VBP-15 FREE ALCOHOL, also known as Vamorolone and VBP-15, is an anti-inflammatory compound used in the treatment of muscular dystrophy. Vamorolone is a dissociative steroid that retains high affinity binding and nuclear translocation of both glucocorticoid (agonist) and mineralocorticoid (antagonist) receptors, but does not show pharmacodynamic safety concerns of existing glucocorticoid drugs at up to 20 mg/kg/day. Vamorolone is a first-in-class steroidal multi-functional drug that shows potent inhibition of pro-inflammatory NFkB pathways via high-affinity binding to the glucocorticoid receptor, high affinity antagonism for the mineralocorticoid receptor, and membrane stabilization properties. Pre-clinical data in multiple mouse models of inflammation showed retention of anti-inflammatory efficacy, but loss of most or all side effects. Vamorolone has received Orphan Drug Designation in the US and Europe and is being developed for chronic treatment of boys with Duchenne Muscular Dystrophy (DMD).

Sotagliflozin (LX4211) is an orally-delivered small molecule compound that is currently in development for the treatment of type 1 and type 2 diabetes mellitus. Sotagliflozin (LX4211) inhibits both sodium-glucose cotransporter type 2, or SGLT2, a transporter responsible for most of the glucose reabsorption performed by the kidney, and sodium-glucose cotransporter type 1, or SGLT1, a transporter responsible for glucose and galactose absorption in the gastrointestinal tract, and to a lesser extent than SGLT2, glucose reabsorption in the kidney. Combining SGLT1 and SGLT2 inhibition in a single molecule would provide complementary insulin-independent mechanisms to treat diabetes.

Palovarotene (R-667, RO-3300074) was developed by Roche Holding AG as a selective retinoic acid receptor gamma agonist for the treatment of emphysema. Phase I clinical trials of palovarotene in patients with emphysema demonstrated that the drug is well tolerated, with improvements observed in markers of emphysema progression. Unlike all-trans retinoic acid, the pharmacokinetic profile of palovarotene appears to be dose-proportional. However, those studies were discontinued. Palovarotene is also being investigated in phase II of the clinical trial in the treatment of Fibrodysplasia Ossificans Progressiva (FOP). Palovarotene received Fast Track designation from the U.S. Food and Drug Administration (FDA) and orphan designations for the treatment of FOP from both the FDA and the European Medicines Agency (EMA).

Pacritinib (SB1518), discovered in Singapore at the labs of S*BIO Pte Ltd., is an oral tyrosine kinase inhibitor (TKI) with activity against two important activating mutations: Janus Associated Kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3). The JAK family of enzymes is a central component in signal transduction pathways, which are critical to normal blood cell growth and development as well as inflammatory cytokine expression and immune responses. Activating mutations of JAK2 are implicated in certain blood-related cancers, including myeloproliferative neoplasms (MPNs), leukemia and certain solid tumors. FLT3 is a gene commonly found mutated in patients with acute myeloid leukemia (AML). Pacritinib has demonstrated encouraging results in Phase 1 and 2 studies for patients with myelofibrosis and may offer an advantage over other JAK inhibitors through effective treatment of symptoms while having less treatment-emergent thrombocytopenia and anemia than has been seen in currently approved and in-development JAK inhibitors. Pacritinib is acquired by Cell Therapeutics, Inc. (CTI) and Baxter international and could effectively address an unmet medical need for patients living with myelofibrosis who face treatment-emergent thrombocytopenia on marketed JAK inhibitors. Currently Pacritinib is undergoing preregistration for myelofibrosis.

Tapinarof (also known as benvitimod, WB-1001; GSK-2894512), a therapeutic aryl hydrocarbon receptor agonist that selectively modulates the cytokine cascade deep under the skin, a process that rapidly decreases inflammations and skin plague. Tapinarof cream 1% (VTAMA®) is being developed by Dermavant Sciences Inc. (a subsidiary of Roivant Sciences Inc.) as a once-daily topical treatment for plaque psoriasis and atopic dermatitis. In May 2022, tapinarof cream 1% was approved in the USA for the topical treatment of plaque psoriasis in adults. Tapinarof cream 1% is also being investigated for the treatment of atopic dermatitis.

Vonoprazan (Vonoprazan fumarate or TAK-438) under brand name Takecab, discovered by Takeda, is a new medicine for treating acid-related diseases with a novel mechanism of action called potassium-competitive acid blockers (P-CABs) which competitively inhibits the binding of potassium ions to H+,K+-ATPase (also known as the proton pump) in the final step of gastric acid secretion in gastric parietal cells. The drug is approved in Japan for the treatment of acid-related diseases, including gastric ulcer, duodenal ulcer, reflux esophagitis and Adjunct to Helicobacter pylori eradication in the case of Helicobacter pylori gastritis.

Trofinetide (NNZ 2566), a proprietary small molecule analogue of glycine-proline-glutamate [Glypromate®], is being developed by Neuren Pharmaceuticals and Acadia Pharmaceuticals for the treatment of brain injuries, fragile X syndrome, Rett syndrome. Trofinetide is a synthetic analogue of a naturally occurring neurotrophic peptide derived from IGF-1, a growth factor produced by brain cells. In animal models, trofinetide exhibits a wide range of important effects including inhibiting neuroinflammation, normalizing the role of microglia and correcting deficits in synaptic function. Trofinetide was approved in March 2023 in the USA for the treatment of Rett syndrome in adult and pediatric patients 2 years of age and older.

Ganaxolone (3alpha-hydroxy-3beta-methyl-5alpha-pregnan-20-one) (GNX) is the 3beta-methylated synthetic analog of allopregnanolone; it belongs to a class of compounds referred to as neurosteroids. GNX is an allosteric modulator of GABA(A) receptors acting through binding sites which are distinct from the benzodiazepine binding site. It has activity in a broad range of animal models of epilepsy. GNX has been shown to be well tolerated in adults and children. In early phase II studies, GNX has been shown to have activity in adult patients with partial-onset seizures and epileptic children with history of infantile spasms. It is currently undergoing further development in infants with newly diagnosed infantile spasms, in women with catamenial epilepsy, and in adults with refractory partial-onset seizures. Ganaxolone is a CNS-selective GABAA modulator being developed in three different dose forms (IV, capsule, and liquid) intended to maximize therapeutic reach to adult and pediatric patients in both acute and chronic care settings.Ganaxolone is a synthetic analog of endogenous allopregnanolone, which has been shown to be an effective anticonvulsant by restoring electrical balance to the seizing brain. While allopregnanolone’s anticonvulsant and anti-anxiety activities are well documented, allopregnanolone has the potential to convert back to its metabolic precursor progesterone, which could lead to hormonal side effects. Ganaxolone has been designed with an added methyl group that prevents back conversion to an active steroid which unlocks ganaxolone’s potential for chronic use. In preclinical studies, ganaxolone exhibited potency and efficacy comparable to allopregnanolone. Both ganaxolone and allopregnanolone bind to GABAA at the synaptic and extrasynaptic binding sites. Activity with extrasynaptic GABAA receptors are of particular importance for treating patients who developed tolerance to benzodiazepines and barbiturates. Ganaxolone binds to the GABAA receptors, which opens the pore to allow chloride ions to move into the postsynaptic neuron, leading to the inhibition of neurotransmission.

ABL-001 (asciminib), a potent and selective allosteric tyrosine-protein kinase ABL1 inhibitor that is undergoing clinical development testing in patients with Chronic myeloid leukemia (CML) and Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia. is a tyrosine-protein kinase ABL1 inhibitor. In contrast to catalytic-site ABL1 kinase inhibitors, ABL001 binds to the myristoyl pocket of ABL1 and induces the formation of an inactive kinase conformation. ABL001 and second-generation catalytic inhibitors have similar cellular potencies but distinct patterns of resistance mutations, with genetic barcoding studies revealing pre-existing clonal populations with no shared resistance between ABL001 and the catalytic inhibitor nilotinib. ABL001 was tested on mice with a particularly aggressive type of CML. The combination of ABL001 and nilotinib led to complete disease control and eradicated CML xenograft tumors without recurrence after the cessation of treatment. ABL001 is being tested in clinical trials for treatment of CML and Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia alone and in combination with niotinib, imatinib or dasatinib.

Ponesimod is an experimental drug for the treatment of multiple sclerosis (MS) graft-versus-host disease and psoriasis. It acts on certain types of white blood cells (lymphocytes) which are involved in the autoimmune attack on myelin seen in multiple sclerosis (MS). Ponesimod is an orally active, reversible, and selective sphingosine-1-phosphate receptor (S1PR1) modulator. The drug is in phase II clinical trial for the treatment of graft-versus-host disease. In addition, the phase III clinical trial comparing ponesimod to teriflunomide in relapsing-remitting MS is ongoing.