NG-350A / Akamis Bio, Sihuan Pharmaceutical - LARVOL DELTA

Phase 1b trial of NG-350A, a CD40 agonist antibody expressing adenoviral vector, in combination with chemoradiotherapy (CRT), in patients with mismatch repair-proficient (pMMR) locally advanced rectal cancer (LARC): Initial results from the FORTRESS study (AACR 2026) - "Abstract is embargoed at this time."

Clinical • Combination therapy • Metastases • Mismatch repair • P1 data • pMMR • Viral vector • Colorectal Cancer • Oncology • Rectal Cancer • Solid Tumor • CD40

Akamis Bio to Present Initial Data from the Phase 1b FORTRESS Study of NG-350A in Mismatch Repair-Proficient Locally Advanced Rectal Cancer at AACR 2026 (Businesswire) - "The ongoing Phase 1b FORTRESS study (NCT06459869) is assessing the anti-tumor effects of NG-350A plus chemoradiotherapy (CRT) following a 12-week active treatment period to establish whether NG-350A can improve response rates relative to expected outcomes from CRT alone....Company to disclose clinical safety and efficacy data for NG-350A in combination with chemoradiotherapy following 12-week active treatment period."

P1 data • Rectal Cancer

First-in-human clinical outcomes with NG-350A, an anti-CD40 expressing tumor-selective vector designed to remodel immunosuppressive tumor microenvironments. (PubMed, J Immunother Cancer) - P1 | "This phase 1a study provided initial proof-of-mechanism for NG-350A, with strong evidence of tumor delivery, viral replication and transgene expression-particularly after intravenous dosing. The lack of transgene-related or off-target viral toxicity was consistent with the highly selective delivery and replication of NG-350A, even after systemic delivery. The efficacy of intravenous-dosed NG-350A will now be evaluated in combination with pembrolizumab (NCT05165433), as well as with chemoradiotherapy (NCT06459869)."

Biomarker • Clinical data • IO biomarker • Journal • P1 data • Tumor microenvironment • Oncology • Solid Tumor • CD40

FORTRESS: NG-350A Plus Chemoradiotherapy for Locally Advanced Rectal Cancer (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Akamis Bio | Trial completion date: May 2028 ➔ Nov 2028 | Trial primary completion date: May 2026 ➔ Nov 2026

Trial completion date • Trial primary completion date • Colorectal Cancer • Oncology • Rectal Adenocarcinoma • Rectal Cancer • Solid Tumor

Study of NG-350A Plus Pembrolizumab in Metastatic or Advanced Epithelial Tumours (FORTIFY) (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: Akamis Bio | Active, not recruiting ➔ Completed | N=198 ➔ 14

Enrollment change • Trial completion • Oncology • Solid Tumor

FORTRESS: NG-350A Plus Chemoradiotherapy for Locally Advanced Rectal Cancer (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Akamis Bio | Trial completion date: Jan 2029 ➔ May 2028 | Trial primary completion date: Feb 2026 ➔ May 2026

Trial completion date • Trial primary completion date • Colorectal Cancer • Oncology • Rectal Cancer • Solid Tumor

REVOLUTION: Exploratory Platform Trial to Evaluate Immunotherapy Combinations With Chemotherapy for the Treatment of Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1 | N=45 | Completed | Sponsor: Cancer Insight, LLC | Active, not recruiting ➔ Completed | Trial completion date: Jan 2025 ➔ Jul 2025

Trial completion • Trial completion date • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

Akamis Bio Receives FDA Fast Track Designation for NG-350A for the Treatment of Mismatch Repair-Proficient Locally Advanced Rectal Cancer (Businesswire)

Fast track • pMMR • Rectal Cancer

Study of NG-350A Plus Pembrolizumab in Metastatic or Advanced Epithelial Tumours (FORTIFY) (clinicaltrials.gov) - P1 | N=198 | Active, not recruiting | Sponsor: Akamis Bio | Trial completion date: May 2025 ➔ Aug 2025 | Trial primary completion date: Mar 2025 ➔ Aug 2025

Trial completion date • Trial primary completion date • Oncology • Solid Tumor

FORTRESS: NG-350A Plus Chemoradiotherapy for Locally Advanced Rectal Cancer (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Akamis Bio | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Oncology • Rectal Cancer • Solid Tumor

Akamis Bio Announces Enrollment of First Patient in Phase 1b FORTRESS Trial of NG-350A in Patients with Locally Advanced Rectal Cancer (Businesswire) - "Akamis Bio...announced enrollment of the first patient in the proof-of-concept FORTRESS study of NG-350A in locally advanced rectal cancer (LARC). FORTRESS is a multi-center, open-label, non-randomized, Phase 1b study designed to measure clinical complete response (cCR) rates in patients with LARC."

Trial status • Rectal Cancer

Akamis Bio Announces $60 Million in Funding Linked to Series A Prime Financing and New Strategic Partnership (Businesswire) - "Akamis Bio...announced $60 million in funding linked to the close of a Series A Prime financing round and entry into a strategic partnership for the development of its lead clinical candidate, NG-350A. The new funding will support the company’s work to advance NG-350A through a Phase 1b clinical proof-of-concept (PoC) study in patients with locally advanced rectal cancer (LARC)....In a separate transaction, Akamis Bio entered into a licensing agreement granting Xuanzhu Biopharma the Greater China Region Rights to NG-350A. Under the terms of the licensing agreement, Akamis Bio is eligible to receive undisclosed upfront payments plus regulatory and sales milestones, as well as tiered royalties in the high single- to low double-digit range on Greater China Region NG-350A sales."

Financing • Licensing / partnership • Rectal Cancer

FORTRESS: NG-350A Plus Chemoradiotherapy for Locally Advanced Rectal Cancer (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Akamis Bio | Initiation date: Nov 2024 ➔ Feb 2025

Combination therapy • Metastases • Trial initiation date • Viral vector • Colorectal Cancer • Oncology • Rectal Cancer • Solid Tumor

Tumor-specific replication and immunoactivity of aCD40-producing T-SIGn vectors (SITC 2024) - P1 | "NG-350A is a T-SIGn vector encoding a full-length agonist aCD40 monoclonal antibody, which is currently in Phase 1 clinical development (NCT05165433, NCT04787991)...NG-1237 is a next-gen aCD40-encoding vector which holds promise for future preclinical and clinical development. Ethics Approval In vivo studies were approved by the UK Home Office (project license PP1421803)."

IO biomarker • Oncology • Pancreatic Cancer • Solid Tumor • CD40 • CXCL9 • IFNG • IL15

Akamis Bio Announces Publication Detailing Initial Proof of Mechanism for NG-350A, an IV-Dosed Tumor Gene Therapy Delivering a CD40 Agonist Payload (Businesswire) - P1 | N=28 | NCT03852511 | Sponsor: Akamis Bio | "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."

P1 data • Oncology • Solid Tumor

Study of NG-350A Plus Pembrolizumab in Metastatic or Advanced Epithelial Tumours (FORTIFY) (clinicaltrials.gov) - P1 | N=198 | Active, not recruiting | Sponsor: Akamis Bio | Recruiting ➔ Active, not recruiting | Phase classification: P1a/1b ➔ P1

Combination therapy • Enrollment closed • Metastases • Phase classification • Viral vector • Oncology • Solid Tumor

FORTRESS: NG-350A Plus Chemoradiotherapy for Locally Advanced Rectal Cancer (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Akamis Bio

Combination therapy • Metastases • New P1 trial • Viral vector • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Rectal Cancer • Solid Tumor

Phase I tolerability, persistence and pharmacodynamic (PD) profile of IV-administered next-generation adenoviral vectors supports clinical expansion in solid cancers (ESMO-TAT 2024) - P1 | "Methods The unarmed tumour-selective chimeric group B adenovirus enadenotucirev (EnAd) was evaluated in phase 1 studies in advanced/metastatic epithelial tumors and in locally advanced rectal cancer (LARC). Conclusions The sustained detection of vector DNA and persistence within tumors suggests next-generation T-SIGn vectors can be successfully administered IV. Preclinical studies support further clinical testing of targeted delivery of a CD40 agonist mAb with NG-350A to build on the intriguing results in the LARC pilot study and in disease-specific expansion cohorts in combination with CPIs."

Clinical • IO biomarker • P1 data • PK/PD data • Viral vector • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Rectal Cancer • Solid Tumor • CD80 • CD86 • IFNG

NG-350A, a tumor-selective anti-CD40 agonist expressing therapeutic, gemcitabine/nab-paclitaxel and ipilimumab for untreated metastatic pancreatic adenocarcinoma: cohort C of the REVOLUTION trial (SITC 2023) - P1 | "Exploratory endpoints include pharmacodynamics and association of tumor, blood, and stool biomarkers with clinical activity. Cohort C is enrolling into Stage 1."

IO biomarker • Metastases • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

REVOLUTION: Exploratory Platform Trial to Evaluate Immunotherapy Combinations With Chemotherapy for the Treatment of Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1 | N=45 | Active, not recruiting | Sponsor: Parker Institute for Cancer Immunotherapy | Trial completion date: Jan 2024 ➔ Jan 2025 | Trial primary completion date: Oct 2023 ➔ Oct 2024

Metastases • Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

REVOLUTION: Exploratory Platform Trial to Evaluate Immunotherapy Combinations With Chemotherapy for the Treatment of Patients With Previously Untreated Metastatic Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1 | N=45 | Active, not recruiting | Sponsor: Parker Institute for Cancer Immunotherapy | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer

Study of NG-350A Plus Pembrolizumab in Metastatic or Advanced Epithelial Tumours (FORTIFY) (clinicaltrials.gov) - P1a/1b | N=198 | Recruiting | Sponsor: Akamis Bio | Trial completion date: Jul 2023 ➔ May 2025 | Trial primary completion date: Mar 2023 ➔ Mar 2025

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

Phase 1 clinical trial results for NG-350A, a novel transgene-armed and tumor-selective vector: Differential effects of intravenous (IV) versus intratumoral (IT) dosing on immune pharmacodynamics (PD). (ASCO 2023) - P1, P1a/1b | "This analysis provides the first clear evidence that an IV-dosed tumor-selective viral vector can drive expression of immuno-stimulatory payloads with functional PD consequences in advanced cancers. The improved PK and PD profile of IV vs IT dosed NG-350A also highlights the benefits of systemic delivery for such vectors. Dose-escalation of NG-350A + pembrolizumab to identify a dose for efficacy assessments continues in the FORTIFY study (NCT05165433)."

Clinical • IO biomarker • P1 data • PK/PD data • Immune Modulation • Oncology • Solid Tumor • IFNG • IL12A • IL17A • IL2

Safe and effective delivery of antibody fragments to the solid tumor microenvironment (AACR 2023) - "NG-350A is currently being evaluated in phase I clinical studies in combination with Pembrolizumab or Ipilimumab. Data from these studies with initial vectors encoding combinations of functionally active antibody fragments will be presented. Collectively, these clinical and preclinical datasets demonstrate the broad utility of the T-SIGn platform for expressing rationally-designed combinations of antibodies and other natural and synthetic agents within tumors and thus enabling the development of new and potent immunotherapies for patients with solid epithelial cancers."

Biomarker • IO biomarker • Tumor microenvironment • Oncology • Solid Tumor • CXCL9 • IFNG • IL17A

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