It’s all in the presentation

A roundup of recent preclinical data presentations

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BURLINGAME, Calif.—Starting our tour through recent poster and oral presentations of the preclinical persuasion is Corvus Pharmaceuticals Inc., which in January announced data from a preclinical study of CPI-818, its investigational small-molecule T cell signaling pathway inhibitor. Study results indicated that orally administered CPI-818 produced tumor regression in three of three companion dogs with spontaneous, naturally occurring T cell lymphomas, without significant toxicity. These preclinical data were presented in a poster entitled “Biochemical, Immunologic and In Vivo Preclinical Studies with CPI-818: A Selective Interleukin-2-Inducible T-cell Kinase Inhibitor That Inhibits T-Cell Receptor Signaling, Promotes Th1 Skewing, and is Efficacious in Dogs with T-Cell Lymphomas,” by Dr. James W. Janc, vice president of pharmacology at Corvus, during the 11th Annual T-cell Lymphoma Forum, held in January in La Jolla, Calif.
Data from in-vitro studies of CPI-818, also presented at the meeting, have demonstrated cytotoxicity against several types of human and mouse T cell lymphomas at concentrations that don’t harm normal T cells. In addition, there is evidence of Th1 skewing in human and mouse lymphocytes, indicating that CPI-818 induced the differentiation of T cells to cytotoxic T cells, thought to be an important component of the immune system’s destruction of cancer cells.
“CPI-818 represents a novel approach to treating T cell lymphomas, which are poorly controlled with existing therapies. Our team’s experience developing ibrutinib, a drug used to treat B cell lymphomas that is an inhibitor of BTK, which is homologous to ITK involved in T cell receptor signaling, gave us an important advantage in generating CPI-818, a highly selective inhibitor of ITK,” said Dr. Richard A. Miller, co-founder, president and CEO of Corvus. “We are encouraged by these results, which suggest the importance of ITK inhibition on T cells and immune function. We believe that CPI-818 has the potential to enhance immune response in a range of cancer types beyond T cell lymphomas, providing additional development opportunities for this program.”
Aptinyx shares data on NYX-2925
EVANSTON, Ill.—Aptinyx Inc. presented two poster presentations highlighting preclinical data on its novel NMDA receptor modulator, NYX-2925, at the American College of Neuropsychopharmacology’s Annual Meeting in Hollywood, Fla.
“We are encouraged by the preclinical effects we see with NYX-2925 on synaptic plasticity and sleep architecture, both of which are known to be NMDA receptor mediated,” pointed out Dr. Joseph Moskal, chief scientific officer at Aptinyx. “These robust preclinical data advance our understanding of this novel mechanism of action and inform our confidence in NYX-2925 as we explore its potential as a treatment for chronic pain.”
Aptinyx presented two posters, the first of which was entitled “NYX-2925 facilitates auditory-evoked long-term potentiation in rats: a translational approach for measuring NMDA receptor-mediated synaptic plasticity.” The second poster was entitled “Enhancement of synaptic plasticity by NYX-2925: Sleep cycle EEG studies in rats.”
NYX-2925 is a novel NMDA receptor modulator in Phase 2 clinical development for the treatment of painful diabetic peripheral neuropathy and under evaluation in an exploratory Phase 2 study in fibromyalgia.
A trio of presentations on SARCONEOS
PARIS—BIOPHYTIS has announced that abstracts highlighting the company’s lead candidate, SARCONEOS (BIO101) were presented at the 11th International Conference on Cachexia, Sarcopenia and Muscle Wasting, held in Maastricht, Netherlands.
Said Dr. Stanislas Veillet, CEO of BIOPHYTIS: “We are pleased with these preclinical results that demonstrate SARCONEOS accelerates skeletal muscle cell differentiation from stem cells and increases their energetic metabolism. These specific effects, combined with the stimulation of muscle protein synthesis, explain the significant effect of SARCONEOS on muscle mass, muscle strength and mobility in animal models of muscular dystrophies.”
CD37-targeting radioimmunotherapies
OSLO, Norway—Nordic Nanovector ASA has noted two new poster presentations from preclinical studies with CD37-targeting radioimmunotherapies, made at the 60th American Society of Hematology Annual Meeting & Exposition in San Diego.
The first poster, entitled “Targeted Alpha Therapy with 212Pb-NNV-003 for the Treatment of CD37 Positive B-Cell Chronic Lymphocytic Leukemia (CLL) and Non-Hodgkin Lymphoma (NHL),” describes results from a research collaboration to develop a novel CD37-targeting alpha therapy for B cell malignancies. The collaboration was established in June 2015 with Orano Med to develop and investigate a next-generation targeted alpha therapy, comprising Nordic Nanovector’s chimeric anti-CD37 antibody (NNV003) and lead-212 (212Pb), for the treatment of B cell malignancies.
The second poster, entitled “Cell Cycle Kinase Inhibitors Potentiate the Effect of 177lu-Lilotomab Satetraxetan in Treatment of Aggressive Diffuse Large B-Cell Lymphoma Cell Lines,” described results from a preclinical study aimed at identifying possible drug combinations involving Betalutin in two aggressive, radioimmunotherapy-resistant diffuse large B cell lymphoma cell lines.
New preclinical data on pan-FLT3/pan-BTK inhibitor
TORONTO—Aptose Biosciences Inc. recently announced the presentation of preclinical data from research led by the University of Texas MD Anderson Cancer Center that explored the mechanism by which CG-806, a highly potent pan-FLT3/pan-BTK inhibitor, overcomes the emergence of resistance common to other FLT3 inhibitors (FLT3i). The data were highlighted in a poster presentation at the American Society of Hematology 60th Annual Meeting & Exposition.
The poster, entitled “Concomitant Targeting of FLT3 and BTK with CG-806 overcomes FLT3-Inhibitor Resistance Through Inhibition of Autophagy,” discussed the importance of FLT-3 targeted therapy for acute myeloid leukemia (AML), during which clinical benefit is often transient to current FLT3i and followed by FLT3i-resistance and treatment failure.
The authors conclude the pan-FLT3/pan-BTK kinase inhibitor CG-806 may overcome FLT3i resistance in AML through the simultaneous inhibition of FLT3, BTK and autophagy signaling, and that CG-806 represents an agent that may prevent or overcome FLT3 inhibitor resistance in AML patients.
“As a pan-FLT3/pan-BTK multi-kinase inhibitor, CG-806 has the ability to overcome the rescue pathways that can lead to the acquired resistance seen with some current standard-of-care therapies,” mentioned Dr. William G. Rice, chairman and CEO of Aptose. “CG-806 has demonstrated a robust safety profile in IND-enabling studies to date, and we look forward to advancing it to the clinic.”
F-star discloses targets on new antibody programs
CAMBRIDGE, U.K.—In late 2018, F-star presented preclinical data on two new proprietary bispecific antibodies at the SITC Annual Meeting, PEGS Summit Europe and the ESMO Immuno-Oncology Congress.
Said Neil Brewis, chief scientific officer of F-star: “With the increase in tumor resistance to checkpoint therapies, there is an urgent need to generate new and efficacious treatment options for cancer patients. F-star’s new programs have the potential to leverage a more targeted, potent and safer immune response, even in highly immune-suppressive tumor microenvironments.”
FS120 is a dual agonist mAb² simultaneously targeting OX40 (CD134, TNFRSF4) and CD137 (4-1BB). FS222 is an agonist/antagonist mAb² against CD137 and PD-L1. Both OX40 and CD137 are co-stimulatory molecules, part of the tumor necrosis factor receptor super family (TNFRSF). Unlike checkpoint antagonists, engagement of OX40 or CD137 on activated T cells triggers a positive signal that enhances several cellular and effector functions, essential to the elimination of tumor cells.
The presented data highlighted the potent antitumor activity of F-star’s FS120 and FS222, and how each outperforms combinations of monospecific agents in multiple syngeneic tumor models. The results also describe how F-star’s bispecific format can alleviate some of the inherent limitations of an antibody-mediated TNFRSF activation, such as low efficacy or dose-dependent liver toxicity.

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