On September 27, 2023 Alligator Bioscience (Nasdaq Stockholm: ATORX) reported the publication of a scientific article highlighting pharmacodynamic data from a Phase 1 dose escalation study of its lead asset mitazalimab, a best-in-class CD40 mAb agonist, in patients with advanced solid stage tumors (NCT02829099) (Press release, Alligator Bioscience, SEP 27, 2023, View Source [SID1234635442]).
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The publication in the journal Cells highlights how RNA sequencing was used to assess peripheral pharmacodynamic activity in patients from the Phase 1 study. The analysis revealed that at the current Phase 2 dose 900 μg/kg mitazalimab induced peripheral transcriptomic alterations consistent with immune activation expected from a strong CD40 agonist.
In particular, the transcriptomic alterations are in line with migration of effector cells (e.g. CD8+ T cells and natural killer cells) and B cells to tissues such as the tumor, while dendritic cells, monocytes, B cells and natural killer cells show transcription profiles consistent with increased immune activation. This activation of the immune system support the potential of mitazalimab to activate myeloid cells and overcome the immune suppressive mechanisms in the tumor microenvironment, which can induce anti-tumor responses and make the tumor more sensitive to other therapies, such as mFOLFIRINOX, in pancreatic cancer patients. The pharmacodynamic activity seen in this study is also in line with the immune phenotypic changes seen in the OPTIMIZE-1 study, with further details to be presented at AACR (Free AACR Whitepaper) Pancreatic on Thursday 28th September 2023.
The full article, entitled "Early pharmacodynamic changes measured by RNA sequencing in peripheral blood from patients in a phase 1 study with mitazalimab, a potent CD40 agonistic monoclonal antibody", is available online via this link.
"The publication of this article in the renowned, peer-reviewed journal Cells further underlines the importance of the CD40 research being carried out by our dedicated scientific team," said Søren Bregenholt, CEO of Alligator Bioscience. "The data presented here reinforce mitazalimab’s mode of action, validate the design of our ongoing OPTIMIZE-1 study and provide yet more clear evidence to support mitazalimab’s continued clinical development. We are now looking forward mitazalimab’s next major milestone, the topline readout from its evaluation in pancreatic cancer due early next year."
Mitazalimab is currently being evaluated in OPTIMIZE-1, a Phase 2 open-label, multi-center study to assess its safety and efficacy in combination with chemotherapy, mFOLFIRINOX, in previously untreated patients with metastatic pancreatic ductal adenocarcinoma (NCT04888312). The study is on track for top-line readout in early Q1 2024.