KAHR Announces Publication of Preclinical Data Indicating Monotherapy and Combination Treatment Potential of its Investigational Anti-CD47 Fusion Protein
KAHR, a clinical stage cancer immunotherapy company developing novel dual-targeting protein therapeutics, today announced publication of preclinical data supporting the development of DSP107, a potential first-in-class investigational CD47x41BB targeting fusion protein designed to activate both the innate and adaptive immune systems, as a monotherapy and in combination for the treatment of cancer.
The paper, titled “DSP107 combines inhibition of CD47/SIRPα axis with activation of 4-1BB to trigger anticancer immunity,” was published in the peer-reviewed Journal of Experimental & Clinical Cancer Research and authored by scientists from University Medical Center Groningen (UMCG), headed by Edwin Bremer, Ph.D., Professor at the Department of Hematology/ Immunohematology, University of Groningen, the Netherlands in collaboration with KAHR scientists.
The preclinical studies were designed to evaluate the potential for clinical development of DSP107 as monotherapy and in combination with standard of care anti-CD20 monoclonal antibody, rituximab, for Diffuse Large B Cell Lymphoma (DLBCL) patients. In these studies, it was demonstrated that:
- DSP107 alone or in combination with rituximab significantly increased macrophage- and PMN-mediated phagocytosis and trogocytosis, respectively, of DLBCL cells in culture;
- DSP107 increased T cell activation by 4-1BB costimulatory signaling only upon concomitant binding to CD47, which supports the targeted dual mechanism of action of DSP107;
- In a DLBCL mouse model, treatment with DSP107 significantly inhibited tumor growth;
- DSP107 had a favorable safety profile in cynomolgus monkeys, with no detectable anemia even at the highest dose.
“The mainstay of treatment for B Cell non-Hodgkin Lymphoma is chemotherapy combined with rituximab, a CD20 monoclonal antibody,” explained Prof. Bremer. “However, some patients are refractory to this treatment or will develop resistance and relapse with a poor prognosis. We believe our findings provide early support for DSP107’s development as a potential monotherapy and in combination with rituximab for refractory or relapsing DLBCL. DSP107 may have the potential to enable specific and localized activation of both the innate and adaptive immune system against the cancer cells.”
Yaron Pereg, Ph.D., Chief Executive Officer of KAHR, added, “We believe this scientific publication provides support for our development of DSP107 as a novel dual-targeting immunotherapy agent for difficult to treat cancers. We are encouraged by the preclinical data that point to a mechanism of action supporting our two clinical programs: the Phase 1b clinical trial of DSP107 in patients with acute myeloid leukemia and myelodysplastic syndrome and the Phase 1/2 study of DSP107 as monotherapy and in combination with an anti-PD-L1 checkpoint inhibitor, in patients with advanced solid tumors.”
DSP107 is a CD47x41BB targeting compound that simultaneously binds cancer cells and immune cells. Specifically, DSP107 binds to and inhibits CD47, an immune checkpoint protein overexpressed in many cancer types that enables the tumor to evade innate immune attack. Simultaneously, DSP107 binds to 41BB on T-cells, thereby, stimulating their activation. As a result, DSP107 on the one hand weakens the tumor’s defenses and on the other hand drives development of an effective, local response of both innate and adaptive immunity. These activities lead to targeted immune activation through both macrophage and T-cell mediated tumor destruction.
KAHR develops novel dual-targeting fusion protein therapeutics engineered to activate both the innate and the adaptive immune systems simultaneously and localize that response in the tumor microenvironment. KAHR’s lead product candidate, DSP107, is a CD47x41BB targeting compound. DSP107 is being tested in a Phase 1/2 clinical trial in advanced solid tumors and a Phase 1b clinical trial in blood cancers. KAHR’s preclinical pipeline includes DSP502, a TIGITxPD1 targeting fusion protein, and DSP216, an HLA-GxCD47 targeting fusion protein. For more information, please visit kahrbio.com.
Global Media Liaison