Cathepsin G (CTSG) is overexpressed and aberrantly localized for antigen presentation on acute myeloid leukemia blasts and stem cells compared to normal hematopoietic progenitors. Earlier this year, Crossbow Therapeutics Inc. announced the nomination of its first development candidate, CBX-250, a TCR-mimetic (TCRm) bispecific T-cell engager (TCE) antibody targeting a CTSG peptide-human leukocyte antigen (pHLA) complex and CD3.
The lack of acute myeloid leukemia-specific antigens is one of the challenges for targeted immunotherapy together with on-target off-tumor toxicities due to the expression of the target in normal myeloid cells. A subset of T cells – Vδ2 T-cells – which represent ~5% of the T-cell population in healthy donors, are seen as part of emerging immunotherapeutic strategies.
In tumoral cells, the modulation of the G1/S phases of cell cycle is destabilized by amplification and high expression of cyclin E (CCNE) or by mutation or loss of retinoblastoma 1 (RB1) gene. Cancer cells meeting these characteristics have been sown to be highly sensitive to cyclin-dependent kinase 2 (CDK2) depletion.
Researchers from Novacyte Therapeutics Co. Ltd. presented preclinical data for NC-18, a novel HER2-targeting antibody drug conjugate (ADC) being developed for the treatment of HER2-positive/expressing advanced solid tumors.
Biohaven Ltd.’s BHV-7000, a selective Kv7.2/7.3 potassium channel activator, is in phase II/III development for the treatment of focal epilepsy, generalized epilepsy, bipolar disorder and major depressive disorder. The company recently presented findings from preclinical testing assessing the candidate’s potential for the treatment of comorbidities associated with epilepsy.
Cyclins and cyclin-dependent kinases (CDKs) regulate the activity of E2F and Rb to drive cell cycle progression. Disrupting this interaction has shown lethality in cancer cells harboring alterations that lead to higher expression of E2F1.
Claudin 18.2 (CLDN18.2) is a member of the claudin family and is overexpressed in gastric, gastroesophageal junction and pancreatic cancer, among others. Researchers from Elevation Oncology Inc. recently presented preclinical efficacy data on the combination of EO-3021, an antibody-drug conjugate (ADC) targeting CLDN18.2, with VEGFR-2 or PD-1 inhibitors in models of gastric adenocarcinoma.
Researchers from University of Toledo and Temple University have performed preclinical studies on the novel beta-lactam, MC-100093, for its potential in the treatment of alcohol dependence.
Researchers form Shanghai Zhimeng Biopharma Inc. presented preclinical data for CB-03, a voltage-gated potassium channel-2/3 (Kv7.2/Kv7.3; KCNQ2/3) opener for the treatment of patients with refractory epilepsy and other neuropsychiatric disorders.
Opna Bio AG has presented promising data regarding their EP300/CBP inhibitor OPN-6602 for the treatment of multiple myeloma (MM). The inhibition of EP300/CBP causes cell cycle arrest and apoptosis in MM cells due to suppression of interferon regulatory factor 4 (IRF4) and MYC repression.