Avalo Therapeutics, Inc. · NASDAQ:AVTX
Avalo Therapeutics — Cerecor — Investor Presentation (March 2021)
44 slides from Avalo Therapeutics's investor presentation, Mar 17, 2021
Slide 1: Establishing a leading rare and orphan disease-focused biopharmaceutical company
Establishing a leading, rare and orphan disease-focused biopharmaceutical company to deliver impactful new medicines to patients Patient Inspired Science 17 March | 2021 Exhibit 99.1
Slide 2: Forward-Looking Statements
2| Forward-Looking Statements 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
Slide 3: Pipeline Highlights
3| Pipeline Highlights • Cerecor has created a rich pipeline of six novel, first-in-class assets in eight clinical development programs across immunology, oncology, and rare diseases • All assets have proven mechanistic rationale, biomarkers or established proof-of-concept to de-risk the pipeline an
Slide 4: Clinical-Stage Pipeline
4| + Orphan Drug Designation, Rare Pediatric Disease Designation; Eligibility for Priority Review Voucher upon approval ‡ Fast Track Designation Clinical-Stage Pipeline Core Research & Development Areas Therapeutic Area Program Mechanism of Action Lead Indication Development Stage Anticipated Milest
Slide 5: CERC-002
Anti-LIGHT monoclonal antibody in clinical studies for COVID-19 ARDS and Severe Pediatric-onset Crohn’s Disease CERC-002
Slide 6: Phase 2 Trial Met Primary Endpoint in COVID-19 ARDS
6| Phase 2 Clinical Trial Met Primary Endpoint in Patients Hospitalized with COVID-19 ARDS Executive Summary – Final Data Analysis • CERC-002 significantly reduced respiratory failure and mortality in Phase 2 clinical trial in patients hospitalized with COVID-19 ARDS – This analysis updates the prel
Slide 7: CERC-002: A Novel First-in-Class Anti-LIGHT mAb
7| SQ: Subcutaneous; NOAEL: No observed adverse effect level The Only Known Clinical Stage Anti-LIGHT Antibody CERC-002: A Novel First-in-Class Anti-LIGHT (TNFSF14) mAb • In-licensed from Kyowa Kirin Co. • Positive toxicology profile – 8-week monkey toxicology study was well tolerated up to 100 mg/k
Slide 8: LIGHT as a Key Driver of Inflammatory Response in Cytokine Storm
8| LIGHT is Potentially a Key Driver of the Inflammatory Response in Cytokine Storm in ARDS HVEM-mediated Signaling Pathways IL-6 Pro-inflammatory Mediators and Cytokines Upregulation of Inflammatory Molecules Overactivation of Immune Response May Lead to Disease Pathology Cytokine Storm Macro- phag
Slide 9: LIGHT is a Central Driver of COVID-19 Cytokine Storm
9| LIGHT is a Central Driver of COVID-19 Related Cytokine Storm Clinical Trial Initiated After Compelling Biomarker Study Completed June 2020 P = 0.021 • In patients over 60, LIGHT levels were significantly higher in those that eventually died than in those patients that recovered (p=0.021) • Observ
Slide 10: Cytokine Storm Drives ARDS Across Etiologies
10| Cytokine Storm Drives ARDS Across Etiologies Patients may progress rapidly and often require invasive mechanical ventilation ARDS Progression Mild ARDS Moderate ARDS Severe ARDS Pre-ARDS Disease Course COVID-19 infection Injury due to various etiologies (e.g., pneumonia, trauma, aspiration) Crit
Slide 11: CERC-002 Treatment of Cytokine Storm-Induced COVID-19 ARDS
11| CERC-002 Treatment of Cytokine Storm-Induced COVID-19 ARDS Primary Endpoint: Respiratory Failure and Mortality Over 28 Days 1:1 Randomization CERC-002 (16 mg/kg [maximum 1200 mg]) on Day 1 by SQ injection + Standard of Care at the site Placebo-matched SQ injection + Standard of Care at the site
Slide 12: Patient Disposition Chart
12| Patient Disposition Chart Screening: Patients with COVID-19 associated Pneumonia and Mild to Moderate ARDS 1:1 Randomization to SoC + CERC-002 or Placebo (n = 83) Patients free of High Flow O2 or Positive Pressure O2 with 28-day Follow-up (n = 62) All Patients administered CERC-002 or Placebo (n
Slide 13: Patient Demographics
13| Patient Demographics Characteristic CERC-002 (n=41) Placebo (n=42) Age, years Mean (SD) 59.2 (14.5) 58.1 (14.2) Age Group <60 years (n, %) ≥60 years (n, %) 20 (48.8%) 21 (51.2%) 21 (50.0%) 21 (50.0%) Gender Male Female 25 (61%) 16 (39%) 32 (76.2%) 10 (23.8%) Race White Black or African American
Slide 14: Single Dose Reduced Free LIGHT Levels Rapidly
14| A Single Dose of CERC-002 Reduced Free LIGHT Levels Dramatically and Rapidly Free LIGHT is inhibited by Day 1 and remains low • Mean free LIGHT levels were comparable at baseline across cohorts • Mean free LIGHT levels were about 100 pg/mL higher in the patients ≥ 60 years-old • Free LIGHT level
Slide 15: Primary Endpoint: Alive and Free of Respiratory Failure at Day 28
15| Primary Endpoint: Percentage of Patients Alive and Free of Respiratory Failure at Day 28 CERC-002 Significantly Reduced Respiratory Failure and Mortality in Phase 2 Clinical Trial in Patients Hospitalized with COVID-19 ARDS Efficacy was highest in patients over the age of 60* (n=34, p=0.042), th
Slide 16: Single Dose Reduced Mortality by ~50%
16| A Single Dose of CERC-002 Reduced Mortality by ~50% in this Study CERC-002 Placebo 28-day Mortality 7.7% 14.3% 60-day Mortality 10.8% 22.5% • A trend in ~50% reduction in mortality was observed at both the 28-day and the 60-day timepoints • Efficacy observed is on top of corticosteroids and stan
Slide 17: Safety and Tolerability
17| Safety and Tolerability • CERC-002 was well-tolerated at a single dose of 16 mg/kg • No serious adverse events attributable to CERC-002 • Majority of AEs judged to be mild or moderate • No evidence of increased infections or adverse events related to immunosuppression CERC-002 (n=40) Placebo (n=
Slide 18: COVID-19 and Broader ARDS Target Populations
18| Source: Rubenfeld et al. N Engl J Med. 2005, 353(16):1685-93. Kissler et al. Science. 2020. UpToDate COVID-19 and Broader ARDS Target Populations COVID-19 ARDS provides a potential path to treat a larger patient population in broader ARDS U.S. COVID-19 Related ARDS Patients Estimated U.S. Broade
Slide 19: Next Steps
19| Next Steps • Applied for FDA Breakthrough Therapy and Fast Track Designations • Plan to meet with FDA to discuss potential path to Emergency Use Authorization • Manuscript in preparation with plan to present full data at a future scientific meeting • Currently exploring the applicability of CERC
Slide 20: Elevated Free LIGHT Levels in Pediatric Crohn's Disease
20| Elevated Free LIGHT Levels Detected in Pediatric Crohn’s Disease Patients Using Cerecor’s Proprietary Free LIGHT Assay Data displayed as box-and-whiskers graph (1 - 99% percentile) * Determined by Kruskal-Wallis test followed by Dunn’s multiple comparisons Plasma samples from CHOP Biobank; contr
Slide 21: CERC-002 Pediatric Crohn's Phase 1b Study Design
21| CERC-002 Pediatric onset Crohn’s Disease Phase 1b Study Design Screening (Visit 1) Open Label Treatment Period (Visits 2-10) (8 weeks) Safety Follow-Up (Visit 11) CERC-002, SQ injections every 14 days (N=8; 4 subjects in each cohort Cohort 1 : 1mg/kg; Cohort 2: 3mg/kg) Telephone Visit Eligibilit
Slide 22: CERC-007
Phase 1b anti-IL-18 monoclonal antibody for Multiple Myeloma and Still’s Disease (AOSD and sJIA) CERC-007
Slide 23: First-in-Class Anti-IL-18 High Affinity Monoclonal Antibody
23| Data on file: AstraZenaca First-in-Class Anti-IL-18 High Affinity Monoclonal Antibody Data from phase 1 study demonstrated favorable PK and safety profile • In-licensed from Medimmune / AZ • Potent and durable IL-18 inhibition – Evaluated in phase 1 SAD for COPD (n = 31) – IV doses of 10, 30, 10
Slide 24: Multiple Myeloma Is the Second Most Common Blood Cancer
24| 1NCI SEER Website; 2Palumbo. NEJM. 2011; 3ClearView Analysis 2017. Multiple Myeloma Is The Second Most Common Blood Cancer Globally Disease OverviewMultiple Myeloma (MM) Pathophysiology A progressive disease with both cell-autonomous genetic abnormalities, and microenvironmental changes contribu
Slide 25: Strong Potential in Multiple Myeloma
25| Source: Nakamura Cancer Cell. 2018. 33(4):634-648.e5 Strong Potential in Multiple Myeloma • Patients with high IL-18 have significantly worse median survival (42 months vs. >84 months, p value= 0.0026, HR = 1.84) • Reducing IL-18 levels prolongs survival in rodent models of multiple myeloma (n=6
Slide 26: CERC-007 in Resistant and Refractory Multiple Myeloma
26| CERC-007 Treatment of Patients with Resistant and Refractory Multiple Myeloma Initiating Trial in Multiple Myeloma as a Single Agent with Plans for Combination CERC-007: Dose Escalation Phase 3 + 3 Design CERC-007 Expansion Phase at RP2D N = 14 A Multicenter, Open-Label, Dose-Escalation Phase 1b
Slide 27: Adult-Onset Still's Disease Overview
27| 1. ClearView Healthcare Partners Analysis, May 2017 2. Gerfaud-Valentin et al. (2014) Autoimmun Rev. 13(7):708-22. 3. Figure from Kudela et al. (2019) BMC Rheumatol. 3:4. Adult-Onset Still’s Disease (AOSD) Overview • Rare disease with estimated U.S diagnosed prevalence of 3,500 to 7,0001 • Sympt
Slide 28: Systemic Juvenile Idiopathic Arthritis Overview
28| 1. ClearView Healthcare Partners Analysis, May 2017 2. Figure from Kudela et al. (2019) BMC Rheumatol. 3:4. Systemic Juvenile Idiopathic Arthritis (sJIA) Overview • Rare childhood onset disease with estimated U.S. diagnosed prevalence of 4,500 to 6,5001 • Intermittent fever, rash and arthritis;
Slide 29: Proof-of-Concept Data: IL-18 Binding Protein in AOSD
29| Gabay et al. Ann Rheum Dis. 2018. 77(6):840-847 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 redu
Slide 30: CERC-007 Treatment of Adult Onset Still Disease
30| CERC-007 7 mg/kg (max 500 mg) q 4 weeks (n=6) CERC-007 Treatment of Patients with Adult Onset Still Disease Potential best-in-class and first-in-class anti-IL-18 mAb 12 weeks AOSD initial data anticipated 2Q 2021 A Multicenter, Phase 1b Study of CERC-007 in Subjects with Active Adult Onset Still
Slide 31: CERC-006
Phase 2-ready, Dual mTORC 1/2 small molecule inhibitor for Complex Lymphatic Malformations CERC-006
Slide 32: Dual Inhibitor of mTORC1/2
32| • 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)1 – Significantly lower doses than MTD likely required to
Slide 33: Complex Lymphatic Malformations
33| Source: Figure adapted from Brouillard et al. (2014) J Clin Invest. 124(3):898-904 Complex Lymphatic Malformations Are a Family of Potentially Life-threatening Congenital Diseases • Neoplastic lesions caused by mutations in PI3K/AKT/mTOR pathway • Leads to local proliferation of lymphatic endoth
Slide 34: Off-label Use of Sirolimus in LM
34| 1 Adams et al. Pediatrics. 2016, 137(2):e20153257. Open-label clinical studies support efficacy, however use is limited by tolerability issues and lack of FDA approval Off-label Use of mTOR Inhibitor Sirolimus in LM • Phase II trial enrolled patients with complicated vascular anomalies1 – Study
Slide 35: CERC-800s
Monosaccharide therapy for Congenital Disorders of Glycosylation (CDGs) CERC-800s
Slide 36: Congenital Disorders of Glycosylation
36| 1Wong et al. (2017) Genet Med. 19(11):1226-1235. 2Harms et al. (2002) Acta Paediatr. 91(10):1065-72. 3Marquardt et al. (1999) Blood. 94(12):3976-85. Impaired glycoprotein production and function can simply be restored with substrate supplementation therapy Congenital Disorders of Glycosylation (
Slide 37: Pharmaceutical Grade Treatments for CDGs
37| D-MannoseD-Galactose L-Fucose OHO OH OH HO OH OHO OH OH HO OH CERC-801 CERC-802 CERC-803 Accelerated Pathway ✓ ✓ ✓ FDA ODD 7-yrs Exclusivity ✓ ✓ ✓ Priority Review Voucher* ✓ ✓ ✓ Pivotal Data Anticipated 2H 2021 2H 2021 2H 2021 Pharmaceutical Grade Treatments for CDGs Opportunity to be the first
Slide 38: Multiple Catalysts and Potential PRV Awards
38| * PRV Eligible 1 COVID-19 Related ARDS; additional pivotal study will be run if necessary 2Broader ARDS. EUA: Emergency Use Authorization Multiple catalysts and 4 potential PRV awards from first-in-class medicines for diseases with no approved treatment options Highlights Through 2022 2021 2022
Slide 39: Key Financial Information
. -+ ee. - ‘ = = \s & e499 Key Financial Information (CERECOR
Slide 40: Financial & Investor Information
40| Financial & Investor Information Key financial highlights Information as of December 31, 2020: • Outstanding common shares – 75M* • Fully diluted shares – 95.3M* • Cash – $18.9M Information as of February 28, 2021: • Unaudited cash balance – $44M • Average daily trading volume – 952K+ NASDAQ: CE
Slide 41: Select Board and Management Team Members
41| Sol J. Barer, PhD Chairman of the Board of Directors • Chairman of the Board of Directors, Teva Pharmaceutical Industries • Former Chairman and CEO, Celgene Corp. Select Board and Management Team Members Proven track record in drug development & commercialization Garry Neil, MD Chief Scientific
Slide 42: www.cerecor.com
www.cerecor.com NASDAQ:CERC
Slide 43: References: CERC-002
43| References: CERC-002 • LIGHT: Lymphotoxin-like, exhibits Inducible expression, and competes with HSV Glycoprotein D for HVEM, a receptor expressed by T lymphocytes; encoded by TNFSF14 (Tumor Necrosis Factor Superfamily 14). • Perlin DS, Zafir-Lavie I, Roadcap L, et al. Levels of the TNF-Related
Slide 44: References: CERC-006, CERC-007, CERC-800s
44| References: CERC-006, CERC-007, CERC-800s CERC-006 • Adams DM, Trenor CC 3rd, Hammill AM, et al. Efficacy and Safety of Sirolimus in the Treatment of Complicated Vascular Anomalies. Pediatrics. 2016;137(2):e20153257. • Bhagwat SV, Gokhale PC, Crew AP, et al. Preclinical characterization of OSI-0