Total Investment of Approx. USD 8.5 Million in Malaria and NTD R&D Projects With Partners Including MMV, GSK, Tanabe Pharma, Eisai and DNDi

Project Title

Preclinical development of a target-based series with potential for treatment, SERCAP and chemoprevention of malaria.

Collaboration

Partners

1. Medicines for Malaria Venture (MMV)

2. Tanabe Pharma Corporation (Japan)

3. University of Georgia

Disease

Malaria

Intervention

Drug

Stage

Pre-clinical

Awarded Amount

JPY 698,830,300 (USD 4.4 million)

Status

Continued project

Summary

[Project objective]

The key project aim is to complete the IND-enabling preclinical development studies on MMV172 targeting monthly single oral dose chemoprevention. The project will also continue to determine the efficacy of MMV172 in the primate model of relapsing P. vivax malaria to develop an understanding of the anti-hypnozoite PK/PD relationship required to determine if MMV172 also meets the dose criterion for SERCAP (Single Encounter Radical Cure and Prophylaxis) or, if necessary, to guide selection of alternative compounds from the series that may be better suited. The second aim of the project is to deliver one or more differentiated Late Lead(s) against a second target product profile; either an oral treatment for relapsing P.vivax malaria or a long-acting injectable for chemoprevention, depending on the outcome of profiling studies and the eventual indication for MMV172. Those compounds would be potential back-up if MMV172 is not meeting TPP (Target Product Profile) criteria. 

[Project design]
A multi-disciplinary project team has been assembled, utilizing the inputs and diverse skills and experiences of experts in medicinal chemistry, biology, parasitology, pharmacokinetics, toxicology, formulation and scale-up chemistry. MMV will also draw on the know-how of its global network of scientific experts to support the activities and review the progress of the project. 

Starting with the confirmed Late Lead MMV172, the necessary candidate profiling and preclinical development studies will be performed to confirm the compound meets the desired candidate profile and has the necessary data package required to obtain authorization from regulatory authorities to progress into first in human study.

Additional parasitology, efficacy, ADME and PK studies will be performed on other compounds to determine their potential to address attrition of MMV172 and/or to meet differentiated target product profiles, and to collect the necessary data package required to confirm them as new Late Lead(s).

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/258/en  

Project Title

Global Evaluation and Registration of Fosravuconazole for Eumycetoma: Translating Research into Patient Impact

Collaboration

Partners

1. Drugs for Neglected Diseases initiatives (DNDi)

2. Eisai Co., Ltd. (Japan)

Disease

Mycetoma

Intervention

Drug

Stage

Clinical Phase III

Awarded Amount

JPY 331,404,733 (USD 2 million)

Status

Continued project

Summary

[Project objective]

The project will generate clinical evidence across diverse endemic regions – Senegal, Kenya, and India – to confirm the efficacy, safety, and pharmacokinetics of fosravuconazole, including against causative organisms beyond Madurella mycetomatis. This follows Phase II results showing good efficacy and a favorable safety profile of fosravuconazole and aims to generate further scientific evidence.

To support global introduction, the project will also implement a comprehensive regulatory strategy, including engagement under consideration with several agencies including the WHO and Swissmedic, and prepare for WHO Pre-Qualification (PQ).

[Project design]
A multi-country, open-label prospective clinical trial will be conducted in Kenya, Senegal, and India to evaluate the efficacy, safety, and pharmacokinetics of fosravuconazole 200 mg in patients with eumycetoma. The trial uses a non‑comparative, open‑label design developed in consultation with the WHO, to accelerate access to a promising therapy with advantages over currently available treatments. Participant recruitment will take approximately 12 months, followed by 12 months of treatment and follow‑up for enrolled patients to ensure complete and reliable clinical data in line with ethical and scientific standards.

To support regulatory readiness, DNDi and Eisai will seek scientific advice from a stringent regulatory authority, currently planned with Swissmedic through the Marketing Authorisation for Global Health Products (MAGHP) procedure, which enables participation from endemic countries and the WHO PQ team. Together, DNDi and Eisai will develop a global regulatory strategy to facilitate WHO recommendation and registration in endemic countries, supported by early consultations with the WHO.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/263/en  

Project Title

Prolyl tRNA Synthetase Inhibitors as New Antimalarials

Collaboration

Partners

1. Medicines for Malaria Venture (MMV)

2. GlaxoSmithKline Investigacion y Desarrollo, S.L. (GSK)

3. The University of Tokyo (Japan)

Disease

Malaria

Intervention

Drug

Stage

Lead Optimization

Awarded Amount

JPY183,557,100 (USD 1.1 million)

Status

Continued project

Summary

[Project objective]

The ultimate objective of this drug discovery collaboration is to deliver a Preclinical Candidate which targets Plasmodium ProRS and meets MMV’s candidate criteria for either prophylaxis (TCP-4) or treatment (TCP-1) shown here; https://www.mmv.org/frontrunner-templates. The objective of this two-year proposal is to initiate optimization of the lead pyridylpyrrolidones series to deliver a Late Lead which meets MMV’s criteria for prophylaxis (TCP-4) and is endorsed by MMV ESAC for entry into candidate profiling studies. The Late Lead could be potentially considered for treatment (TCP-1) if the resistance profile of the late lead improves. In more detail the objectives of the lead optimization project aim to achieve:

1. Increased parasite potency (i.e. 3D7 EC50 < 10nM)

2. Improving the predicted pharmacokinetics in humans (according to MMVSola) such that the series is on track to deliver a late lead which meets the dose criteria for prophylaxis, i.e. a single dose <500mg for t>MIC for 7d (minimum) or a single dose <500mg for t>MIC for 28d (ideal).

3. Addressing the hERG inhibition

4. Confirming selectivity for Pf versus Hu ProRS >1000-fold according to appropriate functional biochemical and cellular assays

5. Determination of the parasitological profile, including rate of kill, potency against lab and clinical strains, efficacy in the SCID model, determination of resistance risk (MIR) etc.

6. Identification and mitigation of additional developability and safety risks; Ames, CYP inhibition, CMC.

[Project design]

A multi-disciplinary drug discovery approach will be used by the project, utilizing the inputs and diverse skills of the project team which has expertise in medicinal chemistry, molecular modeling, parasitology, DMPK and pharmacometrics, toxicology, formulation and scale-up chemistry.  Starting from the Early Lead, rational and systematic modifications will be made to further improve the overal properties based on state-of-the-art capabilities and data generated at MMV, GSK and the University of Tokyo.  As the target of these molecules is an enzyme essential to the growth of the malaria parasite, and structural information is available, a structure-based drug design (SBDD) approach will be applied.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/260/en

Project Title

Hit-to-Lead development of a series of Daiichi Sankyo inhibitors of the novel multi-lifecycle stage target PfPFN (Profilin).

Collaboration

Partners

1. Medicines for Malaria Venture (MMV)

2. DAIICHI SANKYO COMPANY, LIMITED (Japan)

Disease

Malaria

Intervention

Drug

Stage

Lead Identification

Awarded Amount

JPY 129,679,263 (USD 0.8 million)

Status

Continued project

Summary

[Project objective]

The primary objective is to develop a compound series that meets GHIT HTLP/MMV Early Lead criteria. This includes demonstrating in vivo proof-of-concept efficacy and optimizing compounds for potency, stability, and drug-like properties suitable for further development.

[Project design]
The project involves iterative cycles of compound design, synthesis, and testing. The design strategy focuses on improving metabolic stability, maintaining high potency, and optimizing physicochemical properties. The team will explore scaffold modifications and structure-activity relationships (SAR) around key molecular positions to enhance drug-like characteristics while preserving efficacy.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/261/en  

Project Title

Targeting Malaria through Inhibition of Serine Hydroxymethyltransferase (SHMT)

Collaboration

Partners

1. Eisai Co., Ltd. (Japan)

2. Medicines for Malaria Venture (MMV)

Disease

Malaria

Intervention

Drug

Stage

Screening

Awarded Amount

JPY ¥26,589,376 (USD 0.17 million)

Status

New project

Summary

[Project objective]

The primary objective of the project is to identify validated hit compounds that selectively inhibit the activity of plasmodial SHMT.

[Project design]

TropIQ Health Sciences (TropIQ) will lead a primary screen of compounds from Eisai Co., Ltd.’s (Eisai) compound library using a probe-based biochemical assay. To confirm target selectivity of actives, counter-screening against human SHMT will subsequently be performed in the early stage of the project. Hits showing reproducible inhibition and selectivity of plasmodial SHMT over human SHMT will be further assessed using secondary assays.

Confirmed hits will be further assessed by a series of secondary assays. Biochemical assays will be used to further validate actives and generate dose-response curves. To assess biological relevance, compounds will be tested against multiple malaria life cycle stages, including whole parasite asexual blood stage replication, gametocyte and liver stage assays. To exclude toxic compounds, cytotoxicity will be evaluated. All assays will be performed according to TropIQ’s established protocols.

Eisai, Medicines for Malaria Venture (MMV), and TropIQ will review the top hits and assess for clusters of structurally related chemotypes to define chemical series for future work and to establish an early structure-activity relationship.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/262/en