On November 10, 2022 Corbus Pharmaceuticals Holdings, Inc. (NASDAQ: CRBP) ("Corbus" or the "Company"), an oncology company, reported that it is presenting new preclinical data for CRB-601 in a poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in Boston (Press release, Corbus Pharmaceuticals, NOV 10, 2022, View Source [SID1234623864]).
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The latest preclinical data demonstrate significant tumor growth inhibition by CRB-601 as a single agent and in combination with anti-PD-1 treatment in the syngeneic murine tumor models MC38 and EMT6. In addition, treatment with CRB-601 appears to restore sensitivity to checkpoint inhibitors in the Pan02 and 4T1 syngeneic tumor models, regarded as "desert" tumors that are non-responsive to current CPIs. CRB-601 is the only anti-αvβ8 targeting agent known to demonstrate such an effect in these models to date.
The anti-tumor effects in the immune excluded EMT6 model correlated with changes in the immune cell populations in the tumor microenvironment. There were increases in proliferating CD4+ and CD8+ T-cells and Natural Killer cells, and a shift in macrophage polarization to the inflammatory M1 phenotype. Collectively these data suggest that treatment with CRB-601 could address tumors with an immune excluded phenotype, as represented by this model, and facilitate sensitization to anti-PD-1 therapy.
Additionally, tumor protection is associated with a durable T-cell memory response. Tumor-bearing mice initially rendered tumor-free by treatment with the combination of CRB-601 + anti-PD-1 were subsequently reinoculated with the same tumor cells (MC38) and monitored for tumor establishment and growth. After 30 days no tumors had formed in this cohort of animals, whereas implantation and eventual death occurred in 100% of the treatment naïve control animals. T-cell depletion studies indicated that protection against MC38 tumor growth in these rechallenged animals was dependent upon CD8+ T-cells.
"CRB-601 demonstrates robust pre-clinical anti-tumor activity alone and in combination with anti-PD-1 therapy in tumors exhibiting a range of sensitivities to anti-PD-1 therapy. The ability of CRB-601 to significantly reduce the growth of tumors that are non-responsive to CPIs and to sensitize these tumors to CPI therapy continues to support our hypothesis that effective blockade of latent TGFβ activation should lead to enhanced immune cell invasion in the tumor microenvironment and augment the effects of anti-PD-1 therapy. The increased activity of CRB-601 in tumors expressing αvβ8 provides a promising biomarker for patient selection and stratification," commented Rachael Brake, Ph.D., Chief Scientific Officer of Corbus.
Corbus is currently developing CRB-601 as a potential treatment for solid tumor cancers, and the program is on schedule for an IND submission in mid-2023.
Dr. Daqing Wang, PhD will be presenting the new data today in Poster #815 in Hall C from 11:40 am – 1:10 pm and again from 7:30 pm – 9 pm. The SITC (Free SITC Whitepaper) poster is available on the company website at: View Source