Cantargia Ab · OMXSTO:CANTA
Cantargia Ab — Investor Presentation (October 2023)
39 slides from Cantargia Ab's investor presentation, October 2023
Slide 1: Targeting IL1RAP to address unmet needs in severe cancer and autoimmune diseases
Targeting IL1RAP to address unmet needs in severe cancer and autoimmune diseases Corporate Presentation Oct 2023 NASDAQ STOCKHOLM MAIN LIST (CANTA.ST)
Slide 2: Safe Harbor Statement
Safe Harbor Statement Statements in the Investor Presentation, including those regarding the possible or assumed future or other performance of the Company or its industry or other trend projections, constitute forward-looking statements. By their nature, forward-looking statements involve known and
Slide 3: Cantargia – Investment highlights
Cantargia – Investment highlights NOVEL IL1RAP ANTIBODIES, POTENTIAL TO TREAT CANCER & INFLAMMATORY DISEASE • IL1RAP elevated in most solid and liquid tumors • IL1RAP signaling drives several autoimmune and inflammatory diseases NADUNOLIMAB: CLEAR ACTIVITY SIGNALS IN CANCER THERAPY WITH UPCOMING CAT
Slide 4: Current pipeline
Current pipeline proiact Disease Type of Discovery Preclinical Clinical Clinical Clinical 4 treatment phase phase phase | phase II phase III PDAC 1% line Gemcitabine/nab-paclitaxel Nadunolimab TNBC 15*/2"4 line Carboplatin/gemcitabine non-sa “rami non-squamous NSCLC Pie" ine ietilouinctantstas CAN10
Slide 5: Nadunolimab (CAN04) Overview
NADUNOLIMAB (CAN04) OVERVIEW
Slide 6: New strategy to treat cancer supported by clinical results
New strategy to treat cancer supported by clinical results PROMISING DATA IN PANCREATIC CANCER → Stronger efficacy than expected from chemotherapy alone → Patients with higher IL1RAP level benefit more Nadunolimab Durable response 50% Primary Chemo- Short-term Best change in tumor size tumor therapy
Slide 7: Cantargia – Strategy to improve current cancer therapies
Cantargia – Strategy to improve current cancer therapies IL1RAP – A NOVEL TARGET WITH SEVERAL OPPORTUNITIES; CURRENT FOCUS ON SYNERGISTIC COMBINATIONS MDSC – Myeloid-Derived Suppressor Cells 7
Slide 8: IL1RAP overexpressed in most solid tumors
IL1RAP overexpressed in most solid tumors IL1RAP EXPRESSION IN SOLID TUMOR TYPES SEVERAL TUMOR-PROMOTING CELLS EXPRESSING IL1RAP IN THE TUMOR MICROENVIRONMENT 100% IL1RAP-expressing tumors 75% 50% 25% 0% l C C st al ic er er ta SC CL at ge ea Liv d ec ad re NS HN ha Br r nc lo Bl op Co Pa Es Cancer
Slide 9: Targeting IL1RAP provides unique opportunities to treat cancer by IL-1α/β blockade and ADCC
Targeting IL1RAP provides unique opportunities to treat cancer by IL-1α/β blockade and ADCC Nadunolimab NADUNOLIMAB COUNTERACTS IMMUNE SUPPRESSION AND POTENTIATES THERAPY ADCC – Antibody-Dependent Cellular Cytotoxicity; NK – Natural Killer; TIR – Toll-Interleukin-1 Receptor 9
Slide 10: Nadunolimab potentiates antitumor activity of chemotherapy
Nadunolimab potentiates antitumor activity of chemo- therapy Nadunolimab IL-1α Tumor growth * 20 100 Relative expression Tumor volume (%) 15 ** Control Docetaxel 10 50 Anti-IL-1β + Docetaxel Nadunolimab + Docetaxel 5 0 0 4 500 Docetaxel (nM) → Nadunolimab blocks both IL-1α and → Docetaxel induces IL
Slide 11: Chemotherapy induces IL-1α and IL-1β in the tumor
Chemotherapy induces IL-1α and IL-1β in the tumor IL-1α IL-1β-converting enzyme Tumor cell region (T) Stromal cell region (S) 6 * Control Gem/Cis 250 ** Control Gem/Cis 2 Positive cells/mm % Positive cells S 200 T T 4 T 150 S S 100 2 S T T 50 T 0 0 l s t ro Ci is l / ro n /C Co Gem nt m Co Ge → Gem/
Slide 12: Targeting IL1RAP uniquely synergizes with chemotherapy
Targeting IL1RAP uniquely synergizes with chemotherapy Tumor growth Body weight 2000 0 Tumor volume (mm ) 3 1500 Vehicle % Change Iso Control -5 Vehicle 1000 Nadunolimab Gem/Cis Gem/Cis ** Nadunolimab+Gem/Cis Nadunolimab+Gem/Cis -10 500 * 0 -15 0 5 10 15 Day post-treatment → Nadunolimab increases ef
Slide 13: Nadunolimab (CAN04) Clinical Results
NADUNOLIMAB (CAN04) CLINICAL RESULTS
Slide 14: NSCLC – Induction of IL1RAP and IL-1α with therapy
NSCLC – Induction of IL1RAP and IL-1α with therapy Pre-treatment On treatment (Nadunolimab + Gem/Cis) IL1RAP (brown) IL-1α (brown) IL-1α INDUCED BY CHEMOTHERAPY IN LINE WITH PRECLINICAL FINDINGS; WELL ESTABLISHED DANGER SIGNAL – ACTIVITY BLOCKED BY NADUNOLIMAB 14
Slide 15: PDAC – Staging and treatment
PDAC – Staging and treatment Expected number of cases US 2023: 64,000 Stage I - local: 3,200 Stage II - regional LN; 3,200 Stage IV - Stage III - metastatic: locally adv: 32,000 25,600 Stage I Stage II Stage III Stage IV RESECTABLE OR BORDERLINE RESECTABLE DISEASE LOCALLY ADVANCED OR METASTATIC DISE
Slide 16: PDAC – IL1RAP linked to poor prognosis
PDAC – IL1RAP linked to poor prognosis IL1RAP IN PDAC KRAS MUTATIONS IN PDAC IL1RAP IL1RAP KRAS mutations Tumor cells 12 ✱✱ 12 ✱✱✱✱ 8.8% 10 10 Other Log2(TPM) 8 8 15.0% 36.6% Fibroblasts WT G12D 6 6 1.2% G12C 4 4 25.8% 12.7% 2 2 G12V G12R Macrophages 0 0 WT G12D G12R G12V Stage 1-3 4 → IL1RAP levels
Slide 17: PDAC – Positive interim data in 1st line patients
PDAC – Positive interim data in 1st line patients OS and iPFS for mITT patients Best responses according to iRECIST 50% Best change in tumor size 0% -50% -100% iCPD iUPD iSD iPR Nadunolimab combination with Gem/Abraxane in 1st line PDAC (n=73): → 33% response rate with long OS and iPFS → Additional
Slide 18: PDAC – Strong efficacy in patients with high tumor IL1RAP level
PDAC – Strong efficacy in patients with high tumor IL1RAP level OS by IL1RAP subgroup IL1RAP High IL1RAP Low 50% Best change in tumor size iCPD 0% iUPD iSD iPR -50% -100% Efficacy analysis for IL1RAP High (n=29) vs IL1RAP Low (n=20) PDAC patients (1st line, combination with Gem/Abraxane): → Signific
Slide 19: PDAC – Strong efficacy in patients with high tumor IL1RAP level
PDAC – Strong efficacy in patients with high tumor IL1RAP level iPFS by IL1RAP subgroup OS by IL1RAP subgroup Monotherapy efficacy analysis for IL1RAP High (n=5) vs IL1RAP Low (n=12) PDAC patients (late-stage, typically progressed after two lines of chemotherapy): → Significantly prolonged iPFS in I
Slide 20: PDAC – Safety profile is manageable and supports MOA
PDAC – Safety profile is manageable and supports MOA → Neutropenia manageable through G-CSF prophylaxis → In 7 patients given G-CSF prophylaxis, only 1 developed grade 3-4 neutropenia All Patients in All Cycles → Only 1 % peripheral neuropathy grade 3-4 observed (17% in historical controls) 100% n=6
Slide 21: PDAC – Phase IIb study design
PDAC – Phase IIb study design Open-label, randomized, controlled, non-comparative, 3-arm study Primary endpoint: evaluating 2 dose levels of nadunolimab + gemcitabine/ nab-paclitaxel → PFS with gemcitabine/nab-paclitaxel as control: Pre-planned subgroup analysis based on baseline IL1RAP expression o
Slide 22: NSCLC – Promising efficacy of nadunolimab combination therapy
NSCLC – Promising efficacy of nadunolimab combination therapy OS and PFS for mITT patients PFS by dose level Nadunolimab combination with Gem/Cis in 1st/2nd line NSCLC (n=30): → ORR 53%, 13.7 mo median OS, 7.0 mo median PFS (dose-response trend for PFS) → Generally well tolerated; neutropenia freque
Slide 23: NSCLC – Promising efficacy of nadunolimab combination therapy
NSCLC – Promising efficacy of nadunolimab combination therapy Best responses according to RECIST 50% Best change in tumor size High ORR to nadunolimab and 0% platinum doublets in different lines of 1L/2L NCG therapy: 1L/2L NCP → Gem/Cis 1st/2nd line: ORR 53% (n=30) ≥3L NCG -50% → Carbo/Pemtrex 1st/2
Slide 24: NSCLC – Long-term benefit with strong signal in non-squamous subtype
NSCLC – Long-term benefit with strong signal in non- squamous subtype Non- Treatment course for each individual patient All Historical Non-squamous squamous, (n=30) data1,2 (n=16) CR1 historical data3 Median OS 13.7 mo 10.3 mo 15.9 mo 11.3 mo CR2 Median PFS 7.0 mo 5.1 mo 7.3 mo 4.9 mo OS ORR 5
Slide 25: NSCLC – Complete responders with distinct biomarker profile
NSCLC – Complete responders with distinct biomarker profile 150 Target lesion diameter Nadunolimab monotherapy NCG 100 CR (mm) 50 two lymph nodes reduced to ≤5 mm 0 0 12 24 36 48 Months 100 3 80 Positive cells (%) 60 → One CR maintained over 3 yrs (CR1), second CR Score (0-3) 40 2 PD-L1 (tumor cel
Slide 26: TNBC – Promising early safety and efficacy
TNBC – Promising early safety and efficacy Nadunolimab combination with Best responses according to RECIST OS and PFS Gem/Carbo in 1st/2nd line 100% metastatic TNBC: Best change in tumor size 50% 15 patients enrolled in the dose- escalation phase: 0% → Preliminary ORR: 60% (1 CR, 8 PR, 4 SD, 2 PD) -
Slide 27: Key messages
Key messages Resistant → Most chemotherapies induce chemoresistance already after tumor Chemo- a few months of therapy. Chemotherapy can upregulate therapy both IL-1α and IL-1β, signaling through IL1RAP. → Clinical results strongly support potential unique first-in- class opportunities in PDAC, NSCL
Slide 28: CAN10 – Opportunity in Autoimmune/Inflammatory Disease
CAN10 – OPPORTUNITY IN AUTOIMMUNE/INFLAMMATORY DISEASE
Slide 29: CAN10 – New clinical asset in autoimmunity/inflammation
CAN10 – New clinical asset in autoimmunity/inflammation → IL1RAP-binding antibody potently blocking IL-1, IL-33 and IL-36, without ADCC → Unique anti-inflammatory activity observed in different mouse models (myocarditis, systemic sclerosis, psoriasis, inflammation) → Development focusing on systemic
Slide 30: Indications and preclinical development
Indications and preclinical development → Inflammation of the myocardium that can lead to → Chronic, autoimmune connective tissue disorder fibrosis and loss of contractile function characterized by inflammation and fibrosis of the skin and internal organs → Can be both autoimmune and viral → The lea
Slide 31: Systemic sclerosis – mCAN10 inhibits bleomycin-induced skin fibrosis
Systemic sclerosis – mCAN10 inhibits bleomycin-induced skin fibrosis Bleomycin (BLM) model mCAN10 10 mg/kg twice W BLM 2.5 mg/kg (daily s.c.) Nintedanib 50 mg/kg QD C57BL/6 Established fibrosis Termination n=10 per group Week 3 Week 6 No BLM (6 wks) Baseline BLM (3 wks) Dermal thickness Myofibroblas
Slide 32: Viral myocarditis – mCAN10 reduces disease severity
Viral myocarditis – mCAN10 reduces disease severity CVB3 myocarditis experimental design CVB3 Echocardiography → mCAN10 reduced disease severity, based on histological scoring of heart sections, and Balb/c ♂ 10 d.p.i. preserved heart function 10 weeks old Peak of inflammation 4 *** → mCAN10 also red
Slide 33: Experimental autoimmune myocarditis – mCAN10 improves heart function
Experimental autoimmune myocarditis – mCAN10 improves heart function Left Ventricual Ejection Fraction (LVEF) LVEF (treatment from day 7) LVEF (treatment from day 7) 1.1 1.2 1.0 ** * * Ratio to baseline Ratio to baseline Ratio to baseline ** 1.0 * mCAN10 0.9 Ctrl mCAN10 1.0 0.9 Anti-IL-1β 0.8 Ctrl A
Slide 34: Psoriasis and psoriatic arthritis – mCAN10 reduces disease severity
Psoriasis and psoriatic arthritis – mCAN10 reduces disease severity Psoriasis Psoriasis (Day 7) 6 8 ** → mCAN10, but not anti-IL-1β, Total score (0-8) Total score (0-8) Vehicle 6 4 Ctrl Anti-IL-1β reduced the skin inflammation Anti-IL-1β 4 in Imiquimod-induced Ctrl mCAN10 2 mCAN10 psoriasis 2 Dexame
Slide 35: CAN10 – Project status
CAN10 – Project status Status → CAN10 safe in GLP tox study → Strong results in several preclinical models, including lead indications myocarditis and systemic sclerosis → Phase I ongoing, early planning of patient studies (phase IIa) Clinical phase I study – First data set during 2024 → Phase I in
Slide 36: Milestones & Investment Highlights
MILESTONES & INVESTMENT HIGHLIGHTS
Slide 37: Upcoming milestones
Upcoming milestones Nadunolimab Additional PDAC NSCLC TNBC CAN10 milestones • Start of Phase IIb trial • Efficacy/biomarker • Safety and efficacy • Phase I recruitment • New clinical data in 150-200 patients data from CANFOUR data from Phase I at and treatment presented from early 2024 2023 and 2024
Slide 38: Cantargia – Investment highlights
Cantargia – Investment highlights NOVEL IL1RAP ANTIBODIES, POTENTIAL TO TREAT CANCER & INFLAMMATORY DISEASE • IL1RAP elevated in most solid and liquid tumors • IL1RAP signaling drives several autoimmune and inflammatory diseases NADUNOLIMAB: CLEAR ACTIVITY SIGNALS IN CANCER THERAPY WITH UPCOMING CAT
Slide 39: Cantargia IP
Cantargia IP → Lead candidate anti-IL1RAP antibody CAN04 Expiry year 2035 Granted (e.g. Europe, USA, China, Japan) → Anti-IL1RAP for treatment of solid tumors Expiry year 2032 Granted (e.g. Europe, USA, China, Japan) → Anti-IL1RAP for treatment of hematological disorders Expiry year 2030 Granted (e.