Aerovant (pitrakinra) / Aerovance - LARVOL DELTA

HPLC-MS/MS-based quantification of human monoclonal antibodies targeting SARS-CoV-2 in the presence of endogenous SARS-CoV-2 antibodies in human serum. (PubMed, Anal Bioanal Chem) - "To eliminate interference from endogenous anti-spike protein antibodies, an HPLC-MS/MS assay was developed to quantify the investigational monoclonal antibodies (AER001 and AER002) by targeting signature peptides spanning the monoclonal antibodies' CDR regions. In summary, the presented results show that ammonium sulphate precipitation and HPLC-MS/MS allow accurate and precise quantification of monoclonals in clinical studies. The developed methods demonstrate that HPLC-MS/MS can reliably quantify human monoclonal antibodies even when endogenous antibodies with overlapping specificities are present and are crucial for the clinical testing of two investigational COVID-19 monoclonals."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Emerging anti-spike monoclonal antibodies against SARS-CoV-2. (PubMed, Expert Opin Biol Ther) - "Strategies to potentially mitigate this are discussed. Based on prior successful experience, immunocompromised patients will certainly benefit from the utilization of mAbs for the prevention and treatment of COVID-19; thus, we need to design potential interventions to ensure the sustained activity of these agents."

Journal • Review • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

A First-in-Human Randomized Study to Assess the Safety, Tolerability, Pharmacokinetics, and Neutralization Profile of Two Investigational Long-Acting Anti-SARS-CoV-2 Monoclonal Antibodies. (PubMed, Infect Dis Ther) - "AER001 and AER002 showed an acceptable safety profile and extended half-life. High serum neutralization activity was observed against D614G and Omicron BA.1 compared to the placebo group. These data support that LS-modified mAbs can achieve durability, safety, potency, and upper airway tissue penetration and will guide the development of the next generation of mAbs for COVID-19 prevention and treatment."

Clinical • Journal • P1 data • PK/PD data • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Effect of Biologic Therapies on Airway Hyperresponsiveness and Allergic Response: A Systematic Literature Review. (PubMed, J Asthma Allergy) - "Omalizumab reduced AHR to methacholine, acetylcholine or adenosine monophosphate (3/9 studies), and reduced EAR (4/5 studies) and LAR (2/3 studies). Mepolizumab had no effect on AHR (3/3 studies), EAR or LAR (1/1 study)...Pitrakinra reduced LAR, with no effect on AHR (1/1 study). Etanercept reduced AHR to methacholine (1/2 studies). No effects were observed for lebrikizumab, tocilizumab, efalizumab, IMA-638 and anti-OX40 ligand on AHR, EAR or LAR; benralizumab on LAR; tralokinumab on AHR; and Ro-24-7472 on AHR or LAR (all 1/1 study each). No dupilumab or reslizumab studies were identified...These findings provide insights into AHR mechanisms and the precise effects of asthma biologics. Furthermore, findings suggest that tezepelumab broadly targets allergen-specific and non-allergic forms of AHR, and the underlying cells and mediators involved in asthma."

Journal • Review • Allergy • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases

Design of Glycoengineered IL-4 Antagonists Employing Chemical and Biosynthetic Glycosylation. (PubMed, ACS Omega) - "Pitrakinra, an Escherichia coli-derived IL-4 antagonist, has been evaluated in clinical trials for asthma treatment in the past; however, deficits such as short serum lifetime and potential immunogenicity among others stopped further development...To enhance the proteolytic stability of this IL-4 antagonist, additional glycan structures were introduced by glycoengineering utilizing eucaryotic expression. IL-4 antagonists with a combination of chemical and biosynthetic glycoengineering could be useful as therapeutic alternatives to IL-4 neutralizing antibodies already used to treat atopic diseases."

Journal • Asthma • Immunology • Pulmonary Disease • Respiratory Diseases • IL13 • IL4

Mapping knowledge structure and research of the biologic treatment of asthma: A bibliometric study. (PubMed, Front Immunol) - "The search strategies were as follows: topic: TS=(biologic* OR "biologic* product*" OR "biologic* therap*" OR biotherapy* OR "biologic* agent*" OR Benralizumab OR "MEDI-563" OR Fasenra OR "BIW-8405" OR Dupilumab OR SAR231893 OR "SAR-231893" OR Dupixent OR REGN668 OR "REGN-668" OR Mepolizumab OR Bosatria OR "SB-240563" OR SB240563 OR Nucala OR Omalizumab OR Xolair OR Reslizumab OR "SCH-55700" OR SCH55700 OR "CEP-38072" OR CEP38072 OR Cinqair OR "DCP-835" OR DCP835 OR Tezspire OR "tezepelumab-ekko" OR "AMG-157" OR tezspire OR "MEDI-9929" OR "MEDI-19929" OR MEDI9929 OR Itepekimab OR "REGN-3500"OR REGN3500 OR "SAR-440340"OR SAR440340 OR Tralokinumab OR "CAT-354" OR Anrukinzumab OR "IMA-638" OR Lebrikizumab OR "RO-5490255"OR "RG-3637"OR "TNX-650"OR..."

Journal • Asthma • Cough • Immunology • Inflammation • Pulmonary Disease • Respiratory Diseases

Genome-Wide Identification of ERF Transcription Factor Family and Functional Analysis of the Drought Stress-Responsive Genes in Melilotus albus. (PubMed, Int J Mol Sci) - "A total of 100 MaERF genes containing a single AP2 domain sequence were identified in this study, named MaERF001 to MaERF100, and bioinformatics analysis was performed...This work will advance the understanding of the molecular mechanisms underlying the drought response in M. albus. Further study of the promising potential candidate genes identified in this study will provide a valuable resource as the next step in functional genomics studies and improve the possibility of improving drought tolerance in M. albus by transgenic approaches."

Journal

Effect of Biologics on Allergic Response and Airway Hyperresponsiveness: A Systematic Literature Review (ATS 2022) - "Mepolizumab had no effect on EAR or LAR (1/1 study) or AHR (3/3 studies). In one study each, IMA-638, lebrikizumab and tralokinumab had no effect on AHR. Pitrakinra reduced LAR, with no effect on AHR (1/1 study). Etanercept reduced AHR in one study. Benralizumab had no effect on LAR (1/1 study), and no studies were identified assessing AHR. In one study each, efalizumab, tocilizumab, Ro-24-7472 and anti-OX40 ligand had no effect on AHR...No published studies were identified for dupilumab or reslizumab.CONCLUSIONSAcross multiple biologics studied, reductions in both EAR and LAR to allergens were observed with omalizumab and tezepelumab. Tezepelumab also consistently attenuated nonspecific AHR to methacholine or mannitol. These findings provide further insight into the mechanisms of AHR and the clinical benefits of asthma biologics and suggest that tezepelumab may broadly target mediators or cells involved in asthma inflammation."

Review • Allergy • Asthma • Inflammation • Pulmonary Disease • Respiratory Diseases

"Charter Aviation Membership Club AeroVanti Launches, Completely Re-imagines Private Aviation https://t.co/9cZZnBvxxX" (@NewsFromBW)

Targeting IL-4 for the Treatment of Atopic Dermatitis. (PubMed, Immunotargets Ther) - "The dual inhibition of these two cytokines or the selective inhibition of IL-13 proved elevated efficacy in treating AD, whereas the selective inhibition of IL-4 has been poorly investigated as IL-4 inhibiting agents did not show any advance in clinical development programs. This review describes the pathogenic role of IL-4 in AD and briefly resumes the main features of compounds selectively blocking IL-4."

Journal • Review • Atopic Dermatitis • Dermatitis • Dermatology • Immunology • Inflammation • IL13 • IL4

The Discovery and Development of AZD1402/PRS-060, an Inhaled, Potent and Selective Antagonist of the IL-4 Receptor Alpha (ERS 2018) - "...AZD1402/PRS-060 and dupilumab (IL-4R mAb) inhibited IL-4 and IL-13 induced proliferation of TF1 cells with similar potency (IC50 0.9 and 0.3 nM). In an Air Liquid Interface goblet cell differentiation assay induced by IL-13 stimulation, AZD1402/PRS-060 inhibited goblet cell metaplasia to a similar extent as AMG317 (IL-4R mAb) and pitrakinra...In the OVA model, inflammatory cell infiltration was reduced by 78% and TARC (CCL17) was reduced by 98% 48 h post challenge. AZD1402/PRS-060, potently inhibits IL-4 and IL-13 signalling in vitro and in vivo and based on these data and the proven benefit of targeting this receptor, AZD1402/PRS-060 has progressed into human clinical trials."

Asthma • Biosimilar • Immunology

Design and validation of a disease network of inflammatory processes in the NSG-UC mouse model. (PubMed, J Transl Med) - "The combination of the disease network and the NSG-UC animal model might be developed into a powerful tool to predict efficacy or in-efficacy and potential mechanistic side effects."

Journal • Preclinical