Idera Pharmaceuticals has entered into an agreement with Abbott to develop an in-vitro companion diagnostic test for use in Idera’s clinical development programmes to treat certain genetically defined forms of B-cell lymphoma with its lead drug candidate IMO-8400.
Under the terms of agreement, Abbott will develop a test using polymerase chain reaction (PCR) technology to identify the presence of the MYD88 L265P oncogenic mutation in tumour biopsy samples with high sensitivity and specificity.
According to Idera, this mutation can be identified in approximately 90% of patients with Waldenström’s macroglobulinemia and around 30% of patients with the ABC sub-type of diffuse large B-cell lymphoma.
This mutation plays a key role in activating the toll-like receptor (TLR) pathways targeted by IMO-8400, a first-in-class synthetic oligonucleotide-based antagonist of TLRs 7, 8, and 9.
The TLR antagonist drug candidates have been created using a proprietary chemistry-based drug discovery platform, the company reported.
In April, the company unveiled preclinical data at the American Association for Cancer Research Annual Meeting, demonstrating the ability of IMO-8400 to inhibit the survival and proliferation of human B-cell lymphoma cells harbouring the oncogenic MYD88 L265P genetic mutation.
IMO-8400 also has shown activity in preclinical studies of autoimmune diseases, including psoriasis, lupus, and arthritis. It has been well-tolerated in a Phase I trial in 42 healthy subjects at single and multiple escalating doses up to 0.6mg/kg for four weeks, and has shown inhibition of immune responses mediated by TLRs 7, 8, and 9.
In March, Idera announced top-line data from an ongoing Phase II trial that showed evidence of clinical activity in patients with psoriasis who were treated with IMO-8400 at doses of up to 0.3mg/kg/week for 12 weeks.
Idera Pharmaceuticals senior vice-president and chief medical officer Dr Lou Brenner said research by Idera and by independent investigators has established TLR antagonism as a potentially promising and novel therapeutic approach for patients with B-cell malignancies harboring the MYD88 L265P mutation.
"This companion diagnostic will be an important tool for the clinical community in evaluating whether their patients are potential candidates for IMO-8400 therapy for the treatment of these genetically defined forms of B-cell lymphoma," Dr Brenner said.
"We are excited about the opportunity to partner with Abbott, a leader in companion diagnostics, as part of Idera’s mutation-targeted development programme for IMO-8400 in B-cell lymphomas."
Image: Micrograph of a large B cell lymphoma. Photo: courtesy of Nephron.