Appendix.1 New Investments
ID/Status

Project Title

Collaboration Partners

Disease/Intervention

StageAwarded Amount

Viability & Value of theLung Flute ECO for Sputum
Sample Collection andTuberculosis Testing in
Vulnerable Groups (3VTrial)

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

ProductDevelopment¥83,373,809(US$733,408)

G2020-214
New project

Clinical development ofplacental malaria vaccine
candidates

Ehime University (Ehime),
European Vaccine Initiative(EVI), University ofCopenhagen (UCPH), Institutnational de la santé et de larecherche médicale (Inserm), Malaria
Institut de recherche pour le Vaccine
développement, Groupe deRecherche Action en Santé(GRAS), Noguchi Memorial
Institute for Medical
Research

Pre-ClinicalDevelopment¥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
Chagas Disease
Neglected Diseases initiative Drug(DNDi)

Hit Identification¥8,994,695(US$79,123)

S2021-122
New project

Screening project between
Daiichi Sankyo Company
Limited and DNDi

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

Hit Identification¥10,976,301(US$96,554)

T2021-152
New project

Identification and Validationof potential Plasmodium E3
Ligases for PROTAC
Platform

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

Target Identification¥83,858,773(US$737,674)

T2021-153
Continued
project

Autophagy as a novel drugdevelopment target for
Chagas disease

National Institute ofAdvanced Industrial Science
Chagas Diseaseand Technology (AIST),
Drug
Drugs for Neglected Diseases
initiative (DNDi)

Target Identification¥98,920,080(US$870,163)

G2021-114
New project

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

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Appendix.2 Project Details
G2021-114
Project Title

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

Collaboration
Partners

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

DiseaseTuberculosis

Intervention

Diagnostics

StageProduct Development

Awarded Amount ¥83,373,809 (US$733,408)
Status

New project[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 nodevice to aid in sputum production.

SummaryThe secondary objectives are:
1. To compare the proportion of presumptive TB clients who are able to submit sputum samples fortesting 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 inCameroon. The study focuses on evaluating test access and accuracy in patient groups with documentedchallenges 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 Detailhttps://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 ledéveloppement, Groupe de Recherche Action en Santé (GRAS), Noguchi Memorial Institute for
Medical Research

DiseaseMalariaIntervention

VaccineStage

Pre-Clinical Development

Awarded Amount ¥469,292,404 (US$4,128,188)
Status

New project2

[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 anextended 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 toincrease 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 theformulation for further development and the preparation of a larger phase II immunogenicity study.
Summary[Project design]
Recombinant soluble proteins are often thought to induce an immune response of insufficient strengthand 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-endemicareas, 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. PAMVACCLP 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 theinduced 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 Detailhttps://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)

DiseaseIntervention
StageChagas Disease
Drug
Hit Identification

Awarded Amount ¥8,994,695 (US$79,123)
StatusSummary
Project Detail

New projectThis is a screening project between Takeda Pharmaceutical Company Ltd. and DNDi.
https://www.ghitfund.org/investment/portfoliodetail/detail/198/en

S2021-122
Project Title

Screening project between Daiichi Sankyo Company Limited and DNDi

CollaborationPartners

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

DiseaseChagas Disease

3Intervention
Stage

Drug
Target Identification

Awarded Amount ¥10,976,301 (US$96,554)
StatusSummary
Project Detail

New projectThis is a screening project between Daiichi Sankyo Company Limited and DNDi.
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)

DiseaseMalariaIntervention

DrugStage

Target Identification

Awarded Amount ¥83,858,773 (US$737,674)
Status

New project[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.

Summary

Project Detail[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 reductasethymidylate 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 forbiochemical characterization of Plasmodium ubiquitin E3 ligase(s) that interact with the ubiquitin E3ligase warhead and those protein degraders for optimizing the degradation of target.
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)

DiseaseIntervention
Stage

Chagas Disease
Drug
Target Identification

Awarded Amount ¥98,920,080 (US$870,163)
StatusContinued project4

[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.

SummaryProject Detail[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 libraryconsists of compounds already confirmed to have promising intracellular anti-T. cruzi activity inwhole 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 threedimensional structures of the hit compound-target molecule complexes will be a critical part of thisproject, as well. Notably, hit compounds obtained from the FBDD approach will be initially selectedbased only on their target-binding and enzyme inhibition activity independently of theirpharmacological activities. The identified compounds must have the potential to evolve and beoptimized during the subsequent development stages to acquire the required properties.
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.

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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）
2. Portfolio analysis (active projects + completed projects)
Stage■Discovery ¥4,492,192,256 (US$39,516,118)
16.7%(61 projects)■Preclinical ¥15,733,339,612 (US$138,400,243) 58.5%(34 projects)■Clinical ¥6,667,087,367 (US$58,647,848)
24.8%(16 projects)
Disease■Malaria ¥11,605,812,693 (US$102,091,948)
43.2%(48 projects)■Tuberculosis ¥3,000,237,389 (US$26,391,955) 11.2%(21 projects)■NTDs ¥12,286,569,153 (US$108,080,306)45.7%(42 projects)

Intervention■Drugs ¥17,646,985,796 (US$155,233,865)
65.6%(72 projects)■Vaccines ¥6,488,622,163 (US$57,077,957)
24.1%(24 projects)■Diagnostics ¥2,757,011,276 (US$24,252,386) 10.3%(15 projects)*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

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