Feb 2, 2022 (Wed)

GHIT Fund - Product Development Partnerships (PDPs)
Webinar Series Session 4 (FIND)
Advancing innovations through global partnerships
for neglected diseases during and beyond the COVID-19 pandemic

Global Partnerships
to combat Neglected Tropical Diseases
Shinjiro HAMANO M.D., Ph.D.
Institute of Tropical Medicine (NUITM), Nagasaki University
shinjiro@nagasaki-u.ac.jp ℡ +81-95-819-7822

Introduction of the Speaker (Shinjiro HAMANO)l

1987-1993
1993-1997

School of Medicine, Kumamoto University (M.D.)
Graduate School of Biomedical Sciences, Kyushu University (Ph.D.)l

1997-2004

Assistant Professor, Kyushu Universitylülll

2004-2006
2006-2009
2009-

Hamano S, et.al., Immunity. 2003;19(5):657-67., Yoshida H, Hamano S, et.al., Immunity. 2001;15(4):569-78.

Research Associate, Virginia State University (2 years)
Assistant Professor, Kyushu University
Professor, Institute of Tropical Medicine (NEKKEN), Nagasaki UniversityØHis research interests are tropical infectious diseases and host defense mechanisms to microbes, especially parasites. Besides theimmunological approach, he conducts field studies on neglected tropical diseases, especially leishmaniasis and schistosomiasis. inAsia and Africa.

ØSince 2020, he has been involved in a new international multidisciplinary collaboration to develop “A schistosomiasis rapiddiagnostic test” with FIND, LUMC, Merck (MGHI) etc (G2020-104). In addition, he also dedicated himself to develop diagnostic
tools targeting schistosomiasis with Lygature and LUMC (T2017-272, DTECT-Schisto) with the support by the GHIT.

ØHe has also contributed to developing live-attenuated prophylactic vaccines for leishmaniasis (G2015-115 and G2018-102) andtrypanosomiasis (G2019-102) using CRISPR gene editing and leishmanin skin test for detection of Leishmania exposure andimmunity (G2019-213).
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Institute of Tropical Medicine, Nagasaki Univ.
MISSION STATEMENT
The tropics, the most ecologically diverse region on the Earth, presents an ongoingcomplexity of tropical diseases and other health problems. In view of the remarkableadvances made in the field of international exchange in recent years, it is imperative thatthese problems be addressed from a global perspective. Based on this understanding, theInstitute of Tropical Medicine, Nagasaki University, aims to overcome tropical diseases,
particularly infectious diseases, and the various health problems associated with them,in cooperation with related institutions, to strive for excellence in the following areas:
1. Leading research in tropical medicine and international health
2. Global contribution to disease control and health promotion in the tropics
by applying the fruits of the research
3. Cultivation of the researchers and specialists in the fields mentioned above
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The GHIT facilitate international partnerships that bring Japaneseinnovation, investment, and leadership to the global fight against
infectious diseases and poverty in the developing world

G2015-115 à G2018-201G2019-102
Vac

T2017-272 Schistosomiasis
DTECT-Schisto (Ab detection)
Lygature, LUMC

Leishmaniasis Vac
Chagas Disease

OSU, McGill Univ.,
US FDA, NIAID/NIH
GennovaBiopharmaceuticals
OSU,, CIDR-Ecuador

G2019-213 Skin test for Leishmaniasis
G2020-104 Schistosomiasis CAA-RDT
FIND, LUMC, Merck, Mologic, KEMRI & UERM

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A list of specific questions for the GHIT fund - PDPs
webinar series session 4 (FIND)
1. How did we first learn about PDPs and the PDPs of our session (FIND)?
2. Present about the project(s) working with PDPs/FIND (on-going andpast), preferably a GHIT-related project.
(e.g. how the partnership/project started, the PDP’s and yourorganization’s role in the project, its merits/impact to yourorganization)
3. Lessons learned and challenges from the partnership and share howthese lessons can be implemented in future projects with PDPs and/or
our organization’s R&D activities.
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We learnt about PDPs through the GHIT project
to develop live attenuated prophylactic vaccines for leishmaniasis

McGillUniversity
US FDA

Ohio StateUniversityGennova
Biopharmaceuticals

A Multidisciplinary Team With Complementary ExpertiseG2015-115 à G2018-201

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Innovative approach and achievements

G2015-115
G2018-201

lUsing CRISPR-Cas, generated marker free centrin gene deficient L. major (LmCen-/-).

l

Demonstrated safety of LmCen-/- in immunodeficient host, their failure to survive in sand flyvector and inability to revert to virulence after multiple animal passages.

lDemonstrated efficacy of LmCen-/- parasites in preventing sand fly-transmitted cutaneous (CL) as
well as visceral leishmaniasis (VL) in mice and hamsters.

lShowed that LmCen-/- parasites induce protective immune response and parasite-specificeffector memory T cells.

lUsing CRISPR-Cas, generated marker free centrin gene deficient L. mexicana (LmexCen-/-).

Publications
1. Zhang, W.W., Karmakar, S., Gannavaram, S., Dey, R., et.al.: A second generation leishmanization vaccine with amarkerless attenuated Leishmania major strain using CRISPR gene editing. Nat. Commun., 2020; 11(1): 3461.
2. Karmakar, S., Ismail, N., et.al.: Preclinical validation of a live attenuated dermotropic Leishmania vaccine againstvector transmitted fatal visceral leishmaniasis. Commun. Biol. (Nature) , 2021; 4(1): 929.
3. Volpedo, G., et.al.: Centrin-deficient Leishmania mexicana confers protection against new world cutaneousleishmaniasis. npj Vaccines (Nature), 2022; in press
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https://www.ghitfund.org/investment/portfoliodetail/detail/135/en

Further Achievements
Developing Master Cell Bank and Working Cell Bank for LmCen-/- parasites atATCC, USA for manufacturing of cGMP product in an endemic country.
l Validating the assays for final characterization of cGMP LmCen-/- product.
l Preparing regulatory dossier for Phase 1 study with regulatory authorities in theUS.
l Initiated discussions with our Indian vaccine manufacturer for Phase 1 studies inthe India.
l Developed GLP material for L donovani antigens for Skin Test for leishmaniasis
as a surrogate marker for immunity. (G2019-213).
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We learnt about the PDP with FIND throughGHIT-related project

OSU, McGill Univ.,
US FDA, NIAID/NIH
G2015-115 à G2018-201 Leishmaniasis Vac GennovaBiopharmaceuticals
G2019-102
Chagas Disease Vac OSU, CIDR-Ecuador

T2017-272 Schistosomiasis
DTECT-Schisto (Ab detection))with Lygature, LUMC

G2019-213 Skin test for Leishmaniasis
G2020-104 Schistosomiasis CAA-RDT
with FIND, LUMC, Merck, Mologic, KEMRI & UERM

9Globally prevalent schistosomiasis (230 million people are infected)
Global Health Problem
ü Schistosomiasis affects 230 million people worldwide,including many children <14yrs of age
ü Control programs largely based on Mass Drug
Administration (MDA) with praziquantel (PZQ)ü Efforts move from control towards elimination ofschistosomiasis (WHO Roadmap)

Lancet Infect Dis. 2017 Feb;17(2):e42-e48
Human schistosomiasis in the post mass drug administration era

Unmet NeedüNew diagnostic or monitoring tools are urgently
needed to support, monitor and sustain
schistosomiasis control and elimination programs.
Current diagnostic methods have limitations:ü Insensitive for low-intensity infections & not suitable forpost-MDA application AND/ORü Not able to discriminate between current and past
infection AND/ORü Not able to detect infection with different Schistosoma
species AND/ORü Not in rapid test or field-applicable format (invasive, basedon blood collection)

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Schistosomiasis control toward elimination

How can we monitor and survey (re)transmission of schistosomiasis inpre- and post elimination settings ?

11Partners DTECT-Schisto (T2017-272 )Development of defined antigens for detection of schistosoma infection-specific antibodies in blood and urine
NAGASAKI UNIVERSITY•••

Experts with protein
antigens of NTDs
Experts in detecting
antibodies in urine
Access to samples from
Schistosoma-endemic
areas

LUMC

•
•••

Schistosomiasis expert
Expert in anti-glycan
antibody detection
technology applications
Access to controlled humaninfection model
Access to biobanked
samples from Schistosomaendemic areas

LYGATURE•••

Independent “broker”
Experts in managing
multi-stakeholder
consortia in health R&Dand access (>100partnerships since 2007)
Current Global Healthportfolio includes 5projects

FIND

•

•

Bridge between
technology development,
policy and clinical care
Experts in overseeing thedevelopment of diagnostic
tests for NTDs

1. Diagnostic Ab response profiles and protein/glycan targets have been identified.
2. Data analysis to identify and validate specific targets and use cases is ongoing.

12SPOTLIGHT ON SCHISTOSOMIASISR A P I D T E S T S T O S U P P O R T D I S E A S E C O N T R O L & E L I M I N AT I O NSUPPORTING NATIONAL PROGRAMMES TO MONITOR THE IMPACT OF MASS DRUG
ADMINISTRATION CAMPAIGNS AND PRECISION MAPPING EFFORTS
GHIT grant approved July 2020
Consortium of 8 partners
In 2021, first field evaluations ofprototype in Kenya and the Philippines(led by NUITM) yielded very
encouraging results
Further development of the CAA RDT isrequired to meet the sensitivity targets,with a final field evaluation required
prior to design-lock and transfer tomanufacturing – planned for Q2/3 2022
FIND in collaboration with GHIT andthe Merck Global Health Institute aredeveloping an access strategy for theSCH CAA RDTNUITM is monitoring the field studies of the prototype in the Philippines and will manage the clinical trials with the support from FIND.
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Lessons learned and challenges from the partnershipl Lessons learned:
Making international multidisciplinary team with complementary expertise is critical, which
can bring the projects forward from academic research to the product development withovercoming scientific, technical, and regulatory hurdles.
l Managing multi-stakeholder consortia with leadership and coordination is essential andcrucial.
ll Challenges:
Establishing strong relationships in the absence of in-person meetings. The SCH CAA RDT
project got funded in July 2020, in the first year of COVID-19. To this day, we have not had thechance to meet the FIND team nor any of other partners in person. Yet, we’ve successfullycompleted the first field evaluations with very promising results.
l COVID-19: having to monitor field-based studies outside of Japan with new partners. We hadto find innovative ways to work around this, by developing new tools, and hiring a clinicalresearch associate to be present at the field site, instead of us.
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How can these lessons be implemented in future projects withPDPs and/or our organization’s R&D activities?
l In future projects with PDPsll

We will try having an independent “broker” with expertise inmanaging multi-stakeholder consortia in health R&D and access.
We need to be more familiar with the regulatory processes in FDA,EMA, WHO or other national authorities for the development of
new vaccines, drugs and diagnoses.

l Our organization’s R&D activities
lOur organization will promote and strengthen public-private
partnership (PPP) for sustainable, efficient, and fruitfuldevelopment of R&D activities.
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