CAMBRIDGE, Mass.—Idera Pharmaceuticals Inc., a clinical-stage biotechnology company developing novel therapeutics for orphan patient populations with B-cell lymphomas and autoimmune diseases, has entered into an agreement with Abbott Laboratories for the latter to develop an in-vitro companion diagnostic test for use in Idera’s clinical development programs to treat certain genetically defined forms of B-cell lymphoma with IMO-8400.
Under the agreement, Abbott will develop a test utilizing polymerase chain reaction technology to identify the presence of the MYD88 L265P oncogenic mutation in tumor biopsy samples with high sensitivity and specificity. This mutation, which can be identified in approximately 90 percent of patients with Waldenström’s macroglobulinemia and approximately 30 percent of patients with the ABC sub-type of diffuse large B-cell lymphoma, plays a key role in activating the Toll-like receptor (TLR) pathways targeted by Idera’s lead drug candidate, IMO-8400.
“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,” said Dr. Lou Brenner, senior vice president and chief medical officer of Idera Pharmaceuticals, in the news release about the deal. “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.”
“Idera's mission is to develop novel drugs to treat orphan diseases based on our pioneering work in the design of targeted nucleic acid therapeutics,” Idera CEO and President Dr. Sudhir Agrawal tells DDNews. “Our proprietary oligonucleotide drug discovery platforms are targeted to inhibit Toll-like receptors and silence disease-causing genes.”
IMO-8400 is a first-in-class synthetic oligonucleotide-based antagonist of TLRs 7, 8 and 9. In April 2014, Idera presented preclinical data at the American Association for Cancer Research’s annual meeting demonstrating the ability of IMO-8400 to inhibit the survival and proliferation of human B-cell lymphoma cells harboring the oncogenic MYD88 L265P genetic mutation. IMO-8400 also has shown activity in preclinical studies of autoimmune diseases, including psoriasis, lupus and arthritis. IMO-8400 has been well-tolerated in a Phase 1 trial in 42 healthy subjects at single and multiple escalating doses up to 0.6 mg/kg for four weeks, and has shown inhibition of immune responses mediated by TLRs 7, 8, and 9. In March 2014, Idera announced top-line data from an ongoing Phase 2 trial that showed evidence of clinical activity in patients with psoriasis who were treated with IMO-8400 at doses of up to 0.3 mg/kg/week for 12 weeks. Idera is pursuing clinical development of IMO-8400 in genetically defined forms of B-cell lymphoma, including Waldenström’s macroglobulinemia and diffuse large B-cell lymphoma, and in orphan autoimmune diseases, including polymyositis and dermatomyositis.
In addition to its TLR programs, Idera is developing gene-silencing oligonucleotides that it has created using its proprietary technology to inhibit the production of disease-associated proteins by targeting RNA.
“Our Phase 1/2 trial in patients with Waldenström’s macroglobulinemia, who have relapsed or were refractory to prior therapy, is ongoing,” notes Agrawal. “We are also preparing a Phase 1/2 trial of the compound in diffuse large B-cell lymphoma, or DLBCL, and expect to begin enrollment in the trial in the second half of this year. In both of these diseases, patients have significant unmet medical needs and limited treatment options. IMO-8400 has the potential to offer a novel, targeted approach to address this unmet need.
“In the area of rare automimmune disease, we expect to initiate Phase 2 studies of IMO-8400 in polymyositis and dermatomyositis as well as graft versus host disease in the second half of 2014. In all three of these orphan autoimmune diseases, patients experience severe and life-threatening complications, and the overactivation of TLRs is implicated in the disease pathogenesis,” Agrawal concludes.