Serina Therapeutics (SER) Investor presentation summary

Immunogenicity and safety concerns with PEG-lipid LNPs

• High incidence of anaphylaxis observed with mRNA vaccines using PEG-lipid LNPs, with rates much higher than traditional vaccines.

• Anaphylaxis is linked to high titers of anti-PEG IgG and IgM, which bind to LNPs, activate complement, and cause basophil degranulation.

• Anti-PEG antibodies are boosted by mRNA vaccination, especially with Moderna, leading to increased immune cell association and complement activation.

• Pre-existing anti-PEG antibodies are associated with severe allergic reactions to PEGylated drugs, as seen in clinical trials with PEGylated aptamers.

• Anti-PEG antibodies can reduce efficacy of PEGylated therapies, including FVIII for hemophilia and patisiran for amyloidosis.

POZ-lipid (PEOZ) as a non-immunogenic alternative

• PEOZ-lipid can replace PEG-lipid in LNPs, producing similar biophysical properties and payload delivery.

• LNPs with PEOZ-lipid selectively target antigen-presenting cells in vivo, a novel and reproducible observation.

• PEOZ-lipid LNPs fail to elicit detectable IgM or IgG responses in animal models, even at high doses and repeat dosing.

• Biophysical characterization shows PEOZ-lipid LNPs match PEG-lipid LNPs in size, polydispersity, zeta potential, and encapsulation efficiency.

• PEOZ-lipid LNPs may provide a safer and more effective alternative for gene delivery and drug formulations.

Clinical and translational implications

• High anti-PEG antibody titers post-vaccination can neutralize PEGylated therapies, leading to clinical failures and adverse events.

• The broader LNP community is actively seeking alternatives to PEG-lipids due to these safety and efficacy concerns.

• PEOZ-lipid LNPs offer a promising path forward for reducing immunogenicity and improving patient outcomes in gene and drug delivery.