(13MB041) S100A9: CD33/IgG1 Chimera Antibody Trap to Neutralize S100A9 to Treat MDS

Our technology is a chimeric antibody linking the extracellular binding domain of CD33 with an immunoglobulin (Ig) heavy chain region of human IgG1 that binds to circulating S100A9 protein. This biologic agent is for the treatment of hematologic malign…

Our technology is a chimeric antibody linking the extracellular binding domain of CD33 with an immunoglobulin (Ig) heavy chain region of human IgG1 that binds to circulating S100A9 protein. This biologic agent is for the treatment of hematologic malignancies such as MDS, with potential application to inflammatory diseases & enhancement of anti-cancer immune responses. Currently, there are no therapies targeting the key pathogenetic drivers in MDS. Our biologic agent represents a first-in-class, novel strategy targeting a key soluble effector of the disease. This biologic agent would act similarly to Avastin or Zaltrap to neutralize the ligand in the cancer microenvironment to improve hematopoiesis.

Abstract:

  • According to combined Surveillance, Epidemiology and End Results (SEER) and Medicare claims data, approximately 40-50,000 or more MDS patients are diagnosed annually in the USA, with an overall prevalence that exceeds this several fold. MDS is a stem cell malignancy that laregly afflicts individuals >60 years of age and often progresses to acute myeloid leukemia (AML).
  • Aside from bone marrow transplants for severe cases, 5-azacytidine, decitabine, and lenalidomide are the three therapeutics currently approved to treat MDS, delay its progression to AML, and prolong patient survival. Annualized US sales of Celgene’s 5-azacytidine (Vidaza) continue to increase (>$840M in 2013).
  • MDS patients sometimes take Vidaza for up to 6 months ($9200/month) before noticing benefit. They will remain on therapy as long as their disease does not progress and side effects are tolerable. Median progression-free survival with Vidaza treatment has been reported to be close to 2 years, demonstrating the significant long-term use of therapies for MDS.
  • Our biologic is conceptually similar to the FDA approved anti-cancer therapy, Avastin, which binds to circulating Vascular Endothelial Growth Factor (VEGF) and makes it incapable of binding its cellular receptor to initiate blood vessel growth. Inhibiting new blood vessel formation starves tumors and slows their growth. Avastin has generated over $5B in global sales in 2013 as of the end of Q3.
  • We are also developing, in parallel, a family of novel small molecules that inhibit PDE signaling in this pathway. A 1st generation compound has shown excellent efficacy in maintaining normal hemoglobin levels and survival in a S100A9 transgenic mouse model of MDS.

Website:

https://moffitt.org/research-science/academic-and-industry-partnerships/office-of-innovation/available-technologies/immunotherapies/13mb041-s100a9-cd33igg1-chimera-antibody-trap-to-neutralize-s100a9-to-treat-mds-1/