Cyrus Biotechnology has selected CYR212 as its clinical development candidate for chronic IgG-driven autoimmune diseases, following promising preclinical data demonstrating significant improvements over existing therapies. The AI-engineered next-generation IgG protease addresses a potential $20 billion market opportunity across multiple autoimmune conditions.
Preclinical studies in rabbits confirmed CYR212's extended half-life and sustained pharmacodynamic IgG-reducing activity compared to the wild-type (WT) Streptococcus pyogenes IdeS protease from which it was developed. Notably, the candidate showed no immunogenicity response upon first or second dosing, a critical advancement over the wild-type enzyme which typically elicits strong anti-drug antibody (ADA) responses that limit redosing potential.
"We have now demonstrated that CYR212 shows no ADAs up to 30 days at a clinically relevant dose in rabbits and confirmed the subcutaneous bioavailability of CYR212 in preclinical PK studies," said Cyrus CSO Erik Procko, PhD. "Based on modeling of these preclinical PK data and PK of approved related biologics, we anticipate at least a 4-week dosing interval for clinical use of CYR212."
Mechanism of Action and Clinical Advantages
CYR212 maintains the favorable enzymatic properties of the wild-type IdeS, including high stability, manufacturability, and potent in vitro and in vivo activity, while addressing the limitations that have restricted broader clinical applications of IgG-degrading enzymes.
IgG antibodies are the principal antibody type responsible for blocking infections, but in autoimmune diseases, they attack host tissues, causing a range of often severe conditions. In generalized Myasthenia Gravis (gMG), IgG targets neuromuscular receptor proteins, leading to degenerative neurological disease. In Immune Thrombocytopenia (ITP), IgG targets glycoproteins on platelet surfaces, causing platelet depletion and dangerous internal bleeding.
The therapeutic's ability to deplete circulating IgG within hours and its potential for subcutaneous administration via prefilled syringes of less than 1ml volume could provide significant advantages over current anti-FcRn antibody therapeutics, which typically require lengthy infusions and take weeks to achieve peak IgG depletion.
"CYR212 addresses over $20B of potential clinical market opportunities in IgG-driven autoimmune disease, including rheumatological, neurological, dermatological, and hematological immune pathologies," said Cyrus CEO Lucas Nivon, PhD.
Strategic Clinical Development Plan
Cyrus plans to advance CYR212 into clinical studies focusing initially on indications where anti-FcRn therapies have shown limitations. The company is targeting Immune Thrombocytopenia, where no anti-FcRn therapeutic has yet been approved, and generalized Myasthenia Gravis, where lower IgG levels correlate with better clinical outcomes.
In gMG, CYR212 is expected to achieve improved dosing convenience and faster onset of action. Clinical data shows that anti-FcRn therapies like Efgartigimod and Nipocalimab are effective in reducing symptoms, but their limited potency means they cannot achieve the very low IgG levels (<15% of normal) that may provide superior clinical benefits.
For ITP, hematologists seek deeper and more sustained IgG reduction than anti-FcRn therapies can deliver, positioning CYR212 as potentially the first approved IgG-lowering agent for this indication.
Engineering Breakthrough
The development of CYR212 builds on earlier work with CYR241, which demonstrated potent activity in a rabbit redosing model with no anti-drug antibodies following repeat administration at therapeutic doses.
The company's platform combines AI-driven protein engineering with screening-based methods to evaluate thousands of MHC/peptide interactions. This approach has enabled optimization for glycosylation, which shields the protein from neutralizing antibodies (B cell responses), while reengineering the sequence for low MHC binding (T cell activation).
Dr. Tony Manning, Board Director at Cyrus and former CSO at Momenta Therapeutics, highlighted the significance of this advancement: "The IdeS enzyme is the ideal novel product candidate for IgG driven diseases where the anti-FcRn class has established a clear role for IgG reduction as a therapeutic strategy. In the autoimmune field we have not had the technology to create a redosable, half-life extended IdeS until Cyrus's platform."
Company Background
Cyrus Biotechnology is a Seattle-based pre-clinical-stage AI-driven therapeutics company with an internal pipeline of novel biologics primarily in autoimmune indications. The company was co-founded with Prof. David Baker, 2024 Nobel Prize winner and inventor of Rosetta and numerous protein design AI tools.
In addition to its IdeS program, Cyrus is advancing multiple discovery-stage cytokine programs. The company is funded by lead investor Orbimed, with participation from Agent Capital, Hillhouse, Alexandria, and others.
With CYR212's selection as a clinical candidate, Cyrus is positioned to potentially transform the treatment landscape for IgG-mediated autoimmune diseases by addressing the limitations of current therapies while offering improved efficacy, convenience, and redosability.
