P2a Open Label Study to Evaluate 2-HPβCD in Subjects With Diabetic Kidney Disease

Today’s cyclodextrin: After a long time, HPBCD will be evaluated again in clinics, now in a new application.
ZyVersa Therapeutics Inc. is sponsoring this Phase 2a open-label, two- to three-center study to evaluate the clinical efficacy and safety of one dose level of 2-hydroxypropyl-β-cyclodextrin (2-HPβCD) given intravenously in adult patients with type 2 diabetes, diabetic kidney disease (DKD), and proteinuria.

According to the proposed mechanism of action, HPBCD entraps and passively removes intracellular cholesterol from the kidney. It is also believed to promote active cholesterol removal through up-regulation of cholesterol efflux transporters ABCA1 and ABCG1.

Study Details | P2a Open Label Study to Evaluate 2-HPβCD in Subjects With Diabetic Kidney Disease | ClinicalTrials.gov


Insulin formulation and methods of using same in preterm infants

Today’s cyclodextrin is an excellent example of using CDs (in this particular case, HPBCD) in peptide/protein formulations. ELGAN Pharma‘s patent concerns combining insulin, cyclodextrins, and other components, where the role of the CD is stabilization and cryopreservation.

As we see more examples of CD-protein combinations in research and clinical practice, I am convinced that this use will shape future applications.

Espacenet – US2024165205A1

Evaluating the Potential of Cyclodextrins in Reducing Aggregation of Antibody–Drug Conjugates with Different Payloads

Using cyclodextrins to prevent aggregation in protein formulations has been known for some time, and we have already published a lot about this topic.

This paper from Florian Johann, Steffen Wöll, and Henning Gieseler adds some special spice to the application as they investigate the potential of CDs in reducing aggregation of Antibody–Drug Conjugates with different payloads.

The main takeaways of the study are:

Hydroxypropylated (CDs) reduced agitation-induced aggregation in all tested ADCs without causing destabilization during incubation at 40 °C.

Native CDs that are not surface active partially reduced agitation-induced aggregation in ADCs, suggesting the possibility of stabilizing mechanisms beyond mere competition at the air-liquid interface.

ADC-specific formulation effects were observed, e.g., superior performance of the large HPγCD type in stabilizing a highly unstable ADC with a bulky fluorophore payload during incubation.

Evaluating the Potential of Cyclodextrins in Reducing Aggregation of Antibody–Drug Conjugates with Different Payloads – ScienceDirect

Long-Chain Alkylthio Cyclodextrin Derivatives for Modulation of Quorum-Sensing-Based Bioluminescence in Aliivibrio fischeri Model System

Today’s cyclodextrin paper by CarboHyde CSO Milo Malanga PhD, in collaboration with former colleagues from Cyclolab R&D Ltd. and Budapest University of Technology and Economics, sheds light on the potential of cyclodextrins to inhibit bacterial communication through quorum sensing.

Quorum sensing is vital for bacteria to coordinate activities, but inhibiting this process can be a game-changer in combating bacterial infectivity. Cyclodextrins encapsulate signal molecules, disrupting bacterial communication and, consequently, the expression of virulence factors.

Excitingly, our research shows that cyclodextrins exhibit a notable inhibitory effect on the quorum-sensing system of A. fischeri. The impact varies with alkyl chain length, with alkylthio substitution amplifying inhibition and quaternary ammonium groups mitigating it. These findings highlight cyclodextrins’ potential as a promising therapeutic avenue for treating bacterial infections.

IJMS | Free Full-Text | Long-Chain Alkylthio Cyclodextrin Derivatives for Modulation of Quorum-Sensing-Based Bioluminescence in Aliivibrio fischeri Model System (mdpi.com)

FDA Approves Lilly’s Kisunla™ (donanemab-azbt) for Early Symptomatic Alzheimer’s Disease Treatment

As a company also involved in research for Alzheimer’s disease both from the DDS and API perspective, we cheer for this news!

The U.S. Food and Drug Administration (FDA) has approved Kisunla™ (donanemab-azbt), a once-monthly injection (350 mg/20 mL) for IV infusion developed by Eli Lilly and Company.

Kisunla is designed to treat adults with early symptomatic Alzheimer’s disease (AD), which includes mild cognitive impairment (MCI) and mild dementia stages of AD, with confirmed amyloid pathology. This is the first and only amyloid plaque-targeting therapy that allows stopping treatment when amyloid plaques are cleared, potentially reducing costs and the number of infusions needed.

FDA approves new drug to treat Alzheimer’s disease  (nbcnews.com)

Cyclodextrin derivatives for the treatment of gout and hyperuricemia

Inspiring research and patent from our collaborators at Università degli Studi di Torino and Universidad de Murcia

Adrián Matencio Durán, Francesco Trotta, Yousef Khazaei Monfared, Fabrizio Caldera, and José Manuel López Nicolás disclosed an invention in which various cyclodextrins are investigated in the therapy of gout and hyperuricemia.

WO2024133757 CYCLODEXTRIN DERIVATIVES FOR THE TREATMENT OF GOUT AND HYPERURICEMIA (wipo.int)

Using an effective amount of methyl-β-cyclodextrin as a combined auxiliary drug

Today’s cyclodextrin this recent patent of RemeGen Biosciences suggests that cyclodextrins, particularly methyl-beta-cyclodextrin (Fine Chemicals – www.carbohydesolutions.com) can significantly improve the efficacy of antibody-drug conjugates so that some of the ADC drugs with safety issues caused by excessive dosage can be developed. Moreover, due to the reduction in the dosage of ADC drugs, the cost of production and treatment for patients have also been significantly reduced, thereby being beneficial.

Espacenet – US2024189341A1

How do you see the future of cell and gene therapy?

Our concise outlook is the following:

Transformational Potential: Cell and gene therapies are revolutionizing how we treat diseases, promising to cure certain conditions.
They remain at the forefront of healthcare innovation.

Fast-Growing Field: These therapies are the fastest-growing therapeutics areas, with over 50 new in vivo and ex vivo gene therapy launches planned in the next few years.

Challenges and Innovation: While promising, cell and gene therapies require substantial innovation to unlock their full potential for patients. Scaling digital and analytics in discovery and R&D is part of the solution.

Market Resilience: Despite the disruptions caused by the pandemic, stakeholders, including CGT innovators, healthcare providers, and CDMOs, are optimistic that positive developments lie ahead.

Viral-Vector Therapies: Viral-vector gene therapies are here to stay, but addressing challenges and strategizing for patient access is critical for their success.

Overall, the outlook is positive, but ongoing research, regulatory advancements, and manufacturing innovations will shape the future of cell and gene therapy. 🌟

Lipid nanoparticles for nucleic acid delivery

Today’s cyclodextrin is this great patent from Roquette‘s team, Tao Peng, Lucas Goh, Jeff Chang Shih Chieh on a new class of Lipid nanoparticles (LNPs) that can be used for nucleic acid delivery, wherein LNPs comprise a nucleic acid and a nonionic or cationic cyclodextrin compound.

How do you see the future of CDs in gene therapy? Will we see solutions commercialized in the future? In GENEGUT we certainly work towards this goal!

WO2024125823 LIPID NANOPARTICLES FOR NUCLEIC ACID DELIVERY (wipo.int)

Study of progesterone complexation in cyclodextrins and cyclodextrin-based nanosponges as an example of solvent-free complexation

Today’s cyclodextrin makes me feel proud as it is the first paper of your bright young chemist Daniel Bisericaru, sprouting from the intense and fruitful collaboration between Francesco Trotta‘s team and Adrián Matencio Durán at Università degli Studi di Torino and CarboHyde.

In this work and using kneading, we have compared the encapsulation of progesterone, a lipophilic hormone used in hormone replacement therapy, with β-CD and Nanosponges. The project opens the door to new medical formulations of progesterone, supporting the ball-milling kneading as an exciting way of making complexes.

cyclodextrin, progesteron