Cantargia Ab · OMXSTO:CANTA
Cantargia Ab — Investor Day (April 2023)
66 slides from Cantargia Ab's investor day presentation, Apr 24, 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 R&D Day Apr 24, 2023 NASDAQ STOCKHOLM MAIN LIST (CANTA.ST)
Slide 2: Program
Program • Welcome and introduction to Cantargia – Göran Forsberg, CEO • Nadunolimab mechanism of action – David Liberg, VP Research • Clinical results including new biomarker data of nadunolimab – Dominique Tersago, CMO • Pancreatic cancer and relevance of nadunolimab results – Prof. Eric Van Cutsem
Slide 3: Welcome and introduction to Cantargia
WELCOME AND INTRODUCTION TO CANTARGIA
Slide 4: 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 5: Cantargia: Investment highlights
Cantargia: Investment highlights NOVEL IL1RAP ANTIBODIES, POTENTIAL TO ADDRESS CANCER & INFLAMMATORY DISEASE • IL1RAP elevated in most solid and liquid tumors • Potential to breakdown resistance to cancer treatment, enabled by unique dual action approach – nadunolimab • Additional key project for in
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: 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 → Patients with higher IL1RAP benefit more Nadunolimab Durable response 50% Primary Chemo- Short-term Best change in tumor size tumor therapy response 0%
Slide 8: IL1RAP: Broad application in cancer and autoimmune disease
IL1RAP: Broad application in cancer and autoimmune disease 8
Slide 9: Purpose of April R&D day
Purpose of April 24 R&D day • Update on recent positive results generated with nadunolimab • New pancreatic cancer data and relevance • Strategic opportunities for Cantargia • Nadunolimab mechanism of action – David Liberg, VP Research • Clinical results including new biomarker data of nadunolimab –
Slide 10: Nadunolimab mechanism of action
NADUNOLIMAB MECHANISM OF ACTION
Slide 11: 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 IL1RAP-expressing tumors 100 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 cell
Slide 12: 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; TIR – Toll-Interleukin-1 Receptor; NK – Natural Killer 12
Slide 13: Targeting IL1RAP uniquely synergizes with chemotherapy
Targeting IL1RAP uniquely synergizes with chemotherapy IL-1α IL-1β-converting enzyme Tumor cell region (T) Stromal cell region (S) Tumor growth Body weight Control Control 2000 Vehicle 0 Tumor volume (mm ) 3 T Iso Control 6 * T 250 ** Nadunolimab 1500 2 S % Change Positive cells/mm Gem/Cis -5 % Posi
Slide 14: IL1RAP-expressing myeloid cells infiltrate the lung early during metastasis
IL1RAP-expressing myeloid cells infiltrate the lung early during metastasis 14
Slide 15: Targeting of IL1RAP reduces metastasis
Targeting of IL1RAP reduces metastasis IL1RAP IS STRONGLY EXPRESSED IN THE EARLY METASTATIC NICHE AND TARGETING OF IL1RAP REDUCES METASTASIS 15
Slide 16: Expression of IL1RAP and the IL-1 system correlates with early stages of pancreatic cancer
Expression of IL1RAP and the IL-1 system strongly correlates with early stages of pancreatic cancer Stage I: n=21 Stage II: n=145 Stage III/IV: n=10 • mRNA expression from TCGA (94% stage I-II) compared to mRNA from normal pancreas show upregulation of the IL-1 system, IL1RAP level in pancreatic can
Slide 17: IL1RAP is expressed throughout the pancreatic tumor microenvironment
IL1RAP is expressed throughout the pancreatic tumor microenvironment Cancer-associated Tumor-associated Tumor cells Fibroblasts (CAFs) Macrophages (TAMs) CANFOUR pancreatic biopsy CANFOUR pancreatic biopsy CANFOUR liver biopsy PANCREATIC TUMOR CELLS GROW INSIDE A DENSE STROMA WHERE KEY COMPONENTS AR
Slide 18: Nadunolimab strongly modifies pancreatic cancer-associated fibroblasts
Nadunolimab strongly modifies pancreatic cancer- associated fibroblasts RNA sequencing BxPC3 CAF 4 2 292 Nadunolimab induces changes in gene expression primarily in CAF Nadunolimab suppresses chemotactic and migratory gene signatures in CAF Monocyte migration 1.5 Rel cell number ✱ Vehicle 1.0 Monocy
Slide 19: What is the promise of targeting IL1RAP in cancer?
What is the promise of targeting IL1RAP in cancer? • Tumor cells expressing IL1RAP use signaling through IL1RAP to communicate with surrounding cells and induce pathways important for tumor growth and resistance to various therapies. • High levels of IL1RAP may target tumor cells for immune-related
Slide 20: Clinical results including new biomarker data of nadunolimab
CLINICAL RESULTS INCLUDING NEW BIOMARKER DATA OF NADUNOLIMAB
Slide 21: CANFOUR Phase 1/2 study: Part II PDAC gem/nab-PTX
CANFOUR Phase 1/2 study: Part II PDAC gem/nab-PTX Study design Patient characteristics 21
Slide 22: Well manageable safety profile
Well manageable safety profile → Neutropenia manageable through G-CSF prophylaxis → In 7 pts 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 n=15 Grade 3-4 Gem/Abraxan
Slide 23: PDAC – updated results from the CANFOUR study
PDAC – updated results from the CANFOUR study • Updated mITT data at AACR mITT Efficacy parameter (95% CI) (n=73) OS; median, months 12.9 (10.6-15.5) iPFS; median, months 7.2 (5.2-8.5) 1-year survival 58% (45%-68%) iORR 33% (22%-45%) iDoR; median, months 7.3 (5.5-11.0 ) DCR 71% (59.4-81.2) *NE; not
Slide 24: PDAC – translational results from the CANFOUR study
PDAC – translational results from the CANFOUR study Background • IL1RAP is over-expressed on cancer and stromal • CANFOUR study results show clear distribution of cells in pancreatic ductal adenocarcinoma (PDAC) high and low IL1RAP expression in tumors: IL1RAP expression in • High tumor IL1RAP mRNA
Slide 25: PDAC – translational results: IL1RAP target expression on tumor tissue
PDAC – translational results from the CANFOUR study IL1RAP target expression on tumor tissue 25
Slide 26: PDAC – translational results: baseline characteristics
PDAC – translational results from the CANFOUR study Baseline Characteristics • Biopsy subgroup is representative of the mITT population • Baseline characteristics between the High and Low IL1RAP subgroups are similar • Subgroup results are driven by IL1RAP expression, not by imbalances in prognostic
Slide 27: PDAC – efficacy analysis High vs Low IL1RAP: summary
PDAC – translational results from the CANFOUR study Efficacy analysis for High vs Low IL1RAP: Summary of results IL1RAP High IL1RAP Low Efficacy parameter (95% CI) (n=27) (n=19) OS; median, months 14.2 (10.6-28.7) 10.6 (3.1-12.6) iPFS; median, months 8.0 (3.7-11.2) 5.8 (2.7-7.4) 1-year survival 69%
Slide 28: PDAC – efficacy analysis High vs Low IL1RAP: K-M curves
PDAC – translational results from the CANFOUR study Efficacy analysis for High vs Low IL1RAP: K-M curves • TCGA data show that high IL1RAP expression is normally a poor prognostic factor and leads to worse survival outcomes • Nadunolimab appears to turn this around with much improved survival in the
Slide 29: PDAC – efficacy analysis: deeper responses
PDAC – translational results from the CANFOUR study Efficacy analysis for High vs Low IL1RAP: deeper responses IL1RAP High IL1RAP Low Best change in tumor size 50% iCPD 0% iUPD iSD iPR -50% -100% 11 PATIENTS HAD 50% OR MORE TUMOR BURDEN DECREASE IN THE IL1RAP HIGH GROUP 29
Slide 30: PDAC – efficacy analysis: more durable responses
PDAC – translational results from the CANFOUR study Efficacy analysis for High vs Low IL1RAP: more durable responses IL1RAP High IL1RAP Low 8 PATIENTS STILL ONGOING IN THE IL1RAP HIGH GROUP; ALREADY 4 PATIENTS BEYOND 24-MONTHS SURVIVAL 30
Slide 31: Where do these exciting results take us in PDAC?
Where do these exciting results take us in PDAC? • Critical features of next study: • Control arm: SOC gemcitabine/nab-paclitaxel Direct validity of results • Tumor IL1RAP expression sub-group analysis Patient selection • Additional tumor and serum biomarkers for correlative analyses • Evaluate 2 do
Slide 32: Pancreatic cancer and relevance of nadunolimab results
PANCREATIC CANCER AND RELEVANCE OF NADUNOLIMAB RESULTS
Slide 33: Treatment strategy in advanced pancreatic adenocarcinoma
Treatment strategy in advanced pancreatic adenocarcinoma Prof Eric Van Cutsem, MD, PhD Digestive Oncology Leuven, Belgium Eric.VanCutsem@uzleuven.be
Slide 34: Exocrine pancreatic cancers
EXOCRINE PANCREATIC CANCERS (> 95% of all tumors) ❑ Pancreatic ductal adenocarcinoma (PDAC): ✓ aggressive and poor prognosis ❑ Acinar cell carcinoma ✓ Rare:1-2%. ✓ more common in men ✓ develops in the acinar cells at the end of the ducts, which produce the digestive enzymes ❑ Neuroendocrine tumors/n
Slide 35: Pancreatic cancer has high mortality rates and is the seventh leading cause of cancer death
Pancreatic cancer has high mortality rates and is the seventh leading cause of cancer death worldwide1 Cases by Stage at Diagnosis Worldwide incidence, prevalence, and mortality of (based on SEER 2012-2018 data)3 pancreatic cancer during the last 25 years2 7% Unknown 11% Localised 30% 52% Regional M
Slide 36: Pancreatic adenocarcinoma: a very tough disease!
Pancreatic adenocarcinoma: a very tough disease! ❑ ~ 85% of patients are diagnosed with advanced unresectable disease & often rapid progression / very symptomatic ✓ Expertise for diagnosis (BIOPSIES) & endoscopic palliation/drainage!! ✓ Symptom control! ✓ Expertise in all aspects is required ❑ ~ 80%
Slide 37: Many Druggable Alterations in Pancreatic Ductal Adenocarcinoma
Many Druggable Alterations in Pancreatic Ductal Adenocarcinoma PDGFR mutant (1%) BRAF mutant (1%) ▪ Dovitinib ▪ Vemurafenib ROS1 mutant (1%) ▪ RXDX-101 DDR defective (24%) KIT mutant (1%) BRCA1, BRCA2 or PALB2 JAK dependent or mutations, unstable JAK2 dependent (2%) ▪ Dovitinib genome and BRCA ▪ Rux
Slide 38: Biologic Features of Pancreatic Cancer
Wr oven |® Figure 2. Biologic Features of Pancreatic Cancer. Pancreatic cancers have a complex microenvironment that might be a target for therapy. TCA denotes tricarboxylic acid. Ryan D et al. NEJM 2014
Slide 39: There is not ONE pancreatic cancer but SEVERAL types
There is not ONE pancreatic cancer but SEVERAL (at least 4) types with different behaviour 4 subtypes: 1. Squamous: more aggressive and spread more quickly 2. Pancreatic progenitor: triggered by errors in the cells that Subtypes correlate with should guide the development of the pancreas histopathol
Slide 40: Anatomy of pancreatic cancer
Anatomy of pancreatic cancer Ryan D et al. NEJM 2014
Slide 41: Pancreatic adenocarcinoma: treatment strategy clinical grouping
Pancreatic adenocarcinoma: treatment strategy clinical grouping ❑ Metastatic disease ✓ Chemotherapy: modest progress ✓ Targeted therapy & immunotherapy ❑ Resectable disease ❑ Borderline resectable disease ❑ Locally advanced, but clearly not resectable disease
Slide 42: Treatment of Metastatic Pancreatic Cancer: incremental improvement
Treatment of Metastatic Pancreatic Cancer: incremental improvement Benefits Toxicity 1 year 6 mon Gemcitabine1 Gemcitabine Gemcitabine FOLFIRINOX4 • Prolong survival Erlotinib2 nab-Paclitaxel3 NALIRIFOX5 Subgroup of BRCA mt • Improve clinical Olaparib6 symptoms 1. Burris HA 3rd, et al. J Clin Oncol.
Slide 43: Incremental Benefits With New Agents in Frontline
Incremental Benefits With New Agents in Frontline Nalirifox 2023 1. Burris HA et al. J Clin Oncol. 1997;15:2403-2413. 2. Moore MJ et al. J Clin Oncol. 2007;25:1960-1966. 3. Conroy T et al. N Engl J Med. 2011;364:1817-1825 4. Von Hoff DD…Van Cutsem E et al. N Engl J Med. 2013;369:1691-1703. 5. Wainbe
Slide 44: ACCORD trial: Gemcitabine vs FOLFIRINOX
ACCORD trial: Gemcitabine vs FOLFIRINOX Conroy T, et al. N Engl J Med 2011
Slide 45: MPACT trial: Gemcitabine ± Nab-Paclitaxel
MPACT trial: Gemcitabine ± Nab-Placitaxel Von Hoff D, … Van Cutsem E… et al. N Engl J Med 2013
Slide 46: NAPOLI-3 – NALIRIFOX in 1st line
NAPOLI-3 – NALIRIFOX in 1st line Wainberg Z … Van Cutsem E et al ASCO GI 2023 LBA661
Slide 47: Treatment Strategies: ESMO Guideline
Treatment Strategies: ESMO Guideline Nalirifox Updated: Ducreux M, et al. Ann Oncol. 2015;26(Supp 5):v56-v68.
Slide 48: POLO TRIAL: Olaparib vs Placebo in gBRCA Mutant PDAC
POLO TRIAL: Olaparib vs Placebo in gBRCA Mutant PDAC Golan T …Van Cutsem E et al. N Engl J Med. 2019;381(4):317-327.
Slide 49: Targetable Mutations in Pancreatic Cancer
Targetable Mutations in Pancreatic Cancer First line BRCA1/2, PALB2 5%-10% Mutated Nonmutated Second/ Expanding KRAS Targetable Mutations in Pancreatic MSI/MSS third line 10% Cancer Wild G12C G12D/R 1%-2% MSI MS Check for High Stable NTRK NRG1 HER2 BRAF ALK One of the challenges: ROS1 how to make pa
Slide 50: Phase 1/2a trial of nadunolimab with gemcitabine and nab-paclitaxel: study design
Phase 1/2a trial of nadunolimab, a first-in-class fully humanized monoclonal antibody against IL1RAP, in combination with gemcitabine and nab-paclitaxel (GN) in patients with PDAC Study design and patient characteristics Summary of the study design for the PDAC cohorts in part IIa of the CANFOUR stu
Slide 51: Strong efficacy in PDAC
Phase 1/2a trial of nadunolimab + Gem/Nab-paclitaxel: Strong efficacy in PDAC 50% Best change in tumor size 0% -50% -100% iCPD iUPD iSD iPR Nadunolimab combination with Gemcitabine/Nab-Paclitaxel in 1st line (AACR 2023), n=73: → 33% response rate with durable responses → Promising iPFS (7.2 mo) and
Slide 52: Strong efficacy in IL1RAP High subgroup
Phase 1/2a trial of nadunolimab + Gem/Nab-paclitaxel: Strong efficacy in IL1RAP High subgroup OS Nadunolimab/GN IL1RAP High Nadunolimab monotherapy Death On study iUPD/iCPD iSD iPR IL1RAP Low 0 6 12 24 36 48 Months THE IL1RAP HIGH SUBGROUP HAS A LONGER SURVIVAL AND MORE DURABLE B
Slide 53: Manageable safety profile supporting MOA
Manageable safety profile supporting MOA Nadunolimab+Gem/Abraxane Grade 3 or higher AEs CANFOUR (n=76) → All events of febrile neutropenia and 54% of grade Neutropenia 65% 3-4 neutropenia events occurred during Cycle 1 Leukopenia 24% → G-CSF is an approved therapy to counteract Thrombocytopenia
Slide 54: Summary of ASCO and AACR data on Nadunolimab + Gem/Nab-Paclitaxel for PDAC
Summary of ASCO and AACR data on Nadunolimab + Gem/Nab-Paclitaxel for PDAC ❑ Nadunolimab combined with standard Gemcitabine/Nab-Paclitaxel shows promising efficacy in first-line PDAC: ✓ Median iPFS (7.2 months), median OS (12.9 months) and one-year survival (58%) are well above reported values for G
Slide 55: Treatment of Pancreatic Cancer: Key Milestones
Treatment of Pancreatic Cancer Key Milestones Adjuvant gemc./cap. Laroctretenib in NTRK fusions Adjuvant nab-Paclitaxel FOLFIRINOX Gemcitabine + gemc. Erlotinib + nal-IRI 5FU/LV gemcitabine FOLFIRINOX +FU/LV NALIRIFOX 1994 1998 2002 2006 2010 2012 2016 2019 2023 Pembrolizumab MSI- S1 (Japan) H/dMMR
Slide 56: Cantargia's ongoing clinical trials
CANTARGIA'S ONGOING CLINICAL TRIALS
Slide 57: Nadunolimab ongoing clinical studies
Nadunolimab ongoing clinical studies • PDAC: evaluate options for upcoming study to optimise on the recent results and potential for patient selection • NSCLC: • present updated results from the CANFOUR study at an upcoming scientific conference • analyse maturing clinical data and further focus on
Slide 58: Combination strategy in NSCLC – Promising efficacy
Combination strategy in NSCLC – Promising efficacy Nadunolimab combination with Gem/Cis in 1st/2nd line: → 16 of 30 pts with objective response incl. 1 complete response (ORR 53%) (historical control data of 22-28%) → Generally well tolerated; neutropenia freq. higher than expected from chemo (manag
Slide 59: Strong signal in 1st/2nd line non-squamous NSCLC
Strong signal in 1st/2nd line non-squamous NSCLC Nadunolimab combination with Gem/Cis in 1st/2nd line non-squamous NSCLC: → Approx. 75% of all NSCLC cases → 9 of 16 evaluable pts had objective response including 1 complete response (ORR 56%) (historical control data of 19%) → 8 pts were 2nd line to
Slide 60: Promising early safety and efficacy in TNBC
Promising early safety and efficacy in TNBC Nadunolimab combination with Gem/Carbo in 100 % 1st/2nd line metastatic TNBC: Best change in tumor size 15 pts enrolled in the dose-escalation phase 50 % PD → Acceptable safety profile (G-CSF given prophylactically to control neutropenia) SD 0% → 12 pts tr
Slide 61: Upcoming milestones and concluding remarks
UPCOMING MILESTONES AND CONCLUDING REMARKS
Slide 62: IL1RAP: Broad application in cancer and autoimmune disease
IL1RAP: Broad application in cancer and autoimmune disease 62
Slide 63: Strategies forward in lead indications
Strategies forward in lead indications PROMISING DATA IN PANCREATIC CANCER Nadunolimab Durable response → Stronger efficacy than expected from chemotherapy Primary Chemo- Short-term → There is a potential for the subgroup of patients with tumor therapy response the worse prognosis to become the winn
Slide 64: Several upcoming value inflection points
Several upcoming value inflection points Newsflow over next quarters Nadunolimab (CAN04) → Update of results for PDAC, NSCLC, TNBC → Start next trial in PDAC → New preclinical and translational results → New clinical data (efficacy and safety) → CAPAFOUR PDAC FOLFIRINOX → CESTAFOUR Basket trial (NSC
Slide 65: Solid financial position with strong shareholder support
Solid financial position with strong shareholder support → Cash and cash equivalents SEK 427 M (~$41M) at end of Q4 2022 Current owners (Mar 31, 2023) → Runway until mid 2024 4th AP fund 8.8% Alecta 7.3% → Operating expenses SEK 382 M (~$37M) in 2022 1st AP fund 6.3% → R&D - 96% of operating expense
Slide 66: Cantargia: Investment highlights
Cantargia: Investment highlights NOVEL IL1RAP ANTIBODIES, POTENTIAL TO ADDRESS CANCER & INFLAMMATORY DISEASE • IL1RAP elevated in most solid and liquid tumors • Potential to breakdown resistance to cancer treatment, enabled by unique dual action approach – nadunolimab • Additional key project for in