Avalo Therapeutics, Inc. · NASDAQ:AVTX

Avalo Therapeutics — Investor Day (January 2022)

50 slides from Avalo Therapeutics's investor day presentation, Jan 6, 2022

  1. Slide 1: Investor Day Presentation January 2022

    1 © Copyright 2022. Avalo Therapeutics. All rights reserved. Avalo is a leading clinical-stage biopharmaceutical company that employs a precision medicine approach to discover, develop, and commercialize highly targeted therapeutics in areas of significant unmet clinical need. Innovation Driven by C

  2. Slide 2: Forward-Looking Statements

    2 © Copyright 2022. 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: Our Management Team Participating in Today's Presentation

    3 © Copyright 2022. Avalo Therapeutics. All rights reserved. Our Management Team Participating in Today’s Presentation Mike Cola Chief Executive Officer ike Cola Garry A. Neil, MD Chief Scientific Officer Garry A. Neil, DH. Jeff Wilkins, MD Chief Medical Officer H. Jeffrey Wilkins, MD Schond L. Gree

  4. Slide 4: Today's Agenda

    4 © Copyright 2022. Avalo Therapeutics. All rights reserved. Today’s Agenda Topic Presenter Introduction Schond L. Greenway – CFO Executive Summary Mike Cola - CEO AVTX-002 • Phase 1b preliminary data (cohorts 1 and 2) in Crohn’s Disease (CD) • Scientific rationale for new target indication and stud

  5. Slide 5: Differentiating Features of Our Development Programs

    5 © Copyright 2022. Avalo Therapeutics. All rights reserved. Differentiating Features of Our Development Programs Novel first-in class molecules Targeted mechanisms of action with potential for enhanced benefit-risk profile Biomarker approach has potential to increase trial efficiency and probabilit

  6. Slide 6: Executive Summary

    6 © Copyright 2022. Avalo Therapeutics. All rights reserved. AVTX-002 • Results from Phase 1b Crohn’s Disease trial marks the 2nd positive proof-of-concept study for AVTX-002 and further validates the LIGHT MOA in inflammatory diseases. Ulcerative colitis signal finding study underway • Compelling b

  7. Slide 7: AVTX-002 Anti-LIGHT mAb; AVTX-007 Anti-IL-18 mAb; Immunology

    7 © Copyright 2022. Avalo Therapeutics. All rights reserved. AVTX-002 Anti-LIGHT mAb AVTX-007 Anti-IL-18 mAb Immunology

  8. Slide 8: AVTX-002: A Novel First-in-Class Anti-LIGHT mAb

    8 © Copyright 2022. Avalo Therapeutics. All rights reserved. • Novel, first-in-class fully human subcutaneous (SQ) monoclonal antibody (mAb) • Only fully human anti-LIGHT mAb • Only anti-LIGHT mAb in clinical development AVTX-002: A Novel First-in-Class Anti-LIGHT (TNFSF14) mAb *Kyowa Kirin has an o

  9. Slide 9: LIGHT Is a Key Driver of Inflammation

    9 © Copyright 2022. Avalo Therapeutics. All rights reserved. LIGHT Is a Key Driver of Inflammation LIGHT, homologous to Lymphotoxin, exhibits Inducible expression and competes with HSV Glycoprotein D for binding to herpesvirus entry mediator (HVEM), a receptor expressed on T lymphocytes. 1. Ware CF.

  10. Slide 10: AVTX-002 in COVID-19 ARDS: Final Data Analysis

    10 © Copyright 2022. Avalo Therapeutics. All rights reserved. Phase 2 Randomized Controlled Trial Met Primary Endpoint in Patients Hospitalized With COVID-19 ARDS* • AVTX-002 significantly reduced respiratory failure and mortality in a Phase 2 clinical trial in patients hospitalized with COVID-19 ac

  11. Slide 11: A Single Dose of AVTX-002 Reduced LIGHT Levels Dramatically and Rapidly

    11 © Copyright 2022. Avalo Therapeutics. All rights reserved. A Single Dose of AVTX-002 Reduced LIGHT Levels Dramatically and Rapidly • Mean LIGHT levels were comparable at baseline across cohorts • Mean LIGHT levels were ~100 pg/mL higher in patients aged ≥60 years • LIGHT levels declined rapidly i

  12. Slide 12: AVTX-002 Significantly Reduced Respiratory Failure and Mortality

    12 © Copyright 2022. Avalo Therapeutics. All rights reserved. AVTX-002 Significantly Reduced Respiratory Failure and Mortality *Prespecified analysis. Source: Data on file, Avalo Therapeutics, Inc. Primary Endpoint: Percentage of Patients Alive and Free of Respiratory Failure at Day 28 Efficacy was

  13. Slide 13: AVTX-002 for Inflammatory Bowel Disease (IBD) Crohn's Disease

    13 © Copyright 2022. Avalo Therapeutics. All rights reserved. FOR DISCUSSION PURPOSES ONLY AVTX-002 for Inflammatory Bowel Disease (IBD) Crohn’s Disease (CD)

  14. Slide 14: AVTX-002 Demonstrates Efficacy Signal in Proof-of-Concept Phase 1b Study

    14 © Copyright 2022. Avalo Therapeutics. All rights reserved. • Open-label proof-of-concept study in patients with moderate to severe Crohn’s disease who previously failed 3 or more therapies, including biologics and anti-TNFα mAb* – All resistant to at least two biologics • Clinically meaningful mu

  15. Slide 15: AVTX-002 Crohn's Disease Proof-of-Concept Trial Design

    15 © Copyright 2022. Avalo Therapeutics. All rights reserved. AVTX-002 Crohn’s Disease Proof-of-Concept *CDAI, Crohn’s Disease Activity Index; IBDQ, Inflammatory Bowel Disease Questionnaire; SES-CD, Simple Endoscopic Score for Crohn’s Disease. Screening (Visit 1) Open-Label Treatment Period (Visits

  16. Slide 16: AVTX-002 Crohn's Disease: Phase 1b Data (Cohorts 1/2) Moderate Disease

    16 © Copyright 2022. Avalo Therapeutics. All rights reserved. Cohort #2 23 3 mg/kg Humira, Entyvio 10 0 31 9.6 • 100% reduction in SES-CD score • Follow-up ongoing Cohort #1 41 1 mg/kg Remicade, Entyvio, Stelara 11 4 571 27 • 64% reduction in SES-CD score • Informal follow-up: Patient relapsed after

  17. Slide 17: AVTX-002 Crohn's Disease: Phase 1b Data (Cohorts 1/2) Severe Disease

    17 © Copyright 2022. Avalo Therapeutics. All rights reserved. Cohort #1 28 1 mg/kg Remicade, Humira, Stelara, Entyvio 21 15 222 80 • 29% reduction in SES-CD score • Informal follow-up: Patient symptoms worsened; reverted to “severe pain” after cessation of study drug Cohort #1 63 1 mg/kg Remicade, H

  18. Slide 18: Rates of Response and Remission to Placebo in CD Induction Trials are Low

    18 © Copyright 2022. Avalo Therapeutics. All rights reserved. • Prior exposure to tumor necrosis factor (TNF) antagonists and short duration of study was associated with lower rates of response to placebo1-3 • Key opinion leader research noted that they expect low placebo rates (as low as single-dig

  19. Slide 19: AVTX-002 Crohn's Disease: Biomarkers and Safety Data

    19 © Copyright 2022. Avalo Therapeutics. All rights reserved. • Biomarkers – Evaluation of biomarker data is ongoing • Independent Preliminary Safety Data Results – No serious adverse events attributable to study drug  Consistent with 83-patient COVID-19 ARDS clinical trial1 – Adverse events were m

  20. Slide 20: Addressable Patient Populations and Opportunity (U.S. Only)

    20 © Copyright 2022. Avalo Therapeutics. All rights reserved. 0 100 200 300 400 500 600 700 800 900 1000 Topline Prevalence Diagnosed Prevalence Biologics Treated 1L Biologic 2L Biologic 3L+ Biologic N um be r o f P at ie nt s (K ) ~648 K ~865 K ~389 K ~156 K ~116 K ~116 K 75% diagnosis rate 60% bio

  21. Slide 21: AVTX-002 Clinical Program in Inflammatory Bowel Disease: Next Steps

    21 © Copyright 2022. Avalo Therapeutics. All rights reserved. • Crohn’s Disease (CD) – Complete evaluation of biomarker data • Ulcerative Colitis (UC) – Clinical study of patients with moderate to severe UC refractory to anti-TNFα* ongoing – Anticipate top-line data in 3Q22 • Data from proof-of-conc

  22. Slide 22: New AVTX-002 Target Indication Non-Eosinophilic Asthma (NEA)

    22 © Copyright 2022. Avalo Therapeutics. All rights reserved. FOR DISCUSSION PURPOSES ONLY New AVTX-002 Target Indication Non-Eosinophilic Asthma (NEA)

  23. Slide 23: Non-Eosinophilic Asthma (NEA): Subtype of Asthma With a Poor Prognosis

    23 © Copyright 2022. Avalo Therapeutics. All rights reserved. Non-Eosinophilic Asthma (NEA): Subtype of Asthma With a Poor Prognosis 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 Cri

  24. Slide 24: Non-Eosinophilic Asthma: Subtype of Asthma With a Poor Prognosis

    24 © Copyright 2022. Avalo Therapeutics. All rights reserved. • Asthma has been shown to be heterogeneous; many options for eosinophilic subtype • No approved targeted treatment for NEA • Strong scientific rationale for LIGHT – Elevated LIGHT levels were found to be negatively associated with lung f

  25. Slide 25: AVTX-002 for the Treatment of Non-Eosinophilic Asthma (NEA)

    25 © Copyright 2022. Avalo Therapeutics. All rights reserved. Key Secondary / Exploratory EndpointsPrimary Endpoint Estimated Enrollment: N=80 AVTX-002 8 mg/kg (max 600 mg) q4wks (n=40) AVTX-002 for the Treatment of Non-Eosinophilic Asthma (NEA) *LABA, long-acting beta-agonist; †ICS, inhaled cortico

  26. Slide 26: Summary: AVTX-002

    26 © Copyright 2022. Avalo Therapeutics. All rights reserved. • Efficacy signal demonstrated in heavily pre-treated CD patients supports further evaluation in IBD refractory to anti-TNFα therapies, including biologics • Anticipate topline data in 3Q22 for UC • Data from proof-of-concept CD and UC st

  27. Slide 27: AVTX-007 Anti-IL-18 Monoclonal Antibody for Multiple Myeloma and Still's Disease

    27 © Copyright 2022. Avalo Therapeutics. All rights reserved. Phase 1b anti-IL-18 Monoclonal Antibody for Multiple Myeloma and Still’s Disease (AOSD and sJIA) AVTX-007

  28. Slide 28: Fully Human High-Affinity Anti-IL-18 Monoclonal Antibody

    28 © Copyright 2022. Avalo Therapeutics. All rights reserved. IL -1 8 (% o f b as el in e) 150 100 50 0 • In-licensed from Medimmune/AstraZeneca • Potent and durable IL-18 inhibition – Evaluated in Phase 1 SAD* for COPD† (n=31) – IV doses of 10, 30, 100, 300 or 1000 mg – Well tolerated Fully Human H

  29. Slide 29: AVTX-007 Treatment of Relapsed and Refractory Multiple Myeloma Trial Design

    29 © Copyright 2022. Avalo Therapeutics. All rights reserved. Estimated Enrollment Dose Escalation Phase ~14 Expansion Phase = 14 Multicenter, Open-Label, Dose-Escalation Phase 1b Study of AVTX-007 in Patients With Relapsed and Refractory Multiple Myeloma Dose Escalation and Expansion Trial Design A

  30. Slide 30: Executive Summary: AVTX-007

    30 © Copyright 2022. Avalo Therapeutics. All rights reserved. • Three cohorts completed dosing (4 mg/kg, 9 mg/kg, and 14 mg/kg) IV every 4 weeks as single agent • High-dose cohort of 14 mg/kg (~1000 mg per patient) • Expansion phase at high dose near completion • Predictable PK and PD* • No dose-lim

  31. Slide 31: AVTX-007 Multiple Myeloma: PK and PD

    31 © Copyright 2022. Avalo Therapeutics. All rights reserved. • Pharmacokinetics – Predictable Tmax with IV infusion – Drug levels assessed are predictably dose-dependent • Pharmacodynamics – Deep reductions of Total serum IL18 levels occur quickly by 24 hours post-dose – Reductions of ~ 90% are ach

  32. Slide 32: AVTX-007 Multiple Myeloma: Adverse Event Profile

    32 © Copyright 2022. Avalo Therapeutics. All rights reserved. • No drug-related Serious Adverse Events • No safety signals seen in laboratory analyses AVTX-007 Treatment of Resistant and Refractory Multiple Myeloma as a Single Agent: Adverse Event Profile Favorable Tolerability And Predictable PK An

  33. Slide 33: Adult-Onset Still's Disease (AOSD)

    33 © Copyright 2022. Avalo Therapeutics. All rights reserved. Adult-Onset Still’s Disease (AOSD) *IL, interleukin; †CRP, C-reactive protein; ‡NSAID, nonsteroidal anti-inflammatory drug. 1. ClearView Healthcare Partners Analysis, May 2017. 2. Gerfaud-Valentin M et al. Autoimmun Rev. 2014;13(7):708-72

  34. Slide 34: Proof-of-Concept Clinical Data: Tadekinig Alfa in AOSD

    34 © Copyright 2022. Avalo Therapeutics. All rights reserved. Proof-of-Concept Clinical Data *IL, interleukin; †AOSD, adult-onset Still’s disease; ‡t½, elimination half-life. Subcutaneous administration of 80 mg or 160 mg 3 times weekly. Response defined as an improvement of joint count (both Swolle

  35. Slide 35: AVTX-007 Treatment of Adult-Onset Still's Disease

    35 © Copyright 2022. Avalo Therapeutics. All rights reserved. Key Secondary / Exploratory EndpointsPrimary Endpoint Estimated Enrollment: N=12 AVTX-007 7 mg/kg (max 500 mg) q4wks (n=6) AVTX-007 Treatment of Adult-Onset Still’s Disease *IL, interleukin; †CRP, C-Reactive Protein; ‡DAS, Disease Activit

  36. Slide 36: Rare Diseases: AVTX-800s and AVTX-006

    36 © Copyright 2022. Avalo Therapeutics. All rights reserved. AVTX-800s Monosaccharide Therapy for Congenital Disorders of Glycosylation (CDGs) AVTX-006 for Complex Lymphatic Malformations Rare Diseases

  37. Slide 37: AVTX-800s Monosaccharide Therapy for CDGs

    37 © Copyright 2022. Avalo Therapeutics. All rights reserved. Monosaccharide Therapy for Congenital Disorders of Glycosylation (CDGs) AVTX-800s

  38. Slide 38: Congenital Disorders of Glycosylation (CDGs)

    38 © Copyright 2022. Avalo Therapeutics. All rights reserved. Congenital Disorders of Glycosylation (CDGs): 1. Wong et al. Genet Med. 2017;19(11):1226-1235. 2. Harms et al. Acta Paediatr. 2002;91(10):1065-1072. 3. Marquardt et al. Blood. 1991;94(12):3976-3985. • Glycosylation is essential for protei

  39. Slide 39: Leukocyte Adhesion Disorders (LAD) LAD-II

    39 © Copyright 2022. Avalo Therapeutics. All rights reserved. Leukocyte Adhesion Disorders (LAD) LAD-II (SLC35C1-CGD) Pathophysiology LAD Type II: Absence of Sialyl Lewis X of E-selectin (SLC35C1 mutation) • 3 distinct types of LAD CDG • Type II (LAD-II) caused by loss-of-function mutation in SLC35C

  40. Slide 40: AVTX-803 (Fucose) for Treatment of LAD II Trial Design

    40 © Copyright 2022. Avalo Therapeutics. All rights reserved. Key Secondary / Exploratory EndpointsPrimary Endpoint AVTX-803 (Fucose) for Treatment of LAD II (SLC35C1-CDG) *100-300 mg/kg up to 5x/d based on clinical response. • Sialyl Lewis X • Leukocyte function assay • Neutrophil level • Known SLC

  41. Slide 41: AVTX-803 (Fucose) for Treatment of LAD II: Update

    41 © Copyright 2022. Avalo Therapeutics. All rights reserved. AVTX-803 (Fucose) for Treatment of LAD II (SLC35C1-CDG) • Progressing toward first patient enrollment in 1Q22; anticipated completion in FY22 • Primary endpoint to be supportive of clinically meaningful benefit • NDA planned – Toxicology

  42. Slide 42: AVTX-006 Dual mTORC 1/2 Inhibitor for Complex Lymphatic Malformations

    42 © Copyright 2022. Avalo Therapeutics. All rights reserved. Dual mTORC 1/2 Small-Molecule Inhibitor for Complex Lymphatic Malformations AVTX-006

  43. Slide 43: High-Potency, Second-Generation, Dual Inhibitor of mTORC1/2

    43 © Copyright 2022. Avalo Therapeutics. All rights reserved. • In-licensed from Astellas • Phase 2–ready asset – 4-week nonclinical tox studies completed – Previously studied in Phase 1 MAD* (n=128) – Development discontinued upon determination that target efficacious doses were above MTD† (30mg QD

  44. Slide 44: Complex Lymphatic Malformations: Potentially Life-Threatening Congenital Diseases

    44 © Copyright 2022. Avalo Therapeutics. All rights reserved. Complex Lymphatic Malformations: Family of Potentially Life-Threatening Congenital Diseases Source: Figure adapted from Brouillard P et al. J Clin Invest. 2014;124(3):898-904. Flow ValveLECs Lymph Valve Proliferation of Endothelial Cells

  45. Slide 45: Off-Label Use of mTOR Inhibitor Sirolimus in Lymphatic Malformations

    45 © Copyright 2022. Avalo Therapeutics. All rights reserved. Open-Label Clinical Studies Support Efficacy; Use Is Limited by Tolerability Issues and Lack of FDA Approval • Phase II trial enrolled patients with complicated vascular anomalies – Enrolled patients with different subtypes of lymphatic m

  46. Slide 46: AVTX-006 Treatment of Complex Lymphatic Malformations

    46 © Copyright 2022. Avalo Therapeutics. All rights reserved. Key Secondary / Exploratory EndpointsPrimary Endpoint Estimated Enrollment: N=10 AVTX-006 Treatment of Complex Lymphatic Malformations *Pi3K, phosphatidylinositol 3-kinase; †AKT, protein kinase B. AVTX-006 two dose groups: 0.5 mg and 1mg

  47. Slide 47: Summary of FY22 Corporate Goals and Milestones

    47 © Copyright 2022. Avalo Therapeutics. All rights reserved. FOR DISCUSSION PURPOSES ONLY Summary of FY22 Corporate Goals and Milestones

  48. Slide 48: 2022: A Transformational Year

    48 © Copyright 2022. Avalo Therapeutics. All rights reserved. Multiple Meaningful Clinical Catalysts • AVTX-002 UC cohort data in 3Q 2022 to help design the next phase of the IBD development program • AVTX-002 NEA data from 80-patient Phase 2 in 2H 2022 • AVTX-007 AOSD data from both cohorts in mid-

  49. Slide 49: Clinical-Stage Pipeline

    49 © Copyright 2022. Avalo Therapeutics. All rights reserved. Clinical-Stage Pipeline *Avalo remains in dialogue with the FDA and is working through feedback to determine the trial design for a registrational study and accompanying timelines, including the potential expansion to a larger patient pop

  50. Slide 50: Q&A

    50 © Copyright 2022. Avalo Therapeutics. All rights reserved. NASDAQ:AVTX www.avalotherapeutics.com Q&A

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