Zealand Reports Positive Multiple-Dose Safety Results for Kv1.3 Blocker ZP9830

Zealand Pharma reported positive topline results from the multiple ascending dose (MAD) part of its first-in-human Phase 1 trial of ZP9830, an investigational immunomodulator targeting the Kv1.3 potassium ion channel. The randomized, double-blind, placebo-controlled study evaluated the safety, tolerability and pharmacokinetics of repeated dosing in 32 healthy male and female participants.

Participants received multiple doses over four weeks, followed by safety monitoring through Day 41. All treatment-emergent adverse events among participants receiving ZP9830 were non-serious and mild. Investigators observed no dose-limiting safety findings or other significant safety concerns.

Vital signs, 12-lead electrocardiograms, physical examinations and safety laboratory assessments showed no clinically relevant safety findings. Pharmacokinetic results also supported continued investigation in studies with longer treatment durations.

Although these findings establish an encouraging initial safety profile, the trial did not assess clinical efficacy in patients with autoimmune disease. The results therefore do not establish whether ZP9830 can improve disease activity or produce sustained clinical benefits.

Kv1.3 Blockade Offers a Targeted Approach to Autoimmune Disease

ZP9830 is a potent, selective blocker of the Kv1.3 potassium ion channel, which is upregulated on effector memory T cells. These immune cells contribute to autoimmune and chronic inflammatory diseases by releasing pro-inflammatory cytokines that can damage tissues.

Blocking Kv1.3 may reduce the activity of these disease-driving T cells while preserving other immune functions. Preclinical models of immunological disorders have demonstrated anti-inflammatory effects following Kv1.3 channel inhibition, supporting further investigation of the target.

However, whether this selectivity translates into meaningful clinical benefits and an acceptable long-term safety profile remains to be established in human studies.

The approach could potentially support development across multiple immune-mediated inflammatory diseases, although each indication will require clinical evidence demonstrating efficacy and safety.

Phase 1b Psoriasis Trial Advances Clinical Development

Zealand Pharma has already initiated a Phase 1b trial evaluating ZP9830 in people with plaque psoriasis. Unlike the healthy-volunteer Phase 1 study, this trial includes efficacy endpoints and will provide an early assessment of the drug’s therapeutic activity in a patient population.

The company initiated the Phase 1b study following positive topline results from the single ascending dose (SAD) portion of the combined Phase 1a program.

The broader first-in-human study, registered under ClinicalTrials.gov identifier NCT06682975, evaluated single and multiple ascending subcutaneous doses, as well as a single intravenous dose at one dose level. Its objectives included safety, tolerability and pharmacokinetic assessments, alongside an exploratory proof-of-mechanism evaluation.

The SAD component included a pharmacological model to investigate immunomodulatory activity and provide early evidence of the drug’s intended effects on immune-cell biology. The MAD component is now complete, although the overall study continues to evaluate an additional single dose of ZP9830.

Phase 2 Expansion Planned for 2027

David Kendall, MD, Zealand Pharma’s chief medical officer, said the MAD findings support continued development in longer-duration studies. The company plans to initiate a Phase 2 trial in an additional autoimmune disease in the first half of 2027.

The next development milestones will be important for determining whether ZP9830 can translate its favorable initial safety profile and targeted mechanism into clinically meaningful improvements in autoimmune disease.

For now, the Phase 1 results provide early support for further testing, while efficacy, longer-term tolerability and the potential to treat multiple indications remain key questions for the program.

Reference

Zealand Pharma announces positive topline results from the multiple ascending dose part of Phase 1 trial with Kv1.3 ion channel blocker ZP9830, Zealand Pharma, 19 October 2026

A Research Study Looking at the Safety of Single and Multiple Doses of ZP9830 and How it Works in the Body of Healthy Participants, ClinicalTrials.gov ID NCT06682975