Serina Therapeutics (SER) Investor presentation summary

Immunogenicity and safety concerns with PEG-lipid LNPs

• High incidence of anaphylaxis and allergic reactions linked to PEG-lipid in mRNA vaccines, with rates far exceeding those seen with flu vaccines.

• PEG-lipid triggers high titers of anti-PEG IgM and IgG, which bind to LNPs, activate complement, and can cause loss of payload integrity and adverse immune responses.

• Anti-PEG antibodies are boosted by mRNA vaccination, especially with Moderna, and are associated with reduced efficacy of PEGylated therapies and increased risk of adverse events.

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

Limitations of PEG-lipid and clinical impact

• PEG-lipid LNPs induce both IgM and IgG responses in humans and animal models, leading to accelerated blood clearance and reduced therapeutic efficacy.

• High anti-PEG antibody titers after vaccination can neutralize PEGylated therapies, causing clinical failures such as spontaneous hemorrhage in Hemophilia A patients.

• Loss of efficacy in therapies like ONPATTRO is linearly correlated with anti-PEG antibody levels.

PEOZ-lipid as an alternative to PEG-lipid

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

• PEOZ-lipid LNPs selectively target antigen-presenting cells and show less accelerated blood clearance compared to PEG-lipid LNPs.

• Repeat dosing of PEOZ-lipid LNPs in rats fails to elicit detectable IgM or IgG responses, suggesting a safer immunological profile.

• PEOZ-lipid LNPs may provide a safe and effective alternative for programmable drug delivery platforms.