Antibiotics in the clinical pipeline as of December 2022

Do you think we are putting enough effort in developing novel antibiotics?
The need for new antibacterial drugs to treat the increasing global prevalence of drug-resistant bacterial infections has clearly attracted global attention, with a range of existing and upcoming funding, policy, and legislative initiatives designed to revive antibacterial R&D. Despite the promising early-stage antibacterial pipeline, it is essential to maintain funding for antibacterial R&D and to ensure that plans to address late-stage pipeline issues succeed.

See the full article here:

Antibiotics in the clinical pipeline as of December 2022 | The Journal of Antibiotics (

Lactic acid bacterium-containing tablets

Today’s cyclodextrin:
This is a little quiz for you. Guess WHY cyclodextrin is added to this formulation!
It is a product from Kirin Holdings, a novel lactic acid bacterium-containing tablets that comprises a lactic acid bacterium, an excipient, and a lubricant, wherein the excipient is hydroxypropyl cellulose and/or crystalline cellulose or β-cyclodextrin. The tablets prepared accordingly are claimed to have high intake efficiency and excellent hardness.

Lactic acid bacterium-containing tablets on Espacenet

Novel targets for immune-checkpoint inhibition in cancer

Immune-checkpoint inhibitors have revolutionized cancer therapy, yet many patients either do not derive any benefit from treatment or develop a resistance to checkpoint inhibitors. Intrinsic resistance can result from neoantigen depletion, defective antigen presentation, PD-L1 downregulation, immune-checkpoint ligand upregulation, immunosuppression, and tumor cell phenotypic changes. On the other hand, extrinsic resistance involves acquired upregulation of inhibitory immune-checkpoints, leading to T-cell exhaustion. Current data suggest that PD-1, CTLA-4, and LAG-3 upregulation limits the efficacy of single-agent immune-checkpoint inhibitors. Ongoing clinical trials are investigating novel immune-checkpoint targets to avoid or overcome resistance. This review provides an in-depth analysis of the evolving landscape of potentially targetable immune-checkpoints in cancer, highlight their biology, emphasizes the current understanding of resistance mechanisms, and focuses on promising strategies that are under investigation. Current results and ongoing clinical trials in this crucial field that could once again revolutionize outcomes for cancer patients are also collected.

Novel targets for immune-checkpoint inhibition in cancer – Cancer Treatment Reviews


Today’s cyclodextrin:
Oculis makes another great step to cross the final line with its dexamethasone #eyedrop formulated with its unique gamma-CD based #nanotechnology.

Once daily, OCS-01 meets primary endpoints demonstrating superior reduction in inflammation and pain vs. vehicle following cataract surgery.

OPTIMIZE’s results follow the positive and statistically significant top line results from stage 1 of the Phase 3 DIAMOND trial in Diabetic Macular Edema reported earlier this year, further highlighting the product’s potential for treating front- and back-of-the-eye diseases.

If approved, OCS-01 has the potential to become a new standard of care as the first once-daily, topical, preservative-free corticosteroid for treating inflammation and pain following ocular surgery.

Oculis | OCS-01, First Investigational Eye Drop for Front and Back of the Eye, Met Both Primary Endpoints in Phase 3 OPTIMIZE Trial with a Once Daily Regimen for the Treatment of Inflammation and Pain Following Cataract Surgery

Development of Liposome Systems for Enhancing the PK Properties of Bivalent PROTACs

Proteolysis-Targeting Chimeras (PROTACs) are a promising new technology in drug development. They have rapidly evolved in recent years, with several of them in clinical trials. While most of these advances have been associated with monovalent protein degraders, bivalent PROTACs have also entered clinical trials, although progression to market has been limited. One of the reasons is the complex physicochemical properties of the heterobifunctional PROTACs. A promising strategy to improve pharmacokinetics of highly lipophilic compounds, such as PROTACs, is encapsulation in liposome systems. Here liposome systems for intravenous administration to enhance the PK properties of two bivalent PROTAC molecules are described, by reducing clearance and increasing systemic coverage. A PROTAC-in-cyclodextrin liposome system was developed where the drug was retained in the liposome core. In PK studies at 1 mg/kg for GNE-01 the PROTAC-in-cyclodextrin liposome, compared to the solution formulation, showed a 80- and a 380-fold enhancement in AUC for mouse and rat studies, respectively. We further investigated the same PROTAC-in-cyclodextrin liposome system with the second PROTAC (GNE-02), where we monitored both lipid and drug concentrations in vivo. Similarly, in a mouse PK study of GEN-02, the PROTAC-in-cyclodextrin liposome system exhibited enhancement in plasma concentration of a 23× increase over the conventional solution formulation. Importantly, the lipid CL correlated with the drug CL. Additionally, we investigated a conventional liposome approach for GNE-02, where the PROTAC resides in the lipid bilayer. Here, a 5× increase in AUC was observed, compared to the conventional solution formulation, and the drug CL was faster than the lipid CL. These results indicate that the different liposome systems can be tailored to translate across multiple PROTAC systems to modulate and improve plasma concentrations. Optimization of the liposomes could further improve tumor concentration and improve the overall therapeutic index (TI). This delivery technology may be well suited to bring novel protein targeted PROTACs into clinics.
This is a unique industrial collaboration between GenentechArvinas & Bristol Myers Squibb.
#cyclodextrin #liposome #drugdelivery

Pharmaceutics | Free Full-Text | Development of Liposome Systems for Enhancing the PK Properties of Bivalent PROTACs (

Cyclodextrin nanoparticles in targeted cancer theranostics

Today’s cyclodextrin:
Cyclodextrin nanoparticles in targeted cancer theranostics
The field of cancer nanotheranostics is rapidly evolving, with cyclodextrin (CD)-based nanoparticles emerging as a promising tool. CDs, serving as nanocarriers, have higher adaptability and demonstrate immense potential in delivering powerful anti-cancer drugs, leading to promising and specific therapeutic outcomes for combating various types of cancer. The unique characteristics of CDs, combined with innovative nanocomplex creation techniques such as encapsulation, enable the development of potential theranostic treatments. The review here focuses mainly on the different techniques administered for effective nanotheranostics applications of CD-associated complex compounds in the domain of cancer treatments. The experimentations on various loaded drugs and their complex conjugates with CDs prove effective in in vivo results. Various cancers can have potential nanotheranostics cures using CDs as nanoparticles along with a highly efficient process of nanocomplex development and a drug delivery system. In conclusion, nanotheranostics holds immense potential for targeted drug delivery and improved therapeutic outcomes, offering a promising avenue for revolutionizing cancer treatments through continuous research and innovative approaches.

Frontiers | Cyclodextrin nanoparticles in targeted cancer theranostics (

The multifaceted roles of galectins: glycan-binding proteins with multiple personalities

Galectins are an evolutionarily conserved family of glycan-binding proteins with multifunctional roles in immunity. These proteins often shuttle between different intracellular compartments (nucleus, cytoplasm, and organelles) and are released to the extracellular milieu, where they acquire different roles in response to diverse microenvironmental stimuli, including hypoxia, nutrient availability, intracellular and extracellular pH, cytokine milieu and the presence of proinflammatory or immunosuppressive signals. Within the immune system, galectins can elicit a wide array of important functions that tailor both innate and adaptive responses, playing key roles in shaping the choreography of immune cells in health and disease. Interestingly, the same galectin can function as a cytokine, chemokine, cell adhesion molecule, immune checkpoint molecule, danger-associated molecular pattern, or growth factor depending on different cellular programs, including activation, differentiation, and trafficking, or during pathologic conditions, such as pathogen invasion, autoimmune inflammation, fibrosis and cancer.
Learn more from the great white paper by Gabriel Rabinovich!

The multifaceted roles of galectins: glycan-binding proteins with multiple personalities (

A Cyclodextrin-Based pH-Responsive MicroRNA Delivery Platform Targeting Polarization of M1 to M2 Macrophages for Sepsis Therapy

It is so great to see new ideas rising in cyclodextrin-supported gene therapy. Nucleic acid-based drugs have therapeutic potential, although their poor stability and low delivery efficiency have hindered their widespread use.
A pH-sensitive nano-drug delivery system comprising β-cyclodextrin-poly(2-(diisopropylamino)ethyl methacrylate)/distearoyl phosphoethanolamine-polyethylene glycol (β-CD-PDPA/DSPE-PEG) is synthesized and developed to target M1 macrophages and miR-223 is encapsulated into nanoparticles (NPs) for sepsis treatment. NPs/miR-223 demonstrated in vitro pH responsiveness with favorable biosafety, stability, and high delivery efficiency. In vivo studies demonstrate that NPs/miR-223 are preferentially accumulated and retained in the inflammation site, thereby reducing inflammation and improving the survival rate of mice with sepsis while exhibiting ideal biosafety. Mechanically, NPs/miR-223 regulates macrophage polarization by targeting Pknox1 and inhibiting the activation of the NF-κB signaling pathway, thereby achieving an anti-inflammatory effect. Collectively, it is demonstrated that the miRNA delivery vector described here provides a new approach for sepsis treatment and accelerates the advancement of nucleic acid drug therapy.

A Cyclodextrin‐Based pH‐Responsive MicroRNA Delivery Platform Targeting Polarization of M1 to M2 Macrophages for Sepsis Therapy – Ding – Advanced Healthcare Materials – Wiley Online Library

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

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