CORPORATE PRESENTATION - FEBRUARY 2020 - Erytech
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CORPORATE PRESENTATION
FEBRUARY 2020
Forward Looking Statements The statements made in this presentation may include forward-looking statements regarding the future operations of ERYTECH Pharma S.A., including estimates of target market opportunity, timing of planned clinical trials and results from those trials, regulatory strategy and timing of planned regulatory submissions, manufacturing capabilities and strategy for expansion of the ERYCAPS platform. Although we believe that the expectations contained in this presentation are reasonable, these forward-looking statements are only estimates based upon the information available to ERYTECH Pharma S.A. as of the date of this presentation. Except as required by law, we expressly disclaim any responsibility to publicly update or revise our forward-looking statements, whether as a result of new information, future events or otherwise. Thus, the forward- looking statements herein involve known and unknown risks and uncertainties and other important factors such that actual future operations, opportunities or financial performance may differ materially from these forward-looking statements. Undue reliance should not be placed on forward- looking statements, which speak only as of the date hereof. All forward-looking statements contained herein are qualified in their entirety by the foregoing cautionary statement.
Leader in Red Blood Cell-based Cancer Therapeutics
Reproducible encapsulation of therapeutic compounds in red
blood cells Phase 2b in 2L Pancreatic Cancer
OVERALL SURVIVAL (ITT)
Focus on oncology, targeting cancer cells’ altered amino acid
metabolism through encapsulated asparaginase
Lead product candidate eryaspase, first asparaginase to show 40%
efficacy in solid tumors; strongest survival benefit observed in any reduction in
2L pancreatic cancer study to date risk of death
(HR, 0.60;
Phase 3 trial in 2L pancreatic cancer ongoing in EU and US; on
P=0.008)
track for readout 1H21; interim (for superiority) expected 3Q20;
Phase 2 in 1L TNBC and Phase 2 IST in 2L ALL ongoing
Industrialized production: own cGMP production facilities in the
United States and Europe Months
Listed on Nasdaq and Euronext; cash runway into 2021; key Hammel et al., European Journal of Cancer, 2019
shareholders including BVF and RA Capital
ALL: Acute Lymphoblastic Leukemia; TNBC: Triple-Negative Breast Cancer 3
Late Stage Clinical Pipeline and Preclinical Programs
Product Candidate Phase 3/ Next Anticipated
Mode of action Indication Discovery Pre-clinical Phase 1 Phase 2
or Program Pivotal Milestone
Pancreatic Cancer Interim: Q320
TRYbeCA-1
2L Final: 1H21
Triple Negative
TRYbeCA-2 Final: 2021
® Breast Cancer 1L
eryaspase/GRASPA
Cancer metabolism (asparaginase)
Acute Lymphoblastic Interim: 1H20
NOPHO IST
Tumor starvation Leukemia 2L Final: 2H20
Pancreatic cancer
IST Launch: 2H20
1L
erymethionase
Solid tumors
(methionine-γ-lyase)
Immune Immune-oncology
TBD*
modulation Tolerance induction
Enzyme Therapeutic
Metabolic diseases
replacement enzymes
1L First Line; 2L Second Line; IST Investigator Sponsored Trial; NOPHO : Nordic Organization of Pediatric Hematology and Oncology
* To be determined by SQZ Biotech
4
Red Blood Cells, Ideal Carriers for Amino Acid Lowering Agents
Readily available at blood Permeable membrane
banks Potential to load with drugs
Established sourcing Plasma metabolites can pass
Well known Protective membrane
biocompatibility Reduced toxicity
Routine allogeneic use
Prolonged activity
Most abundant cell in
Long circulating life
human body
Prolonged activity
Extensive biodistribution
5
ERYCAPS, an Innovative Technology Platform
Reproducibly encapsulating drug substances inside allogeneic red blood
cells using proprietary hypotonic loading technology
Drug substance
Reproducible
proprietary ‘osmotic fragility’ process enables
reproducible loading
Pores
Fast
industrialized process can deliver tailored therapy
within 24 hours
Controlled
Hypotonic Loading Broad range
peptides, RNA, proteins, antibodies, …
Hypertonic Strong IP
Resealing 265 granted patents in 15 patent families
6
Industrialized and Scalable Process
1 2 3 4 5
1 Sourcing 2 Preparation 3
Encapsulation Batch4release Shipping
5
PRESCRIPTION
SOURCING PREPARATION ENCAPSULATION BATCH RELEASE SHIPPING
Sourcing of Identification of key ERYCAPS automated QC Control Patient
Manufacturing Shipping
compatible RBC parameters (3-5 hours) Release by QP
Possible in 24h
Validated supply &
Fully-owned GMP Established partnerships More than a decade
manufacturing model – 2000+
production capacity in EU with blood banks in EU and experience in manufacturing
batches, 460+ patients treated,
and the US the US and supply chain management
9 countries
7
Targeting Cancer Cells Amino Acid Metabolism, an Emerging Field
Many cancers exhibit increased demand Amino acids
for specific amino acids, becoming
dependent on exogenous supply or de
Depleting select amino
novo synthesis of these amino acids1-3
acids in blood (e.g.
asparaginase)
Blocking uptake by
blocking transporters
(e.g., LAT 1-4)
Inhibiting biosynthetic or
catabolic enzymes (e.g.
arginase inhibitor)
1. Lukey et al., Drug Discovery Today, 2017
2. Pavlova & Thompson, Cell Metabolism, 2016
3. Luengo et al., Cell Chemical Biology, 2017 8
Asparaginase, First Amino Acid Targeting Anticancer Drug1
Mode of action
MODE OF Asparaginase breaks down circulating asparagine (and glutamine), and deprives
ACTION tumor cells of amino acids essential for their growth
Current use • Cornerstone treatment in Phi-neg pediatric acute lymphoblastic leukemia (ALL)
• Four forms of L-asparaginase products currently marketed in ALL; worldwide sales
est. $400M in 2018
CURRENT
USE • E-coli derived: Native asparaginase: e.g., Kidrolase (Kyowa Hakko)
Recombinant asparaginase: Spectrila (medac)
Pegylated asparaginase: Oncaspar (Servier)
• Erwinia derived: Erwinaze (Jazz Pharmaceuticals)
Limitations • Important side effects (e.g., allergies, coagulation disorders, pancreatic and hepatic
toxicities) limit therapeutic window to essentially pediatric ALL
• Beyond ALL, some use in AML and lymphoma; no known use in solid tumors
1. Lukey et al., Drug Discovery Today, 2017 9
Eryaspase (GRASPA®), Enabling Broader Use of Asparaginase
A novel circulating ‘bioreactor’ to degrade asparagine (and glutamine)
Y Y
Active transporters in membrane
of red cell pump circulating
Y
Prolonged activity
Y
asparagine and glutamine into
Y
the red cell… Y Reduced toxicity
Y
Asparaginase Y Potential to provide
Asparagine and glutamine asparaginase to patients
…where the encapsulated that are unable to
Degradation products L-asparaginase hydrolyzes the tolerate non-
Antibody
asparagine and glutamine encapsulated products
Y
10Positive Results in ALL Confirmed Proof of Concept
• ERYTECH started development in fragile ALL patients, confirming the concept of prolonged activity and
reduced toxicity in different clinical trials, including a Phase 2/3 trial in Relapsed/Refractory ALL:
Key results of Phase 2/3 trial in R/R ALL Eryaspase (N=26) L-ASP (N=28)
% of patients with ≥ 1 hypersensitivity reaction during induction** 0% 46%
Mean duration of asparaginase activity above 100 U/L during induction (days)** 18.9 8.5
Complete Remission rate (CR)* 65% 36%
• Overall Survival (OS) HR = 0.72
** Statistically significant (pPancreatic Cancer, Large Unmet Medical Need
• Pancreatic cancer is one of the leading
causes of cancer death in the world, with an Lung and bronchus
160
increasing incidence1,2
Projected cancer deaths in the US (1000’s)
• In 2018, approximately 185,000 people were 140
newly diagnosed with pancreatic cancer in 80
Europe and the United States1 Pancreas
60 Colon and rectum
• Overall prognosis for pancreatic cancer is Liver
poor, with a 5-year survival rate ofAltered Metabolic Pathways in PAC, a Role for Asparaginase?
• Pancreatic cancer (PAC) is characterized by extensive reprogramming of cellular metabolism leading to
increased asparagine and glutamine requirements. Deprivation of glutamine and asparagine results in loss of
cancer cell viability1
• In vitro studies demonstrated promising anti-cancer effects for asparaginase against human pancreatic tumor
cell lines2-3
• Attempts at evaluating asparaginase in solid tumor indications in the clinic have been unsuccessful due to
toxicity4-7
• In a Phase 1 trial in metastatic pancreatic cancer, eryaspase demonstrated an acceptable safety profile8-9
• The tolerability of eryaspase and the potential role of metabolic dysregulation in this disease provided
rationale for further clinical evaluation
1. Kawanda Int J Clin Oncol 2017; 2. Cui, Cancer Res 2007; 3. Dufour, Pancreas 2012;
4. Lessner Cancer Treat Rep 1980; 5. Hays Molec Clin Oncol 2013; 6. Agrawal Cancer 2003;
7. Borad Cancer Investigation 2015; 8. Bachet Pancreas 2015; 9. ClinicalTrials.gov: NCT01523808 13Phase 2b Trial in 2L Pancreatic Cancer Launched in 2014
Patients (N=141) Co-primary endpoints
Eryaspase + 03
Randomize 2 to 1
• ≥18 years chemotherapy PFS and OS in ASNS 0/1
• Stage III or IV (gemcitabine or subpopulation
• One prior systemic mFOLFOX) option
Key secondary endpoints
chemotherapy in
advanced setting • PFS and OS (all comers)
Chemotherapy alone • Objective response rate
• Measurable disease (gemcitabine or
• Disease control rate
• ECOG PS 0 or 1 mFOLFOX)
• Safety and tolerability
Stratified by chemotherapy • Quality of life
Trial in collaboration with the GERCOR in 16 clinical sites in France
Reference: ClinicalTrials.gov: NCT02195180
ECOG: Eastern Cooperative Oncology Group, PS: performance status, FOLFOX: 5FU, leucovorin and oxaliplatin; GERCOR: Multidisciplinary Group in Oncology
ASNS 0/1 subpopulation: patients with no/low asparagine synthetase expressing tumors
14Clear Overall Survival (OS) Benefit1
Eryaspase Phase 2b Trial
40% I T T P O P U L AT I O N
reduction in risk of 100
Eryaspase +
death 90 chemotherapy Chemotherapy
80 (n=95) (n=46)
(HR 0.60; P=0.008)
Survival probability (%)
70 Events,
Events nn(%)
(%) 82 (86.3)
79 (83%) 42 (91.3)
40 (87%)
60 Median OS, CI)
OS HR (95% 0.60 (0.40, 0.88)
P-value
months 6.0 0.008 4.4
For reference: Onyvide Phase 3: HR 0.67 50
(95% CI) (4.8–6.6) (3.0–5.0)
40 Median OS (mo) 6.0 4.4
P
OSvalue
rate at 1yr 15.8% 0.008
6.5%
30
OS rate at 18m 8.4% 0%
20
10
0
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36
No. at risk
Months
E +CT 95 83 67 45 29 24 15 11 8 8 4 4 4 1 1 1 1 0
CT 46 35 22 15 8 6 3 0
I T T P O P U L AT I O N
HR, Hazard Ratio; OS, Overall Survival
1. Hammel et al., European Journal of Cancer, 2019; 15Overall Survival Benefit Consistent Across Subgroups1
Eryaspase Phase 2b Trial All patients (E+CT n=95, CT n=46) 0.60 (0.40, 0.87)
ITT POPULATION
ASNS category ASNS 0/1+ (E+CT n=66, CT n=32) 0.63 (0.39, 1.01)
ASNS 2+/3+ (E+CT n=29, CT n=14) 0.52 (0.26, 1.03)
Gender Male (E+CT n=53, CT n=30) 0.47 (0.29, 0.77)
Female (E+CT n=42, CT n=16) 0.95 (0.51, 1.79)
Time from randomizationSimilar Progression-Free Survival Benefit1
44% Eryaspase Phase 2b Trial
ITT POPULATION
reduction in the
Progression-free survival probability (%)
100 I T +T P O P U L A T I O N
Eryaspase
risk of chemotherapy Chemotherapy
90
progression (n=95) (n=46)
80
(HR, 0.56; P=0.005) Events n (%)
Events, n 70
70(74%) 36 (78%)
36
70 (%)HR (95% CI) (73.7)0.56 (0.37, 0.84)
(78.3)
OS
60 P-value
Median PFS, 0.005
50 monthsPFS
Median 2.08.6 1.6
6.9
40
(95% CI)
(weeks) (1.8–3.4) (1.4–1.8)
30
P value 0.006
20
10
0
0 2 4 6 8 10 12 14 16
Months
No. at risk
E +CT 95 36 18 12 6 4 3 0
CT 46 9 6 1 1 1 0
1. Hammel et al., European Journal of Cancer, 2019; 17
17 17Improved Response Rates and Fewer New Lesions1
new lesions
Eryaspase Phase 2b Trial
ITT POPULATION
PD 50
45 47,4 Eryaspase +
chemotherapy
40
Chemotherapy
SD
35
30
Patients, %
** ** CR OR
25
23,9
20
SD
new lesions 15
PD SD
10 11,6
5 OR 6,5
OR
0
SD Disease control rate Overall response rate
PD = Progressive disease
OR SD = Stable disease
PR = Partial response
CR= Complete response
OR = Overall response (PR +CR)
1. Hammel et al., European Journal of Cancer, 2019; 18 DCR = Disease control rate (OR+SD) 18No Additional Toxicity Over Chemotherapy Alone
All grade adverse events (%)
0 10 20 30 40 50 60 70
Eryaspase
80
Phase 2b Trial
ITT POPULATION
Asthenia
Nausea
Anemia
Vomiting
Thrombocytopenia
Abdominal pain
Diarrhea
Decreased appetite
Pyrexia
Constipation
Neutropenia
TREATMENT EMERGENT EVENTS
GGT increased REGARDLESS OF RELATIONSHIP TO
Physical health deterioration STUDY DRUG
Antibody test positive 86%
Weight decreased
Peripheral edema 77%
Upper abdominal pain
Stomatitis
ALT increased
Hypokalemia
Neuropathy peripheral 50%
Fatigue 45%
Back pain
Cough
Mucosal inflammation
Alopecia
Hyperthermia
Lymphopenia
Chemotherapy
Hyperglycemia
AST increase
Anxiety
Eryaspase +
Hypoalbuminemia
Patients
> Gradewith
3/4 ≥1 Patients
>=1 SAEwith
chemotherapy
Insomnia
Grade 3 or 4 AE ≥1 SAE
19Trybeca-1, Phase 3 trial in 2L Pancreatic Cancer Launched in 2018
Pascal Hammel Manuel Hidalgo
Co-PI, Hôpital Beaujon, Paris, France Co-PI, Weil Cornell Medicine, New York, U.S.
Patients (N ≈ 500) Chemotherapy Primary endpoint
(gemcitabine+nabpaclitaxel
03
Randomize 1:1
• ≥18 years • Overall Survival
or FOLFIRI)
• Stage III or IV PAC plus eryaspase
Key secondary endpoints
• One prior systemic option
chemotherapy in Chemotherapy alone • Progression-free survival
advanced setting (gemcitabine+nabpaclitaxel • Objective response rate
• Measurable disease or FOLFIRI) • Disease control rate
• ECOG PS 0 or 1 • Safety and tolerability
Stratification by ECOG PS, chemotherapy regimen
• Quality of life
and time since diagnosis of advanced disease
Trial expected to run in approximately 100 clinical sites in 11 European countries and the U.S.
Reference: ClinicalTrials.gov: NCT03665441
ECOG, Eastern Cooperative Oncology Group; PS, performance status
FOLFIRI, 5FU/leucovorin/irinotecan; the irinotecan can be Onivyde (nanoliposomal irinotecan or NALIRI) 20Trybeca-1 on Track for Complete Enrollment in 3Q20
• More than 50% of projected patients enrolled (since Dec 2019)
• Trial enrolling patients since September 2018 in Europe
• Clinical trial authorizations in 11 European countries
• 50+ clinical sites activated
• Trial opened for enrollment in the United States in October 2019
• First sites activated; approximately 20 U.S. sites targeted
• Safety data of first 150 patients reviewed by independent data monitoring committee in October 2019:
• No safety issues identified
• Recommendation to continue trial as planned
• Trial on track for full enrollment in Q3 2020
• Interim analysis (for superiority) expected in Q3 2020
• Based on comparison of OS when 2/3 of events will have occurred
• Two outcomes possible: continue as planned or stop for superiority (no futility analysis planned)
21Broadening Scope to Other Solid Tumor Indications
Phase 2 proof of concept trial ongoing in Triple-Negative Breast Cancer (TNBC)
• Randomized Phase 2 proof-of-concept trial in Europe
• Approximately 64 patients with newly diagnosed metastatic disease
• Chemotherapy (gemcitabine/carboplatin) +/- eryaspase
• Primary endpoint: objective response rate
• Clinical trial authorizations obtained in all four participating countries PI: Ahmed Awada
Head of the Medical Oncology
• Close to 20 sites activated; patient enrollment ongoing Clinic at Jules Bordet Cancer
Institute Brussels, Belgium
• Results expected in 2021
Broadening of indication scope to first line (1L) pancreatic cancer in preparation
• Investigator sponsored Phase 1 trial (IST) of eryaspase in combination with FOLFIRINOX in the United States
22Industrialized and Scalable Manufacturing
Own cGMP production in Europe and US, scaled
for clinical and early-commercial manufacturing
• Europe: Lyon (France)
• 12 cleanrooms
• Producing GMP batches for clinical trials
• United States: Princeton, NJ
• 16 cleanrooms, 4 equipped
• Ready to manufacture cGMP batches for clinical
trials
23Preclinical Programs
Gastric adenocarcinoma
Tumor regression in gastric cancer model
Erymethionase, methionine-gamma-lyase encapsulated in RBC 1800 ****
Mean tumor volume (mm 3 + SEM)
1600 Erymethionase + PN
• Promising preclinical data in gastric cancer and glioblastoma 1400
1200
suggest potential as a new treatment approach against cancers 1000
800 **
***
that rely on methionine metabolism 600
400
• Further preclinical data show potential synergistic effect of
200
0
methionine restriction with immune checkpoint inhibitors and
0 10 20 30 40 50 60 70 80
Days post-tum or im plantation
asparaginase Vehicle
Erymethionase 80 U/kg
ERYZYME, encapsulating enzymes used in certain enzyme
therapies to treat rare metabolic diseases
• E.g. Arginase-1-deficiency: preclinical data showing sustained
lowering of arginine levels with arginine deiminase encapsulated
in RBC in arginase deficient mice
24Strategic Collaboration with SQZ Biotechnologies
• ERYTECH granted SQZ Biotechnologies, a Cambridge (MA) based cell therapy
company, an exclusive worldwide license to develop antigen-specific immune
modulating therapies employing red blood cell-based technology.
• SQZ to develop RBC-derived therapeutics to induce antigen-specific immune
modulation by combining SQZ’s Cell Squeeze® cell engineering platform with
ERYTECH’s IP and knowhow related to RBC-based therapeutics
• ERYTECH is eligible to receive:
• Upfront and potential milestone payments up to $57 million for the first product
successfully developed by SQZ under agreement
• Royalties on sales, and potential commercial milestone payments up to $50
million for each additional approved product or approved indication
25Q3 2019 Financial Results
• Net loss of €43.3 million at 09-2019 09-2018
(Cumulative figures in '000€) Var° in K€ Var° in %
end of Q3 2019 (9 months), (9 months) (9 months)
up €13.6 million yoy Revenues
Other income 3 881 2 666 1 216 46%
Total operating income 3 881 2 666 1 216 46%
Total Research and development (36 977) (25 726) (11 251) 44%
• Cash position of €81.9 General and administrative (13 743) (10 566) (3 177) 30%
Total operating expenses (50 720) (36 292) (14 427) 40%
($89.2) million as of Total operating loss (46 839) (33 627) (13 212) 39%
September 30, 2019 Financial income 3 975 3 994 (19)
Financial expenses (392) (15) (377)
Financial income (loss) 3 582 3 979 (396) -10%
Income tax 1 (1) 2 -150%
Net loss (43 256) (29 649) (13 606) 46%
• Cash variation of €52.4 million in the first nine months of 2019
• Cash runway confirmed into 2021
26Key Milestones Anticipated over Next 12 Months
ü Start of GMP production at Princeton facility
ü Safety review by IDMC of first 150 patients in TRYbeCA-1
q Interim results of Phase 2 IST in 2L acute lymphoblastic leukemia (ALL)
q Interim (superiority) analysis in TRYbeCA-1
q Initiation of Phase 1 IST with eryaspase in 1L pancreatic cancer
27Shareholder Base
Retail
20-25%
Institutional EU/RoW
30-35%
Institutional US
40-45%
Source: Euroclear Identifiable Bearer Securities (‘TPI’), June 28, 2019
28Leadership Team Jérôme Bailly Gil Beyen Jean-Sébastien (JS) Cleiftie VP Pharmaceuticals Operations & Qualified Person Chief Executive Officer Chief Business Officer
Board of Directors
Jean-Paul Kress Sven Andréasson Philippe Archinard Gil Beyen
Chairman Independent Director Independent Director Chief Executive Officer & Director
Luc Dochez Martine George Hilde Windels
Independent Director Independent Director Independent Director
30ERYTECH Pharma SA ERYTECH Pharma Inc
60 Avenue Rockefeller 1 Main Street
69008 Lyon Cambridge, MA 02142
France USA
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