update on clinical topics in antiretroviral therapy workshop · janssen’s goal is to develop a...

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

-- Property of Janssen - Do not distribute--

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.


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.


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 …


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


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


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*


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%)*


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


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

√

-- Property of Janssen - Do not distribute--12

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


https://www.janssen.com/janssen-announces-exclusive-worldwide-license-agreement-arrowhead-pharmaceuticals-develop-and

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


update on clinical topics in antiretroviral therapy workshop · janssen’s goal is to develop a...

Documents