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Precision Therapy for Diabetes
Company Profile
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Islex Therapeutics, a biotechnology startup spun off from Johns Hopkins University, is dedicated to developing precision therapies for patients with type 1 diabetes, latent autoimmune diabetes in adults (LADA) and severe type 2 diabetes. The commonality among these insulin-dependent diabetes lies in the destruction of beta cells in the pancreatic islets, the sole source of insulin production in the body. Islex Therapeutics is a pioneer in the development of the world's only drug delivery platform specifically designed for targeted beta cell therapies. This groundbreaking platform is anchored in the discovery of an islet-specific cell-surface autoantigen, ZnT8. By harnessing the natural islet-homing ability of a cell-surface ZnT8 autoantibody, Islex Therapeutics re-engineers it to guide antibody-conjugated therapeutics to islets, enhancing drug efficacy within the islet microenvironment while minimizing off-target toxicity. Currently, the company is focused on preclinical development of islet-targeted immunoregulatory and regenerative therapeutics on a proprietary drug delivery platform, validating therapeutic candidates for future clinical testing.
Unmet medical needs
Diabetes encompasses a spectrum of metabolic disorders from type 1 diabetes (T1D) to type 2 diabetes (T2D). Irrespective of their diverse etiologies, late-stage diabetes is characterized by a severe loss of the insulin producing β-cells.
The current last-resort treatment for diabetes, pancreas transplantation, faces limitations due to the scarcity of donor organs and the necessity for immunosuppression. Emerging treatments involve stem cell transplants, pharmacotherapies targeting β-cell regeneration and artificial pancreas systems.
However, these approaches encounter challenges such as the risk of abnormal cell growth, off-target toxicity, a lack of durable efficacy, and the need for refining blood sugar control.
The quest for safe and effective treatments for late-stage diabetes remains a formidable undertaking.
Solutions and Goals
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I
We discover and develop precision therapies to preserve and restore beta cell function in the pancreatic islets.
We validate islet-targeted therapies in animal models and develop surrogate endpoints to accelerate clinical valuation and regulatory approval.
We aim to developing next-generation medicines that make insulin injections and pancreas transplant unnecessary for people living with severe diabetes.
Journey of our discoveries
ZnT8, a zinc-specific transporter, is exclusively expressed in the pancreatic islet.
ZnT8 is a major autoantigen targeted by the autoimmune system in T1D.
Naturally occurring ZnT8 loss-of-function mutations in humans provide robust protection against T2D without adverse effects.
To translate ‘experiments of nature' - naturally occurring mutations that modify a particular protein target to yield disease resistance in humans - to efficacious and safe ZnT8-specific therapeutics, we have been focused on ZnT8 research along a continuum of increasing insights marked by the following milestone.
1. Elucidate how ZnT8 functions at the molecular level.
2. Elucidate the dynamic process of ZnT8 surfacing and identify cell-surface ZnT8 autoantibody in a subset of patients with type-1 diabetes.
3. Identify a monoclonal cell-surface ZnT8 autoantibody (mAb43) and demonstrate its islet homing and beta cell uptake in mouse models of both T1D and T2D.
4. Complete preclinical evaluation of mAb43 in a T1D mouse model and demonstrate a complete protection of T1D onset and reversal of established T1D in the absence of adverse effects during long-terming monitoring of mAb43 treatment.
ZnT8 biotechnologies
Our scientific discovery is driven by technological innovation. ZnT8 is an important yet intractable membrane protein for biochemical characterization, intracellular tracking and therapeutic targeting. These technical barriers have been summoned by a suite of novel technologies highlighted by the following issued, granted and provisional patents.
Pipeline
Our pipeline of precision therapies targets T1D, LADA and severe T2D with the mAb43 monotherapy and combination therapies with Iset-directed antibody-drug conjugates (ADCs). These multifunctional biologics comprise four interconnected modules:
1. An islet-homing module that guides systematically administered ADCs to pancreatic islets,
2. A mitogenic module that stimulates adult beat cell growth.
3. A cell-surface masking module that provides a protective shield against autoimmune attacks in T1D.
4. A stress-suppressing module that safeguards β-cells from stress-induced apoptosis in T2D.