Akari Therapeutics Plc · NASDAQ:AKTX
Akari Therapeutics — Investor Presentation (October 2024)
40 slides from Akari Therapeutics's investor presentation, Oct 29, 2024
Slide 1: Akari Therapeutics: A Multi-Faceted Biotech Company
Akari Virtual KOL Event Nomacopan Potential in Hematopoietic Stem Cell Transplant-Related Thrombotic Microangiopathy Akari Therapeutics October 19, 2023 A Multi-Faceted Biotech Company Q4-2024 1
Slide 2: Forward-Looking Statements
Forward-Looking Statements This communication relates to the proposed transaction pursuant to the terms of the Merger Agreement, by and among Akari, Pegasus Merger Sub, Inc., and Peak Bio. This communication includes express or implied forward-looking statements within the meaning of Section 27A of
Slide 3: Additional Disclosures
Additional Disclosures Additional Information and Where to Find It The Registration Statement on Form S-4 includes a prospectus of Akari and a joint proxy statement of Akari and Peak Bio. INVESTORS AND SECURITY HOLDERS ARE URGED TO READ CAREFULLY THE REGISTRATION STATEMENT ON FORM S-4, JOINT PROXY S
Slide 4: Merger of Akari Therapeutics and Peak Bio Creates a Multi-Faceted Biotech Company
Merger of Akari Therapeutics and Peak Bio Creates a Multi-Faceted Biotech Company Diverse pipeline provides potential for multiple shots on goal • TROP2 PH1 ADC: Antibody-drug conjugate (ADC) – pre-clinical program for solid tumors • PAS-nomacopan: Geographic atrophy (GA) – pre-clinical program for
Slide 5: Prioritized Pipeline Focuses on Areas of High Unmet Medical Need
Prioritized Pipeline Focuses on Areas of High Unmet Medical Need Program Indication Discovery Preclinical Phase I Phase II Phase III Strategy • Ongoing pre-clinical activities Active programs TROP2 PH1 ADC Solid • Pursue licensing/strategic ADC with novel payload Tumors partnership in 2025 PAS-Nomac
Slide 6: Led by a Management Team With Extensive Experience in Life Sciences
Led by a Management Team With Extensive Experience in Life Sciences Samir Patel, M.D. Wendy F. DiCicco Interim President & CEO Interim CFO Strategic leader with extensive Strategic financial leader with operational, financial and extensive background in life commercial experience sciences Miles Nunn
Slide 7: Antibody Drug Conjugate (ADC)
Antibody Drug Conjugate (ADC) • Innovative platform
Slide 8: Our ADCs Leverage Novel Linker Technology and Mechanism of Action
Our ADCs Leverage Novel Linker Technology and Mechanism of Action Targeted killing of cancer cells by specific antibody coupled to a cytotoxic (payload) Traditional o Over 70% of payloads in currently approved ADCs target tubulin or DNA* ADC o Industry standard payloads can have off-target effects a
Slide 9: ADC Market is Projected to Reach Over $22B by 2030
ADC Market is Projected to Reach Over $22B by 2030 Approved Therapies Projected Revenue: $22B+ by 20301 Strong Deal Flow Even for Pre-Clinical ADC Assets* Partners Asset Target Deal Type Date Phase Deal Value Multitude ADCE-T02 ADC Tissue Factor Licensing Aug-24 Pre-clinical Upfront not revealed; Po
Slide 10: Novel Payload Platforms
Novel Payload Platforms • Most advanced payload PH1 targets the spliceosome • Linker toolkit • Linker toolkit for PH1 – leveragesBinding • Resistance both cleavable and non-cleavable mechanisms to MDR transporters • Novel mechanisms• ofAnti- Splicing MoA action • Generation of neoepitopes ▪ Generati
Slide 11: We Have Developed a Diverse Toxin Linker Toolkit for PH1 ADCs
We Have Developed a Diverse Toxin Linker Toolkit for PH1 ADCs Our Library Permits Selection of Optimal Linker for PH1 ADC Cytotoxic Potency* Linkers Non-Cleavable Cleavable L2 L91 L92 Lys L22 (PH1) L94 L18 L11 Cys *Tested in vivo. 11
Slide 12: PH1 Payload Is a Spliceosome Modulator With a Multi-Pronged Anti-Tumor Activity
PH1 Payload Is a Spliceosome Modulator With a Multi-Pronged Anti-Tumor Activity By targeting normal splicing and PH1 ADC tumor specific splicing of introns PH1: TUMOR CELL 1. Disrupts tumor specific alternative Target binding + splicing, a fundamental process for internalization T-cell / B-cell tumo
Slide 13: PH1 Greatly Elevates Abundance and Diversity of Mis-Spliced RNA
PH1 Greatly Elevates Abundance and Diversity of Mis-Spliced RNA Average (n=4 wells) expression of spliced RNA transcripts showing effect of DM4 and PH1 payloads compared to control DM4 (anti-tubulin) vs. CTR PH1 (anti-spliceosome) vs. CTR Mis-spliced RNAs including some potentially contributing 1 –
Slide 14: PH1 May Prevent Development of MDR-Mediated Resistance
PH1 May Prevent Development of MDR-Mediated Resistance PH1 Is a Poor Substrate for MDR Transporters Method: MES-SA uterine sarcoma cell line Normal MES-SA cells & MES-SA cells selected for MES-SA cells expressing high levels of MDR transporter 1 and 2 which overexpression of MDR transporter 1/2 expo
Slide 15: Trop2 PH1 ADC
Trop2 PH1 ADC • Proprietary Trop2 mAb (M2.1) • Optimization of payload linker • Trophoblast cell surface antigen 2 (Trop2) PH1 ADC • Low off-target activity • Differentiated efficacy in xenograft model • Potential increased efficacy as combination therapy • Differentiated safety in NHP model
Slide 16: Our Trop2 mAb Demonstrates High Affinity for TROP2 Comparable to Trodelvy
Our Trop2 mAb Demonstrates High Affinity for TROP2 Comparable to Trodelvy® Daiichi mAb (Datopotamab DXd) Immunomedics mAb (Trodelvy®) PEAK Trop2 mAb (M2.1) Kd: 24.6nM Kd: 2.50nM Kd: 8.97nM • M2.1 variant has high binding affinity akin to that of Immunomedics mAb • The Daiichi mAb (TINA) has a very d
Slide 17: Trop2-PH1 ADC Linker Screen for Optimal Efficacy
Trop2-PH1 ADC Linker Screen for Optimal Efficacy: Lysine Conjugates With Non-Cleavable Linker Have the Highest Potency hRS7 IgG1κ monoclonal antibody from Trodelvy® and was conjugated to PH-1 suite of linker toxins L2, L22 (PH1), L18 and L92 at the indicated drug antibody ratios (DAR) Experimental D
Slide 18: Clinically Validated Trop2 Target as First Named PH1 Program
Clinically Validated Trop2 Target as First Named PH1 Program Trop2 PH1 ADC-potent in-vitro activity Normal human fibroblasts NCI-N87 gastric Trop2high • Data (top R figure) shows superior specificity of Trop2 PH1 to cancer cells (possibly due to linker stability) compared to Trodelvy® which exhibits
Slide 19: Payload Superiority of PH1 Over SN-38; Tumor Regression Is Dose Dependent
Payload Superiority of PH1 Over SN-38 on IMMU-132 Antibody Anti- Trop2-PH1 ADC-Induced Tumor Regression Is Dose Dependent Method: DAR8 DAR4 ADCs used: • Human NCI-N87 cell line used anti-RSV PH1, 3mg/kg 3mpk IMMU-132,10mg/kg 10mpk hRS7 PH1, 3mg/kg 3mpk Anti-RSV PH1 = anti-respiratory Percent tumor v
Slide 20: Trop2 PH1 ADC in Gastric Cancer Model: Tumor Regression at Lower DAR and Dose
Trop2 PH1 ADC in Gastric Cancer Model: Tumor Regression At Lower Drug-Antibody Ratio (DAR) and Lower Dose Than Trodelvy® 10mg/kg 3mg/kg 3mg/kg Tumor Volume (mm3) Method At DAR4, TR in 50% of treated At DAR2, stable disease in 50% of • NCI-N87 cell xenograft model mice over a period of ~5 months trea
Slide 21: Trop2 PH1 ADC Combines With Standard-Of-Care Immunotherapy and Prolongs Survival
Trop2 PH1 ADC Combines With Standard-Of-Care Immunotherapy and Prolongs Overall Survival in Syngeneic Urothelial Cancer Model in Mice With Intact Immune System Superior anti-tumor efficacy for Improved OS for Trop2 PH1 ADC plus SOC combination therapy Trop2 PH1 ADC plus SOC combination therapy hTrop
Slide 22: Trop2 PH1 ADC Safety By Intravenous Administration
Trop2 PH1 ADC Safety By Intravenous Administration: Proof-of-Concept Demonstrated Differentiated Safety Profile in NHP ▪ Doses examined 2mg/kg, 6mg/kg and 18mg/kg IV Q3W x 3 repeat doses at DAR2 and DAR4 o 3 animals in each group, 2 sacrificed at end of dosing and 1 after further 3-week recovery per
Slide 23: Summary of Trop2 PH1 ADC Characteristics
Summary of Trop2 PH1 ADC Characteristics • Nanomolar potency against multiple types of solid tumors with potential utility against wide range of cancers either alone or in combination with I/O therapy • Superior specificity to cancer cells (possibly due to linker stability) and unique ability to gen
Slide 24: PASylated-Nomacopan Geographic Atrophy (GA)
PASylated®-Nomacopan Geographic Atrophy (GA) • Bispecific inhibitor of C5 and LTB4 • Potential for 3 – 4 injections/year • Potential for better safety than approved complement only drugs Nomacopan is the parent asset that was evaluated in two phase 3 clinical trials in hematopoietic stem cell transp
Slide 25: Currently Approved Treatments in GA
Currently Approved Treatments in GA • GA is an advanced form of dry age-related Non-central atrophy macular degeneration (dAMD) with growth of Some loss of peripheral, low atrophic lesions causing loss of photoreceptors light vision and ultimately legal blindness in a median of c.6 years1 Growth of
Slide 26: PAS-Nomacopan Is Designed to Address Unmet Needs in GA Identified by Retinal Specialists
PAS-Nomacopan Is Designed to Address Unmet Needs in GA Identified by Retinal Specialists PAS-nomacopan’s target product profile Inhibition of two proinflammatory pathways in eye has potential to improve Results from Proprietary Survey of Retinal Specialists efficacy over complement only inhibitors T
Slide 27: What is PASylated (PAS)-Nomacopan?
What is PASylated®(PAS)-Nomacopan? Why PAS-nomacopan for Geographic Atrophy PAS-nomacopan is a long-acting bispecific inhibitor of complement C5 and leukotriene B4 (LTB4) derived from nomacopan by fusion of a 600 amino acid proline-alanine-serine (PAS) repeat • PASylation1 is a biological alternativ
Slide 28: PAS-Nomacopan Inhibits Two Pathways That Can Cause Damaging Inflammation
PAS-Nomacopan Inhibits Two Pathways That Can Cause Damaging Inflammation, While Preserving Beneficial Immune Functions Complement (C5) inhibition Leukotriene (LTB4) inhibition Complement system activated by IgG, foreign carbohydrate, damage associated Eicosanoid system activated by Fc receptor engag
Slide 29: Development of Long-Acting PAS-Nomacopan: Current Data and Potential Final IND-Enabling Steps
Development of Long-Acting PAS-Nomacopan: Current Data and Potential Final IND-Enabling Steps Drug concentration OBSERVED DATA INafter single IVT RABBITS • Data from non-clinical studies supports potential dose interval of 3 months or 1. Complement C5 inhibition to slow GA progression longer: PAS-no
Slide 30: IVT Injected Drugs for Treatment of GA Are Potential Blockbusters
IVT Injected Drugs for Treatment of GA Are Potential Blockbusters 5 million people worldwide have GA Market cap $3.3 billion million people >1 as of Oct 10, 2024 in the U.S. are1-3 living with GA Astellas acquisition for $5.9 billion The GA treatment market is expected to have CAGR as of Jul 11, 202
Slide 31: Nomacopan and PHP-303 Available for Licensing/Strategic Partnership
Available for Nomacopan licensing/strategic partnership • Phase 3-ready • Efficacy and safety validated in PNH PHP-303 • 5th generation inhibitor selective for bioactive form of neutrophil elastase • In phase 1 multiple ascending study, 5-40 mg 1x daily PHP-303 regimen achieved >90% neutrophil elast
Slide 32: Nomacopan and PHP-303 Are Phase 2 and 3-Ready Clinical Assets Available for Licensing
Nomacopan and PHP-303 Are Phase 2 and 3-Ready Clinical Assets Available for Licensing and Strategic Partnership Summary of nomacopan opportunity Summary of PHP-303 opportunity • Phase 3-ready • Phase 2-ready program • Recombinant compact globular (16.7kDa) • 5th generation small molecule inhibitor o
Slide 33: Akari Therapeutics Is a Multi-Faceted Biotech Company
Akari Therapeutics Is a Multi-Faceted Biotech Company Diverse pipeline provides potential for multiple shots on goal Lead assets in areas of high unmet medical need provide multi-billion-dollar market opportunities in oncology and geographic atrophy Lead programs leverage unique mechanisms of action
Slide 34: Supplementary Slides
Supplementary Slides
Slide 35: Nomacopan and PHP-303 Available for Licensing/Strategic Partnership
Available for Nomacopan licensing/strategic partnership • Phase 3-ready • Efficacy and safety validated in PNH PHP-303 • 5th generation inhibitor selective for bioactive form of neutrophil elastase • In phase 1 multiple ascending study, 5-40 mg 1x daily PHP-303 regimen achieved >90% neutrophil elast
Slide 36: Nomacopan Is a Novel Bispecific Recombinant Protein
Nomacopan Is a Novel Bispecific Recombinant Protein Summary of nomacopan’s properties • Phase 3-ready Detailed understanding of C5 and LTB4 binding that is relevant to both nomacopan and PAS-nomacopan • Recombinant compact globular (16.7kDa) protein • Administered by subcutaneous injection for syste
Slide 37: Potential Paths Forward for Monetization of Nomacopan Asset
Potential Paths Forward for Monetization of Nomacopan Asset Partner or license nomacopan for: A) An acute treatment indication such as trauma or traumatic brain injury using current formulation B) Indication such as PNH for ROW (i.e. ex US/EU/Japan) using current formulation • Leverage existing PNH
Slide 38: PHP-303
Available for licensing/strategic partnership PHP-303 • 5th generation inhibitor selective for bioactive form of neutrophil elastase • In Ph1 multiple ascending study, 5-40 mg 1x daily PHP-303 regimen achieved >90% neutrophil elastase inhibition with largely grade 1 AEs
Slide 39: PHP-303 Is a Potentially Best-in-Class Neutrophil Elastase Inhibitor for AATD
PHP-303 Is a Potentially Best-in-Class Neutrophil Elastase Inhibitor (NEI) for Treatment of Alpha-1 Antitrypsin Deficiency (AATD) Next Generation NEI • PHP-303 is a small molecule, oral QD, reversible and highly selective NEI potentially addressing shortfalls of previous therapies • PHP-303 can be a
Slide 40: Dose-Dependent Inhibition of NE Activity by PHP-303 in Phase 1 Study
Dose-Dependent Inhibition of NE Activity by PHP-303 in Phase 1 Multiple Ascending Dose Study • Sustained, dose-dependent suppression NE Daily dosing for 28 days activity N = 10 per group • ~90% inhibition of NE activity by doses >5mg QD • PHP-303 well-tolerated with largely grade 1 % of baseline NE
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