Looking back and forward to the discovery of new antimalarials

Dr David P. Jacobus, President of Jacobus Pharmaceutical

Dr Jacobus has had a notable career in the field of research spanning more than 60 years. He was instrumental in the early years of the Antimalarial Drug Discovery and Development programme at the Walter Reed Army Institute of Research, playing a critical role in setting up the infrastructure and methods used to discover drugs such as mefloquine, halofantrine and tafenoquine.

He then went on to specialize in anti-infective drug discovery at Merck for a number of years before founding his own company in 1977, Jacobus Pharmaceutical, in Princeton, New Jersey, USA.

At MMV’s Discovery Partner Meeting held in Geneva, Dr Jacobus shared his experience and observations on antimalarial drug discovery.

1. Over the course of your more than 20-year career in antimalarial research, what has been your greatest achievement?

I played a part in establishing the antimalarial programme at the Walter Reed Army Institute of Research. I believe the programme was really significant because it led to a long-term scientific interest in malaria.

In the early 1970’s drug-resistant malaria was reported around the Burmese-Chinese border. Chloroquine wasn’t working anymore and there was a real need for a new treatment. From a previous anti-radiation programme, we had a National Chemistry Advisory Board as well as equipment in place. So when we were asked to start an antimalarial programme, we knew what needed to be done. We were able to correct the mistakes from the anti-radiation programme and 7 years later, we saw mefloquine and halofantrine selected for clinical trials.

A key factor that contributed to the programme’s success was that it was wide open (it wasn’t classified). This facilitated large-scale collaborations between a diverse set of organizations, including companies and academia, with no exchange of money. There was no fee and any interested entity could participate. Furthermore, we submitted many publications, on which we never put our (individual) names and we were confident in the integrity of the data. This all started with chemistry and with a screen that was highly accurate and fundamental to the programme.

2. What critical advancements have you seen in antimalarial drug discovery over the decades?

The biggest advancement is combination therapies, using the artemisinin family in combination with another compound to knock down the parasite. This contribution came from the British antimalarial group and was really wonderful to see. It was an important new way of thinking, which led people working in labs to ask different questions and discuss new ways of reducing the parasite count.

3. What are the major challenges facing the discovery of drugs for malaria today?

The pipeline is long, so we need to know the objectives from the start and we need to know this in a highly technical way. For example, we need to be able to cure every patient; to get the parasites out of every patient and to not have the parasites linger. We also need medicines that are child-friendly.

We also mustn’t forget about resistance. You can’t make a molecule that is perfect. And at one point, the organism will do what all organisms do, which is to develop mutations and find their way around the latest therapy. This is why we are so focused today on combination therapies.

It can be difficult to see this bigger picture when you’re starting out as a single scientist working at the early discovery side of drug development. You have to look way down the path and see where it ends, with the patient. That’s what this meeting is helping us to do: to see the big picture and to generate enthusiasm about what we need to achieve.

4. What is your interest in attending this Discovery Partner Meeting?

The value of a meeting like this is that everybody listens and talks to each other and has a sense of participation and contact. You have the opportunity to meet someone who is working, maybe 3 years away from you on a drug development line, and you can discuss the challenges together. Your discussion might open the door for someone to think about something in a way they never thought of before and they may really benefit from your vision. The real value is meeting people working in your field in another institution in another part of the world.