Cantargia Ab · OMXSTO:CANTA
Cantargia Ab — Investor Day (May 2021)
83 slides from Cantargia Ab's investor day presentation, May 20, 2021
Slide 1: R&D Day
R&D Day Göran Forsberg, CEO May 20, 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: Cantargia – Opportunity to save lives and create value
Cantargia – Opportunity to save lives and create value Ø Potentially more effective treatment against novel target in clinically validated pathway Ø First in class platform technology against novel target Ø Well financed to build a broad, diversified pipeline Ø Right team and clear plan to position
Slide 4: Cantargia highlights
Cantargia highlights UNIQUE IMMUNOTHERAPY ANTIBODY CAN04 IN PHASE IIA CLINICAL DEVELOPMENT • Positive interim data set - response rates higher than historical control Current owners (31 Mar 2021) • First in class antibody with broader MOA than competitors Swedbank Robur Funds 9.7% VISION OF BECOMING
Slide 5: Todays program
Todays program → 15.00 Welcome and introduction to Cantargia – Göran Forsberg, CEO → 15.05 Nadunolimab (CAN04) Mechanism of action – David Liberg, VP Research → 15.25 Nadunolimab updated phase IIa clinical results in pancreatic cancer – Prof Ahmad Awada, Inst. Jules Bordet, Brussels, Belgium → 15.50
Slide 6: CAN04 – Preclinical Rationale
CAN04 – PRECLINICAL RATIONALE
Slide 7: Targeting IL1RAP in cancer
Targeting IL1RAP in cancer • 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 suppression – both on tumor cells and on tumor-supporting cells • IL1RA
Slide 8: Nadunolimab (CAN04) – an anti-IL1RAP antibody with dual functions
Nadunolimab (CAN04) – an anti-IL1RAP antibody with dual functions Effector cell binding (NK cells and macrophages) and induction of cell killing IL1RAP binding and signaling inhibition 8 8
Slide 9: 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, both on cancer cells and stromal cells NSCLC – non-small cell lung cancer 9HNSCC – head and neck squamous carcinoma 5
Slide 10: 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 11: IL-1a/b and resistance to therapy
IL-1a/b and resistance to therapy 11 7
Slide 12: 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 12 9
Slide 13: 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 13 8
Slide 14: 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 14 10
Slide 15: Pancreatic cancer
Pancreatic cancer KRAS-driven inflammation and the potential of CAN04 https://www.proteinatlas.org/ • > 90% of PDAC tumors have mutated KRAS • IL1a induced by KRAS has been shown to be important for 15 tumor development in PDAC 11
Slide 16: 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 17: 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 The inhibition of tumor cell growth induced by CAN04 is mediated by cancer- associated fibroblasts (CAFs) 17 13
Slide 18: 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 19: CANFOUR - Pancreatic ductal adenocarcinoma
CANFOUR - Pancreatic ductal adenocarcinoma Cancer-associated Tumor-associated Tumor cells Fibroblasts (CAFs) Macrophages (TAMs) CANFOUR pancreatic biopsy CANFOUR pancreatic biopsy CANFOUR liver biopsy • IL1RAP is expressed in tumor and stromal cells in primary and metastatic tumors from PDAC patient
Slide 20: Nadunolimab (CAN04, anti-IL1RAP) in Pancreatic Cancer
Nadunolimab (CAN04, anti-IL1RAP) in Pancreatic Cancer Interim analysis April 20 based ongoing trial Professor Ahmad Awada Institut Jules Bordet, Brussels 20 May 2021
Slide 21: IL1RAP relevance in pancreatic cancer
IL1RAP relevance in pancreatic cancer • Pancreas cancer still an unmet medical need. • One of the few indications where immunotherapy does not have a role. • IL1RAP, overexpressed on pancreatic cancer cells and associated stroma • IL1RAP and IL-1 system has documented roles in pancreatic cancer tumo
Slide 22: The first nadunolimab clinical trial CANFOUR
The first nadunolimab clinical trial CANFOUR Started 2017 with the aim to identify a safe dose, evaluate biomarkers and find early efficacy signals of: • Nadunolimab monotherapy (N=48) • Nadunolimab in combination with gemcitabine/cisplatin in NSCLC (plan N=31) • Nadunolimab in combination with gemc
Slide 23: Nadunolimab with gemcitabine/nab-paclitaxel (GN) in PDAC
Nadunolimab with gemcitabine/nab-paclitaxel (GN) in PDAC • Patient population: Stage III/IV PDAC in first line of systemic chemotherapy • Patient Disposition: • 36 PDAC patients were treated in 10 sites in 5 EU countries from March 2019 up to October 2020. • 8 patients were treated initially at 7.5
Slide 24: CANFOUR population seems to be similar to MPACT
Baseline patient characteristics vs. MPACT trial CANFOUR MPACT* 36 431 Age Median 62 62 Range 46-87 27-86 <65 yr 64% 59% >=65 yr 36% 41% Sex Female 53% 43% Male 47% 57% PS 0 64% 58% 1 36% 42% Site of metastases Liver 74% 85% Lung 34% 35% Lymph nodes 40% ND Peritoneum 28% 4% CA19-9 N 33 379 Median 44
Slide 25: PDAC efficacy evaluation and summary
PDAC efficacy evaluation and summary Efficacy evaluation: • CT scan every 2nd month • Serum CA19-9 Efficacy evaluation summary: • Durable responses observed • Promising PFS and OS • Important finding of pseudoprogression-like response in 5 (15%) patients predicting long PFS. 25
Slide 26: Evaluation of tumor shrinkage by the investigator
Evaluation of tumor shrinkage by the investigator • Waterfall plot is based on largest percentage tumor shrinkage (target lesions) and best overall response during study • PD is >20% increase vs baseline and PR is >30% tumor shrinkage. • Central review ongoing • 1CR • 7PR (incl 1 unconfirmed CR) • 3
Slide 27: Pseudoprogression (PsP) in PDAC
Pseudoprogression (PsP) in PDAC • Evidence of tumor growth (including the appearance of new lesions) not corresponding with treatment failure but with long-term benefit. • In solid tumors, PsP is observed with checkpoint inhibitors. The apparent increase in tumor burden may precede antitumor effects
Slide 28: 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 28
Slide 29: Liver metastases evolution subject 1
Liver metastases evolution subject 1 Screening 2 months 3 months 7 months 12 months Target lesions +32% (PD/iUPD) -35% (iPR) -56% (iPR) -62% (iPR) PD= progressive disease iUPD= unconfirmed progressive disease by iRECIST iPR= immune partial response by iRECIST 29
Slide 30: Liver metastases evolution subject 2
Liver metastases evolution subject 2 Screening 2 months 4 months 5 months Target lesions +25% (PD/iUPD) +14% (iSD) 0% (iSD) PD= progressive disease iUPD= unconfirmed progressive disease by iRECIST iSD= immune stable disease by iRECIST 30
Slide 31: PDAC response parameters and benchmark
PDAC response parameters and benchmark Response parameter CANFOUR (N=33) Reference (von Hoff; Fernández) ORR per investigator 27 % (9 PR) 29% (95%CI: 25-34) Pseudoprogression iRECIST 15% 0% Disease control rate (PR+SD+ 72% 48% (95% CI: 43-53) iRECIST iUPD/iSD) Median duration of response 6.8 months
Slide 32: Progression Free Survival by iRECIST
Progression Free Survival by iRECIST • Median iPFS is 7.8 months (95% CI 5.2 to 10.2) with 55% of events. iPFS range 0 to 15.6 months • iPFS rate at 6 months: 62%; at 1 year: 19% • Seven patients at cut-off are still receiving treatment. The observed iPFS is longer than expected from chemotherapy al
Slide 33: Overall Survival
Overall Survival • Median OS is 12.6 months (95% CI not estimable) with 42% of OS events. • 6-month survival rate: 71%, 1-year survival rate: 55% • Data needs further maturation before firm conclusions Early survival data compare favourable to benchmark, but needs longer follow up 33 33
Slide 34: PDAC efficacy parameters and benchmark
PDAC efficacy parameters and benchmark Efficacy parameter CANFOUR (N=33) MPACT trial* (N=431) Median iPFS (iRECIST)/PFS Median iPFS 7.8 mo [95%CI: 5.2-10.2] Median PFS: 5.5 mo (95% CI: 4.5-5.9) (RECIST1.1) iPFS at 6 months: 62% PFS at 6 months: 44% Mean duration of treatment 4.8 months 3.9 months Ov
Slide 35: Nadunolimab/GN in PDAC safety summary
Nadunolimab/GN in PDAC safety summary •Only infusion related reaction (IRR) and neutropenia are considered nadunolimab safety findings. •Both reflect pharmacodynamic effects of nadunolimab. •Infusion Related Reactions: •IRR in 16/36 (44%) of the patients. Mild in 38% and moderate in 56% of these. On
Slide 36: G-CSF is effective for neutropenia prevention
G-CSF is effective for neutropenia prevention • There is greater than expected frequency of neutropenia and febrile neutropenia with the addition of CAN04 • G-CSF accelerates recovery and seems to be effective at preventing future episodes. For patients currently treated, G-CSF is used proactively t
Slide 37: CAN04/GN in PDAC safety summary and benchmark
CAN04/GN in PDAC safety summary and benchmark Gem/Abraxane CANFOUR FOLFIRINOX The beneficial effect in Grade 3 or higher AEs (von Hoff) CAN04/GN (Conroy 2011) fatigue and chemotherapy- N=421 N=36 N=171 induced neuropathy2 (nab- Neutropenia 38% 67% 46% paclitaxel or oxaliplatin) Febrile neutropenia 3
Slide 38: Conclusions
Conclusions • Adding nadunolimab to gemcitabine/nab-paclitaxel in first line treatment of metastatic PDAC: • Promising efficacy: • Long duration of response • Identification of a pseudoprogression-like phenomena that predicts longer treatment benefit • Emerging PFS and OS seems to be better than his
Slide 39: Therapeutic Opportunities in Pancreatic Cancer
Therapeutic Opportunities in Pancreatic Cancer Manuel Hidalgo, M.D., Ph.D.
Slide 40: COI Disclosure
COI Disclosure • Board of Directors o BMS • Founder: o Champions Oncology, Nelum Pharmaceuticals • Stock holder: o Champions Oncology, Agenus, Nelum Pharmaceuticals, Highlight Pharmaceuticals, Oncomatrix, Inxmed, Pharmacyte, BMS. • Research support: o Erytech, PanCan, TBA alliance • Honorarium: o Ag
Slide 41: The Problem
The Problem Rahib et al, JAMA Net 2014 41
Slide 42: Pillars of Cancer Treatment
Pillars of Cancer Treatment 42
Slide 43: Stage IV Management Algorithm
Stage IV Management Algorithm 43
Slide 44: Selected Agents in Development
6 Selected Agents in Development Nevala Plagemann et al, Nat Can Rev 2019 44
Slide 45: PDAC Genetics
5 no NALCN ADAMTS20 ane CDKNIA 45
Slide 46: Putative Targets and Inhibitors
Putative Targets and Inhibitors Collisson et al, Nat Can Rev 2019 46
Slide 47: Example of Precision Medicine
Example of Precision Medicine 47
Slide 48: Olaparib in BRCA mut PDAC
Olaparib in BRCA mut PDAC Golan et al, NEJM 2019 48
Slide 49: PDAC TME
PDAC TME Hosein et al, Nat Rev Gastroenterology and Hepatology 2020 49
Slide 50: IO in PDAC
IO in PDAC Joyce at al, Science 2015 50
Slide 51: Depletion of FAP+ Cells and Immune Response
Depletion of FAP+ Cells and Immune Response Joyce at al, Science 2015 51
Slide 52: Effects on T cell Infiltrate in Tumor Tissues
Effects on T cell Infiltrate in Tumor Tissues 1600 D Screening End of Cycle 2 Cell Density (#Cells/mm2) 1400 1200 1000 800 600 400 200 0 3 4 8 ce d SC C or R or D D D T te lls an um ) XC m C C C ) ic v a K+ D 4+ C Tu -M i T ox ct ot A G (P K+ yt C C an (P Bockorny et et al, Nat Med 2020 52
Slide 53: Responses Water Fall Plot
Responses Water Fall Plot N % Evaluable patients 22 100% ORR 7 32% DCR (PR + SD) 17 77% PR 7 32% SD 10 45% Bockorny et et al, Nat Med 2020 53
Slide 54: Tumor cell-derive IL1 in PDAC
Tumor cell-derive IL1 in PDAC Das et et al, Can Res 2021 54
Slide 55: Evaluation of tumor shrinkage by the investigator
Evaluation of tumor shrinkage by the investigator • Waterfall plot is based on largest percentage tumor shrinkage (target lesions) and best overall response during study • PD is >20% increase vs baseline and PR is >30% tumor shrinkage. • Central review ongoing • 1CR • 7PR (incl 1 unconfirmed CR) • 3
Slide 56: 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 reduction of CA19-9 Ongoing Subject 3 Subject 4 Subject 5 Ongoing 56
Slide 57: Monitoring Pseudoprogression
Monitoring Pseudoprogression Bratman et et al, Can Res 2021 57
Slide 58: Liver metastases evolution subject 2
Liver metastases evolution subject 2 Screening 2 months 4 months 5 months Target lesions +25% (PD/iUPD) +14% (iSD) 0% (iSD) PD= progressive disease iUPD= unconfirmed progressive disease by iRECIST iSD= immune stable disease by iRECIST 58
Slide 59: Weill Cornell Medicine
Weill Cornell Medicine = = NewYork-Presbyterian
Slide 60: Nadunolimab, ongoing and upcoming clinical trials
Nadunolimab, ongoing and upcoming clinical trials Ignacio Garcia-Ribas, CMO
Slide 61: Nadunolimab PDAC highlights
Nadunolimab PDAC highlights • Nadunolimab appears to increase the efficacy of gemcitabine and nab-paclitaxel (Abraxane®) in patients with metastatic PDAC. • Several patients benefit with durable responses or pseudoprogression (benefit after initial disease progression). These patient populations con
Slide 62: 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 CANFOUR PDAC Gemcitabine/nab- Extension phase ongoing. Main study results presented 20 May paclitaxel (Dosing sc
Slide 63: CANFOUR: Tumor shrinkage – NSCLC combination
CANFOUR: Tumor shrinkage – NSCLC combination → CAN04 in combination with gem/cis in 1st line chemotherapy → Press release September 2020: 6 of 9 evaluable patients with metastatic non-small cell lung cancer (NSCLC) showed objective response including 1 complete response (67% vs historical control da
Slide 64: CIRIFOUR: US Phase I clinical trial
CIRIFOUR: US Phase I clinical trial → First patient started 2020. Enrollment according to plan, results expected H2. → Combination with checkpoint inhibitor in patients no longer responding to PD1/PDL-1 therapy. • Investigating the safety of the combination • Exploring CAN04 as immune-oncology drug
Slide 65: Nadunolimab clinical trials to be started
Nadunolimab clinical trials to be started → First line combination with modified FOLFIRINOX in pancreatic cancer • Up to 30 patients, initial dose escalation followed by dose expansion • Approximately 9 centres in France and Spain • First patient planned June 2021 → “Basket trial” in new indications
Slide 66: Rationale for the novel indications/combinations
Rationale for the novel indications/combinations (1) Colorectal cancer: → 3rd most common tumor, incidence 150.000 per year USA. → Oxaliplatin is a cornerstone in CRC. Immunotherapy doesn’t work in 90% of CRC. → Potential clinical synergy of CAN04 with oxaliplatin → IL-1β is required for macrophages
Slide 67: Rationale for the novel indications/combinations
Rationale for the novel indications/combinations (2) NSCLC → Docetaxel standard therapy in late stage patients → Based on CANFOUR results and chemosensitization hypothesis, an interesting opportunity for CAN04 → IL-1 system has a well described role in NSCLC development Triple negative breast cancer
Slide 68: CAN10 Research and Development
CAN10 RESEARCH AND DEVELOPMENT
Slide 69: CAN10 – indications and preclinical development
CAN10 – indications and preclinical development → Inflammation of muscular tissues of the heart → Chronic, autoimmune connective tissue disorder that can lead to fibrosis and loss of contractile characterized by inflammation and fibrosis of the skin function and internal organs → Characterized by in
Slide 70: CAN10 – rationale
CAN10 – rationale IL1RAP binding and signaling inhibition Engineered to minimize Opportunity: target all IL1RAP-dependent signaling pathways FcgR binding → The CAN10 antibody is developed as a therapy for inflammatory/autoimmune diseases → CAN10 blocks all signaling pathways mediated by IL1RAP and d
Slide 71: 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 72: 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 73: CAN10 – indications and preclinical development
CAN10 – indications and preclinical development 7
Slide 74: CAN10 – indications and preclinical development
CAN10 – indications and preclinical development 7
Slide 75: Systemic sclerosis and fibrotic disease
Systemic sclerosis and fibrotic disease → Characterized by diffuse fibrosis and vascular abnormalities in the skin, joints, and internal organs → Lung fibrosis and Pulmonary Arterial Hypertension often accounts for death → IL1/33/36 are involved in several aspects of fibrosis → Experiments on human
Slide 76: CAN10 – indications and preclinical development
CAN10 – indications and preclinical development 9
Slide 77: CAN10 – indications and preclinical development
CAN10 – indications and preclinical development 9
Slide 78: The IL-1 family in Cardiovascular Inflammation
The IL-1 family in Cardiovascular Inflammation → Inflammation of muscular tissues of the heart Dying cardiomyocyte that can lead to fibrosis and loss of contractile function → IL-1 is central to the development of cardiac inflammation and is a potential driver of Myocarditis, ongoing clinical trial
Slide 79: mCAN10 improves heart function in experimental autoimmune myocarditis
mCAN10 improves heart function in experimental autoimmune myocarditis 11
Slide 80: mCAN10 reduces inflammation and fibrosis in experimental autoimmune myocarditis
mCAN10 reduces inflammation and fibrosis in experimental autoimmune myocarditis 12
Slide 81: CAN10 – summary
CAN10 – summary → CAN10 blocks IL1a/b, IL33 and IL36a/b/g signaling through targeting of IL1RAP and is in late-stage preclinical development for clinical trials → Blocking IL1RAP is a potent anti- inflammatory strategy that is qualitatively different from pure IL1a/b blockade. → IL1RAP-blockade coun
Slide 82: CAN10 – milestones
CAN10 – milestones 2021 → CMC development and production for safety and clinical studies → Completion of safety program → Interactions with health authorities 2022 → CTA submissions → Initiation of clinical studies → Preparations for clinical development in myocarditis and/or SSc 14
Slide 83: Q&A
Q&A