2 weeks Ago
For decades, the only option available to patients suffering from debilitating autoimmune diseases, which attack the body’s own tissues, has been to suppress the immune system with corticosteroids or anti-cytokine antibodies. But while these treatments can ease symptoms, they come with a hidden long-term cost. Dampening the immune system’s normal function over many years makes patients more vulnerable to opportunistic infections and cancer, creating a significant need for more sophisticated alternatives.
As a venture investor following emerging trends in public health, I’ve been particularly concerned by data indicating that these diseases are on the rise. According to the U.S.
National Health Council, rates of autoimmunity are approaching epidemic levels, with most autoimmune diseases being diagnosed in growing numbers in recent decades. The causes are not fully understood, but they’re thought to range from changing lifestyle factors such as dietary patterns and sleep deprivation, to increasing exposure to harmful environmental toxins or viruses. We need better therapies, and fortunately, there are a few emerging technologies which could change the treatment landscape.
CAR T-cell therapy is best known as a form of cancer immunotherapy, but it could also be a way of eliminating autoreactive B cells, a category of immune cells which underpin many autoimmune diseases by producing autoantibodies which target the body’s own cells and tissues, causing damage. Back in 2022, researchers at the University of Erlangen-Nuremberg in Germany showed that administering CAR T-cell therapy to five people with severe lupus could completely remove the aberrant B cells, sending all of the patients into remission. But CAR T-cell therapy is not easy to scale for thousands of patients.
However, a company called Coding Bio is working on an approach which CEO and co-founder Simon Bornschein describes as a more ‘off-the-shelf’ solution, developing so-called immune engager molecules which can help trigger precision killing of the autoreactive B cells. “A lot of companies are moving towards such immune engagers, as they can be manufactured at scale to address a large patient population,” says Bornschein. One of the main causes of autoimmune diseases are immunoglobulin G (IgG) autoantibodies.
Many patients are thus treated with intensive and laborious infusions of intravenous immunoglobulin (IVIG) therapy. While IVIG can be effective, it is often difficult for patients to tolerate because it is administered in large doses, with infusion sessions of up to eight hours at a time. One of Leaps by Bayer’s portfolio companies, Nuvig Therapeutics, is working on a more effective and convenient alternative.
One of the reasons that IVIG works is because there is a crucial fraction of the IgGs present in IVIG that are sialylated. Sialylation, or the addition of a sugar group to the antibody, alters where these antibodies eventually bind, helping switch the immune environment back to a more anti-inflammatory state. Pamela Conley, co-founder and CSO at Nuvig, says that the company has identified a way to capture the anti-inflammatory activity of sialylated IgGs in a novel drug.
The resulting molecule, named NVG-2089, has been found to be 10-20 times more potent than IVIG in preclinical studies and so can be administered in much lower doses. “It means it can be a much shorter therapy, smaller volumes, and an easier infusion to tolerate because of the increased potency of our drug,” she says. Nuvig has since completed a Phase 1 study in healthy volunteers which showed NVG-2089 to be safe and well-tolerated and are now moving into a Phase 2 trial in patients with a neuro-autoimmune disease called chronic inflammatory demyelinating polyneuropathy.
While normal RNA vaccines train the immune system to recognize and attack antigens associated with a virus or cancer cells, a growing number of companies have been considering a so-called ‘inverse vaccine.’ Because autoimmune diseases are caused by autoantibodies binding to autoantigens on the body’s own cells, their concept is to use RNA to train the immune system to forget these autoantigens. This can be done through boosting the numbers of regulatory T cells, which suppress a particular immune response, linked to a particular autoantigen.
Belgian-based biotech etherna is now collaborating with Hasselt University with the aim of using this concept to develop a mRNA-based treatment for multiple sclerosis and other autoimmune diseases. “The benefit of amplifying disease-suppressing Tregs is the potential to restore self-tolerance to autoantigens, resulting in long-term therapeutic effects,” says Bernard Sagaert, CEO of etherna. Instead of changing the function of IgG antibodies, we could also just use enzymes to break them down into fragments, an approach known as antibody cleaving.
This strategy is being pioneered by a Swedish biotech called Hansa Biopharma, which is running a series of clinical trials in various autoimmune conditions where disease progression is linked to IgG antibodies mistakenly launching inflammatory attacks on the body’s organ systems. The company has developed two enzymes, imlifidase and HNSA-5487, which are capable of rapidly degrading IgG antibodies and inhibiting their activity. “We believe that they have the potential to address unmet need in IgG-driven autoimmune diseases where faster acting treatment options are needed,” says Hitto Kaufmann, Hansa Biopharma’s Chief R&D Officer.
The company recently completed patient enrollment for a global Phase 3 trial in anti-glomerular basement membrane (anti-GBM) disease, a rare condition where the immune system mistakenly attacks the kidneys and the lungs. An intriguing Phase 2 trial of imlifidase in addition to IVIG treatment, showed positive results in patients with Guillain Barré Syndrome, helping them recover muscle strength and independent walking ability. As these emerging therapies develop, I’m cautiously optimistic that we’re nearing some major breakthroughs in our decades-long quest to stop the body attacking its own tissues and organs, which will hopefully allow people diagnosed with these debilitating illnesses to live longer and better lives.
Thank you to David Cox for additional research and reporting on this article..
