CAL101 treatment for scarring safe, well tolerated in Phase 1 trial

Developer planning to launch Phase 2 trials in fibrotic diseases in 2025
by Patricia Inácio, PhD | October 29, 2024

CAL101, a therapy candidate for fibrosis (scarring) in scleroderma and related disorders, was found to be safe and well tolerated in a Phase 1 clinical trial, according to new data from the study.

Developed by Calluna Pharma, CAL101 is a first-in-class antibody that targets S100A4, a protein previously associated with SSc and idiopathic, or of unknown cause, pulmonary fibrosis.

Calluna expects to test the investigational therapy in Phase 2 trials of fibrotic and fibrotic-inflammatory-related disorders in 2025, the company said in a press release.
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“We are encouraged by the findings from the Phase 1 study. These results are an important step forward in the development of our lead asset, CAL101, particularly for fibrotic and fibro-inflammatory diseases where there remains a critical need for innovative therapeutic options,” said Jonas Hallén, MD, PhD, co-founder and chief medical officer of Calluna. “We are excited as we now move into the next phase of clinical development.”

​CAL101 may target fibroblasts that contribute to fibrosis
Cells in damaged tissues release molecules — called damage-associated molecular patterns, or DAMPs — as a way of activating the immune system and pro-inflammatory pathways. Several DAMPs have been reported to be involved in SSc.

A previous study last year showed that the blood levels of one of the proteins in this family, called S100A4, are increased in individuals with SSc compared with healthy people.

According to Calluna, preclinical studies suggest that CAL101 may prevent fibrosis by targeting fibroblasts, which are cells found in connective tissue that contribute to fibrosis.

This Phase 1 trial first tested single ascending doses of CAL101 or a placebo in healthy volunteers. That was followed by tests of multiple ascending doses of the therapy in patients with mild to moderate chronic plaque psoriasis, an inflammatory skin disorder marked by red, thickened patches of skin.

The study’s main goal was to assess CAL101’s safety and tolerability, as well as its immunogenicity — its ability to provoke an immune response — and pharmacokinetics. Pharmacokinetics is the movement of a medicine into, through, and out of the body.

The complete results showed that CAL101 was well tolerated, with adverse events of mild to moderate severity. No serious adverse events were reported across any of the doses tested.

Pharmacokinetics analyses showed a dose-dependent increase in the levels of CAL101, which supports the therapy’s monthly dosing schedule, according to the company. CAL101 also was able to target S100A4 at clinically relevant doses.
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In participants with antibodies against the therapy, those levels were deemed very low and with no impact on CAL101’s pharmacokinetics or safety profile.