Sep 27, 2023 · Regulatory information

Cantargia presents new clinical data further supporting nadunolimab’s antitumor activity and a key role of its target IL1RAP in pancreatic cancer

Cantargia (Cantargia AB; Nasdaq Stockholm: CANTA) today reported new clinical and biomarker data in further support of nadunolimab (CAN04) for treatment of pancreatic cancer (PDAC). Updated results in first-line combination with chemotherapy, as well as new results in late-stage monotherapy, show the strongest efficacy in patients with high levels of IL1RAP, the target of nadunolimab. Biomarker data consolidate these observations as levels of IL1RAP increase during PDAC development and appear to be linked to specific KRAS mutations associated with aggressive disease. These data will be presented at the AACR Special Conference: Pancreatic Cancer 2023, 27-30 September.

“This new dataset is a major step forward in the development of nadunolimab for treatment of pancreatic cancer. Our results from first-line combination therapy are strong, and new monotherapy results also indicate a single-agent effect. Additionally, the new biomarker data demonstrate the significance of targeting IL1RAP as it is clearly linked to aggressiveness of the disease,” said Göran Forsberg, CEO of Cantargia.

In the clinical phase I/IIa trial CANFOUR, a total of 23 late-stage PDAC patients received nadunolimab monotherapy, typically after failure on at least two previous chemotherapy regimens. Of these, IL1RAP levels were assessed in tumor biopsies taken before treatment from 17 patients, categorized as either IL1RAP high or IL1RAP low. Notably, IL1RAP high patients had stronger clinical benefit compared to IL1RAP low patients, including prolonged median overall survival (5.8 vs 2.6 months; p=0.078) and progression-free survival (iPFS 3.6 vs 1.6 months; p=0.0073), indicating target engagement by nadunolimab leading to antitumor activity.

Similar observations were made for the 73 first-line patients treated with a combination of nadunolimab and gemcitabine/nab-paclitaxel in CANFOUR, although as expected the median survival was generally longer compared to the late-stage patients. Significantly prolonged median overall survival was observed in IL1RAP high compared to IL1RAP low patients (14.2 vs 10.6 months; p=0.026), with a trend for higher response rates, with deeper and more durable responses. Efficacy parameters for the total 73 first-line patients, the two IL1RAP subgroups, and historical control data are summarized below:

Efficacy parameter according to iRECIST1.1	All patients (n=73)	IL1RAP high (n=29)	IL1RAP low (n=20)	Historical control [1] (n=431); RECIST
Overall survival (OS); median	13.2 mo	14.2 mo	10.6 mo	8.5 mo
Progression-free survival (iPFS); median	7.2 mo	7.4 mo	5.8 mo	5.5 mo (PFS)
1-year survival	58%	67%	39%	35%
Overall response rate (iORR)	33%	48%	30%	23%
Duration of response (iDoR); median	7.3 mo	9.5 mo	5.6 mo	NA

These results are complemented by biomarker data obtained from publicly available gene databases, in collaboration with world-leading experts in PDAC, as well as molecular profiling data from pancreatic cancer patients included in the Know Your Tumor® programme by Pancreatic Cancer Action Network (PanCAN).

Collectively, the biomarker data show that levels of IL1RAP, as well as IL-1alpha and IL-1beta which signal via IL1RAP, are increased in PDAC tumors compared to healthy pancreas. Further, the highest levels of IL1RAP were observed in late-stage PDAC tumors, and patients with high IL1RAP levels had shorter overall survival. Notably, high IL1RAP levels also correlated with the presence of KRAS mutations, in particular G12D, which is the most common KRAS mutation in PDAC. This is a key finding as KRAS mutations are considered a crucial component for disease progression in PDAC, and few effective therapies for targeting such mutations have been developed.

These data are presented in detail in a poster session at the AACR Special Conference: Pancreatic Cancer 2023 held in Boston, MA. More information on the poster session can be found below. At the time of presentation, the poster will also be made available at Cantargia’s webpage (www.cantargia.com/en/research-development/publications).

Abstract title: Interleukin-1 receptor accessory protein (IL1RAP) overexpression is associated with worse prognosis in PDAC and is targetable by nadunolimab
Date and time: September 29, 2023, 4:40 PM – 6:40 PM EDT
Presenter: Dr. David Liberg

Cantargia’s lead asset nadunolimab is currently investigated clinically in PDAC, non-small cell lung cancer and triple-negative breast cancer, with over 200 patients treated to date. A clinical phase IIb trial in PDAC is currently in preparation.

References
[1] Von Hoff et al, N Engl J Med 2013; 369:1691-1703

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. The main 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 interim 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 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 nadunolimab binds strongly to its target IL1RAP and functions by inducing ADCC and blocking IL-1alpha and IL-1beta 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 evaluates nadunolimab in combination with standard chemotherapies in patients with PDAC (gemcitabine/nab-paclitaxel) or NSCLC (platinum-based chemotherapies) (NCT03267316). Positive interim 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 30 NSCLC patients with median PFS of 7.0 months and a response rate of 53%; 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 50% response rate for nadunolimab combined with carboplatin/gemcitabine. Nadunolimab is also investigated with chemotherapy in the clinical trials CAPAFOUR (NCT04990037) and CESTAFOUR (NCT05116891), and with the checkpoint inhibitor pembrolizumab in the CIRIFOUR trial (NCT04452214).