Nykode’s inverse vaccines ease disease severity in MS mouse model

Two inverse vaccines from Nykode Therapeutics — developed to teach the immune system not to respond against its own body — worked to reduce disease severity in a mouse model of multiple sclerosis (MS), new data show.

This adds to earlier findings that the company’s experimental approach and its TV004 inverse vaccine can prevent the disease from developing in mice by making the immune system unresponsive to a protein involved in MS — without fully disrupting the immune response.

“These findings represent progress in our ongoing research into inverse vaccines and autoimmune disease treatment,” Agnete Fredriksen, PhD, Nykode’s chief scientific officer and co-founder, said in a company press release.

A poster detailing the findings, titled “Tolerogenic APC-targeted Vaccibody Vaccines Treat Disease in Mouse Models of Experimental Autoimmune Encephalomyelitis and Non-Obese Diabetes,” was presented at the Federation of Clinical Immunology Societies (FOCIS) 2024 annual meeting, held June 18-21 in San Francisco.

Michael Engsig, Nykode’s CEO, said the company is “planning initiatives to advance our efforts” in developing an inverse vaccine, also known as a Vaccibody.

“We are excited about the progress and promise of Nykode’s inverse vaccine platform for the treatment of autoimmune diseases,” Engsig said.

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In MS, the immune system mistakenly attacks the myelin sheath, a fatty layer that protects nerve fibers in the brain and spinal cord. Such attacks cause inflammation and damage, and result in a range of symptoms that worsen over time.

Nykode’s inverse vaccine technology is designed to teach the immune system not to respond against a given target, inducing immune tolerance to that target.

It does that by delivering lab-made DNA molecules to muscles cells with instructions to produce an inverse vaccine, or Vaccibody. The Vaccibody proteins are then secreted by the cells and, once in circulation, they recruit and bind to antigen-presenting cells, called APCs.

APCs are immune cells that present antigens — any substance that triggers an immune response — to immune T-cells, triggering an immune response against those antigens. But Vaccibody vaccines are instead developed to recruit APCs that present antigens to regulatory T-cells, which limit the activity of other immune cells.

In addition to TV004, the company developed another Vaccibody inverse vaccine called TV036. Both are designed to induce tolerance against myelin oligodendrocyte glycoprotein (MOG), a myelin protein. However, they bind to different targets in APCs.

In experimental autoimmune encephalomyelitis, a widely used model of MS, mice usually develop their first symptoms within one week, and tail paralysis within about two weeks. As the disease progresses, paralysis spreads to the hind legs and then to the forearms.

In the lab, the mice were given an intravenous (into-the-vein) injection of TV004 or TV036 at seven and three days before experimental autoimmune encephalomyelitis was induced. In these animals, disease severity was reduced, and tail and hind paralysis were prevented for up to 28 days.

Similar findings were obtained when the intravenous injections were given at seven and 10 days after experimental autoimmune encephalomyelitis was induced, when some symptoms could have already developed.

[Nykode is] aiming to develop a new class of drugs that are antigen-specific, with the potential to be both long-lasting and have limited side effects. … By exploring different targeting units and their impact compared to antigen delivery, Nykode aims to refine therapies that could offer new options for autoimmune conditions.

“Using targeting units toward two different receptors on APCs,” both Vaccibody inverse vaccines “showed potent disease protection in preventive and early therapeutic settings,” the researchers wrote in an abstract to the poster presented at FOCIS 2024.

Fredriksen said Nykode is “aiming to develop a new class of drugs that are antigen-specific, with the potential to be both long-lasting and have limited side effects.”

“By exploring different targeting units and their impact compared to antigen delivery, Nykode aims to refine therapies that could offer new options for autoimmune conditions,” Fredriksen said.

According to Engsig, Nykode is establishing a subsidiary within the company “focused on further progressing the immune tolerance platform.”