic medicines for devastating rare diseases and to distribute these treatments globally," said GEMMABio President and Chief Executive Officer James M. Wilson, MD, PhD. "We believe our work with Profluent will lead to a novel and powerful base-editing approach that can be applied across diverse mutations and genetic diseases where the only unique component is guide RNA (gRNA). We believe these attributes may permit significant cost reductions and have the potential to increase access around the world."

"Profluent has built a core set of base editor variants derived from a single scaffold that leverage programmable PAM specificity and context-selective deaminases. The editors can be manufactured at large scale and combined with patient-specific gRNA, leading to a truly personalized gene editing platform," said Profluent's SVP of Gene Editing and Translation Peter Cameron, PhD. He added, "Developing a single scaffold is critical for simplifying clinical development and reaching platform approval."

Key project objectives include:

• Generation of engineered base editors: Profluent will bring its frontier AI models and base editors to the collaboration. Ultimately, a relatively small number of base editors will be selected, each with (1) a single Cas nickase scaffold designed with programmable PAM specificity, (2) a deaminase with context-selectivity to avoid bystander edits, and (3) a patient-specific gRNA that will lead to correction of the target mutation.
• Selection of LNP: In parallel, GEMMABio will identify a candidate LNP formulation for in vivo hepatocyte delivery of the optimized base editors from among a clinically validated library of LNPs.
• Creation of a collaboration on rare diseases with a number of Medicinal Product Regulators for this grant, and initiation of genetic screening protocol: A collaboration of regulators coordinated by the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA) will be assembled. All regulator feedback will be shared among collaboration partners in order to address concerns and streamline regulatory decision making for future clinical trial initiation in those locales. In addition, GEMMABio plans to develop a genetic screening protocol to support identification of patient populations with the selected founder mutations causing HoFH and MSUD.

"This unique opportunity brings together the AI-designed base editor technology of Profluent with the deep experience in rare diseases, genetic medicine technologies, and translational science of the GEMMABio team," said R. Jason Lamontagne, PhD, co-principal investigator for the RAPID project and Executive Director, Discovery Research, at GEMMABio. "This project has the potential to achieve maximal therapeutic effect with low cost of goods, which is critical for scaling in rare disease to allow for broader patient access."

GEMMABio's existing clinical and regulatory partnerships, business relationships, and R&D experience paired with Profluent's protein language models aim to fulfill THRIVE's goal of accelerating safe and scalable precision genetic medicines (PGMs) to deliver rapidly built, one-time treatments that can progress from concept to clinic in a few years while addressing needs across diverse patient populations. The RAPID project will provide critical proof-of-concept for future implementation of a broader base-editing strategy in rare disease therapeutics.

About Homozygous Familial Hypercholesterolemia (HoFH)
FH is a rare, life-threatening genetic disease that results in increased levels of circulating plasma LDL-cholesterol (LDL-C) and premature cardiovascular disease, most often caused by mutations in the LDLR gene. Most patients with one pathogenic variant (heterozygotes, HeFH) can be managed with aggressive pharmacologic therapy. Patients that inherit two pathogenic LDLR variants (homozygotes or compound heterozygotes, HoFH) have a more severe phenotype, are less common (0.3/100,000 births), and respond poorly to lipid-lowering agents. The most effective treatments for HoFH are liver transplant or LDL apheresis.

About Maple Syrup Urine Disease (MSUD)
MSUD is a rare metabolic disorder (<0.5/100,000 live births) in which the ability to break down branched-chain amino acids (BCAA) is impaired. It is caused by mutations in 1 of 3 genes responsible for making the enzyme complex that breaks down BCAA, and is characterized by sweet smelling urine, earwax, and sweat. Classic MSUD, the most common and most severe form of the disease, usually presents within the first days of life and can have significant neurological impacts that ultimately lead to death. The only definitive treatment is liver transplantation.

About GEMMABio
GEMMABio is a clinical-stage therapeutics company focused on speeding the research of and global access to life-changing advanced therapies for those living with rare diseases. The company conducts research and product development functions to bring gene therapy discoveries from the bench to the bedside faster and affordably. GEMMABio is led by gene therapy industry pioneer Jim Wilson and his team of experts, who previously conducted their work in academia. Learn more about GEMMABio at gemmabiotx.com and follow us on LinkedIn.

About Profluent
Profluent is the frontier AI lab for biology. Profluent builds powerful foundation models for all of life's molecules, unlocking solutions that transform medicine, agriculture, and beyond. Founded in 2022 and headquartered in Emeryville, CA, Profluent is backed by leading investors including Altimeter Capital, Bezos Expeditions, Spark Capital, Insight Partners, Air Street Capital, AIX Ventures, and Convergent Ventures. To learn more, visit profluent.bio or follow the company on LinkedIn, X, and YouTube.

SOURCE GEMMA Biotherapeutics