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 Compassion March 2022 Corporate Presentation EX-99.1
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 subject to significant risks and uncertainties that are subject to change based on various factors (many of which are beyond the control of Avalo Therapeutics, Inc. (“Avalo” or the “Company”), which could cause actual results to differ from the forward-looking statements. Such statements may include, without limitation, statements with respect to Avalo’s plans, objectives, projections, expectations and intentions and other statements identified by words such as “projects,” “may,” “might,” “will,” “could,” “would,” “should,” “continue,” “seeks,” “aims,” “predicts,” “believes,” “expects,” “anticipates,” “estimates,” “intends,” “plans,” “potential,” or similar expressions (including their use in the negative), or by discussions of future matters such as: the future financial and operational outlook; the development of product candidates or products; timing and success of trial results and regulatory review; potential attributes and benefits of product candidates; and other statements that are not historical. These statements are based upon the current beliefs and expectations of Avalo’s management but are subject to significant risks and uncertainties, including: drug development costs, timing and other risks, including reliance on investigators and enrollment of patients in clinical trials, which might be slowed by the COVID-19 pandemic; reliance on key personnel, including as a result of recent management changes; regulatory risks; Avalo’s cash position and the potential need for it to raise additional capital; general economic and market risks and uncertainties, including those caused by the COVID-19 pandemic and the war in Ukraine; and those other risks detailed in Avalo’s filings with the Securities and Exchange Commission. Actual results may differ from those set forth in the forward-looking statements. Except as required by applicable law, Avalo expressly disclaims any obligations or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Avalo’s expectations with respect thereto or any change in events, conditions or circumstances on which any statement is based. Forward-Looking Statements
3 © Copyright 2022. Avalo Therapeutics. All rights reserved. Experienced Management Team Decades of successful leadership, product development, commercialization in pharma and biotech *Presenter Garry A. Neil, MD President, Chief Executive Officer* Lisa Hegg, PhD SVP, Program Management and Corporate Infrastructure Colleen Matkowski SVP, Global Regulatory Affairs and Quality Assurance Scott White, MD VP, Clinical Development Dino C. Miano, PhD SVP, CMC and Technical Operations Chris Sullivan Chief Financial Officer
4 © Copyright 2022. Avalo Therapeutics. All rights reserved. Avalo Therapeutics (AVTX) 1POC: Proof of Concept studies; 2COVID-19 ARDS: SARS-COV2 associated acute respiratory distress syndrome (ARDS), program also has Fast Track designation from FDA 3RPDD: Rare pediatric disease designation ; 4CDG: Congenital disorder of glycosylation AVTX-002 (anti-LIGHT mAb) POC1 in COVID-19 ARDS2 with Fast Track, and IBD, NEA trial underway - phase 2 data 4Q22 Pivotal trial data for orphan/RPDD3 CDG4 program (AVTX-803) 4Q22 Second orphan/RPDD CDG program (AVTX-801) will initiate 2022 Focused portfolio emphasizing high value “first in class” immunology mAb
5 © Copyright 2022. Avalo Therapeutics. All rights reserved. New management team: Experienced experts who know the pipeline and people Drive value for shareholders: allocate capital to most promising programs: – Focus on highest value indications for promising novel biologics: AVTX-002 and AVTX-007 – Advance pivotal orphan/RPDD CDG programs: AVTX-803 and AVTX-801 – Out-license/divest non-strategic assets: AVTX-006 Emphasize: Rigorous scientific studies Operational excellence Strategic partnerships AVTX 2022 Corporate Highlights
6 © Copyright 2022. Avalo Therapeutics. All rights reserved. Clinical-Stage Pipeline * The Company is considering a possible randomized, double-blind, placebo-controlled clinical trial in moderate to severe refractory patients with IBD ** Further development of AVTX-002 for treatment of COVID-19 ARDS is currently dependent on third party funding ‡ Management is currently reviewing preliminary data and path forward related to this indication; updates will be forthcoming upon finalization of the review ‡‡ This study is sponsored by a third party; currently working with study sponsor to refine milestone timing ARDS, acute respiratory distress syndrome; CDG, congenital disorder of glycosylation; IL, interleukin; LAD, leukocyte adhesion deficiency; mAb, monoclonal antibody; NEA, non-eosinophilic asthma; ODD, orphan drug designation; PGM1, phosphoglucomutase 1; RPDD, rare pediatric disease designation, Inflammatory bowel disease (IBD) Program Mechanism of Action Lead Indication Designation Clinical Development Stage Anticipated MilestonePhase 1 Phase 2 Phase 3/Pivotal Immunology AVTX-002 Anti-LIGHT mAb NEA Phase 2 Top-line Data 4Q 2022 Inflammatory bowel disease – * COVID-19 ARDS Fast Track ** AVTX-007 Anti-IL-18 mAb Still’s disease – Top-line Data 2023‡ Rare Genetic Diseases AVTX-803 L-Fucose replacement LAD II (SLC35C1-CDG) ODD RPDD Fast Track Pivotal Trial Data 4Q 2022 AVTX-801 D- Galactose replacement PGM1-CDG Pivotal Trial Data 2023‡‡
8 © Copyright 2022. Avalo Therapeutics. All rights reserved. • Fully human monoclonal antibody (mAb) to LIGHT • POC in 2 indications: COVID-19 ARDS & IBD1 • Currently in phase 2 for non-eosinophilic asthma (NEA) AVTX-002: First-in-class anti-LIGHT (TNFSF14) mAb *Worldwide rights licensed from Kyowa Kirin Corpoation (KKC). KKC has an option to retain the rights in Japan. 1Inflammatory Bowel Disease (IBD)
9 © Copyright 2022. Avalo Therapeutics. All rights reserved. LIGHT is a Key Driver of Acute & Chronic Inflammation • LIGHT/TNFSF14 is an immunoregulatory cytokine • Critical for neutrophil, NK, T and B cell function • 2 primary receptors: LTβR, HVEM receptors • Pivotal role in lung, GI tract, & other tissues1 • Reducing LIGHT can moderate immune dysregulation in many acute and chronic inflammatory disorders 1. Ware, C., Croft, M., and Neil, G. Manuscript in preparation CD4Tem, effector-memory T cells; DC, dendritic cell; MAC, macrophage; NK, natural killer cell; Tfh, T follicular helper cells
10 © Copyright 2022. Avalo Therapeutics. All rights reserved. AVTX-002 Significantly Reduced Respiratory Failure and Mortality in Phase 2 POC COVID-19 ARDS Study 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 Period Percentage of Patients with Respiratory Failure of death by Day 28 AVTX-002 (n=36) Placebo (n=34) LI G HT L ev el s ( pg /m L) 400 300 200 100 0 Day 5Day 1 (Baseline) Day 2
11 © Copyright 2022. Avalo Therapeutics. All rights reserved. • A single dose rapidly reduced serum free-LIGHT levels by ⋍ 85%1 • Well-tolerated; no increase in serious adverse events vsplacebo • Evidence of clinically important anti-inflammatory effect in the lung • Granted Fast Track designation by FDA • Potential for benefit in other causes of ARDS, and other lung inflammation AVTX-002 POC in COVID-19 ARDS 1. Perlin DS et al. Randomized, double-blind, controlled trial of human anti-LIGHT monoclonal antibody in COVID-19 acute respiratory distress syndrome
12 © Copyright 2022. Avalo Therapeutics. All rights reserved. FOR DISCUSSION PURPOSES ONLY AVTX-002 for Non-Eosinophilic Asthma (NEA) New Indication
13 © Copyright 2022. Avalo Therapeutics. All rights reserved. Non-Eosinophilic Asthma (NEA) 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 al. Allergy Asthma Clin Immunol. 2021;17(1):45. 4. Centers for Disease Control and Prevention. AsthmaStats: Uncontrolled asthma among adults, 2016. https://www.cdc.gov/asthma/asthma_stats/uncontrolled-asthma-adults.htm. Accessed January 3, 2022. 5. Carr, T. F., Zeki, A. A. & Kraft, M. Eosinophilic and Noneosinophilic Asthma. Am J Resp Crit Care 197, 22–37 (2017). 6. Esteban-Gorgojo I et al. J Asthma Allergy. 2018;11:267-281. 7. ClearView Healthcare Partners Analysis, June 2021. 8. Hastie AT et al. J Allergy Clin Immunol. 2010;125(5):1028-1036. 9. Romeo J et al. J Allergy Clin Immunol. 2013;131(2 Suppl):AB203. Abstract 725. 10. Rørvig et al J Leukocyte Biol 94, 711–721 (2013). Treatment Approach4 • Typical asthma symptoms; often more severe/resistant to treatment5 • Associated with smoking, pollution, infections, obesity5 • Sputum LIGHT levels negatively associated with lung function (FEV1 and FVC) in asthma8,9 • Higher LIGHT levels in sputum in asthma patients with neutrophilia8 • Neutrophils have high pre-formed LIGHT levels10 Patient Population • US Prevalence of asthma ⋍ 25M1 • NEA accounts for ⋍ 47% of asthma2,3 • 50% of patients with asthma remain controlled4 • Standard therapies for asthma; many NEA patients remain uncontrolled6,7 • Currently no approved targeted therapies for NEA Signs and Symptoms4 Rationale for AVTX-002
14 © 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 NEA: Trial Design *LABA, long-acting beta-agonist; †ICS, inhaled corticosteroid; ‡FEV1, forced expiratory volume in 1 second; §ACQ, asthma control questionnaire. • Time to exacerbation • Proportion of patients with exacerbation • Change in FEV1 ‡ from baseline • Change in ACQ§ from baseline • Poorly controlled asthma on LABA* (salmeterol) and ICS† (fluticasone) • Exacerbation within 1 year previously • Blood eosinophil count <250 cells/dL Placebo (n=40) 12 weeks Multicenter, Phase 2 Study of AVTX-002 in patients with NEA Clinical Trial Design Inclusion Criteria • Discontinue LABA at Week 2 • Reduce ICS at Week 4 by 50% • Discontinue ICS at Week 6 Topline Data Expected 4Q22 Trial Design Performed With Dupilumab (Demonstrated Kaplan-Meier Curve Difference in Time to Exacerbation)
15 © Copyright 2022. Avalo Therapeutics. All rights reserved. • Open-label uncontrolled study in patients with moderate - severe Crohn’s disease who previously failed anti-TNFα mAb1 and other biologics • Rapid reduction in serum free LIGHT levels • Well-tolerated: no drug-related serious adverse events observed • Clinically meaningful mucosal healing signal observed in preliminary analysis – 3 out of 7 patients demonstrated evidence of mucosal healing as determined by colonoscopy and adjudicated by a central reader with one patient achieving remission in preliminary analysis2 • Randomized placebo-controlled trial in ulcerative colitis under evaluation Efficacy signal observed in Crohn’s disease phase 1B study 1TNFα, tumor necrosis factor alpha; mAb, monoclonal antibody; †SES-CD, Simple Endoscopic Score for Crohn’s Disease 2Updated since 1/06/22 release; final analysis of colonoscopy (SES-CD) scores, symptom scores and biomarkers ongoing expected in 2Q22
16 © Copyright 2022. Avalo Therapeutics. All rights reserved. Congenital Disorders of Glycosylation (CDGs) AVTX-803
17 © Copyright 2022. Avalo Therapeutics. All rights reserved. AVTX-803: Leukocyte Adhesion Disorders (LAD-II) LAD-II (SLC35C1-CGD) 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 Inability to fucosylate certain critical proteins • Absence of sialyl Lewis X results in neutrophil dysfunction Diagnosis/ Evaluation • Facial dysmorphism/ Growth & cognitive impairment • Recurrent bacterial infections due to neutrophil dysfunction Treatment • Currently no FDA-approved treatment; patients use OTC fucose • AVTX-803 granted orphan drug, Fast Track & rare pediatric disease designation Patient Population • Ultraorphan disease: worldwide prevalence ~10-20 pt • Nonfunctional GDP-fucose transporter with decreased fucosylation • Absence of sialyl Lewis X (CD15a) expression • Flow cytometry for sialyl Lewis X (CD15a) expression • Leukocytosis/neutrophil function assay • H antigen expression (for pharmacodynamic effect) Overview Signs and Symptoms AVTX-803 is an oral formulation of L-fucose that enhances fucosylation of proteins in the absence of a functioning GDP-fucose transporter, partially restoring protein function
18 © Copyright 2022. Avalo Therapeutics. All rights reserved. Key Secondary / Exploratory EndpointsPrimary Endpoint AVTX-803 (L-fucose) for Treatment of LAD II (SLC35C1-CDG) *100-300 mg/kg up to 5x/d based on clinical response • Restoration of sialyl Lewis X biomarker • Leukocyte function assay • Neutrophil counts • Known SLC35C1 mutation • Previous known response to L-fucose Clinical Program Single-Center (US), Double-Blind (plus Open-Label Extension) Pivotal Study of AVTX-803 in patients with LAD II (SLC35C1-CDG) Trial Design Inclusion Criteria Topline pivotal data expected 4Q22 AVTX-803* + Food Vehicle Food Vehicle Open-Label Ext. AVTX-803* Screening/ Baseline AVTX-803* + Food Vehicle Food Vehicle Randomization Period 1 Up to 8 wks Period 2 Up to 8 wks 6 months
19 © Copyright 2022. Avalo Therapeutics. All rights reserved. Clinical-Stage Pipeline * The Company is considering a possible randomized, double-blind, placebo-controlled clinical trial in moderate to severe refractory patients with IBD ** Further development of AVTX-002 for treatment of COVID-19 ARDS is currently dependent on third party funding ‡ Management is currently reviewing preliminary data and path forward related to this indication; updates will be forthcoming upon finalization of the review ‡‡ This study is sponsored by a third party; currently working with study sponsor to refine milestone timing ARDS, acute respiratory distress syndrome; CDG, congenital disorder of glycosylation; IL, interleukin; LAD, leukocyte adhesion deficiency; mAb, monoclonal antibody; NEA, non-eosinophilic asthma; ODD, orphan drug designation; PGM1, phosphoglucomutase 1; RPDD, rare pediatric disease designation Program Mechanism of Action Lead Indication Designation Clinical Development Stage Anticipated MilestonePhase 1 Phase 2 Phase 3/Pivotal Immunology AVTX-002 Anti-LIGHT mAb NEA Phase 2 Top-line Data 4Q 2022 Inflammatory bowel disease – * COVID-19 ARDS Fast Track ** AVTX-007 Anti-IL-18 mAb Still’s disease – Top-line Data 2023‡ Rare Genetic Diseases AVTX-801 D-Galactose replacement PGM1-CDG ODD RPDD Fast Track Pivotal Trial Data 2023‡‡ AVTX-803 L-Fucose replacement LAD II (SLC35C1-CDG) Pivotal Trial Data 4Q 2022
21 © Copyright 2022. Avalo Therapeutics. All rights reserved. NASDAQ: AVTX Financial & Investor Information The following data is as of December 31, 2021 • Cash – $54.6M* • Outstanding common shares – 112.8M • Fully diluted shares – 132M • Average daily trading volume – 0.5M Key Financial Highlights * Preliminary unaudited cash balance as of February 28, 2022 is $46.1 million.
22 © Copyright 2022. Avalo Therapeutics. All rights reserved. New Management Team and Pipeline Focus Multiple Meaningful Clinical Catalysts • AVTX-002 NEA data from 80-patient Phase 2 trial in 4Q22 • AVTX-803 LAD II (SLC35C1-CDG) pivotal data 4Q22 • AVTX-801 pivotal study initiation 2022 New Business Development Opportunities • AVTX-006 potential for out-licensing/ divestiture • AVTX-002, evaluate additional strategic opportunities for future AVTX-002 indication expansion, e.g. ulcerative colitis 2022: A Transformational Year for AVTX