Cantargia Ab · OMXSTO:CANTA
Cantargia Ab — Investor Presentation (August 2021)
28 slides from Cantargia Ab's investor presentation, Aug 12, 2021
Slide 1: IL1RAP as a target for antibody therapy in oncology and inflammation
IL1RAP as a target for antibody therapy in oncology and inflammation Göran Forsberg, CEO Aug 2021
Slide 2: Safe Harbour Statement
Safe Harbour 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 an
Slide 3: I. Introduction
I. INTRODUCTION
Slide 4: Targeting IL1RAP and relevance in cancer
Targeting IL1RAP and relevance in cancer • IL1RAP is an essential part of the IL-1 receptor complex • IL1RAP is an inflammatory protein expressed by tumor cells and by tumor-supporting cells in the tumor vicinity • IL1RAP is involved in chronic tumor inflammation and promotes tumor growth and immune
Slide 5: Nadunolimab (CAN04) – Mechanism of action
Nadunolimab (CAN04) – Mechanism of action ADCC – Reduced activation Reduced Tumor cell death and infiltration of angiogenesis immunosuppressive cells CAN04 BLOCKS BOTH FORMS OF IL-1 AND CAN ERADICATE CELLS MEDIATING THE EFFECTS OF IL-1 Note: ADCC = Antibody-Dependent Cellular Cytotoxicity. CAF = Can
Slide 6: IL1RAP expression in solid tumors
IL1RAP expression in solid tumors ,,,,,, % IL1RAP-expressing tumors NSCLC biopsy CANFOUR, IL1RAP staining IL1RAP IS EXPRESSED BROADLY IN SOLID TUMORS NSCLC – non-small cell lung cancer HNSCC – head and neck squamous carcinoma 5
Slide 7: IL1RAP expression in solid tumors
IL1RAP expression in solid tumors IL1RAP is expressed by: • tumor cells • cells in the tumor microenvironment: o cancer-associated fibroblasts (CAF) o tumor-associated macrophages (TAM) o monocytes o neutrophils o endothelial cells IL1RAP-expressing cells react to IL1a or IL1b in the tumor microenvi
Slide 8: The pancreatic tumor microenvironment in vitro
The pancreatic tumor microenvironment in vitro Human pancreatic cancer cells cultured with human cancer associated fibroblasts CAF PDAC CAF PDAC - CAN04 + CAN04 - CAN04 + CAN04 4 genes changed 230 genes changed by CAN04 by CAN04 CAF = Cancer-associated fibroblast NPF = Normal pancreatic fibroblast R
Slide 9: Inhibition of pancreatic tumor growth by CAN04
Inhibition of pancreatic tumor growth by CAN04 Tumor growth in a CAF-PDAC xenograft model of human pancreatic cancer PDAC *** CAF PDAC – cancer cells CAF – tumor stroma n=10 INHIBITION OF TUMOR CELL GROWTH BY CAN04 MEDIATED BY CAF-S 13
Slide 10: The IL-1 system is induced by chemotherapy
The IL-1 system is induced by chemotherapy 3 1. Chemotherapy induces cell killing and IL1a upregulation in tumor 2 1 cells 2. IL1b is induced in the tumor stroma 3. IL1a and IL1b mediates chemoresistance 9
Slide 11: The IL-1 system is induced by chemotherapy
The IL-1 system is induced by chemotherapy Immunohistochemistry of tumor tissue in a NSCLC patient-derived xenograft model IL-1a is upregulated in tumor cells after chemotherapy and Interleukin 1b-converting enzyme (ICE/Caspase-1) in the tumor stroma 8
Slide 12: CAN04 increases the efficacy of chemotherapy
CAN04 increases the efficacy of chemotherapy Tumor growth in a NSCLC patient-derived xenograft model n=10 CAN04 increases efficacy of chemotherapy regimens and counteracts weight loss 10
Slide 13: mCAN04 targets metastatic niches and counteracts lung metastases
mCAN04 targets metastatic niches and counteracts lung metastases in the IL1RAP low/neg 4T1 and B16 syngeneic models Orthotopic implantation of 4T1 TNBC cells Intravenous injection of B16 melanoma cells, n=10 mice mCAN04 is an anti-murine IL1RAP CAN04 surrogate antibody 13
Slide 14: Summary
Summary • CAN04 (nadunolimab) blocks IL1a/IL1b signaling and induces antibody-mediated cell killing of IL1RAP-expressing cells • IL1RAP is broadly expressed in solid tumors, both on tumor cells and in tumor stroma • CAN04 targets both tumor cells and components of the tumor stroma • Chemotherapy act
Slide 15: II. Clinical Trials and Results
II. CLINICAL TRIALS AND RESULTS
Slide 16: Cantargia – Opportunity to save lives and create value
Cantargia – Opportunity to save lives and create value ➢ Potentially more effective treatment against novel target in clinically validated pathway ➢ First in class platform technology against novel target ➢ Well financed to build a broad, diversified pipeline ➢ Right team and clear plan to position
Slide 17: Positive data in pancreatic cancer
Positive data in pancreatic cancer CAN04 in combination with 1st line gem/abraxane: • Durable responses observed (median DOR 6.8 mo, 27% response rate) • Important finding of pseudoprogression-like response in 5 (15%) patients predicting long PFS. • Promising PFS (7.8 mo) and OS (12.6 mo, 42 % event
Slide 18: Patients with Pseudoprogression-like response
Patients with Pseudoprogression-like response Subject 1 Subject 2 • All presented PD at 1st CT scan evaluation (8 weeks) • All showed concomitant Ongoing reduction of CA19-9 Subject 3 Subject 4 Subject 5 Ongoing PSEUDOPROGRESSION VERY UNCOMMON IN PANCREATIC CANCER INDICATE IMMUNE RELATED MECHANISM O
Slide 19: CAN04/GN in PDAC safety summary and benchmark
CAN04/GN in PDAC safety summary and benchmark Gem/Abraxane CANFOUR FOLFIRINOX Grade 3 or higher AEs (von Hoff, 2013) CAN04/GN (Conroy 2011) The beneficial effect in N=421 N=36 N=171 fatigue and chemotherapy- Neutropenia 38% 67% 46% induced neuropathy2 (nab- paclitaxel or oxaliplatin) Febril
Slide 20: Tumor shrinkage – NSCLC combination
Tumor shrinkage – NSCLC combination → CAN04 in combination with gem/cis in 1st line chemotherapy Patient → 6 of 9 evaluable patients with metastatic non-small cell lung 1 2 3 4 5 6 7 8 9 0 cancer (NSCLC) showed objective response including 1 Percent tumor reduction complete response (67% vs historic
Slide 21: Nadunolimab clinical development status
Nadunolimab clinical development status Study Indication CAN04 combination Status Planned milestone(s) CANFOUR NSCLC Gemcitabine/cisplatin Recruitment ongoing, Results planned for Q3 2021 PDAC Gemcitabine/nab- Extension phase ongoing. Main study interim results presented 20 May paclitaxel (Dosing sc
Slide 22: III. Targeting IL1RAP in Autoimmune Diseases
III. TARGETING IL1RAP IN AUTOIMMUNE DISEASES
Slide 23: CAN10 – New development project
CAN10 – New development project → IL1RAP binding antibody potently blocking IL-1, IL-33 and IL-36 → Unique anti-inflammatory activity observed in different mouse models (myocarditis, psoriasis, inflammation) → Development focusing on unmet medical need in systemic sclerosis and myocarditis. Disease
Slide 24: IL1RAP inhibition is a potent strategy to block inflammation
IL1RAP inhibition is a potent strategy to block inflammation MSU-induced peritonitis (i.p. injection with MSU-crystals, measure cells and cytokines after 6h) Peritoneal lavage Cytokines in lavage 600000 *** 1.5 IL1RA …in a way that is Ratio (treated/control) ** Neutrophils (cells/mL) ** mCAN10 40000
Slide 25: IL1RAP inhibition modulates local and systemic inflammation
IL1RAP inhibition modulates local and systemic inflammation IMQ-induced Psoriasis (topical daily administration of IMQ, biweekly i.p treatment with ab or daily topical with dex) Total back score Total back score • Skin inflammation involves IL1, 6 Vehicle Isotype aIL-1b 6 IL33 and IL36 • Experiments
Slide 26: mCAN10 improves heart function in experimental autoimmune myocarditis
mCAN10 improves heart function in experimental autoimmune myocarditis 11
Slide 27: IV. Summary
IV. SUMMARY
Slide 28: Targeting IL1RAP is a novel strategy in treatment of cancer and autoimmune disease
Targeting IL1RAP is a novel strategy in treatment of cancer and autoimmune/inflammatory disease CAN04 (Nadunolimab) → In phase II clinical development with lead indications NSCLC and PDAC → Early clinical results in combination with chemotherapy are encouraging → Several clinical trials ongoing or s