Project Title

Lead optimization and candidate selection of a novel long-acting injectable which targets malarial electron transport chain for malaria chemoprevention and prophylaxis

Collaboration

Partners

1. Shionogi & Co., Ltd. (Japan)

2. Nagasaki University (Japan)

3. National Institute of Infectious Diseases (Japan)

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

Disease

Malaria

Intervention

Drug

Stage

Lead Optimization

Awarded Amount

JPY 332,074,377  (USD 2.2 million)

Status

New project

Summary

[Project objective]

The objective of this project is to identify a preclinical candidate for long-acting injectables (LAI) in malaria chemoprevention. A promising lead series has been identified, in collaboration with Nagasaki University, Shionogi, National Institute of Infectious Diseases, and Medicines for Malaria Venture (MMV), which targets malarial electron transport chain, a well validated target for antimalarial medications. The project aims to optimize the lead and obtain a preclinical development candidate that meet MMV's preclinical candidate criteria.

[Project design]
The project aims to provide a preclinical candidate in two years. A frontrunner compound will be evaluated for the in vivo safety and DMPK studies. In parallel, a lead optimization study will be conducted in search for the second runner candidate with even greater promise than the frontrunner candidate. The most promising compounds will be subjected to extensive in vivo safety and pharmacokinetics studies to satisfy MMV's preclinical candidate criteria.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/221/en

Project Title

Preclinical development of a novel mechanism-of-action antimalarial

Collaboration

Partners

1. Eisai Co., Ltd. (Japan)

2. The Scripps Research Institute (USA)

3. International Centre for Genetic Engineering and Biotechnology (ICGEB) (India)

Disease

Malaria

Intervention

Drug

Stage

Lead Optimization

Awarded Amount

JPY 112,000,000 (USD 0.7 million)

Status

Continued project

Summary

[Project objective]

The goal of this proposal is to evaluate the safety, pharmacokinetic and efficacy profiles of next-generation cPheRS-inhibitor antimalarials, with potentially lower cost of treatment and improved safety profiles.

[Project design]

Promising, recently generated novel antimalarial compounds will be synthesized and profiled in in vivo efficacy studies, exploratory safety studies and multi-species pharmacokinetic studies with the goal of selecting a preclinical development candidate.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/218/en

Project Title

Pre-clinical development of the macrofilaricide corallopyronin A (CorA) to treat onchocerciasis and lymphatic filariasis.

Collaboration

Partners

1. Eisai Co., Ltd. (Japan)

2. University Hospital Bonn (UKB) (Germany)

3. Helmholtz Centre for Infection Research (HZI) (Germany)

Disease

Onchocerciasis

Lymphatic filariasis

Intervention

Drug

Stage

Pre-Clinical Development

Awarded Amount

JPY 904,017,487 (USD 5.9 million)

Status

New project

Summary

[Project objective]

The objective of this project is to progress CorA through final preclinical development activities to prepare for the first in human trial (phase 1).

[Project design]

To achieve this goal, we will conduct the following studies to improve our knowledge of CorA and produce GMP drug substance that will be used in the phase 1 trial. Because CorA is a predicted substrate of enzymes that detoxify substances in the body, we will determine the metabolism of CorA by the enzymes that are predicted to metabolize CorA. Prior to applying for a phase 1 trial authorization, new drugs must be shown to be nontoxic. Therefore, we will conduct a GLP toxicity study, including measuring plasma levels of CorA. With the latter data, we will refine our PK/PD model that will allow us to determine the best human dose and regimen for the phase 1 trial. Our research and innovation packages will provide us with a better understanding of the chemical nature of CorA (e.g., can it be crystalized or co-crystallized?) that may be used to improve the production or stability of CorA. With the GHIT funding we will also produce CorA material for the phase 1 study, including highly pure standards needed for bioanalysis of plasma samples in the phase 1 study.  

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/220/en

Project Title

Lead optimization of a novel chemical series for Chagas disease

Collaboration

Partners

1. Mitsubishi Tanabe Pharma Corporation (Japan)

2. DNDi – Drugs for Neglected Diseases initiative (Switzerland)

Disease

Chagas Disease

Intervention

Drug

Stage

Lead Optimization

Awarded Amount

JPY 294,532,531 (USD 1.9 million)

Status

Continued project

Summary

[Project objective]

The main objective of this two-year project is to deliver optimized lead candidate(s) meeting the efficacy and in vitro safety requirements described in the DNDi Target Candidate Profile (TCP). Fulfilling the TCP efficacy criteria compound(s) would be ready to enter preclinical development enabling studies addressing the complementary safety, DMPK (Drug Metabolism and Pharmacokinetics) and CMC (Chemistry, Manufacturing, and Controls) criteria of the TCP. The lead optimization efforts will focus on a novel spirocyclic series (Spiro 5) active against T. cruzi infection. In addition, this project aims at identifying the mechanism of action of this new series.

[Project design]

DNDi and Mitsubishi Tanabe Pharma Co. (MTPC) aim at developing through a two-year lead optimization collaboration a novel and very promising T. cruzi active series identified from a high throughput screening of a 51,200 MTPC proprietary library and progressed to date to lead stage. The project partners plan to chemically derivatize the lead series using a well-defined and diversified medicinal chemistry strategy to improve its in vitro T. cruzi potency, maintain its favorable DMPK properties while mitigating any safety liabilities. In parallel DNDi and MTPC plan to elucidate the mechanism of action of the series notably with the expert support of University of Dundee and make use of this information to guide the lead optimization program.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/219/en