Avalo Therapeutics, Inc. · NASDAQ:AVTX

Avalo Therapeutics — Investor Presentation (January 2023)

32 slides from Avalo Therapeutics's investor presentation, Jan 17, 2023

1. Slide 1: Avalo Therapeutics, Inc. January 2023 Corporate Presentation

   1 © Copyright 2023. Avalo Therapeutics. All rights reserved. FOR DISCUSSION PURPOSES ONLY Avalo Therapeutics, Inc. January 2023 Corporate Presentation (AVTX) EX-99.2

2. Slide 2: Forward-Looking Statements

   2 © Copyright 2023. Avalo Therapeutics. All rights reserved. This presentation may include forward-looking statements made pursuant to the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts. Such forward-looking statements are su

3. Slide 3: Avalo Therapeutics (AVTX)

   3 © Copyright 2023. Avalo Therapeutics. All rights reserved. Exclusive consulting arrangement with Carl Ware, PhD, Sanford Burnham Prebys (discoverer of the LIGHT-signaling network) LIGHT, Lymphotoxin-like, exhibits Inducible expression, and competes with HSV Glycoprotein D for HVEM, a receptor expr

4. Slide 4: Pipeline: Immune Dysregulation Disorders

   4 © Copyright 2023. Avalo Therapeutics. All rights reserved. * The Company will assess the next stage of development for these indications, as well as potentially others, upon or close to data readout of the NEA trial. ARDS, acute respiratory distress syndrome; BTLA, B and T lymphocyte attenuator, I

5. Slide 5: AVTX-002 Anti-LIGHT mAb

   5 © Copyright 2023. Avalo Therapeutics. All rights reserved. AVTX-002 Anti-LIGHT mAb

6. Slide 6: LIGHT is a Key Driver of Acute & Chronic Inflammation

   6 © Copyright 2023. Avalo Therapeutics. All rights reserved. Ware, C., Croft, M., and Neil, G. J.Exp Med. 2022 Jul 4;219(7):e20220236. 10.1084/jem.20220236. CD4Tem, CD4 effector-memory T cells; DC, dendritic cell; HVEM, herpes virus entry mediator; LTβR, Lymphotoxin beta receptor; MAC, macrophage; N

7. Slide 7: AVTX-002: First-in-Class Neutralizing Anti-LIGHT mAb

   7 © Copyright 2023. Avalo Therapeutics. All rights reserved. • Fully human monoclonal antibody to LIGHT • CMC at 2,000 L scale; 6-month toxicology study near completion • POC in two indications: – COVID-19 ARDS – Crohn’s Disease • Currently in Phase 2 (POC) for NEA • Additional indications in immune

8. Slide 8: TNF SuperFamily of Ligands and Receptors

   8 © Copyright 2023. Avalo Therapeutics. All rights reserved. TNF SuperFamily of Ligands (TNFSF) and Receptors (TNFRSF) C. F. Ware, Ruddle, N.H. TNF Superfamily of Cytokines and Receptors. M. F. Flajnik ed. Paul's Fundamental Immunology. Publisher: Wolters Kluwer Health 2022 8th ed. Vol. Ch 10, 308-3

9. Slide 9: POC Demonstrated in Phase 2 COVID-19 ARDS Trial

   9 © Copyright 2023. Avalo Therapeutics. All rights reserved. • Demonstrated target engagement: Single-dose rapidly reduced serum free- LIGHT levels by 80%1 • Well-tolerated; no increase in serious adverse events vs.placebo1 • Evidence of clinically important anti-inflammatory effect in the lung1 • G

10. Slide 10: Significant Reduction in COVID-19 Induced Respiratory Failure and Mortality

    10 © Copyright 2023. Avalo Therapeutics. All rights reserved. Perlin, D. S. et al., Randomized, double-blind, controlled trial of human anti-LIGHT monoclonal antibody in COVID-19 acute respiratory distress syndrome. J Clin Invest (2021) doi:10.1172/jci153173. LIGHT Levels (pg/mL) Over Treatment Peri

11. Slide 11: AVTX-002 Non-Eosinophilic Asthma

    11 © Copyright 2023. Avalo Therapeutics. All rights reserved. FOR DISCUSSION PURPOSES ONLY AVTX-002 Non-Eosinophilic Asthma

12. Slide 12: Non-Eosinophilic Asthma

    12 © Copyright 2023. Avalo Therapeutics. All rights reserved. Non-Eosinophilic Asthma 1. Asthma and Allergy Foundation of America. Asthma facts and figures. https://www.aafa.org/asthma-facts/. Accessed January 3, 2022; 2. McGrath KW et al., Am J Resp Crit Care Med. 2012;185(6):612-619; 3. Jiang Y et

13. Slide 13: LIGHT (TNFSF14) in Asthma and Pulmonary Fibrosis

    13 © Copyright 2023. Avalo Therapeutics. All rights reserved. LIGHT (TNFSF14) in Asthma and Pulmonary Fibrosis Persistent insults: antigens toxins viruses Human Patients* • LIGHT expression in lung inflammatory cells (T and NK cells), alveolar epithelial, fibroblasts, goblet cells • LIGHT expression

14. Slide 14: PEAK Trial: Phase 2 in NEA

    14 © Copyright 2023. Avalo Therapeutics. All rights reserved. Key Secondary/Exploratory EndpointsPrimary Endpoint Estimated Enrollment (n=80) • Proportion of patients who experience an asthma related event defined as:  ≥6 additional reliever puffs of SABAʈ (compared to baseline) in a 24-hour period

15. Slide 15: LIGHT-Signaling Network & AVTX-008 BTLA agonist fusion protein

    15 © Copyright 2023. Avalo Therapeutics. All rights reserved. LIGHT-Signaling Network & AVTX-008 BTLA agonist fusion protein

16. Slide 16: The LIGHT-Signaling Network

    16 © Copyright 2023. Avalo Therapeutics. All rights reserved. • BTLA - B and T lymphocyte attenuator (Ig superfamily checkpoint) – Co-expressed with HVEM in T and B cells – “Dampens” the immune response • LIGHT activates HVEM – Inhibits BTLA signaling, allowing immune stimulation • LIGHT activates L

17. Slide 17: AVTX-008 MOA: Distinct from Other Autoimmune Therapeutics

    17 © Copyright 2023. Avalo Therapeutics. All rights reserved. • Activation of the BTLA inhibitory receptor by its ligand HVEM turns on SHP phosphatases* limiting lymphocyte activation and inflammatory cytokine signaling AVTX-008 MOA: Distinct from Other Autoimmune Therapeutics Ward-Kavanagh, et al.,

18. Slide 18: AVTX-008: BTLA Agonist Fusion Protein

    18 © Copyright 2023. Avalo Therapeutics. All rights reserved. Fully human, bioengineered HVEM, specific and high-affinity agonist for BTLA Stage • Immunoregulatory disorders: potentially SLE, GVHD and non-responders to TNF inhibitors • Inhibition of inflammatory cytokine production predicts efficacy

19. Slide 19: World Class Scientific Advisor

    19 © Copyright 2023. Avalo Therapeutics. All rights reserved. • Carl Ware, PhD, Head of Avalo Scientific Advisory Board – Director, Sanford Burnham Prebys (SBP) Infectious and Inflammatory Diseases Center – Professor, SBP Immunity and Pathogenesis Program – Director, SBP Laboratory of Molecular Immu

20. Slide 20: Finance Update

    20 © Copyright 2023. Avalo Therapeutics. All rights reserved. Finance Update

21. Slide 21: Financial & Investor Information

    21 © Copyright 2023. Avalo Therapeutics. All rights reserved. NASDAQ: AVTX Financial & Investor Information The following data is as of September 30, 2022 • Cash and cash equivalents – $16.9M* • Outstanding common shares – ~9.4M • Fully diluted shares1 – ~11.2M • Average daily trading volume – ~47K

22. Slide 22: Experienced Management Team

    22 © Copyright 2023. Avalo Therapeutics. All rights reserved. Decades of successful leadership, product development, and commercialization in pharma and biotech Garry A. Neil, MD Chief Executive Officer Chairman of the Board Lisa Hegg, PhD SVP, Program Management, Corporate Infrastructure Colleen Ma

23. Slide 23: Avalo Therapeutics (AVTX)

    23 © Copyright 2023. Avalo Therapeutics. All rights reserved. Exclusive consulting arrangement with Carl Ware, PhD, Sanford Burnham Prebys (discoverer of the LIGHT-signaling network) LIGHT, Lymphotoxin-like, exhibits Inducible expression, and competes with HSV Glycoprotein D for HVEM, a receptor exp

24. Slide 24: Appendix

    24 © Copyright 2023. Avalo Therapeutics. All rights reserved. Appendix

25. Slide 25: AVTX-803 Leukocyte Adhesion Deficiency Type II

    25 © Copyright 2023. Avalo Therapeutics. All rights reserved. AVTX-803 Leukocyte Adhesion Deficiency Type II (LAD II, also known as SLC35C1-CDG)

26. Slide 26: LAD II (SLC35C1-CDG) Pathophysiology

    26 © Copyright 2023. Avalo Therapeutics. All rights reserved. LAD II (SLC35C1-CDG) Pathophysiology LAD Type II: Absence of sialyl Lewis X of E-selectin (SLC35C1 mutation) • Type II (LAD II) caused by LOF mutation in SLC35C1 gene resulting in the inability to fucosylate certain critical proteins • Ab

27. Slide 27: AVTX-803 for LAD II: Pivotal Trial Design

    27 © Copyright 2023. Avalo Therapeutics. All rights reserved. Key Secondary/Exploratory EndpointsPrimary Endpoint Estimated Enrollment (n=2) *100-340 mg/kg up to 5x/d based on clinical response • Restoration of sialyl Lewis X biomarker • Leukocyte function assay • Neutrophil counts • Known SLC35C1 m

28. Slide 28: AVTX-002 TNF SuperFamily

    28 © Copyright 2023. Avalo Therapeutics. All rights reserved. AVTX-002 TNF SuperFamily

29. Slide 29: TNF SuperFamily: Proven Target-rich Opportunities

    29 © Copyright 2023. Avalo Therapeutics. All rights reserved. TNF SuperFamily: Proven Target-rich Opportunities TNF inhibitors (Autoimmune) Humira Cimzia Remicade Simponi ENBREL LIGHT inhibitor AVTX-002 TL1A inhibitors PRA023 PF-06480605 HVEM mimetics - BTLA agonists: AVTX-008, LY3361237, MB272, ANB

30. Slide 30: AVTX-002 Crohn's Disease Phase 1b Proof of Concept Trial

    30 © Copyright 2023. Avalo Therapeutics. All rights reserved. AVTX-002 Crohn’s Disease Phase 1b Proof of Concept Trial

31. Slide 31: Efficacy Signal Observed in Crohn's Disease Phase 1b Trial

    31 © Copyright 2023. Avalo Therapeutics. All rights reserved. • Phase 1b Escalating Dose, Open-Label, Signal-Finding Trial to Evaluate the Safety, Tolerability, and Short-Term Efficacy of the Anti-Light Monoclonal Antibody AVTX-002 in Adults with Moderate to Severe Active Crohn’s Disease (CD) who ha

32. Slide 32: Crohn's Disease Phase 1b Proof of Concept Trial Design

    32 © Copyright 2023. Avalo Therapeutics. All rights reserved. AVTX-002 Crohn’s Disease Phase 1b, Proof of Concept Trial Design * SES-CD, Simple Endoscopic Score for Crohn’s Disease; † CDAI, Crohn’s Disease Activity Index; ‡ IBDQ, Inflammatory Bowel Disease Questionnaire; Screening (Visit 1) Open-Lab

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