KAHR, a Jerusalem clinical-stage cancer immunotherapy company, has just announced the publication of their preclinical data that supports the development of DSP107. DSP107 is a potential first-in-class investigational CD47x41BB targeting fusion protein designed to activate both innate and adaptive immune systems, as a monotherapy and in combination for the treatment of cancer.
Gur Roshwalb MD, Partner, aMoon, said,” KAHR’s multifunctional immunotherapeutic platform has enormous potential to address unmet needs in immuno-oncology. We are particularly excited about KAHR’s differentiated first-in-class CD47x41BB targeting compound, which potentially harnesses both the innate and adaptive immune systems to target solid and hematologic tumors.”
The studies were set up to evaluate the potential for the clinical development of DSP107 as a functioning monotherapy and in conjunction with standard of care, rituximab, an anti-CD20 monoclonal antibody for Diffuse Large B Cell Lymphoma patients. DSP107 is a CD47x41BB compound that works to simultaneously bind immune cells and cancer cells. It binds to and inhibits the immune checkpoint, CD47, which is overexpressed in many cancer types enabling many tumors to avoid the immune attack. In addition to weakening the tumor’s defense mechanism, DSP107 powers the effective response of adaptive and innate immunity by binding and activating 41BB on T-cells. The studies have shown significant results including that of:
- DSP107 significantly inhibited tumor growth within a DLBCL mouse model.
- Within cynomolgus monkeys, DLBCL had a favorable safety profile with no anemia even at the highest dose.
- Upon concomitant binding to CD47, DSP107 increased T cell activation by 4-1BB costimulatory signaling. This supports the dual mechanism of action of DSP1-7
- Whether in combination with rituximab or alone, DSP107 has significantly increased macrophage and PMN-mediated phagocytosis and trogocytosis, respectively of DLBCL cells in culture
“The mainstay of treatment for B Cell non-Hodgkin Lymphoma is chemotherapy combined with rituximab, a CD20 monoclonal antibody,” explained Prof. Bremer, University of Groningen. “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.”
This preclinical data was published in the peer-reviewed Journal of Experimental & Clinical Cancer Research headed by Edwin Bremer, Ph.D., Professor at the Department of Hematology/ Immunohematology, University of Groningen, and in collaboration with other scientists from the University Medical Center Groningen (UMCG), and KAHR scientists.
“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.” Yaron Pereg, Ph.D., Chief Executive Officer of KAHR.
KAHR develops smart immune-recruitment cancer drugs that activate a targeted immune response by converting cancer camouflage into beacons for the immune system to attack. The Company’s lead product candidate, DSP107 is a first-in-class CD47x41BB targeting compound that simultaneously binds cancer cells and immune cells, linking them together for maximal activation of the immune system against the tumor. DSP107 is designed to weaken the tumor’s defenses on one hand, and activate an effective, local response of both innate and adaptive immunity on the other hand. Specifically, DSP107 binds to and inhibits CD47, an immune checkpoint protein overexpressed in many cancer types that enables the tumor to evade immune recognition and attack. DSP107 targets CD47-overexpressing tumors, simultaneously blocking macrophage inhibitory signals and delivering an immune costimulatory signal to tumor antigen-specific, activated T-cells. CD47 is overexpressed on many cancer cells and binds SIRPα on immune phagocytic cells to produce a “don’t eat me” signal. DSP107 binds CD47 on cancer cells, blocking interaction with SIRPα and thus, blocking the “don’t eat me signal”.Simultaneously, DSP107 binds 41BB on T-cells, stimulating their activation. These activities lead to targeted immune activation through both macrophage and T-cell mediated tumor destruction.
DSP107 is currently 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 a TIGITxPD1 targeting fusion protein, DSP502, and an HLA-GxCD47 targeting fusion protein, DSP216.
Established in 2005, KAHR is an immuno-oncology drug development company whose mission is to develop novel fusion protein pharmaceuticals for the treatment of cancer and autoimmune diseases. The Company’s lead product candidate, KAHR, is a first-in-class CD47x41BB targeting compound that simultaneously targets cancer cells, weakens their innate defenses, and activates an effective, local response of both innate and adaptive immunity. KAHR’s technology platform is based on multi-functional immuno-recruitment proteins (MIRP) that utilize overexpression of checkpoint antigens on cancer cells to selectively target and bind to the tumor. MIRPs bridge cancer cells to immune cells to produce a targeted synergistic effect by combining immune checkpoint inhibition with localized immune cell activation, unmasking cancer cell camouflage to enable innate immune response, while recruiting the adaptive immune system to bind and selectively kill the cancer cells.
KAHR‘s technology is based on many years of research by Dr. Michal Dranitzki Elhalel, Head of Nephrology and a senior researcher at the Hadassah Medical Center, and Professor Mark Tykocinski, Dean of the School of Medicine at Jefferson University in Philadelphia and former Chief of Pathology at the University of Pennsylvania.
Investors in the Company include Amoon, Flerie Invest AB, Oriella Limited a Consensus Business Group Limited subsidiary, Hadassit Bio Holdings, Pavilion Capital, Mirae Asset, Korean Investment Partners, and DSC Investments.
Source: PR Newswire
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