NG-350A

Published in the Journal for ImmunoTherapy of Cancer (JITC), Intravenous Dosing Shows Strong Evidence of Tumor Delivery, Viral Replication and Transgene Expression CAMBRIDGE, Mass.--(BUSINESS WIRE)--Akamis Bio, a clinical-stage oncology company using a proprietary Tumor-Specific Immuno-Gene Therapy (T-SIGn®) platform to deliver novel immunotherapeutic proteins, biomolecules and transgene combinations to treat solid tumors, today announced the publication of data supporting the continued clinical development and intravenous route of administration of NG-350A, its lead program for the treatment of advanced metastatic cancers. NG-350A is a next-generation transgene-armed tumor gene therapy designed to drive intratumoral expression of a CD40 agonist monoclonal antibody resulting from selective replication in both primary and metastatic epithelial-derived solid tumors. Data from the first-in-human dose escalation FORTITUDE study in patients with metastatic/advanced epithelial tumors supports proof-of-mechanism for NG-350A, with strong evidence of tumor-selective delivery, replication and transgene expression. Additionally, this study demonstrates that intravenous delivery of NG-350A results in a superior overall pharmacokinetic and pharmacodynamic profile, with no apparent disadvantages versus intratumoral injection. Blood sample analysis from patients showed sustained persistence of NG-350A up to seven weeks after intravenous dosing was completed (maximum follow up), particularly at higher dose levels. Further, a dose-dependent pattern was also seen with systemic delivery, resulting in four patients remaining positive for vector DNA in biopsies nearly two months after receiving the treatment. Transgene messenger RNA from replicating NG-350A was detected in nearly half the patients with intravenous treatment but only in one patient that had received intratumoral injection. Sustained increases in inflammatory cytokines were also observed following dosing, particularly with higher intravenous dose levels. “These findings are highly supportive of our ongoing focus on intravenous administration of NG-350A to safely drive sustained transgene expression within the tumor microenvironment. Systemic delivery offers considerable advantages over current intratumoral approaches, particularly with transgene-containing viral vectors where the cargo needs to reach both the primary tumor and metastases throughout the body – an application for which direct injection or dependence on an abscopal effect is not viable,” said Oliver Rosen, M.D., Chief Medical Officer at Akamis. Dr. Rosen continued: “This study demonstrated that a T-SIGn therapeutic armed with targeted immunostimulatory proteins such as CD-40 agonists can be successfully delivered intravenously, resulting in a superior overall pharmacokinetic and pharmacodynamic pro to intratumoral administration. Our preliminary data suggest that the local expression of immunostimulatory therapies following intravenous administration can overcome toxicity that limits non-targeted systemic administration. We look forward to continuing to understand the potential of this treatment in upcoming proof-of-concept studies.” NG-350A will now be studied in combination with chemoradiotherapy in FORTRESS, a multicenter open-label non-randomized Phase 1b trial of patients with locally advanced rectal cancer. A link to the publication “First-in-human clinical outcomes with NG-350A, an anti-CD40 expressing tumor-selective vector designed to remodel immunosuppressive tumor microenvironments” can be found here. About T-SIGn Akamis Bio’s T-SIGn® therapeutics are based on a replication competent, chimeric group B adenovirus backbone which has been adapted via directed evolution to home specifically to both primary and metastatic epithelial-derived solid tumor tissue following intravenous delivery. Once at the tumor site, T-SIGn therapeutics can drive the intratumoral expression of multiple transgene payloads, turning solid tumor cells into “drug factories” while leaving healthy tissue unaltered and intact. The intratumoral expression of immunologically active biomolecules and therapeutic proteins can result in the remodeling of the solid tumor microenvironment, triggering robust antitumor immune responses. T-SIGn therapeutics have the potential to be used in the monotherapy setting, as well as in combination with other immuno-oncology agents to target the key mechanisms that tumors use to evade the immune system. About Akamis Bio Akamis Bio is a clinical-stage oncology company using a proprietary Tumor-Specific Immuno-Gene Therapy (T-SIGn®) platform to deliver novel immunotherapeutic proteins, biomolecules and transgene combinations to treat solid tumors. The company is developing a portfolio of solid tumor-targeted T-SIGn therapeutics which aim to enable a patient’s own immune system to recognize, attack, and clear their cancer. Akamis Bio has a growing pipeline of T-SIGn therapeutics anchored by its lead clinical-stage program, NG-350A (an immuno-stimulatory tumor gene therapy driving intratumoral expression of a CD40 agonist monoclonal antibody) being investigated in ongoing Phase 1 clinical studies in patients with metastatic or advanced epithelial tumors. In addition to internal pipeline development efforts, Akamis Bio has a number of T-SIGn platform-focused collaborations with leaders in the immuno-oncology field including Merck and the Cancer Research Institute (CRI). To learn more, please visit . Contacts Media: Jason Glashow Glashow Strategic Communications Jason.Glashow@akamisbio.com

I.V.-Delivered Vector Core to Akamis Bio T-SIGn® Therapeutics; Phase 1 Study Data to be Presented at the 2023 American Society for Radiation Oncology (ASTRO) Annual Meeting CAMBRIDGE, Mass. & OXFORD, England--(BUSINESS WIRE)-- Akamis Bio, a clinical-stage oncology company using a proprietary Tumor-Specific Immuno-Gene (T-SIGn®) therapy platform to deliver novel immunotherapeutic proteins, biomolecules and transgene combinations to treat solid tumors, shared data today from a Phase 1 study of its adenovirus vector technology in combination with radiotherapy that showed improved response rates relative to expectations for radiation alone in patients with locally advanced rectal cancer. The CEDAR study, sponsored by Cancer Research UK and Akamis Bio, found that Enadenotucirev (EnAd), a tumor selective, I.V.-administered oncolytic adenovirus (on which T-SIGn therapeutics are based), in combination with chemoradiotherapy, showed significantly higher response rates by MRI assessed tumor regression grade (mrTRG – 41.6%) and pCR/cCR (41.6%) than expected rates (~20%) for standard chemoradiation. In the two dose schedules with administration pre-CRT and post-CRT, mrTRG of 1 or 2 was observed in 5 out of 10 (50%) of the treated patients. Further, hexon staining of patient samples suggested EnAd localization in both the primary tumor and in metastatic sites. The combined therapy was well tolerated with an acceptable safety profile. “These data are compelling given the higher-than-expected pCR/cCR rate, and the low adverse event rate highlights the ability to deliver the oncolytic virus concurrently with chemoradiation. This demonstrates the potential of a more reliable systemic administration compared to intratumoral injection,” said Dr. Maria A. Hawkins, Chair of Radiation Oncology at University College in London and the principal investigator of the study. “We are further encouraged by the potential of this systemic treatment to reach micro-metastatic cancer sites and we believe this approach should be pursued in additional studies as we look to improve the efficacy of chemoradiation for a wide range of solid tumors.” EnAd is a group B adenovirus designed for the systemic treatment of metastatic or advanced epithelial tumors. It is a precursor to Akamis Bio’s clinical-stage Tumor-Specific Immuno-Gene (T-SIGn®) therapeutics platform, which selectively delivers multiple transgene combinations, such as cytokines, chemokines, and antibodies for expression by tumor cells. The primary objective of the Phase 1 CEDAR study was to determine the optimal dose and frequency that EnAd can be administered with chemoradiation for rectal cancer, with secondary objectives focused on demonstrating the ability to deliver EnAd with chemoradiation and to measure the local response rate to combined therapy compared to pre-treatment status. “These results are very encouraging as they demonstrate the acceptable safety pro potent efficacy achievable with our first-generation adenovirus vector, EnAd,” said Dr. Oliver Rosen, Akamis Bio’s Chief Medical Officer. “As our T-SIGn therapeutics combine the EnAd backbone with an ability to selectively deliver transgenes to solid tumors, we look forward to building upon the clinical insights from the CEDAR study and demonstrating the potential of T-SIGn in conjunction with chemoradiation to positively impact the lives of patients living with rectal cancer and other solid tumors.” Data from the CEDAR study will be presented today at the 2023 American Society for Radiation Oncology Annual Meeting in San Diego, CA. Details of the presentation are as follows: Poster Presentation Title: A Phase 1 Trial of the Safety, Tolerability, and Biological Effects of Intravenous Enadenotucirev (EnAd), a Novel Oncolytic Virus, in Combination with Chemoradiotherapy in Locally Advanced Rectal Cancer (CEDAR) Poster Session: Gastrointestinal Cancer and Sarcoma Date and Time: October 3 at 12:45 - 2:00 p.m. ET Presenter: Dr Séan M. O’Cathail, MSc DPhil MRCPI FRCP FRCR, Senior Research Fellow, School of Cancer Sciences, University of Glasgow About T-SIGn Akamis Bio’s T-SIGn® therapeutics are based on a replication competent, chimeric group B adenovirus backbone which has been adapted via directed evolution to home specifically to both primary and metastatic epithelial-derived solid tumor tissue following intravenous delivery. Once at the tumor site, T-SIGn therapeutics can drive the intratumoral expression of multiple transgene payloads, turning solid tumor cells into “drug factories” while leaving healthy tissue unaltered and intact. The intratumoral expression of immunologically active biomolecules and therapeutic proteins can result in the remodeling of the solid tumor microenvironment, triggering robust antitumor immune responses. T-SIGn therapeutics have the potential to be used in the monotherapy setting, as well as in combination with other immuno-oncology agents to target the key mechanisms that tumors use to evade the immune system. About Akamis Bio Akamis Bio is a clinical-stage oncology company using a proprietary Tumor-Specific Immuno-Gene Therapy (T-SIGn®) platform to deliver novel immunotherapeutic proteins, biomolecules and transgene combinations to treat solid tumors. The company is developing a portfolio of solid tumor-targeted T-SIGn therapeutics which aim to enable a patient’s own immune system to recognize, attack, and clear their cancer. Akamis Bio has a growing pipeline of T-SIGn therapeutics anchored by its lead clinical-stage program, NG-350A (an immuno-stimulatory tumor gene therapy driving intratumoral expression of a CD40 agonist monoclonal antibody) being investigated in ongoing Phase 1 clinical studies in patients with metastatic or advanced epithelial tumors. In addition to internal pipeline development efforts, Akamis Bio has a number of T-SIGn platform-focused collaborations with leaders in the immuno-oncology field including BMS, Merck, and the Parker Institute for Cancer Immunotherapy (PICI). To learn more, please visit .