A sea anemone’s venom provides the blueprint for a new class of drug that disables the immune cells driving autoimmune diseases while leaving the rest of the immune system intact. Current treatments for conditions like Inflammatory Bowel Disease, Type 1 Diabetes, and Rheumatoid Arthritis often work poorly or suppress the entire immune system, leaving patients vulnerable to infections. The problem is that the immune cells causing the damage—a subset of T cells—depend on a specific ion channel called Kv1.3 to function. Blocking that channel could precisely disable those rogue cells, but making antibody drugs that block ion channels has proven extremely difficult despite decades of effort. Maxion has fused a Kv1.3-blocking knottin from sea anemone venom directly into the surface of an antibody, creating a “KnotBody” that combines the stability and long circulation of an antibody with the ion-channel-blocking ability of the venom protein. The company will now use antibody engineering tools to improve the potency of this hybrid molecule and advance it toward clinical trials. If successful, the approach could yield a new class of precisely targeted drugs for autoimmune diseases, offering patients better control of their condition without compromising their ability to fight infections.
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Autoimmune diseases such as Inflammatory Bowel Disease, Type 1 Diabetes, Rheumatoid Arthritis and Psoriasis are driven by the protective immune system attacking the body itself. These conditions are often poorly treated with existing therapeutics. Autoimmune diseases are driven by a subset of T cells (part of the body's immune system) which are uniquely dependent on an ion channel called Kv1.3\. Blockade of the action of Kv1.3 therefore provides an "Achilles heel" to precisely disable this subset of autoimmunity-driving T cells while leaving the rest of the immune system intact to continue fighting infections. Creating an antibody drug to block Kv1.3 is an attractive option. Antibody drugs have ideal properties for disease intervention and over 100 different antibody drugs have been approved in the last 20 years. Making antibodies which block ion channels, however, remains a challenge despite decades of effort. Nature provides the answer in the form of "miniproteins" (knottins) which are found in venoms and which block ion channels. This includes a knottin present in the venom of a sea anemone that blocks Kv1.3\. Unlike antibodies, knottins suffer from problems such as rapid removal from the blood circulation and unwanted cross-reactivity in the body causing side-effects. By fusing a Kv1.3-blocking knottin directly into the surface of an antibody, Maxion has created a "hybrid molecule" (a "KnotBody") which combines the best of both worlds. The resulting molecule has the optimal characteristics of an antibody AND blocks Kv1.3\. Within this project Maxion will use powerful antibody engineering tools, invented by Maxion's founder Dr. John McCafferty, to improve the potency of the initial KnotBody and progress the resulting drug candidate towards clinical trial. Ultimately Maxion aim to develop a KnotBody drug which will significantly improve the quality of life of patients by preventing conditions such as Inflammatory Bowel Disease, Type 1 Diabetes and Atopic Dermatitis.
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