University of Southern Denmark

Overview:
The University of Southern Denmark welcomed the first students onto the campus in Odense in September 1966, and things have been developing by leaps and bounds ever since. SDU now have five faculties with more than 32,000 students, almost 20% of whom are from abroad, and more than 4,000 employees distributed across our main campus in Odense and regional campuses in Slagelse, Kolding, Esbjerg and Sønderborg.
SDU conducts world-class research and are one of the top fifty young universities in the world. Every day more than 2,000 researchers and 32,000 students build on the university’s reputation as a centre of academic excellence.
Research:
The University of Southern Denmark consists of five faculties:
<ul>
<li>Faculty of Engineering</li>
<li>Faculty of Health Sciences</li>
<li>Faculty of Science</li>
<li>Faculty of Business and Social Sciences</li>
<li>Faculty of Humanities</li>
</ul>
Every faculty consists of several departments, where the departments have a noticeable academic and economic independence and responsibility. Together departments and centres cover a wide range of research fields and educational opportunities.
Industry Partnerships:
SDU works purposefully to create dialogue between the university’s researchers and the surrounding society. To promote and make communication and knowledge exchange visible, faculties cooperate with various external parties. These activities are organised in centres. The centres serve to promote special purposes in research, education or knowledge exchange.
SDU RIO (SDU Research &amp; Innovation Organisation) supports collaboration between research, education, the business community and the public sector.

<h1 id="background">Background</h1>
Antibiotic resistance has infected global health and will continue to do so, only faster and with deadlier outcomes. CDC and WHO consider MRSA and VRE as the two Gram-positive pathogens with the highest priority and urgency in antibiotic drug discovery and development (2018).
The pleuromutilin class possess inherent advantages over many antibiotic classes:
<ul>
<li>Unique mode of action</li>
<li>Three resistance mechanisms exists, however they have slow onset and often result in bacterial growth defects</li>
</ul>
Four pleuromutilin conjugates have been approved for clinical use, all developed with the same design strategy. In 2019, Lefamulin (Nabriva Therapeutics) was approved for PO and IV use against community acquired pneumonia, cementing pleuromutilins as a systemic drug class.
<h1 id="technology-overview">Technology Overview</h1>
SDU researchers have developed a novel pleuromutilin subclass with excellent activity against MRSA, VRE as well as other resistant Staphylococci (<img src="https://s3-eu-west-1.amazonaws.com/assets.in-part.com/figures/45P1qybJQRFyJC5Gbd9r_pleuro1.PNG" alt="Figure 1" />).
The current lead compound (10) has already been successfully validated and optimized: 
Antibacterial activity: The lead compund (10) shows good antibacterial activity aginst a spectrum of virulent pathogens (<img src="https://s3-eu-west-1.amazonaws.com/assets.in-part.com/figures/npvBS07uTSG3wqVwcX9u_pleuro2.PNG" alt="Table 1" />)
Solubility: The lead compund (10) is highly soluble (<img src="https://s3-eu-west-1.amazonaws.com/assets.in-part.com/figures/cWvl1nKFSxCs32xF86nq_pleuro3.PNG" alt="Table 2" />)
Safety: Pleuromutilins are known as potential in vitro hERG and Pgp binders. This also manifested itself in vivo, although to a limited degree. SDU analysed these potential safety issues for the new subclass, due to the shared pleuromutilin core. The lead compund (10) shows no hERG or Pgp safety concerns (<img src="https://s3-eu-west-1.amazonaws.com/assets.in-part.com/figures/frJJpbGUQOCEDflwzTT3_pleuro5.PNG" alt="Table 3" />). The cytotoxicity analysis for this pleuromutilin subclass was also positive (<img src="https://s3-eu-west-1.amazonaws.com/assets.in-part.com/figures/GtcvY7fPTh66xopPwhC4_pleuro4.PNG" alt="Figure 2" />).
<h1 id="benefits">Benefits</h1>
<ul>
<li>Unique and versatile scaffold which defines a new and superior subclass of pleuromutilins</li>
<li>Potent antibacterial activity against a broad selection of problematic Gram-positive pathogens, including MRSA and VRE</li>
<li>The subclass has a strong safety profile and will be the first among pleuromutilins in MRSA and VRE treatment line</li>
<li>Pleuromutilins are known for low inherent rates of resistance and cross resistance development</li>
<li>An extensive patent protects SDU’s scaffold</li>
</ul>
<h1 id="applications">Applications</h1>
Treating antibiotic-resistant infections