Kupando has dosed the first patient in a Phase 1 study of KUP101, a dual TLR4 and TLR7 agonist being developed for advanced solid tumours.

KUP101 enters clinical development

The first patient dosing marks the transition of KUP101 from preclinical development into human testing, with the Phase 1 study evaluating the candidate in patients with selected advanced solid tumours.

The registered trial is designed primarily to assess the safety and tolerability of KUP101, alongside pharmacokinetic and pharmacodynamic measures and early signals of efficacy. The study plans to enrol 21 patients and is being conducted at clinical centres in Germany. The cancers being studied include cutaneous melanoma, mucosal melanoma, cutaneous squamous cell carcinoma, Merkel cell carcinoma and basal cell carcinoma.

Following administration to the first patient, Kupando said its safety committee reviewed the initial dosing and approved continued enrolment across the activated sites.

Johanna Holldack, founder and chief executive officer of Kupando, said: “Dosing our first patient is a defining inflection point in Kupando’s history. By leveraging the power of innate immune stimulation and the induction of trained immunity, KUP101 represents a fundamentally different way of approaching hard-to-treat cancers.”

Dual TLR4 and TLR7 approach targets innate immunity

KUP101 is designed to activate Toll-like receptor 4 (TLR4) and Toll-like receptor 7 (TLR7), which are involved in innate immune responses.

Rather than directly targeting a tumour-specific mutation, the approach is intended to stimulate immune cells within the tumour microenvironment. Kupando is developing KUP101 as a tissue-agnostic approach, meaning its potential activity is intended to extend across different tumour types rather than depend on a specific cancer mutation.

The company is also investigating the concept of trained immunity, in which innate immune cells undergo functional changes that can alter their response to subsequent challenges.

Kupando’s preclinical work has examined KUP101 both as a single agent and in combination with immune checkpoint inhibitors. The company has reported additive and synergistic effects in preclinical models, providing a rationale for exploring whether innate immune stimulation could complement existing immunotherapies.

However, those findings have not yet been demonstrated in patients. The newly initiated Phase 1 study is primarily designed to establish the safety, tolerability and appropriate dosing of KUP101 before its potential development in later-stage trials.

Kupando expands pipeline beyond oncology

The company is also developing its dual TLR agonist platform for infectious diseases, with a particular focus on antimicrobial resistance (AMR).

Kupando’s approach in infectious disease is based on stimulating the host immune response rather than directly targeting individual pathogens. The company is investigating whether activation of innate and trained immunity could provide a pathogen-agnostic approach to treating or preventing infections.

For now, however, KUP101’s move into Phase 1 represents the company’s most advanced clinical programme.

The trial is expected to provide the first human safety and pharmacological data for the candidate, with the study designed to establish a recommended Phase 2 dose while assessing changes in cytokine levels and other pharmacodynamic measures.

The transition into clinical testing gives Kupando an opportunity to determine whether its dual TLR4/7 approach can translate the immune responses observed in preclinical research into a viable treatment strategy for patients with advanced cancers.