Akamis Bio Announces Encouraging Preliminary Results from the Phase 1b FORTRESS Study of NG-350A in Mismatch Repair-Proficient Locally Advanced Rectal Cancer

NG-350A combined with chemoradiotherapy demonstrated promising efficacy and a favorable safety profile

Composite response rate of 50 percent observed across the first 10 patients who completed the active treatment period, with no serious adverse events or new safety signals identified related to NG-350A

Initial results to be presented at the American Association of Cancer Research 2026 Annual Meeting

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Akamis Bio, a clinical-stage oncology company working to advance the standard of care in colorectal cancer, today announced early data from the on-going Phase 1b FORTRESS study of NG-350A, an oncolytic immunotherapy for the treatment of mismatch repair-proficient (pMMR) locally advanced rectal cancer (LARC). NG-350A combined with chemoradiotherapy (CRT) demonstrated a composite response rate of 50 percent across the first 10 patients who completed the 12-week active treatment period, with no serious adverse events or new safety signals identified related to NG-350A.

The ongoing Phase 1b FORTRESS study (NCT06459869) is assessing the anti-tumor effects of NG-350A combined with CRT following a 12-week active treatment period to establish whether NG-350A can improve composite response rates in pMMR LARC patients relative to expected outcomes from CRT alone. The primary endpoint of the FORTRESS study is the composite response rate defined as the proportion of patients achieving a clinical complete response (cCR) or a near clinical complete response (ncCR) at 12 weeks. The benchmark composite response rate (cCR + ncCR) for CRT alone at 12 weeks is approximately 25 percent. The CEDAR study, an investigator-initiated trial of EnAd (a predecessor to NG-350A without a transgene) plus CRT in patients with LARC, demonstrated a composite response rate of 50 percent. The preliminary 50 percent composite response rate observed to date in the FORTRESS study provides confirmation of the CEDAR results and underscores the promise of NG-350A plus CRT to improve pMMR LARC outcomes relative to expectations for CRT alone.

“While still early data, observation of such a significant composite response rate with NG-350A plus CRT after only 12 weeks of treatment could be a significant development for locally advanced rectal cancer treatment,” said Eric Miller, MD, PhD, associate professor of radiation oncology at Ohio State University and a FORTRESS study investigator. “A therapy that increases the proportion of patients who respond to treatment, as well as the speed with which that response is achieved, could enable responding patients to pursue a ‘watch-and-wait’ protocol, to both avoid surgery and preserve organ function.”

LARC is defined by the spread of rectal cancer to nearby tissues or lymph nodes. Patients with pMMR tumors account for approximately 95 percent of all LARC cases (~30,000 newly diagnosed patients annually in the US). CRC is now the leading cause of cancer related death in patients under 50 years old in the US and the incidence of CRC continues to rise in this younger population. Consistent with this trend, the average age of pMMR LARC patients included in this initial FORTRESS data analysis is 52 years.

The composite response rate (cCR + ncCR) used as the primary endpoint in the FORTRESS study reflects the dynamic process of tumor regression. As a patient’s tumor begins to respond to therapy, the tumor moves through the ncCR phase (characterized by nearly complete disappearance of the tumor mass with some residual mucosal abnormality) before final achievement of a cCR (a return to fully healthy, normal mucosa). While the time to convert from ncCR to cCR can vary by patient and therapeutic intervention, across studies, achievement of a ncCR has been strongly predictive of subsequent achievement of a cCR, with up to 90 percent of ncCRs converting to cCRs following the initial assessment.

“We believe that these early FORTRESS data provide the first key evidence of clinical proof of concept for NG-350A plus CRT in pMMR LARC,” said Howard Davis, PhD, CEO of Akamis Bio. “When treated with the current standard of care, patients need to undergo life-altering surgery to remove portions of the rectum. We believe that NG-350A plus CRT has the potential to advance the pMMR LARC standard of care, offering more patients access to a non-operative approach to management of their disease, as well as the opportunity for organ preservation – a critically important treatment goal as LARC continues to impact increasingly younger patient populations.”

The data will be shared in a poster presentation on April 20^th at the American Association for Cancer Research (AACR) Annual Meeting 2026 in San Diego.

AACR Poster Presentation Details

Title: 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
Session Title: Phase II and Phase III Clinical Trials
Date and Time: April 20, 2:00PM – 5:00PM PDT
Location: Poster Section 52
Poster Number: 19

About NG-350A
NG-350A is a clinical-stage, intravenously delivered Tumor-Specific Immuno-Gene (T-SIGn®) therapeutic designed to drive intratumoral expression of a CD40 agonist monoclonal antibody triggering the activation of antigen-presenting cells (APCs) resident in solid tumors and their draining lymph nodes. Once activated, APCs recruit T cells into the vicinity of the tumor to deliver a potent anti-tumor immune response. Akamis Bio has evaluated NG-350A’s safety, tolerability, and preliminary efficacy as a monotherapy (FORTITUDE study) and in combination with pembrolizumab (FORTIFY study) in patients with metastatic or advanced epithelial tumors. Across these studies, NG-350A has demonstrated a consistent safety and tolerability profile, as well as strong evidence of tumor-selective delivery, replication and transgene expression.

About the FORTRESS Study
The Phase 1b FORTRESS study (NCT06459869) is an open-label, single-arm, and multicenter trial of NG-350A in combination with chemoradiotherapy (CRT) in adult patients with mismatch repair-proficient (pMMR) locally advanced rectal cancer (LARC) and at least one risk factor for local or distant recurrence or with oligometastatic disease. The FORTRESS study builds upon the Akamis Bio-supported CEDAR study which showed a significantly greater composite response rate in LARC patients treated with a combination of Akamis Bio’s first generation oncolytic immunotherapy (EnAd) and chemoradiotherapy (CRT), relative to expected outcomes using standard-of-care CRT alone. The FORTRESS study is planning to enroll approximately 30 patients aged eighteen and older with histologically confirmed adenocarcinoma of the rectum which is locally advanced (clinical stage II-III based on pelvic MRI). During the 12-week active treatment period, patients will receive NG-350A plus CRT (oral capecitabine plus long-course intensity-modulated radiotherapy). The primary endpoint of the FORTRESS study is the composite response rate defined as the proportion of patients achieving a clinical complete response (cCR) or a near clinical complete response (ncCR) at 12 weeks. Key secondary endpoints include the incidence and severity of adverse events, characterization of the anti-tumor effects of NG-350A in combination with CRT (including clinical response outcome and magnetic resonance tumor reduction grade [mrTRG]), and measurement of levels of circulating tumor DNA (ctDNA) clearance. The FORTRESS study continues to enroll pMMR LARC patients with recruitment expected to conclude in 2H 2026. Patients recently diagnosed with pMMR LARC interested in learning more about the FORTRESS trial can visit www.FortressStudy.org.

About Locally Advanced Rectal Cancer (LARC)
Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States, and it has recently emerged as the leading cause in patients under 50 years of age. There are 159,000 people newly diagnosed with CRC each year, with about 53,000 of those people diagnosed specifically with rectal cancer of which approximately 30,000 are diagnosed with LARC. LARC is defined by the spread of rectal cancer to nearby tissues or lymph nodes. In patients with LARC, tumors have either grown through muscle and into the outermost layers of the rectum, or in more severe cases, through the wall of the rectum where they may attach to other organs or structures and/or into the lymph nodes. Approximately 95 percent of LARC patients have mismatch repair-proficient (pMMR) tumors which have a functional DNA repair system.

About Akamis Bio
Headquartered in Cambridge, Massachusetts, Akamis Bio is a clinical-stage oncology company developing systemically administered oncolytic immunotherapies to treat colorectal cancer, with an initial focus on locally advanced rectal cancer (LARC). Its proprietary Tumor-Specific Immuno-Gene Therapy (T-SIGn®) platform is designed to deliver novel immunotherapeutic proteins, biomolecules and transgene combinations to treat solid tumors, with its lead clinical-stage program, NG-350A, driving intratumoral expression of a CD40 agonist monoclonal antibody. To learn more, please visit www.akamisbio.com.