CERo Therapeutics Holdings, Inc. · OTC:CERO
CERo Therapeutics — SPAC Merger (June 2023)
45 slides from CERo Therapeutics's SPAC merger presentation, Jun 5, 2023
Slide 1: The Next Era in Cell Therapy
The Next Era in Cell Therapy MAY 2023 Exhibit 99.2
Slide 2: Disclaimers and Other Important Information
Disclaimers and Other Important Information This presentation (this “Presentation”) is provided for informational purposes only and for no other purpose and has been prepared to assist interested parties in making their own evaluation with respect to a potential business combination by and among CER
Slide 3: Disclaimers: Forward-Looking Statements
Disclaimers and Other Important Information Forward-Looking Statements Certain statements included in this Presentation are not historical facts but are forward-looking statements for purposes of the safe harbor provisions under the United States Private Securities Litigation Reform Act of 1995. For
Slide 4: A Simple Idea Turned into a Novel Therapeutic: Engineering Engulfment into T-Cells
A Simple Idea Turned into a Novel Therapeutic Engineering Engulfment into T-Cells
Slide 5: T Cells Are the Right Chassis
Lysis, tumor cell apoptosis Proliferation and serial killing Trafficking to tumors Release of anti-tumor cytokines Persistence and memory formation 20+ years of research and clinical experience 10+ years of manufacturing expertise FDA experience, familiarity and comfort T Cells Are the Right Chassis
Slide 6: CER-T Cells Designed to Eliminate the Entire Tumor
CER-T Cells Designed to Eliminate the Entire Tumor Tumor Cell PS CER CER-T Cell Chimeric engulfment receptor T cells (CER-T) binds to phosphatidylserine (PS), the “eat me” signal on tumor cell BIND
Slide 7: CER-T Cells Designed to Eliminate the Entire Tumor
CER-T Cells Designed to Eliminate the Entire Tumor Tumor Cell PS CER CER-T Cell Peptide processing and presentation Tumor cell fragments ENGULFMENT Chimeric engulfment receptor T cells (CER-T) binds to phosphatidylserine (PS), the “eat me” signal on tumor cell BIND Binding to PS mediates the capture
Slide 8: CER-T Cells Designed to Eliminate the Entire Tumor
Tumor Cell PS CER CER-T Cell Peptide processing and presentation MHC I MHC II Helper T cells Cytotoxic T cells ADAPTIVE Immune Responses Tumor cell fragments ENGULFMENT CER-T Cells Designed to Eliminate the Entire Tumor Chimeric engulfment receptor T cells (CER-T) binds to phosphatidylserine (PS), t
Slide 9: CER-T Cells Designed to Eliminate the Entire Tumor
Chimeric engulfment receptor T cells (CER-T) binds to phosphatidylserine (PS), the “eat me” signal on tumor cell Binding to PS mediates the capture and uptake of tumor cell fragments, which are engulfed Tumor cell phagocytosis leads to efficient tumor antigen capture, antigen processing, and antigen
Slide 10: In Vivo Evidence of Anti-Tumor Killing
In Vivo Evidence of Anti-Tumor Killing A Single Infusion of CER-T Cells EGFR-mutant NSCLC cells Robust anti-tumor in vivo responses across solid and hematologic models Single infusion of 2.5e^6 CER-1236 T cells All animals (mice) received EGFR inhibitor therapy Specifically kills non-small cell lung
Slide 11: Hematologic Malignancy Target Survey: PS Upregulation
Hematologic Malignancy Target Survey Demonstrates Upregulation of the “Eat Me” Signal Phosphatidylserine Surface Expression Measured Using Recombinant human TIM-4 Target Expression Identified on AML Blasts and Lymphomatous B Cells From Clinical Samples TIM-4 binding Normalized to Mode MCL AML BMMC H
Slide 12: Solid Tumor Target Survey: Ovarian Cancers Upregulate PS
Solid Tumor Target Survey Ongoing: Ovarian Cancers Demonstrate Upregulation of PS Ovarian Cancer specimens from the University of Washington Gynecologic Oncology Division shows 7 of 9 adenocarcinoma specimens and 2 of 3 clear cell cancers with upregulated PS using Immunofluorescence Tim4 FC Chimera
Slide 13: Next Generation T Cell Therapy Candidate
MHC II MHC I Perforin/ granzyme release Tumor cell fragments ENGULFMENT Peptide processing and presentation CER-T CELL Next Generation T Cell Therapy Candidate THE POTENTIAL OF CER-T CELLS Multi-modal tumor elimination: lysis + phagocytosis One platform, many cancers Adapting known and proven T cell
Slide 14: Highlights
IND and clinical signal expected within investment timeframe GROUNDBREAKING BIOLOGY Powerful multi-modal approach to eliminating the entire tumor PREPARING FOR THE CLINIC Process development and pre-IND meeting completed, going into liquid tumors and potentially solid tumors (complete data set in 25
Slide 15: Management Team
Brian Atwood Chief Executive Officer Co-founder, President and CEO of Cell Design Labs (acquired by Gilead in 2017) Chair, Phoenix Biotech Acquisition Corp Former Chair, Locust Walk Acquisition Corp (NASD: LWAC) Managing Director of Versant Ventures, co-founder in 1999 Director and Chair Atreca, Inc
Slide 16: CAR-T Has Been Transformative, but Challenges Persist
CAR-T Has Been Transformative, but Challenges Persist Tumor Escape Myeloid Dysfunction THE CONSEQUENCE Limited widespread use Antigen Heterogeneity T Cell Exhaustion Tumor Microenvironment Suppression Ineffective in Solid Tumors
Slide 17: Beyond CAR-T: The Next Era in Cancer Immunotherapy
Beyond CAR-T: The Next Era in Cancer Immunotherapy Ca Cancer Cell Destruction Lyse Cytotoxic elimination $ Billions in value created Eat Phagocytic elimination FIRST in discovery FIRST to patent FIRST-in-class CER-T CELLS
Slide 18: What is a CER-T cell?
What is a CER-T cell? himeric ngulfment eceptor C E R Uses TIM-4 Phagocytic Receptor to Engage Tumor Targets via the Cell of Damage Receptor Phosphatidylserine (PS) Tumor Cell PS Tumor Cell CER-T Cell Multifunctional Construct Transmembrane Extracellular Domain Tumor binding and phagocytosis Intrace
Slide 19: Phagocytosis by TIM-4 Receptor
Phagocytosis by TIM-4 Receptor CERo has observed TIM-4-mediated phagocytosis in CER-T cells Tumor Cell CER-T Cell A natural phagocytic receptor Involved in clearing billions of unwanted cells each second in our body Acquires tumor associated antigens to activate anti-tumor responses Initiates a clea
Slide 20: Multi-modal approach to tumor cell sensing, killing, and elimination
Multi-modal approach to tumor cell sensing, killing, and elimination Combining the body’s natural clearance machinery with enhanced T cell cytotoxic effects can amplify the body’s anti-tumor response Favorable potential toxicity profile is quieter (less cytokine release), though cytolytic killing AP
Slide 21: What We Learned: CER-1236 Lead Program
What We Learned Serial killing, high proliferative capacity, and multi-functionality Absence of tonicity, auto-activation, or premature exhaustion Preservation of naïve and memory phenotype Distinct transcriptome, cytokine, and chemokine repertoire Enhanced antigen acquisition, antigen processing, a
Slide 22: CER-1236 Empowered T Cells with Phagocytic Potency
Tumor elimination via target-dependent phagocytosis Phagocytosis (%) CER-1236 Empowered T Cells with Phagocytic Potency Untransduced CER-1236 Mutant TIM-4 CER-1251 CER T cell Tumor cell Phagocytosis NSCLC Cieniewicz, B., & Corey, D. (in press) Molecular Therapy, May, 2023.
Slide 23: Comprehensive RNA Analysis of CER-1236
Comprehensive RNA Analysis Showed CER-1236 Possesses Phagocytic and Cytotoxic Transcriptional Signatures RNA-seq IPA analysis Combines cytotoxic and phagocytic function into single T cells Differentially expressed genes among CER 1236 stimulated vs. mutTIM-4 ICD matched controls Cieniewicz, B., & Co
Slide 24: CER-1236 Induced Potent Cytotoxic Responses In Vitro
CER-1236 Induced Potent Cytotoxic Responses In Vitro to Both B Cell Tumors and Solid Tumors Mantle Cell Lymphoma (MCL) EGFR-mutant NSCLC NSCLC Cells JeKo-1 TMEM30a No T cells Untransduced CER-1236 No T cells Untransduced CER-1236 Untransduced JeKo-1 TMEM30A KO CER-1236
Slide 25: CER-T Cells Eliminated Lymphoma Xenografts In Vivo
CER-T Cells Eliminated Lymphoma Xenografts In Vivo A Single Infusion of CER-1236 T Cells Single infusion of 2.5e^6 CER-1236 T cells Eliminated TP53 mutant MCL tumors Observed improvements in survival without evidence for toxicity Ibrutinib at clinical doses has little effects on MCL growth; combinat
Slide 26: No Safety Signals in Small Animal Tumor Models
CER-1236 T Cells Have Not Elicited Safety Signals in Small Animal Tumor Models Single infusion of 7.5e^6 CER-1236 T cells NO anemia, thrombocytopenia, neutropenia, or coagulation abnormalities NO weight loss, morbidity, unexpected mortality NO histological abnormalities across organs A Single Infusi
Slide 27: CER-1236 T Cells Rapidly Proliferated, No Premature Exhaustion
CER-1236 T Cells Rapidly Proliferated and Showed No Premature Exhaustion A Single Infusion of CER-1236 T Cells Rapid Cell Expansion Repeat Antigen Stimulation Shows No Exhaustion Single infusion of 7.5e^6 CER-1236 T cells Copy/ul Blood Day 5000 10000 15000 20000 Repeat antigen stimulation shows no e
Slide 28: Building on Success, Poised for Translation
Building on Success, Poised for Translation CER receptor humanization, molecular optimization, splice-site testing, Immunogenic Cell Death (ICD), tonicity, and stability screening, promoter selection, vector backbone harmonization, lead selection Mechanism of action studies Solid and Hematological a
Slide 29: CER-T Cells: The Next Era in T Cell Therapy
CER-T Cells: The Next Era in T Cell Therapy Attribute CAR-T Cell CER-T Cell T cell activation Target-directed cytotoxic killing Induction of inflammatory cytokines Innate Function [phagocytosis/endocytosis, induction of myeloid programs, antigen processing and presentation] Amplification of adaptive
Slide 30: Unique and Singular Strategic Positioning
Unique and Singular Strategic Positioning Killing Capability Starting Cell Source T cells / Lymphocytes Macrophages / Monocytes Phagocytosis Lysis Phagocytosis + Lysis Phagocytosis
Slide 31: Patent Portfolio Overview
Patent Portfolio Overview 11 Main Patent Families Covering Various Aspects of CER Constructs and Uses 11 US pending patent applications and 2 US allowed applications 29 pending foreign applications and 7 granted foreign applications in first family Will continue to monitor and prosecute strategicall
Slide 32: Plug and Play Manufacturing
Plug and Play Manufacturing GMP-ready process Experienced CDMO partner in place Currently transferring process Optimal product characteristics Completed Pre-IND review (preclinical and CMC) with FDA Process is analogous to CAR-T Cell
Slide 33: Positioned for Phase I Success
Positioned for Phase I Success Deep preclinical data set, novel mechanism of action, clinical history with CAR-T Adaptive Phase I design: explore patient response in step-wise protocol, maximize opportunity to elicit clinical signal while evaluating safety Determine dose, conditioning therapy requir
Slide 34: Different MOA – Phagocytosis and Lysis
Different MOA – Phagocytosis and Lysis Extensive prevalence of naturally elevated PS across diverse cancer types CER-1236 preclinical activity in multiple liquid and solid tumor types, including untreatable (by CAR T) MCL, CLL Acute Myeloid Leukemia (AML), etc. Promising efficacy data in preclinical
Slide 35: IND Approach
Expected initial IND submission with safety first and efficient patient recruitment (e.g., within next 12 months) Initially “all-comer” B-Cell Lymphoma patients, monotherapy, 3-5 patients With initial dose established, focus down on MCL, Chronic Lymphocytic Leukemia (CLL) CLL Monotherapy 3-5 patient
Slide 36: Single Product Across Multiple Hematological Indications
Single Product Across Multiple Hematological Indications Clinical Development Strategy CER-T PROGRAM Hematology Phase I Phase II IND Monotherapy arm N=5 INITIAL TRIAL PIND Completed Q4 22 Initiate Phase I/II study in MCL and CLL: confirm POC and determine initial safety 1 FOLLOW-ON STUDIES Data from
Slide 37: Budget 2023-2025
2 Year Budget 2023 2024 2025 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Starting Balance 40,000 32,699 28,914 22,962 18,447 13,500 8,500 3,077 Cash for Operations (1,503) (3,913) (6,041) (4,774) (5,132) (5,135) (5,507) (2,852) Deal Payments (6,198) − − − − − − − CAPEX − (200) (200) − − − − − Interest Income (1%/Qtr) 4
Slide 38: Investment Highlights
Investment Highlights CERo ‘reverse merge’ into Phoenix Biotech Acquisition Corp. (“PBAX”) Raising $40M to file IND, conduct human clinical data in several tumor types $15M from insiders and SPAC Remainder from new investors Sponsor willing to share up to two-thirds of “promote” shares Founder share
Slide 39: Transaction Summary
Transaction Summary SOURCES ($ in Millions) CERo Rollover $50.0 Cash in Trust 7.5 Proceeds from PIPE 32.5 Total $90.0 USES ($ in Millions) Equity to CERo $50.0 Cash to Balance Sheet 32.5 Est. Transaction Expenses 7.5 Total $90.0 PRO FORMA VALUATION Pro Forma Shares Outstanding (M)(1) 14.5 Share Pric
Slide 40: The Next Era in Cell Therapy
The Next Era in Cell Therapy Designed to Be a More Powerful Cancer Cell Killer CER-T CELL UNIQUE APPROACH Powerful, multi-modal tumor clearing NEAR TERM VALUE IND anticipated in 12 months, and human data in 24 months PROVEN SUCCESS Experienced team, top investors, and capital efficient LARGE OPPORTU
Slide 41: Summary Risk Factors
Summary Risk Factors All references to “we,” “us,” “our” and the “Company” refer to the business and operations of CERo Therapeutics, Inc. (“CERo”) prior to the consummation of the proposed Business Combination (as defined below) or to the business and operations of New CERo (as defined below) follo
Slide 42: Summary Risk Factors (continued)
We have grown rapidly and will need to continue to grow the size of our organization, and we may experience difficulties in managing this growth. We may form or seek additional strategic alliances or enter into additional licensing arrangements in the future, and we may not realize the benefits of s
Slide 43: Summary Risk Factors (continued)
We may not be able to obtain orphan drug exclusivity for one or more of our product candidates, and even if we do, that exclusivity may not prevent the FDA from approving other competing products. We are subject to stringent and changing privacy laws, regulations and standards as well as policies, c
Slide 44: Risks Related to New CERo's Common Stock
Risks Related to New CERo’s Common Stock An active trading market for New Cero’s common stock, may not be available on a consistent basis to provide stockholders with adequate liquidity. The price of the New Cero common stock may be extremely volatile, and stockholders could lose all or part of thei
Slide 45: Risks Related to the Business Combination
There is no guarantee that a stockholder’s decision to continue to hold Class A Common Stock will put the stockholder in a better future economic position than if they decided to redeem their Class A Common Stock for a pro rata portion of the Trust Account will put the stockholder in a better future