Serina Therapeutics, Inc. · AMEX:SER
Serina Therapeutics — 3rd Immunogenicity & Toxicity Summit 2024
32 slides from Serina Therapeutics's conference presentation, Dec 11, 2024
Slide 1: Overcoming Anti-PEG Antibody Responses - A Novel PEOZ-lipid
a Overcoming Anti-PEG Antibody Responses - A Novel PEOZ-lipid That Fails to Elicit an Immune Response to the Polymer-lipid in mRNA-LNP Formulations Randall Moreadith, MD, PhD, Chief Development Officer December 2024 3" Immunogenicity & Toxicity Summit - Boston, MA
Slide 2: POZ Platform for Programmable Drug Delivery
December 2024 Non-confidential Presentation NYSE: SER POZ Platform’ for Programmable Drug Delivery Small Molecules / Lipid Nanoparticles / Antibody Drug Conjugates
Slide 3: Forward Looking Statements
Forward Looking Statements 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,” “wo
Slide 4: Today's Messaging
Today’s Messaging: * 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
Slide 5: Balancing immunogenicity and reactogenicity
Balancing immunogenicity and reactogenicity Review www.nature.com/emm REVIEW ARTICLE OPEN A) Check for updates Knife’s edge: Balancing immunogenicity and reactogenicity in mRNA vaccines Jisun Lee", Matthew C. Woodruff2*6, Eui Ho Kim*”” and Jae-Hwan Nam@'>* © The Author(s) 2023
Slide 6: Balancing immunogenicity and reactogenicity
Balancing immunogenicity and reactogenicity List of adverse events reported with the mRNA vaccines |Psychiatric disorders Rese pte malignant syndrome Eye/Ear diaorders Tinnitus/Vertigo Meniere's disease a Site injection Systemic circulation joss Uveitis/Blurred vision palsy Optic neuropathy Respirat
Slide 7: In A Consecutive Cohort Study in Stanford Medical Center Network
In A Consecutive Cohort Study in Stanford Medical Center Network 4212410 Living patients in Stanford Medicine Network as of January 26, 2021 of Allergic and to mRNA COVID-19 Vaccines With Confirmatory Testing in a US Regional Health System. JAIMA Network J Open. 2021;4(9):e2125524. 38895 Vaccines ad
Slide 8: Figure 2. Basophil Activation Testing (BAT) Assay
Figure 2. Basophil Activation Testing (BAT) Assay on Example Participant Using Vaccine, Anti-Immunoglobulin E (IgE), and Saline [A] vaccine Anti-IgE Saline 2000005 2000005 2000005 150000- 150000+ 1500004 = y 100000- 100000+ 100000 50000~ 500004 50000+ ah . eee Adam 2, 0 Op oo Oh NET 10? 104 105 O 10
Slide 9: Is PEG the culprit? Yes.
Is PEG the culprit ? Yes. MAIN OUTCOMES AND MEASURES Allergic reactions were graded using standard definitions, including Brighton criteria. Skin prick testing was conducted to polyethylene glycol (PEG) and 10 of 11 patients a . . . had positive polysorbate 80 (P80). Histamine (1 mg/mL) and filtered
Slide 10: We've seen this before ... The Regado Bioscience story
We’ve seen this before ... The Regado Bioscience story Factor IXa Pegnivacogin (RBO06) e ¢€ Ac Y ¢ oe ry r e 3 . ( Anivamersen oo Figure 1 The REG1 anticoagulation system, consisting of peg- nivacogin (RBO06) and its complementary controlling agent aniva- mersen (RB007). The REG1 system was a ration
Slide 11: We've seen this before ... The Regado Bioscience story
We’ve seen this before ... The Regado Bioscience story TABLE I. Subjects experiencing SARs in RADAR Patient Onset Resolution Allergy ID (min) Symptoms Treatment (h) history 602-004 5 GI,D,P,H IVF, HI, 6 2 mo prior IVV, S diffuse urticaria to unknown agent 406-003 25 D S, HI, H2 0.4 Contrast dye, hay
Slide 12: We've seen this before ... The Regado Bioscience story
We’ve seen this before ... The Regado Bioscience story © No inhibitor 1.87 B+PEG A405 3 0.24 MAHATMA ANI ATT 0.0 418-008 pre Al 602-004 d 88 post 406-003 pre Samples by increasing A405 in the absence of PEG (blue bars) J ALLERGY CLIN IMMUNOL MAY 2016 The IgGs in these patients were shown to bind lin
Slide 13: We've seen this before ... The Regado Bioscience story
We’ve seen this before ... The Regado Bioscience story TABLE I. Incidence of allergic reactions within 24 hours by treatment arm Bivalirudin Pegnivacogin Total Type of allergic reaction (n = 1601) (n = 1605) (N = 3206) OR (95% Cl) Any allergic reaction 10 (0.62) 24 (1.5) 34 (1.06) 2.4 (1.2-5.1) Seri
Slide 14: Does vaccination induce high titers of anti-PEG antibodies?
Does vaccination induce high titers of anti-PEG antibodies ? Review of recent literature Anti-PEG Antibodies Boosted in Humans by SARS-CoV-2 Lipid Nanoparticle mRNA Vaccine Yi Ju,* Wen Shi Lee, Emily H. Pilkington, Hannah G. Kelly, Shiyao Li, Kevin J. Selva, Kathleen M. Wragg, Kanta Subbarao, Thi H.
Slide 15: Does vaccination induce high titers of anti-PEG antibodies?
Does vaccination induce high titers of anti-PEG antibodies ? Absolutely. But there are differences between Pfizer/BioNTech vs Moderna. A BNT162b2 Vaccination B mRNA-1273 Vaccination PEG-dma PEG-dmg Anti-PEG IgG Anti-PEG IgM Anti-PEG IgG Anti-PEG IgM = - a a <0.0001 é aa S 4 <20001 ae = = <0.0001 = =
Slide 16: Do these antibodies bind to immune cells?
Does vaccination induce high titers of anti-PEG antibodies ? Do these antibodies bind to immune cells ? COVID-19 lipid a nanoparticle mRNA vaccine » Influences + Anti-PEG antibodies PEGylated nanoparticle- boosted inhuman plasma _ immune cell association in human blood Ee. serina ,
Slide 17: Does vaccination lead to binding of nanoparticles to immune cells?
Does vaccination lead to binding of nanoparticles to immune cells ? High titers of anti-PEG IgG bind to granulocytes & monocytes Association Anti-PEG IgG vs. 400- Granulocyte Change in Granulocyte Association (%) ~ Co iT 20- 1=0.7383 a | 0.0 05 1.0 1.5 2.0 Log;9 Fold Change (Post-Boost/Pre-Vax) of A
Slide 18: Does vaccination lead to complement activation?
Does vaccination lead to complement activation ? It is clear that the anti-PEG antibodies bind complement ... but do they compromise the LNP (study 2022) ? Anti-PEG antibodies compromise the integrity of PEGylated lipid-based nanoparticles via complement Mariona Estapé Senti”»®'', Caroline A. de Jon
Slide 19: Does complement activation lead to anaphylaxis?
Does complement activation lead to anaphylaxis ? Additional pathways to anaphylaxis include C5a anaphylatoxin lg vaccines (MoI) Article Anaphylatoxin Complement 5a in Pfizer BNT162b2-Induced Immediate-Type Vaccine Hypersensitivity Reactions Xin Rong Lim !*©, Grace Yin Lai Chan !, Justina Wei Lynn Ta
Slide 20: Does vaccination alter response to PEGylated therapies?
Does vaccination alter response to PEGylated therapies ? Yes. Patient 1 BNT162b2 PEG-FVIII infusion (Prizer-BioNTech) FVIII activity: Pre < 1% 1st dose 2"4 dose rot April 30 May 27 June 21 Days 0 27 Patient 2 BNT162b2 PEG-FVIII infusion (Prizer-BioNTech) FVIII activity: Pre 4% 1% dose 2"¢ dose senna
Slide 21: Anti-PEG IgG & IgM alter response to ONPATTRO therapy
Anti-PEG IgG & IgM alter response to ONPATTRO therapy The loss of efficacy was linearly correlated with anti-PEG antibody levels Amyloid The Journal of Protein Folding Disorders ISSN: (Print) (Online) Journal Anti-PEG antibodies associated with reduced therapeutic effect of patisiran in patients wit
Slide 22: Anti-PEG IgG & IgM alter response to ONPATTRO therapy
Anti-PEG IgG & IgM alter response to ONPATTRO therapy The loss of efficacy was linearly correlated with anti-PEG antibody levels % . © 0 © © | GP | 960 TR G/L) © {> TIR G/L) 100 1000 10009 ° 1006 2000 3000 4000 ‘s-Anti-PEG IgG (u/ML) s-anti-PEG IgM (u/ML) Figure 1. A. Association between s-TTR and s
Slide 23: Evaluation of Pfizer/BioNTech LNP in rat - PEG-dma
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) n pj va CC i n e Ss www.nature.com/npjvaccines ® Check for updates ARTICLE OPEN Polyethylene glycol (PEG)-associat
Slide 24: Does vaccination with clinically relevant LNPs lead to anti-PEG Abs
Does vaccination with clinically relevant LNPs lead to anti-PEG Abs Rat immunogenicity study (Pfizer/BioNTech vaccine formulation) Clinically relevant dosing modeled after First injection Second injection C-19 vaccines a x a © Control (PBS) © L-LNP ( 0.009 mg phospholipids/kg LNP) X ~~ X ‘ © M-LNP (
Slide 25: 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) D Cc = Control = Control + = L-LNP = M-LNP 4 = H-LNP IgG (Logyy CONC) sv Anti-PEG IgM (Logi) CONC) e i Anti-PEC a ae T Fw T T TF T " T 0357 14 21 242628 35 a 49 6 S27 14 21 2426 28 35 a 49 T
Slide 26: Does vaccination with PEOZ-dma vs PEG-dma lead to different anti-PEG response
Does vaccination with PEOZ-dma vs PEG-dma lead to different anti-PEG response Serina study design to evaluate PEOZ-dma and PEG-dma First Injection Second Injection & \@ The High Dose — 2.0 mg phospholipid / kg body weight The Mid Dose — 0.2 mg \Y ‘ X phospholipid / kg body weight ws ie +444 }——+-++4
Slide 27: Phospholipid content, Particle size, Polydispersity, Zeta Potential & Encapsulation efficiency
Phospholipid content, Particle size, Polydispersity, Zeta Potential & Encapsulation efficiency pGFP PEG PEOZ PEG PEOZ w/ TX Standard Curve w/o TX Signal Concentration Phospholipid Standards After Buffer Exchange in Tris-HCl, pH 7.1 Sample Name Z-Average (nm) Polydispersity Index (PI) Zeta Potential
Slide 28: 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 A Moderna LNP MC3 LNP. c B t ) ys are = Total RNA Dose: 1.00 mg/kg mouse t e. “Gx Total RNA Dose: 0.25 mg/kg mouse 100 4 Moderna-PEG, Moderna-
Slide 29: Anti-IgM antibodies to PEG-dma vs PEOZ-dma
Anti-lgM antibodies to PEG-dma vs PEOZ-dma Serina LNP Laboratory a 10000 -e IgM PEG 20 E "3000 Py g > 6000 + IgMPEGO2 = =e IgM PEOZ 2.0 _ — IgM PEOZ0.2 2000 = > f a f fo) o. p=] 0 c¢ =z T T T T T T T 0 10 20 30 Days 0 - 28 Anti-lgM antibodies are readily detected, and boosted, at the High Dose and M
Slide 30: Anti-IgG antibodies to PEG-dma vs PEOZ-dma
Anti-lgG antibodies to PEG-dma vs PEOZ-dma Serina LNP Laboratorv = 12005 © IgGPEG20 > 1000- “= IgGPEG02 Q 00+ —t- IgG PEOZ 2.0 = =% IgG PEOZ0.2 i 600-4 = 400-4 re} { sd 2004 € Of <= T T T T T T T 0 10 20 30 Days 0 - 28 Anti-IlgG antibodies are readily detected at both the High Dose and Mid Dose when
Slide 31: Today's Messages
Today’s Messages : . 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 tite
Slide 32: Acknowledgements
Acknowledgements Team Serina The James DahIman Lab Gaurav Sahay, Serina SAB Pfizer Vaccines Other Collaborators
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