- Both parts of the IL-1 system are upregulated in tumor tissue after chemotherapy
- CAN04, blocking the activity of both forms of IL-1, increases the efficacy of several different chemotherapy regimes
STOCKHOLM, June 22, 2020 /PRNewswire/ -- Cantargia AB ("Cantargia") today presented new preclinical data giving additional knowledge around the mechanisms and thereby relevance of adding the clinical stage antibody CAN04 to chemotherapy. CAN04 combined with different chemotherapy regimens resulted in additive or synergistic antitumor effects and the results were presented at the 2020 Annual Meeting of the American Association for Cancer Research (AACR), June 22-24.
Cantargia develops antibody-based pharmaceuticals against interleukin-1 receptor accessory protein (IL1RAP). The antibody CAN04 binds IL1RAP with high affinity and functions through both Antibody-Dependent Cellular Cytotoxicity (ADCC) and blockade of interleukin-1 (IL-1) signaling. CAN04 is investigated in an open label three-armed phase I/IIa clinical trial, CANFOUR, examining monotherapy as well as combination with two different frequently used chemotherapy regimes in patients with non-small cell lung cancer (NSCLC) or pancreatic cancer (PDAC) (https://clinicaltrials.gov/ct2/show/NCT03267316). Positive interim combination therapy data showing higher response rates than expected from chemotherapy alone was presented in December 2019. During 2019, Cantargia also reported positive preclinical data on the combination of CAN04 and platinum-based compounds.
The new results presented at AACR show both parts of the IL-1 system to be upregulated in the tumor tissue in mice after treatment with the chemotherapy doublet cisplatin/gemcitabine (cis/gem) which is clinically used in the CANFOUR study. This finding strengthens the rationale to combine the IL-1 blocking antibody CAN04 and cis/gem. In more detail, cis/gem treatment resulted in death of cancer cell which correlated to IL-1a upregulation on the remaining cancer cells. At the same time, IL-1b converting enzyme (ICE, part of the inflammasome that induces active IL-1b) was activated in the tumor microenvironment. This supports a mechanism where IL-1a is induced in the tumor cells upon chemotherapy-induced cell death followed by IL-1b activation in the tumor. CAN04 has a unique mechanism of action and blocks the activity of both these inflammatory cytokines, in sharp contrast to other antibodies in clinical development blocking only one of the two forms. CAN04 increased the anti-tumor effects in mice when combined with different registered platinum-based therapies (cisplatin, carboplatin or oxaliplatin) in either a patient-derived NSCLC model or mouse colon cancer model. Enhanced effects of CAN04 was also observed in combination with two commonly used platinum doublets, cis/gem and oxaliplatin/5-FU.
Using zebrafish tumor models of NSCLC and PDAC, designed to investigate intrinsic resistance to therapy and early events in the cancer progression, CAN04 could increase the effect of chemotherapy efficacy already after 3 days of therapy. This study was performed in collaboration with BioReperia AB.
The two posters can be accessed through the meeting homepage, https://aacr20vm2.onlineeventpro.freeman.com/. The titles are "The anti-IL1RAP antibody CAN04 increases tumor sensitivity to platinum-based chemotherapy" and "Zebrafish patient tumor-derived xenograft models used for pre-clinical evaluation of CAN04 for lung and pancreatic cancer". The posters are also displayed on www.cantargia.com.
"These new data strengthen Cantargia's strategies. The results provide additional support on an important role of both forms of IL-1 as an inflammatory tumor counterreaction to chemotherapy. It further shows that CAN04, blocking these cytokines, can increase the efficacy of chemotherapy", says Göran Forsberg, CEO of Cantargia.
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 15.00 CET on 22 June 2020.
Cantargia AB (publ), reg. no. 556791-6019, is a biotechnology company that develops antibody-based treatments for life-threatening diseases. The basis for this is the protein IL1RAP that is involved in a number of diseases and where Cantargia has established a platform. The main project, the antibody CAN04, is being studied in the clinical phase I/IIa CANFOUR study with a primary focus on non-small cell lung cancer and pancreatic cancer. The study is focused on combination therapies, but also includes a monotherapy arm. Positive interim data from the combination therapies were presented in December 2019. 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 http://www.cantargia.com.
The antibody CAN04 binds IL1RAP with high affinity and functions through both ADCC and blockade of IL-1α and IL-1β signaling. CAN04 is investigated in an open label phase I/IIa clinical trial, CANFOUR, examining first line chemotherapy combination with two different standard regimes in 31 patients with NSCLC (gemcitabine/cisplatin) and 31 patients with PDAC (gemcitabine/nab-paclitaxel) as well as monotherapy in late stage patients (www.clinicaltrials.gov). The phase I monotherapy data from 22 patients were presented at ASCO 2019 and showed a good safety with infusion related reaction being the most common side effect. In addition, the biomarkers IL6 and CRP were decreased with treatment and 9/21 patients had stable disease. Positive interim data from the combination therapies were presented in December 2019. A phase I trial investigating CAN04 in combination with an immune checkpoint inhibitor is planned to start during 2020.
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