P3, N=3, Completed, Immedica Pharma AB | Active, not recruiting --> Completed | Trial completion date: Oct 2025 --> Jun 2025

P3, N=3, Active, not recruiting, Immedica Pharma AB | Trial completion date: Dec 2025 --> Oct 2025

The arginase BCT-100 profoundly disrupts neuroblastoma growth in vitro and in vivo, an effect enhanced in combination with standard-of-care chemo-immuno-therapy. Our data supports further assessment of arginine-depleting combination therapies as a new treatment strategy for neuroblastoma.

P3, N=3, Active, not recruiting, Immedica Pharma AB | Recruiting --> Active, not recruiting | Trial primary completion date: Dec 2025 --> Jun 2025

From our in-house cohort and online database analysis, we found that the majority of the pancreatic cancer patients exhibited deficiencies in both ASS1 and OTC enzymes, suggesting that the combination of arginine deprivation and canavanine could be particularly effective in these patients. The ASS1- and OTC-negativity could also serve as predictive biomarkers for the response in other arginine-dependent cancers.

P3, N=3, Recruiting, Immedica Pharma AB | Not yet recruiting --> Recruiting

P3, N=3, Not yet recruiting, Immedica Pharma AB

Moreover, BCT-100 is highly efficacious in a patient-derived xenograft model, causing > 90% reduction in the number of human leukaemic stem cells (LSCs). These findings indicate arginine depletion to be a promising and novel strategy to eradicate therapy resistant LSCs.

Small cell lung cancer (SCLC) displays marked arginine auxotrophy due to inactivation of the rate-limiting enzyme argininosuccinate synthetase 1 (ASS1), and as a consequence may be targeted with pegylated arginine deiminase or ADI-PEG20 (pegargiminase) and human recombinant pegylated arginases (rhArgPEG, BCT-100 and pegzilarginase). Moreover, recent work has identified an intriguing role for targeting arginine in combination with PD-1/PD-L1 immune checkpoint inhibitors and clinical trials are in progress. Thus, future studies of arginine-depleting agents with chemoimmunotherapy, the current standard of care for SCLC, may lead to enhanced disease control and much needed improvements in long-term survival for patients.

Pegylated arginase (BCT-100) is currently in phase I/II trials in relapsed pHGG. Our results suggest that therapeutic arginine depletion may also be useful in other tumour types and IHC analysis of patient tumour samples could help identify patients likely to benefit from this treatment.

Furthermore, the results also revealed a significant reduction in activities of ALT, AST, and ALP in the Peg-Arginase group compared to MNU untreated or native-Arginase groups, suggesting that Peg-Arginase may eliminate the hepatotoxic effect of the MNU. All in all, our results suggested that the arginine-depleting enzyme, Peg-Arginase, exerted an anticancer effect against both T-47D and MDA-MB-231 breast cancer cell lines through cell proliferation inhibition and apoptosis induction.

PEG-BCT-100 in chemo naïve post-sorafenib HCC is well tolerated with moderate DCR. ASS-negative confers OS advantage over ASS-positive HCC. ASS-negativity is a potential biomarker for OS in HCC and possibly for other ASS-negative arginine auxotrophic cancers.