GenrAb’s proprietary AGS algorithm identifies a distinct class of antibodies expressed by B cells in the CSF.
The Approach
This approach allows GenrAb to bring a new class of neurotherapies to the MS market. Current treatment of MS relies almost entirely on immunosuppressive therapeutic strategies. Although suppressing immune dysregulation helps reduce stress on neurons, treated patients still demonstrate an accumulation of neuronal loss resulting in increased lifetime disability1. The pharmaceutical industry has responded to this unmet need by merely increasing the efficacy, and the cost, of these immunosuppressants. This has come with an increased risk to patients by further compromising their immune system2. Identifying non-immunosuppressive therapies that can protect neurons from death would be profoundly beneficial to the MS community. Additionally, the identification of neuroprotective agents may have broad applicability, given the role of neuronal health in neurologic diseases like ALS, Alzheimer’s and Parkinson’s but has remained elusive as there are currently no marketed drugs that protect neurons. Accordingly, there remains a clear and significant opportunity to help patients maintain neuronal health and reduce the risk of long-term disability.
By creating a drug discovery platform that analyzes influential regions of B cell DNA taken from a relevant compartment (Cerebrospinal Fluid) in human patients experiencing neurological stress, GenrAb has created models and algorithms to identify B cells that have been activated. This allows the targeted identification of human/endogenous antibodies (Abs) that are specific and highly relevant to neurological diseases of the brain. These Abs can then be rapidly screened for therapeutic performance via a drug development platform that includes well-understood preclinical models using proprietary protocols that are efficient in the use of Ab, allowing GenrAb to put the best candidates on a fast track to clinical trials. The platform has already identified therapeutic antibody candidates, like TGM-010, across the spectrum of neurological dysfunction, being applicable to diseases like MS, ALS, Alzheimer’s and stoke.
1 Tur C, Carbonell-Mirabent P, Cobo-Calvo Á, et al. Association of Early Progression Independent of Relapse Activity With Long-term Disability After a First Demyelinating Event in Multiple Sclerosis. JAMA Neurol.2023;80(2):151–160. doi:10.1001/jamaneurol.2022.4655
2 Winkelmann, A., Loebermann, M., Reisinger, E. et al. Disease-modifying therapies and infectious risks in multiple sclerosis. Nat Rev Neurol 12, 217–233 (2016). https://doi.org/10.1038/nrneurol.2016.21
TGM-010 is the first antibody that has progressed to this stage of development, as GenrAb’s platform currently consists of >250 outstanding rhAb candidates. To further explore this pipeline, the Company recently opened a lab (@ BioLabs, Pegasus Park) where we are actively characterizing the top 100 AGS scored rhAbs to prioritize those with clear binding affinity for neurons.
The AGS technology is key to finding the needle
in a stack of needles
Patents
A US patent has been issued for TGM-010’s mAb composition and fragments thereof, with planned expansion of claims to include therapeutic indications. Intellectual Property has been exclusively licensed from the University of Texas Southwestern Medical Center.
Peer-Reviewed Publications
GenrAb has contributed to peer-reviewed, high-impact journals with research revealing the proliferation of autoreactive B cells in early multiple sclerosis patients and the potential of a unique antibody gene signature to foresee the progression to clinically definite multiple sclerosis. These studies underline the predictive power and therapeutic promise of GenrAb’s antibody-based platform in identifying and countering neurological autoimmunity at its inception.
Rivas JR, Ireland SJ, Chkheidze R, Rounds WH, Lim J, Johnson J, Ramirez DM, Ligocki AJ, Chen D, Guzman AA, Woodhall M, Wilson PC, Meffre E, White C 3rd, Greenberg BM, Waters P, Cowell LG, Stowe AM, Monson NL. Peripheral VH4+ plasmablasts demonstrate autoreactive B cell expansion toward brain antigens in early multiple sclerosis patients. Acta Neuropathol. 2017 Jan;133(1):43-60. doi: 10.1007/s00401-016-1627-0. Epub 2016 Oct 11. PMID: 27730299; PMCID: PMC5312707.
Cameron EM, Spencer S, Lazarini J, Harp CT, Ward ES, Burgoon M, Owens GP, Racke MK, Bennett JL, Frohman EM, Monson NL. Potential of a unique antibody gene signature to predict conversion to clinically definite multiple sclerosis. J Neuroimmunol. 2009 Aug 18;213(1-2):123-30. doi: 10.1016/j.jneuroim.2009.05.014. Epub 2009 Jul 24. PMID: 19631394; PMCID: PMC2785005.
Ligocki AJ, Rivas JR, Rounds WH, Guzman AA, Li M, Spadaro M, Lahey L, Chen D, Henson PM, Graves D, Greenberg BM, Frohman EM, Ward ES, Robinson W, Meinl E, White CL 3rd, Stowe AM, Monson NL. A Distinct Class of Antibodies May Be an Indicator of Gray Matter Autoimmunity in Early and Established Relapsing Remitting Multiple Sclerosis Patients. ASN Neuro. 2015 Oct 21;7(5):1759091415609613. doi: 10.1177/1759091415609613. PMID: 26489686; PMCID: PMC4710131.
Rounds WH, Salinas EA, Wilks TB 2nd, Levin MK, Ligocki AJ, Ionete C, Pardo CA, Vernino S, Greenberg BM, Bigwood DW, Eastman EM, Cowell LG, Monson NL. MSPrecise: A molecular diagnostic test for multiple sclerosis using next generation sequencing. Gene. 2015 Nov 10;572(2):191-7. doi: 10.1016/j.gene.2015.07.011. Epub 2015 Jul 11. PMID: 26172868; PMCID: PMC4702260.