Pipeline & Programs
Fulfilling the Promise of Centyrin-based Therapies
Aro Biotherapeutics is harnessing its Centyrin platform to develop therapies that change the course of treatment for the most devastating diseases. We are building a product pipeline that will focus on novel medicines that will enable targeted delivery of oligonucleotides - and potentially other drug payloads - to a number of different cell types. Our initial wholly owned internal Aro pipeline is focused on orphan genetic and immune mediated diseases.
Our strategy also includes building a partnered pipeline of new therapies by forming collaborations with industry leaders. Via external partnerships, we can combine Centyrins with a variety of different drug classes to enable effective targeting and delivery of diverse therapeutics.
What is Pompe Disease?
Pompe Disease is a rare, inherited/genetic disease characterized by debilitating muscle weakness that progresses over time. While every patient’s journey is unique, common symptoms include difficulty walking, problems swallowing, digestive issues, difficulty breathing, and fatigue. Those with the most severe form of Pompe Disease display symptoms at birth and have cardiac complications alongside profound muscle weakness. Hypertrophic cardiomyopathy and onset at birth separates this subgroup of patients with the infantile-onset form of the disease (IOPD) from those with the late-onset form (LOPD).
Pompe Disease arises from a mutation in the enzyme called acid alpha-glucosidase (GAA) that is responsible for the breakdown of glycogen in muscle. When there isn’t enough GAA present, glycogen accumulates, and this toxic build-up drives disease progression. Current approved enzyme replacement therapy (ERT) for Pompe disease aims to replace the missing enzyme with recombinant forms of GAA, in order to and reduce glycogen buildup in the muscle, and to restore normal muscle function; however a recognized shortcoming of these medicines is their relatively inefficient delivery to muscle tissue. Additionally, ERTs require biweekly intravenous infusions, are immunogenic in many patients, and the disease continues to progress leading to requirements for assisted ventilation, loss of mobility, and significantly reduced life expectancies. Thus it is well recognized that there is a substantial need for new treatment options that deliver enhanced efficacy, improved safety, and better convenience for patients with Pompe Disease.
What is Aro’s approach?
Aro is developing a novel approach in Pompe Disease known as substrate reduction therapy (SRT). ABX1100 is a first-in-class Centyrin-siRNA conjugate that is designed to reduce glycogen levels in the muscle by inhibiting the expression of the enzyme responsible for glycogen production, glycogen synthase 1 (GYS1). A mouse cross reactive Centyrin – siRNA conjugate demonstrated robust and muscle-specific inhibition of the GYS1 gene in preclinical animal studies, which has led to significant reductions of glycogen in target tissues. We plan on advancing ABX1100 to human clinical studies in 2023.
ABX1100 for Pompe Disease
ABX1100 is a human CD71 specific Centyrin covalently conjugated to the sense strand of a Gys1 specific siRNA via a non cleavable linker
Each component of ABX1100 has been optimized for specificity and potency vs human CD71 or Gys1 mRNA targets
Aro’s unique Centyrin-siRNA conjugate approach demonstrates durable and tissue-specific activity in muscle and lack of effect in kidney or liver
Preclinical studies in the Pompe mouse model with a mouse specific Centyrin-siRNA conjugate demonstrated durable, efficient and specific GYS1 mRNA and protein knockdown, leading to robust glycogen reduction in skeletal muscle
Centyrin-siRNA conjugates demonstrate lack of immunogenicity in human T cell screens, and are well tolerated in preclinical in vivo models