A randomized, single-blind, Phase I trial (INVICTAN-1) assessing the bioequivalence and safety of BI 695502, a bevacizumab biosimilar candidate, in healthy subjects.

Objectives: This Phase I trial (INVICTAN®-1) evaluated three-way bioequivalence and safety of BI 695502 a bevacizumab biosimilar candidate, and reference product bevacizumab from two sources (US-approved Avastin®, Genentech; EU-approved Avastin, Roche).

Methods: Healthy male subjects (N = 91) were randomized 1:1:1 to receive a single intravenous infusion of 1 mg/kg of BI 695502 or US- or EU-approved Avastin. An interim analysis was planned when ~50% of subjects were evaluable for the primary end point to determine if the prespecified criteria for bioequivalence were achieved; if demonstrated, the study could be stopped early.

Modular synthesis of polyene side chain analogues of the potent macrolide antibiotic etnangien by a flexible coupling strategy based on hetero-bis-metallated alkenes.

An efficient procedure for the concise synthesis of hetero-bis-metallated alkenes as useful building blocks for the modular access to highly elaborate polyenes and stabilized analogues is reported. By applying these bifunctional olefins in convergent Stille/Suzuki-Miyaura couplings, novel, carefully selected side chain analogues of the potent RNA polymerase inhibitor etnangien were synthesized by a modular late stage coupling strategy and evaluated for antibacterial and antiproliferative activities.

Design, synthesis and biological evaluation of simplified side chains of the macrolide antibiotic etnangien.

Novel simplified side chains of the potent RNA polymerase inhibitor etnangien were designed, synthesized and evaluated for antibacterial activity against Gram-positive bacteria and one Gram-negative bacterium.

Efficient synthesis of diverse hetero-bis-metallated alkenes as modular reagents towards highly conjugated and isolated olefinic systems.

An efficient synthesis of diverse hetero-bis-metallated alkenes with conjugated and isolated olefin subunits is reported. Relying on those useful tin/boron reagents a convergent, palladium-catalyzed fragment coupling strategy has been developed as an elegant methodology to construct highly conjugated polyenes and stabilized olefinic analogues thereof. The utility of these reagents was further demonstrated in a concise and modular construction of extended polyene side chains of the potent polyketide antibiotic etnangien.