NG-641 / Akamis Bio - LARVOL DELTA

STAR: First in Human Study With NG-641, a Tumour Selective Transgene Expressing Adenoviral Vector (clinicaltrials.gov) - P1 | N=186 | Completed | Sponsor: Akamis Bio | Active, not recruiting ➔ Completed

Trial completion • Oncology • Solid Tumor

NEBULA: Study of NG-641 in Combination With Nivolumab in Metastatic or Advanced Epithelial Tumours (clinicaltrials.gov) - P1 | N=30 | Completed | Sponsor: Akamis Bio | Active, not recruiting ➔ Completed

Trial completion • Oncology • Solid Tumor

MOAT: A Study of NG-641 and Pembrolizumab in Squamous Cell Carcinoma of the Head and Neck (clinicaltrials.gov) - P1 | N=36 | Completed | Sponsor: Akamis Bio | Active, not recruiting ➔ Completed

Monotherapy • Trial completion • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

NEBULA: Study of NG-641 in Combination With Nivolumab in Metastatic or Advanced Epithelial Tumours (clinicaltrials.gov) - P1 | N=30 | Active, not recruiting | Sponsor: Akamis Bio | Recruiting ➔ Active, not recruiting | Phase classification: P1a/1b ➔ P1 | Trial completion date: Jul 2024 ➔ Dec 2024 | Trial primary completion date: May 2024 ➔ Aug 2024

Combination therapy • Enrollment closed • Metastases • Phase classification • Trial completion date • Trial primary completion date • Viral vector • Oncology • Solid Tumor

MOAT: A Study of NG-641 and Pembrolizumab in Squamous Cell Carcinoma of the Head and Neck (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: Akamis Bio | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Monotherapy • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

STAR: First in Human Study With NG-641, a Tumour Selective Transgene Expressing Adenoviral Vector (clinicaltrials.gov) - P1 | N=186 | Active, not recruiting | Sponsor: Akamis Bio | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Aug 2024

Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Viral vector • Oncology • Solid Tumor

STAR: First in Human Study With NG-641, a Tumour Selective Transgene Expressing Adenoviral Vector (clinicaltrials.gov) - P1 | N=186 | Recruiting | Sponsor: Akamis Bio | N=128 ➔ 186 | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Viral vector • Oncology • Solid Tumor

MOAT: A Study of NG-641 and Pembrolizumab in Squamous Cell Carcinoma of the Head and Neck (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: Akamis Bio | Trial completion date: Dec 2023 ➔ Oct 2024 | Trial primary completion date: Aug 2023 ➔ Sep 2024

Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

NEBULA: Study of NG-641 in Combination With Nivolumab in Metastatic or Advanced Epithelial Tumours (clinicaltrials.gov) - P1a/1b | N=30 | Recruiting | Sponsor: Akamis Bio | Trial completion date: Dec 2022 ➔ Jul 2024 | Trial primary completion date: Oct 2022 ➔ May 2024

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Viral vector • Oncology • Solid Tumor

Safety and tolerability of T-SIGn vectors when administered using “flat” versus “low-high-high” (LHH) dosing regimens. (ASCO 2022) - P1 | " Data were pooled from three Phase 1 dose-escalation studies in advanced/metastatic epithelial cancer: SPICE (EnAd + pembrolizumab/nivolumab; NCT02636036), FORTITUDE (NG-350A ± pembrolizumab; NCT03852511) and STAR (NG-641; NCT04053283). LHH dosing appears to induce a desensitization mechanism allowing higher cumulative doses of T-SIGn vectors to be given without the associated acute reactions to viral infusions. This finding may have implications for optimizing safety-efficacy profiles of viral vectors in cancer."

Clinical • Inflammation • Oncology • Solid Tumor • IFNG • IL6 • TNFA

Akamis Bio Announces $30 Million Financing, Provides Clinical Program Update and Relaunches with Name Change from PsiOxus Therapeutics (Businesswire) - "Akamis Bio (formerly PsiOxus Therapeutics)...announced a $30 million convertible note financing co-led by a group of leading US life science investors....The $30 million convertible note financing was co-led by new US investors ARCH Venture Partners, the Parker Institute for Cancer Immunotherapy, and Westlake Village BioPartners. It will further fund development activities for the clinical stage NG-350A and NG-641 programs, as well as general corporate purposes."

Financing • Oncology • Solid Tumor

Akamis Bio Announces $30 Million Financing, Provides Clinical Program Update and Relaunches with Name Change from PsiOxus Therapeutics (Businesswire) - "As the ongoing clinical studies for NG-350A (FORTITUDE and FORTIFY) and NG-641 (STAR, NEBULA, and MOAT) advance in 2023, Akamis Bio will continue to assess safety, tolerability, and preliminary efficacy in both monotherapy and combination (with checkpoint inhibitors) settings, as well as the potential benefits of multiple cycles of T-SIGn^® therapeutic dosing. Akamis Bio anticipates the initiation of a set of expansion cohort studies for NG-350A and NG-641 in early 2024 to demonstrate clinical proof-of-concept in patient populations with a single type of epithelial-derived solid tumor."

Trial status • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma of Head and Neck

First-in-human Phase 1a study of NG-641, a tumour-selective vector expressing a FAP-TAc bispecific antibody and immune enhancer module, in patients with metastatic/advanced epithelial tumours (STAR) (SITC 2022) - P1, P1a/1b | "These results suggest that NG-641 drives local immunological tumour changes without systemic toxicity. A further trial (NEBULA, NCT05043714 ) examining NG-641 with nivolumab is ongoing."

Clinical • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CD8 • CXCL10 • CXCL9 • FAP • IFNA1 • IFNG • IL12A • IL17A

A multicentre phase 1b study of NG-641, a novel transgene-armed and tumour-selective adenoviral vector, and pembrolizumab as neoadjuvant treatment for squamous cell carcinoma of the head and neck (SITC 2021) - P1 | "Pharmacodynamic outcomes will be assessed following NG-641 ± pembrolizumab, including characterising immune/inflammatory biomarkers in both tumour and blood. The study is to be conducted at 4 sites in the UK; up to 36 patients will be enrolled."

Clinical • IO biomarker • P1 data • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CAFs • CXCL9

NEBULA: A multicenter phase 1a/b study of a tumor-selective transgene-expressing adenoviral vector, NG-641, and nivolumab in patients with metastatic or advanced epithelial tumors. (ASCO 2022) - P1, P1a/1b | "Background: Tumor-Specific Immuno Gene Therapy (T-SIGn) vectors are next-generation transgene-armed variants of the adenoviral vector enadenotucirev that selectively replicate in epithelial tumor cells. Serial blood samples will be analyzed to study cytokine production and changes in peripheral immune cell subsets. Enrollment to the first dose-escalation cohort is ongoing."

Clinical • IO biomarker • P1 data • Gene Therapies • Inflammation • Oncology • Solid Tumor • CAFs • CXCL9 • FAP • IFNA1

A multicenter phase 1a/b study of NG-641, a tumor-selective transgene-expressing adenoviral vector, and nivolumab in patients with metastatic or advanced epithelial tumors (NEBULA) (AACR 2022) - P1, P1a/1b | "Background: T-SIGn (Tumor-Specific Immuno Gene Therapy) vectors are transgene-expressing variants of the blood-stable adenovirus enadenotucirev. Analyses of serial blood samples will explore cytokine production and changes in peripheral immune cell subsets. Enrollment to the first dose-escalation cohort is ongoing."

Clinical • IO biomarker • P1 data • Oncology • Solid Tumor • CAFs • CXCL10 • CXCL9 • FAP • IFNA1

MOAT: A Study of NG-641 and Pembrolizumab in Squamous Cell Carcinoma of the Head and Neck (clinicaltrials.gov) - P1 | N=36 | Recruiting | Sponsor: PsiOxus Therapeutics Ltd | Trial completion date: Sep 2022 ➔ Dec 2023 | Trial primary completion date: Jun 2022 ➔ Aug 2023

Combination therapy • Monotherapy • Trial completion date • Trial primary completion date • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

NEBULA: Study of NG-641 in Combination With Nivolumab in Metastatic or Advanced Epithelial Tumours (clinicaltrials.gov) - P1a/1b | N=30 | Recruiting | Sponsor: PsiOxus Therapeutics Ltd | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • MSI

MOAT: A Study of NG-641 and Pembrolizumab in Squamous Cell Carcinoma of the Head and Neck (clinicaltrials.gov) - P1; N=48; Recruiting; Sponsor: PsiOxus Therapeutics Ltd; Not yet recruiting ➔ Recruiting

Clinical • Combination therapy • Enrollment open • Monotherapy • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

MOAT: A Study of NG-641 and Pembrolizumab in Squamous Cell Carcinoma of the Head and Neck (clinicaltrials.gov) - P1; N=48; Not yet recruiting; Sponsor: PsiOxus Therapeutics Ltd; Initiation date: Jun 2021 ➔ Nov 2021

Clinical • Combination therapy • Monotherapy • Trial initiation date • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

NEBULA: Study of NG-641 in Combination With Nivolumab in Metastatic or Advanced Epithelial Tumours (clinicaltrials.gov) - P1a/1b; N=30; Not yet recruiting; Sponsor: PsiOxus Therapeutics Ltd

Clinical • Combination therapy • New P1 trial • Breast Cancer • Esophageal Cancer • Gastric Cancer • Gastrointestinal Cancer • Head and Neck Cancer • Hepatocellular Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • MSI

PsiOxus and bluebird bio Present Novel Data Combining PsiOxus T-SIGn Platform with CAR-T Therapy to Clear Primary Tumors and Metastases (Businesswire) - "PsiOxus Therapeutics, Ltd...and bluebird bio, Inc...presented preclinical data at the American Association for Cancer Research (AACR) Annual Meeting 2021. The study, 'T-SIGn cancer gene therapy and anti-EGFR CAR-T cells synergize in combination therapy to clear A549 lung tumor xenografts', assessed anti-tumor synergy between PsiOxus’ T-SIGn® vectors and an anti-epidermal growth factor receptor (EGFR) chimeric antigen receptor (CAR)-T cell therapy from bluebird bio in xenograft lung tumors."

Preclinical • Lung Cancer • Oncology • Solid Tumor

PsiOxus Therapeutics Updates Agreement with Bristol Myers Squibb to Advance their Clinical Stage Immuno-Oncology Collaboration (Businesswire) - "PsiOxus Therapeutics...today announced an updated agreement to advance its clinical collaboration with Bristol Myers Squibb....The first stage of this collaboration combined Bristol Myers Squibb’s Opdivo with PsiOxus’ enadenotucirev in the Phase 1 SPICE study to determine the safety and tolerability of combining these two agents...The revised collaboration announced today will build upon the initial study data and will combine Opdivo with PsiOxus’ NG-641...Under the terms of this agreement, PsiOxus will be responsible for conducting the Phase 1 study with patient recruitment expected to start in the third quarter of 2021."

Licensing / partnership • New P1 trial • Oncology

MOAT: A Study of NG-641 and Pembrolizumab in Squamous Cell Carcinoma of the Head and Neck (clinicaltrials.gov) - P1; N=48; Not yet recruiting; Sponsor: PsiOxus Therapeutics Ltd

New P1 trial • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

PsiOxus Therapeutics announces clinical trial with third cancer gene therapy treatment and appointment of new chief medical officer (Businesswire) - “PsiOxus® Therapeutics, Ltd…announced that it has started a clinical trial with NG-641, a four transgene tumor-microenvironment modifying cancer gene therapy, to cancer patients. This is the first time that a tumor-specific virus containing four different therapeutic transgenes has been administered to cancer patients….In addition to the FAP-targeted T-cell activator, NG-641 also delivers three other molecules to further recruit and activate T-cells to induce an anti-tumor immune response. NG-641 is thus the first quadrivalent viral gene therapy vector for cancer to be studied in patients.”

New P1 trial