New molecule to protect vulnerable and migratory populations

2018
Dr Alfred Tonelli, Head of External Innovation, Johnson and Johnson Global Public Health

As more countries move towards elimination of malaria, natural immunity will decline and there will be an increasing need for new chemoprotective medicines to ensure populations remain malaria free.

In 2016, MMV and Janssen Pharmaceuticals formed a new partnership to help develop better medicines to treat and protect vulnerable populations from malaria. The partnership focuses on the development of new medicines suitable for reduced dosing regimens, in particular, long-acting injectable formulations for chemoprotection that meet target product profile 2.

The MMV/Janssen team has begun this work with the compound known as P218, originally discovered through an MMV partnership with BIOTEC (Thailand), Monash University (Australia) and the London School of Hygiene and Tropical Medicine (UK). P218 is currently being developed as a potential long-acting injectable chemoprotective medicine that would deliver a regimen with less frequent dosing.

Dr Alfred Tonelli, Head of External Innovation, Johnson and Johnson Global Public Health, talks about chemoprotection and the development plan for P218.

1. What is interesting about P218?

Currently, there are few well-defined, clinically validated malaria drug targets against which we can direct our drug discovery efforts. The best known such target is Plasmodium falciparum dihydrofolate reductase (PfDHFR). The P218 molecule was designed based on three-dimensional structures of PfDHFR to hit this target and circumvent mutations that have led to resistance to pyrimethamine, a well-tolerated and previously effective drug for the treatment of malaria.

P218 also has activity against liver-stage parasites. The malaria parasite enters the liver before it multiplies in the blood, causing the symptoms of malaria. Killing the parasite at this liver stage can therefore prevent malaria infection and stop the progression of the disease before the symptoms emerge.

2. How is the development plan progressing?

The phase I study for P218 is now complete. We have also performed various modelling studies to investigate the type of profile needed for P218 as a long-acting injectable.

We are working with MMV to assess P218 in a sporozoite volunteer infection study (VIS). This study will assess P218’s chemoprotective activity and will also inform the concentration needed for P218 to achieve chemoprotection. This is being done in parallel with the development of long-acting injectable formulations that need to meet cost, stability, release and drug-loading requirements for use in malaria-endemic regions.

What is great about this is that all the study data are published in journals that are freely accessible to everyone, so all scientists can use these data to further understand and refine their own protocols, advancing the science together.

3. What did Janssen and MMV each bring to the partnership? How has working with MMV added to this process?

The MMV team is a great group of people to work with. Within Janssen Global Public Health, we have interest and experience in infectious diseases, such as tuberculosis (TB), HIV and malaria, as well as in the development of long-acting injectables. Throughout our collaboration, we have seen that MMV is passionate about what it does and is dedicated and focused on delivering treatments to those most in need.

One of the strengths of MMV is its network of leading scientists in all aspects of antimalarial drug discovery and development. When a programme is being set up, MMV invites experts who have a tremendous amount of experience and understanding of the field to work together.

MMV also has a stringent drug selection process, augmented by its Expert Scientific Advisory Committee, adding further scrutiny and rigour.

Of the three big infectious diseases in the world – TB, HIV and malaria – malaria probably has the biggest chance of being eradicated. MMV has played a huge role in tackling the multiple issues and obstacles that must be overcome to achieve this. This has been an extremely productive relationship, we have learned a lot and really enjoy working with them.