GHIT, Takeda and MMV progress first-in-class antimalarial DSM265 to patient trials in Peruvian Amazon

Discussions are underway to further strengthen collaboration

05 Jun 2015

A collaboration between the Global Health Innovative Technology (GHIT) Fund, Takeda Pharmaceutical Company and MMV has recently progressed a promising antimalarial compound, DSM265, into a phase IIa clinical trial in Iquitos, Peru.

This ongoing Peruvian study is exploring the safety and efficacy of DSM265 as a treatment against the two main species of malaria parasite (Plasmodium falciparum and Plasmodium vivax). In parallel with the treatment study, the prophylactic potential of DSM265 is being assessed in two studies in collaboration with Prof. Peter Kremsner at the Tropical Institute of the University of Tübingen, Germany and Dr Jim Kublin at the Fred Hutchinson Cancer Research Center, USA.

Despite significant progress over the last decade in reducing malaria deaths, approximately half a million children still die each year from the disease. An additional 75,000–200,000 infant deaths annually are estimated to result from malaria infections in pregnant women. However, the emergence of multidrug-resistant malaria parasites in the Mekong Delta region may pose a threat to malaria control efforts and highlights the need for improved medicines with new mechanisms of action against the parasite for treatment of some of the most vulnerable patient populations.

DSM265 belongs to a class of triazolopyrimidine-based, highly-selective inhibitors that target Plasmodium’s dihydroorotate dehydrogenase (DHODH), a key enzyme for the malaria parasite’s survival and reproductive cycle. Since DSM265 and similar compounds in the class do not target human DHODH at therapeutic doses, they hold promise as potent and selective inhibitors of the malaria parasite, with a robust safety margin to support their use in malaria-infected people. If successful, DSM265 would be the first antimalarial to target DHODH.  

DSM265 is an MMV-led project stemming from a collaboration with three other research teams including Prof. Margaret Philips at the University of Texas Southwestern, Prof. Pradip Rathod, University of Washington, and Prof. Sue Charman, Monash University. Prof. Phillips' team identified DSM265 via high throughput screening. MMV joined forces with GHIT and Takeda in 2013 to move the compound into studies first in healthy human volunteers and now into patients.

“The advancement of DSM265 into phase IIa clinical trials represents a significant step towards developing new and better drugs to treat, and possibly even prevent, malaria,” said Dr. BT Slingsby, CEO of the Tokyo-based GHIT Fund, which draws upon Japanese research and development expertise to fight neglected infectious diseases. “GHIT is proud to invest in this work and excited to see such incredible progress in our malaria portfolio.”

Based on this initial success the GHIT Fund, Takeda and MMV are in discussions to strengthen their collaborative efforts on and commitment to antimalarial drug research and development. This will include financial support for the continued development of this promising class of antimalarial medicines.

“We are delighted to be collaborating with Takeda and GHIT on the development of DSM265,” said David Reddy, MMV’s CEO. “Their support has enabled us to progress the compound to phase IIa trials and investigate its safety and efficacy in malaria patients in Peru. We look forward to continuing the successful collaboration on this promising antimalarial compound series, hoping to eventually bring this new class to many more malaria patients in need around the world.”