IM Therapeutics, a clinical-stage company developing first-in-class human leukocyte antigen (HLA)-targeted therapies to treat autoimmune diseases, today announced positive results on safety, tolerability, pharmacokinetics (PK) and mechanistic action in a Phase 1b study of IMT-002 in patients with type 1 diabetes (T1D). The study, a first for the industry, was performed in patients who have a specific genetic trait known as HLA-DQ8, which significantly increases the risk for T1D and is present in the majority of patients. Certain isoforms of genes called HLAs are known to play a strong role in activating autoimmunity in a broad range of autoimmune diseases. IMT-002 is designed to block the HLA-DQ8 isoform and offers the potential for a first-in-class, genetically targeted, orally available medicine to slow down onset or progression of life-threatening T1D.
“We are pleased with the timely completion of the IMT-002 Phase 1b study and the favorable findings on safety and tolerability, the primary study endpoints, in patients with T1D,” said Sarah Bird, Ph.D., Vice President, Clinical Development of IM Therapeutics. “It is also very encouraging that PK profiles and PD readouts have met our expectations as we finalize and execute our plan for an upcoming Phase 2 clinical study.”
The single-blinded Phase 1b Multiple Ascending Dose (MAD) trial enrolled 30 T1D patients preselected for HLA-DQ8 between the ages of 18 and 45 into four groups. Each group had six subjects receiving doses of IMT-002 between 350 mg and 1050 mg administered as a once-daily or twice-daily regimen over a two-week duration. Six people received placebo and were interspersed in the four groups. The study assessed drug versus placebo for safety, tolerability, PK profiles and pharmacodynamic (PD) activity over the two-week duration of dosing and a one-week follow-up after dose completion. The PD activity measured the ability of IMT-002 to block presentation by HLA-DQ8 of “self-antigens” or the body’s own proteins, such as insulin or gliadin, a gluten peptide, that are known to activate autoimmunity.
Results of the Phase 1b study showed that IMT-002 was safe and well-tolerated. There were no serious adverse events (SAEs) and adverse events were similar between placebo and treatment and did not increase with dose. PK profiles were followed for a once-daily dose (1050mg) and three twice-daily doses (350mg, 700mg, 1050mg) over a 24-hour period after drug administration. IMT-002 showed increasing maximum concentrations (Cmax) at four hours after dose for the twice-daily regimens and proportionally higher trough-level concentrations (Ctrough) while the once-daily dose showed the lowest Cmax and Ctrough.
In addition, the drug demonstrated mechanism of action as engagement with HLA-DQ8 in an ex vivo cell-based assay to assess inhibition of self-peptide presentation (insulin and gliadin as autoantigens for T1D and celiac disease, respectively). In the assay, peripheral blood-derived mononuclear cells (PBMCs) derived from a patient’s blood sample served as antigen-presenting cells to engineered T cells and provided an immunological readout when stimulated by a specific antigen. Inhibition by the drug of both self-peptides, insulin and gliadin, was observed to be significant when compared to placebo samples or when compared to inhibition of a T cell response to representative pathogenic antigens.
“With this important clinical milestone demonstrating safety and novel mechanism of our first lead drug, our team is focused on advancing IMT-002 into Phase 2 and accelerating additional programs to the clinic,” said Nandan Padukone, Ph.D., CEO of IM Therapeutics. “The scientific community has shown a very positive reception to the Company’s approach of tailoring drugs to switch off HLA isoforms as the earliest triggers of autoimmune disease. With our HLA-directed development pipeline, we hope to benefit patients by advancing a personalized medicine approach for autoimmunity across a range of diseases.”
IMT-002, the lead drug candidate of IM Therapeutics, is the first oral genetically targeted drug candidate to be tested in patients with T1D, an incurable autoimmune disorder that affects 1.6 million people in the United States and more than 18 million people worldwide. IMT-002 completed a Phase 1a study in 2020 and has completed a Phase 1b study in T1D patients preselected for the HLA-DQ8 isoform. IMT-002 is designed to block HLA-DQ8 to prevent the immune system from attacking insulin-producing beta cells, thereby preserving function in newly diagnosed patients, and is being investigated as a once- or twice-daily drug candidate.
About IM Therapeutics
IM Therapeutics is a clinical-stage company pioneering personalized, oral medicines that target human leukocyte antigen (HLA) isoforms to treat the root cause of autoimmune diseases. The Company’s IMT-HALT platform enables the development of small molecule drugs using in silico docking of millions of compounds into pockets of an HLA isoform where self-antigens may bind to trigger autoimmunity. Selected drug hits are then optimized using proprietary structure-based design and activity screening with cell-based assays for specificity of HLA inhibition. Lead drugs developed against an HLA isoform have the ability to block a series of self-antigens and therefore the potential to treat a range of autoimmune diseases related to a selected HLA. The Company is building a broad HLA-targeted pipeline in autoimmune disorders including type 1 diabetes, celiac disease, and lupus. Learn more at www.IMTherapeutics.com.