Slide 1: Innovation Driven by Compassion
1 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Innovation Driven by Compassion September 2021
Slide 2: Forward-looking statements
2 © Copyright 2021. Avalo Therapeutics, Inc. 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 statem
Slide 3: Pipeline Highlights
3 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. • Avalo has a pipeline of six novel, first - in - class assets in eight clinical development programs across Immunology, Immuno - oncology, and Rare Genetic Diseases • All assets have demonstrated mechanistic rationale, biomarkers, or
Slide 4: Clinical-Stage Pipeline
4 © Copyright 2021. Avalo Therapeutics, Inc. 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 st udy and accompanying timelines, including the potential expansion to a larger pati
Slide 5: AVTX-002: Anti-LIGHT monoclonal antibody for Crohn's Disease and COVID-19 ARDS
5 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. 5 Anti - LIGHT monoclonal antibody in clinical studies for Crohn’s Disease and COVID - 19 ARDS AVTX - 002
Slide 6: AVTX-002: A Novel First-in-Class Anti-LIGHT (TNFSF14) mAb
6 © Copyright 2021. Avalo Therapeutics, Inc. 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
Slide 7: AVTX-002: Crohn's Disease
7 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. 7 AVTX - 002: Crohn’s Disease
Slide 8: Executive Summary: AVTX-002 Potential Proof-of-Concept in Initial Low-Dose Cohort
8 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. • Open - label proof - of - concept study in patients with moderate to severe Crohn’s disease who previously failed 3 or more lines of biologic therapies, including anti - TNF α * • Clinically meaningful mucosal healing, determined by
Slide 9: Inflammatory Bowel Disease Overview
9 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. • Inflammatory bowel disease (IBD) is a broad term indicating chronic inflammation of the gastrointestinal (GI) tract and includes both Crohn’s disease (CD) and ulcerative colitis (UC) 1 – Relapsing and remitting course characterized
Slide 10: Substantial Opportunity Remains in the Treatment of IBD
10 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Substantial Opportunity Remains in the Treatment of IBD • Majority of patients are designated moderate/severe and treated with pharmacologic intervention • Almost all patients with moderate to severe IBD will receive biologics over t
Slide 11: LIGHT Is a Key Driver of Inflammation
11 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. LIGHT Is a Key Driver of Inflammation LIGHT, homologous to L ymphotoxin, exhibits I nducible expression and competes with HSV G lycoprotein D for binding to herpesvirus entry mediator ( H VEM), a receptor expressed on T lymphocytes.
Slide 12: Multiple Lines of Evidence Support Importance of LIGHT in IBD
12 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Multiple Lines of Evidence Support Importance of LIGHT in IBD 1. Data on file, Avalo Therapeutics, Inc. 2. Moraes L et al. Inflamm Bowel Dis. 2020;26(6):874 - 884. 3. Cohavy O et al. J Immunol. 2005;174(2):646 - 653. 4. Wang J et al.
Slide 13: Elevated LIGHT Levels Detected in Pediatric Crohn's Disease
13 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. • Approximately 83% of pediatric patients with CD had significantly elevated LIGHT levels – Cross - sectional study of pediatric patients with CD from Center for Applied Genomics at CHOP – Studied pediatric patients with CD (n=183) v
Slide 14: AVTX-002 Crohn's Disease Proof-of-Concept Trial Design
14 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. • Moderate to severe disease • Anti - TNF α failure • Heavily pre - treated patients • Dose escalation starting at 1mg/kg every 2 weeks • Short duration (8 weeks) AVTX - 002 Crohn’s Disease Proof - of - Concept CDAI, Crohn’s Disease
Slide 15: Severe Patients Less Likely to Achieve Spontaneous Remission
15 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Clinical Trials in CD Consistently Suggest More Severe Patients Are Less Likely to Achieve Spontaneous Remission PBO, placebo; KOL, key opinion leader. Source: Su . Gastroenterology. 2004; Su . Gastroenterology. 2007; Physician Inter
Slide 16: Crohn's Disease Proof-of-Concept: Phase 1b Initial Data (Cohort 1)
16 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Subject 1 42 Remicade, Entyvio, Stelara 11 4 455 24 Significant mucosal healing: • 64% reduction in SES - CD score (moderate to mild) • Patient relapsed post treatment and needed surgery Subject 2 63 Remicade, Humira, Entyvio, Stelar
Slide 17: Preliminary Efficacy Results (Patient-Level Data)
17 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. SES - CD Scores Plasma LIGHT Levels SES - CD Score 25 Baseline (Day 0) Week 8 20 10 5 0 15 Plasma LIGHT Levels (pg/mL) 500 Baseline (Day 0) Week 8 400 200 100 0 300 Subj. 1 Subj. 2 Subj. 3 Subj. 4 Subj. 1 Subj. 2 Subj. 3 Subj. 4 AVTX
Slide 18: Independent Preliminary Safety Data Results
18 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. • No serious adverse events attributable to study drug – Consistent with 83 - patient COVID - 19 ARDS clinical trial 1 • Adverse events were mild to moderate in nature – Most common: GI symptoms consistent with CD • No evidence of in
Slide 19: Crohn's Disease Opportunity
19 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Crohn’s Disease Opportunity Despite the Number of Agents Available, There Remains Significant Opportunity Among Later Line CD Patients DIRECTIONAL U.S. Crohn’s Disease Cases (2021) Key Takeaways According to claims data, ~60% of the
Slide 20: AVTX-002: COVID-ARDS
20 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. 20 AVTX - 002: COVID - 19 ARDS
Slide 21: AVTX-002 Reduced Respiratory Failure and Mortality in Phase 2 Trial
21 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. • AVTX - 002 significantly reduced respiratory failure and mortality in a Phase 2 clinical trial in patients hospitalized with COVID - 19 acute respiratory distress syndrome (ARDS) – This analysis updates the preliminary top - line d
Slide 22: LIGHT Is a Central Driver of COVID-Related Cytokine Storm
22 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. LIGHT Is a Central Driver of COVID - 19 – Related Cytokine Storm • In patients ≥60 years, LIGHT levels were significantly higher in those who eventually died than in those who recovered ( P =0.021) • Observed mortality rate was highe
Slide 23: Cytokine Storm Drives ARDS Across Etiologies
23 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. ARDS Progression Pre - ARDS Disease Course Cytokine Storm Drives ARDS Across Etiologies Source : Physician Interviews; Papazian L et al. Ann Intensive Care 2019;9(1):69; Bhatraju PK et al. N Engl J Med. 2020;382(21):2012 - 2022. Pati
Slide 24: AVTX-002 Treatment of Cytokine Storm-Induced COVID-19 ARDS
24 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. AVTX - 002 Treatment of Cytokine Storm - Induced COVID - 19 ARDS PaO 2 , partial pressure of oxygen, FiO 2 , fraction of inspired oxygen. Primary Endpoint: Respiratory Failure and Mortality Over 28 Days Randomized, Double - Blind, Pl
Slide 25: Patient Disposition
25 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Patient Disposition ITT, intent - to - treat; SoC, standard of care. Source: Data on file, Avalo Therapeutics, Inc. Screening: Patients With COVID - 19 – Associated Pneumonia and Mild to Moderate ARDS 1:1 Randomization to SoC + AVTX
Slide 26: Patient Demographics
26 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Age (yrs), mean (SD) 59.2 (14.5) 58.1 (14.2) Age Group, n (%) <60 yrs ≥60 yrs 20 (48.8) 21 (51.2) 21 (50.0) 21 (50.0) Gender, n (%) Male Female 25 (61) 16 (39) 32 (76.2) 10 (23.8) Race, n (%) White Black or African American Asian Oth
Slide 27: A Single Dose of AVTX-002 Reduced LIGHT Levels Dramatically and Rapidly
27 © Copyright 2021. Avalo Therapeutics, Inc. 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 ra
Slide 28: AVTX-002 Significantly Reduced Respiratory Failure and Mortality
28 © Copyright 2021. Avalo Therapeutics, Inc. 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 Effica
Slide 29: A Single Dose of AVTX-002 Reduced Mortality by ~50%
29 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. 28 - day Mortality 7.7% 14.3% 60 - day Mortality 10.8% 22.5% A Single Dose of AVTX - 002 Reduced Mortality by ~50% Source : Data on file, Avalo Therapeutics, Inc. • A trend in ~50% reduction in mortality was observed at both the 28 -
Slide 30: Safety and Tolerability
30 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Subjects with ≥1 AE, n (%) Subjects with ≥1 drug - related AE, n (%) 16 (40) 8 (20) 21 (50) 6 (14.3) AEs >5%, n (%) Leukocytosis Anemia Hepatic enzyme increase Acute kidney injury Respiratory failure 6 (15) 4 (10) 4 (10) 3 (7.5) 3 (7
Slide 31: Broader ARDS Target Populations
31 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Broader ARDS Target Populations CAGR, compound annual growth rate. Sources: Eworuke E et al. J Crit Care . 2018;47:192 - 197; Bellani G et al. JAMA . 2016;315(8):788 - 800; Rubenfeld GD et al. N Engl J Med . 2005;353(16):1685 - 1693;
Slide 32: AVTX-002 Clinical Program Next Steps
32 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. • Crohn’s Disease – Further evaluation of cohort data, including tissue LIGHT levels – Cohort 2 (3 mg/kg dose) fully enrolled; complete data anticipated in 2H 2021 • Ulcerative Colitis – Expand clinical study to patients with moderat
Slide 33: AVTX-007: Anti-IL-18 mAb for Multiple Myeloma and Still's Disease
33 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. 33 Phase 1b anti - IL - 18 monoclonal antibody for Multiple Myeloma and Still’s Disease (AOSD and sJIA) AVTX - 007
Slide 34: First-in-Class Anti-IL-18 High-Affinity Monoclonal Antibody
34 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. IL - 18 (% of baseline) 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 • Phase
Slide 35: Multiple Myeloma: Second Most Common Blood Cancer Globally
35 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Multiple Myeloma: Second Most Common Blood Cancer Globally 1. NCI SEER. Cancer stat facts: myeloma. https://seer.cancer.gov/statfacts/html/mulmy.html. Accessed July 22, 2021. 2. Palumb o A et al. N Engl J Med . 2011;364(11):1046 - 10
Slide 36: Strong Potential in Multiple Myeloma
36 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Strong Potential in Multiple Myeloma *HR, hazard ratio; † IL, interleukin . Source : Nakamura K et al. Cancer Cell. 2018;33(4):634 - 648.e5. • Patients with high IL - 18 have significantly worse median survival (42 mo vs >84 mo; P =0
Slide 37: AVTX-007 Treatment of Resistant and Refractory Multiple Myeloma
37 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Estimated Enrollment Dose Escalation Phase ~14 Expansion Phase = 14 Multicenter, Open - Label, Dose - Escalation Phase 1b Study of AVTX - 007 in Subjects With Relapsed or Refractory Multiple Myeloma Dose Escalation and Expansion Tria
Slide 38: Adult-Onset Still's Disease (AOSD) Overview
38 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Serum IL - 18* Levels Significantly Elevated in AOSD Patients 3 Adult - Onset Still’s Disease (AOSD) Overview • Rare disease with estimated US diagnosed prevalence of 3,500 to 7,000 1 • Symptoms include fever, rash, pharyngitis, arth
Slide 39: Systemic Juvenile Idiopathic Arthritis (sJIA) Overview
39 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Systemic Juvenile Idiopathic Arthritis (sJIA) Overview *IL, interleukin; † NSAID, nonsteroidal anti - inflammatory drug; ‡ DMARD, disease - modifying anti - rheumatic drug; † CRP, C - reactive protein. 1. ClearView Healthcare Partner
Slide 40: Proof-of-Concept Clinical Data
40 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Proof - of - Concept Clinical Data • AB2 Bio clinical proof - of - concept in AOSD (n=23) using IL - 18 binding protein ( t ½ † = 40 h) – >50% of AOSD patients treated with IL - 18 binding protein achieved response • Serum IL - 18 co
Slide 41: AVTX-007 Treatment of Adult-Onset Still's Disease
41 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Key Secondary / Exploratory Endpoints Primary Endpoint Estimated Enrollment: N=12 AVTX - 007 7 mg/kg (max 500 mg) q4wks (n=6) *IL, interleukin; † CRP, C - Reactive Protein; ‡ DAS, Disease Activity Score; Α ESR erythrocyte sedimentati
Slide 42: AVTX-006: mTORC1/2 inhibitor for Complex Lymphatic Malformations
42 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. 42 Phase 2 - ready, dual mTORC 1/2 small - molecule inhibitor for Complex Lymphatic Malformations AVTX - 006
Slide 43: High-Potency, Second-Generation, Dual Inhibitor of mTORC1/2
43 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. High - Potency, Second - Generation, Dual Inhibitor of mTORC1/2 • In - licensed from Astellas • Phase 2 – ready asset – 4 - week nonclinical tox studies completed – Previously studied in Phase 1 MAD* (n=128) – Development discontinue
Slide 44: Complex Lymphatic Malformations
44 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. • Neoplastic lesions caused by mutations in PI3K/AKT/mTOR pathway • Leads to local proliferation of lymphatic endothelial cells and perturbation of lymph flow Complex Lymphatic Malformations: Family of Potentially Life - Threatening
Slide 45: Off-Label Use of mTOR Inhibitor Sirolimus in Lymphatic Malformations
45 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. • Phase II trial enrolled patients with complicated vascular anomalies – Enrolled patients with different subtypes of lymphatic malformations not controlled by previous medication, sclerotherapy, and/or surgery – Sirolimus was admini
Slide 46: AVTX-006 Treatment of Complex Lymphatic Malformations
46 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Estimated Enrollment: N=10 AVTX - 006 Treatment of Complex Lymphatic Malformations *Pi3K, phosphatidylinositol 3 - kinase; † AKT, protein kinase B. Dual mTOR Inhibitor to Modulate PI3K* and AKT † Activity AVTX - 006 two dose groups:
Slide 47: AVTX-800s: Monosaccharide therapy for CDGs
47 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. 47 Monosaccharide therapy for Congenital Disorders of Glycosylation (CDGs) AVTX - 800s
Slide 48: Congenital Disorders of Glycosylation: Life-Threatening, Ultra-Rare Disease
48 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. • Glycosylation is essential for protein structure & function, particularly for circulating proteins and enzymes such as hormones and coagulation factors • Currently approximately 150 CDGs identified • Due to a genetic mutation, CDG
Slide 49: Opportunity to Be the First FDA-Approved Drugs for CDGs
49 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. D - Mannose D - Galactose L - Fucose OHO OH OH HO OH O HO OH OH HO OH AVTX - 801 AVTX - 802 AVTX - 803 Accelerated pathway ض ض ض FDA ODD* † ض ض ض Priority Review Voucher † ض ض ض Pivotal data anticipated 2022 2022 1H 2022 Pharmaceutic
Slide 50: Key Financial Information
50 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. 50 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Key Financial Information
Slide 51: Financial & Investor Information
51 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. NASDAQ: AVTX Financial & Investor Information The following data is as of June 30, 2021 • Outstanding common shares – ~96M • Fully diluted shares – 114.8M • Average daily trading volume – ~2M • Cash – $40.4M* Key Financial Highlights
Slide 52: Select Management Team Members
52 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. Select Management Team Members Michael Cola | Chief Executive Officer, Chairman of the Board • Former President of Specialty Pharmaceuticals, Shire plc • Senior Management, AstraMerck and AstraZeneca plc Garry Neil, MD | Chief Scient
Slide 53: www.avalotherapeutics.com
53 © Copyright 2021. Avalo Therapeutics, Inc. All rights reserved. NASDAQ:AVTX www.avalotherapeutics.com