Clinical study will be conducted at multiple leading sites in the United States
JERUSALEM, Nov. 12, 2020 /PRNewswire/ -- KAHR, a cancer immunotherapy company developing novel multifunctional immuno-recruitment proteins, today announced dosing of the first patient in its Phase 1/2 clinical trial (NCT04440735) assessing its lead product, DSP107, a bi-functional CD47x41BB candidate for the treatment of solid tumors.
The first-in-human, multicenter, open-label, dose-escalation and expansion study is estimated to enroll up to 115 patients. The study will include 2 parts. The first part will evaluate the safety, pharmacokinetics and pharmacodynamics of DSP107 as a monotherapy and in combination with Roche's PD-L1-blocking checkpoint inhibitor atezolizumab (Tecentriq®) in patients with advanced solid tumors. In part 2, the trial will assess the preliminary efficacy of both DSP107 monotherapy and combination therapy with atezolizumab in patients with advanced non-small-cell lung carcinoma (NSCLC) who progressed after treatment with PD-1/PD-L1 inhibitors. The study will be conducted at multiple leading sites in the United States under a clinical collaboration with Roche.
KAHR's technology is based on multi-functional immuno-recruitment proteins (MIRP) that utilize overexpression of checkpoint antigens on cancer cells in order to selectively target the tumor. DSP107's dual functional arms trigger a local, synergistic immune response by binding CD47 over-expressed on cancer cells, disabling their "don't eat me" signal, followed by binding to 4-1BB receptors expressed on activated, tumor-reactive T-cells stimulating their proliferation and activation. The trimeric structure of DSP107 and its binding to CD47 enables cross presentation of 4-1BBL for conditional, tumor-localized, 4-1BB receptor activation on tumor reactive T-cells.
"A hallmark of cancer is the ability to evade recognition and elimination by the body's own immune system," explained Yaron Pereg, Ph.D., Chief Executive Officer of KAHR. "The MIRP technology is tailored to overcome this and re-educate the immune system. MIRPs deliver a multi-layered attack by binding to key evasion markers on cancer cells to effectively unmask them for immune recognition. At the same time, MIRPs provide signals to effectively trigger a targeted synergistic activation of anticancer innate and adaptive immunity. We are very pleased to begin the clinical development of DSP107 and believe it can become a best-in-class CD47 checkpoint inhibitor in light of its dual functionality."
"CD47 has emerged as a highly promising immuno-oncology molecular target," said Mark Tykocinski, MD, Dean of Medical School and Provost, Thomas Jefferson University and inventor of MIRP. "However, maximizing its full therapeutic potential has proven challenging, with blocking monoclonal antibodies and Fc-fusion proteins eliciting off-tumor effects and hematologic toxicities. DSP107 bypasses this problem in lacking an Fc region and not binding red blood cells. DSP107's structural configuration promotes both selective binding to CD47-positive tumors and localizes conditional T cell activation through the 4-1BB receptor. It is exciting to see this novel platform moving forward into clinical development for the benefit of cancer patients."
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.
KAHR develops the next generation of immuno-oncology drug candidates for the treatment of multiple types of cancer. The Company's lead product, DSP107, is a second generation 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 in order to selectively target and bind to the tumor. MIRPs binding 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. Investors in the Company include Flerie Invest AB, Oriella Limited a Consensus Business Group Limited subsidiary, Hadassit Bio Holdings, Pavilion Capital, Mirae Asset, Korean Investment Partners and DSC Investments. For more information, please visit https://kahrbio.com/
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SOURCE KAHR Medical