H3D: Africa’s First Integrated Drug Discovery and Development Platform

By Catherine Jewell, Information and Digital Outreach Division, WIPO

Kelly Chibale, is a Professor of Organic Chemistry at the University of Cape Town (UCT), holds the Neville Isdell Chair in African-centric Drug Discovery & Development and is also Director of H3D, Africa’s first integrated drug discovery and development center. H3D was founded at UCT in April 2010 and focuses on translational medicine, which involves early-stage medicines discovery in the lab through to the treatment of patients in clinical settings. “The lessons we learn in the clinical setting are fed back into our lab work,” Chibale says. “We are an integrated center and, as such, we draw on multiple disciplines, including chemistry, biology and pharmacology.” WIPO Magazine recently sat down with Chibale to learn more about H3D and the role intellectual property (IP) plays in its ground-breaking work.

What is the potential of drug discovery in Africa?

Africa is arguably the most genetically diverse continent. Everybody came from Africa and went somewhere else. That means diseases are not African problems or African diseases, they are human diseases, human problems. So, drug discovery in Africa has huge potential to contribute to humanity and to create local jobs.

We need to support drug discovery in Africa given the relationship between the genetics of a population, the social, economic, and physical environment in which they live, and effective treatment outcomes. That’s why it makes sense to do the drug discovery in proximity to patients. Only then can we fully understand patient needs. For example, in rural Mozambique, there are no fridges to store vaccines, so we have to ensure a product is usable in locations where there are no hospitals.

How is H3D impacting health innovation in Africa?

H3D is having an impact at various levels, in particular, by creating drug discovery infrastructure and platforms capable of contributing to the global pipeline of innovative products that could be further developed. In other words, we have strengthened our capacity to translate basic science knowledge into potential life-saving medicines. And we are bridging the gap between the lab and the patient.

Tell us about H3D’s role in developing a drug development ecosystem in Africa. Why did you focus initially on malaria?

Malaria was an opportunity for us to build the infrastructure required for translational medicine. At the end of the day, beyond understanding the biology of the human malaria parasite, the drug discovery principles are the same for malaria or cancer. For example, regardless of the disease, among other things, the common goal is to understand how the human body will handle the drug candidate.

Malaria was an anchor program that enabled us to acquire the skills and experience we wanted to develop, and which we then transferred to other diseases.

The malaria project was an opportunity to work with the Medicines for Malaria Venture (MMV) and to subsequently engage with new partners, such as Merck and the Bill and Melinda Gates Foundation. Once we developed the infrastructure we needed for that project, we began adding other diseases, including tuberculosis (TB), and antimicrobial resistance. In 2022, we had an opportunity to work with Johnson & Johnson as one of the company’s three satellite centers for global health discovery. In sum, malaria was an anchor program that enabled us to acquire the skills and experience we wanted to develop, and which we then transferred to other diseases.

What were the biggest challenges you faced in that process?

Timely procurement of the chemicals and reagents we needed for our research purposes was an initial challenge. This forced us to anticipate our needs well in advance and to find new ways to solve some of these problems.

Doing this work in a university environment was another big challenge, because whereas the mission of a university is educational in nature and has an established academic performance management system, the mission of a drug discovery center like H3D, is translational medicine, which requires a non-academic performance management system.

Managing the performance of people involved in drug discovery using a university system designed to further academic goals is almost impossible. So, we had to develop a bespoke performance management system for team-based translational research. Thankfully, we had the University’s support in this and the help of our partner, Novartis. We began as a pilot and have used it for several years now. It’s been transformational in training, incentivizing, and retaining local talent as well as in raising awareness about the importance of drug research and development at the community level.

What is the current focus of H3D's work?

In terms of drug discovery, we’re focusing on action studies to identify biological targets and to better understand the mechanism of resistance of these targeted organisms to drugs. These organisms are very clever. Our job is to outsmart them.

We need to understand the mechanism of resistance and then find new ways to overcome them. That buys us time before the organisms figure out what the drug is doing to them. It can take a long time, depending on the drug and how it works. The use of combination regimens is one way to further delay resistance.

How important are partnerships to H3D's work, and to developing a robust health innovation ecosystem in Africa?

Partnerships are extremely important, even for innovative pharmaceutical companies with financial muscle. Indeed, some of the product portfolios they offer include drug candidates licensed in from third parties. This enables them to de-risk the early stages of drug development.

For H3D, partnerships were important from the start, for three reasons. First, to tackle infrastructure challenges; second, to build the technology platforms we needed; and third, to access skilled people.

Partnerships are extremely important, even for innovative pharmaceutical companies with financial muscle.

Partnerships are also important to secure funding. When you have a project with global support, you attract partners who share the same goals, funding grows, and you gain access to a network of centers of excellence. Partnerships can bring to the table what you don't have, because everyone is interested in the project’s success. When there is mutual interest, you can make a huge difference.

What about the importance of building a local procurement support system?

One of the main barriers to scientific innovation in Africa has been a lack of infrastructure in the broad sense. This includes a local procurement support system with functioning laboratories, access to the spare parts you need when something breaks down, the ability to access re-agents and chemicals readily and rapidly, and so on.

One of the main barriers to scientific innovation in Africa has been a lack of infrastructure in the broad sense.

Of course, from a business perspective, we need scale that justifies the business. At present, there are too few players, so business opportunities are limited. That's why we’re working to expand the community to create the demand that will foster the businesses we need to supply the chemicals and reagents required for research and development, for example.

What is the role of intellectual property in all this?

When there’s an unmet medical need, you have to innovate, and IP incentivizes innovation. IP is an enabler and underpins robust innovation ecosystems.

When there’s an unmet medical need, you have to innovate, and intellectual property incentivizes innovation.

Cash-strapped universities can use IP to generate new sources of income from their research, through university spinouts, for example. IP is also a magnet for investment. People want to invest in a country where there is respect for rules and laws, including IP.

Do you still need IP in Africa for infectious diseases, where commercial returns are low?

Absolutely. Because IP is also a responsibility, even for infectious diseases where commercial returns are perceived to be low. Without IP you would have a free for all. When it comes to health equity, it’s important to remember that the person who owns the IP can decide whether to share it voluntarily or not.

When you hold IP rights in a medicine, you can control its use to some extent.

When you hold IP rights in a medicine, you can control its use to some extent. That’s why, in Africa, we need to be owning IP. When we do, and we find an appropriate partner to take the IP forward, we get a return. I would rather own one percent of one billion than 99.99 percent of zero.

You have spoken before about the need for a regulatory framework and the importance of setting up the African Medicines Agency (AMA) – can you explain why this is important?

Whether it's clinical trials, or medical products, a harmonized environment where there is mutual recognition and identical policies across countries, makes securing regulatory approval cheaper, quicker, and less cumbersome. Also, certain drugs require multi-centre studies in different countries and regions, where regulators have varying capacities and regulations. This holds the process back. A unified system will bring important efficiency gains.

Also, one of Africa’s biggest problems is the availability of fake or sub-standard medicines. With a unified regulatory agency like the AMA, we can coordinate surveillance, and we can collect and share data through a centralized mechanism, thereby improving safety and lowering costs. Harmonization will bring more business to Africa because people know they'll deal with a single agency and/or harmonized regulations.

But it will take time for the AMA to become fully operational. In the meantime, we need to advance regulatory systems at a regional level.

Do you still see the need for new approaches to further advance what you have achieved so far?

Yes. At a scientific level, I’m an advocate for Afro-centric drug discovery. You need to find a target to hit – an enzyme or a protein – which may respond differently in different populations for genetic reasons.

Drug development needs to move from a one-size-fits-all focus towards a population-centric approach.

Genetic differences in the expression and activity of drug metabolizing enzymes can lead to variable responses to therapeutics. For example, in people of African descent, due to genetic mutations, enzymes responsible for metabolizing the antiretroviral drug Efavirenz work more slowly than in other populations and can result in toxicity, even death, due to drug overdose if dosages aren’t adjusted appropriately. So, drug development needs to move from a one-size-fits-all focus towards a population-centric approach.

We really need to invest in understanding the genetics of the African population with respect to biological drug targets we go after and the enzymes responsible for metabolising specific drugs.

Also, we need to address the funding gap in translational medicine, which many investors find too risky. This will require policy changes to encourage investors to see drug development as a continuum that requires investment at each stage of the value chain. This would create opportunities to share both risks and benefits, and ultimately will benefit everyone.

What can academic institutions in Africa do to support improved drug discovery?

Our universities need to include entrepreneurship in all curricula. While universities herald multidisciplinary research, their reward mechanisms favor individuals not teams, and teams are where drug discovery and development happen.

Drug discovery is a powerful tool for innovation.

Drug discovery is a powerful tool for innovation. It can only succeed with contributions from different disciplines, but success offers great societal benefit. Universities can do more by championing drug discovery as one of the pathways to translate basic science knowledge into life-saving medicines, and in so doing can demonstrate impact and attract more government funding.

Are you optimistic about the future of health innovation in Africa?

Yes, I’m very optimistic about the future. The COVID-19 pandemic has shown that we must be prepared. Whatever we do has to be locally driven, we cannot rely on other countries, because they have to prioritize their own needs. I'm very confident and very excited about the future. It doesn't have to be accomplished in my lifetime. It's about planting a seed for other people to nurture and grow.

Our plans are to catalyze job creation by driving the expansion of Africa’s drug discovery community and ecosystem to unlock some of the challenges we face.

What’s the one message you have for policymakers and youth in Africa?

My one message to the policymakers is: we need policies that prioritize and incentivize local innovators and local manufacturers and that require approval of medical products only when they’ve been tested on our people. That will ensure there's capacity for that.

My message to youth is: people who make history don't conform. Make the most of every opportunity, be consistent and recognise that you are unique. Africa is the next growth market for pharma. And while there are challenges, there are also great opportunities.

And what are H3D’s plans for the future?

Our plans are to catalyze job creation by driving the expansion of Africa’s drug discovery community and ecosystem to unlock some of the challenges we face. This has given rise to the newly established Grand Challenges African Drug Discovery Accelerator (GCADDA) network. The infrastructure we have created is showing the potential to spin out commercial entities, which is great news. Exciting things are starting to happen and there’s more to come.