By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1
I’ve been following Kriya for quite some time. Last year, I had the pleasure of talking to Kriya Therapeutics’ CEO and Co-Founder, Dr. Shankar Ramaswamy about computational biology’s role in gene therapy on Cell & Gene: The Podcast. If you attended this year’s JPM, you may have heard Kriya’s update on its pipeline of gene therapies for prevalent conditions including geographic atrophy, thyroid eye disease, diabetes, NASH, trigeminal neuralgia, and epilepsy. Following the company’s announcements at JPM, I wanted to check back in with Dr. Ramaswamy for a brief update. Here’s what he had to say.
How does Kriya employ computational biology to make progress on each gene therapy in its pipeline?
Our platform is built on three foundational pillars: translational research, computational biology, and scalable manufacturing. The integration of these three core elements allows us to accelerate the design and development of gene therapies with optimal packaging, expression, and immune profiles. We use multiple proprietary computational algorithms to engineer each individual component of our vectors, often generating dozens of different versions with subtle yet important differences. Importantly, we can screen the manufacturability – in addition to biological performance and immune profile – of these constructs within our platform manufacturing process since this is a fully internalized capability. This gives us confidence in the reliability of scale up of our lead candidate. As you can imagine, we generate large volumes of data across our platform and pipeline programs, which require a sophisticated deployment of computational tools to analyze and integrate for future iterations of product design.
Kriya operates its own scalable GMP manufacturing facility. Explain how this asset will enable scalability and compliance across the entire pipeline.
Our scalable manufacturing facility is based in Research Triangle Park, North Carolina. Within this facility, we’ve built an integrated product development and manufacturing operation to accelerate translation into the clinic and drive manufacturing scale at a lower cost of production. Our platform supports the manufacturing of multiple AAV serotypes with industry-leading purity and yield, and extensive analytical characterization of product quality. We have the capability to seamless scale manufacturing in-house up to 3,000L bioreactors and can undertake multiple GMP campaigns to support our broad pipeline. Also, we deploy our manufacturing platform and analytical characterization tools from the very earliest stages of research through clinical development and future commercialization. This is important because it means we can scale without fundamental changes in process that can impact product quality or potency. This gives us higher degrees of confidence in the translation of our preclinical work into the clinic.
What is the 2024 outlook for Kriya’s pipeline?
Kriya’s current pipeline of gene therapies for common diseases spans three major therapeutic areas: ophthalmology, metabolic disease, and neurology with plans to advance the first of its gene therapy product candidates into the clinic in 2024. We expect up to five programs to enter the clinic by the end of 2025. Our publicly disclosed programs are for the following diseases:
- Ophthalmology: Geographic Atrophy, Thyroid Eye Disease
- Metabolic Diseases: Diabetes, NASH
- Neurology: Trigeminal Neuralgia, Epilepsy
Geographic Atrophy (GA): KRIYA-825 is designed as a one-time gene therapy expressing a fusion protein inhibiting complement C3 and C5, delivered by an in-office suprachoroidal injection with the objective of slowing GA lesion growth and vision loss.
Thyroid Eye Disease (TED): KRIYA-586 is designed as a one-time gene therapy expressing an antibody blocking insulin-like growth factor-1 receptors (IGF-1R), delivered by an in-office peribulbar injection with the objective of reducing proptosis and diplopia as well as other key features of TED.
Diabetes: KRIYA-839 is designed as a one-time gene therapy expressing insulin and glucokinase, delivered intramuscularly with the objective of driving durable glycemic control and reducing or eliminating the need for exogenous insulin.
Nonalcoholic Steatohepatitis (NASH): KRIYA-497 is designed as a one-time gene therapy expressing the native FGF21 protein, delivered intramuscularly with the objective of reducing fibrosis, reversing steatosis, and improving the overall metabolic profile of patients with later stages of NASH with liver predominant pathology (F3 and compensated F4).
Trigeminal Neuralgia (TN): KRIYA-748 is designed as a one-time gene therapy expressing a chemogenetically-gated ion channel, delivered through an injection into the trigeminal nerve with the objective of reducing the frequency and severity of debilitating paroxysmal pain attacks. Once expressed in the nerve, the channel is designed to selectively open in the presence of the orally-administered CNS-penetrant small molecule, varenicline (the FDA-approved generic medication for smoking cessation originally marketed under the brand name "Chantix®"), leading to the passage of chloride ions and reduced excitation of target neurons.
Focal Epilepsy: KRIYA-382 is designed as a one-time gene therapy expressing a chemogenetically-gated ion channel, delivered through a direct injection into epileptic foci within the brain with the objective of reducing the frequency and severity of seizures. Kriya’s epilepsy gene therapy uses a similar chemogenetic technology as is utilized in its trigeminal neuralgia program.