Feeding the drug development pipeline through the discovery of novel chemistry

Dr Thierry Diagana (front left) and his team at NITD, Singapore
2010
Dr Thierry Diagana, Novartis Institue for Tropical Diseases, Singapore

Dr Thierry Diagana leads the malaria programme at Novartis Institute for Tropical Diseases (NITD), Singapore. Over the last few years he and his team have been working in close collaboration with MMV to explore new drug discovery approaches for malaria.

NITD609 is a novel, synthetic investigational molecule belonging to the spiroindolone class. Awarded MMV’s Project of the Year 2009, NITD609 is one of only a handful of molecules capable of completely curing a preclinical laboratory model of blood-stage malaria. NITD609 is currently in Phase I clinical trials and, if proven to be well tolerated, will be the first antimalarial not belonging to either the artemisinin or peroxide class to enter clinical efficacy studies in recent years.

 

1. The project has moved forward at a record pace – 3 to 5 years ahead of time – how did you and the team achieve this?

In retrospect it’s difficult to pinpoint any one particular reason. But, once we saw the promise in the molecule we quickly focused our efforts and didn’t pursue other less favorable projects. We had to be pragmatic, opportunistic and focused. The malaria programme was designed to be flexible – so this really allowed us to move forward quickly.

2. What’s the most exciting feature of the molecule?

It’s novel. The structure is completely different from anything that has been described as an antimalarial before. This makes it exciting, while also making it difficult to assess how it will fare as we don’t know much about this kind of molecule. In all the clinical models we have used it looks promising, but the true test will be out in the field when we test it in patients in our studies.

3. What is the added value you get from working with MMV as a partner?

The network of expertise is really the biggest added value. It’s really a huge plus to have the ESAC1 review every year where we receive a lot of valuable expert feedback and input. This is incredibly important. The project directors also provide a lot of input to the project; they monitor progress and help to make decisions about the next steps. As we get closer to clinical trials, I believe MMV’s network of clinicians and knowledge of the field is going to be invaluable.

4. In a best-case scenario when could we expect to see this molecule as a drug in the clinic?

NITD609 will need to be combined with another antimalarial partner drug, which has yet to be selected. This will lengthen the development time. However, if everything goes as we hope, typical development timelines indicate a novel antimalarial combination therapy could be available as soon as 5 to 7 years from now.

Dr Thierry Diagana is the Head of the Drug Discovery Unit at Novartis Institute for Tropical Diseases.


1. ESAC: Expert Scientific Advisory Commitee