US-based Idera Pharmaceuticals and Abbott have entered into an agreement to develop an in-vitro companion diagnostic test for use in Idera's clinical development programs for the treatment of certain genetically defined forms of B-cell lymphoma with its lead drug candidate IMO-8400.
As part of the deal, Abbott will be responsible for developing 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.
Idera said that 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.
The mutation plays a major 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 company reported that the TLR antagonist drug candidates have been created using a proprietary chemistry-based drug discovery platform.
In April 2014, the company reported preclinical data at the American Association for Cancer Research Annual Meeting, showing 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 has also shown activity in preclinical studies of autoimmune diseases including psoriasis, lupus and arthritis.
In a Phase I trial carried out in 42 healthy subjects at single and multiple escalating doses up to 0.6mg/kg for four weeks, IMO-8400 has been well-tolerated as well as shown inhibition of immune responses mediated by TLRs 7, 8, and 9.