Belgian start-up Dualyx is developing a novel approach with the potential to treat a wide range of autoimmune disorders. The method uses llama-derived antibodies to flip a master switch and create regulatory T cells, which help restore order to overzealous immune systems.
By Amy LeBlanc
T cells are an integral part of our immune system, which exist in a variety of subtypes. When our body is threatened by pathogens, CD8+ “killer” T cells attack the invaders and release cytokines to sound the alarm and trigger a full-scale immune response. Meanwhile, CD4+ “helper” T cells support this response by activating other types of cells (like memory B cells).
To stop this reaction from snowballing out of control, regulatory T cells (Tregs) deescalate the aggression. In the heat of the battle, they help immune cells recognize “self” from “other”, preventing the immune system from attacking our own cells. Once the threat has been eliminated, Tregs dampen the immune response to reset our system to the status quo.
“Our aim at Dualyx: expanding Treg populations in vivo to restore the immune system’s natural balance.” – Wouter Verhoeven
Autoimmune disorders – like rheumatoid arthritis (RA), type 1 diabetes, or inflammatory bowel disease (IBD) – are often the result of an imbalance between these aggressive T cell types and the pacifying Tregs. Wouter Verhoeven, CEO of Belgian start-up Dualyx, explains:
“When Tregs aren’t there to stop the cascading immune reaction, or to protect the body’s own cells, you end up with autoimmune diseases. We’ve found that if we increase the number of Tregs, we could bring the body back to a stable condition and have a long-lasting impact on a huge number of debilitating conditions. This is exactly our aim at Dualyx: expanding Treg populations in vivo to restore the immune system’s natural balance.”
A clean target for treating a range of diseases
Dualyx was founded two years ago by CSO Luc Van Rompaey – formerly argenx’ Vice President of Translational Medicine – with a EUR 7 million seed round supported by V-Bio Ventures, BGV, PMV, VIB, HTGF, and GFF. The start-up initially operated as a virtual company but has now set up shop in the VIB Bio-Incubator in Ghent, Belgium. There are three main programs in the pipeline, with technology in-licensed from argenx, VIB, and the University of Würzburg. The lead program is a llama-derived antibody targeting a receptor called TNFR2, Verhoeven shares:
“We’ve created a multivalent antibody that acts as an agonist to TNFR2, a membrane receptor on Treg cells. TNFR2 functions as a master switch, inducing immune suppression by activating and expanding a subpopulation of highly potent and stable Tregs. Although the target itself is well-described, our approach in triggering this anti-inflammatory pathway is unique, and our therapy would be a first-in-class drug.”
“TNFR2 is purely immunosuppressive. What’s more: our approach could have a synergistic effect with TNF-alpha inhibitors like Humira.” – Wouter Verhoeven
Autoimmune treatments are among the world’s top-selling drugs, with blockbusters like Humira and Enbrel raking in tens of billions of dollars each year. Incentivized by such an enormous market, investors have also been giving keen attention to another novel autoimmune approach using IL-2 muteins. Although promising, this technology has yet to succeed in the autoimmune disease clinical trials currently ongoing. The stakes are high: the once-largest licensing deal in biotech history – a USD 3.6 billion agreement between Bristol Myers Squibb and Nektar – recently ended in failure after phase 3 flops in oncology.
“What sets our technology apart from IL-2 muteins and other approaches in the industry is that TNFR2 is a much cleaner target,” says Verhoeven. “The IL-2 receptor is quite complex, and you need to have the right balance to activate it only on the immune-suppressive Tregs. TNFR2, on the other hand, is purely immunosuppressive. What’s more: our approach could have a synergistic effect with TNF-alpha inhibitors like Humira, which are the current first-line treatments for multiple autoimmune diseases.”
Fundraising for future indications
It’s exciting times for the company, which is rapidly expanding its team and gearing up for a Series A financing round. With the IP for this new approach in hand, Dualyx is now in the process of selecting a lead candidate, aiming to enter the clinic in 2024.
Read this article about V-Bio portfolio company AgomAb developing antibodies for regenerative medicine
“We have fantastic in vivo data for graft-versus-host disease,” Verhoeven enthuses, “and we are exploring other target indications where we also think our technology could be efficacious. Though we have to choose an initial focus, there are many conditions where this technology could be hugely beneficial, including IBD, RA, MS, psoriasis, Graves’ disease, and more. What really excites me about our company is that we have a very interesting target with TNFR2, which we can use to create a powerful immune therapy for doctors treating a wide range of autoimmune diseases. The potential impact is enormous.”
