OZ439: A winning network of partners

2011
Prof. Jonathan Vennerstrom, Prof. Susan Charman & Dr Sergio Wittlin

The synthetic endoperoxide project was the very first discovery project taken into MMV’s portfolio back in 2000. Today, OZ439, one of the key molecules to emerge, and one of the next generation antimalarials, is on track to potentially replace artemisinin and become a part of the much-needed one-dose cure for malaria.

The success of this project can be attributed to the commitment, enthusiasm and range of scientific expertise of its partners from across the globe. Chemistry expertise was provided by the Nebraska (USA) and Monash (Australia) teams who synthesized the target compounds and explored how the human body reacts to the drug, SwissTPH (Switzerland) evaluated the antimalarial potential of the molecules. MMV has led the coordination of the project, and is leading the clinical development.

Representatives of the project partners:

Prof. Susan Charman is the Director of the Centre for Drug Candidate Optimisation, Monash Institute of Pharmaceutical Sciences, Melbourne, Australia.

1. What attracted you to antimalarial drug research and, particularly, the ozonide project?

“The initial motivation came from knowing I would be involved in a truly unique project that could really make a difference. The project was MMV’s first drug discovery project so we were involved in pioneering a new model. Along the way, I also realized how rewarding it was to be part of a fantastic project team, and to work with terrific mentors from MMV.” 

2. What was your main role in the project?

“Providing expertise and support on all aspects related to drug metabolism and pharmacokinetics. While each role was critical, I’m convinced that the success of this project was the result of mutual respect, trust, and genuine dedication of the team to delivering outcomes. We realized early on that as a team, we were far stronger than any of us were as individuals – this can be a tremendous driver when times are tough and nothing seems to be going the way you planned!”

3. What is most exciting about OZ439 as a future antimalarial?

“OZ439 is fairly unique in that it represents a balance between having excellent efficacy, but also having good pharmacokinetic properties which hopefully, will translate to improved clinical outcomes.”

4. OZ439 is now in Phase II clinical trials. What have been the main challenges the project team has encountered and how did you overcome them?

“The biggest challenge for me was probably believing that we could deliver a drug candidate outside of a “big pharma” environment. Fortunately, the project team always had a very strong working relationship with excellent support from MMV. We were also lucky in that we had team members each with considerable experience in industrial drug development which helped keep the project focused and on-track. I learned so much from these individuals and highly value their judgment and advice.”

5. How have you and your team most benefited from working with MMV as a scientific partner?

“MMV has an incredibly strong support base and is linked with the best scientists and clinicians in the world for antimalarial drug discovery and development. MMV’s model provided a mechanism to harness our creativity and enthusiasm yet still provide the required structure and framework to convert this into two new drug candidates. I’m sure I’m a better scientist for having had the opportunity to work with MMV and its extensive network over the years.”

Prof. Jonathan Vennerstrom, Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE, USA

1. What attracted you to antimalarial drug research and, particularly, the ozonide project?

“My interest in antimalarials came from growing up in Ethiopia and seeing the effects of malaria first hand… combined with a love of chemistry. It was my postdoc, Yuxiang Dong, who synthesized the first ozonides (OZ). In the hallways of the WHO, Rob Ridley introduced me to Bill Charman and urged us to work together with scientists at Swiss TPH and Roche to write a proposal to MMV – the rest is history.” 

2. What was your main role in the project?

“Listening to and learning from OZ family members.”

3. What is most exciting about OZ439 as a future antimalarial?

“In combination with a partner drug, OZ439 could potentially be used as a single-dose cure.”

4. OZ439 is now in Phase II clinical trials. What have been the main challenges the project team has encountered and how did you overcome them?

“The discovery of OZ439 was made possible only as we more completely understood the first-generation ozonides, most particularly, their pharmacological characteristics and stability in the red blood cell in relation to their structure.”

5. How have you and your team most benefited from working with MMV as a scientific partner?

“Beyond the financial support that made the work possible, we enjoyed tremendous personal support from many at MMV.  In addition, we had strong support from ESAC members Alan Hudson and Simon Campbell.”

 

 

Dr Sergio Wittlin, Head of the Malaria Drug Discovery Group, Swiss Tropical and Public Health Institute (Swiss TPH), Basel, Switzerland

1. What attracted you to antimalarial drug research and, particularly, the ozonide project?

“I was actually doing my postdoc at the The Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia. At that time I was working in the breast cancer field and looking for a job back home in Switzerland. It so happened that Reto Brun was offering this really interesting position in malaria drug discovery in his group. The chosen person would be in charge of leading the team working on the OZ project in collaboration with MMV. I applied and was invited for an interview, but not in Basel. As luck would have it, the interview was walking distance from my lab in Melbourne at Monash University with Bill Charman. That interview with Bill was tough, but fair. And it obviously went well, because soon afterwards I was offered the job ...”

2. What was your main role in the project?

“Testing the antimalarial potency of the OZ compounds in vitro and in vivo.”

3. What is most exciting about OZ439 as a future antimalarial?

“In addition to Jon and Sue’s points, OZ439 is also fully synthetic. This means we are completely free from any issues, such as price fluctuations and unreliable supply, surrounding the agricultural production of artemisinin.”

4. OZ439 is now in Phase II clinical trials. What have been the main challenges the project team has encountered and how did you overcome them?

“Well, there have indeed been challenges. I remember one particular thing: it was back in 2003 at a meeting about 20km away from Frankfurt. The goal of the meeting was to select the clinical candidate and Bill Charman was presenting on behalf of the OZ team to an audience of a few selected ESAC members. The process took much longer than expected given the numerous queries raised by the newly chosen Pharma partner, who were obviously keen to know every detail about the drug candidate. In fact, Bill’s presentation took more than 5 hours...but it all ended on a positive note.”

5. How have you and your team most benefited from working with MMV as a scientific partner?

“I think we benefit from each other. Our institute has a very long history for working in the field of tropical diseases. For some time now, MMV has been the partner for malaria drug discovery. So working with MMV makes us really proud.”