Therapeutic can address $20 Billion autoimmune market
SEATTLE, WA, USA I January 09, 2025 I Cyrus Biotechnology, an AI-driven therapeutics company, announced today that its CYR212, an engineered next-generation reduced-immunogenicity and half-life extended Immunoglobulin-G (IgG) protease, has been selected as its clinical development candidate for chronic IgG-driven autoimmune disease. CYR212 was selected based on promising recent preclinical data from evaluations of pharmacokinetics, pharmacodynamics and immunogenicity in animal models. Preclinical studies in rabbits confirmed a significant extension of half-life and pharmacodynamic IgG-reducing activity compared to the wild type (WT) Streptococcus pyogenes IdeS protease, from which CYR212 has been developed.
Studies during the development of CYR212 have shown rapid, titratable, dose-dependent and sustained depletion of IgG, and no immunogenicity response upon either a first or second dose in rabbits. This is in contrast with WT IdeS, which shows a high anti-drug antibody (ADA) response similar to what is observed in patients.
CYR212, engineered for extended half life and reduced T- and B-cell mediated immunogenicity using Cyrus’s AI platform, maintains the favorable properties of the WT enzyme, including high stability, manufacturability, and in vitro and in vivo enzymatic activity. This profile is consistent with a superior therapeutic candidate for the treatment of a broad range of IgG-mediated diseases.
“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. “IgG is the principal antibody type responsible for blocking infections, but in IgG-mediated autoimmune disease it attacks host tissues, causing a broad range of often severe disease,” Nivon added. An example is generalized Myasthenia Gravis (gMG) where IgG targets neuromuscular receptor proteins leading to degenerative neurological disease. In Immune Thrombocytopenia (ITP), IgG targets glycoproteins on the surface of platelets leading to platelet depletion, disruption of the clotting cascade and dangerous internal bleeding.
A clinically approved version of WT IdeS is marketed for narrow indications and is being evaluated in several acute IgG-mediated indications, but short half-life and high immunogenicity – both of which CYR212 directly addresses – limit its much broader utility.
The very low anticipated doses required for CYR212 efficacy will likely make administration of the drug far more convenient than it is for anti-FcRn biologics – the current best in class therapeutics for multiple chronic IgG-mediated autoimmune diseases. Anti-FcRn antibody therapeutics reduce IgG levels via binding of the neonatal Fc receptor (FcRn), inhibiting IgG recycling and lowering circulating IgG levels. The ability of CYR212 to deplete circulating IgG in a matter of hours and the potential for prefilled-syringe sub-1ml subcutaneous administration would greatly benefit patients. The FcRn drugs show peak IgG depletion only after several weeks of administration using lengthy (up to 60 minutes) infusions of large volumes – typically over 10mL.
“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.”
Cyrus plans to take CYR212 into clinical studies in indications where the anti-FcRn class have so far not proven sufficiently potent for clinical approval (ITP), or where lower IgG levels achievable by CYR212 are likely to lead to better efficacy (gMG).
In gMG, CYR212 is likely to achieve improved dosing convenience and faster speed of action. Clinical data in gMG shows that the anti-FcRn’s such as Efgartigimod and Nipocalimab are potent in symptom reduction, but lower IgG levels correlate with better clinical outcomes and IgG levels <15% of normal have never been tested because these therapeutics have limited potency.
In ITP, no anti-FcRn therapeutic has yet been approved, and hematologists are looking for lower IgG levels to be achieved over longer periods of time than the anti-FcRn class can deliver. Therefore, CYR212 has the potential to be the first approved IgG-lowering agent in ITP.
About Cyrus Biotechnology
Cyrus Biotechnology is a Seattle-based pre-clinical-stage AI-driven therapeutics company with an internal pipeline of novel biologics primarily in autoimmune indications. In addition to IdeS, Cyrus is also advancing multiple discovery stage cytokine programs based on years of experience with partners in cytokine optimization. The company was co-founded with Prof. David Baker, 2024 Nobel Prize winner and inventor of Rosetta and numerous protein design AI tools. Cyrus has worked with dozens of Pharma firms on protein redesign for novel therapeutics, including Genentech and Janssen. In 2021 Cyrus started an internal therapeutics pipeline. The company is funded by lead investor Orbimed, with Agent Capital, Hillhouse, Alexandria, and others.
For more information about Cyrus please visit https://cyrusbio.com/
SOURCE: Cyrus Biotechnology
Post Views: 153
Therapeutic can address $20 Billion autoimmune market
SEATTLE, WA, USA I January 09, 2025 I Cyrus Biotechnology, an AI-driven therapeutics company, announced today that its CYR212, an engineered next-generation reduced-immunogenicity and half-life extended Immunoglobulin-G (IgG) protease, has been selected as its clinical development candidate for chronic IgG-driven autoimmune disease. CYR212 was selected based on promising recent preclinical data from evaluations of pharmacokinetics, pharmacodynamics and immunogenicity in animal models. Preclinical studies in rabbits confirmed a significant extension of half-life and pharmacodynamic IgG-reducing activity compared to the wild type (WT) Streptococcus pyogenes IdeS protease, from which CYR212 has been developed.
Studies during the development of CYR212 have shown rapid, titratable, dose-dependent and sustained depletion of IgG, and no immunogenicity response upon either a first or second dose in rabbits. This is in contrast with WT IdeS, which shows a high anti-drug antibody (ADA) response similar to what is observed in patients.
CYR212, engineered for extended half life and reduced T- and B-cell mediated immunogenicity using Cyrus’s AI platform, maintains the favorable properties of the WT enzyme, including high stability, manufacturability, and in vitro and in vivo enzymatic activity. This profile is consistent with a superior therapeutic candidate for the treatment of a broad range of IgG-mediated diseases.
“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. “IgG is the principal antibody type responsible for blocking infections, but in IgG-mediated autoimmune disease it attacks host tissues, causing a broad range of often severe disease,” Nivon added. An example is generalized Myasthenia Gravis (gMG) where IgG targets neuromuscular receptor proteins leading to degenerative neurological disease. In Immune Thrombocytopenia (ITP), IgG targets glycoproteins on the surface of platelets leading to platelet depletion, disruption of the clotting cascade and dangerous internal bleeding.
A clinically approved version of WT IdeS is marketed for narrow indications and is being evaluated in several acute IgG-mediated indications, but short half-life and high immunogenicity – both of which CYR212 directly addresses – limit its much broader utility.
The very low anticipated doses required for CYR212 efficacy will likely make administration of the drug far more convenient than it is for anti-FcRn biologics – the current best in class therapeutics for multiple chronic IgG-mediated autoimmune diseases. Anti-FcRn antibody therapeutics reduce IgG levels via binding of the neonatal Fc receptor (FcRn), inhibiting IgG recycling and lowering circulating IgG levels. The ability of CYR212 to deplete circulating IgG in a matter of hours and the potential for prefilled-syringe sub-1ml subcutaneous administration would greatly benefit patients. The FcRn drugs show peak IgG depletion only after several weeks of administration using lengthy (up to 60 minutes) infusions of large volumes – typically over 10mL.
“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.”
Cyrus plans to take CYR212 into clinical studies in indications where the anti-FcRn class have so far not proven sufficiently potent for clinical approval (ITP), or where lower IgG levels achievable by CYR212 are likely to lead to better efficacy (gMG).
In gMG, CYR212 is likely to achieve improved dosing convenience and faster speed of action. Clinical data in gMG shows that the anti-FcRn’s such as Efgartigimod and Nipocalimab are potent in symptom reduction, but lower IgG levels correlate with better clinical outcomes and IgG levels <15% of normal have never been tested because these therapeutics have limited potency.
In ITP, no anti-FcRn therapeutic has yet been approved, and hematologists are looking for lower IgG levels to be achieved over longer periods of time than the anti-FcRn class can deliver. Therefore, CYR212 has the potential to be the first approved IgG-lowering agent in ITP.
About Cyrus Biotechnology
Cyrus Biotechnology is a Seattle-based pre-clinical-stage AI-driven therapeutics company with an internal pipeline of novel biologics primarily in autoimmune indications. In addition to IdeS, Cyrus is also advancing multiple discovery stage cytokine programs based on years of experience with partners in cytokine optimization. The company was co-founded with Prof. David Baker, 2024 Nobel Prize winner and inventor of Rosetta and numerous protein design AI tools. Cyrus has worked with dozens of Pharma firms on protein redesign for novel therapeutics, including Genentech and Janssen. In 2021 Cyrus started an internal therapeutics pipeline. The company is funded by lead investor Orbimed, with Agent Capital, Hillhouse, Alexandria, and others.
For more information about Cyrus please visit https://cyrusbio.com/
SOURCE: Cyrus Biotechnology
Post Views: 153
