AskBio’s Heart Failure Gene Therapy AB-1002 Shows Ability to Improve NYHA Class in Phase 1 Trial

AskBio’s AB-1002, an investigational adeno-associated virus (AAV) vector-based gene therapy, has demonstrated the ability to improve New York Heart Association (NYHA) class in patients with NYHA class III nonischemic heart failure with reduced ejection fraction (HFrEF) who were treated in the phase 1 NAN-CS101 clinical trial (NCT04179643).^1,2 The 12-month data from the trial were published in Nature Medicine.

According to the Nature Medicine paper, NAN-CS101 treated 6 patients with a dose of 3.25 × 10¹³ viral genomes of AB-1002 (cohort 1) and 5 patients with 1.08 × 10¹⁴ viral genomes of AB-1002 (cohort 2). The study population was composed of 9 men and 2 women. It was reported that 2 of 3 patients in cohort 1 with available data achieved NYHA class II as of 3 months posttreatment and 5 of 6 patients had achieved NYHA class I or II as of 6 months posttreatment, with these changes being maintained at 12 months posttreatment. For the 4 patients in cohort 2 who remained alive at 12 months posttreatment, 2 had achieved NYHA class II as of 3 months posttreatment and maintained this change at 12 months; the other 2 patients in the cohort showed no changes in NYHA class at any time point. In addition to the NYHA class improvements, the Nature Medicine paper notes that improvements in left ventricular ejection fraction were seen among patients in both cohorts and that in cohort 1 improvements in peak oxygen consumption and 6-min walk test performance were observed.

In terms of safety, there were no adverse events (AEs) or serious AEs deemed related to AB-1002 and most AEs that occurred were deemed mild or moderate with respect to severity. In some patients, primarily in cohort 2, self-limiting, mild, asymptomatic elevations in liver enzymes were reported. It was noted that 1 patient died while participating in the study, but the death was not deemed related to the treatment.

“We believe there is a critical need to progress innovative therapies that target the root causes of congestive heart failure, so we’re pleased to see these data for AB-1002 published and shared with the scientific community via Nature Medicine, a high-impact peer-reviewed journal,” Canwen Jiang, MD, PhD, the chief development officer and chief medical officer at AskBio, said in a statement.¹ ”We’re eager to further assess the safety and efficacy of AB-1002 in our ongoing phase 2 trial, GenePHIT (NCT05598333), which is currently enrolling in Canada, Europe, the United Kingdom, and the United States, and look forward to sharing those results once available.”

GenePHIT takes the form of an adaptive, randomized, double-blind, placebo-controlled study. It includes 46 study sites in countries including the US, Austria, Germany, the Netherlands, Spain, and the UK.

CGTLive® previously spoke to Luke Roberts, MBBS, PhD, the medical director of Clinical Development at AskBio, at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland, about the challenges of evaluating AB-1002 in the NAN-CS101 study.³ Roberts noted the breadth of the indication and discussed details on the patient who died on-study.

“One thing that's really interested me is the different approaches that people are taking to AAV therapy,” Roberts told CGTLive. “I think AB-1002 is quite unique because we're looking at a really big indication rather than the sort of ultra rare diseases that many investigators are focused on. So, for me, it's been quite interesting to see the sheer breadth of conditions that are being presented here.”

REFERENCES
1. AskBio announces publication in Nature Medicine of 12-month data from phase 1 trial of AB-1002 gene therapy in participants with congestive heart failure. News release. AskBio Inc. October 21, 2025. Accessed October 22, 2025. https://www.askbio.com/askbio-announces-publication-in-nature-medicine-of-12-month-data-from-phase-1-trial-of-ab-1002-gene-therapy-in-participants-with-congestive-heart-failure/
2. Henry TD, Chung ES, Alvisi M, et al. Cardiotropic AAV gene therapy for heart failure: a phase 1 trial. Nat Med. Published online October 21, 2025. doi: 10.1038/s41591-025-04011-z
3. Roberts L, Henry T, Chung E, et al. Safety and Efficacy of AB-1002 Gene Therapy in Patients with Advanced Heart Failure: Results from an Ongoing Phase 1 Clinical Trial. Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland. Abstract #9