-Akamis Bio, a clinical-stage oncology company working to advance the standard of care in colorectal cancer, 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.”