Dec 18, 2024

Cantargia publishes strong preclinical effects and clinical monotherapy results on nadunolimab in pancreatic cancer in Journal for Immunotherapy of Cancer

Cantargia (Cantargia AB; Nasdaq Stockholm: CANTA) today announced the publication of preclinical and clinical results using the IL1RAP targeted antibody nadunolimab (CAN04) in pancreatic cancer (PDAC). Nadunolimab had pronounced effects on PDAC associated fibroblasts and inhibited recruitment of tumor promoting immune cells. These results were linked to monotherapy data in late-stage metastatic PDAC patients showing both clinically meaningful progression free survival and survival in patients with high IL1RAP levels. The studies were performed as a collaboration between Cantargia, Lund University and PanCAN.

“Nadunolimab’s unique mechanism of action is highly relevant for treatment of pancreatic cancer. This important publication in an impactful scientific journal confirms its significance to the medical community” said Göran Forsberg, CEO of Cantargia.

PDAC is one of the cancer forms with the highest medical need. The incidence is increasing, and the survival is poor. A major clinical challenge in PDAC is its distinct and protective tumor microenvironment (TME), which shields the tumor from the immune system and facilitates tumor growth, metastasis, and resistance to therapy. The crosstalk between cancer cells and cancer-associated fibroblasts (CAFs) plays a pivotal role in shaping this TME.

The IL-1 family, through IL1RAP, helps activate CAFs, which attract myeloid immune cells like monocytes and neutrophils into the tumor. This study reveals that nadunolimab blocks this process by inhibiting IL1RAP, reducing the number of immune cells recruited, which weakens the tumor’s defenses. Through its other mechanism of action (ADCC), nadunolimab enhances tumor destruction.

The relevance of these preclinical results could be linked to clinical results using nadunolimab monotherapy in the CANFOUR study. In late stage metastatic PDAC patients, high tumor baseline levels of IL1RAP strongly correlate with increased progression free survival (IL1RAP high vs low: 3.5 vs 1.2 months; p=0.0023) and a trend for survival advantage (5.0 vs 2.2 months) with a follow up of 11.5 months. This is in line with previous published results examining nadunolimab with chemotherapies, gemcitabine and nab-paclitaxel, which showed promising efficacy in first line IL1RAP-high PDAC patients.

These findings strongly signify the clinical relevance of targeting IL1RAP in PDAC using nadunolimab. This is particularly noteworthy since IL1RAP is considered as a prognostic marker where high IL1RAP expression is linked to shorter survival in PDAC patients.

“This study reveals how PDAC tumor cells and cancer-associated fibroblasts drive the immunosuppressive microenvironment through IL-1 signaling. It highlights IL1RAP targeting as a promising therapeutic approach for pancreatic cancer patients” said Dr Marcus Järås, corresponding author and Cantargia co-founder, from Lund University.

This study used data from the Pancreatic Cancer Action Network’s (PanCAN) Know Your Tumor® precision medicine program as a validation dataset, accessed through the PanCAN SPARK health data platform. This dataset was used to study the impact of IL1RAP expression in PDAC and revealed IL1RAP as a prognostic marker.

“These results underscore the importance of biomarker testing that allows patients to learn about the genetic makeup of their tumor and allow researchers access to treatment and outcomes data. Ongoing research using real-world datasets like from the Know Your Tumor program in the PanCAN SPARK platform brings researchers one step closer to better treatments and improved outcomes for patient with pancreatic cancer,” said Anna Berkenblit, MD, MMSc, Chief Scientific and Medical Officer at PanCAN.

The article, titled “Blocking IL1RAP on cancer associated fibroblasts in pancreatic ductal adenocarcinoma suppresses IL-1 induced neutrophil recruitment”, by Hansen et al., is available via Journal for Immunotherapy of Cancer website: https://jitc.bmj.com/ and at Cantargia’s website https://cantargia.com. This publication is based on results that, in part, have been presented at scientific conferences during 2022 and 2023.

About Cantargia
Cantargia AB (publ), reg. no. 556791-6019, is a biotechnology company that develops antibody-based treatments for life-threatening diseases and has established a platform based on the protein IL1RAP, involved in a number of cancer forms and inflammatory diseases. Cantargia’s oncology program, the antibody nadunolimab (CAN04), is being studied clinically, primarily in combination with chemotherapy with a focus on pancreatic cancer, non-small cell lung cancer and triple-negative breast cancer. Positive data for the combinations indicate stronger efficacy than would be expected from chemotherapy alone. Cantargia’s second development program, the antibody CAN10, blocks signaling via IL1RAP in a different manner than nadunolimab and addresses treatment of serious autoimmune/inflammatory diseases, with initial focus on hidradenitis suppurativa and systemic sclerosis.

Cantargia is listed on Nasdaq Stockholm (ticker: CANTA). More information about Cantargia is available at www.cantargia.com.

About nadunolimab (CAN04)
The antibody nadunolimab binds strongly to its target IL1RAP and functions by inducing ADCC and blocking IL-1α and IL-1β signaling. Nadunolimab can thereby counteract the IL-1 system which contributes to the immune suppressive tumor microenvironment and development of resistance to chemotherapy. Nadunolimab is investigated in multiple clinical trials; the phase I/IIa trial CANFOUR, NCT03267316, evaluates nadunolimab in combination with standard chemotherapies in patients with PDAC (gemcitabine/nab-paclitaxel) or NSCLC (platinum-based chemotherapies). Positive data show durable responses for the combination therapy in 73 PDAC patients, resulting in median iPFS of 7.2 months and median OS of 13.2 months. An even higher median OS of 14.2 months was observed in a subgroup of patients with high tumor levels of IL1RAP. Strong efficacy was also observed in 40 NSCLC patients with median PFS of 7.2 months and a response rate of 55%; even higher responses were observed in non-squamous NSCLC patients. Early efficacy data from the phase Ib/II trial TRIFOUR, NCT05181462, also shows signs of promising efficacy in TNBC with a 60% response rate for nadunolimab combined with carboplatin/gemcitabine.