OUR PIPELINE IS MAKING THE IMPOSSIBLE POSSIBLE
CAPSIDA APPROACH
Capsid Engineering, Cargo Optimization, Translational Biology, Process Development and Manufacturing, and Clinical Development All Under One Roof
Capsida Biotherapeutics has designed one of the industry’s only fully integrated, end-to-end gene therapy solutions.
Built through a combination of in-house R&D and industry partnerships, our therapeutic approaches are designed to bring therapies to patients with both monogenic and polygenic diseases.
CAPSID ENGINEERING
At Capsida, the scale at which we can engineer and screen capsids is unrivaled. Our scientists build large-scale libraries of diverse capsid variants and biologically screen them, identifying optimal capsids to target tissues and cells in diseased organs. Our process benefits from:
Precise targeting:
Our therapies are designed to target specific organs and cell types while limiting off-target tissue tropism and cell transduction, generating a significantly increased therapeutic index.
Positioning for superior safety and efficacy:
Our non-invasive, IV-delivered therapies have the potential to be administered at lower doses than wild-type AAV vectors, opening opportunities for indications previously inaccessible by gene therapy.
High-throughput screening and Automation:
By biologically screening billions of capsid variants in models relevant to humans, we’re able to select for organ and cell-type specificity through a desired route of administration. Our automation platform significantly increases throughput yielding larger data sets to improve accuracy and reproducibility to identify optimal capsids more efficiently.
Iterative processes:
Through iterative rounds of engineering and screening, we have generated an unrivaled depth of biological data which we mine for improved capsids for targets in our pipeline. Continued efforts allow for building of the capsid profile to meet the needs of a specific program.
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DISCOVERY AND PRECLINICAL
To quickly advance our mission of providing meaningful therapeutic opportunities for patients with unmet medical need, Capsida progresses preclinical disease proof-of-concept in parallel with capsid engineering. Our R&D efforts begin by assessing the therapeutic efficacy needed to treat a given disease indication, providing guidance for the capsid engineering efforts, and then performing continuous discovery efforts in the disease model of interest to refine therapeutic expectations.
In each case, the novel engineered capsid is just half of the drug product. Our development process for the other half, the encapsidated gene cargo, begins by investigating the appropriate therapeutic strategy suited for the disease of interest – whether that is gene supplementation, targeted knock-down, vectorized antibodies or gene editing. Our scientists progress development and optimization of cargo in lockstep with that of the capsid, providing parallel and complementary paths for improvement of efficacy and safety profiles for our novel drug products.
Optimized cargo is then paired with the novel capsid and the complete drug substance is characterized for its ability to safely achieve efficacy thresholds expected to treat the disease. Once a development candidate has been selected, IND-enabling translational efforts begin to define the safe and efficacious therapeutic index of the drug product and establish clinical dosing rationale.
MANUFACTURING OPERATIONS
At Capsida, we are singularly focused on rapidly getting our high quality, life-changing therapies to patients who are suffering from debilitating diseases. Our end-to-end internal process development, analytical development and manufacturing capabilities, keeps the entire process in-house, eliminating the need for contract development and manufacturing organizations (CDMOs). With a robust quality management system overseeing our internal operations, we can reliably deliver high quality medicines to patients in need.
Our AAV suspension manufacturing process is currently scaled to 200L, with the ability to expand to 1000L scale. Through close integration with our Capsid Engineering team, we conduct extensive manufacturability assessments to ensure the productivity and product quality of our selected capsid/cargo candidates to enable speed to clinic at the lowest possible cost.
In 2021, we commissioned our cGMP manufacturing facility in Thousand Oaks, California. The facility includes modular clean-room suites for drug substance and filling operations that have been designed and constructed with environmental and personnel controls to meet commercial cGMP requirements. Internal Analytical Development and Quality Control laboratories are in place to support rapid assay development and product release. As our product portfolio grows, we have the ability to expand our manufacturing footprint as needed.
IOur mission is to serve patients, and our fully integrated manufacturing capabilities differentiate us from others in our ability to fulfill that mission.
DISCOVERY AND PRECLINICAL
At Capsida, we are focused on improving the lives of patients with severe and debilitating diseases. First and foremost, we approach patients holistically, working closely with advocacy groups, patients, and caregivers to ensure we are meeting patient needs.
Our highly skilled clinical development leadership has extensive experience across a wide range of adult and pediatric diseases, treatment modalities, and innovative trial design with a proven track record of bringing novel medicines to market. We collaborate closely with regulatory science and clinical operations experts to ensure a holistic and comprehensive approach to drug development.
We are excited to partner with patients, caregivers, physicians, and health authorities to bring Capsida’s differentiated gene therapies to patients.
MANUFACTURING OPERATIONS
At Capsida, we are singularly focused on rapidly getting our high quality, life-changing therapies to patients who are suffering from debilitating diseases. Our end-to-end internal process development, analytical development and manufacturing capabilities, keeps the entire process in-house, eliminating the need for contract development and manufacturing organizations (CDMOs). With a robust quality management system overseeing our internal operations, we can reliably deliver high quality medicines to patients in need.
Central Nervous System Disorders
Crossing the blood-brain barrier to target the brain, while limiting exposure to non-targeted organs — such as the liver – has been a significant challenge in the gene therapy field. With our next-generation capsids, we can transduce brain cells with lower doses, which limits accumulation in the liver and other organs. As our capsids further evolve, we are achieving even higher on-target tropism while simultaneously de-targeting the liver.
Almost all gene therapies in CNS have been aimed at treating ultra-rare disorders, most often in infants. Typically, AAV9-delivered treatments penetrate a very small percentage of brain cells, restricting their use to diseases where limited penetration is sufficient – mostly a subset of ultra-rare, infant diseases.
Capsida’s proprietary technology enables the creation of engineered capsids that can penetrate a larger proportion of brain cells, enabling our pipeline of rare and more common CNS diseases with high unmet medical needs across all age groups.
These CNS therapies are engineered to target specific organs and to simultaneously limit the penetration of non-targeted organs – especially the liver, enabling intravenous (IV) administration. IV delivery is important because this allows the greatest potential for efficacy by using the body’s natural blood flow to deliver our gene therapy to the CNS. Additionally, IV delivery limits the risks associated with more invasive delivery methods such as intra-cisterna magna (through the base of the skull into the cerebrospinal fluid surrounding the brain), intrathecal (across the spine into the cerebrospinal fluid bathing the spinal cord), or direct administration into the brain tissue. Capsida has developed IV-delivered capsids with greater than 1000-fold difference in CNS expression versus liver targeting relative to naturally occurring AAV9.
We have two wholly owned programs. One remains undisclosed, but the other is described below:
Genetic Epilepsy Due to STXBP1 Mutations
Genetic epilepsy caused by mutations in the syntaxin-binding protein 1 (STXBP1) gene is a devastating developmental epileptic encephalopathy estimated to affect one in 30,000 children globally. It is associated with severe developmental delay and intellectual disability, treatment-resistant seizures, and sudden unexpected death in epilepsy (SUDEP). STXBP1 genetic epilepsy is caused by mutations in the STXBP1 gene encoding a protein involved in the release of neurotransmitters and neuropeptides, which are responsible for communication across neurons in the brain and throughout the central nervous system. There are no disease-modifying therapies for STXBP1 genetic epilepsy. Current treatments are supportive only, and include anti-seizure medication, and physical, occupational, and speech therapy.
Capsida is developing a novel gene therapy, CAP-002, for the treatment of this severe disorder with high unmet need. CAP-002 is designed to stably supplement STXBP1 protein throughout the brain after a single intravenous infusion, with the goal of providing a disease modifying therapy that corrects the underlying disease pathology and significantly improves the quality of life for patients with genetic epilepsy due to STXBP1 mutations. Capsida has a license agreement and research collaboration with Baylor College of Medicine and Associate Professor of Neuroscience Mingshan Xue, who has developed multiple STXBP1 mouse models and AAV gene therapy approaches, to support development of this program.
López-Rivera et al, 2020, Abramov et al, 2020, Stamberger et al, 2016, Saitsu et al., 2008; Stamberger et al., 2016