Orphan Drug Weekly. Mercado Targets The Nobel Prize Signaling Pathway anti-tumor small molecule therapy.

Last week the FDA issued 11 orphan drug qualifications, including oncternal Therapeutics research monoclonal antibody cirmtuzumab won 2 orphan drug qualifications, Mershadon (MSD) targeted oxygen-sensing pathways of new anti-tumor small molecular therapy, thalassemia RNAi therapy, etchave been on the list, today this article drug MingKant content team will be shared with youdrugs: Nanatinostat and valganciclovirResearch and Development: Viracta TherapeuticsTreatment of Diseases: T-cell lymphomaProfile: Nanatinostat (VRx-3996) is an oral histone deacetylase (HDAC) inhibitor developed by Viracta TherapeuticsNanatinostat is selective to specific subtypes of Class I HDAC, which is key to inducing latent virus genes in EBV-related malignanciesThe combination therapy has been fda fast-track eligibility for the treatment of recurrent/refractive EBV-positive lymphoma, as well as FDA orphan drug eligibility for post-transplant lymping disease, plasma cell lymphoma, and T-cell lymphoma (including angioimmune mother cell T-cell lymphoma and extravascular NK/T cell lymphoma)Currently, the therapy is undergoing Phase 2 clinical trialsDrugs: CirmtuzumabResearch and Development Enterprise: Oncternal TherapeuticsTreatment Of Diseases: Chronic Lymphocytic Leukemia/Small Lymp hocCy, Set LymphomaProfile: Cirmtuzumab is a "first-in-class" humanized monoclonal antibody combined with ROR1 (Suffer-tyrosine Kinase-Orphan 1) ROR1 is a type 1 transmembrane protein that is essential for fetal development and is expressed on the body membrane, with an extracellular region that is critical for ligand binding and signal transductionTumor cells expressing ROR1 have the initial characteristics of tumors associated with dedifferentiationofic cancer-causing statesWhen expressed in malignant tumors of the hematologic system, such as cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), ROR1 acts as a receptor-mediated signal of the tumor growth factor Wnt5aWhen cirmtuzumab is combined with ROR1, it can block Wnt5a activation, induce tumor cell differentiation, and inhibit tumor cell proliferation, migration and survivalEarly clinical data indicate that cirmtuzumab and ibrutinib (listed under the commodity name Imbruvica) can be used as a potential therapeutic combination of CLL and MCL, and cirmzumazumab is currently in Phase 1/2 clinical trialDrugs: IMR-687Research and Development: IMARATreatment Of Diseases: Beta-ThalassemiaProfile: IMR-687 is a highly selective and powerful PDE9 small molecule inhibitor, PDE9 can be uniquely degraded cyclophosphate glycosides (cGMP)The FDA previously qualified IMR-687 with orphan drugs for the treatment of sickle cell anemiaLower levels of cGMP are commonly found in patients with sickle cell anemia and beta-thalassemia, associated with blood flow disorders, increased inflammation, increased cell adhesion and reduced vasculation of nitric oxide-mediated blood vesselsBlocking PDE9 increases cGMP levels associated with the reactivation of fetal hemoglobin (HbF, a natural hemoglobin produced during fetal development)Studies have shown that elevated levels of HbF in red blood cells can improve the symptoms of sickle cell anemia and beta-thalassemia, reducing the burden of diseaseThe drug is currently in Phase 2b clinical studiesDrugs: Using a slow viral vector that carries the gene encoded alpha-L-Adualalacidase, in vitro transduction of an automated CD34 plus enriched cell group containing hematopoietic stem cells and progenitor cells
Research and Development Enterprise: Orchard TherapeuticsTreatment Disease: AOfadmic acid I : Muscoolized mydite type I (MPS-I) is a rare genetic neurometabolic disease caused by a lack of alpha-L-Adualalase (IDUA) lysosome enzyme, which breaks down the sugaramine (also known as GAGs) moleculesThe accumulation of GAGs across multiple organ systems causes symptoms, including neurocognitive impairment, bone malformations, vision and hearing loss, and cardiovascular and lung complicationsOrchard Therapeutics is developing an outlier-selfgene therapy that treats genetic diseases by inserting genetic modifications to the patient's own blood stem cells to replace missing or defective genes and giving these genes corrected cells to the patientThis method relies on the internal ability of blood stem cells (also known as hematopoietic stem cells or HSCs) to self-renew in the patient's bone marrow and produce all types of new blood cells, avoiding the need for bone marrow transplantation Drugs: MK-6482 (PT2977) Research and Development: MsD Treatment Of Diseases: Von Hippel-Lindau Profile: Von Hippel-Lindau (VHL) disease is a rare inherited neuropathy characterized by benign and malignant tumors of multiple organs VHL (a tumor-suppressing protein) protein inactivation can abnormally activate the hypoxia induced factor (HIF-2 alpha) protein in cancer patients The study of this pathway won the Nobel Prize in Physiology or Medicine last year MK-6482 (PT2977) is a research, new, powerful, selective oral HIF-2 alpha inhibitor that is currently being evaluated in a number of clinical studies In May, Mercado published the results of a Phase 2 trial to evaluate MK-6482 treatment of VHL disease-related transparent cell cellcarcinoma (clear cell cellcarcinoma, ccRCC), which showed long-lasting remission of MK-6482 Drugs: PBP1510 Research and Development: Prestige Biopharma Treatment Of Diseases: Pancreatic Cancer Profile: PBP1510 is a human-derived anti-PAUF antibody that can target specifically expressed PAUF (pancreatic adenocarcinoma) in pancreatic cancer, and has been shown to have anti-tumor activity in pancreatic cancer The drug is in clinical phase 1 studies, according to the official website Drugs: SLN124 Research and Development: Silence Therapeutics Treatment Of Diseases: Beta-Thalassemia Profile: Beta-Thalassemia is an inherited blood disease caused by mutations in genes that encode hemoglobin beta SLN124 is a synthetic small interference RNA (siRNA) that targets TMPRSS6 mRNA, using Silence Therapeutics' proprietary RNA chemistry and delivery system to improve molecular stability and enhance effective delivery to target cells Previously, the FDA qualified the drug for orphans that treats bone marrow hyperplasia syndrome Drugs: nipocalimab (M281) Research and Development: Momenta Pharmaceuticals Treating Diseases: Prevention of of Fetal and Neonatal Hemolytic Diseases: The Presence of Pathogenic Antibodies Promotes Tissue Damage and Organ Dysfunction as markers of immune-mediated disease Using proprietary antibody engineering techniques, Momenta Pharmaceuticals developed a full human-derived IgG1 monoclonal antibody called Nipocalimab (M281) that targets FcRn's IgG binding site Blocking FcRn reduces pathogenic IgG in circulation by inhibiting IgG recirculation and inhibits the transport of pathogenic IgG through the placenta during pregnancy Drugs: Geranylgeranylacetone Research and Development: RNR BioMedical Treatment Of Diseases: Spinal Muscular Muscular Dystrophy (Spinal Muscular Dystrophy) Profile: Spinal Myelin Atrophy (SBMA) is a cause of chromosome X The genetic abnormality of the coded androgen receptor (AR) on q11-12 causes X-chain recessive genetic neurodegenerative disease, which occurs mainly in adult males and can manifest as varying degrees of lower motor neuronal damage, sensory disorders, and endocrine system abnormalities (including male androgen insensitivity) Geranylgeranylacetone is a cyclic polyoprene compound with a frame of virace, which has been developed as an oral anti-ulcer drug in Japan It has the ability to protect the gastric mucous membranes from various stress-inducing injuries and is also a powerful inducing agent of the heat shock protein (HSPs) Heat shock proteins are induced by various environmental or physiological stresss (e.g heat, hypoxia, ischemia, and infection) within cells and play a key role in providing cell protection Previously, the FDA granted it the right to prevent acute radiation syndrome and liver failure after liver removal Drugs: ISA101 Research and Development Enterprise: ISA Therapeutics Treatment Of Diseases: HPV16 Positive Cervical Cancer Profile: ISA101 is a therapeutic vaccine targeting the HPV16 E6/E7 protein, consisting of 12 synthetic long peptides derived from the HPV16 virus E6 and E7 carcinogenic proteins (25 to 35 amino acids long) Subcutaneous administration is currently used Although most HPV16 infections do not cause symptoms, are self-limiting and can be removed through a natural immune response, in some cases the virus can be integrated into the dna of cells, causing persistent infections that can lead to precancerous lesions and cancer ISA101 has completed the phase 2 trial of vulvar epithelial endothelioma, and a clinical proof of concept has been established In the case of cervical cancer, ISA101 has successfully completed a Phase 1/2 trial and ISA Therapeutics has partnered with Regeneron for further clinical development .