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Adenovirus infections of immunocompromised patients can cause life-threatening disseminated disease. While there are presently no drugs specifically approved to treat these infections, there are several compounds that showed efficacy against adenovirus in preclinical studies. For any such compound, low toxicity is an essential requirement. As cumulative drug effects can accentuate pathology, especially in patients with other morbidities, it is important to limit antiviral exposure to what is absolutely necessary. This is achievable by monitoring the virus burden of the patients and administering antivirals to suppress virus replication to a non-pathogenic level. We modeled such a system using Syrian hamsters infected with a replication-competent adenovirus vector, in which luciferase expression is coupled to virus replication. We found that virus replication could be followed in vivo in the same animal by repeated measurement of luciferase expression. To test the utility of an interrupted treatment regimen, we used NPP-669 and valganciclovir, two antiviral compounds with high and moderate anti-adenoviral efficacy, respectively. We found that short-term treatment of adenovirus-infected hamsters at times of peak virus replication can prevent virus-associated pathology. Thus, we believe that this animal model can be used to model different treatment regimens for anti-adenoviral compounds. [ABSTRACT FROM AUTHOR]

Assessing innovative technologies and venture opportunities in the biopharma-life science space involves a complicated effort. However, should it be? This question is especially relevant when screening new opportunities. This paper addresses how established firms can quickly and efficiently assess new biomedicallife science ventures of different maturity (development and commercial) levels. Boni's (2012, 2019) "quick screen" and metaphorical "3 Ps" (project, product, platform) provide a practical framework to examine new biopharma-life science ventures (assets). Boni's works (2012, 2019) frame these elements. They intend to provide a framework to complement case studies for use separately in a workshop or "boot camp" format. Our present effort includes multiple case studies to provide practical guidance for the framework's use. Accordingly, this paper extends Boni's work by examining eight practical cases gathered via a purposeful sample to illustrate the use of the "quick screen" relative to each metaphorical category: project (4), product (2), and platform (2). Data sources included company and market information from company documents, firm websites, peer-review sources, market reports, and business portals. Data were mapped against "quick screen" criteria and categorized as positives, negatives, or uncertainties. Evaluation of the mapped data led to low to medium to high ratings relative to opportunity, monetary, and competitive advantage criteria. Descriptions provide qualitative insights to situate each case example relative to its specific "3 P" category, with six cases subclassified (e.g., moderatelow, low-moderate, high-moderate) when graded. This paper provides four practical contributions: 1) multiple "real world" cases to illustrate the framework, 2) a risk-opportunity-maturity relationship model, 3) scenarios of when or when not to use the "quick screen", and 4) engagement strategies based on "P" classification as practice contributions. It concludes that Boni's (2012, 2019) construct provides a useful and efficient tool for examining new biopharma-life science ventures (assets) at differing maturities. Future work should build on these case examples, findings, and contributions while embracing a more-structured case study evaluation methodology to further practice and theory contributions. [ABSTRACT FROM AUTHOR]

New antibiotics are needed to treat gram-positive bacterial pathogens. MRS-2541 is a novel inhibitor of methionyl-tRNA synthetase with selective activity against gram-positive bacteria. The minimum inhibitory concentrations (MICs) against Staphylococcus aureus, Streptococcus pyogenes, and Enterococcus species range from 0.063 to 0.5 µg/mL. Given orally to mice at 50 mg/kg every 8 hours, MRS-2541 shows sustained plasma levels well above these MICs. In the mouse thigh infection model, MRS-2541 decreased methicillin-resistant Staphylococcus aureus and Streptococcus pyogenes bacterial loads to the same degree as linezolid. MRS-2541 is a promising new antibiotic for development against skin and soft tissue infections., Competing Interests: The authors declare no conflict of interest.

Dissolution testing is a major tool used to assess a drug product's performance and as a quality control test for solid oral dosage forms. However, compendial equipment and methods may lack discriminatory power and the ability to simulate aspects of in vivo dissolution. Using low buffer capacity media combined with an absorptive phase (biphasic dissolution) increases the physiologic relevance of in vitro testing. The purpose of this study was to use non-compendial and compendial dissolution test conditions to evaluate the in vitro performance of different formulations. The United States Pharmacopeia (USP)-recommended dissolution method greatly lacked discriminatory power, whereas low buffer capacity media discriminated between manufacturing methods. The use of an absorptive phase in the biphasic dissolution test assisted in controlling the medium pH due to the drug removal from the aqueous medium. Hence, the applied non-compendial methods were more discriminative to drug formulation differences and manufacturing methods than conventional dissolution conditions. In this study, it was demonstrated how biphasic dissolution and a low buffer capacity can be used to assess in vitro drug product performance differences. This can be a valuable approach during the early stages of drug product development for investigating in vitro drug release with improved physiological relevance., Competing Interests: The authors declare no conflict of interest. Gregory K Webster is an employee of AbbVie may own AbbVie stock. AbbVie helped sponsor and fund the study; contributed to the design; participated in the collection, analysis, and interpretation of data, and in writing, reviewing, and approval of the final publication. The other authors declare no conflicts of interest related to this work.