On September 5, 2024 Asgard Therapeutics, a privately held biotech company pioneering in vivo direct cell reprogramming for cancer immunotherapy, reported the publication of key proof-of-concept data supporting its lead program, AT-108, in the high-impact, peer-reviewed journal, Science (Press release, Asgard Therapeutics, SEP 5, 2024, View Source [SID1234646366]). Novel data shows that AT-108 reprograms tumor cells, directly within the immunosuppressed tumor microenvironment, into an immunogenic cell fate, which mounts strong anti-tumor, antigen-specific responses and durable tumor shrinkage even upon metastatic rechallenge.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
The study, co-led by Asgard Therapeutics and the Pereira Lab at Lund University, demonstrated efficient dendritic cell reprogramming in mouse models resistant to checkpoint blockade treatment and patient-derived tumor samples. The data provides preclinical proof-of-concept for an off-the-shelf, yet tumor-specific, first-in-class cancer immunotherapy, paving the way for first-in-human trials of AT-108. Reprogramming tumor cells so that they are converted into antigen-presenting dendritic cells "elicits systemic and long-term antitumor immunity," stated the authors of the study. The study entitled, In vivo dendritic cell reprogramming for cancer immunotherapy, also shows the systematic selection of an optimal delivery system for expression of key reprogramming factors in the tumor, which led to the nomination of Asgard’s lead program.
Publication of the study follows Asgard’s €30 million Series A financing to advance its cell reprogramming platform, as the Company continues to make significant progress in preparing AT-108 for clinical development. Asgard recently commenced activities to establish CMC process for scale-up manufacturing of GMP-grade AT-108 for Phase I/II trials.
Cristiana Pires, Co-founder and Chief Executive Officer of Asgard Therapeutics, said: "This study demonstrates that Asgard’s platform converts tumor cells into dendritic cells within living organisms – and not just in vitro. This publication in such a high-impact journal as Science demonstrates the enormous potential of our cell reprogramming approach and the quality of our scientific methodology. Together with ongoing work to establish manufacturing process for lead program, AT-108, we are focused on completing IND-enabling studies, including pharmacokinetic and GLP toxicology studies, in advance of our near-term objective of filing a clinical trial application for testing of AT-108 in patients."
Co-Lead author Fábio Rosa, PhD, Co-founder and Head of Research of Asgard Therapeutics, commented: "We are very pleased with the publication of this joint effort with Filipe Pereira and his team at Lund University, as it represents a significant milestone for the company ahead of clinical development. The new findings support the selection of a replication-deficient adenoviral vector for AT-108, demonstrating its proof-of-concept and prompting the start of advanced preclinical development. We were very excited to see that AT-108 induces complete tumor regressions and protects mice from tumor re-challenge – even in the metastatic setting."
The reprogramming of tumor cells to cDC1-like cells restores tumor antigen presentation and remodels the tumor microenvironment, reducing exhausted and regulatory populations, and promoting infiltration and activation of cytotoxic T cells. Importantly, in vivo dendritic cell reprogramming induces complete responses as a monotherapy and synergizes with immune checkpoint blockade in aggressive immune-deserted tumor models. The finding of an abscopal effect on distant non-treated tumors highlights that benefits extend beyond the primary tumor.
Alongside the Pereira Lab from where the technology spun-out, Asgard collaborated with additional researchers at Lund University, Inge Marie Svane and Özcan Met from CCIT-DK, Denmark, and Irina Agarkova and team from InSphero, Switzerland to complete the study. The Company’s research has received support from Eurostars-2 Joint Program with co-funding from the European Union’s Horizon 2020 research and innovation program, Sweden’s Innovation Agency, E!115376 REPRINT Grant 2021-03371, and the Strategic innovation programs, Swelife.