Treatment of hypertriglyceridemia with 2-hydroxypropyl-beta-cyclodextrin

drug development, drug discovery,

Fascinating therapeutic application of cyclodextrins have been published by Beren Therapeutics. Earlier the company already patented the use in the therapy of familial hypercholesterolemia, now they propose using hydroxypropyl-BCD against hypertriglyceridemia.
In the 2nd patent composition and purification is reported of a compounds that has a surprisingly high DS (DS-10 being the main component), which composition is far from the materials used as excipients.

WO2023156970 TREATMENT OF HYPERTRIGLYCERIDEMIA WITH 2-HYDROXYPROPYL-BETA-CYCLODEXTRIN (wipo.int)

US20230265219 COMPOSITIONS OF HYDROXYPROPYL-BETA-CYCLODEXTRIN AND METHODS OF PURIFYING THE SAME (wipo.int)

Glycovaccinology: The design and engineering of carbohydrate-based vaccine components

carbohydrates, drug development

Of the many possible candidate antigens for subunit vaccine development, carbohydrates are particularly appealing because of their ubiquitous presence on the surface of all living cells, viruses, and parasites as well as their known interactions with both innate and adaptive immune cells. Carbohydrates have also garnered attention in other aspects of vaccine development, for example, as adjuvants that enhance the immune response by either activating innate immune responses or targeting specific immune cells. Additionally, carbohydrates can function as immunomodulators that dampen undesired humoral immune responses to entire protein antigens or specific, conserved regions on antigenic proteins. 
Spectecular review by Cornell University, Columbia University and Stanford University (Sophia Hulbert, Primit Desai, Michael Jewett, Matt DeLisa and Asher Williams)

Glycovaccinology: The design and engineering of carbohydrate-based vaccine components – ScienceDirect

Oligosaccharide compositions and methods of use thereof for treating inflammatory lung diseases

carbohydrates, drug development, ,

DSM proposes to use oligosaccharide compositions as microbiome metabolic therapies for treating inflammatory lung diseases and disorders, such as chronic obstructive pulmonary disease (COPD) and asthma.
See the original patent on Espacenet:

Espacenet – Oligosaccharide compositions and methods of use thereof for treating inflammatory lung diseases

Long-term administration of intravenous Trappsol® Cyclo™ (HP-β-CD) results in clinical benefits and stabilization or slowing of disease progression in patients with Niemann-Pick disease type C1: Results of an international 48-week Phase I/II trial

carbohydrates, drug development, ,

Long-term administration of intravenous Trappsol® Cyclo™ (HP-β-CD) results in clinical benefits and stabilization or slowing of disease progression in patients with Niemann-Pick disease type C1: Results of an international 48-week Phase I/II trial.
Niemann-Pick disease type C (NPC) is a rare, fatal, pan-ethnic, autosomal recessive lysosomal storage disease characterized by progressive major organ failure and neurodegeneration. Preclinical studies confirmed the critical role of systemically administered hydroxypropyl-β-cyclodextrin (HP-β-CD; Trappsol® Cyclo™) in cholesterol metabolism and homeostasis in peripheral tissues of the body, including the liver, and in the central nervous system (CNS). Herein, the pharmacokinetics (PK), safety, and efficacy of HP-β-CD and biomarkers of NPC were assessed in pediatric and adult patients with NPC1.
Cyclo Therapeutics, Inc. –  Caroline Hastings, Sharon Hrynkow et al

Long-term administration of intravenous Trappsol® Cyclo™ (HP-β-CD) results in clinical benefits and stabilization or slowing of disease progression in patients with Niemann-Pick disease type C1: Results of an international 48-week Phase I/II trial – ScienceDirect

Cyclodextrin-based anti-microbial therapy

carbohydrates, drug development, ,

Cyclodextrin-based antimicrobial/antiviral therapy discovered at the University of Southern California
A rapidly deployable nanoscale biodegradable system using hydroxypropyl beta cyclodextrin-based combination product is presented as an agnostic barrier blocking pathogenic microbes that has localized on the mucocutaneous lining of the conjunctiva, mouth and nose, lung, or gastrointestinal tract. The cyclodextrin may bind the viral particles and/or disrupt viral entry mechanisms by removing cholesterol from viral particles to reduce infectivity. Cyclodextrins also may facilitate the removal of the viral cholesterol molecules, thus rendering them less viable.
Stan Louie; Gianluca Lazzi; Jean-Marie Bouteiller

You can read the patent on Espacenet!

Novel FDA Drug Approvals 2Q 2023

drug development, drug discovery,

26 new drugs approved by the FDA’s Center for Drug Evaluation and Research (CDER) for 1H! Lots of exciting new mechanisms and modalities.

Highlights from the 2Q include –

💉 Tofersen (Qalsody), an antisense oligonucleotide indicated for the treatment of adult amyotrophic lateral sclerosis caused by SOD1 mutation.

💉 Pegunigalsidase alfa (Elfabrio), a recombinant form of human α-galactosidase-A indicated for long-term enzyme replacement therapy in patients with Fabry disease.

💊 Fezolinetant (Veozah), a selective neurokinin-3 (NK3) receptor antagonist used to treat moderate to severe vasomotor symptoms due to menopause.

👁 Perfluorohexyloctane (Miebo) is a drug used to treat dry eye disease. Check out structure! Mechanism unknown.

💉Epcoritamab (Epkinly), a bispecific CD20-directed CD3 T-cell engager used to treat relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in adults.

💊 Sulbactam/durlobactam (Xacduro), a co-packaged medication used for the treatment of bacterial pneumonia caused by Acinetobacter baumannii-calcoaceticus complex. It contains sulbactam, a beta-lactam antibacterial and beta-lactamase inhibitor; and durlobactam, a beta-lactamase inhibitor.

💊 Nirmatrelvir/ritonavir (Paxlovid), a co-packaged medication used as a treatment for COVID‑19. It contains the antiviral medications nirmatrelvir and ritonavir. Nirmatrelvir is a SARS-CoV-2 main protease inhibitor while ritonavir is a HIV-1 protease inhibitor and strong CYP3A4 inhibitor.

💉Flotufolastat F-18 (Posluma), a radiopharmaceutical diagnostic agent used in PET imaging to visualize PSMA-positive lesions in men with prostate cancer with suspected metastasis or recurrence.

💊 Sotagliflozin (Inpefa), a dual SGLT1/2 inhibitor used to reduce the risk of CV, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure or type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors

💉Glofitamab (Columvi), a bispecific mAb directed against CD20 and CD3 which is used for the treatment of relapsed or refractory diffuse large B-cell lymphoma.

💊 Ritlecitinib (Litfulo), a dual JAK3/TEC kinase family inhibitor used to treat severe alopecia areata in adults and adolescents 12 years and older.

💉Rozanolixizumab (Rystiggo), a humanized mAb targeting the human neonatal Fc receptor (FcRn) used to treat generalized myasthenia gravis.

💉Somatrogon (Ngenla), a long-acting recombinant human growth hormone used as the long-term treatment of pediatric patients who have growth failure due to growth hormone deficiency.

Again, a fascinating collection from Chris de Savi!

Oral polysaccharide for treating inflammatory bowel disease and preparation method therefor

drug development,

Great invention using refined heparin-like polysaccharides for the treatment of inflammatory bowel disease and related complications. After the de-anticoagulant treatment and enzymatic hydrolysis of raw heparin, the heparin-like polysaccharides are separated by using a gel size exclusion chromatography column and specific oligosaccharides are used in the preparation of medicaments.
Further potential target diseases include irritable bowel syndrome, arthritis and other extraintestinal complications, including ankylosing spondylitis, gangrenous pyoderma disease, erythema nodosum, iritis, uveitis, episcleritis, primary sclerosing cholangitis, and rheumatoid arthritis.

See the full patent on Espacenet

Targeted protein degradation (TPD)

drug development, , ,

Clinical Degrader Drugs 
Targeted protein degradation (TPD) is an emerging field in drug discovery that aims to selectively remove disease-causing proteins from cells. By directly targeting and eliminating proteins, TPD has the potential to address a wider range of disease targets, including those that have been traditionally considered “undruggable.”
Many highly selective PROTAC molecules with improved drug-like properties are entering clinical trials.
Some of the most exciting compounds being profiled are highlighted below

💊Vepdegrestrant (ARV-471), an orally bioavailable estrogen receptor (ER) protein degrader for the treatment of patients with locally advanced or metastatic ER+/HER2- breast cancer.

💊Bavdegalutamide (ARV-110), an orally bioavailable androgen receptor (AR) protein degrader for the treatment of metastatic castration-resistant prostate cancer (mCRPC).

💊ARV-766, an orally bioavailable AR degrader for the treatment of mCRPC.

💊NX-2127, an orally bioavailable Bruton’s tyrosine kinase (BTK), Ikaros (IKZF1) and Aiolos (IKZF3) degrader for the treatment of R/R B cell malignancies.

💊NX-5948, an orally bioavailable BTK degrader for the treatment of R/R B cell malignancies.

💉DT-2216, an IV administered selective B-cell lymphoma-extra large (Bcl-XL) protein degrader for the treatment of T-cell lymphomas.

💉FHD-609, an IV administered BRD9 protein degrader for the treatment of synovial sarcoma.

💊CFT1946, an orally bioavailable mutant BRAF kinase protein degrader for the treatment of various BRAF V600E-driven cancers.

💊CFT8634, an orally bioavailable BRD9 protein degrader for the treatment of synovial sarcoma.

💊KT-474, an orally bioavailable IRAK4 protein degrader for the treatment hidradenitis suppurativa (HS) and atopic dermatitis (AD).

💉KT-413, an IV administered IRAK4, IKZF1 and IKZF3 protein degrader for the treatment of  MYD88-mutant B cell lymphomas.

💉KT-333, an IV administered STAT3 protein degrader for the treatment of Peripheral T-cell Lymphoma (PTCL).

💉KT-253, an IV administered MDM2 protein degrader for the treatment of r/r high grade myeloid malignancies and solid tumors.

Tools

💉SD-36, an IV administered STAT3 tool protein degrader.

💉MD-224, an IV administered MDM2 tool protein degrader.

Another amazing summary from Chris De Savi. 

Roquette announces strategic investment and innovation agreement with Beren Therapeutics P.B.C.

carbohydrates, drug development

Roquette, a leading provider of pharmaceutical excipients and global leader in plant-based ingredients, announced a strategic investment with Beren Therapeutics and the launch of an innovation agreement to expand the full potential of Beren’s cyclodextrin technologies and their medicinal applications. 
These collaborations among key players are vital to advance cyclodextrin-based innovations and to bring bright ideas closed to the market.
Way to go, guys!

Original press release here!

Reduction of thyroid radioactive iodine exposure by oral administration of cyclic oligosaccharides

drug development, ,

Radioactive iodine may cause thyroid cancer and hypofunction and accordingly must be properly managed. If the absorption of radioactive iodine is suppressed, it can be expected to lead to a reduction in thyroid exposure. This study the inhibition of radioactive iodine absorption by the oral administration of α-cyclodextrin is shown in a murine model. The uptake of radioactive iodine into the thyroid gland in mice administered with radioactive iodine and an α-cyclodextrin solution was approximately 40% lower after 24 h. The finding that oral uptake of α-cyclodextrin has an inhibitory effect on the transfer of radioactive iodine to the thyroid gland has potential for application in many fields such as food, pharmaceuticals, nuclear emergency preparedness, and medicine.
Kumamoto University, JAPAN

See the full article on nature.com