Strictly Confidential

Session 5: EVI and PATH MVI Developing Effective andAffordable Vaccines through Partnerships
Working until everyone has a cure

Our Company Mission

Contribute to society byproviding critical but
neglected pharmaceuticals
and medical devices

2Nobelpharma has focused on the area of Rare and Orphan Diseases

Proven Track Record

2003

 Has launched drugs for rare diseases such as Wilson'sdisease, tuberous sclerosis-associated skin lesions, amongothers

Founded60+~350

R&DPartnerships

Employees

Differentiated R&D Platform Development exclusively with external partners Specializing in Late-phase Development

15“Contribute to society byproviding critical butneglected pharmaceuticals
and medical devices.”

Launched
Products1

12Key Pipeline
Products12Orphan
Designations2

Outsourcing Manufacturing
 Outsourcing manufacturing to external partners to pursue
an asset light business model

Strong Distribution Capabilities
 Exclusive partnership with MEDIPAL HOLDINGS, one ofJapanese leading pharmaceutical distributors

3

Note: (1) Number of products launched by NPC(2) Including products under development

When/How the collaborative work started with EVI◎ In Feb 2012, Prof. Horii, Osaka University, and Dr. Leroy,EVI, met first time during WHO Malvac meeting in Geneva◎ In Aug 2013, an introductory letter was sent to Prof. Horii
from Dr. Stefan Jungbluth introducing EVI as a ProductDevelopment Partnership.
◎ In Sept 2013, first T-con to discuss potential collaboration◎ EVI introduced Dr. Sodiomon Sirima, CNRFP (now Chief
Executive Officer @Gras) in Burkina Faso, to Prof. Horii– and the three entities agreed to come together withshared interest and strong commitment to develop NPCSE36 vaccine candidate◎ In Apr 2014, the three partners applied for GHIT Fund.
The proposal was approved in Aug 2014 and the grant agreement was signed.
The CONSORTIUM agreement between partners was signed in August 2014 anda clinical trial agreement was in place in November 2014.
◎ Just at that time, Nobelpharma joined this CONSORTIUM
4

Burkina Faso

ブルキナファソu Name was changed from “Upper Volta”
by President Thomas Sankara
u Population : 22.7M (2019)u Capital: Ouagadougou
Clinical trials in Burkina Faso
☆ P1b/AHG in Banfora☆ P1b/CpG in Ouagadougou

5AFRICAMalaria Parasites Life Cycle and Potential Vaccine Targets
Human

Anopheles Mosquito

Trophozoite

Transmission Blocking Vaccine:
Prevent Transmission
Challenge:– Difficulty in efficacy
evaluation– “Mass” vaccination

SchizontRing
Gametocyte

Blood Stage
Liver Stage

Mosquito Stage

Red Blood Cell
Merozoite
Sporozoite

Liver Stage Vaccine: Prevent Infection

RTS,S/AS01

R21/Matrix-M

Limitation:– High polymorphism of csp– Escape parasite can lead to bloodstage infection

6Note: Revised scheme from original scheme in RIMD/Osaka University HP.

6Blood Stage Vaccine: Prevent Disease

NPC-SE36
Advantage:– Limited polymorphism of SE36
Challenge:– Low seroconversion in malaria
highly exposed population

CONSORTIUM organization, R&R

Organization
Name

DesignatedDevelopment
Partner

Collaboration
Partner 1

Collaboration
Partner 2

Collaboration
Partner 3

EuropeanVaccine Initiative(EVI)

Osaka University

Groupe deRecherche Action
en Santé（GRAS)

Nobelpharma(NPC)

••

R&R

7

Research Institute forMicrobial Diseases(RIMD)
Medical Center forTranslational
Research(MTR)ü Overallü Scientificcoordination
developerandü Coordinate formanagement of
immunogenicity
the programme
assessments
ü Representative
fundingrecipientü Involved inü Development
Africa P2
partner andprotocol andSponsor
study dossierü Lead andpreparation
provide GMPü Help in trial site
grade batch
selection/evaluand CpGation process inODN(K3)AfricaContract Structure with GHIT Fund◆ Investment Agreement
üüü
üüüü

ü

Award of Budget to the CONSORTIUM
Nomination of Partnership
Requires Collaboration Agreement among the Partners
Collaboration Partners Indemnification
Payment and bi-Annual Progress Report schedules
GHIT-monitored Milestones and Activities
Requires Record Maintenance and Inspection by GHIT on how theInvestment was expendedAudit Rights to confirm the Partners compliance with Investment Agreementu Collaboration Agreement◆ Memorandum of UnderstandingØ
8among EVI, RIMD/Osaka Univ. and NPC in July 2018

EVI is responsible for and dedicate to:★ Project governance (among others)ü troubleshoot partnershipü recommendation of expert pool (ISAC, DSMB, etc)
ü engagement with GHIT, contractors and regulatory bodies if

needed★ Financial management
ü as lead coordinator, receive and allocate the budget from GHIT

to each Partner
ü budget reporting★ Communication
ü reporting to GHIT
ü annual and regular meetings with consortium partners9

NPC-SE36 Clinical Development History
Jan 2019
in Heidelberg

Jan 2018in Tokyo

SE36/AHG
BK-SE36
preclinicalstudies

First clinical
trials inhumans
Phase 1aJapan

2003

2005

Phase 1bUganda:
6-40 y-old
2007

Early
development

SE36/CpG

Phase 1b
Follow-up
study
6-20 y-old

2010 2011

Phase 1b
Burkina Faso:
1-5 years-old
2013

preclinicalFirst clinicalMay 2018 in Ouagadougou
studiestrials inhumans
Phase 1aJapan

2015

2018
Phase 1b
Burkina Faso:
1-45 y-old

2020

NPC-SE36 Phase 1b study Outline

Indication
StageStudy Period
Study Site: Malaria vaccine (P. falciparum clinical malaria): Phase 1b: May 2018 – April 2020
: One site in Burkina Faso

Study Population: Cohort 1 : 21 - 45 years, n=45 (A:C=2:1)
Cohort 2 : 5 - 10 years of children, n=45 (A:C=2:1): Cohort 3 : 12 - 24 months of children, n=45 (A:C=2:1)

Vaccination schedule
Observation period
Primary objectives
Secondary objectives: Three immunizations on 0W, 4W and 16W: 12 month after 1st immunization: Safety, assess solicited and unsolicited AEs and SAEs
: Anti-SE36 protein IgG antibody titres
Preliminary vaccine efficacy against naturally occurring:
P. falciparum infection

Exploratory objectives

11