Serina Therapeutics, Inc. · AMEX:SER
Serina Therapeutics — ACS – Division of Polymer Chemistry (March 2025)
36 slides from Serina Therapeutics's conference presentation, Mar 24, 2025
Slide 1: Characterization of Poly(oxazoline) Lipid Nanoparticles (LNP)
HIGHLY CONFIDENTIAL & TRADE SECRET 1 March 2025 ACS – Division of Polymer Chemistry Characterization of Poly(oxazoline) Lipid Nanoparticles (LNP) A Non-immunogenic LNP for Gene Delivery Randall Moreadith, MD, PhD, Chief Development Officer rmoreadith@serinatherapeutics.com
Slide 2: POZ Platform for Programmable Drug Delivery
Small Molecules / Lipid Nanoparticles / Antibody Drug Conjugates POZ Platform® for Programmable Drug Delivery April 2025 Non-confidential Presentation NYSE: SER
Slide 3: Forward Looking Statements
Forward Looking Statements 3 This presentation contains forward-looking statements that are based on management’s beliefs and assumptions and on information currently available to management. In some cases, you can identify forward-looking statements by the following words: “may,” “will,” “could,” “
Slide 4: Anatomy of LNPs
Anatomy of LNPs What if replacing the PEG-lipid with a POZ-lipid resulted in something truly extraordinary ? 4 Ionizable lipid Cholesterol mRNA Phospholipid PEG-lipid Ionizable lipid Cholesterol mRNA Phospholipid POZ-lipid
Slide 5: Anti-PEG antibodies and anaphylaxis summary
T • Consecutive cohort studies show that anaphylaxis occurs at an unusually high incidence rate in patients receiving the approved mRNA vaccines; current data suggest this is not classically characterized IgE-mediated (mast cell degranulation) • The high titers of anti-PEG IgM & IgG that are boosted
Slide 6: Balancing immunogenicity and reactogenicity Review
Balancing immunogenicity and reactogenicity Review 6
Slide 7: List of adverse events reported with the mRNA vaccines
Balancing immunogenicity and reactogenicity List of adverse events reported with the mRNA vaccines 7
Slide 8: Cohort study: incidence of anaphylaxis with mRNA vaccines
In A Consecutive Cohort Study in Stanford Medical Center Network The incidence rate of anaphylaxis meeting Brighton anaphylaxis criteria was 1:2,287 (the incidence of anaphylaxis with flu vaccine is ~ 1:2,000,000) Assessment of Allergic and Anaphylactic Reactions to mRNA COVID-19 Vaccines With Confi
Slide 9: Basophil activation tests in anaphylaxis patients
9 Eleven of the seventeen patients consented to additional studies. BAT assays revealed that patients with anaphylaxis gated activated CD63+ basophils in the presence of vaccine (A), PEG (not shown) - but not saline (C) The Anti-IgE panel (B) is the positive control IgG-mediated degranulation of bas
Slide 10: Is PEG the culprit? Yes.
Is PEG the culprit ? Yes. 10 of 11 patients had positive basophil activation tests to PEG 11 of 11 patients had positive basophil activation tests to the administered vaccine 10
Slide 11: We've seen this before: The Regado Bioscience story
We’ve seen this before … The Regado Bioscience story 11 • The REG1 system was a rationally-designed strategy to replace the anticoagulant heparin in the cardiac catheterization lab as an adjunct to percutaneous coronary artery procedures • Pegnivacogin (RB006) was a 40 kDa methoxy-PEG attached to an
Slide 12: The Regado Bioscience story
We’ve seen this before … The Regado Bioscience story 12 • All three patients were female with a history of allergic reactions • The onset of these SAEs occurred within minutes of the infusion • Review of the nonhuman primate studies revealed no aggregation, degradation or evidence of inflammatory cy
Slide 13: The Regado Bioscience story
We’ve seen this before … The Regado Bioscience story 13 • The IgGs in these patients were shown to bind linear PEG and branched PEG, presented as either methoxyPEG or hydroxyPEG (PEG diol) • The anti-PEG IgG titers ranged from 1:120 to 1:3100 • The anti-PEG antibodies also bound PEGloticase (Krystex
Slide 14: The Regado Bioscience story
We’ve seen this before … The Regado Bioscience story 14 • The trial was halted due to an excess of SAEs in the Pegnivacogen arm vs Bivalirudin; included one fatality • Of the 16 patients who developed SAEs in < 1 hr in the Pegnivacogen arm 15 (94%) had high titer IgGs to PEG • The authors speculated
Slide 15: Does vaccination induce high titers of anti-PEG antibodies?
Does vaccination induce high titers of anti-PEG antibodies ? Review of recent literature 15
Slide 16: Pfizer/BioNTech vs Moderna anti-PEG titers
Does vaccination induce high titers of anti-PEG antibodies ? Absolutely. But there are differences between Pfizer/BioNTech vs Moderna. 16 Anti-PEG Abs were present in 71% of patients prior to vaccination Moderna vaccination induced a much higher titer of both IgG and IgM post- boost than the Pfizer
Slide 17: Do these antibodies bind to immune cells?
Does vaccination induce high titers of anti-PEG antibodies ? Do these antibodies bind to immune cells ? 17
Slide 18: Anti-PEG IgG bind to granulocytes and monocytes
Does vaccination lead to binding of nanoparticles to immune cells ? High titers of anti-PEG IgG bind to granulocytes & monocytes 18 The high titers of anti-PEG IgG lead to association of Onpattro nanoparticles to the granulocyte and monocyte populations of immune cells in the plasma (Onpattro is a P
Slide 19: Does vaccination lead to complement activation?
19 Does vaccination lead to complement activation ? It is clear that the anti-PEG antibodies bind complement … but do they compromise the LNP (study 2022) ?
Slide 20: Does complement activation lead to anaphylaxis?
20 Does complement activation lead to anaphylaxis ? Additional pathways to anaphylaxis include C5a anaphylatoxin (study 2023) The patients who developed anaphylaxis (n=10) were compared to non-reactors (n=67) BAT assays were negative in 4 of the 10 The majority of patients had elevated C5a and Th-2
Slide 21: Does vaccination alter response to PEGylated therapies?
21 Does vaccination alter response to PEGylated therapies ? Yes. • Both patients were stable (without bleeding events) on standard short- acting rFVIII • Both patients were transitioned to the longer-acting PEGrFVIII formulation (Patient 1 - turoctocog alfa pegol; Patient 2 – damoctocog alfa pegol)
Slide 22: Acute hemorrhage in a Hemophilia A patient after Moderna vaccination
22 Does vaccination alter response to PEGylated therapies ? Yes. Acute hemorrhage in a Hemophilia A patient following Moderna vaccination • The patient is a 21 yo who has been treated with QOD infusions of rFVIII since age 3; transitioned to PEGrFVIII • He had previously been tested for anti- PEG an
Slide 23: Anti-PEG IgG & IgM alter response to ONPATTRO therapy
23 Anti-PEG IgG & IgM alter response to ONPATTRO therapy The loss of efficacy was linearly correlated with anti-PEG antibody levels This study followed the therapeutic response to ONPATTRO in patients in Vasterbotten County, Sweden (n=21) In 7 of 21 patients there was an abnormal response to therapy
Slide 24: Anti-PEG IgG & IgM alter response to ONPATTRO therapy
24 Anti-PEG IgG & IgM alter response to ONPATTRO therapy The loss of efficacy was linearly correlated with anti-PEG antibody levels The loss of efficacy correlated with ELISA levels of anti-PEG IgG & IgM (p<0.001, p<0.002, respectively) Patients were transitioned to vutrisiran with an enhanced thera
Slide 25: Evaluation of Pfizer/BioNTech LNP in rat - PEG-dma
25 Evaluation of Pfizer/BioNTech LNP in rat - PEG-dma Rat immunogenicity study (The LNPs in this study employed ALC-0315 and ALC-0159 (Acuitas) at identical mol% for the published vaccine) Nature Vaccines (2023)
Slide 26: Does vaccination with clinically relevant LNPs lead to anti-PEG Abs
26 Does vaccination with clinically relevant LNPs lead to anti-PEG Abs Rat immunogenicity study (Pfizer/BioNTech vaccine formulation) Clinically relevant dosing modeled after C-19 vaccines
Slide 27: POZ-lipid LNPs Have Unique Properties – IV Infusion
POZ-lipid LNPs Have Unique Properties – IV Infusion LNPs which incorporate PEOZ-dmg selectively express the payload in macrophage (M) and dendritic (D) cells 27 • In vivo results are reproducible and generalizable to other LNP formulations • The initial observation that a PEOZ- lipid LNP selectively
Slide 28: Evaluation of Pfizer/BioNTech LNP in rat - PEG-dma
28 Evaluation of Pfizer/BioNTech LNP in rat - PEG-dma Rat immunogenicity study (The LNPs in this study employed ALC-0315 and ALC-0159 (Acuitas) at identical mol% for the published vaccine) Nature Vaccines (2023)
Slide 29: Anti-PEG antibody induction in rat
Anti-PEG antibody induction in rat Anti-PEG antibodies - IgM and IgG are both boosted (similar to human data) Both anti-PEG IgM and IgG antibodies are induced in the rat following vaccination of relevant doses of LNPs Low levels of antibodies are produced by the Low Dose Higher levels of anti-PEG an
Slide 30: PEOZ-dma vs PEG-dma study design
30 Does vaccination with PEOZ-dma vs PEG-dma lead to different anti-PEG response Serina study design to evaluate PEOZ-dma and PEG-dma Day 0 3 5 7 10 14 17 19 21 24 28 First Injection Second Injection _______ This study design dosed rats with two injections (two doses – mid & high) at a 14-day interv
Slide 31: LNP phospholipid content, size, polydispersity and encapsulation
Phospholipid content, Particle size, Polydispersity, Zeta Potential & Encapsulation efficiency After Buffer Exchange in Tris-HCl, pH 7.1 Sample Name Z-Average (nm) Polydispersity Index (PI) Zeta Potential (mV) Encapsulation Efficiency PEG LNP after BXC (Avg) 88.26 0.1592 -16.43 >98% PEOZ LNP after B
Slide 32: Anti-IgM antibodies to PEG-dma vs PEOZ-dma
32 Anti-IgM antibodies to PEG-dma vs PEOZ-dma Serina LNP Laboratory Anti-IgM antibodies are readily detected, and boosted, at the High Dose and Mid Dose when LNPs employing PEG-dma are injected (similar to published data) LNPs prepared with PEOZ-dma failed to elicit an IgM response at either the Hig
Slide 33: Anti-IgG antibodies to PEG-dma vs PEOZ-dma
33 Anti-IgG antibodies to PEG-dma vs PEOZ-dma Serina LNP Laboratory Anti-IgG antibodies are readily detected at both the High Dose and Mid Dose when LNPs employing PEG-dma are injected (similar to published data) LNPs prepared with PEOZ-dma failed to elicit an IgG response at either the High Dose or
Slide 34: Summary and conclusions
T • Anaphylaxis to the vaccines appears to be primarily due to basophil degranulation, likely the result of high titer IgG (possibly IgM) to the PEG in the formulation • Now recognized as an uncommon mechanism of anaphylaxis, first described clinically ~ 15 years ago • The high titers of IgM & IgG a
Slide 35: Acknowledgements
HIGHLY CONFIDENTIAL & TRADE SECRET 35 Acknowledgements Team Serina The James Dahlman Lab Gaurav Sahay, Serina SAB Pfizer Vaccines Other Collaborators
Slide 36: Slide 36
Serina Therapeutics — ACS – Division of Polymer Chemistry (March 2025) on 6ix