Dr Mukul Jain tells us how the Malaria Drug Development Catalyst is helping to find a combination partner for the promising translational candidate MMV253.
To minimize the risk of drug resistance when developing antimalarial treatments, two compounds with complementary properties are paired up to form a combination therapy. The rationale behind this is that each compound can protect the other and therefore resistance generation is delayed. With 15 candidate compounds currently in preclinical and clinical development, understanding how these different compounds interact in order to select the best combinations for further development is a complex and critical process. In 2019, MMV launched the Malaria Drug Development Catalyst – a new legal and scientific platform to promote effective collaboration between industry partners and accelerate the development of next-generation drug combinations.
The Catalyst is curated by MMV and contains successful single molecules that have entered translational development. Based on the complementary partner characteristics of the drug candidates, the Catalyst helps to identify the best combinations to take forward for clinical testing and to allow a dialogue and exchange of information between MMV’s partners. This enables faster identification and progression of viable combinations. The Catalyst is open to MMV’s pharmaceutical partners with drugs in translational development, and currently has four members – Zydus Cadila, Novartis, Merck KGaA and MMV – and of the 30 combinations studied so far, 12 have already demonstrated positive results
Can you tell us about MMV253’s journey so far?
MMV253 came out of a discovery partnership between MMV and AstraZeneca in 2014 and was acquired by Zydus in 2016 for non-clinical and clinical development. MMV253 has an exciting profile, rapidly clearing parasites from the blood after a single dose and staying in the blood above the concentration needed to kill parasites for >6 days. The compound has an unknown mechanism of action, is active against both Plasmodium falciparum and Plasmodium vivax, and has shown low resistance potential in in vitro studies. It has also shown a good safety profile in both non-clinical toxicology studies in the lab, as well as in Phase I studies in humans, with no indication currently of potential harm for the developing foetus. This suggests it may be suitable for use during pregnancy.
How is the Malaria Drug Development Catalyst assisting Zydus in the search for a combination partner?
The Catalyst is a great initiative and we are very excited to be a part of it. Given the promising efficacy and safety data we have gathered from studies conducted so far in healthy volunteers, now is the right time to identify a partner for MMV253 and map out a clinical development strategy. By bringing together industry partners of different sizes and backgrounds, and with candidates at similar stages of development, the Catalyst is helping us identify compatible partners for MMV253. Such collaboration is not always common among the private healthcare sector, so this is a really innovative model.
What has it been like working with MMV?
No other organization in the world has the same depth of knowledge and expertise in malaria drug development as MMV. At Zydus, being able to tap into MMV’s expertise is a great benefit to us and will hopefully ensure that MMV253 can one day become a treatment option for malaria. Zydus recognizes the need to bring forward new and affordable therapies for malaria, especially for use in highly endemic countries such as India, which currently carries the world’s highest burden of P. vivax malaria.1
1. According to the WHO World Malaria Report 2019, 47% of the global P. vivax burden is in India: https://www.who.int/publicationsdetail/world-malaria-report-2019