top of page
aibst-footer-logo.png
What is this project about?

The African institute of Biomedical Science and Technology (AiBST) in Zimbabwe has established a DMPK expertise capable of supporting drug discovery projects. AiBST is applying this DMPK expertise to characterize the metabolic properties of drugs from pharmaceutical companies, but such activities are few and far in-between. This is resulting in the expertise being extremely underutilized and going through start-stop cycles that make it difficult to retain skilled manpower and assays running. The reasons for this underutilization include (1) lack (few) drug discovery programs in Africa that would require such expertise, (2) lack of knowledge by researchers on the importance of DMPK in both drug discovery and development, (3) for those aware of its importance, lack of funding to pay for such services and (4) lack of visibility of the facility and its expertise to the international pharmaceutical industry which is increasingly being interested in the safety and efficacy of their products in understudied populations.


Unique aspects of AiBST expertise:

(1) Access to liver tissue from people of African ancestry hence hepatocytes and microsomes from donors with unique genetic variants commonly found in Africans such as CYP2D6*17, *29; CYP2C9*5, *8, *11, etc. This enables AiBST to study the metabolism of NCE by such variants in an integrated cellular and subcellular environment hence more predictive of the effects of these variants in drug metabolism than when they are studied in recombinant systems. Such unique variants cannot be easily secured from liver tissue vendors and CROs in Europe or America.

(2) DMPK at AiBST is Knowledge Driven. This is because the leadership and DMPK team at AiBST has more than 30 years of experience in DMPK and has a strong research component which integrates in silico, in vitro and in vivo approaches to address ADME/PK issues. This is attested by a strong research publication record on various aspects of DMPK.


Outputs and Outcomes

Through the establishment of the Pan Africa DMPK Centre of Excellence at AiBST the following is expected to manifest over the coming 5 years:

  1. Supporting the Malaria and TB early lead discovery projects in Ghana and South Africa with DMPK expert representatives to come up with project DMPK strategies, results analysis & decision making and recommendation of follow up ADME/PK assays.

  2. Supporting the Malaria lead discovery project with Tier 1 and 2 ADME/PK assays.

  3. Supporting the TB lead discovery project with a DMPK strategy for the BacPROTAC novel class of compounds.

  4. Establishing and developing the African DMPK network

  5. Training 100 DMPK scientists through an annual DMPK workshop

Immediate success and impact of this initiative will be measured by how successfully the Pan African DMPK CoE will support two lead discovery projects being funded under the Grand Challenges Africa, one on anti-TB and another on anti-Malaria lead discovery. These projects have identified AiBST as their provider of DMPK support. The support will focus on knowledge and expertise in integrating DMPK results and strategy for the selection and the design of compounds predicted to have favorable DMPK related efficacy and safety properties.


What it will take to establish this Pan African DMPK CoE

To build a CoE that will be sustainable in the long run, funding at the level of 1 000 000 USD over a 5-year period is proposed to ensure the following:

a.   Hiring and retention of Senior DMPK scientists (each with at least 3-5 years post PhD experience): a Bioanalytical Chemist (LC-MSMS expertise), a Pharmacometrician (PBPK modeling), a Biotransformation (molecular modeling of ADME properties) and a Biologists/Biochemist for assay development.  Such a staff would provide both good quality data and scientific support with respect to how the projects should proceed.

b.   Continue to grow the African Liver Tissue Biorepository by collecting and characterizing more liver tissue (hepatocytes and subcellular tissue). This resource will attract many drug discovery projects as it will enable researchers to study the ADME/PK of their compounds using tissue from people of African ancestry. Most international providers of metabolism research tissue (HLM or PHH) have limited access to such a resource.

c.   Provide DMPK support for BacPROTAC novel compounds, though developing a strategy on how to assess this family of compounds and setting up relevant in vitro assays and/or modeling and simulation approaches to predict and optimize  ADME/PK properties.

d.   Integrate DMPK data for PBPK model building and better understanding of DMPK issues in African populations.


Risks

  1. Post funding sustainability of the African DMPK Network poses a risk for the continuity of the project. The network was launched on the 2nd of August, 2023, with members from 7 institutions and 4 countries, and a estimate of 20 active scientists. Over the funding period of 5 years, we expect the number of institutions, countries and members t increase. With the planned activities and available resources, we will also build the network to be a highly valued and respected entity. At that point, we plan to start asking for membership fees to support the management of the network. We will also apply for network grants to support activities. With the expectation of having used the network to establish the ISSX African chapter and/or having established official links with other international societies such as DMDG, thus increase our chances of surviving beyond the 5-year funded period.

  2. The AiBST CoE might find it challenging to attract the mid-career DMPK scientists (3-5 years post PhD in specialized aspects of DMPK) given that they are very few such candidates in Africa and most of them prefer to be in South Africa, Europe or USA. Should this happen, AiBST plans to expand its search of such DMPK scientist to India which has been increasing the training of analytical chemists, computational scientists and chemists. Should this also fail, AiBST will use short visits by experts from industry and leading DMPK scientist (1-3 months periods) over the 5-year period to build local capacity as well as training local early career scientists (PhD graduates) in DMPK.  Either of these approaches will then enable AiBST to develop a career development program for MSc and PhD students under these out of Africa senior scientists over the 5-year period.

  3. The research environment in Africa is very challenging and is associated with flight of skilled human resources. So there is a risk that the DMPK scientists we will train under this program, e.g. In Ghana might leave their country. This will make it difficult to have sustainable local DMPK support for the project in Ghana. Should this happen, the CoE at AiBST will continue to support the malaria project with both Tier 1 and 2 ADME analysis beyond year 1 and have its DMPK expert be part of the malaria drug discovery group to provide the needed DMPK knowledge and strategic support.

  4. The TB project working on the unique PROTAC heterobifunctional molecules might encounter non-tractable DMPK issue that might lead to project termination. We believe that the DMPK knowledge we will have developed on these molecules could be useful for other disease indication this approach is being pursued.

  5. The liver tissue biobank is extremely valuable and is at risk of freeze-thaw cycles that would destroy this resource given the power supply challenges in Zimbabwe despite the proposed purchase of power backup generator. To mitigate against this, we propose to purchase a -80oC freezer that will be located off site at a hospital (where power supply is better guaranteed) . Half of the tissue collected will be stored on site and the other half in this of site freezer.

Conclusion

The overall outcome/impact of this initiative is having a world class DMPK CoE in Africa that will be able to effectively support BMGF’s investments in drug discovery on the continent and to also build capacity for research and innovation in DMPK to support pharmaceutical R&D initiatives that will need DMPK expertise.

Funder
  • BMGF

  • LifeArc

  • INV-061515 (Investment)

PI & Team Members

Collen Masimirembwa (PI)

Collaborators

None

Period
01 October 2023  - 30 September 2028 

DMPK Africa

Pan Africa DMPK Center of Excellence
Project Media

Publications

None

The Aim

The overall aim of this initiative is having a world class DMPK CoE in Africa that will be able to effectively support BMGF’s investments in drug discovery on the continent and to also build capacity for research and innovation in DMPK to support pharmaceutical R&D initiatives that will need DMPK expertise.

Navigate Between Projects

Objectives
  1. Establish a core of Senior DMPK scientists at the Pan African DMPK CoE and develop their expertise and knowledge to support drug discovery projects in addressing DMPK liabilities.

  2. Formation and operationalization of the African DMPK Research Network

  3. Support of the Malaria and TB Flagship Projects with DMPK assays:

  4. Annual Hands-on DMPK workshop for drug discovery scientists.

Additional Links

Additional Docs

bottom of page