Leniolisib (JOENJA®) is an oral selective phosphoinositide 3-kinase-delta (PI3Kdelta) inhibitor being developed by Pharming Group NV in-licensed from Novartis for the treatment of immunodeficiency disorders. Leniolisib inhibits PI3K-delta by blocking the active binding site of PI3K-delta. In cell-free isolated enzyme assays, leniolisib was selective for PI3K-delta over PI3K-alpha (28-fold), PI3K-beta (43-fold), and PI3K-gamma (257-fold), as well as the broader kinome. In cell-based assays, leniolisib reduced pAKT pathway activity and inhibited proliferation and activation of B and T cell subsets. Gain-of-function variants in the gene encoding the p110-delta catalytic subunit or loss of function variants in the gene encoding the p85-alpha regulatory subunit each cause hyperactivity of PI3K-delta. Leniolisib inhibits the signalling pathways that lead to increased production of PIP3, hyperactivity of the downstream mTOR/AKT pathway, and to the dysregulation of B and T cells. In March 2023, leniolisib received its first approval for the treatment of activated PI3Kdelta syndrome (APDS) in adult and paediatric patients 12 years of age and older. Leniolisib is also under regulatory review in European Union for the treatment of APDS. Development of leniolisib for the treatment of Sjögren's syndrome has been discontinued.

Ibrexafungerp (BREXAFEMME®) is an orally active triterpenoid antifungal drug being developed by SCYNEXIS, Inc. for the treatment of fungal infections. The inhibition of β-1,3-D glucan synthetase by ibrexafungerp compromises the integrity of fungal cell walls. Ibrexafungerp has been recently approved for the treatment of vulvovaginal candidiasis (VVC), and it is the first novel antifungal drug class to be approved in more than 20 years. Food and Drug Administration's decision was based on positive results from two pivotal phase III studies in which oral ibrexafungerp proved both safe and effective in patients with vulvovaginal candidiasis. Development for the treatment of recurrent VVC and invasive fungal infections is ongoing.

Osilodrostat (INN, USAN) (developmental code name LCI-699) is an orally active, non-steroidal corticosteroid biosynthesis inhibitor which is under development by Novartis for the treatment of Cushing's syndrome and pituitary ACTH hypersecretion (a specific subtype of Cushing's syndrome). Osilodrostat specifically acts as a potent and selective inhibitor of aldosterone synthase (CYP11B2) and at higher dosages of 11β-hydroxylase (CYP11B1). Osilodrostat decreases plasma and urinary aldosterone levels and rapidly corrects hypokalemia, in patients with primary aldosteronism and hypertension. At doses ≥1 mg o.d. Osilodrostat markedly increases 11-deoxycortisol plasma levels and blunts ACTH-stimulated cortisol release in ≈20% of patients, consistent with the inhibition of CYP11B1. In patients with resistant hypertension, Osilodrostat produces a non-significant reduction in blood pressure, possibly due to the increase in 11-deoxycortisol levels and the stimulation of the hypothalamic-pituitary-adrenal feedback axis. Because of the lack of selectivity, poor antihypertensive effect, and short half-life, the development of Osilodrostat as antihypertensive was halted. As of 2017, Osilodrostat is in phase III and phase II clinical trials for the treatment of pituitary ACTH hypersecretion and Cushing's syndrome, respectively.

Baricitinib (trade name Olumiant) is an investigational drug for rheumatoid arthritis (RA), being developed by Incyte and Eli Lilly. Baricitinib is a selective JAK1 and JAK2 inhibitor with IC50 of 5.9 nM and 5.7 nM in cell-free assays. In February 2017 Baricitinib was approved for use in the European Union as a second-line therapy for moderate to severe active rheumatoid arthritis in adults, either alone or in combination with methotrexate. On 31 May 2018 FDA approved Barictinib for the treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies.

Amifampridine (Firdapse), currently approved in the European Union, is the first and only approved drug for the symptomatic treatment of Lambert-Eaton Myasthenic Syndrome (LEMS) in adults, a rare autoimmune disease with the primary symptoms of muscle weakness. In LEMS, the body’s own immune system attacks connections between nerves and muscles and disrupts the ability of nerve cells to send signals to muscle cells. Amifampridine blocks voltage-dependent potassium channels, thereby prolonging pre-synaptic cell membrane depolarization. Prolonging the action potential enhances the transport of calcium into the nerve ending. The resulting increase in intracellular calcium concentrations facilitates exocytosis of acetylcholine containing vesicles, which in turn enhances neuromuscular transmission. Amifampridine phosphate has been granted Orphan Drug Designation and Breakthrough Therapy designation by the FDA for the treatment of Lambert-Eaton Myasthenic Syndrome (LEMS).

Rucaparib is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for the treatment of advanced mutant BRCA ovarian cancer. Rucaparib is being investigated in clinical trials against prostate cancer, breast cancer and other neoplasms.

Sonidegib, also known as LDE225 and marketed as Odomzo, is a Hedgehog signaling pathway inhibitor (via smoothened antagonism) developed as an anticancer agent by Novartis. It was approved by the FDA for treating basal cell carcinoma in July 2015 and is awaiting approval in the EU. The hedgehog pathway is involved in many human cancers. Sonidegib effectively inhibits the regulator called smoothened (Smo), preventing the hedgehog pathway from functioning. As a result, tumours that depend on the hedgehog pathway are unable to grow. Sonidegib is approved for use in the US and EU for treatment of adults with locally advanced basal cell carcinoma (BCC) that has recurred post surgery or radiation therapy. It is also approved for adult patients with BCC who are not eligible for surgery or radiation therapy.

Tedizolid phosphate is an oxazolidinone prodrug which in the body is dephosphorylated to the active compound tedizolid. The antibacterial activity of tedizolid is mediated by binding to the 50S subunit of the bacterial ribosome resulting in inhibition of protein synthesis. Tedizolid inhibits bacterial protein synthesis through a mechanism of action different from that of other non-oxazolidinone class antibacterial drugs; therefore, cross-resistance between tedizolid and other classes of antibacterial drugs is unlikely. Tedizolid is bacteriostatic against Gram Positive bacteria such as enterococci, staphylococci, and streptococci. No drug-drug interactions were identified with tedizolid.

Tedizolid phosphate is an oxazolidinone prodrug which in the body is dephosphorylated to the active compound tedizolid. The antibacterial activity of tedizolid is mediated by binding to the 50S subunit of the bacterial ribosome resulting in inhibition of protein synthesis. Tedizolid inhibits bacterial protein synthesis through a mechanism of action different from that of other non-oxazolidinone class antibacterial drugs; therefore, cross-resistance between tedizolid and other classes of antibacterial drugs is unlikely. Tedizolid is bacteriostatic against Gram Positive bacteria such as enterococci, staphylococci, and streptococci. No drug-drug interactions were identified with tedizolid.

Ruxolitinib (trade names Jakafi and Jakavi, by Incyte Pharmaceuticals and Novartis) is a drug for the treatment of intermediate or high-risk myelofibrosis, a type of myeloproliferative disorder that affects the bone marrow. It is also being investigated for the treatment of other types of cancer (such as lymphomas and pancreatic cancer), for polycythemia vera, for plaque psoriasis, and for alopecia areata. Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) known to be associated with dysregulated JAK1 and JAK2 signaling. Ruxolitinib is a Janus-associated kinase (JAK) inhibitor with potential antineoplastic and immunomodulating activities. Ruxolitinib specifically binds to and inhibits protein tyrosine kinases JAK 1 and 2, which may lead to a reduction in inflammation and an inhibition of cellular proliferation. The JAK-STAT (signal transducer and activator of transcription) pathway plays a key role in the signaling of many cytokines and growth factors and is involved in cellular proliferation, growth, hematopoiesis, and the immune response; JAK kinases may be upregulated in inflammatory diseases, myeloproliferative disorders, and various malignancies. In a mouse model of JAK2V617F-positive MPN, ruxolitinib prevented splenomegaly, preferentially decreased JAK2V617F mutant cells in the spleen and decreased circulating inflammatory cytokines (eg, TNF-α, IL-6). Ruxolitinib was initially synthesized at Incyte Corporation that acquired the rights to develop and commercialize the drug in US. Incyte amended its Collaboration and License Agreement with Novartis, granting Novartis exclusive research, development and commercialization rights for ruxolitinib outside the U.S.