Driven by our mission to profoundly improve the lives of people affected by serious diseases, our proprietary AOC™ platform expands the ability to address targets and diseases previously unreachable with existing RNA therapies. Our AOC platform is built from years of in-house engineering that integrates oligonucleotide therapeutics, modulation of RNA processes, antibody engineering and conjugation, and advanced drug delivery techniques. We continue to follow the data as we advance our skeletal muscle clinical and early-stage programs and expand into other disease areas by targeting a range of different cells and tissues beyond the liver, which up until now have been inaccessible with existing RNA-based therapeutics. Our vision is to leverage the broad flexibility of our AOC platform to target the root cause of diseases including both rare and common diseases.
We followed the data to engineer each component of our AOCs:
Components
Characteristics
Monoclonal
Approved mAbs offer:
- Well-established safety profiles
- High specificity and affinity
- Long half-lives
- Designed through engineering to be effector function null
- Epitope selection designed for optimal activity
Linker
- Known linker
- Applicable to multiple oligo modalities
- Enhanced for durability
- Engineered sites of conjugation
- Optimized ratio of oligonucleotides to antibodies
siRNA
Approved siRNA drugs have shown:
- Attractive safety profiles – no known thrombocytopenia, liver or renal toxicity
- Potency in the nanomolar range
- Sustained activity in the cytoplasm and nucleus
- Engineered to withstand lysosomal enzymes
- Selected and modified to diminish off-target effects
PMO
Approved PMO drugs have shown:
- Attractive safety profile
- Potency in the nanomolar range
- Sustained activity
- Engineered for efficient delivery to muscle – increased drug to antibody ratio
The flexibility of our AOC platform allows us to deploy various types of oligonucleotides, including small interfering RNAs (siRNAs) and phosphorodiamidate morpholino oligomers (PMOs), each of which modify RNA function in different ways. This allows us to use oligonucleotides that are tailored to modulate specific disease processes. Mechanisms of these oligonucleotides can range from reducing the expression of a disease-related RNA with siRNAs to correction of aberrant processing of RNAs with splice-modifying oligonucleotides.
OUR AOCS OFFER DISTINCT ADVANTAGES
We believe that the product candidates derived from our AOC platform will have the potential to impact a diverse set of diseases with the following advantages:
Expanding Scope of
Diseases Beyond Liver
Targeting new tissue and cell types, including muscle, immune cells and others
Selecting Most Potent
Oligonucleotide Type
Achieving ED50s at the nanomolar concentration
Enabling
Infrequent Dosing
Maximizing durability with sustained single dose RNA reductions in NHP beyond 12 weeks
Readily Reproducible
and Scalable
Utilizing the same monoclonal antibody across multiple programs
Beginning with our muscle disease franchise, our platform targets the underlying genetic cause of disease — from here our deep pipeline continues to advance and expand into additional cells and tissues, including research and development programs in cardiology and immunology.
Some of these programs are in development based on research collaborations while others are based on internal discovery efforts. We look forward to pursuing all of these programs as we work to revolutionize the delivery of RNA therapeutics to profoundly improve people’s lives.