GHIT Fund Announces New Investments: A Total of 750 Million Yen in Drugs for Malaria and Chagas Disease, Vaccine for Malaria, and Diagnostics for Tuberculosis

TOKYO, Nov. 4, 2021 /PRNewswire/ — The Global Health Innovative Technology (GHIT) Fund announced today a total of approximately 750…

TOKYO, Nov. 4, 2021 /PRNewswire/ — The Global Health Innovative Technology (GHIT) Fund announced today a total of approximately 750 million yen (US$6.6 million*) to invest in six partnerships to develop new lifesaving drugs for malaria and Chagas Disease, a vaccine for malaria, and diagnostics for tuberculosis (TB).** (Appendix 1 & 2)

«We are pleased to announce our new investments in diagnostics for tuberculosis, a vaccine and drug for malaria, and drug discovery for Chagas diseases,» said GHIT’s acting CEO Kio Yamabe. «Even in the midst of a pandemic, we are committed to advancing product development for patients suffering from neglected diseases by strengthening partnerships with R&D and funding partners.»

A Diagnostic for Tuberculosis

GHIT will invest 83.4 million yen (US$733K) in evaluating the performance of the Lung Flute/Lung Flute ECO to improve sputum-based TB diagnosis primarily in vulnerable groups in a TB-endemic setting. The Lung Flute, invented in the early 2000s, is a positive expiratory pressure (PEP) device that creates sound waves that, when blown, loosens phlegm in the lungs and enables individuals to increase the quantity and quality of sputum they can produce. The Lung Flute ECO is a more recently developed paper-based version of the Lung Flute that is inexpensive enough to be used as a disposable, point-of-care tool to aid in sputum production in low-resource settings.

A Vaccine and Drug for Malaria

GHIT will also invest 469 million yen (US$4.1M) in clinical development of two Placental Malaria (PM) vaccine candidates known as PAMVAC and PRIMVAC. PM constitutes a major health problem, causing an estimated 10,000 maternal and 200,000 infant deaths annually. Animal immunization and clinical trial data and results show lasting immune responses and have demonstrated that both adjuvanted vaccine candidates are safe and well-tolerated. However, further optimization of the current candidates is essential to address emerging different variants. GHIT will make another investment of 83.8 million yen (US$737K) in malaria drug development for a new drug design approach known as PROteolysis-TArgeting Chimeras or PROTACs. PROTACs acts not as an inhibitor of target functions, but as a protein degrader hijacking the proteasome to destroy target proteins.

Chagas Drug Discovery

GHIT will also invest 98.9 million yen (US$870K) in further development of novel anti-Trypanosoma cruzi (T. cruzi) drugs acting against the selected target identified in a previous GHIT-invested study: the T. cruzi autophagy-regulating factor that is essential to the T. cruzi life cycle.

Finally, GHIT will invest 19.8 million yen (US$170K) for drug screening programs. In collaboration with the Drugs for Neglected Diseases initiative (DNDi), Daiichi Sankyo Company, Limited and Takeda Pharmaceutical Company Limited will conduct a screening for hit identification for Chagas disease by utilizing their compound libraries.

As of November 4, there are 63 ongoing projects, including 29 discovery, 24 preclinical and 10 clinical trials, in the GHIT portfolio (Appendix 3). The total amount of investments since 2013 is 26.9 billion yen (US$236 million).

* USD1 = JPY¥113.68, the approximate exchange rate on October 29, 2021.

** These awarded projects were selected from a number of proposals to the RFP2021-001 for Target Research Platform, Screening Platform, Hit-to-Lead Platform, and Product Development Platform, which was open for applications from November 2020 to July 2021. The GHIT board conducted in July 2021 approved these new investments.

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

G2021-114

New project

Viability & Value of the Lung Flute ECO for Sputum Sample Collection and Tuberculosis Testing in Vulnerable Groups (3V Trial)

Research Institute of Tuberculosis, Acoustic Innovation (AI), Institute for Tropical Medicine (ITM), Center for Health Promotion and Research (CHPR) also known as the TB Reference Laboratory Bamenda (TRLB)

Tuberculosis

Diagnostics

Product Development

¥83,373,809

(US$733,408)

G2020-214

New project

Clinical development of placental malaria vaccine candidates

Ehime University (Ehime), European Vaccine Initiative (EVI), University of Copenhagen (UCPH), Institut national de la santé et de la recherche médicale (Inserm), Institut de recherche pour le développement, Groupe de Recherche Action en Santé (GRAS), Noguchi Memorial Institute for Medical Research

Malaria

Vaccine

Pre-Clinical Development

¥469,292,404

(US$4,128,188)

S2021-121

New project

Screening project between Takeda Pharmaceutical Company Ltd. and DNDi

Takeda Pharmaceutical Company Ltd., Drugs for Neglected Diseases initiative (DNDi)

Chagas Disease

Drug

Hit Identification

¥8,994,695

(US$79,123)

S2021-122

New project

Screening project between Daiichi Sankyo Company Limited and DNDi

Daiichi Sankyo Company Limited, Drugs for Neglected Diseases initiative (DNDi)

Chagas Disease

Drug

Hit Identification

¥10,976,301

(US$96,554)

T2021-152

New project

Identification and Validation of potential Plasmodium E3 Ligases for PROTAC Platform

FIMECS, Inc., National Center for Genetic Engineering and Biotechnology (BIOTEC)

Malaria

Drug

Target Identification

¥83,858,773

(US$737,674)

T2021-153

Continued

project

Autophagy as a novel drug-development target for Chagas disease

National Institute of Advanced Industrial Science and Technology (AIST), Drugs for Neglected Diseases initiative (DNDi)

Chagas Disease

Drug

Target Identification

¥98,920,080

(US$870,163)


*All amounts are listed at the exchange rate of USD1 = JPY¥113.68, the approximate exchange rate on October 29, 2021.

Appendix.2 Project Details

G2021-114

Project Title

Viability & Value of the Lung Flute ECO for Sputum Sample Collection and Tuberculosis Testing in Vulnerable Groups (3V Trial)

Collaboration

Partners

Research Institute of Tuberculosis, Acoustic Innovation (AI), Institute for Tropical Medicine (ITM), Center for Health Promotion and Research (CHPR) also known as the TB Reference Laboratory Bamenda (TRLB)

Disease

Tuberculosis

Intervention

Diagnostics

Stage

Product Development

Awarded Amount

¥83,373,809 (US$733,408)

Status

New project

Summary

[Project objective]

The primary objective is to evaluate the proportion of presumptive TB clients who test positive for TB after using the Lung Flute ECO or the Lung Flute® HR, as compared to the standard of care with no device to aid in sputum production.

 

The secondary objectives are:

1. To compare the proportion of presumptive TB clients who are able to submit sputum samples for testing after using Lung Flute ECO prototype, Lung Flute® HR and the standard of care

2. To compare average quality and quantity of sputum samples submitted using Lung Flute ECO prototype, Lung Flute®, and the standard of care

3. To assess the feasibility, safety, user satisfaction, and cost effectiveness of the Lung Flute ECO prototype and the Lung Flute® HR as compared to the standard of care

 

[Project design]

We will evaluate performance of the Lung Flute ECO and the Lung Flute® HR across multiple sites in Cameroon. The study focuses on evaluating test access and accuracy in patient groups with documented challenges to produce sputum on demand, including children 6-14 years of age, women, the elderly, people living with HIV, people admitted to hospital, and asymptomatic persons screening positive for TB by digital chest x-ray.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/194/en

G2020-214

Project Title

Clinical development of placental malaria vaccine candidates

Collaboration

Partners

Ehime University (Ehime), European Vaccine Initiative (EVI), University of Copenhagen (UCPH), Institut national de la santé et de la recherche médicale (Inserm), Institut de recherche pour le développement, Groupe de Recherche Action en Santé (GRAS), Noguchi Memorial Institute for Medical Research

Disease

Malaria

Intervention

Vaccine

Stage

Pre-Clinical Development

Awarded Amount

¥469,292,404 (US$4,128,188)

Status

New project

Summary

[Project objective]

This project will advance and accelerate the development of a PM vaccine by establishing a global portfolio of vaccine candidates that will be evaluated according to the following objectives:

 

1. Objective 1: to assess the longevity of the immune response induced by PRIMVAC through an extended follow up of PRIMVAC vaccinated women in Burkina Faso

2. Objective 2: to assess the capacity of adjuvanted PRIMVAC to boost naturally acquired VAR2CSA specific immune responses

3. Objective 3: to assess the potential of a capsid-like particle (CLP) based vaccine formulation to increase vaccine induced immune responses

4. Objective 4: to evaluate cross-reactivity of the immune responses induced by VAR2CSA antigens

 

Generated data will inform the next steps of PM vaccine development, will allow a decision on the formulation for further development and the preparation of a larger phase II immunogenicity study.

 

[Project design]

Recombinant soluble proteins are often thought to induce an immune response of insufficient strength and breadth to confer full protection. However, we have observed that our vaccine candidates, especially PRIMVAC, produced a lasting immune response. We propose therefore to further characterize the longevity of the PRIMVAC-induced immune response in women in malaria-endemic areas, as well as the capacity of the vaccine to boost and broaden a natural acquired immune response.

We will also undertake an in-depth analysis of the cross-reactivity against the different haplotypes by the immune response elicited by the PM vaccine candidates.

Additionally, we propose to undertake the pre-clinical development of PAMVAC-CLP. PAMVAC-CLP is an improved version of PAMVAC, where a capsid-like particle (CLP) has been added as backbone, thereby potentially improving immunogenicity, cross-reactivity and longevity of the induced immune response. Taken together, PRIMVAC and PAMVAC-CLP, together with additional PRIMVAC variants in early pre-clinical evaluation constitute a promising portfolio of PM vaccine candidates.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/195/en

S2021-121

Project Title

Screening project between Takeda Pharmaceutical Company Ltd. and DNDi

Collaboration

Partners

Takeda Pharmaceutical Company Ltd., Drugs for Neglected Diseases initiative (DNDi)

Disease

Chagas Disease

Intervention

Drug

Stage

Hit Identification

Awarded Amount

¥8,994,695 (US$79,123)

Status

New project

Summary

This is a screening project between Takeda Pharmaceutical Company Ltd. and DNDi.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/198/en

S2021-122

Project Title

Screening project between Daiichi Sankyo Company Limited and DNDi

Collaboration

Partners

Daiichi Sankyo Company Limited, Drugs for Neglected Diseases initiative (DNDi)

Disease

Chagas Disease

Intervention

Drug

Stage

Target Identification

Awarded Amount

¥10,976,301 (US$96,554)

Status

New project

Summary

This is a screening project between Daiichi Sankyo Company Limited and DNDi.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/199/en

T2021-152

Project Title

Identification and Validation of potential Plasmodium E3 Ligases for PROTAC Platform

Collaboration

Partners

FIMECS, Inc., National Center for Genetic Engineering and Biotechnology (BIOTEC)

Disease

Malaria

Intervention

Drug

Stage

Target Identification

Awarded Amount

¥83,858,773 (US$737,674)

Status

New project

Summary

[Project objective]

To identify a chemical warhead(s) that can recruit a parasite ubiquitin E3 ligase(s) to degrade a target parasite protein, which will constitute a platform for the design of protein degrader antimalarials.

 

[Project design]

We will design and synthesize a library of protein degraders for degradation experiments. The test compounds will be designed with various chemical warheads against a variety of ubiquitin E3 ligases joined to a warhead specific to the Plasmodium parasite bifunctional dihydrofolate reductase-thymidylate synthase, a well-studied parasite protein. The protein degrader that trigger target protein degradation will be used for designing follow-on compounds, including probe compounds for biochemical characterization of Plasmodium ubiquitin E3 ligase(s) that interact with the ubiquitin E3 ligase warhead and those protein degraders for optimizing the degradation of target.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/196/en

T2021-153

Project Title

Autophagy as a novel drug-development target for Chagas disease

Collaboration

Partners

National Institute of Advanced Industrial Science and Technology (AIST), Drugs for Neglected Diseases initiative (DNDi)

Disease

Chagas Disease

Intervention

Drug

Stage

Target Identification

Awarded Amount

¥98,920,080 (US$870,163)

Status

Continued project

Summary

[Project objective]

The overall goal of this project is to obtain initial hit compounds amenable for further development as novel anti-T. cruzi drugs acting through inhibition of the parasite autophagy-regulating factor.

 

[Project design]

To achieve the goals of the project, we use two different but complementary screening approaches, a Fragment-Based Drug Discovery (FBDD) approach and a «classical» screening of an anti-T. cruzi compound library (the DNDi library) against the autophagy-regulating factor target. For the FBDD approach, we employ the DNA-encoded library (DEL) technology, where two fragments are intended to bind simultaneously to the protein in the same vicinity. On the other hand, the DNDi library consists of compounds already confirmed to have promising intracellular anti-T. cruzi activity in whole cell-based assays. In this project, we will require that both the identified hits and the target protein be druggable. We consider that the ideal initial hit compound should not only bind to the drug target and inhibit enzyme activity, but also have a protein-compound binding state that will facilitate subsequent modification during Hit-To-Lead and Lead Optimization steps. Since this requires a structural understanding of the compound-protein interactions, determination of the three-dimensional structures of the hit compound-target molecule complexes will be a critical part of this project, as well. Notably, hit compounds obtained from the FBDD approach will be initially selected based only on their target-binding and enzyme inhibition activity independently of their pharmacological activities. The identified compounds must have the potential to evolve and be optimized during the subsequent development stages to acquire the required properties.

Project Detail

https://www.ghitfund.org/investment/portfoliodetail/detail/197/en


*All amounts are listed at the exchange rate of USD1 = JPY¥113.68, the approximate exchange rate on October 29, 2021.

Appendix.3 Investment Overview (As of November 4, 2021)

 1. Investment to date

Total investments 26.9 billion yen (US$236 million*)

Total invested projects 111(active projects 63, completed projects 48)

Portfolio analysis (active projects + completed projects) 

Portfolio analysis of active and completed projects. Note: all amounts are listed at the exchange rate of USD1 = JPY¥113.68, the approximate exchange rate on October 29, 2021.

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

­For more information, contact:

Katy Lenard at +1-301-280-5719 or klenard@burness.com

Bumpei Tamamura at +81-36441-2032 or bumpei.tamamura@ghitfund.org

Cision View original content to download multimedia:https://www.prnewswire.com/news-releases/ghit-fund-announces-new-investments-a-total-of-750-million-yen-in-drugs-for-malaria-and-chagas-disease-vaccine-for-malaria-and-diagnostics-for-tuberculosis-301416071.html

SOURCE GHIT Fund