Cantargia presents preclinical data demonstrating unique treatment effects of nadunolimab on pancreatic cancer stromal cells
Cantargia (Cantargia AB; Nasdaq Stockholm: CANTA) today reported preclinical data for its lead candidate, the IL1RAP-binding antibody nadunolimab (CAN04), further supporting the promising clinical efficacy seen in pancreatic cancer (PDAC) patients. The new results show that nadunolimab reduces PDAC tumor growth through a strong impact on cancer-associated fibroblasts (CAF), a major component of tumor-supporting stromal cells within PDAC tumors. Furthermore, the broad and unique mode-of-action of nadunolimab disrupts crosstalk between PDAC cells and CAF in sharp contrast to blockade of IL-1β alone. The data will be presented in a poster session at AACR Special Conference: Pancreatic Cancer, being held in Boston, September 13-16, 2022.
“The findings indicate that IL1RAP blockade by nadunolimab has an influence on the microenvironment of PDAC tumors not achieved by IL-1β blockade only. Combined with potential direct effects on tumor cells and synergies with standard chemotherapy, the elucidation of this mechanism gives us further confidence as we advance the development of nadunolimab in PDAC patients,” said Göran Forsberg, CEO of Cantargia.
A defining feature of PDAC is the extensive tumor stroma, consisting of tumor-supporting cells such as CAF and myeloid cells, which contribute to progression of this very difficult-to-treat type of cancer. The new data, generated in collaboration with Dr. Marcus Järås’ research group at Lund University, demonstrate that nadunolimab disrupts the interaction between PDAC cells and CAF. Nadunolimab affects multiple markers in the CAF, including factors that control migration of myeloid cells to the tumor. Full IL1RAP blockade is required for this effect as it is not achieved with an antibody which blocks IL-1β alone. Notably, nadunolimab also reduces growth of PDAC tumors only in the presence of CAF. This suggests that the effect of nadunolimab on tumor-supporting stromal cells is strongly connected to its anti-tumor properties, in addition to potential direct effects on tumor cells.
“This work simulated the detailed interaction between cancer cells and CAF seen in PDAC tumors and found that nadunolimab extensively disrupts gene expression in CAF. In particular, nadunolimab down-regulated a range of cytokines and reduced monocyte migration, with major potential consequences for the PDAC tumor microenvironment,” said Dr. Marcus Järås.
These findings support the promising clinical interim efficacy data presented recently at the ASCO Annual Meeting 2022. In over 70 PDAC patients evaluated in the phase IIa part of the clinical trial CANFOUR, nadunolimab in combination with chemotherapy results in efficacy substantially above historical controls for chemotherapy alone. Currently, Cantargia is preparing the next steps in the late-stage clinical development of nadunolimab in PDAC. Nadunolimab will be included in the adaptive clinical phase II/III trial Precision PromiseSM, designed by Pancreatic Cancer Action Network (PanCAN).
The new results will be presented at the AACR Special Conference: Pancreatic Cancer as a poster, which will be made available on Cantargia’s webpage (https://cantargia.com/en/research-development/publications) after the presentation on September 15.
For further information, please contact
Göran Forsberg, CEO
Telephone: +46 (0)46-275 62 60
This is information that Cantargia AB is obliged to make public pursuant to the EU Market Abuse Regulation. The information was submitted for publication, through the agency of the contact person set out above, at 23.30 CET on 13 September 2022.
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. The main project, the antibody nadunolimab, is being studied clinically in combination with chemotherapy or immune therapy with a primary focus on non-small cell lung cancer and pancreatic cancer. Positive interim data from the combination with chemotherapy indicate stronger efficacy than would be expected from chemotherapy alone. Cantargia’s second project, the antibody CAN10, addresses treatment of serious autoimmune/inflammatory diseases, with initial focus on systemic sclerosis and myocarditis.
Cantargia is listed on Nasdaq Stockholm (ticker: CANTA). More information about Cantargia is available at www.cantargia.com.
About nadunolimab (CAN04)
The antibody CAN04 binds strongly to its target IL1RAP and functions by inducing ADCC and blocking IL-1α and IL-1β signaling. Thereby, CAN04 can counteract the contribution of the IL-1 system to the immune suppressive tumor microenvironment and development of resistance to chemotherapy. CAN04 is investigated in multiple ongoing clinical trials. In the phase I/IIa study CANFOUR, first line combination therapy is investigated with standard chemotherapies in patients with PDAC (gemcitabine/nab-paclitaxel) and patients with NSCLC (cisplatin/gemcitabine) (NCT03267316). Positive interim data for the combination therapies show durable responses in 73 patients with PDAC, resulting in median iPFS of 7.2 months and median survival of 12.7 months. Stronger efficacy was also observed in 30 NSCLC patients with median PFS of 6.8 months. A response rate of 53% was achieved, with even higher responses in non-squamous NSCLC patients previously treated with pembrolizumab. These results show stronger efficacy than expected from chemotherapy alone. CAN04 is investigated with chemotherapy also in the phase I study CAPAFOUR, with the FOLFIRINOX regimen for first line treatment of metastatic PDAC (NCT04990037), and in two further clinical studies, CESTAFOUR (NCT05116891) and TRIFOUR (NCT05181462), in additional forms of cancer, including biliary tact cancer, colorectal cancer and triple negative breast cancer. CAN04 is also evaluated with the immune checkpoint inhibitor pembrolizumab, with or without chemotherapy, in the phase I study CIRIFOUR (NCT04452214).