IM Therapeutics is developing personalized immuno-therapeutic drugs for autoimmune diseases based on the genetic risk attributed by human leukocyte antigen genes. The lead candidate drug is an oral small molecule that starves the autoimmune process in type 1 diabetes by blocking DQ8 on specific immune cells. Our goal is to preserve pancreatic beta cell function and maintain normal insulin production in at-risk and early-stage patients with type 1 diabetes.
1.25M Americans are living with T1D including about 200,000 youth (less than 20 years old) and over a million adults (20 years old and older)¹,²,³
40,000 people are diagnosed with T1D each year in the U.S.¹,²
INSULIN IS NOT A CURE
While insulin injections or infusion allow a person with T1D to stay alive, they do not cure the disease, nor do they necessarily prevent the possibility of the disease’s serious effects, which may include: kidney failure, blindness, nerve damage, heart attack, stroke, and pregnancy complications.⁴
Autoimmune disease is promoted when the immune system becomes “intolerant” of self-tissues such that it attacks specific cells of the respective disease, for example, the insulin-producing cells of the pancreas in Type 1 Diabetes (T1D).
The antigen-presenting cells (APCs) of the immune system normally maintain immune tolerance by presenting specific parts of self-tissues, termed self-antigens (autoantigens), on their surface to harmful autoreactive immune cells to induce their death or to generate protective immune cells.
These APCs do not simply place autoantigens anywhere on their surface, but rather use special “platter” molecules, termed Human Leukocyte Antigen (HLA) class II, to make the autoantigen recognizable (palatable) to such harmful or protective immune cells. However, because HLA molecules arise from genes that are slightly different among individuals (i.e., alleles), some HLA alleles function in an abnormal way to “mis-present” autoantigens that leads to autoimmune diseases. The HLA-DQ8 allele is one such gene known to predispose for T1D by mis-presenting autoantigens that favors the generation and function of harmful immune cells. It occurs in 50 – 60% of all Type 1 diabetes patients and is easily identified by established genetic screening techniques.
IMT’s approach to T1D is to develop a small molecule drug that effectively starves the autoimmune process by blocking the peptide binding groove on the HLA-DQ8 gene. Our lead drug, IMT-002, occupies this peptide binding groove of DQ8 on the surface of APCs to block the binding of proinsulin or insulin and presentation to CD4 T-lymphocytes. When HLA-DQ8 function is inhibited, the immune system will no longer attack insulin producing beta-cells, thus creating the potential for at risk or early stage patients to maintain normal insulin production.
Advantages of IMT’s approach:
- A personalized medicine that blocks the autoimmune response at its earliest initiation
- An easy, safe and convenient once-a-day drug
- Does not interfere with other normal immune responses such as infections
- Preserves insulin production in the pancreas
Ostrov DA, Alkanani A, McDaniel KA, Case S, Baschal EE, Pyle L, Ellis S, Pöllinger B, Seidl KJ, Shah VN, Garg SK, Atkinson MA, Gottlieb PA, Michels AW. Methyldopa blocks MHC class II binding to disease-specific antigens in autoimmune diabetes . J Clin Invest 2018 Feb; 128(5):1888-1902
Michels AW, Gottlieb GS. Learning From Past Failures of Oral Insulin Trials. Diabetes
Atkinson MA, Eisenbarth GS, Michels AW. Type 1 Diabetes. Lancet 2014; 383: 69-82
Simmons KM, Gottlieb PA, Michels AW. Immune Intervention and Preservation of Pancreatic Beta Cell Function in Type 1 Diabetes. Current Diabetes Reports 2016 Oct; 16(10):97 (subscription required)
Michels AW, Ostrov DA, Zhang L, Nakayama M, Fuse M, McDaniel K, Roep BO, Gottlieb PA, Atkinson MA, Eisenbart GS. Structure-based selection of small molecules to alter allelespecific MHC class II antigen presentation J Immunol. 2011 December 1; 187(11): 5921-5930
Gough SCL, Simmonds MJ. The HLA Region and Autoimmune Disease: Associations and Mechanisms of Action. Current Genomics 2007 Nov; 8(7): 453-465
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