Several parts of the project were not well-defined. The PI had a prior company that owned the assets, and the wishes of earlier collaborators who no longer contributed had to be taken into consideration. The intellectual property situation was confused. The market reception for antimicrobials, despite the global tidal wave of antimicrobial resistance that continues to grow, was lukewarm at best. Global NGOs were living as risk-free as possible. A small group of advisors who had promised to move things forward almost two years earlier had not helped in any substantive way. These were all barriers to attracting some level of investment/ funding/ partnership that might help advance the project.
First I had to convince myself of the underlying science. Was the target and its pathway critical to the pathogen? Could disabling it be potentially curative? As might be expected for a novel target, it was relatively obscure and its criticality to pathogen survival had to understood against the backdrop of a complicated life cycle. Moreover, the Standard of Care (SOC) was constantly evolving. Somehow, we would have to fit all these pieces together.
After developing a good working relationship with the PI, we started to piece things together. We had a written Patent Office opinion that an unpublished series of related compounds was patentable, so that was good, but no issued patent. We decided it was not worth investing in a patent filing since there was still an unknown amount of lead optimization work to be done and the final compounds could be quite different. To clarify future ownership, the PI wrote to previous collaborators who had now lost interest and obtained their agreement to drop any claims, to which they understandingly agreed.
The literature was culled to find evidence supporting our unique approach. Gene expression data from multiple independent sources suggested – theoretically at least – a unique way to block a critical escape mechanism of the pathogen. Susceptibility to SOC anti-infectives and their specific mechanisms of action suggested our compounds could synergize with existing treatments – a huge plus. Now we had the beginnings of a medically-relevant and novel narrative. After further refinement, we had a good, science-backed story, and we reached out to our network, friends of contacts, decision makers, NGOs, KOLs and world-class investigators of this infectious disease. The feedback was all encouraging and positive. We realized that if we could augment our preliminary in vitro data with a demonstration of synergy with SOC drugs, this would elicit even greater interest and a willingness to invest resource and or money. The PI had some unspent grant money that could be allocated to demonstrating synergy, and now with a clear focus, designed some experiments with an experienced CRO. The experiments are now underway. Also, another group has expressed a willingness to invest resources and take it to the next step. At this point, my work is done: the project has become ‘unstuck’ and is moving forward.