Poseida Showcases Advances in Genetic Medicine at ASGCT 27th Annual Meeting

Poseida Therapeutics, Inc., a clinical-stage biopharmaceutical company specializing in genetic medicines and allogeneic cell therapies, has announced promising preclinical data from its non-viral gene therapy programs. These findings, presented at the American Society of Gene and Cell Therapy (ASGCT) 2024 Annual Meeting, underscore the potential of Poseida’s proprietary technologies to treat genetic disorders such as Hereditary Angioedema (HAE) and Hemophilia A.

Hereditary Angioedema (HAE), a rare inherited condition, is marked by recurrent swelling episodes that can be life-threatening. Poseida's investigational therapy, P-KLKB1-101, employs the Cas-CLOVER™ gene editing system for precise, non-viral gene editing. This therapy targets the KLKB1 gene and has shown high specificity and efficiency in preclinical studies. Early data from non-human primates (NHP) indicate successful liver gene editing with minimal off-target effects, along with favorable safety and tolerability profiles. Ongoing research includes dose-finding studies in NHPs and preparations for Investigational New Drug (IND)-enabling studies.

Hemophilia A, another focus of Poseida's research, is an X-linked bleeding disorder caused by a deficiency in Factor VIII. Poseida's P-FVIII-101 leverages the company's transposon technology combined with nanoparticle delivery to achieve targeted gene insertion. Preclinical data demonstrate that a single dose can sustain Factor VIII levels for over 13 months in mice, with potential for repeat dosing thanks to its non-viral approach. Additionally, the therapy can be fine-tuned to adjust Factor VIII levels as needed, an important aspect for patient-specific treatment. Further optimization and validation in NHP models are underway.

Another innovative approach presented by Poseida combines adeno-associated virus (AAV) vectors with the company's piggyBac DNA insertion system. This hybrid method aims to achieve stable gene integration in a high percentage of liver cells, which is challenging with standard AAV or episomal approaches. Preclinical studies have shown exceptional efficacy in treating mouse models of severe Ornithine Transcarbamylase Deficiency (OTCD) and Phenylketonuria (PKU) using low AAV doses, demonstrating the potential of this method to reduce required dosages while maintaining therapeutic benefits.

Poseida's presentations also highlighted advancements in gene editing technology, featuring the enhanced Cas-CLOVER nuclease system. This system offers improved on-target editing efficiency without increasing off-target effects. Preclinical models have shown successful gene integration and phenotypical disease rescue, affirming the system's potential for precise gene editing applications.

Additionally, Poseida's research on lipid nanoparticle (LNP) formulations has focused on overcoming DNA delivery challenges to achieve high-efficiency transgene integration in vivo. Novel ionizable lipids and small molecules called Poseida Delivery Excipients (PDEs) have been identified, significantly enhancing DNA delivery and reducing pro-inflammatory responses when included in LNPs. These innovations could further strengthen Poseida's non-viral DNA platform for treating serious genetic disorders.

In conclusion, Poseida Therapeutics' non-viral gene editing and insertion technologies are showing significant promise in preclinical studies for the treatment of genetic disorders like HAE and Hemophilia A. The company's advancements in lipid nanoparticle formulations and gene editing systems underscore the potential for precise, effective, and safer genetic therapies, with ongoing research aimed at further validating and optimizing these approaches for clinical application.