Funders Forum

Chair: Ambassador Tom Mboya

The Chair welcomed invitees (TF members, ministers and international organisations) to the breakfast meeting and allowed participants to introduce themselves. He again stressed the importance of ministers to help implement the ANDI board/governance and raise awareness for ANDI. He also made a call for increase of in-country budget allocation to biomedical R&D. Funding can only commence once legal status is finalized and hosting arrangements concluded. A project development team for the AfDB proposal has been identified and these efforts will commence following the 2^nd Stakeholders meeting. The plan will be that this proposal will be presented to the ANDI board once it is constituted.

Presentation on ANDI governance, financials and implementation - Solomon Nwaka.

• Governance (Board)
• Budget expectations
• Nature of Innovation Fund
• Relationship with AfDB

Comments from AfDB representative (Tshinko Ilunga) - AfDB have been looking at two ways to support ANDI 1) help TDR establish ANDI through funds to initiate projects but this is a small funding window (technical assistance funds from country contributions as trust funds to WHO/TDR to help in establishing ANDI). This is available to member states. 2) African Development Fund is a window that is provided directly to countries allocated every 2-3 years. Also a portion allocated to “multinational” funds that could finance specific ANDI projects e.g. infrastructure building, equipment, training etc. Discussion:

• Uganda - ANDI Task Force could be tasked to collect funds directly from countries -this may be the best method of raising initial funds.
• Zambia - Positions on the board and executive director important
• TF member - Need to make clear what benefits are drawn from countries that contribute to the capitation funds => important to articulate value proposition to countries so they can make case to their governments
• TF member - How can interim funding start ahead of capitation fund? Potential to tap existing pools like EDCTP, TDR, etc. and then eventually fees put on all countries for running/capitation
• EDCTP - How will ANDI’s regional hubs link up with the recently proposed regional centers of excellence discussed at the recent WHO Health Ministers meeting Centers of excellence will be encouraged and supported by WHO but not actively created by WHO. ANDI will have overlaps but can also harmonise/synergise with these centers given the focus on drugs and diagnostics - e.g. reinforce, leverage or complement activities in this area. Currently there is no organization with the ability to translate R&D to products in Africa so really no competition with any existing organization.
• Egypt - Can EU take a role in coordinating calls on ANDI? (EU response - no specific calls on ANDI or role in leading coordination but do have regular calls on Africa and can certainly raise discussions pertaining to ANDI)
• EU - EU support of R&D in Africa has calls that are open to all researchers on Africa but cannot be made specific to ANDI or preferential to those supported by ANDI - rules of the call for proposals and evaluation cannot be changed - we are looking at other possibilities of providing support to ANDI
• Egypt - maybe use these EU calls as a way to identify promising projects that are closer to a product
• TF member - think it needs to start with a call for proposals to galvanize and begin operations such that in 18 months ANDI is operational and can sign contracts with investigators. To do so there needs to have a good prospect for several million that could be leveraged with other funders. Believe that initial money should come from Africa. Two approaches - can ask for running funds or overall endowment (10-15 M per country for 5 yrs but not contribute again or several hundreds of thousands per country every year)

“Bright Ideas” Parallel session A: Moderator: Ivan Addae-Mensah

Development, Validation and Application of a New Rapid Semi-Quantitative TLC Assay Method for Antimalarial Drugs Currently in use in Africa Ivan Addae-Mensah, Ghana (addae-mensah.pdf)

Discussions points:

• Automation of the process is in view with the expectation of more funding. At the moment communities are encouraged to use the developed kits.
• What control was used to compare the TLC data? Were TLC and HPLC run simultaneously? Bioequivalence study could be done before reporting to the drug regulatory authority. TLC was to get the possible range, and those that were seemingly complying subjected to the HPLC. Standards from the WHO collaborating centers in Sweden were used. No bioequivalence studies yet.
• What was responsible for the variation in the results from the TLC and HPLC? The ranges for the TLC facilitated a good selection for the range to be used for the HPLC. There was not very much variation.
• The spray reagents used was anisaldehyde in methanol and WHO protocol was used for the HPLC. The method used was not subjective, rather, it is a simplified method to detect fake drugs.

Discovery of specific plasmodium enoyl-ACP reductase and dihydrofolate reductase inhibitors from Sudanese medicinal plants and antimalarial candidates: Asaad Khalid, Sudan (asaad.pdf)

Discussions points:

• What percentage of the work was done in Sudan and in the USA? Enzyme is not commercially available; enzyme is received from the USA. The screening is done in Pakistan. Production of the enzyme is envisaged in Sudan.
• Was the toxicity of these compounds measured? Toxicity could be eliminated by emerging techniques so the toxicity would be done but it is not a priority.
• The currently available active components should be developed to finished products instead of continuous screening of more plants. Further studies will continue as well as screening for more active plants.
• Database of the plants have been established in other centres and should not be a priority.
• How good did some of structures presented work? About 70 % activity.
• What was the methodology used to discover the inhibitors? Spectrophotometry.
• What are the genetic differences between the parasite and the host enoyl-ACP reductase? Plasmodium has a different fatty acid synthesis pathway and is not available in the host. Most enzymes are shared with the host pathway but a few specific enzymes are the most potential targest.
• What are the functional groups at the binding site? To be explored.

Recombinant Viral Vectors as Suitable Surrogates for Pilot Antiviral Screening Studies of Medicinal Plants Esimone Charles Okechukwu, Nigeria (esimone.pdf)

Discussion Points:

• Results within days - how is this possible? Cytotoxicity? The assay takes about 36 hours for results to start showing up. The MTT method as well as the stable cell lines expressing luciferase were used for toxicity assay.
• Possible effects transferring these products into oral compounds? The method of formulating these compounds is currently been explored.
• Did you use a microscope to follow gene expression? Human cytomegalovirus (CMV) promoters were used and fluorescence microscopes was used to count GFP positive cells.

Pharmacognostic Standardization of some Herbal Medicines used in Nigeria, Towards Monograph Development Adeola Jegede, Nigeria (jegede.pdf)

Discussion Points:

• Names of plant used to be indicated on the boxes, how do you detect non compliance with the law? All raw samples provided were labeled, but there is no guarantee that these were correct.
• Standardization of raw material and the products, what are the components involved? Enlightenment seminars with traditional healers is envisaged to help the standardization process.
• Endangered species of plants - it is possible to mass propagate plants and so collaboration with NABDA (National Biotechnology Development Agency) Abuja should be sought to develop and mass produce such plants. Regulation at country level is needed and should be enforced. NIPRD is helping to facilitate the development of the products and a clearly transparent procedure is followed to involve the traditional healers.

Antimicrobial and Wound Healing Activities of the Extract of Dissotis Theifolia (Melastomataceae) Stem Formulated in Topical Pharmaceutical Vehicle Damian Chukwu Odimegwu, Nigeria (odimegwu.pdf)

Discussion Points:

• What was the control? Gentamycine cream was used as positive control.
• Was the antifungal activity tested? Were the rats used in the experiments matched for age, sex? Weight, age and sex were standardized.
• Were there any toxicity studies done? This will be done in the near future.
• Negative control was required as well as the positive control. Broth sensitivity testing was required.
• What was the range of bacteria as well as the standardization used? Wide range, the wounds were of particular size about 22 sq mm for all the animals.
• Why the choice of the rare species instead of the common plant in the region? The choice is based on previous work done by the group and the plant is also quite common in the area and generally consumed extensively.

“Bright Ideas” Parallel session B: Moderator: Barthelemy Nyasse

Anticancer antifolates for the treatment of malaria: examples of methothrexate and trimetrexate Alexis Nzila, Kenya (nzila.pdf)

Discussion points

• Were the Phase I studies conducted on children to establish toxicity?

The study sample consisted of 25 adults, Methothrexate (MTX) has been used for a long for the treatment of arthritis in adults and children and its safety has been established.

• Have you reviewed the chemistry of MTX to establish whether there are problems of resistance?

A lot has been done to on the chemistry of MTX, the drug is active against Fansidar resistant strains of P falciparum and it remains active.

Miracidial assay as a simple, inexpensive biological test for sensitivity to Praziquantel (PZQ) using field and laboratory PZQ - susceptible Schistosoma mansoni isolates Abdel Nasser Sabra, Egypt (sabra.pdf)

Discussion points

• What method have you used to assess reversal of resistance to PZQ?

An in vivo model was used to assess resistance at doses 11.5 mg - 200 mg/kg for 5 consecutive days and then sacrificed to establish susceptibility.

Molecular basis of human infectivity of Trypanosoma brucei gambiense: Potential for antisleeping sickness drug discovery Emmanuel Olofu Ogbadoyi, Nigeria (ogbadoyi.pdf)

Discussion points

• Have you compared the sequence of the Serum Resistance associated (SRA) genes available on the Database to see if there are any similarities with respect to Trypanosoma brucei gambiense? There is no need to repeat what has been done already

From the laboratory to a patent to a product: A success story from KEMRI Sophia Matu, Kenya (matu.pdf)

Discussion points

• Have you established toxicity of Tbcide?

Tbcide is used as disinfectant for use by laboratory workers to curb the risk of infection with Tuberculosis, appropriate concentrations and exposure time were confirmed to ensure effectiveness as well as establish side effects.

Industrial preclinical drug absorption, distribution, metabolism & excretion (ADME) and Pharmacokinetics (PK) for lead discovery and lead optimization Collen Masimirembwa, Zimbabwe (masimirembwa.pdf)

Discussion points

• You mentioned testing plant compounds at your facility, what are the costs?

You can send a few compounds and the facility can test them for free. However, providing for research supplies such as recombinant enzymes and reagents can be very costly. Therefore, testing of compounds will depend on the availability of funds

• The risk associated with unsafe products has been clearly reflected in one of your slides. There have been studies conducted, which involved a number of withdrawn products from the market, most of these were cold preparations, slimming agents, etc. From this study it is clear that there has been one key enzyme identified, Cytochrome P450 (CYP450) which has contributed significantly to major drug safety problem. The work you are doing is important as it will lead to safer products. Other similar offending enzymes should be identified. There are other related initiatives targeting genes, pharmacogenetics as well as pharmacogenomics that will also contribute to safety

CYP450 is the basis for selection of compounds that are tested at the facility. I also have a poster that looks at tools to support drug/ diagnostic discovery, development and optimal use of medicines with the hope to address the influence of genetics on the response to therapeutics.

Aptamer and nanotechnology based approaches for active targeted drug delivery of anti-TB drugs Boitumelo Semete, South Africa (semete.pdf)

Discussion points

• Have you considered assessing acute toxicity of the nano particles?

To establish toxicity of the nano material, histopathology assays were carried out. There are reference points available for industrial nano particles such as silica but none available for nano particles we are currently using

• It would be interesting to see interaction of nano particles with the cells in the brain since you have established that the nano particles do cross the blood - brain barrier

Post session, the judges suggested that for the next meeting, consideration be given to having two categories for the contests, namely Junior and Senior Scientist level to motivate younger scientists. Winners of best oral (Bright Ideas) and poster presentations are listed below.

	Presenter	Affiliation	Title	Category
1.	Esimone Charles	University of Nigeria, Nsukka, Nigeria; Ruhr University, Bochum, Germany	Recombinant viral vectors as suitable surrogates for pilot antiviral screening studies of medicinal plants	Bright Ideas
2.	Semete Boitumelo	Council for Scientific and Industrial Research, Polymers and Bioceramics, Pretoria, South Africa	Aptamer and nanotechnology based approaches for active targeted drug delivery of anti-TB drugs	Bright Ideas
3.	Masimirembwa Collen	African Institute of Biomedical Science and Technology, Harare, Zimbabwe	Biobank and pharmacogenetics database of African populations – tools to support drug/diagnostic discovery, development and optimal use of medicines	Poster
4.	Traore Zoumana	Malaria Research and Training Center, Bamako, Mali	Comparative efficacy of sulfadoxine – pyrimethamine + amodiaquine vs. sulfadoxine-pyrimethamine+artesunate vs. sulfadoxine-pyrimethamine alone on uncomplicated falciparum malaria in Mali	Poster
5.	Oduor Richard	Jomo Kenyatta University of Agriculture &Technology, Nairobi, Kenya; TDR , WHO, Geneva	Trypanosomal Glycogen Synthase Kinase 3: a potential drug target for Human African Trypanosomiasis	Poster
6.	Ubalijoro Eliane	McGill University, Canada	Pan - African Natural Product Library (P-ANPL): A natural Products Repository and On-site Antiparasitic Drug Discovery Platform in Africa	Poster

 

Plenary Sessions 4 & 5: Moderators: Sanaa Botros and Alex Ochem

Public-Private Partnerships, Regional Industry Focused Presentations – R&D Case Studies

Strengthening Capacity, Collaboration and Quality of Clinical Research in Africa: EDCTP Networks of Excellence - Michael Makanga (1_makanga.pdf)

Contributions and questions from participants:

1. Nigeria: How EDCTP can promote ANDI by making participation in ANDI a requirement/advantage for support from EDCTP. The major beneficiary of EDCTP is African scientists; 63% of EDCTP projects are by African PIs.
2. http://www.edctp.org/ is the website where all information on EDCTP is available.
3. Unequal distribution of projects with most in East Africa and only 10 in Central Africa. Calls are made and scientists respond. More coming from East Africa and of higher quality. EDCTP is engaging in capacity building to enable more competitive bidding.
4. University of Nairobi, Kenya: Need for skills in ethics and proposal writing or else IRBs will be burdened with low quality proposals. EDCTP has a multidisciplinary approach to clinical trials and so addresses all aspects. They leave applicants to identify where their gaps are to include various training components as deemed necessary. EDCTP currently running a project in collaboration with COHRED on mapping IRB capacity on a country-by-country basis in Africa utilizing a Wikipedia approach. Information will be freely available on the EDCTP website.

South African industry overview from Department of Trade and Industry - Anthony Mbewu (on behalf of Andre Kudlinski - 2_kudlinski_mbewu.pdf)

Contributions and questions from participants:

1. Diaspora: Wanted to know why Fansidar imports were significantly large. The response to this was not available since Dr. Mbewu was presenting for the director and so had no further details available on this.
2. Nigeria: Increase in pharmaceutical imports into South Africa over the past 15 years is worrisome. Also wanted to know how many APIs are produced in South Africa. The number of pharmaceutical companies closed down in South Africa each year is an issue of concern. Not many APIs are produced in SA; the specific number is not known. About 37 companies close down in South Africa not on account of GMP issues but based on decisions by multinationals to consolidate their operations.
3. Nigeria: How examples from India and China can be replicated in South Africa and the rest of Africa by ANDI. India and China were not signatories to the WTO agreements and so were not bound by them. Brazil is a large economy and so was able to flout WTO agreements and not get into trade wars that would severely damage their economies unlike South Africa. Brain re-gain was recommended as a means to achieve the status of India and China by making incentives available to Africans in the diaspora who wish to return to build capacity in Africa.

Prioritization of Drug Targets – The TDR Targets Database - Fernan Aguero (3-aguero.pdf)

Contributions and questions from participants:

1. Does the TDR targets database integrate other sources of information relevant to drug discovery? This TDR database does integrate other sources of information relevant to drug discovery and TDR targets makes it possible for users to ask questions and make more refined searches online.
2. Support to ANDI for docking studies. This is not offered by the TDR targets database but others in Argentina can offer this support.
3. Suggestion of a possible upgrade to an “ANDIpedia” kind of database which users can edit and include comments. TDR targets receive user information in a moderated fashion in order to avoid scams. A survey is also available for users to provide new information which will be published online.

Coordination Rationalization and integration of antimalarial drug discovery & development Initiatives (CRIMALDDI) – Steve Ward (4_crimalddi.pdf)

Contributions and questions from participants:

1. Website is up and active

http://www.crimalddi.org/. Concern about any overlap in work being done regarding antimalarials. Issues regarding various stages of work on potential antimalarials is best addressed by MMV.

2. How CRIMALDDI can help scientists. CRIMALDDI will not necessarily be funding projects but will only be coordinating existing efforts; expected to last for 24 months.

An introduction to the ICGEB - Iqbal Parker

• 75 member countries
• 3 components worldwide: Trieste, Italy; New Delhi, India; Cape-Town, South Africa
• 3-year funded projects available to researchers in member countries by competitive bid
• Doctoral and post doctoral training with returnees grants
• Organizing of meetings and training courses
• Technology transfer such as e-poetin, interferons etc available to any company and industry in member countries/li>
• ICGEB can collaborate with ANDI by training of scientists, capacity building activities and pursuing of projects in collaboration with ANDI

Plenary Session 6: Meeting Summary. Moderator: Rob Ridley

Presentation of meeting summary and conclusions was provided by Dr Tshinko Ilunga, who described the meeting as fruitful with exciting contributions throughout (meeting_summary.pdf).

Day 1: Ministers of Health, Science & Technology and other agencies pledge their support towards ANDI. The Minister for Science & Technology, Ms Naledi Pandor gave a keynote address.

Day 2: Presentation of the Strategic Business Plan and discussion on issues related to the ANDI stakeholders. Most notably the Plan was formally adopted and the draft resolution passed. This was followed by a high level roundtable discussion with the ministers who wholeheartedly gave support to ANDI and suggested broader engagement with other African ministers.

Day 3: on the concluding day, discussions continued at the Funders Forum and technical presentations were given during the parallel sessions (Bright Ideas) to demonstrate the level of capacity on the continent. Additional presentations were provided by representatives from Public private partnerships and regional industry.

CSIR, South Africa: When will ANDI project funds be available? Depending on availability, this could be possible by early 2010.

U Ghana, Ghana: A full list of representative countries should be included in the final report, to reflect the strength of ANDI.

National Centre of Research, Sudan: What will TDR do after ANDI is established? TDR will continue to give full support to ANDI.

Olabisi Onabanjo U, Nigeria: What will happened at country level in advocacy for ANDI? The establishment of hubs will be quick and they will be responsible for providing a structural framework in which the country level advocacy will be done.

The moderator thanked the ministers that attended the program and also other invitees for their invaluable contributions.

Prof. Mbewu concluded the meeting by stating that ANDI is part of a rebirth in Africa for medical research. Being the birthplace of medicine and medical sciences, the continent must not be left behind in the new wave of biorevolution.

 

Rapporteurs: Ahmed Adedeji, John H. Amuasi, Raymond De Vre, Foluke Fakorede, Noluntu Funani, Doan Hackley, Palmer Netongo and Bernadette Ramirez.