Cantargia Ab · OMXSTO:CANTA
Cantargia Ab — Investor Presentation (March 2024)
43 slides from Cantargia Ab's investor presentation, March 2024
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 March 2024 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 Project Disease Type of Discovery Preclinical — Clinical Clinical Clinical ' treatment phase phase phase | phase II phase Ill PDAC 1% line Gemcitabine/nab-paclitaxel Nadunolimab TNBC 15*/2"4 jine Carboplatin/gemcitabine NSCLC/ ' non-squamous NSCLC ine Platinum doublets Systeme se TT
Slide 5: Nadunolimab (CAN04) Overview
NADUNOLIMAB (CAN04) OVERVIEW
Slide 6: 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 6
Slide 7: 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% al al st C C ic er r de SC CL at ct ge ea L iv ad re re NS HN ha Br nc lo Bl op Co Pa Es Cancer
Slide 8: 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 8
Slide 9: 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
Slide 10: 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 i s ro /C nt l s ro i /C Co m nt Ge m Co Ge → Gem
Slide 11: 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
Slide 12: Nadunolimab (CAN04) Clinical Results
NADUNOLIMAB (CAN04) CLINICAL RESULTS
Slide 13: 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 13
Slide 14: 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 15: 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 Stage 1- 3 4 G12D G12V WT G12R → IL1RAP level
Slide 16: 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 → Additiona
Slide 17: 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 18: 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 19: 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 20: PDAC – Phase IIb study design
PDAC – Phase IIb study design Analysis Groups All Primary endpoint: → PFS Nadunolimab 80 mg + G/nabP Treatment groups Pre-planned interim review : N = 150-200 Randomized Nadunolimab 200 mg + G/nabP → After 60 pts to allow strategic next steps incl. regulatory 1:1:1 With interim Timelines: after 60 p
Slide 21: Nadunolimab PDAC milestone targets
Nadunolimab PDAC milestone targets mid-2024 H1 2025 H2 2025 H1 2026 H1 2027 H1 2028 H2 2028 Start PANFOUR PANFOUR enrolment PANFOUR study study completed results FDA meeting FDA EOP2 meeting Phase III study preparation Start Phase III Phase III enrolment Phase III study study completed results Poten
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 ce
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: Nadunolimab and alleviation of neuropathy
Nadunolimab and alleviation of neuropathy → Chemotherapy induce neuropathy by several pathways including IL-1 (neuroinflammation) → Nadunolimab, phase 2 data in PDAC with Gem/nabP → lower Grade 3-4 peripheral neuropathy than expected from historical controls (1% vs 17%). → Further analysis from this
Slide 28: Key messages
Key messages → Nadunolimab, investigated in almost 300 pts, shows efficacy both as monotherapy as well as in combination. Resistant tumor → Clinical results strongly support potential unique first-in-class Chemo- therapy opportunities in PDAC, NSCLC and TNBC. Controlled phase 2 trial ongoing in TNBC
Slide 29: CAN10 – Opportunity in Autoimmune/Inflammatory Disease
CAN10 – OPPORTUNITY IN AUTOIMMUNE/INFLAMMATORY DISEASE
Slide 30: External validation of IL-1 pathway - lutikizumab in HS
External validation of IL-1 pathway - lutikizumab in HS • Lutikizumab is a dual variable domain antibody against IL-1α and IL-β • Patients treated with lutikizumab experienced higher response rates in the primary endpoint of HiSCR 50 and the secondary endpoint of skin pain NRS30 at week 16 than thos
Slide 31: CAN10 – Added value vs IL-1 blockade only
CAN10 – Added value vs IL-1 blockade only → 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 sclerosis and
Slide 32: IL1RAP and the IL-1/33/36 pathways are upregulated in SSc patient skin
IL1RAP and the IL-1/33/36 pathways are upregulated in SSc patient skin 2 publicly available human SSc cohorts show differential expression of IL1RAP and associated genes in SSc skin 14 SSc vs. 11 healthy Agilent 2-channel Mahoney et al. 2015 GSE59787 Microarray Skaug et al. Ann Rheum Dis 2020. GSE13
Slide 33: IL-1, IL-33 and IL-36 directly promotes fibrosis in SSc fibroblasts
IL-1, IL-33 and IL-36 directly promotes fibrosis in SSc fibroblasts which can be counteracted by CAN10 Isotype CAN10 Collagen I SMA Collagen I staining ✱ ✱✱✱✱ ✱✱✱✱ ✱ ✱✱ 1.6 ### #### 2.0 ✱✱ #### # ## #### Fold changes #### Fold changes 1.5 1.2 1.0 0.8 0.5 0.4 0.0 0.0 DPBS TGF ILs$ ILs$ DPBS TGF IL
Slide 34: 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 35: Systemic sclerosis: Therapeutic mCAN10 treatment reduces lung fibrosis
Systemic sclerosis: Therapeutic mCAN10 treatment reduces lung fibrosis in the Topo and cGvHD models Ashcroft score Collagen area 4 * 3 **** No fibrosis ** *** Topo model 3 Fold change Fold change 2 2 1 No fibrosis 1 Vehicle Iso Control 0 0 l i c le t ro 1 0 n ib 0 l ib c le AN da ro eh on N1 an nt h
Slide 36: 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 preserved Balb/c 10 d.p.i. heart function 10 weeks old Peak of inflammation 4 *** → mCAN10 also reduce
Slide 37: 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
Slide 38: CAN10 first-in-human study
CAN10 first-in-human study IL1RAP dependent signaling up in HS and Psoriasis (Pso) → Combined SAD/MAD protocol → IV administration in healthy volunteers (SAD) → SC administration in subjects with mild to moderate plaque psoriasis (MAD) → Safety and PK Witte-Händel et al., JID 2018 → Building value b
Slide 39: CAN10 – a potent blocker of IL1RAP function with effects in skin, lung, heart and vasculature
CAN10 – a potent blocker of IL1RAP function with effects in skin, lung, heart and vasculature Status → CAN10 safe in GLP tox study → Strong results in several preclinical models, including lead indications systemic sclerosis and myocarditis → Phase I ongoing, early planning of patient studies (phase
Slide 40: Milestones & Investment Highlights
MILESTONES & INVESTMENT HIGHLIGHTS
Slide 41: Upcoming milestones
Upcoming milestones Nadunolimab Additional PDAC NSCLC TNBC CAN10 milestones • Start of Phase IIb trial • Efficacy/biomarker • Full recruitment H2 • Phase I data updates • New clinical data in 150-200 patients data from CANFOUR 2024 during 2024 (including presented from H1 2024 during 2024 safety and
Slide 42: 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 43: Cantargia IP
Cantargia IP → Lead candidate anti-IL1RAP antibody CAN04 Expiry year 2035 Granted (e.g. Europe, USA, China, Japan) Mother patent and divisionals → Lead candidate anti-IL1RAP antibody CAN10 Expiry year 2041 Granted (USA) Examination at early stage in remaining territories → Anti-IL1RAP for treatment