Janssen: ¿where are we headed?
Martin Freeman, UntitledDiagnosed with AIDS in 1990, Martin lives in San Francisco where he continues to create new pieces.
Update on Clinical Topics in Antiretroviral Therapy Workshop
Eugenia VispoMedical Affairs Therapeutic Area Leader, Infectious DiseasesJanssen Spain
30th May 2019
Prevention Treatment Cure
Discover and develop transformational products
that treat, cure and prevent infectious diseases
and change people’s lives worldwide
Janssen Infectious Diseases
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HIV Overview
•SYMTUZA® (complete regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide)
•REZOLSTA/PREZCOBIX® (Fixed Dose Combination [FDC] of darunavir/cobicistat)
•PREZISTA® (darunavir)
•EDURANT® (rilpivirine)
• JULUCA®† (dolutegravir/rilpivirine)
• INTELENCE® (etravirine)
•EVIPLERA/COMPLERA®* (complete regimen of rilpivirine/emtricitabine/tenofovir disoproxil fumarate)
•ODEFSEY®* (complete regimen of rilpivirine/emtricitabine/tenofovir alafenamide)
Portfolio
•Rilpivirine + Cabotegravir (Long-Acting Injectables)†
Research & Development
•Prophylactic HIV Vaccine
•Therapeutic HIV Vaccine
Vaccines
*Through a collaboration with Gilead Sciences. †Through collaboration with ViiV Healthcare.
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Fig. 2. Schematic representation of the RPV LA MAP manufacturing process (A);micrographs of exemplar RPV LA MAPs generated (B) and digital images of RPV LAMAPs (C).
Microarray patch for intradermal RPV delivery
McCrudden M. et al. J. Controlled Release 292 (2018) 119 - 129
Halt HIV epidemic by vaccination & achieve a functional cure by
developing a therapeutic vaccinePrevent respiratory infections
caused by RSV and Influenza impacting children,
elderly and at risk patients
Prevent multi-drug resistant bacterial
infections by vaccination
Respond fast and efficient to outbreaks of pathogens of global concern such as Ebola, Filoviruses
and Zika
JANSSEN VACCINES VISION
To develop transformational vaccines that are first and/or best in class in areas of high unmet medical need
Prevent all cancers induced by HPV by
developing a therapeutic vaccine
Develop an affordable Sabin inactivated polio vaccine to contribute to
elimination of polio.
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Global partnershipsworking together to overcome the challenge of infectious diseases
6
Beth Israel Deaconess
Medical Center
Harvard Medical School
Inserm
MIT
National Institutes of
Health (USA)
University of Oxford
And many more …
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Janssen’s goal is to develop a prophylactic HIV vaccine that protects against multiple clades of HIV-1
Heterologous vaccine regimen in development:
• Ad26 viral vectors for the induction of potent cellular and humoral immune responses
• Mosaic designs of HIV genes Gag, Pol and Env for coverage of globally circulating HIV-1 strains
• Soluble trimeric gp140 envelope proteins co-formulated with aluminum phosphate to enhance Env-specific immunity
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Pre-clinical efficacy (Non Human Primates)
Ad26 (Months 0, 3), Ad26 + gp140 (Months 6, 12) regimen provided 67% completeprotection from intrarectal challenge in non-human primates*
(*) Barouch, Tomaka, Wegmann, et al., The Lancet, 2018
Ad26, Ad26 35% 0%
Ad26, Clade C gp140 84% 33%
Ad26, Ad26+Clade C gp140 94% 67%
Ad26, MVA 71% 8%
Ad26, MVA+Clade C gp140 87% 42%
Sham 0% 0%
Risk reductionper exposure
Full protection6 challenges
0 2 4 60
20
40
60
80
100
week post first challenge
Pe
rce
nt
un
infe
cte
d Ad prime /Ad boost
Ad prime /gp140 boost
Ad prime /Ad+gp140 boost
Ad prime /MVA boost
Ad prime /MVA+gp140 boost
ShamNumber of IR challenges(virus SHIV-SF162P3, expressing clade B Env)
Pe
rce
nta
ge u
nin
fect
ed
Vaccinations
Mo 6, 12Mo 0, 3
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Group N Vacc 1, 2 wk 0, wk 12
Vacc 3, 4wk 24, wk 48
1 50 Ad26.Mos.HIV Ad26.Mos.HIV + High Dose Clade C gp140
2 50 Ad26.Mos.HIV Ad26.Mos.HIV + Low Dose Clade C gp140
3 50 Ad26.Mos.HIV Ad26.Mos.HIV
4 50 Ad26.Mos.HIV MVA- Mosaic + High Dose Clade C gp140
5 50 Ad26.Mos.HIV MVA- Mosaic + Low Dose Clade C gp140
6 50 Ad26.Mos.HIV MVA- Mosaic
7 50 Ad26.Mos.HIV + High Dose Clade C gp140
8 50 Placebo Placebo
Follow upwk 52 to 96
(*) Barouch, Tomaka, Wegmann, et al., The Lancet, 2018
Phase 1/2a clinical study: APPROACH
Long term extensionUp to 5 years post last vx
9
APPROACH: Phase 1/2a / HIV-V-A004/ IPCAVD009
Countries: USA, Rwanda, South Africa, Uganda and Thailand
Study Design*
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B L W 2 8 W 5 2 W 2 8 W 5 2 W 2 8 W 5 2 W 2 8 W 5 2 W 2 8 W 5 2 W 2 8 W 5 2 W 2 8 W 5 2 W 2 8 W 5 2
1 0 0
1 0 2
1 0 3
1 0 4
1 0 5
1 0 6
EL
ISA
tit
er
A . B in d in g A n tib o d y C la d e C g p 1 4 0 E L IS A
G M T :
R e s p % :
2 2 1 8 0 5 1 2 3 1 73 2 8 4 1 3 9 5 52 1 0 4 7 1 8 7 0 14 7 3 6
0 1 0 0 9 81 0 0 1 0 0 1 0 0 1 0 0 1 0 0
4 0 5 7 8 2 1 8 6 81 1 8 3 2 7 1 5 98 0 3 1 2 2 6 3 81 2 3 9 1
9 8 9 71 0 0 9 8 1 0 0 1 0 0 1 0 0 22
23
L L O Q (1 5 6 )
B a s e lin e W 2 6 /2 8 R e s p o n d e r W 5 0 /5 2 R e s p o n d e r W 2 6 /2 8 N o n R e s p o n d e r W 5 0 /5 2 N o n R e s p o n d e r
A d 2 6 + E n v
H D
A d 2 6 + E n v
L D
A d 2 6 M V A + E n v
H D
M V A + E n v
L D
M V A E n v H D P la c e b o
G M T
APPROACH post 3rd and post 4th vaccinationTotal IgG Env ELISA Clade C gp140
APPROACH: Phase 1/2a / HIV-V-A004/ IPCAVD009
(*) Barouch, Tomaka, Wegmann, et al., The Lancet,
2018
Ad26 (Months 0, 3), Ad26 + gp140 HD (Months 6, 12) regimen was the most immunogenic in humans; it elicited Env-specific binding antibody responses (100%) and antibody-dependent cellular phagocytosis responses (80%) at week 52, and T-cell responses at week 50 (83%)*
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Progress towards evaluation of clinical efficacy
Phase 1 Phase 1/2a Phase 2b
HIV-V-A002
HIV-V-A003
HPX1002
HIV-V-A004 (APPROACH)
HPX2004 (TRAVERSE)
HPX2003 (ASCENT)
HPX2008/HVTN705 (Imbokodo)
Completed
Completed
Completed
Ongoing (in long term extension phase)
Commenced November 2017
This investigational, mosaic-based vaccine regimen is designed as a ‘global vaccine’ with the aim to prevent infections due to a wide range of HIV-1 strains around the world
that are responsible for the HIV pandemic.
Ongoing (in long term extension phase)
Ongoing
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Development of Janssen prophylactic HIV vaccine
▪ Although there have been great advances in HIV treatment and prevention in recent years, nearly two million people become infected with HIV every year
▪ An effective vaccine could have a major impact
• Janssen HIV-1 vaccine candidate is based on a wide range of different subtypes (mosaic inserts) with the goal to achieve global subtype coverage
▪ Preliminary data suggest that HIV-1 vaccine candidate appears to be well- tolerated and able to elicit anti-HIV immune responses
▪ Based on this, a large-scale study, known as Imbokodo, has started in 2017 to evaluate safety and efficacy of the vaccine in reducing the incidence of HIV infection
The ultimate goal is to deliver a ¨global vaccine¨ that could be effective in any geographic region
√
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Antivirals
▪ JNJ-39891 (JNJ-73763989, ARO-HBV) - RNA interference (RNAi)
▪ JNJ-6379 (JNJ-56136379) - Capsid Assembly Modulator
▪ JNJ-0440 (JNJ-64530440, ALS-003440) - Capsid Assembly Modulator
Immunomodulators
▪ JNJ-4964 (AL-034, TQ-A3334) - TLR-7 Agonist
▪ JNJ-0535 (JNJ-64300535) - HBV Therapeutic Vaccine
HBV Overview
HBV, hepatitis B virusTLR-7, toll-like receptor 7
1. Janssen Announces Exclusive, Worldwide License Agreement With Arrowhead Pharmaceuticals Press Release October 4, 2018.
Research & Development
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Bedaquiline Clinical Development Program, 2005 to Present
SIRTURO® (bedaquiline) for Pulmonary Multi-Drug Resistant Tuberculosis
▪ Novel mechanism of action1
– First-in-class of diarylquinolines with novel mechanism of action as an ATP-synthase inhibitor with high potency against Mycobacterium tuberculosis
▪ Approved by the FDA in December 2012 as part of combination therapy to treat adults with multi-drug resistant pulmonary tuberculosis (TB) when other alternatives are not available2
– Accelerated approval program
▪ In studies, SIRTURO® resulted in shorter time to culture conversion as compared to placebo in patients with MDR-TB3-5
▪ Collaboration with the International Union Against Tuberculosis and Lung Disease to include SIRTURO® in the STREAM study6
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