Chemomab Therapeutics Ltd. · NASDAQ:CMMB
Chemomab Therapeutics — Technical Presentation (November 2021)
39 slides from Chemomab Therapeutics's technical presentation, Nov 3, 2021
Slide 1: Chemomab Therapeutics Systemic Sclerosis Live Webinar
Chemomab Therapeutics Systemic Sclerosis Live WebinarNovember 3, 2021
Slide 2: Forward-looking statements
This presentation contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act. These forward-looking statements include, among other things, statements regarding the clinical development pathway for CM-101; the future operations of Chemomab and its abilit
Slide 3: Agenda
Agenda Dr. Dale Pfost, CEO Introduction Dr. Adi Mor, CSO CM-101 Overview:A Novel CCL24 Neutralizing Monoclonal Antibody Dr. Dinesh Khanna, U MI Med. SchoolSystemic Sclerosis:OverviewClinical Trial & Endpoint Considerations Dr. Arnon Aharon, CMO Clinical Program: CM-101 Phase 2 in Systemic Sclerosis
Slide 4: Clinical stage biotech focused on inflammatory and fibrotic diseases
Discovery and development of innovative therapeutics for rare inflammatory and fibrotic diseases with high unmet need CM-101, a first-in-class CCL24 neutralizing monoclonal antibody targeting:Primary Sclerosing Cholangitis (PSC)Systemic Sclerosis (SSc)Liver fibrosis (MoA*) Conducting 2 Phase 2 clini
Slide 5: CM-101 Overview: CCL24 Neutralizing Monoclonal Antibody
CM-101 Overview: CCL24 Neutralizing Monoclonal Antibody for Treatment of Systemic Sclerosis & Other Fibrotic–Inflammatory diseases Dr. Adi MorChemomab CSO
Slide 6: CCL24 is a Novel Therapeutic Target for Inflammation & Fibrosis
CCL24 is a Novel Therapeutic Target for Inflammation & Fibrosis Dual role in promoting fibrosisdirectly activates fibroblastsenhances local immune cell recruitmentUnique and differentiated activityex vivo and in vivo data confirm unique role vs other CCLscorrelates with disease outcome and fibrotic
Slide 7: CM-101: First-in-Class mAb Blocking CCL24
CM-101: First-in-Class mAb Blocking CCL24 Fully humanized antibody, binds and blocks CCL24 with high affinity CM-101’s epitope directly interfering with Receptor-Ligand interactionSignificant attenuation of fibrosis across multiple skin and lung fibrosis modelsFavorable PK profile supports dosing on
Slide 8: Proof of Concept: Animal Models and Ex Vivo Patient Samples
Systemic sclerosisProphylactic Bleomycin-induced skin fibrosisTherapeutic Bleomycin-induced skin fibrosisProphylactic Bleomycin induced lung fibrosisTherapeutic Bleomycin induced lung fibrosisPrimary sclerosing cholangitisANIT induced cholestasis-chronic and acute (mice)Bile duct ligation (rat)MDR2
Slide 9: CCL24 Plays a Key Role in SSc Pathophysiology
* Collaboration with University of Florence Patient samples support the targeted patient population and clinical trial endpoints CCL24 is elevated in skin and serum samples of dSSc patients CCL24 receptor is overexpressed in key cells related to SSc pathophysiology CCL24 correlates with disease prog
Slide 10: CCL24 Blockade Alone is Sufficient to Attenuate Fibrosis in SSc
Fold increase expression Dermal thickness compared to average control groups * # cells infiltrating to BAL * WT-BLM CCL24 KO-BLM CCL24 Blockade Alone is Sufficient to Attenuate Fibrosis in SSc Knocking Out the CCL24 Gene Attenuates Inflammation and Fibrosis in SSc Bleomycin Experimental Model Mor A
Slide 11: CM-101 Profoundly Reduces Skin and Lung Fibrosis in SSc Models
Collagen concentration (µg/gr tissue) Vehicle BLM BLM+CM-101 0.5mg/kg BLM+CM-101 1mg/kg BLM+CM-101 2.5mg/kg BLM+lgG * * ** Bleomycin (SC) induced dermal fibrosis Bleomycin (IT) induced lung fibrosis CM-101 Profoundly Reduces Skin and Lung Fibrosis in SSc Models Bleomycin Models Relevant to Systemic
Slide 12: Phase 1: Excellent Safety Profile & First Confirmation of Anti-Fibrotic Effects
PK-Target Engagement PK-PD 2.5mg/kg IV PK-PD 5mg/kg SC Liver Stiffness Relative change from baseline (%) Nordic Biosciences , Denmark Fibrotic Biomarkers Improved* FibroScan™ ProC4 *Concordant results across 6 relevant fibrotic markers TIMP1 Elastography Decreased Relative change from baseline (%) E
Slide 13: Systemic Sclerosis Overview: Clinical Trial & Endpoint Considerations
Systemic Sclerosis Overview: Clinical Trial & Clinical Endpoint Considerations Dr. Dinesh KhannaFrederick G. L. Huetwell Professor of RheumatologyProfessor of MedicineUniversity of Michigan [email protected]
Slide 14: Systemic Sclerosis
Systemic Sclerosis Dinesh Khanna, MD, MSFrederick G. L. Huetwell Professor of RheumatologyProfessor of Medicine, University of Michigan [email protected]
Slide 15: Scleroderma
Scleroderma The word “scleroderma” comes from two Greek words: “sclero” meaning hard, and “derma” meaning skin. There are approximately 200,000 patients in USApproximately 75,000-80,000 have systemic sclerosis (SSc) Scleroderma Localized Systemic Scleroderma or Systemic Sclerosis
Slide 16: SSc—Epidemiology
SSc—Epidemiology Rare diseaseEstimated prevalence1 US 276/millionEurope 88-160/millionEstimated incidence 18.7 cases/ million/ year2 With US population at ~ 328 million people, there are ~ 6,000 new SSc cases diagnosed each year 1Chifflow H Semin Arthritis Rheum 37:223-235 2Mayes et al. Arthritis Rh
Slide 17: Pathogenesis of SSc
Fibroproliferative obliterationVascular remodelingDigital ischemiaLeaky capillaries Inflammation/autopimmunity ECM myofibroblasts Pathogenesis of SSc
Slide 18: Christopher P Denton ▪ Dinesh Khanna ▪ www.thelancet.com ▪ Published online April 13, 2017
Christopher P Denton ▪ Dinesh Khanna ▪ www.thelancet.com ▪ Published online April 13, 2017 ▪ http://dx.doi.org/10.1016/50140-6736(17)30933-9
Slide 19: Usual Timing of Problems in Systemic Sclerosis
DIFFUSE CUTANEOUS VARIANT joint contractures skeletal myopathy interstitial lungdisease myocardial involvement esophageal disease pulmonary hypertension malabsorption LIMITEDCUTANEOUS VARIANT “renal crisis” TIME Raynaud, digital ischemia SKIN THICKNESS tendon/bursal friction rubs; inte
Slide 20: Clinician Viewpoint
Clinician Viewpoint Vasodilators Anti-inflammatory medicationsGlucocorticoidsACE inhibitorsH2 blockers/ Proton pump inhibitors Immunosuppressive medicationsAnti-fibrotic therapiesStem cell transplant
Slide 21: Patient's own illustration of skin symptoms of SSc
Patient’s own illustration depicting their experience of skin symptoms of SSc Khanna D, et al. Journal of Scleroderma and Related Disorders 2020
Slide 22: The Patient Journey with dcSSc
The Patient Journey with dcSSc from Initial Symptoms to Progressive Disease Initial SymptomsSkin thickeningRaynaud’s phenomenonTrivialized by patients DiagnosisDelays reaching appropriate specialist Shock at severity of diseasePoor prognosis TreatmentHigh treatment burdenLimited optionsNo cure Worse
Slide 23: Unmet Need
Unmet Need Lack of holistic approach to manage early SScCurrent management by a clinicianScreen for early organ involvementOrgan specific and supportive treatmentFDA approved therapyNintedanib and Tocilizumab for lung fibrosis PAH specific therapies as part of Group 1 PAH Off label treatments
Slide 24: Endpoints in Systemic Sclerosis
Endpoints in Systemic Sclerosis End points for inflammatory/ fibrotic manifestationsModified Rodnan skin scoreForced Vital CapacityComposite IndexAmerican College of Rheumatology Composite Response Index (ACR CRISS)Revised CRISS
Slide 25: Modified Rodnan Skin Score (MRSS)
Modified Rodnan Skin Score (MRSS) Histological correlation of skin score Skin Score: 3 Skin Score: 1 Skin Score: 2 Face Upper arm Chest Forearm Hand Fingers Thigh Leg Foot Upper arm Abdomen Forearm Hand Fingers Thigh Leg Foot Total _____ / 51 1 3 2 0 1 3 2 0 1 3 2 0 1 3 2 0 1 3 2 0 1 3 2 0 1 3 2 0 1
Slide 26: Forced Vital Capacity
Forced Vital Capacity Physiological assessment of lung volumes Surrogate measure to assess for systemic sclerosis-associated interstitial lung disease
Slide 27: Why a Combined Response Index for SSc?
Why a Combined Response Index for SSc? SSc has validated outcomes for individual manifestations SSc is a multisystem disorderCombined indices successful in other complex systemic rheumatic diseases:RCTs FDA approval of new therapiesRA-ACR Responder Index/Disease activity index: joint count, HAQ, AP
Slide 28: U.S. FDA Clinical Outcome Assessment (CoA) Compendium
U.S. FDA Clinical Outcome Assessment (CoA) Center for Drug Evaluation and Research, U.S. Food & Drug Administration. Clinical Outcome Assessment (CoA) Compendium
Slide 29: ACR Response Criteria
ACR Response Criteria (Originally 20% but evolved to include 50% and 70%) BenefitsAcceptable FDA endpointLed to approval of multiple biologic therapiesUnderstood by regulators and physicians A decrease in both tender and swollen joint counts An improvement in at least 3 of the following 5 measures:-
Slide 30: COMET – Combo vs Monotherapy
COMET – Combo vs Monotherapy Emery et al. Lancet 2008; 372: 375–82 ACR20 ACR50 ACR70
Slide 31: Composite End Point Revised CRISS
Composite End Point Revised CRISSCaptures global improvement in SSc 2-step process Ann Rheum Dis 2020;0:1-10. doi:10.1136/annrheumdis-2020-219100
Slide 32: 2-Step Process
2-Step Process Step 1 Step 2 Internal organ worsening? No Yes CRISS Score=0.00 Proceed to Step 2 Modified Rodnan skin score Assess skin involvement Forced vital capacity Assess lung involvement Patient global assessment Captures global improvement Physician global assessment Captures physician’s ass
Slide 33: Revised CRISS
Revised CRISS Holistic measure that assesses internal organ involvement and improvement in 5 core set measures.Assessed as proportion of patients who achieved a certain improvement (as percent change) in ≥ 3 of 5 measures.This is similar to ACR response index for rheumatoid arthritis Acceptable endp
Slide 34: CM-101 Systemic Sclerosis Phase 2 Clinical Program
CM-101 Systemic Sclerosis Phase 2 Clinical Program Dr. Arnon Aharon Chemomab CMO
Slide 35: Phase 2 Trial Design in Diffuse Cutaneous Systemic Sclerosis
Phase 2 Trial in Diffuse Cutaneous Systemic Sclerosis (dcSSC) Territories: US, EU and Israel Number of sites: 100 sites globally Expected initiation – Q1/2022 Randomization 220 patients 1:1 Randomization ScreeningPeriod Treatment Period CM-101 10 mg/kg; I.V. Q3W Placebo; I.V. Q3W Week 45 EoT visit W
Slide 36: Phase 2 Trial Targeted Population
Phase 2 Trial in Diffuse Cutaneous Systemic Sclerosis Targeted Population Key Inclusion Criteria Diagnosis of systemic sclerosis diffuse subtype early disease; < 5 years from onset of 1st non-Raynaud's sign/ symptommRSS > 15 and <45Evidence of disease activity: new/worsening of skin involvement, ILD
Slide 37: Phase 2 Trial Efficacy Endpoints
Phase 2 Trial in Diffuse Cutaneous Systemic Sclerosis Efficacy Endpoints Primary endpoint Proportion of participants who meet the Revised CRISS responder criteria after 48 weeks of treatment Key secondary endpoint Change in Forced Vital Capacity (FVC) % predicted after 48 weeks of treatment We selec
Slide 38: CM-101 in Systemic Sclerosis – Key Clinical Program Features
CM-101 in Systemic Sclerosis – Key Clinical Program Features CM-101 development program aimed at a label for the treatment of Systemic Sclerosis - Addressing high unmet medical need in Systemic Sclerosis - Leveraging unique dual MoA of CM-101 to support a disease modification label - Targeting the w
Slide 39: Q&A: All Speakers
e. “x. Chemomab Q&A: All Speakers
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