HyBryte™ use in early-stage cutaneous T-cell lymphoma

Cutaneous T-cell lymphoma (CTCL) is a rare type of non-Hodgkin lymphoma of the skin, where at later stages skin-homing malignant T-cells affect lymph nodes, blood, and visceral organs. Even though early CTCL does not affect survival, it can progress to more advanced stages of disease and have a significant effect on the quality of life of patients. Although expectant management is a treatment consideration in early disease stages, most patients cycle through different skin-directed therapies throughout their lifetime. It can become a challenge to manage the serious and accumulating risk of side effects of these therapies, including various skin cancers and skin damage. Adverse effects from topical therapies limit their long-term utility. Thus, there is an unmet need for well-characterized therapies that have a rapid onset of action and minimal long-term/cumulative side effect profile. Most recently, the results of a Phase 3 study of topical HyBryte™ as a potential treatment for CTCL demonstrated its efficacy and safety profile. This article summarizes what is known about HyBryte™, focuses on its mechanism of action, and highlights its effectiveness, safety, and tolerability in the context of other current FDA-approved topical therapies for CTCL

The trispecific DARPin ensovibep inhibits diverse SARS-CoV-2 variants

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with potential resistance to existing drugs emphasizes the need for new therapeutic modalities with broad variant activity. Here we show that ensovibep, a trispecific DARPin (designed ankyrin repeat protein) clinical candidate, can engage the three units of the spike protein trimer of SARS-CoV-2 and inhibit ACE2 binding with high potency, as revealed by cryo-electron microscopy analysis. The cooperative binding together with the complementarity of the three DARPin modules enable ensovibep to inhibit frequent SARS-CoV-2 variants, including Omicron sublineages BA.1 and BA.2. In Roborovski dwarf hamsters infected with SARS-CoV-2, ensovibep reduced fatality similarly to a standard-of-care monoclonal antibody (mAb) cocktail. When used as a single agent in viral passaging experiments in vitro, ensovibep reduced the emergence of escape mutations in a similar fashion to the same mAb cocktail. These results support further clinical evaluation of ensovibep as a broad variant alternative to existing targeted therapies for Coronavirus Disease 2019 (COVID-19)