Mar 30, 2020 SOURCE: PR NewsWire
GHIT Fund Announces New Investments: A Total of 3.29 Billion Yen in Drugs for Malaria, Tuberculosis, Chagas Disease, Lymphatic Filariasis, and Onchocerciasis, Vaccines for Malaria, and Diagnostics for Leishmaniasis and Mycetoma
TOKYO, March 30, 2020 /PRNewswire/ -- The Global Health Innovative Technology (GHIT) Fund announced today a total of 3.29 billion yen (US$30 million*) to invest in 11 partnerships to develop new lifesaving drugs, vaccines and diagnostics for malaria, tuberculosis, Chagas disease, leishmaniasis, lymphatic filariasis, onchocerciasis, and mycetoma. This includes five new projects and six that will receive continued funding**. (Appendix 1 & 2)
"Although we are in the midst of unprecedented COVID-19 crisis globally, GHIT works closely with our product development partners more than ever to conduct research and development for neglected patients. I believe that innovative technologies and approaches in partnership with Japanese and overseas entities will advance science steadily and contribute to the development of new drugs, vaccines, and diagnostics for neglected patients," said Ms. Catherine Kaseri Ohura, the CEO of GHIT.
Currently, there are 52 ongoing projects, including 26 discovery, 20 preclinical and six clinical trials in the GHIT portfolio. (Appendix 3)
* USD1 = JPY109.42, the approximate exchange rate on February 31, 2020.
** These awarded projects were selected from a number of proposals to the RFP2020-002 for Target Research Platform, Hit-to-Lead Platform, and Product Development Platform, which was open for applications from July to October 2019. The GHIT board conducted in February 2020 approved these new invesments.
The GHIT Fund is a Japan-based international public-private partnership fund (PPP) between the Government of Japan, multiple pharmaceutical companies, the Bill & Melinda Gates Foundation, the Wellcome, and the United Nations Development Programme (UNDP). The GHIT Fund invests and manages an R&D portfolio of development partnerships aimed at neglected diseases, such as malaria, tuberculosis and neglected tropical diseases that afflict the world's vulnerable and Underserved populations. The GHIT Fund mobilizes the Japanese industry, academia, and research institutes to create new drugs, vaccines, and diagnostics for malaria, tuberculosis, and neglected tropical diseases, in collaboration with global partners.
Appendix.1 New Investments
ID/Status
Project Title
Collaboration Partners
Disease/ Intervention
Stage
Awarded Amount
---
G2019-208 Preparatory phase II for the malaria RIMD, Osaka University, Nobelpharma Co., Ltd.
vaccine candidate NPC-SE36/CpG (NPC), European Vaccine Initiative (EVI),
Groupe de Recherche Action en Santé (GRAS)
Malaria Phase 1 Clinical Development
YEN187,077,716 (US $1,709,721)
Continued
project
Vaccine
---
G2019-213 Production, validation and use of Institute of Tropical Medicine (NEKKEN)
Leishmanin skin test (LST) for Nagasaki University, The Ohio State
detection of Leishmania exposure University, McGill University, Gennova
and immunity Biopharmaceuticals, US-FDA
Leishmaniasis
Product Design
YEN225,769,996 (US$2,063,334)
New project
Diagnostic
---
G2019-215 Preclinical and Clinical Development
of SJ733, a Novel PfATP4 Inhibitor
for the Treatment of Severe Malaria Eisai Co., Ltd., University of Kentucky
Malaria
Preclinical Development
YEN559,009,168 (US $5,108,839)
New project
Drug
---
G2019-219 Preclinical studies of potent Gwt1p Eisai Co. Ltd., Medicines for Malaria Venture
inhibitor toward IND for (MMV)
antimalarial agent with novel
mechanism of action
Malaria
Preclinical Development
YEN682,839,480 (US$6,240,536)
Continued
project
Drug
---
G2019-202 Development of AWZ1066S, A Small Eisai Co., Ltd., Liverpool School of Tropical
Molecule anti-Wolbachia Candidate Medicine (LSTM), University of Liverpool
Macrofilaricide Drug
Lymphatic filariasis, Onchocerciasis
Preclinical Development YEN433,581,260 (US$ $3,962,541)
Continued
project
Drug
---
G2019-205 Preclinical development of malaria Ehime University, Sumitomo Dainippon Pharma
transmission-blocking vaccine Co., Ltd., PATH
candidate Pfs230D1+ formulated with
SA-1 adjuvant
Malaria
Preclinical Development
YEN500,728,372 (US$4,576,205)
Continued
project
Vaccine
---
G2019-209 Lead optimization of a candidate Daiichi Sankyo Company Limited, Drugs for
series active against Chagas Neglected Diseases initiative (DNDi)
Disease
Chagas disease
Lead Optimization
YEN431,856,560 (US $3,946,779)
Continued
project
Drug
---
H2019-201 Hit-to-Lead Development of Chugai Pharmaceutical Co., Ltd., The Global
Phenotypic Screening Hits Alliance for TB Drug Development
Tuberculosis
Lead Identification
YEN95,315,987 (US$871,102)
Continued
project
Drug
---
T2019-254 Development of a novel Pvs25 Ehime University, Mahidol University, Technology Platform
nucleoside-modified mRNA vaccine University of Pennsylvania Identification
that induces potent and long-
lasting transmission blocking
immunity
Malaria
YEN96,077,193 (US$878,059)
New project
Vaccine
---
T2019-252 Made-in-Japan next-generation Kanazawa University, Hokkaido University, Jichi
vaccine platform effective for Medical University, Toyama University,
multistage Plasmodium for infants University of Cambridge
Malaria
Concept Development
YEN52,690,000 ($481,539)
New project
Vaccine
---
T2019-260 MycEXomics aims to develop a field- RIKEN, Mycetoma Research Centre (MRC),
friendly point-of-care diagnostic University of Khartoum, Erasmus University
test for mycetoma Medical Center, Hospital General de Mexico
Mycetoma
Concept Development
YEN28,593,793 (US$261,321)
New project
Diagnostics
---
*All amounts are listed at the exchange rate of USD1 = JPY109.42, the approximate exchange rate on February 31, 2020.
Appendix.2 Project Details
G2019-208
Project Title
Preparatory phase II for the malaria vaccine candidate NPC-SE36/CpG
---
Collaboration
Partners RIMD, Osaka University, Nobelpharma Co., Ltd. (NPC), European Vaccine Initiative (EVI), Groupe de Recherche Action en Santé (GRAS)
---
Disease
Malaria
---
Intervention
Vaccine
---
Stage
Phase 1 Clinical Development
---
Awarded Amount
YEN187,077,716 (US $1,709,721)
---
Status
Continued project
---
SE36 is a blood stage malaria vaccine candidate that primarily targets young children in endemic areas to reduce morbidity and mortality due
to malaria. Though in principle all stages of parasite development are potential vaccine targets, the blood stage is the one that causes
the symptoms of malaria and its complications, and thus has a public health impact. A blood-stage vaccine, either alone or as a component
of a multi-stage vaccine, is needed to protect against clinical or epidemic malaria. Early stage clinical trials have demonstrated that
the BK-SE36 vaccine, SE36 recombinant protein and aluminium hydroxide gel, has acceptable reactogenicity, has no unexpected safety signals
and was immunogenic. Vaccine responders experienced less malaria infection and have lower risk of developing clinical symptoms. Moreover,
a better immune response was achieved in Japanese adults when CpG-ODN (K3) adjuvant was added to the formulation. A safety and
immunogenicity phase Ib trial is currently underway in adults to 1-year old children in Burkina Faso with this new formulation.
Preliminary results do not indicate unexpected safety concerns. This project builds on these initial trials and allows the next step in
Summary further clinical development, before initiation of phase II proof-of-concept clinical trial.
Test the quality of a new and larger batch of SE36 vaccine adsorbed on aluminium hydroxide (NPC-SE36 vaccine), manufacture new CpG-ODN
(K3) adjuvant GMP lot; and select sites and prepare protocol for phase IIb clinical trial. Successful development of a large-scale
formulation will enable us to have full evaluation of GMP produced vaccine that can be used for multi-site trials. Moreover, a well-
designed phase IIb protocol with selected clinical sites ready to implement the phase IIb clinical trial would address the safety and
efficacy of NPC-SE36 in a malaria endemic area.
The project aims to: 1) Conduct pre-clinical studies on the new GMP lot of NPC-SE36 to show suitable formulation for clinical trial
testing and importation. 2) Deliver a new GMP lot of CpG-ODN (K3) as adjuvant for clinical trials. 3) Select phase IIb clinical trial
sites and prepare clinical trial documentation.
---
Project Detail
https://www.ghitfund.org/investment/portfoliodetail/detail/157/en
---
G2019-213
Project Title
Production, validation and use of Leishmanin skin test (LST) for detection of Leishmania exposure and immunity
---
Collaboration Institute of Tropical Medicine (NEKKEN) Nagasaki University, The Ohio State University, McGill University, Gennova Biopharmaceuticals, US-
Partners FDA
---
Disease
Leishmaniasis
---
Intervention
Diagnostics
---
Stage
Product Design
---
Awarded Amount
YEN225,769,996 (US$2,063,334)
---
Status
New project
---
The leishmaniases comprise a number of diseases caused by obligate intracellular parasites of the genus Leishmania that is transmitted by
the bites of infected sandflies. With over 350 million people worldwide at risk of contracting leishmaniasis and, the WHO classifies
leishmaniasis as a neglected tropical disease. The leishmanin skin test (LST) was used for decades to determine exposure and immunity to
Leishmania infection but the leishmanin antigen used in the LST is no longer available. There are compelling reasons to bring back the LST.
Firstly, the LST could identify districts and villages where there is active or past transmission. This information will help to support
visceral leishmaniasis elimination programs. Second, since promising vaccines are advancing, the LST would be an effective surrogate marker
Summary to help determine vaccine efficacy.
The objectives of this proposal are to: 1. Produce and determine the stability of the L. donovani antigen (Leishmanin antigen). 2. Validate
the Leishmania donovani LST leishmanin antigen in immune animals. 3. Validate the LST in visceral leishmaniasis cured and asymptomatic
infected individuals.
A protocol for making Leishmanin antigen from L. donovani parasites will be established and GMP grade Leishmanin will be produced for the
Leishmanin skin test (LST). Pre-clinical animal models of visceral leishmaniasis in hamsters and cutaneous leishmaniasis in mice will be
used to test Leishmanin antigen and validate LST for detection of latent infection and immunity. Immune responses will also be analyzed in
these pre-clinical animal models. After completion of animal studies, LST will be validated in visceral leishmaniasis patients as well as
asymptomatic individuals from endemic regions.
---
Project Detail
https://www.ghitfund.org/investment/portfoliodetail/detail/159/en
---
G2019-215
Project Title
Preclinical and Clinical Development of SJ733, a Novel PfATP4 Inhibitor for the Treatment of Severe Malaria
---
Collaboration
Partners
Eisai Co., Ltd., University of Kentucky
---
Disease
Malaria
---
Intervention
Drug
---
Stage
Preclinical Development
---
Awarded Amount
YEN559,009,168 (US $5,108,839)
---
Status
New project
---
Severe malaria (SM) is a medical emergency requiring immediate parenteral or enteral treatment. SM affects two million people per year. The
current WHO treatment of choice is IV Artesunate (AS), available in 34 developing countries. IV AS is not registered in the US, Europe,
Australia, Japan, and many other countries. Other SM treatments have significant liabilities (efficacy/tolerability). SJ733 is an
antimalarial entering Phase 2 for oral 3-day treatment of non-severe malaria. In humans, SJ733 is active against blood and sexual stages
and possesses an excellent safety profile. SJ733 demonstrated rapid parasite killing in a Phase 1b human challenge. Animal models indicate
Summary a lack of embryofetal developmental (EFD) toxicity. SJ733's clinical profile makes SJ733 a strong candidate for the treatment of SM.
The project objectives are:
1) Manufacture a GMP lot of the current SJ733 drug substance to provide enough material to carry out the proposed preclinical and clinical
studies.
2) Conduct IND-enabling bridging GLP dog toxicity studies to establish a therapeutic window when SJ733 is administered via an intravenous
route.
3) Carry out formulation studies and manufacture of drug product to support development of SJ733 for intravenous (IV) bolus and continuous
infusion administration.
4) Submit an Investigational New Drug (IND) filing to enable first-in-human studies of IV SJ733.
5) Carry out a Phase 1a trial using IV SJ733 to establish safety and tolerability of both bolus and continuous infusion administration
routes.
We will explore SJ733 as a novel treatment for SM. Formulation studies will help select the lead formulation with the optimal dose volume
for parental use. Preclinically, the dog was the most sensitive toxicology species. Therefore, GLP dog toxicity studies will bridge from
existing IND to the proposed route and schedule. The clinical work will focus on examining safety, tolerability, and pharmacokinetics for
two schedules: a bolus IV schedule mirroring AS use and a continuous infusion schedule more closely related to the IV quinine schedule.
---
Project Detail
https://www.ghitfund.org/investment/portfoliodetail/detail/160/en
---
G2019-219
Project Title
Preclinical studies of potent Gwt1p inhibitor toward IND for antimalarial agent with novel mechanism of action
---
Collaboration
Partners
Eisai Co. Ltd., Medicines for Malaria Venture (MMV)
---
Disease
Malaria
---
Intervention
Drug
---
Stage
Preclinical Development
---
Awarded Amount
YEN682,839,480 (US$6,240,536)
---
Status
Continued project
---
Malaria is a mosquito-borne, life-threating infectious disease caused by Plasmodium protozoa parasites. An estimated 405,000 people died
in 2018, mainly children in African countries. The current standard of care for the treatment of malaria typically involves combination
therapy with artemisinin derivatives. However, there is evidence of emerging resistance to artemisinin and its partner drugs in some
countries such as Cambodia, Thailand, Myanmar and Vietnam. This highlights the urgent need for new classes of compounds with novel
mechanisms-of-action (MoA) to treat resistant strains of malaria parasites and support the global malaria eradication strategy. In this
project, we aim to conduct Investigational New Drug(IND)-enabling Good Laboratory Practice (GLP) preclinical studies on an antimalarial
candidate compound with a well-characterized and novel MoA. Glycosylphosphatidylinositol (GPI) is a common moiety in all eukaryotes which
has a role in anchoring many proteins to the cell surface. Gwt1p, one of the essential enzymes in the GPI biosynthesis pathway, was
identified by Eisai as a novel target for an antifungal drug. After conducting discovery research, Eisai discovered E1210, an antifungal
drug clinical candidate, and found that the GWT1 gene encoding Gwt1p enzyme is highly conserved among eukaryotes, including Plasmodium
protozoa, the etiological pathogens for malaria. Eisai has screened an internal compound library targeting fungal Gwt1p and found a hit
compound with inhibitory activities on plasmodial Gwt1p. This compound showed anti-Plasmodium activities in vitro and in vivo and was
subjected to chemical modification in GHIT Hit-to-Lead and Lead Optimization Platforms. MMV and Eisai succeeded in creating the candidate
Summary compound with improved anti-Plasmodium activity and the long half-life required for single-dose malaria treatment.
The objective of this proposal is to complete preclinical development and IND-enabling GLP studies with a candidate identified in a project
funded through the GHIT grant G2017-109.
The current synthetic route will be optimized in a collaboration between Charles River's medicinal chemists and Eisai's process chemists,
and a salt form screening will be conducted. Based on the optimized route, Eisai will focus on the following specific objectives:
1) Manufacture the drug substance required for preclinical studies and phase I trials. The drug substance for preclinical studies will be
released around year 1.
2) Manufacture drug product for phase I trial by the end of the second year.
3) Conduct preclinical DMPK and safety studies required for First-in-Human (FiH) study submission, such as GLP preclinical toxicity in
rodents and non-rodents, genotoxicity, safety pharmacology, metabolite identification in the second year.
4) Validate the bioanalytical method to support clinical trials.
5) Prepare for submission to conduct FiH studies in March 2022.
MMV will also conduct in vivo evaluations to identify possible partner drugs using a humanized murine model. After these studies, MMV will
support the selection of sites for phase I FiH and a Volunteer Infection Study, the preparation of the study protocols, the Investigator's
Brochure, the Investigational Medicinal Product Dossier (IMPD) and other documentation required for FiH submission in collaboration with
Eisai.
---
Project Detail
https://www.ghitfund.org/investment/portfoliodetail/detail/161/en
---
G2019-202
Project Title Development of AWZ1066S, A Small Molecule anti-Wolbachia Candidate
Macrofilaricide Drug
---
Collaboration Eisai Co., Ltd., Liverpool School of Tropical Medicine (LSTM), University of
Partners Liverpool
---
Disease
Lymphatic filariasis, Onchocerciasis
---
Intervention
Drug
---
Stage
Preclinical Development
---
Awarded Amount
YEN433,581,260 (US$ $3,962,541)
---
Status
Continued project
---
Lymphatic filariasis (elephantiasis) and onchocerciasis (river blindness) are two
neglected tropical diseases that are caused by parasitic worms. These diseases
affect more than 150 million people globally. The international community
agrees that these diseases should and could be eradicated with the correct tools
and there are ongoing mass drug administration campaigns underway to achieve
this goal. However, in the absence of a drug that can kill adult parasites,
current programmes require many years of annual (or greater) rounds of drug
administration to large populations in the rural communities blighted by these
diseases. We have demonstrated that adult worms can be killed by eliminating a
Summary bacterium that they contain called Wolbachia.
This approach has the potential to significantly reduce the timescale of
eradication programmes, to provide alternatives to current drugs and to deliver
an additional tool that can be used in areas where current approaches are
failing, or cannot be deployed. The antibiotic doxycycline works in this way and
proof of concept has already been proven in human field trials. Results were
excellent but required 4 to 6 weeks of daily treatment. Also this drug cannot be
used in children and pregnant women, who represent a large proportion of the
target population.
We have identified a new drug candidate that acts more quickly and efficiently
than doxycycline and has been shown to be safe in pre-clinical testing.
The objective of this project is to continue the development of this drug
candidate further by completing a series of Phase I clinical trials which will
assess safety in humans. This is an essential step in the development of a new
drugs and brings us closer to a new treatment for these diseases.
The project will involve:
---
-- the manufacture of sufficient quantity of the drug candidate to the
required quality,
-- application and granting of permission to conduct the clinical trial
--
completion of the trial in line with international requirement for the licencing of new drugs.
---
Project Detail https://www.ghitfund.org/investment/portfoliodetail/detail/155/en
---
G2019-205
Project Title
Preclinical development of malaria transmission-blocking vaccine candidate Pfs230D1+ formulated with SA-1 adjuvant
---
Collaboration
Partners
Ehime University, Sumitomo Dainippon Pharma Co., Ltd., PATH
---
Disease
Malaria
---
Intervention
Vaccine
---
Stage
Preclinical Development
---
Awarded Amount
YEN500,728,372 (US$4,576,205)
---
Status
Continued project
---
Summary Malaria remains one of the leading causes of deaths in young African children. New tools are urgently needed to ensure global control,
elimination, and eventual eradication goals are met; our vaccine approach has the potential to serve as one such transformational tool.
This proposal seeks support for the preclinical development of a vaccine candidate that blocks parasite transmission from human to
mosquito.
The goal of this proposal is to generate all the preclinical information necessary to advance a novel candidate Plasmodium falciparum
(malaria) vaccine to the clinical testing stage. This transmission-blocking vaccine (TBV) incorporates an optimized immunogen, Pfs230D1+
formulated with novel TLR7 adjuvant (SA-1). At the end of the project, the partners will be ready for clinical phase manufacturing and the
filing of an Investigational New Drug (IND) application to the US Food and Drug Administration (US FDA).
This project is a continuation of a GHIT Fund grant (T2016-207) in which the optimal region of the Pfs230 protein was identified for
inclusion in a TBV. The current project includes the generation of the high-quality vaccine and adjuvant suitable for performance of
definitive safety/toxicology studies. Contact with the US FDA will be made to assure that our plans are appropriate for testing of both a
novel vaccine and adjuvant.
---
Project Detail
https://www.ghitfund.org/investment/portfoliodetail/detail/156/en
---
G2019-209
Project Title
Lead optimization of a candidate series active against Chagas Disease
---
Collaboration
Partners
Daiichi Sankyo Company Limited, Drugs for Neglected Diseases initiative (DNDi)
---
Disease
Chagas disease
---
Intervention
Drug
---
Stage
Lead Optimization
---
Awarded Amount
YEN431,856,560 (US $3,946,779)
---
Status
Continued project
---
Chagas disease, also known as American trypanosomiasis, is a potentially life-threatening illness caused by Trypanosoma cruzi (T. cruzi).
About 6 to 7 million people worldwide are estimated to be infected mainly in Latin American countries where the disease is endemic.
Existing drugs for Chagas diseases are associated with serious side effects and suboptimal efficacy for chronic Chagas patients. Drugs for
Neglected Diseases initiative (DNDi) and Daiichi Sankyo Co., Ltd. (DS) have been collaborating since early 2016 on the development of a
Summary totally new orally active drug with objective to deliver a safe and efficacious treatment for people affected by Chagas disease.
This specific 2-year project aims at engineered out via Lead Optimization this promising class of compounds into one optimized lead
candidate for Chagas Disease and at elucidating its mechanism of action by end Q1 2022. This optimized lead candidate shall meet the
criteria of the Chagas Disease Target Candidate Profile (TCP) defined by DNDi.
The project team has developed a tailored-to-the needs assay cascade to address the development of this series. Basically, compounds with
suitably balanced T. cruzi activity, selectivity and metabolic stability in vitro profiles will be considered as candidates for
pharmacokinetic studies. Provided sufficient drug exposure is reached in animals used in those studies, compounds will then be tested in a
Chagas acutely infected mouse assay model to assess its ability to clear an established T. cruzi infection targeting a non-detectable
level of T. cruzi parasites at end of treatment. Compounds meeting this latter criterion as well as fulfilling a few additional safety-
related requirements related to in vitro testing will be tested in the Chagas chronically infected assay model to assess their ability to
clear an established T. cruzi chronic infection. Compounds able to sustainably clear out T. cruzi infection in this assay will be
considered as curative and meet the Optimized Lead candidate stage criteria. Safety studies for those candidates will be completed in
parallel or right after efficacy studies. The relationship between drug dosing and efficacy will be deduced from PK and PD studies
conducted on a few carefully selected candidates using adequate treatment regimens and modeling to identify the pharmacokinetic parameters
driven efficacy in vivo. Safety and tolerability data will be considered to define the most appropriate dose regimen to be used in PK and
PD studies. Various medicinal chemistry strategies will be applied to efficiently optimize the chemical series addressing the identified
liabilities including metabolic stability. To manage and mitigate risks of lead molecules effectively, careful assessment of
physicochemical properties, in vitro ADME (absorption, distribution, metabolism, and excretion) properties, in vivo pharmacokinetics, in
vitro and in vivo safety, and formulation will be performed in parallel with routine in vitro parasitological assay.
---
Project Detail
https://www.ghitfund.org/investment/portfoliodetail/detail/158/en
---
H2019-201
Project Title
Hit-to-Lead Development of Phenotypic Screening Hits
---
Collaboration
Partners
Chugai Pharmaceutical Co., Ltd., The Global Alliance for TB Drug Development
---
Disease
Tuberculosis
---
Intervention
Drug
---
Stage
Lead Identification
---
Awarded Amount
YEN95,315,987 (US$871,102)
---
Status
Continued project
---
Summary Chugai Pharmaceutical Co., Ltd. and TB Alliance collaborated in a program under a sponsorship of the GHIT. A set of natural products were
discovered to have potent activity against Mycobacterium tuberculosis (M.tb), and they appear to be unprecedented in the pipelines for TB
drug development. They are now ready to be examined further in the next phase of drug development.
The main objective of this project is to develop compounds we discovered through our process of testing natural products against M.tb, the
bacteria that causes TB. This involves not only improving the potency of the compounds against M.tb but improving their pharmacokinetic
properties and safety liabilities so that we can demonstrate their activity in animal models. We plan to identify a compound at the end of
the two-year period to move to the next phase of development, known as lead optimization.
The original hits were discovered from natural products that were produced by microorganisms through a fermentative process. For the next
step, instead of fermentation processes, we plan to employ synthetic chemistry to prepare a large number of analogues in a relatively short
time. The new analogues will be tested for potency, metabolic properties, safety, and eventually efficacy in mice. We are already
investigating how these hit compounds kill M.tb and once this is deciphered, it should inform the design of new analogues by taking the
structure of the target biomolecule into account.
---
Project Detail
https://www.ghitfund.org/investment/portfoliodetail/detail/151/en
---
T2019-254
---
Project Title
Development of a novel Pvs25 nucleoside-modified mRNA vaccine that induces potent and long-lasting transmission blocking immunity
---
Collaboration
Partners
Ehime University, Mahidol University, University of Pennsylvania
---
Disease
Malaria
---
Intervention
Vaccine
---
Stage
Technology Platform Identification
---
Awarded Amount
YEN96,077,193 (US$878,059)
---
Status
New project
---
Vivax malaria is recognized as a leading neglected tropical disease worldwide. Plasmodium vivax parasite poses a major challenge to malaria
elimination due to its ability to cause recurring blood infections. These 'relapses' of malaria are caused by hypnozoites, the dormant form
of the parasite in the liver. Therefore, hypnozoites is considered as the major challenge towards malaria elimination in vivax endemic
countries. The only drugs available to clear hypnozoites are primaquine and tafenoquine. However, these drugs cause severe hemolysis in
people with G6PD deficiency and are difficult to deploy in large scale to drive vivax malaria elimination. Vaccination is an alternative
Summary and the most cost-effective way to control malaria, however, malaria vaccine which target P. vivax has not been developed.
The goal of this project is to develop a novel nucleoside-modified mRNA vaccine targeting Pvs25 protein that induces potent and long-
lasting transmission blocking immunity and is able to interrupt transmission of P. vivax from human to mosquito.
To achieve our objective, we will combine our experiences in malaria vaccine development (Mahidol and Ehime Universities) and mRNA vaccine
technology (the University of Pennsylvania) to develop nucleoside-modified mRNA vaccines that block transmission of P. vivax, a major
malaria parasite outside Africa. The vaccine target is the protein Pvs25 which is expressed on the surface of the transmission-stage
parasite, a well-validated target. In our vaccines, nucleoside-modified mRNA encoding Pvs25 will be delivered by lipid nanoparticles
(LNP), an approach which has been shown to be highly effective in other vaccines. Several mRNA-LNP formulations will be tested in animals
to identify the best candidate. Several routes of administrations and immunization schedules will also be explored. Vaccine efficacy will
be determined by the ability of the immune sera of immunized animals to block mosquito infection using membrane feeding assay with P. vivax
parasites isolated in Thailand. In addition to developing a new transmission blocking vaccine, we will also investigate the immune
mechanism that results in transmission blocking activity.
---
Project Detail
https://www.ghitfund.org/investment/portfoliodetail/detail/153/en
---
T2019-252
---
Project Title
Made-in-Japan next-generation vaccine platform effective for multistage Plasmodium for infants
---
Collaboration
Partners
Kanazawa University, Hokkaido University, Jichi Medical University, Toyama University, University of Cambridge
---
Disease
Malaria
---
Intervention
Vaccine
---
Stage
Concept Development
---
Awarded Amount
YEN52,690,000 ($481,539)
---
Status
New project
---
As a valuable addition to sustain realistic and affordable malaria control, a candidate anti-malarial vaccine must perform safely and
efficiently during neonatal and early life vaccination in resource-poor settings. Accordingly, such a malaria childhood vaccine would
ideally be tailored for integration into the current Expanded Programme on Immunization (EPI) vaccines. At the same time, we should
consider host factors which may severely impair vaccine efficacy. Because RTS,S vaccine can induce higher protective immune response for
volunteers in developed countries, compared with those in developing countries and infants in Africa. We (and others) hypothesize that
helminths and maternal antibodies are critical host factors to be considered when developing a malaria vaccine. Significant numbers of
individuals living in tropical areas are demonstrably co-infected with helminths, which are known to adversely affect immune responses to
a number of different existing vaccines. In addition to the host factors, there is an inevitable risk involved in monovalent vaccines such
as RTS,S. Gene polymorphisms and mutations may cause drastic reduction of protective efficacy, resulting in vaccine failure. A recent study
has reported that vaccines capable of inducing both antibodies against pre-erythrocytic stage (protection) and sexual-stage parasites
Summary (transmission blocking [TB]) possess strong synergistic effects on parasite reduction in prevalence.
Development of a highly effective and durable next-generation multistage malaria vaccine effective against both pre-erythrocytic stage and
sexual-stage parasites based on two viral vectors for African infants with pre-existing helminths and maternal antibodies. It is proven
that successful implementation of this strategy would lead to enhanced parasitic elimination.
Two viral-vectored vaccines expressing both pre-erythrocytic-stage and sexual-stage antigens will be generated. Protective and
transmission blocking (TB) efficacies of the heterologous prime-boost immunization regimen will be assessed by sporozoite challenge and
Direct Membrane Feeding Assay (DMFA) in a robust and proven mouse model, and then the regime will be further optimized (e.g., dose, route,
interval and outbred mice). Desired protection rate >90%. Surrogate markers responsible for protection will be identified. This will be key
to allow efficient and robust measurements of efficacy. Humoral and cellular immune responses induced by the heterologous prime-boost
immunization regimen will be assessed.
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Project Detail
https://www.ghitfund.org/investment/portfoliodetail/detail/152/en
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T2019-260
Project Title
MycEXomics aims to develop a field-friendly point-of-care diagnostic test for mycetoma
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Collaboration
Partners
RIKEN, Mycetoma Research Centre (MRC), University of Khartoum, Erasmus University Medical Center, Hospital General de Mexico
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Disease
Mycetoma
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Intervention
Diagnostics
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Stage
Concept Development
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Awarded Amount
YEN28,593,793 (US$261,321)
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Status
New project
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Summary Mycetoma is a neglected tropical disease of the subcutaneous tissue and is characterized by large tumor-like lesions. It is caused by more
than 70 different causative agents, but four of these are responsible for 79.5% of all mycetoma cases world-wide. Appropriate treatment
outcome depends on proper identification of the causative organism. The current mycetoma diagnostics tools are tedious, invasive of low
sensitivity and specificity and expensive. Presently there is no point-of-care diagnostic test for mycetoma.
To identify species-specific markers for the 4 most common causative agents of mycetoma in urine and plasma of mycetoma patients
In order to identify species-specific markers a five step-approach will be taken
1) Urine and plasma will be isolated from patients with mycetoma
2) The causative agent will be identified by PCR
3) Exosomes will be isolated from urine and plasma, as they will most likely contain species specific markers
4) RNA will be isolated from the exosomes and sequenced
5) The transcriptomes will be profiled and markers identified
The markers identified in MycEXomics can later be used to develop Point-of-Care diagnostic tools to detect early cases of mycetoma.
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Project Detail
https://www.ghitfund.org/investment/portfoliodetail/detail/154/en
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*All amounts are listed at the exchange rate of USD1 = JPY109.42, the approximate exchange rate on February 31, 2020.
Appendix.3 Investment Overview (As of March 31, 2020)
1. Investment to date
Total investments 20.9 billion yen (US$191.2 million*)
Total invested Projects 91?active projects 52, completed projects 39?
2. Portfolio analysis (active projects + completed projects)
To know more about GHIT investments, please visit
Investment Overview: https://www.ghitfund.org/investment/overview/en
Portfolio: https://www.ghitfund.org/investment/portfolio/en
Advancing Portfolio: https://www.ghitfund.org/investment/advancingportfolio/en
Clinical Candidates: https://www.ghitfund.org/investment/clinicalcandidates/en
*All amounts are listed at the exchange rate of USD1 = JPY109.42, the approximate exchange rate on February 31, 2020.
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SOURCE Global Health Innovative Technology (GHIT) Fund
