Total Investment of Approx. USD 7.3 Million in Malaria and TB R&D Projects With Partners Including European Vaccine Initiative, University of Copenhagen, and University of Tübingen USA – English India – English

Project Title

Biomanufacture and preclinical development of the blood-stage malaria vaccine
candidate SE36/cVLP

Collaboration

Partners

1. European Vaccine Initiative (Germany)

2. RIMD, Osaka University (Japan)

3. University of Copenhagen (Denmark)

4. AdaptVac (Denmark)

5. University of Tübingen (Germany)

6. Ajinomoto Co., Inc. (Japan)

7. Nobelpharma Co., Ltd. (Japan)

Disease

Malaria

Intervention

Vaccine

Stage

Preclinical

Awarded Amount

JPY 800,715,002 (USD 5.5 million)

Status

Continued project

Summary

[Project objective]

This team’s goal is to fast-track the clinical development of the SE36/cVLP vaccine
candidate and obtain supporting evidence for a safe and efficacious blood-stage
vaccine that could be deployed as a stand-alone or potentially combined in a second-
generation multi-stage malaria vaccine. The main objectives are to:

1.         Manufacture a large GMP batch of SE36

2.         Produce a GMP batch of SE36/cVLP

3.         Conduct a GLP-compliant nonclinical toxicology study for SE36/cVLP + Sepivac
            SWE adjuvant

4.         Prepare clinical trial documentation for the conduct of a phase I/IIa (CHMI) trial
            for SE36/cVLP (+/- Sepivac SWE) to assess safety, immunogenicity, and time-to-
            first episode of clinical malaria in malaria-naïve vaccinated subjects

[Project design]
The previous GMP manufacturing process for SE36 was largely based on the E. coli
expression system with modest yield after several chromatography steps. Benefiting
from recent collaborations and new adaptive vaccine technologies, the project team
now proposes to manufacture a larger batch of SE36 using a simplified, high-yield
process with Corynex™, which utilizes Corynebacterium glutamicum. Moreover, to
increase the vaccine immunogenicity, SE36 antigens will be displayed on capsid
virus-like particles (cVLP) ensuring unidirectional and high-density display. A
previously manufactured small lab-scale batch of SE36/cVLP showed that coupling
was stable and that coupled SE36 was highly immunogenic in the mouse model.
Armed with this success, the project team now expands its efforts to manufacture a
larger GMP batch of SE36/cVLP, conduct a GLP-compliant nonclinical toxicology
study and prepare trial documentation to conduct a phase I/IIa trial with this newly
optimised formulation of the SE36 vaccine candidate. A successful completion of
these activities will set the stage for a first-in-human safety, immunogenicity and
efficacy trial.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/242/en

Project Title

ZOO-RDT: Validating a novel biomarker and associated reagents for diagnosis of
acute zoonotic malaria in southeast Asia

Collaboration

Partners

1. Ehime University (Japan)

2. Universiti Malaysia Sabah (Malaysia)

Disease

Malaria

Intervention

Diagnostics

Stage

Target Research

Awarded Amount

JPY 64,693,198 (USD 0.4 million)

Status

New project

Summary

[Project objective]

There are no P. knowlesi-specific point-of-care (PoC) tests. Rapid diagnostic tests
based on the pLDH biomarker show high cross-reactivity between P. vivax and P.
knowlesi making them impossible to distinguish. Current diagnostic practices take
time and delay patient access to treatment. Simple, accessible PoC tools are urgently
required. Identification of P. knowlesi-specific diagnostic markers has been largely
neglected. The serine repeat antigen (sera) multigene family has been extensively
studied in P. falciparum and rodent parasite lines and plays critical roles across the
parasite life cycle. The P. knowlesi Serine Repeat Antigen 3 (PkSERA3) antigen 2
has been identified as a P. knowlesi-specific exposure marker, with laboratory and
population-level evaluations showing no cross-reactivity with P. vivax, a
phylogenetically closely related species. The project team will use this antigen to
develop reagents for a P. knowlesi PoC diagnostic test.

[Project design]
Overall aim: Validate novel biomarker(s) and associated monoclonal antibodies for
lateral flow assay development for the diagnosis of acute infections. 

Objective 1: Reagent optimisation: the optimised PkSERA3 ag 2 protein plus two
variants will be used in the generation of monoclonal antibodies (mAbs). 

Objective 2: Analytical and clinical validation of PkSERA3 Ag2 and variants as
species-specific indicators of acute P. knowlesi infection across epidemiological
zones. 

Objective 3: Assessment of Technical Feasibility in the lateral flow system. The best
performing mAbs will be assayed by ELISA, and further down-selection will lead to
selected mAbs being printed onto test strips. Antibody reagents will be provided to a
diagnostic test developer Contract Research Organization (CRO) to validate the
technical feasibility of integrating the developed mAbs into a lateral-flow RDT.

Objective 4: Stakeholder consultation to understand the preferred test design, and to
inform Product Design and generate evidence for a business case for this novel
malaria RDT.

Target results: Validated P. knowlesi-specific mAb reagent for use in LFA
development.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/243/en

Project Title

Harnessing genome mining for novel tuberculosis antibiotics

Collaboration

Partners

1. The University of Auckland (New Zealand)

2. The University of Tokyo (Japan)

Disease

Tuberculosis

Intervention

Drug

Stage

Target Research

Awarded Amount

JPY 100,000,000 (USD 0.6 million)

Status

New project

Summary

[Project objective]

In the short term, this project aims to enhance TB antibiotic discovery by identifying
secondary metabolites that specifically target essential metabolic pathways in M.
tuberculosis. By focusing on mechanisms absent in mammalian cells, the project
team aims to identify secondary metabolites with selective antimicrobial activity and
minimal side effects in humans. This selectivity is expected to improve patient
experience, compliance, and treatment outcomes. Early identification and testing of
these compounds against purified proteins, M. tuberculosis cells, and human
macrophage infection models will provide critical insights into their efficacy and
potential as new therapeutic agents.

In the long term, this project team’s goal is to translate these research findings into
clinical applications, offering new treatment options for TB patients worldwide. A
key strength of this proposal is this project team’s established expertise and drug
development pipeline, specifically in the TB context, which will be instrumental in
advancing subsequent research and development phases.

[Project design]
Despite significant advances in understanding the metabolic features essential for M.
tuberculosis, developing new antibiotics remains a major challenge. Enzyme
inhibitors often exhibit limited activity against M. tuberculosis, and many bioactive
compounds have unclear modes of action. To overcome these challenges, the project
team will (a) identify secondary metabolites that specifically target key metabolic
pathways in M. tuberculosis, and (b) test these metabolites against purified proteins
and M. tuberculosis cells to assess their effects on bacterial growth and pathogenesis.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/244/en

Project Title

Machine learning-based deconvolution of antimalarial drug mechanisms of action
through cell painting of compound-treated Plasmodium falciparum-infected
erythrocytes

Collaboration

Partners

1. Medicines for Malaria Venture (MMV) (Switzerland)

2. LPIXEL Inc. (Japan)

3. University of Dundee (UK)

Disease

Malaria

Intervention

Drug

Stage

Target Research

Awarded Amount

JPY 99,628,772 (USD 0.6 million)

Status

New project

Summary

[Project objective]

The project ultimately aims to deliver a new high-throughput and information-rich
platform for informing and classifying antimalarial modes of action (MoA) and
highlighting novel compound-induced phenotypes. This proposal seeks to leverage
advances in cellular imaging and machine learning-led pattern recognition. The final
goal is to develop a robust, reproducible method to deliver information on a
compound’s biological impact (whether its MoA or pathway is novel or known) in
synchrony with the confirmation of growth inhibition and thus allow clustering on
both chemistry and biology, potentially saving months in the context of Hit
Generation.

[Project design]
The project relies on high-content imaging and subsequent analysis of drug-treated
Plasmodium falciparum parasites. The initial assay development phase will optimise
methodologies for staining, fixation, and imaging of parasite-infected red blood cells,
including both healthy untreated parasites and those treated with a pilot set of
compounds with defined MoA. This will allow preliminary development of artificial
intelligence (AI) models to classify parasite morphology across the 48 hour lifecycle,
as well as the phenotypic impact of drug-treatment. Once treatment and imaging
parameters have been optimised, data collection will be performed with an expanded
set of compounds covering a diverse range of MoA, in order to refine and validate the
development of AI models for pattern recognition. AI models will ultimately be
packaged into a cloud-based, user-friendly application so that images generated by
researchers can be analysed without specialist AI knowledge.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/245/en