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Jeffrey Wilkins, MD | Chief Medical Officer Former VP, Worldwide Clinical Research, Inflammation/Oncology at Cephalon and SVP of Clinical Development with Ception Therapeutics Former VP of Discovery Medicine for GSK's Center of Excellence in External Drug Disc overy Proven Track Record in Drug Development and Commercialization 53 Copyright 2021. Avalo Therapeutics, Inc.
All three AVTX - 800 compounds granted Rare Pediatric Disease Designation prior to September 30, 2020; eligible for Priority Revie w Voucher upon approval. GMP, Good Manufacturing Practices; ODD, Orphan Drug Designation; RPDD; Rare Pediatric Disease Designation. Established therapeutic proof - of - concept GMP manufacturing and FDA approval will ensure quality and consistency Potential for reimbursement Opportunity to Be the First FDA - Approved Drugs for CDGs 50 Copyright 2021.
Pediatrics . 2016;137(2):e20153257. Overall Response 6 - month (n=57) 12 - month (n=53) Grade 2 or >AEs Complete response 0 0 Blood/bone marrow (50%) Gastrointestinal (55%) Metabolic/laboratory (20%) Infection (15%) Partial response 47 (83%) 45 (85%) Progressive disease 7 (12%) 8 (15%) Stable disease 3 (5%) 0 Open - Label Clinical Studies Support Efficacy; Use Is Limited by Tolerability Issues and Lack of FDA Approval 46 Copyright 2021.
J Clin Invest. 2014;124(3):898 - 904. Fluid accumulation in limbs, abdomen, and chest which can lead to major disability and death Complex lymphatic malformations are not readily treatable by sclerosing agents or surgery many times due to their complexity and location Flow Valve LECs Lymph Valve Proliferation of Endothelial Cells 45 Copyright 2021.
Response defined as an improvement of joint count (both Swollen Joint Count [SJC] and Tender Joint Count [TJC] according to a 44 - joint assessment) by 20% from baseline values, and a 70% decrease of CRP levels compared with baseline values (or reduction to normal levels) or normalization of ferritin. *IL, interleukin; t , elimination half - life. Gabay C et al.
ClearView Healthcare Partners Analysis, May 2017. 2. Gerfaud - Valentin M et al. Autoimmun Rev. 2014;13(7):708 - 722. 3. Kudela H et al. BMC Rheumatol . 2019;3:4. Active AOSD AOSD in Partial Remission AOSD in Remission Comparison Grp CRP >5 Comparison Grp CRP 5 Serum IL - 18 (pg/mL) 1000000 100000 10000 1000 100 10 * 39 Copyright 2021. Avalo Therapeutics, Inc.
AVTX - 007: Expansion Phase at RP2D N = 14 Treatment - resistant and refractory multiple myeloma with exposures to IMiDs*, proteasome inhibitors, and anti - CD38 mAb No more than 4 - 6 lines of therapy Establishment of RP2D in Dose Escalation Phase Response rate by International Myeloma Working Group criteria at 8 weeks in Expansion Phase Change in SPEP from baseline Safety and tolerability Change in IL - 18 levels in blood and bone marrow Change in myeloid - derived suppressor cells in bone marrow from baseline to 8 weeks AVTX - 007: Dose Escalation Phase 3 + 3 Design Initiating Trial in Multiple Myeloma as a Single Agent With Plans for Combination Initial cohort successfully completed 1Q 2021 Proof - of - concept top line data anticipated 2H 2021 Primary Endpoint Key Secondary / Exploratory Endpoints Inclusion Criteria 38 Copyright 2021.
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 - 1060. 3. ClearView Analysis 2020. Treatment Approach Majority may present with anemia, bone pain, or elevated creatinine, while fatigue, hypercalcemia, and weight loss observed in a minority of patients 2 Prognosis Estimated 5 - year survival is ~50% in the US, though specific genetic deletions such as 17p may be associated with shorter survival 1 Patient Population Prevalence in US ~140,000 1 Occurs in older people (median age at diagnosis, 69) 1 35% of patients are younger than 65 1 Progressive disease with both cell - autonomous genetic abnormalities and microenvironmental changes contributing to growth of the malignant neoplasm 2 Treated with at least one of three main classes of agents, utilized in combination across all lines of therapy 3 : - Immunomodulators - Revlimid , Pomalyst - Protease inhibitors - Velcade , Kyprolis - Anti - CD38 - Darzalex , Sarclisa Disease Overview Multiple Myeloma (MM) Pathophysiology Characterized by Neoplastic Proliferation of Plasma Cells With Overproduction of Monoclonal Proteins (M - proteins) Signs and Symptoms 36 Copyright 2021.
ARDS Incidence (K) Historically, ARDS has been underdiagnosed due to lack of physician awareness of the wide range of underlying causes - particularly for mild to moderate disease Prior to the pandemic, it is estimated that the number of diagnosed ARDS cases may have only represented about half of the true incidence due to limited physician experience triaging patients with acute respiratory failure Looking forward, the COVID - 19 pandemic experience will likely significantly increase physician awareness and ability to accurately diagnosis less severe forms of ARDS 400 200 800 300 500 0 100 600 1,000 700 900 90 2023 381 854 424 924 2026 347 398 2020 80 358 2021 394 370 770 393 2022 390 102 384 113 2024 416 139 126 2025 369 377 872 404 890 907 836 Current diagnosed incidence Incremental diagnosed patients post pandemic True incidence DIRECTIONAL COVID - 19 ARDS Provides Potential Path to Treat a Larger Patient Population in Broader ARDS There is a high unmet need for effective therapy in cytokine storm - induced ARDS beyond COVID - 19 Annual US ARDS Incidence (non - COVID) 32 Copyright 2021.
CERC - 002, a human anti - LIGHT mAb reduces respiratory failure and death in hospitalized COVID - 19 ARDS patients ( https://medrxiv.org/cgi/content/short/2021.04.03.21254748v1). Rapid and significant reduction in LIGHT levels after a single SQ dose (16 mg/kg) AVTX - 002 (n=36) Placebo (n=34) LIGHT Levels (pg/mL) 400 300 200 100 0 Day 5 Day 1 (Baseline) Day 2 LIGHT Levels (pg/mL) Over Treatment Period 28 Copyright 2021.
Arunachalam PS et al. Science . 2020;369 (6508):1210 - 1220. Clinical Trial Initiated After Compelling Biomarker Study Completed June 2020 Free LIGHT Levels (pg/mL) 10000 8000 1500 1000 500 0 Healthy Controls 60 y (n=14) Recovered 60 y (n=5) Deceased 60 y (n=23) P =0.021 Association Between Elevated LIGHT and Mortality Strongest in Patients >60 Years Key Implications Elevated LIGHT levels in hospitalized COVID - 19 patients were most strongly associated with mortality in patients 60 years 23 Copyright 2021.
Digestive Disease Week . 2021. Fine. Gastroenterol Hepatol. 2019. Yu. Aliment Pharmacol Ther.2018. Physician Interviews; ClearView Analysis. 0 100 200 300 400 500 600 700 Diagnosed Prevalence Biologics Treated 1L Biologic 2L Biologic 3L+ Biologic Number of Patients (K) ~360 K ~620 K ~144 K ~108 K ~108 K Area of Opportunity Approximately 70% of patients are on a 1/2L biologic, with the remaining 30% in 3L 20 Copyright 2021.
Crohn's Disease Cases (2021) Key Takeaways According to claims data, ~60% of the CD population is likely to be treated with a biologic agent Based on physician insights and published scientific literature, ~60% of biologics - treated CD patients will fail a 1L biologic and ~50% of those patients will fail a 2L biologic "About 30% of CD patients may require a 3L intervention, but the options are limited." - KOL Source: Cohen.
Screening (Visit 1) Open - Label Treatment Period (Visits 2 - 10) (8 weeks) Safety Follow - Up (Visit 11) AVTX - 002, SQ injections every 14 days (N=8, 4 subjects in each cohort; Cohort 1: 1mg/kg; Cohort 2: 3mg/kg) Telephone Visit Eligibility & Washout Week: - 10 0 1 2 3 4 5 6 - 8 12 7 8 Visit #: 1 2 3 4 5 6 7 10 8 9 11 Safety Tolerability Pharmacokinetics Short - term efficacy - as measured by SES - CD, CDAI, and IBDQ scores Open - Label Proof - of - Concept Clinical Trial of AVTX - 002 in adults with moderate to severe, active Crohn's disease who have previously failed anti - tumor necrosis factor alpha (anti - TNF ) treatment Proof - of - Concept Trial Design Primary Endpoint Key Secondary / Exploratory Endpoints 15 Copyright 2021.
Plasma samples from CHOP Biobank; controls matched for age and sex. Determined by Mann - Whitney U test. Source : Cardinale C et al. Manuscript in preparation. LIGHT level (pg/mL) Healthy Controls (n=9) Crohn's Disease (n=183) 1000 500 0 P <0.0001 Plasma LIGHT levels Were Significantly Elevated in Patients With CD vs Healthy Individuals 14 Copyright 2021.
Jungbeck M et al. Immunology . 2009;128(3):451 - 458. 7. Schaer C et al. PLoS One. 2011;6(4):e18495. Patient data - Elevated levels of LIGHT in patients with CD 1 and UC 2 - High LIGHT mRNA levels detected in human inflamed intestinal tissue compared with normal tissue 1,3 - LIGHT gene upregulation is observed in CD and UC 4 Animal models of IBD - LIGHT overexpression increases intestinal inflammation in rodents 5 - Anti - LIGHT monoclonal antibody (mAb) treatment ameliorates inflammation in the dextrate sulfate sodium (DSS) - induced colitis model 6 - Knockout of the LIGHT (or its ligand, HVEM) gene results in reduced intestinal inflammation (in some models) 7 13 Copyright 2021.
J Invest Dermatol. 2015;135(8):2109 - 2118. 4. Herro R et al. J Allergy Clin Immunol. 2015;136(3):757 - 768. 5. Giles DA et al. Front Immunol. 2018;9:2585. LIGHT (TNFSF14) is a pro - inflammatory cytokine and a co - stimulator of T cells and Th1 cytokines, including interferon (IFN) - 1 LIGHT is expressed on activated T cells, natural killer (NK) cells, monocytes, granulocytes, and immature dendritic cells 2 LIGHT is an important immuno - regulator in the barrier tissues: GI tract, skin, lung, and others 3 - 5 Member of the TNF Superfamily (TNFSF14) of Proteins, Involved in T - Cell Activation and Inflammation Inflammation HVEM - Mediated Signaling Pathways LT R - Mediated Signaling Pathways 12 Copyright 2021.
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. 1. Ware CF. Annu Rev Immunol. 2005;23:787 - 819. 2. Wang J, Fu YX. Immunol Res. 2004;30(2):201 - 214. 3. Herro R et al.
Lancet . 2020;5:17 - 30. 6. Crohn's and Colitis Foundation of America. The facts about inflammatory bowel disease. https://www.crohnscolitisfoundatio n.o rg/sites/default/files/2019 - 02/Updated%20IBD%20Factbook.pdf. Accessed July 19, 2021. 7. Shivashankar R et al. Clin Gastroenterol Hepatol. 2017;15(6):857 - 863. 8. EMR Reports. https://www.expertmarketresearch.com/reports/inflammatory - bowel - disease - treatment - market.
Centers for Disease Control and Prevention. Inflammatory bowel disease. https://www.cdc.gov/ibd/features/IBD - more - chronic - dis eases.html. Accessed July 17, 2021. 2. Atreya R et al. Front Med (Lausanne). 2020;7:517. 3. Knowles SR et al. Inflamm Bowel Dis . 2018;24(4):742 - 751. 4. Byron C et al. J Clin Nurs . 2020;29(3 - 4):305 - 319. 5. GBD 2017 Inflammatory Bowel Disease Collaborators.
Program Mechanism of Action Lead Indication Designation Clinical Development Stage Anticipated Milestone Early - Stage Mid - Stage Late - Stage Immunology/Immuno - oncology AVTX - 002 Anti - LIGHT mAb COVID - 19 ARDS Fast Track Received Fast Track Designation* Inflammatory bowel disease - Crohn's Top - line Data 2H 2021 AVTX - 007 Anti - IL - 18 mAb Still's disease - Initial Data 4Q 2021 Multiple myeloma - Top - line Data 2H 2021 Rare Genetic Diseases AVTX - 006 Dual mTOR inhibitor Complex lymphatic malformations ODD RPDD PRV eligible Initial Data 4Q 2021 AVTX - 801 D - Galactose replacement PGM1 - CDG ODD RPDD PRV eligible Fast Track Pivotal Trial Data 2022 AVTX - 802 D - Mannose replacement MPI - CDG Pivotal Trial Data 2022 AVTX - 803 L - Fucose replacement LAD II (SLC35C1 - CDG) Pivotal Trial Data 1H 2022 5 Copyright 2021.
Actual results may differ from those set forth in the forward - looking state ments. Except as required by applicable law, Avalo expressly disclaims any obligations or undertaking to release publicly any update s o r 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.
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