IDWeek 2022

IDWeek is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS) and the Society of Infectious Diseases Pharmacists (SIDP). For the first time since the COVID-19 public health emergency began, IDWeek 2022 returned to in-person attendance. It was held in Washington, D.C., and the meeting comprised 5 days of live sessions and on-demand content that included posters and oral presentations.Copyright © 2023 Clarivate.

Ensovibep, a SARS-CoV-2 antiviral designed ankyrin repeat protein, is safe and well tolerated in healthy volunteers: Results of a first-in-human, ascending single-dose Phase 1 study.

AIMS: This study aimed to assess safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) effects of ensovibep, a designed ankyrin repeat protein antiviral being evaluated as a COVID-19 treatment, in healthy volunteers in a first-in-human ascending single-dose study. METHODS: Subjects were dosed intravenously, in a randomized double-blinded manner, with either ensovibep at 3, 9 or 20 mg/kg or with placebo, and followed until Day 100. PK and safety were assessed throughout the study duration. Immunogenicity and PD via viral neutralization in serum were also assessed. RESULTS: All adverse events were of mild to moderate severity, and no serious adverse events were observed. One subject who received the 20-mg/kg dose presented with moderate hypersensitivity vasculitis 3 weeks after infusion, which fully resolved using standard procedures. In most subjects ensovibep showed expected mono-exponential decline with a half-life of around 2 weeks. Anti-drug antibodies were detected in 15 of 17 subjects, with the earliest onset detected on Day 29. Viral neutralization assays on subject serum showed effective viral neutralization over the first 3 weeks following dosing with titre values in a dose dependent manner. CONCLUSION: Ensovibep proved safe in this first-in-human safety study and exhibited PK and PD parameters consistent with the expected treatment period required for acute COVID-19 infection.

Faster clinical recovery with ensovibep compared to placebo in patients with mild-to-moderate COVID-19: interim results from the EMPATHY Phase 2 trial

Background: Ensovibep is a multi-specific DARPin (designed ankyrin repeat protein) therapeutic in clinical development for treatment of COVID-19. In Part A (Phase 2) of the EMPATHY study, ensovibep treatment demonstrated greater viral load decline versus placebo (Pbo), and a relative risk reduction for hospitalization, ER visits and death. We report the sustained clinical recovery data from Phase 2 of EMPATHY. Method(s): Patients (pts) were eligible for EMPATHY (NCT04828161) when presenting >=2 mild-to-moderate COVID19 symptoms (onset within 7 days) and a positive SARS-CoV-2 rapid antigen test on day of dosing. 407 pts were randomised (1:1:1:1) to ensovibep (600, 225 or 75mg) or Pbo as single, IV infusion. The FDA COVID-19 symptom questionnaire was used (daily to Day 15, and on Days 22, 29) to assess time to sustained clinical recovery (secondary endpoint). Result(s): Ensovibep treatment was associated with a shorter time to sustained clinical recovery versus Pbo (Fig 1). The median time to sustained recovery were 23 days, 15 days, 14 days, and 29 days in 600mg, 225mg, 75mg, placebo arms, respectively. The cumulative proportion of patients with sustained clinical recovery by Day 15 were 44%, 54%, 55% and 36% in 600mg, 225mg, 75mg, and placebo arms, respectively. Conclusion(s): Ensovibep administration was associated with earlier sustained clinical recovery versus placebo.

IDWeek 2022 Washington, DC - October 19-23, 2022

IDWeek is the joint annual meeting of the Infectious Diseases Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS) and the Society of Infectious Diseases Pharmacists (SIDP). For the first time since the COVID-19 public health emergency began, IDWeek 2022 returned to in-person attendance. It was held in Washington, D.C., and the meeting comprised 5 days of live sessions and on-demand content that included posters and oral presentations.

American Society for Microbiology (ASM) Microbe-2022 Annual Meeting Washington, DC - June 9-13, 2022 Abstrcats

Two years after the COVID-19 public health emergency began, the 2022 annual American Society for Microbiology (ASM) Microbe Conference returned to in-person attendance. ASM is one of the largest scientific professional societies with approximately 30,000 scientists and health practitioners. Its mission is to promote and advance the microbial sciences. This meeting comprised plenary sessions, scientific s and presentations across 9 scientific tracks exploring topics in microbiology including infectious pathogens like SARS-CoV-2, antimicrobial resistance, the role of microbes in climate change, agriculture and food microbiology, clinical infections and vaccines, and synthetic and applied microbiology. This report highlights a selection of presentations about treatment updates provided during the conference.

[Current and future therapeutic options for COVID-19]

The anti-inflammatory agents dexamethasone (corticosteroid), and tocilizumab and sarilumab (IL6-inhibitors) are effective in the treatment of late COVID-19. Other anti-inflammatory agents, like anakinra (IL1-inhibitor), baricitinib and tofacitinib (JAK-inhibitors) and lenzilumab (GM-CSF-inhibitor) have also shown positive results in late COVID-19. For the treatment of early COVID-19, the inhalation corticosteroid budesonide is regarded as an off-label treatment option. Virus-inhibitors, like remdesivir, molnupiravir and nirmatrelvir/ritonavir decrease the risk of hospitalization and the development of severe COVID-19 by patients with early symptoms. Monoclonal antibodies have shown limited or no efficacy against the omicron-variant of SARS-CoV-2. Fluvoxamine, l-arginine, AT-527 and ensovibep are considered as potential promising new therapies for the treatment of early COVID-19.

Thermostable designed ankyrin repeat proteins (DARPins) as building blocks for innovative drugs.

Designed ankyrin repeat proteins (DARPins) are antibody mimetics with high and mostly unexplored potential in drug development. By using in silico analysis and a rationally guided Ala scanning, we identified position 17 of the N-terminal capping repeat to play a key role in overall protein thermostability. The melting temperature of a DARPin domain with a single full-consensus internal repeat was increased by 8 °C to 10 °C when Asp17 was replaced by Leu, Val, Ile, Met, Ala, or Thr. We then transferred the Asp17Leu mutation to various backgrounds, including clinically validated DARPin domains, such as the vascular endothelial growth factor-binding domain of the DARPin abicipar pegol. In all cases, these proteins showed improvements in the thermostability on the order of 8 °C to 16 °C, suggesting the replacement of Asp17 could be generically applicable to this drug class. Molecular dynamics simulations showed that the Asp17Leu mutation reduces electrostatic repulsion and improves van-der-Waals packing, rendering the DARPin domain less flexible and more stable. Interestingly, this beneficial Asp17Leu mutation is present in the N-terminal caps of three of the five DARPin domains of ensovibep, a SARS-CoV-2 entry inhibitor currently in clinical development, indicating this mutation could be partly responsible for the very high melting temperature (>90 °C) of this promising anti-COVID-19 drug. Overall, such N-terminal capping repeats with increased thermostability seem to be beneficial for the development of innovative drugs based on DARPins.