Insights from Dr Maneesh Paul. S on the invention of antimicrobials and their impact

Timing is critical in drug discovery and development, particularly in making decisions at the right moment. It’s essential to remain objective and know when to make key decisions. Many researchers become too emotionally attached to their projects, which can cloud judgment leading to late failure with heavier costs. 

By removing subjectivity, the process becomes clearer. For example, during my lecture, I presented a Gantt chart and a flow diagram to highlight various project timelines and activities. These charts are vital for keeping our research structured. Once a molecule is invented, it’s important to define the development timelines to avoid endless iterations. Without market success, there’s no revenue, and without which new inventions can't be funded. Therefore, both scientific and commercial aspects must work together to ensure progress is made on time. 

We rely on two main drivers: data and predetermined gates. These checkpoints ensure that data passes each stage of the process before moving forward. If a molecule doesn’t meet expectations at any gate, tough decisions have to be made, whether to discontinue it or continue its development. I encourage developing novel methods of assessment in addition to the known paths of invention. This approach applies to the composition of the team members involved as well. 

We use external validation to strengthen our confidence in data and ensure that decisions are data-driven rather than emotional attachment to a particular outcome.

Another key step was Orchid’s timely out licensing of the NCE to Allecra Therapeutics who further developed this invention into a product from clinical development up until its approval; without them this NCE would not have seen the light of the day. 

In low- and middle- income countries (LMICs), the challenges are often specific to the local context and differ from those faced in high income countries. Transplanting solutions from high income countries into LMICs without considering the local context can be ineffective. 

The real issue is not just the availability of funding but understanding the local problems. It’s crucial that the people in LMICs identify their own challenges. They have a better understanding of their needs and can develop solutions in partnership with global experts/organisations that offer support and guidance. As research experts, our role is to assist or guide them in the right direction, but the identification of the problems must always come from the local context. 

India’s regulatory environment presents its own learnings in the space of new antimicrobial drug discovery which, at present, is a small part of its focus (Enmetazobactam, Zidebactam, Nafithromycin, etc.).

I favour the extension of novel drug invention’s patent life in India. India has traditionally been a hub for generics, but with the impending short available duration before the expiration of patents, it’s crucial to incentivise local inventions. It would be great to see patent provisions, similar to the GAIN Act exclusivity of the U.S. also adopted in LMICs. While there are regulatory considerations at this time, Indian invention pioneers like Orchid Pharma, Wockhardt, Bugworks, FNDR, etc. continue to make efforts in new antimicrobial discovery. 

Another challenge is the limited commercial viability of developing anti-infective drugs. Antibiotics typically treat short term conditions (3 to 21 days), making them financially less attractive compared to treatments for lifestyle disorders like hypertension or diabetes. This has led many companies to pull out of the anti-infective space where the return on investment is lower. 

As a responsible scientist, I believe that the commercial side of healthcare must align with the broader goal of societal benefit. Prebiotics are essential to strengthen our microbiota which in turn facilitates improved host response to pathogens. Similarly for example, though Orchid Pharma has intellectual property and antimicrobial products, when marketing a product, they ensure that clinicians have access to information on the best available treatments, even if that means recommending products marketed by other companies. This represents social responsibility, in holistic marketing. 

In 2022, I transitioned from being a full-time employee to advising multiple companies and startups. Now I focus on guiding companies in areas like antimicrobial development, Microbiota and ID diagnostics. I work with organisations located worldwide. I also serve on a few committees in India and abroad including UKRI’s PACE, IDSA, GARDP-REVIVE, etc. This shift allows me to share my expertise with multiple organisations to develop innovative solutions helping multiple companies and startups achieve their goals. 

Though running a discovery program at my own company Microvioma, my primary engagement is advising and supporting other organisations in this space. This new phase of my career is about guiding the next generation of innovators and multiplying experiences.