Quarterly Health Topics Series Sanofi’s Vision in Oncology · 2016 2020 2025 Source: IMS Health European Thought Leadership PD-1/PD-L1 PD-1/PD-L1 PD-1/PD-L1 CTLA-4 CTLA-4 CTLA-4
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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
cemiplimab* Anti-PD-1 mAb
1st line NSCLC
cemiplimab* Anti-PD-1 mAb
Advanced BCC
cemiplimab* Anti-PD-1 mAb
2nd line Cervical Cancer
isatuximab Anti-CD38
RRMM (ICARIA)
REGN3767*** Anti-LAG3
Advanced Cancers
isatuximab Anti-CD38
RRMM (IKEMA)
isatuximab Anti-CD38
1st line Te
isatuximab Anti-CD38
1st line Ti (IMROZ)
SAR439459 Anti-TGFβ + cemiplimab*
Solid Tumors
SAR439859 SERD + palbociclib
Metastatic Breast Cancer
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
isatuximab Anti-CD38 + cemiplimab
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
Metastatic Breast Cancer
SAR439459 Anti-TGFβ mAb
Advanced Solid Tumors
cemiplimab* Anti-PD-1 mAb
Advanced CSCC
cemiplimab* Anti-PD-1 mAb
1st line NSCLC
cemiplimab* Anti-PD-1 mAb
Advanced BCC
cemiplimab* Anti-PD-1 mAb
2nd line Cervical Cancer
isatuximab Anti-CD38
RRMM (ICARIA)
REGN3767*** Anti-LAG3
Advanced Cancers
isatuximab Anti-CD38
RRMM (IKEMA)
isatuximab Anti-CD38
1st line Te
isatuximab Anti-CD38
1st line Ti (IMROZ)
SAR439459 Anti-TGFβ + cemiplimab*
Solid Tumors
SAR439859 SERD + palbociclib
Metastatic Breast Cancer
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
isatuximab Anti-CD38 + cemiplimab
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
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