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 December 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 Asset Indication Discovery Preclinical Phase 1 Phase 2 Phase 3 PDAC**, Nadunolimab TNBC*, NSCLC** Hidradenitis Suppurativa CAN10 Systemic Sclerosis New opportunities within IL1RAP CANxx platform PDAC – pancreatic cancer; TNBC – triple-negative breast cancer; NSCLC – non-small cell l
Slide 5: CAN10 – Opportunity in autoimmune/inflammatory disease
CAN10 – OPPORTUNITY IN AUTOIMMUNE/INFLAMMATORY DISEASE
Slide 6: CAN10 developed to block IL-1 family with precision
CAN10 developed to block IL-1 family with precision • CAN10 prevents signaling from IL1/, IL-33 and IL36// • CAN10 binds IL1RAP with pM affinity and prevents IL1RAP interaction with the IL-1, IL-33 and IL-36 receptors • CAN10 has shown robust efficacy in preclinical models of several diseases •
Slide 7: CAN10 first-in-human study - SAD part
CAN10 first-in-human study - SAD part Design Results • Blinded, placebo-controlled study • No safety signals • Nine dose groups from 1 to 400 mg CAN10 incl. 2 patients on • Receptor occupancy documented (at Cmax) placebo in each group • Potent PD effects on IL-1 & IL-36 at Cmax and day 8 Receptor Oc
Slide 8: Full blockade of IL-1β signaling at Cmax and at day 8 in treated subjects
Full blockade of IL-1β signaling at Cmax and at day 8 in subjects treated with CAN10 IL-1β induced IL-6 release 3 fold change vs pre-dose IL-1β induced IL-6 2 1 0 D1 D8 D1 D8 400 mg Presumed CAN10 placebo Whole blood from the participants in the 400 mg cohort stimulated with IL-1β pre-dose, 1 hour p
Slide 9: CAN10 - Targeting IL-1 family in inflammation
CAN10 - Targeting IL-1 family in inflammation • Evidence of IL-1 family cytokines (IL-1, IL-33, IL-36) driving inflammatory diseases • These cytokines are commonly upregulated and operate together in several diseases • Blockade of individual IL-1 family members insufficient • IL-1 and IL-36 targeti
Slide 10: Overview of Hidradenitis Suppurativa (HS)
Overview of Hidradenitis Suppurativa (HS) HS – a severe chronic inflammatory skin disease • HS is a diverse disease with several inflammatory components involved in the pathology • Estimated HS prevalence of 0.7-1.2% Inadequate current treatments • Antibiotics • Steroids • Anti-TNFα (Humira), anti-I
Slide 11: External clinical results strongly support CAN10 in Hidradenitis Suppurativa
External clinical results strongly support CAN10 in Hidradenitis Suppurativa (HS) Spesolimab Spesolimab 100 10 IL-36R-blockade (spesolimab, BI) positive results on disease severity1 Draining Tunnel count Change in IHS4 5 • Efficacy in Phase 2 randomized controlled study (NCT04762277): iHS4, HASI- (%
Slide 12: CAN10 for treatment of Hidradenitis Suppurativa (HS)
CAN10 for treatment of Hidradenitis Suppurativa (HS)
Slide 13: IL1RAP and the IL-1/33/36 pathways are upregulated in skin from Systemic Sclerosis patients
IL1RAP and the IL-1/33/36 pathways are upregulated in skin from Systemic Sclerosis (SSc) patients 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
Slide 14: IL-1, IL-33 and IL-36 directly promote fibrosis in Systemic Sclerosis fibroblasts
IL-1, IL-33 and IL-36 directly promotes fibrosis in Systemic Sclerosis 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$ IL
Slide 15: 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 16: 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 0 0 l ib l b c le c le ro ro i N1 N1 an an nt nt hi hi ed e
Slide 17: 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 reduc
Slide 18: 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 19: Nadunolimab (CAN04) Overview
NADUNOLIMAB (CAN04) OVERVIEW
Slide 20: 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 20
Slide 21: 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% t l r al er L C t ic as ta e e C C SC re a r e re c L iv ag NS ad d N nc B lo ph H Bl Pa Co Es o
Slide 22: 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 22
Slide 23: 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 24: 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 25: 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 26: Nadunolimab (CAN04) Clinical Results
NADUNOLIMAB (CAN04) CLINICAL RESULTS
Slide 27: Pancreatic Cancer (PDAC) – Staging and treatment
Pancreatic Cancer (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 ADVANCE
Slide 28: Pancreatic Cancer – IL1RAP linked to poor prognosis
Pancreatic Cancer – 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 →
Slide 29: Pancreatic Cancer – Positive data in 1st line patients
Pancreatic Cancer – Positive 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 → Addi
Slide 30: Pancreatic cancer – Efficacy and IL1RAP level
Pancreatic cancer – Efficacy and IL1RAP level OS by IL1RAP subgroup IL1RAP High IL1RAP Low 50% Best change in tumor size iCPD 0% iUPD iSD iPR -50% -100% → High IL1RAP levels associated with worse prognosis and KRAS mutations. → Significantly prolonged OS in ILRAP High vs IL1RAP Low patients (14.2 vs
Slide 31: 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 32: 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 33: 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%). → Correlation between naduno
Slide 34: Nadunolimab and alleviation of neuropathy
Nadunolimab and alleviation of neuropathy Percent with neuropathy Day of onset 80 250 1 mg/kg Day until first event 200 Percent of patients 60 2.5 mg/kg in dose group 5 mg/kg 150 40 7.5 mg/kg 100 20 50 0 0 Any grade neuropathy Any grade neuropathy CORRELATION BETWEEN NADUNOLIMAB DOSE LEVEL AND DECRE
Slide 35: NSCLC – Promising efficacy of nadunolimab combination therapy
Non-small cell lung cancer (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 N
Slide 36: 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 37: NSCLC – Strongest effects in patients no longer responding to PD1-inhibitors
NSCLC – Strongest effects in patients no longer responding to PD1-inhibitors MODIFICATIONS IN TUMOR MICROENVIRONMENT FAVORABLE FOR NADUNOLIMAB THERAPY AND MAY BE LINKED TO STRONG EFFICACY OBSERVED
Slide 38: Keytruda combination – Promising signs of clinical activity
Keytruda combination – Promising signs of clinical activity with remarkable benefit in a subset of patients COMBINATION WITH KEYTRUDA SHOWS LONG SURVIVAL CORRELATING WITH TUMOR MICROENVIRONMENT CHARACTERISTICS
Slide 39: Triple-negative breast cancer (TNBC) – Promising early safety and efficacy
Triple-negative breast cancer (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
Slide 40: Milestones & Investment Highlights
MILESTONES & INVESTMENT HIGHLIGHTS
Slide 41: Upcoming milestones
Upcoming milestones Nadunolimab Additional PDAC TNBC AML/MDS CAN10 milestones • Phase 2b trial in 150- • Randomized Phase 2 • Start phase 1/2 Q4 • Phase 1 final data H1 • New preclinical and 200 patients top-line data in H1 2024 (DOD sponsored 2025 translational results 2025 with MDA*) • Start phase
Slide 42: 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