Advancing innovations for neglecteddiseases during and beyond the pandemic
James Duffy, Director Drug Discovery

GHIT-PDP Webinar, Geneva, 3 September 2021
1 Defeating Malaria Together

Malaria | Human impact
Takes the life of a child every 2 minutes

Can kill within 24 hrs of symptom onset

Threatens almost half
the world’s population

Deprives African countries of$12-30 billion every year
Is associated with drug resistance inSoutheast Asia, where an estimated> 20 million cases occur every year
Is both a cause and consequence of poverty and predominantlyaffects vulnerable populations such as pregnant women andchildren

A malaria-free world | Future scenarios“A malaria-free world, which has been WHO’s vision since at least 1955,
Global Fund to Fight AIDS, TB andremains the ultimate goal of the global health community,” Dr. Pedro Alonso,
Malaria raised US$14B for its next 3director of WHO’s Global Malaria Programmeyear funding cycle (Lyon, 2019)2018
405,000 deaths
228 million cases

Global Fund to Fight AIDS, TB andMalaria raised US$14B for its next
3-year funding cycle (Lyon, 2019)• Strengthen existing malaria controls by improving management and use ofavailable tools• Stimulating the R&D pipeline for new malaria medicines, vaccines, andmosquito control tools• Mobilizing new financing from malaria-endemic countries and donors($2 billion annually)

PDP model | Transforming drug discovery

MMV | Mission and strategy
MMV was launched in 1999. Our mission is
to discover, develop and deliver new,effective and affordable antimalarial drugs
for vulnerable populations in diseaseendemic countries

While the antimalarial drug market ishuge in terms of those in need,
it is small in terms of profit…

…so MMV shares the costs and risks ofdrug development with partners and makes
antimalarial drug research happen

Antimalarial drug discovery | Target profileDiscoverDevelop

1. New drugs for treatment or protection•••

Fast acting

Long duration

Kill up to 1012 parasites in a patient (c.f. ACTs clear 4 log10 units in 48 h)
Typically requires a duration of exposure > efficacious concentration for to 4-6 days(treatment) or 7-28 days (prophylaxis) (c.f. Chloroquine T1/2 = 20-60 days)
Oral dose < 100 mg

2. Efficacy against all known field resistance•DeliverLow propensity for resistance

New antimalarial drugs must have a low risk of resistance generation (MIR < 7)

3. Developable as a cheap, fixed dose child-friendly combo••

Patient population

Cost of treatment/prophylaxis course < $1 (adult) / < $0.25 (infants under 2 years)
No contra-indication for use by children and women of child-bearing potential

Burrows, J. N. et al. Malar. J. 16, 26 (2017)

GHIT | Unlocking Japanese innovation• Japanese scientists have an unparalleled trackrecord in infectious disease drug discovery• Japanese organizations have access to novelcompound libraries• Prior to GHIT, MMV had very limited successengaging with Japanese organizations• Connected MMV to potential partners andhelped to build relationship andunderstanding1• Provided clear RFPs, portfolio management,
milestone criteria2 and governance• Generous investment (> ¥150,000,000)
1.
2.

Katsuno, K. Parasitology International, 80, 102232 (2021)
Katsuno, K., et al. Nature Reviews Drug Discovery, 14, 751–758 (2015)

GHIT-MMV | Malaria drug discovery portfolio
Number of projects

16Target Research Platform

14Screening Platform

12

Hit to Lead Platform

10Product Development Platform

864202013

20142015

2016

2017
Year2018

201920202021• > 500,000 (novel) Japanese compounds/isolated natural products screened• Resulting in 5 Hit to Lead projects and 2 Product development projects• Novel and ‘high value’ malaria drug targets investigated: lipid kinases (PI4K),
aminoacyl tRNA synthetases (KRS, PRS, etc.), enzymes (DHODH, etc.), etc.
• 4 projects with potential to deliver a drug candidate in 2022-2023

A malaria-free world | Impact of COVID-19
Global Fund to Fight AIDS, TB and• Disruptions in malaria service delivery were projected
to leadUS$14B
to a possible
Malaria raisedfor its next 3doubling in malaria deaths in 2020 compared year
to 2018,equating
tofunding cycle (Lyon, 2019)
approximately 800,000 lives lost1• Initial data indicates that COVID-19 has had a significant negative impact onmalaria diagnosis and treatment2

1.
2.

World Malaria Report 2020 (2020)
The Global Fund: “The Impact of COVID-19 on…Malaria Services and Systems” (2021)

PDP model | Beyond the target disease• PDPs are equipped to help prevent and respond to health threats*• MMV catalyzed the discovery of drugs for
COVID-19 with the COVID BOX (a set of 80
drugs with predicted activity against SARSCoV-2)• Worked with partners on COVID-19 clinicalstudies, including ReACT and ANTICOV• PDPs build local capacity to perform research and strengthen health systems*• Decades of investment in healthcare
infrastructure/personnel enabled swift
adaptation of malaria programmes in the light ofCOVID-19• State-of-the-art MMV-supported medical
centers and staff used for COVID-19 testing*Keeping the Promise Executive Summary: https://www.keepingthepromisereport.org/report-resources

GHIT-MMV | Learnings from the partnership• Screening Japanese compound
libraries has identified novel
chemistry and novel targets• Japanese partners have given
expert drug discovery anddevelopment input• Japanese scientists see the value of working
on NTD projects and have built productive
project teams with strong mutual respect•

GHIT framework has enabled gooddecision making•

GHIT flexible ‘open innovation’ culturehas allowed different (productive) project
team configurations

Final thoughts | Opportunities for partners• Current focus of MMV discovery• Target-based as well as phenotypicprojects• Series with potential for prophylaxis as
well as case-management• Neglected patients ‘mothers and babies’• …and the challenges• Novel mechanism of action• Low risk of drug resistance• Long duration• Pediatric and maternal drug safety• …and the (new) opportunities.
• Machine learning (AI)• Target ID• Development of low clearancecompounds (and preclinical assays)• Development of preclinical assays forreprotoxicity, etc.

Final thoughts | Benefits for partners

Patents or patentablematerial, know-how
and research tools

Incentive schemes(e.g. orphan designation,accelerated regulatory review
and Priority Review Voucher)

Expanded R&D capacity in infectious
diseases, strengthened reputation in
the global health community

Non-dilutive
financing

Scientific and access expertise(external and in-house)GHIT-MMV | Project collaborators"The GHIT Fund has…a pioneering model ofpartnership that brings Japanese innovation,
investment and leadership to the global fight againstinfectious disease.“ Dr. Margret Chan, former
Director-General of the WHOBuilt on partnerships | Stronger togetherThank you