nadunolimab (CAN04) / Cantargia - LARVOL DELTA

A Non-Randomized Phase 2 Trial of Nadunolimab in Patients With a Smoking History and High-Risk Lung Nodules (IASLC-WCLC 2026) - "Early antagonism of IL-1α and IL-1β in these models delayed progression to invasive lung cancer, a finding consistent with the secondary analysis of the CANTOS trial, which demonstrated reduced lung cancer incidence among patients treated with the IL-1β inhibitor canakinumab. Patients will have imaging performed at 3 months, 6 months, and 12 months following the start of therapy as well as serial blood draws to investigate immunodynamic changes in response to treatment, including analysis of blood cytokines, proteomics, and transcriptomics. The trial will be a Simon's optimal two-stage design, with an initial enrollment of 20 patients in the first stage."

Clinical • P2 data • Lung Cancer • Solid Tumor • IL1B

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 pancreatic adenocarcinoma (PDAC). (ASCO 2022) - P1/2 | "Nadunolimab combined with GN shows promising iPFS and OS and manageable safety in PDAC pts. A phase 2/3 trial of nadunolimab combined with chemotherapy in PDAC is planned and nadunolimab is also currently evaluated in additional combination trials with chemotherapy or IO."

Clinical • Combination therapy • P1/2 data • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Neutropenia • Oncology • Pain • Pancreatic Adenocarcinoma • Pancreatic Cancer • CSF3 • CXCL8 • IL1B • IL1R1 • IL1RAP • IL6

Phase 1/2a trial of nadunolimab, a first-in-class fully humanized monoclonal antibody against IL1RAP, in combination with cisplatin and gemcitabine (CG) in patients with non-small cell lung cancer (NSCLC). (ASCO 2022) - P1/2 | " Patients (pts) with unresectable, locally advanced or metastatic NSCLC, progressed on pembrolizumab or in first line for advanced disease, were eligible. Nadunolimab combined with CG shows manageable safety and promising efficacy with a response rate of 53% in NSCLC pts. Nadunolimab is currently evaluated in several clinical trials investigating chemotherapy or IO combinations, including carboplatin and pemetrexed in non-squamous NSCLC."

Clinical • Combination therapy • P1/2 data • Anemia • Febrile Neutropenia • Hematological Disorders • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thrombocytopenia • CSF3 • CXCL8 • IL1B • IL1R1 • IL1RAP • IL6

Efficacy and safety of the anti-IL1RAP antibody nadunolimab (CAN04) in combination with gemcitabine and nab-paclitaxel in patients with advanced/metastatic pancreatic cancer. (PubMed, Clin Cancer Res) - "Nadunolimab combined with GN shows promising efficacy and manageable safety in locally advanced/metastatic PDAC. Higher tumor baseline IL1RAP expression correlated with better outcome."

Combination therapy • Journal • Metastases • Gastrointestinal Cancer • Hematological Disorders • Hepatology • Neutropenia • Oncology • Pain • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CXCL8 • IL1B • IL1RAP

A phase 1b/2 study of toripalimab and nadunolimab for the treatment of chemotherapy-refractory metastatic microsatellite stable (MSS) colorectal cancer (CRC) (AACR 2026) - P1/2 | "Eligible patients must have biopsy-proven MSS CRC (non-MSI-H or Mismatch Repair-proficient) whose disease has progressed after 5-FU, oxaliplatin and/or irinotecan-based chemotherapy...The operating characteristics for 21 patients will test a null hypothesis of poor ORR of 5% or less versus an alternative hypothesis of a promising ORR of 20% or more at a 10% one-sided significance level and 80% power. For exploratory analyses, we will conduct comprehensive genomic, transcriptomic, proteomic, and digital pathology analyses of biopsies and blood samples to characterize the dynamic immune responses to IL1RAP blockade, identify biomarkers of responses, and define the mechanisms of resistance."

IO biomarker • Metastases • P1/2 data • Colorectal Cancer • Microsatellite Instability • Oncology • Solid Tumor • IL1RAP • IL33 • MSI

Cantargia Announces Publication of Data Supporting IL1RAP as a Therapeutic Target and Predictive Biomarker in PDAC (Yahoo Finance) - "Treatment with the surrogate antibody strongly inhibited tumor growth in this difficult-to-treat model and led to distinct changes in the tumor microenvironment. This effect primed the tumor for response to chemoimmunotherapy, which is otherwise ineffective in this model...Analyses of human PDAC samples showed that IL1RAP expression is elevated in the tumor microenvironment and selectively enriched in tumors from treatment-resistant patients. Furthermore, in tumor specimens from patients enrolled in the CANFOUR trial and treated with nadunolimab in combination with gemcitabine and nab-paclitaxel, high IL1RAP expression in stromal and immune cells was associated with prolonged duration of response."

P1/2 data • Preclinical • Pancreatic Ductal Adenocarcinoma

Cantargia accelerates towards the next clinical phase - subscription period underway in rights issue (BioStock) - "...Cantargia is now conducting a rights issue of approximately SEK 124 million. In addition, the company has entered into a loan agreement of up to SEK 75 million with Fenja Capital....The capital will primarily be used to initiate the combination study with nadunolimab and daraxonrasib, expand the haematology program and prepare an internally sponsored phase IIa study in MDS and AML, as well as cover general working capital needs."

Financing • New P2a trial • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

Cantargia AB…reported that the first patient has been dosed in a Phase 2 clinical trial investigating nadunolimab in up to 59 current or previous smokers with multifocal high-risk lung nodules, and therefore at risk of developing lung cancer (Cantargia Press Release) - "The new phase 2 investigator-initiated trial will be conducted at Mount Sinai Tisch Cancer Center, New York. The study, led by principal investigator Dr. Robert Samstein, is designed to investigate nadunolimab monotherapy in the high-risk population for 3 months."

Trial status • Non Small Cell Lung Cancer

Cantargia and H.C. Wainwright to Host KOL Call on The Case for Nadunolimab in PDAC (Yahoo Finance) - "The KOL Call will be facilitated by Dr. Sara Nik, Vice President Equity Research at H.C. Wainwright, with the purpose of discussing IL1RAP as a therapeutic target in pancreatic ductal adenocarcinoma (PDAC) and the emerging clinical role of nadunolimab (CAN04), Cantargia's anti-IL1RAP antibody....Against this evolving backdrop, we believe this KOL call presents a timely opportunity to explore the biology of IL1RAP in PDAC, discuss how nadunolimab may complement emerging RAS-directed strategies, and assess the potential of a planned Phase 1b/2a program to advance the treatment of this difficult disease."

Clinical • New P1/2 trial • Pancreatic Ductal Adenocarcinoma

TRIFOUR: Nadunolimab in Combination With Gemcitabine Plus Carboplatin in Patients With Advanced Triple Negative Breast Cancer. (clinicaltrials.gov) - P1/2 | N=117 | Completed | Sponsor: Cantargia AB | Active, not recruiting ➔ Completed

BRCA Companion diagnostic • PARP Companion diagnostic • Trial completion • Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • BRCA1 • BRCA2 • CD4 • ER • HER-2 • PD-L1 • PGR

Interleukin-1α (IL-1α) in pancreatic ductal adenocarcinoma: implications for immunotherapy and molecular biomarkers. (PubMed, Clin Transl Oncol) - "Therapeutically, IL-1α blockers using agents such as anakinra, canakinumab, and nadunolimab show synergy with immune checkpoint inhibitors and chemotherapy. This includes the recruitment of neutrophils and myeloid-derived suppressor cells (MDSCs), which collectively maintain an immunosuppressive ('cold') tumor microenvironment (TME) and contribute to therapeutic resistance. Future multi-omics stratification, targeted delivery systems, and rational combination strategies hold promise for improving PDAC outcomes."

Biomarker • IO biomarker • Journal • Review • Fibrosis • Immunology • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • CA 19-9 • IL1A

Cantargia Announces Early Results from Trial of nadunolimab in MDS and AML (Cantargia Press Release) - "The Phase 1b dose-escalation stage has now been completed, encompassing six patients in the high-risk MDS cohort and six in the AML cohort, and the study is progressing into the Phase 2a part...In the high-risk MDS cohort, six patients have been dosed, five of which are efficacy-evaluable. Notably, all five achieved complete remissions. The sixth patient is pending evaluation. These findings, while preliminary, suggest a promising signal of clinical activity for nadunolimab in combination with standard-of-care therapy in high-risk hematologic malignancies....Further progress updates from the ongoing trial are expected later in 2026. The study will include approximately 40 patients in total."

P1/2 data • Trial status • Acute Myelogenous Leukemia • Myelodysplastic Syndrome

Cantargia Announces AACR 2026 Presentation of Study Design and Supportive Pre-Clinical Data for Investigator-Initiated Nadunolimab Study in MSS CRC (ACCESS Newswire) - "The new phase 1b/2 study...is designed to investigate nadunolimab in combination with the anti-PD-1 inhibitor toripalimab in patients with MSS CRC....The study has, as of January 12, 2026, enrolled two patients with the aim of treating up to 21 patients. Preclinical work from researchers at Mount Sinai Tisch Cancer Center strongly implicates IL1RAP dependent signaling in immunosuppressive and treatment resistant pathways in this disease. Synergistic effects of combining a nadunolimab surrogate antibody and immune-checkpoint inhibitors are shown by reducing tumor burden and counteracting the immunosuppressive tumor microenvironment..."

Clinical protocol • Preclinical • Colorectal Cancer

ILRAP blockade mediates anti-fibrotic effects in pancreatic cancer-associated fibroblasts (AACR 2024) - P1/2 | "IL-1 activated fibroblasts and induced type III collagen formation (PRO-C3), suggesting that IL-1 is a driver of tumor fibrosis. In support, pancreatic tumor cells induced collagen type III formation (PRO-C3) in pancreatic CAFs and blockade of IL1RAP with nadunolimab inhibited this collagen formation. Thus, nadunolimab may have anti-fibrotic properties and PRO-C3 could potentially be used for prognostic/predictive enrichment and as a pharmacodynamic marker in future studies evaluating anti-IL-1 modalities in PDAC."

Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CAFs • IL1B • IL1RAP • TGFB1

Adding nadunolimab to chemotherapy or antibody drug-conjugates (ADCs) may improve antitumor efficacy and counteract peripheral neuropathy (AACR 2025) - "Building on these promising findings, our aim was to further investigate nadunolimab's additional potential in mitigating neuropathies associated with chemotherapy and ADCs. The potential neuroprotective effect of nadunolimab was analyzed in two clinical trials: one involving 14 pts with 8 different cancer indications treated with FOLFOX and nadunolimab at 1 mg/kg (n=7) or 0.5 mg/kg (n=7), and another involving 18 PDAC pts treated with FOLFIRINOX and nadunolimab at doses of 0.5 mg/kg (n=8), 1 mg/kg (n=3), 1.5 mg/kg (n=4), and 2.5 mg/kg (n=3). In mice, neuropathy was induced by vincristine, nab-paclitaxel, nab-paclitaxel plus gemcitabine, or ADC payloads... Overall, our current findings in conjunction with previous results, suggest that nadunolimab may not only offer anti-tumor benefits but also protection against the neuro-inflammatory component driving chemotherapy- and ADC-induced neuropathy."

ADC • Clinical • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL1RAP

TRIFOUR: Nadunolimab in Combination With Gemcitabine Plus Carboplatin in Patients With Advanced Triple Negative Breast Cancer. (clinicaltrials.gov) - P1/2 | N=117 | Active, not recruiting | Sponsor: Cantargia AB | Trial primary completion date: Jun 2025 ➔ Apr 2026

BRCA Companion diagnostic • PARP Companion diagnostic • Trial primary completion date • Breast Cancer • Hormone Receptor Negative Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • BRCA • BRCA1 • BRCA2 • CD4 • ER • HER-2 • PD-L1 • PGR

New Preclinical Data on Anti-Tumor Effects of Nadunolimab in Metastatic Colorectal Cancer Presented at the Keystone Cancer Immunotherapy Conference (Yahoo Finance) - "The new preclinical results further indicate that IL1RAP dependent signaling is part of an immunosuppressive axis within both the primary tumor and metastatic sites...Combining the nadunolimab surrogate antibody with anti-PD-1 immune-checkpoint inhibitors showed a synergistic effect by reducing tumor burden in a CRC model that is otherwise unresponsive to immunotherapy. Disruption of this immune suppressive axis presents a unique opportunity to overcome resistance to immunotherapy, which has the potential to transform outcomes for metastatic MSS CRC patients."

Preclinical • Colorectal Cancer

Immunoprevention for High-risk Lung Lesions (clinicaltrials.gov) - P2 | N=59 | Recruiting | Sponsor: Robert Samstein | Not yet recruiting ➔ Recruiting | Initiation date: Dec 2025 ➔ Apr 2026

Enrollment open • Trial initiation date

Combination Immunotherapy for the Treatment of Chemotherapy-refractory Metastatic MSS CRC (clinicaltrials.gov) - P1/2 | N=24 | Recruiting | Sponsor: Dan Feng | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Oncology • Solid Tumor • MSI

Cantargia Reports First Patient Dosed in New US Investigator-Initiated Colorectal Cancer Study (Yahoo Finance) - "The new phase 1b/2a investigator-initiated trial will be conducted at Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York. The study (NCT07281716), led by principal investigator Dr. Dan Feng, is designed to investigate nadunolimab in combination with an anti-PD-1 inhibitor in up to 24 patients with MSS CRC. In addition to investigating anticancer effects, the study will include a comprehensive biomarker assessment package."

Trial status • Colorectal Cancer

Myeloid-stromal IL1RAP as a therapeutic vulnerability in pancreatic cancer: Rationale for a neoadjuvant chemoimmunotherapy clinical trial. (ASCO-GI 2026) - P1/2 | "Combination CAN04, gemcitabine+nab-paclitaxel (GnP), and anti-PD1 therapy was tested in survival studies. IL1RAP-expressing myeloid-stromal networks may represent a distinct therapeutic barrier in PDAC, which can be disrupted pharmacologically to invigorate immunotherapy-permissive CD8+ T-cell subsets and improve chemoimmunotherapy sensitivity. These findings support an upcoming neoadjuvant trial combining CAN04 with chemoimmunotherapy in patients with operable PDAC."

Clinical • IO biomarker • Stroma • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • CD14 • CD69 • CD8 • GZMB • IL1RAP • IL2 • ITGAM • KRAS

Immunoprevention for High-risk Lung Lesions (clinicaltrials.gov) - P2 | N=59 | Not yet recruiting | Sponsor: Robert Samstein

New P2 trial

Combination Immunotherapy for the Treatment of Chemotherapy-refractory Metastatic MSS CRC (clinicaltrials.gov) - P1/2 | N=24 | Not yet recruiting | Sponsor: Dan Feng

New P1/2 trial • Colorectal Cancer • Oncology • Solid Tumor

Cantargia Provides Update on Overall Survival Data from TRIFOUR (ACCESS Newswire) - "The analysis showed no difference in median overall survival (mOS) between the group treated with nadunolimab plus gemcitabine/carboplatin (GC) and the GC control group. Notably, both groups achieved a survival duration of 26 months, which exceeds historical expectations for this patient population. Earlier findings, reported in July 2025, showed no meaningful difference in the study's primary endpoint, overall response rate (ORR), between the treatment arms....Based on these results, Cantargia will discontinue further development in TNBC."

Discontinued • P1/2 data • Triple Negative Breast Cancer

AK135, a novel antagonistic antibody targeting IL-1RAP for CIPN therapy (SITC 2025) - "A CIPN model in B6-hIL1RAP transgenic mice were established via intermittent low-dose paclitaxel induction. Then the pharmacological efficacy of AK135 in this model was evaluated.Results AK135 shows high affinity to IL-1RAP and exhibits potent neutralizing bioactivity in IL-1/IL-33/IL-36 signaling pathways, while Nadunolimab (CAN04) has a weaker blocking effect on the IL-33 and IL-36 signaling pathways, as shown in table 1...Additionally, AK135 treatment led to a dose-dependent decrease in pain-related cytokines in spinal cord tissue homogenates, supporting its anti-inflammatory mechanism in pain relief.Conclusions As a potential chemotherapy companion drug, AK135 potently targets IL-1RAP to block IL-1/IL-33/IL-36-driven inflammatory signaling, mitigates proinflammatory cytokine release, and alleviates chemotherapy-induced peripheral neuropathy (CIPN) in preclinical models. Its dose-dependent efficacy in pain relief, coupled with good tolerability, underscores..."

Oncology • CXCL8 • IL1RAP • IL33 • IL6