Kardigan Extends Phase 2 Ataciguat Trial Assessment, Targets 2027 Results

Key Points

• Kardigan’s fully enrolled phase 2 KATALYST-AV trial will assess its primary endpoint—change in aortic valve calcium—at 48 weeks instead of 24 weeks, with top-line results expected in the second half of 2027. The 24-week point will be an interim analysis, but the company does not expect to release data then.
• The extended assessment is intended to evaluate valve calcium alongside valve area and heart-function measures, helping guide the phase 3 trial’s patient population, duration and endpoints. Kardigan expects to share more about phase 3 planning in the first half of 2027; ataciguat’s potential benefit remains unproven.
• A real-world analysis found that 27% of patients with mild-to-moderate aortic stenosis were fast progressors. Compared with normal progressors, they had 3.1 times the risk of valve replacement or repair and 1.5 times the risk of acute all-cause hospitalization.

Kardigan NASDAQ: KARD said its phase 2 trial of investigational drug ataciguat in aortic stenosis is fully enrolled and that it will assess the study’s primary endpoint at 48 weeks, rather than 24 weeks. Top-line results are expected in the second half of 2027.

The KATALYST-AV trial’s primary endpoint remains the change in aortic valve calcium. Cheryl Abrams, Kardigan’s global product head for ataciguat, said the longer observation period will allow the company to interpret calcium changes alongside changes in aortic valve area and measures of heart function.

Ataciguat is being studied as a potential treatment to slow progression of aortic stenosis, a narrowing of the aortic valve. CEO Tassos Gianakakos said there is no approved medicine for the condition and that patients currently wait until the valve is sufficiently impaired to be replaced.

Trial readout and phase 3 planning

Abrams said the 24-week assessment will become a planned interim analysis. The company will examine trends in valve calcium, valve area and ventricular function, but Gianakakos said investors should not expect data at that point. He said Kardigan would provide qualitative updates on how the findings inform its registrational program.

The changes were made while the study remained blinded and were not based on efficacy results, Abrams said. She added that the trial’s statistical assumptions and targeted effect size had not changed. Kardigan expects the placebo group’s valve calcium to increase by about 20% from baseline to week 48, consistent with published literature, she said.

Aortic valve area is a key secondary endpoint, but the phase 2 trial is not powered to establish an effect on that measure, Abrams said. She described valve area as a potential endpoint for a future registrational trial. The study also includes a substudy measuring peak oxygen consumption, a measure of functional capacity that could inform phase 3 planning.

Kardigan expects to share more about its phase 3 registrational trial in the first half of 2027. Abrams said the phase 2 findings could help determine the later trial’s patient population, duration and endpoints.

Real-world analysis identifies faster progression

Dr. Sreekanth Vemulapalli, associate professor of medicine and medical director of the Echo Lab at Duke, presented a real-world analysis drawn from multiple health systems. Researchers identified an analysis population of about 45,000 patients with mild, moderate or discordant aortic stenosis; approximately 20,000 had enough echocardiogram data within two years to assess annual progression.

Using definitions from published literature, the analysis found that 27% of patients with mild to moderate disease were fast progressors. Vemulapalli said those patients had 3.1 times the risk of valve replacement or repair and 1.5 times the risk of acute all-cause hospitalization compared with normal progressors.

About 80% of patients in the mild-to-moderate cohort had cardiac dysfunction as defined in the analysis. Fast progression was more prevalent among patients with cardiac damage than among those without it, at 28% versus 19%, Vemulapalli said. He also cautioned that the two were related but distinct: some patients without cardiac damage progressed rapidly, while some slower progressors had cardiac dysfunction.

Measuring effects on the valve and heart

Professor Philippe Pibarot of the Quebec Heart and Lung Institute said KATALYST-AV baseline data showed that patients with similar valve areas could have markedly different calcium burdens. He described valve calcium as an independent marker of clinical risk and said valve area and ventricular measures provide additional information.

Pibarot said ataciguat may have effects on both the valve and the heart muscle, but those potential effects remain under investigation. He argued that aortic valve area could be a useful measure for a drug targeting both pathways because changes in blood flow can complicate interpretation of other commonly used measures.

Gianakakos said the baseline and real-world analyses would help Kardigan identify patients more likely to progress rapidly and refine its phase 3 design. Any benefit from ataciguat remains to be established in the company’s clinical trials.

About Kardigan (NASDAQ:KARD)

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