Quarterly Health Topics Series Sanofi’s Vision in Oncology · 2016 2020 2025 Source: IMS Health...

Quarterly Health Topics Series Sanofi’s Vision in Oncology

Wednesday, June 13, 2018

Agenda

2

• Welcome coffee

• Advances in Cancer Care Jorge Insuasty, Global Head of Development

• A New Vision for Immuno-Oncology Dmitri Wiederschain, Head of Immuno-Oncology Research Therapeutic Area

Sanofi’s Vision in Oncology

• Advances in Molecular Oncology Laurent Debussche, Head of Oncology Research Therapeutic Area

• The Future of Cancer Treatment Joanne Lager, Head of Oncology Development.

• Q&A session

Advances in Cancer Care

Jorge Insuasty Senior Vice President,

Global Head of Development

Population Unspecified Patient Subgroup Individual

Oncology: Three Waves of Advances

4

< 1990s 2000s > 2010

Single disease marker

TARGETED

MEDICINES CHEMOTHERAPY

TARGETED

MEDICINES

+

IMMUNOTHERAPY

Co

mp

lex

ity

Group Size Large Medium Medium/Small

Genomic sequencing and

response monitoring

Real-World Progress for Patients

5

Increased 5-Year Survival

Since 1975, a 41% increase in probability a cancer patient will live at least 5 years after diagnosis.

32.6M

∼1%

Cancer Survivors

Globally, a steady upwards trajectory over the last 10 years.

Reduction in Mortality

Per year due to cancer (overall).

R&D Drives Advances for Patients

6

73% of recent survival gains in cancer are attributable to treatment advances including new medicines.

1 Liver Cancer

1 Thyroid Cancer

2 3

3

6 4

3

8%

6%

4%

2%

0%

-2%

-4%

-6%

-8%

-3.5% -2.5% -1.5% -0.5% 0.5% 1.5% 2.5% 3.5%

5 Pancreatic Cancer

Kidney Cancer Breast

Cancer Lung Cancer

Prostate Cancer

Colorectal Cancer

Melanoma Cancer

Change in Survival (ASR)

Inc

rea

se

in

In

cid

en

ce

(A

SR

)

Sources: QuintilesIMS, ARK R&D Intelligence, February 2017; WHO Cancer Database, March 2017; QuintilesIMS, March 2017;

IQVIA, ARK R&D Intelligence, February 2017; IQVIA Institute for Human Data Science, March 2017

Notes: Includes initial and subsequent indications. Excludes supportive care.

But there is a Continuing Need for Innovation

7

70%

Expected increase in cancer cases worldwide in the next two decades.

13M Cancer

deaths are

expected to

rise by 2030.

Sanofi is committed to matching the right patient population with effective cancer therapies by developing treatments in our key R&D areas.

Sanofi’s Vision for People Living with Cancer

8

Immunotherapy Genetically-defined cancers

Hormone-dependent cancers

Continued efforts to address Non-Small Cell Lung Cancer (NSCLC), which represents 85% of lung cancer cases.

While progress has been made in immuno-oncology approaches, challenges remain in defining combinations to test and which patients will benefit.

News from ASCO: Key Research Trends

9

Presented data on targeting difficult-to-treat cancers, including Cutaneous Squamous Cell Carcinoma (CSCC)

Shared new clinical results for PD-1 inhibition in NSCLC

Highlights of Sanofi’s Research at ASCO

10

Sanofi’s Pipeline – At a Glance

* Partnered with Regeneron ** Partnered with BioNTech *** Opt-in rights products for which rights have not been exercised yet,

ADC= Antibody Drug Conjugate; AML= Acute Myeloid Leukemia; BCC= Basal Cell Carcinoma; CSCC= Cutaneous Squamous Cell Carcinoma; GBM= glioblastoma multiforme;

MDS= Myelodysplastic Syndrome; MM= Multiple Myeloma; NSCLC= Non-Small Cell Lung Cancer; RCC= Renal Cell Carcinoma; RRMM= Relapsed Refractory Multiple Myeloma;

SERD= Selective Estrogen Receptor Degrader; TNBC= Triple Negative Breast Cancer; Te= Transplant eligible; Ti= Transplant ineligible,

2018 Oncology Development Pipeline

10

New entries

Ongoing

Phase 1 Phase 2 Pivotal

SAR408701 Anti-CEACAM5 ADC

Solid Tumors

SAR439859 SERD

Metastatic Breast Cancer

SAR439459 Anti-TGFβ mAb

Advanced Solid Tumors

cemiplimab* Anti-PD-1 mAb

Advanced CSCC


1st line NSCLC


Advanced BCC


2nd line Cervical Cancer

isatuximab Anti-CD38

RRMM (ICARIA)

REGN3767*** Anti-LAG3

Advanced Cancers


RRMM (IKEMA)


1st line Te


1st line Ti (IMROZ)

SAR439459 Anti-TGFβ + cemiplimab*

Solid Tumors

SAR439859 SERD + palbociclib


SAR440234 T-Cell Engager

AML/MDS

SAR441000 Immuno mRNA**

REGN IO mAB T-Cell Engager

Ovarian Cancer

REGN IO mAB Checkpoint Inhibitor

Solid Tumors

isatuximab Anti-CD38 + cemiplimab

MM


Solid Tumors

REGN3767***+ cemiplimab Anti-LAG3 and anti-PD-1

Malignancies

cemiplimab* + DNA vaccine Anti-PD-1 mAb

1st L GBM*

cemiplimab* + oncolytic

virus Anti-PD-1 mAb / Advanced RCC*

A New Vision for Immuno-Oncology

Dmitri Wiederschain Head of Immuno-Oncology Research

Defining Immuno-Oncology (“I-O”)

Immuno-oncology treatment boosts the body's natural defenses to fight cancer.

PD-1

PD-L1

Tumor cell

Tumor specific immune cell (T cell)

T-cell receptor

Peptide

MHC

13

major histocompatibility

complex

The Rise of Immunotherapies

14

1st Wave

2nd Wave

2025 2020 2016

Source: IMS Health European Thought Leadership

PD-1/PD-L1

PD-1/PD-L1 PD-1/PD-L1 CTLA-4

CTLA-4 CTLA-4

LAG3

LAG3

TIM3 TIM3

OX40

OX40 Combos

Triple-Combos

IDO Oncolytic viruses

CSF1R

3rd Wave

41BB

41BB

TLR7/8/9 CD40

Emerging Challenges: Anti-PD-1 Resistance

Anti PD-L1 treatment blocks tumor signaling so

that immune system can recognize cancer.

A large fraction of people with cancer do not respond to existing Immunotherapies.

Resistance can be primary or acquired, with some patients who initially respond to treatment acquiring resistance over time.

PD-1 PD-L1

15

Turn "Cold" Tumor to "Hot" Tumor

• Immune modulatory multi-specific mAbs

• Synthetic mRNA cocktails

• Tumor-directed immune conjugates

The Future

For Patients

Our Vision: Leaping to Next Generation I-O

16

Leverage Regeneron I-O Antibody Collaboration

• anti-PD-1

• anti-PD-1 Combo with Sanofi Compounds

Probe Underlying Mechanism of PD-1 Resistance

• Innate Resistance (e.g. TGFβ)

• Acquired Resistance (e.g. CD38) Partner

Probe

Leap

Multi-targeting: Next Generation of IO Therapies

Immune evasion by tumor 17

TGFβ Inhibition Can Change The Tumor Micro-environment

18

Excess TGFβ

Strengthens the tumor by forming a protective shield around it.

TGFβ Inhibition

Can support better immune response and weaken cancer defenses.

mRNA Injections Stimulate T-cell Activation

mRNA

injection

T cell

expansion/activation

Increased

Tumor

Immune response

19

Tumor cell T cell

T-cell Engagers Help Direct T-cells Towards Cancer Cells

CD3 antigen

T cell engager binds simultaneously to tumor and

T cell bringing them in close proximity

20

Advances in Molecular Oncology

Laurent Debussche Head of Oncology Research

Defeating Cancer: Immuno- and Molecular Oncology

22

Molecular Oncology Immuno-oncology

"complementary"

and key R&D

areas

Bringing These Worlds Together

23

Human and Hormone biology

Deepening our understanding of biology to tailor

precise treatments for patients.

Genomics Revolution

Identifying the genetic basis and mechanisms of

how cancer develops.

By linking genetics

and biology, we can

achieve precision

medicine for

individual patients

across a range of

cancer types.

Advances in Molecular Biology

24

Molecular biology has transformed our understanding of the complexity of cancer.

The World Health Organization (WHO) estimates that there are more than 100

different kinds of cancer, each with specific treatment needs.

1996 2006 2016

NSCLC

Breast Cancer

Non Segmented Lung Cancer

EGFR

ALK

Squamous

ROS

BRAF

PD-1+

HR +ve

HR -ve pre

TNBC pre

HER2-BR+ post

HR-ve

HR- pre

TNBC post

HER2+ HR- pre

HR +ve pre

HR- post

HER2- HR+ pre

HER2+ HR- post

Source: FDA.gov and Drugs@FDA, Mar 2017; IQVIA, ARK R&D Intelligence, Feb 2017; IQVIA Institute for

Human Data Science, Mar 2017

Case Study: Metastatic Breast Cancer

25

Metastatic breast cancer is a form of cancer that is often hormone dependent.1

Patients diagnosed with metastatic breast cancer have an average survival rate of approximately two years.1

Despite one approved endocrine therapy, there are still unmet medical needs in ER+ metastatic breast cancer as well as in early-setting populations.1

REFERENCES: (1) Başaran, G. A., Twelves, C., Diéras, V., Cortés, J., & Awada, A. (2018). Ongoing unmet needs in treating

estrogen receptor-positive/HER2-negative metastatic breast cancer. Cancer Treatment Reviews, 63, 144-155.

doi:10.1016/j.ctrv.2017.12.002

Resistance to endocrine therapy remains dependent on presence of active Estrogen receptor alpha (ERα).1

SERDs can induce ERα degradation and inhibit ERα driven breast cancer cell growth.2

Spotlight: Selective Estrogen Receptor Degraders (SERDs)

SERD 1 Green: ERα staining Blue: Nuclear staining

REFERENCES: (1) Kurebayashi, J. (2003). Endocrine-resistant breast cancer: Underlying mechanisms and strategies for

overcoming resistance. Breast Cancer, 10(2), 112-119. doi:10.1007/bf02967635 (2) Patel, H. K., & Bihani, T. (2018). Selective

estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) in cancer treatment. Pharmacology &

Therapeutics, 186, 1-24. doi:10.1016/j.pharmthera.2017.12.012 26

Leveraging Our Leading Partnerships

The Future of Cancer Treatment

Joanne Lager Head of Oncology Development

Progress in our Oncology Pipeline, 2018

29

4 potential

proof-of-concept

study read-outs

BLA: Biologic license application - MAA: Marketing authorization application

14 new

proof-of-concept

indications

6 preclinical

programs enter

phase 1

Early Development

1 launch

in the U.S.

3 BLA/MAA

submissions

9 pivotal studies

ongoing or planned

Late Development

Phase 3 Study Regulatory Filing Marketing

First in Human Early efficacy evidence

Our Focus: Improving Therapeutic Options across cancer types

30

Cancers currently targeted by Sanofi Alone or with its partners

Early-stage research

Late-stage research

In market

Cemiplimab and Isatuximab

31 *FDA designations

Cemiplimab (PD-1) Isatuximab (CD38)

Granted Breakthrough Therapy Designation*

Granted Orphan Drug Status*

Cutaneous Squamous Cell Carcinoma (CSCC)

32

The incidence of CSCC varies by country2

People ages 65 and older are more likely to be diagnosed,6 and incidence and mortality rates increase with age2

Ultraviolet (UV) light exposure significantly increases the risk of developing CSCC3

The majority of CSCC-related deaths are attributable to advanced CSCC2

new cases/year

in the U.S.

One of the most

common cancers

Worldwide1

CSCC is increasing by as much as

3-7% annually in most countries2

REFERENCES: (1) Howell JY, et al. Cancer, Squamous Cell, Skin. [Updated 2017 Oct 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2017 Jun. (2) Lucas, et al.

Solar Ultraviolet Radiation. Global burden of disease from solar ultraviolet radiation. Environmental Burden of Disease Series, No. 13. World Health Organization 2006. (3) Skin Cancer Foundation. Squamous cell carcinoma (SCC). http://www.skincancer.org/skin-cancer-information/squamous-cell-carcinoma.

Non-small Cell Lung Cancer (NSCLC)

33

NSCLC is up to 85% of lung cancer diagnoses, the most deadly cancer.1

Only 12.3 percent in Europe and 15 percent in the U.S percent of lung cancer patients will be alive after five years. 2

Approximately 70% of cases are not diagnosed until advanced stage with decreasing probability of cure. 1

REFERENCES: (1) Non–Small Cell Lung Cancer: Epidemiology, Risk Factors, Treatment, and Survivorship”, Julian R. Molina et al. Mayo Clin Proc. 2008 May; 83(5): 584–594. doi: 10.4065/83.5.584 (2) United Kingdom Lung Cancer Coalition. Access Date: June 2018: http://www.uklcc.org.uk/patient-information/facts-about-lung-cancer.

ASCO Data on Cemiplimab

34

Multiple Myeloma (MM)

35

Worldwide, nearly 103,000 new cases are diagnosed annually.1

The five‐year survival rate is 42% for metastasized MM.2

REFERENCES: (1) World Health Organization. Globocan 2008: World. http://globocan.iarc.fr/factsheet.asp. Accessed November

21, 2013.National Cancer Institute. A Snapshot of Myeloma: Incidence and Mortality. (2) National Cancer Institute. Surveillance,

Epidemiology, and End Results Program. http://seer.cancer.gov/statfacts/html/mulmy.html. Accessed November 21, 2013.

Clinical Roadmap for Isatuximab

36

First Submission Initial submission planned in Relapsed Refractory Multiple Myeloma.

Expand in Multiple Myeloma Utilization in 1L and 2L along treatment continuum of Multiple Myeloma.

Combination Use in Solid Tumors Further enhance response to immuno-oncology agents.

Sanofi’s Pipeline – At a Glance

* Partnered with Regeneron ** Partnered with BioNTech *** Opt-in rights products for which rights have not been exercised yet,

ADC= Antibody Drug Conjugate; AML= Acute Myeloid Leukemia; BCC= Basal Cell Carcinoma; CSCC= Cutaneous Squamous Cell Carcinoma; GBM= glioblastoma multiforme;

MDS= Myelodysplastic Syndrome; MM= Multiple Myeloma; NSCLC= Non-Small Cell Lung Cancer; RCC= Renal Cell Carcinoma; RRMM= Relapsed Refractory Multiple Myeloma;

SERD= Selective Estrogen Receptor Degrader; TNBC= Triple Negative Breast Cancer; Te= Transplant eligible; Ti= Transplant ineligible,

2018 Oncology Development Pipeline

10

New entries

Ongoing

Phase 1 Phase 2 Pivotal

SAR408701 Anti-CEACAM5 ADC

Solid Tumors

SAR439859 SERD


SAR439459 Anti-TGFβ mAb

Advanced Solid Tumors


Advanced CSCC


1st line NSCLC


Advanced BCC


2nd line Cervical Cancer


RRMM (ICARIA)

REGN3767*** Anti-LAG3

Advanced Cancers


RRMM (IKEMA)


1st line Te


1st line Ti (IMROZ)

SAR439459 Anti-TGFβ + cemiplimab*

Solid Tumors

SAR439859 SERD + palbociclib


SAR440234 T-Cell Engager

AML/MDS

SAR441000 Immuno mRNA**

REGN IO mAB T-Cell Engager

Ovarian Cancer

REGN IO mAB Checkpoint Inhibitor

Solid Tumors


MM


Solid Tumors

REGN3767***+ cemiplimab Anti-LAG3 and anti-PD-1

Malignancies

cemiplimab* + DNA vaccine Anti-PD-1 mAb

1st L GBM*

cemiplimab* + oncolytic

virus Anti-PD-1 mAb / Advanced RCC*

Q&A session

Quarterly Health Topics Series Sanofi’s Vision in Oncology · 2016 2020 2025 Source: IMS Health...

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Transcript of Quarterly Health Topics Series Sanofi’s Vision in Oncology · 2016 2020 2025 Source: IMS Health...