Akamis Bio Publishes Initial Proof of Mechanism for IV CD40 Agonist Tumor Gene Therapy

In a recent publication in the Journal for ImmunoTherapy of Cancer (JITC), Akamis Bio, a clinical-stage oncology company, has shared promising data related to NG-350A, a next-generation tumor gene therapy. The data support further clinical development and the use of intravenous administration for treating advanced metastatic cancers. The company employs a proprietary platform called Tumor-Specific Immuno-Gene Therapy (T-SIGn®) to deliver innovative immunotherapeutic proteins, biomolecules, and transgene combinations aimed at combating solid tumors.

NG-350A, the company's leading program, is crafted to promote the intratumoral expression of a CD40 agonist monoclonal antibody. This action stems from selective replication within both primary and metastatic epithelial-derived solid tumors. Data from the FORTITUDE study, an initial dose-escalation trial involving patients with metastatic or advanced epithelial tumors, provide compelling proof of NG-350A’s mechanism, particularly its tumor-selective delivery, replication, and transgene expression. The study's results indicate that intravenous administration of NG-350A yields a superior pharmacokinetic and pharmacodynamic profile when compared to intratumoral injection, without any apparent drawbacks.

Analysis of blood samples from study participants revealed that NG-350A persisted for up to seven weeks following the completion of intravenous dosing, especially at higher levels. Additionally, systemic delivery of the therapy showed a dose-dependent pattern, with four patients retaining vector DNA in their biopsies nearly two months post-treatment. Transgene messenger RNA resulting from NG-350A replication was detected in almost half of the intravenously treated patients but was present in only one patient who received intratumoral injection. Significant increases in inflammatory cytokines were also observed post-dosing, most notably with higher intravenous doses.

Dr. Oliver Rosen, Chief Medical Officer at Akamis Bio, emphasized that these findings strongly support the company’s focus on intravenous administration of NG-350A. He highlighted the advantages of systemic delivery over current intratumoral methods, particularly for transgene-containing viral vectors, which need to reach both primary tumors and metastases throughout the body. Dr. Rosen further noted that the study underscores the potential of T-SIGn therapeutics, armed with targeted immunostimulatory proteins like CD-40 agonists, to be delivered intravenously, offering a better overall pharmacokinetic and pharmacodynamic profile than intratumoral administration. Preliminary data suggest that this approach can overcome toxicity issues associated with non-targeted systemic administration.

Going forward, NG-350A will be evaluated in combination with chemoradiotherapy in the FORTRESS trial, a multicenter, open-label, non-randomized Phase 1b study involving patients with locally advanced rectal cancer.

Akamis Bio's T-SIGn® therapeutics use a replication-competent, chimeric group B adenovirus backbone, which has been adapted to target primary and metastatic epithelial-derived solid tumor tissues following intravenous delivery. Upon reaching the tumor site, T-SIGn therapeutics drive the intratumoral expression of multiple transgene payloads, effectively turning solid tumor cells into “drug factories” while leaving healthy tissue undisturbed. This process results in the remodeling of the tumor microenvironment and triggers strong antitumor immune responses. T-SIGn therapeutics have the potential for use as monotherapy or in combination with other immuno-oncology agents to target key mechanisms that tumors employ to evade the immune system.

Akamis Bio is focused on leveraging its proprietary T-SIGn platform to develop a portfolio of solid tumor-targeted therapeutics. Their lead clinical program, NG-350A, is being studied in ongoing Phase 1 trials involving patients with metastatic or advanced epithelial tumors. In addition to internal pipeline development, Akamis Bio collaborates with leading entities in the immuno-oncology field, including Merck and the Cancer Research Institute (CRI).