Rigel Pharmaceuticals has dosed the first subject in its Phase Ib clinical trial of investigational therapy R289 to treat lower-risk myelodysplastic syndrome (MDS) patients who are refractory or resistant to previous therapies.

The open-label trial will enrol nearly 22 such patients. The safety of R289 is its primary objective.

Evaluating the initial efficacy and characterising the pharmacokinetic (PK) and pharmacodynamic (PD) profile of the therapy are the trial’s secondary and exploratory objectives. 

The company plans to use the safety and efficacy findings from this trial, as well as the safety and PK/PD results from the concluded first-in-human trial in healthy subjects, to identify the recommended Phase II dose to progress further clinical development of R289 for lower-risk MDS. 

An R835 prodrug, R289 is an oral, dual inhibitor of interleukin receptor-associated kinases 1 and 4 (IRAK1/4).

It was demonstrated to hinder inflammatory cytokine production against toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) family signalling in preclinical studies. 

Rigel chief medical officer Wolfgang Dummer said: “R289’s dual inhibition of IRAK1 and IRAK4 has the potential to provide a more robust suppression of the pro-inflammatory environment that causes lower-risk MDS by blocking inflammatory cytokine production. 

“The initiation of our Phase Ib study demonstrates our continued ability and commitment to bringing innovative, investigational candidates for haematology-oncology indications into the clinic. 

“We believe R289 may represent a promising new approach to treating patients with lower-risk MDS and look forward to investigating R289 further in this Phase Ib study.”

In November this year, the company reported top-line findings from the Phase III FOCUS trial of fostamatinib in hospitalised Covid-19 patients.

The double-blind, multicentre, placebo-controlled trial enrolled 280 such patients without respiratory failure, but had some high-risk prognostic factors.