Bringing Breakthrough Pioneering Therapies to Patients with Life-Threatening Diseases Corporate Presentation January 2018 - Celyad
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Bringing Breakthrough Pioneering Therapies to
Patients with Life-Threatening Diseases
Corporate Presentation
January 2018
Disclaimer
In addition to historical facts or statements of current condition, this presentation contains forward-looking statements, including
statements about the potential safety and feasibility of CYAD-01 cell therapy, including current and planned preclinical and clinical trials for
Celyad’s product candidates; the clinical and commercial potential of these product candidates and the adequacy of Celyad’s financial
resources; Celyad’s intellectual property portfolio, including plans related thereto; Celyad’s expectations regarding its strategic
collaborations and license agreements with third parties, including Novartis, Celdara Medical, and Dartmouth College, and the potential
impact of such collaborations on Celyad’s future financial condition; and Celyad’s expected cash burn, which reflect Celyad’s current
expectations and projections about future events, and involve certain known and unknown risks, uncertainties and assumptions that could
cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These forward-
looking statements are further qualified by important factors and risks, which could cause actual results to differ materially from those in the
forward-looking statements, including risks associated with conducting clinical trials; the risk that safety, bioactivity, feasibility and/or
efficacy demonstrated in earlier clinical trials or preclinical studies may not be replicated in subsequent trials or studies; risks associated with
the timely submission and approval of anticipated regulatory filings; the successful initiation and completion of clinical trials, including its
clinical trials for CYAD-01; risks associated with the satisfaction of regulatory and other requirements; risks associated with the actions of
regulatory bodies and other governmental authorities; risks associated with obtaining, maintaining and protecting intellectual property,
Celyad’s ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties; risks associated
with competition from others developing products for similar uses; risks associated with Celyad’s ability to manage operating expenses; and
risks associated with Celyad’s ability to obtain additional funding to support its business activities and establish and maintain strategic
business alliances and business initiatives. A further list and description of these risks, uncertainties and other risks can be found in Celyad’s
U.S. Securities and Exchange Commission (SEC) filings and reports, including in its Annual Report on Form 20-F filed with the SEC on April 4,
2017 and subsequent filings and reports by Celyad. Given these uncertainties, the reader is advised not to place any undue reliance on such
forward-looking statements. These forward-looking statements speak only as of the date of publication of this document. Celyad expressly
disclaims any obligation to update any such forward-looking statements in this document to reflect any change in its expectations with
regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless required by law or
regulation.
2
Focused on the discovery and development
of specialized cell-based therapies to target cancer
• Novel and proprietary CAR-T platform targeting treatment of solid and
hematological tumors
• Lead candidate, CYAD-01 (CAR-T NKG2D), currently enrolling in THINK trial
• CAR-T NKG2D target supported with complete response in one AML patient
• Expertise in cell manufacturing with intense focus on process improvements
• Strong IP position
• Collaborations with world-class corporate, academic institutions
3
Stress ligands, the making of an ubiquitous CAR-T
SIGNAL 1
CD19-CAR-T CYAD-01 CAR-T
SIGNAL 2
scFv
NKG2D
• Derived from a
CD8TM • Derived from
(murine) antibody human NK receptor
• 2nd generation CAR- DAP10 • Similar primary and
CD28
T signaling CD3ζ secondary signaling
CD3ζ
• scFv targeting • NKG2D receptor
specific cancers targeting stress
signals present on
many cancers
4
NKG2D binds to 8 stress induced ligands, expressed in a broad range
of cancer indications
Expression of at least one of
NKG2D ligands:
• Triple negative breast: 88%
• Colorectal: 88%
• Ovarian: 68%
• Bladder: 78% of the primary
tumors and 100% of the
metastases
• Pancreatic: 86%
• NSCLC Lung: 92% (100%
non-squamous NSCLC)
Dulphy N., Toubert A. et al. 2017. Unpublished data. Celyad 2017. Unpublished data, IHC.
5
Beyond direct cell killing, inducing multi faceted attack on the tumor
RELEASE OF THE IMMUNOSUPPRESSION OF
THE TUMOR MICROENVIRONMENT
Immunosuppressive cells
DIRECT TUMOR
CELL KILLING
Tumor cells Blood vessels
CYAD-01 ANTI-NEOANGIOGENEIC EFFECT DRIVEN
THROUGH TARGETING OF TUMOR ENDOTHELIAL
CELLS EXPRESSING NKG2D LIGANDS
Host Immune cells
ADAPTIVE IMMUNE RESPONSE: SPECIFIC ANTITUMOR
RESPONSE POST CYAD 01 TREATMENT
6
Lonez et al. 2017 BMJ Open 7:e017075.CYAD-01 preclinical models showing activity with multiple
injections and without pre-conditioning
OVARIAN CANCER LYMPHOMA MULTIPLE MYELOMA
Barber et al. 2009 J Immunol. 183(4):2365-72 Zhang et al., 2007 Cancer Res; 67: (22) Barber et al., 2011 Gene Ther. 18(5):509-16
7FIM Phase I Study: CYAD-01 showed acceptable safety profile and
early signs of activity
2015 2016
Safety Phase I
• Conducted at Dana Farber Cancer Institute
• No treatment related SAEs
▪ 1 administration • One relapsed refractory AML Patient at highest dose (3x107) showed
▪ No lymphodepletion normalization of all hematologic parameters for 6 months
▪ Low sub-therapeutic
doses
▪ Hematological tumors
(AML/MM)
8THINK Study (THerapeutic Immunotherapy with NKG2D-based
therapy)
o 3 dose levels (3x108,1x109 and 3x109)
THINK Trial
1st CYAD-01 (D1)
2nd CYAD-01 (D2)
Tumor
3rd CYAD-01 (D3)
Washout period assessment
D-35 D-21 D1 D15 D29 D43 D57
▪ 3 administrations End safety
Apheresis
▪ Primary Endpoint: Safety &
Tolerability 13 weeks w/o any other non-investigational cancer therapy
▪ Secondary Endpoint: Efficacy as
▪ Seven advanced refractory tumor indications
Monotherapy (w/o preconditioning)
▪ Hematological & solid ▪ Global development: EU and USA
tumors
9THINK Study: Primary endpoint – Safety – Interim Data
THINK: Safety & Tolerability Data in 15 Patients
All adverse events if occurred in >= 2 patients
Solid (n=8) and hematologic (n=7) cancer patients
Dose-level 1 (solid and hematologic cohorts) and dose-level 2 (solid cohort and one patient
hematologic cohort)
Adverse Events Grade 3 Grade 4 Grade 5 Total % of Patients*
Events (Patients) Events (Patients) Events (Patients)
Anaemia 3 (2) 13.3%
Back pain 3 (2) 13.3%
Febrile neutropenia 3 (2) 13.3%
General physical health deterioration 2 (2) 13.3%
Hypophosphataemia 4 (2) 13.3%
Lymphocyte count decreased 5 (2) 13.3%
Data as of December 31, 2017
10Secondary Endpoint: Early readout: Clinical activity in 3/3 Relapsed
Refractory AML Patients treated at the per-protocol dose
Best
Response
to date Months 1 2 3 4 5 6
Level 1
Dose
CRi Demethylation Agent
CR
Level 1
(MRD-
Dose
Post
HSCT)
Level 2
Dose
SD HI Demethylation Agent
• 1 Patient reached MLFS, allowing HSCT. Patient further improved to CR
Treatment Cycle 1 MRD negative status, ongoing at 6 month
• 3/3 patients showed blast reduction during treatment administration
• All patients had hematological improvements
Allo- End of Treatment
• 4th patient treated at dose lower then per-protocol dose did not show
HSCT Evaluation
signs of clinical activity
CRi – Complete remission with incomplete hematological recovery
CR (MRD-) – Complete response without minimal residual disease
SD HI – Stable disease with hematological improvement 11
HSCT – Hematopoietic stem cell transplant Data as of December 31, 2017Preliminary take away from AML patients with CYAD-01 as
monotherapy at per-protocol dose (without preconditioning)
• CYAD-01 active against AML tumor in 3/3 patients treated at the intended dose
• Blast reduction in Bone Marrow in patients up to and including at least the third
injection
• Hematological parameters improving in patients
• No significant Adverse Events (low grade (CYAD-01 AML Clinical Development Plan
Boosting potency:
Prolong durability as
• Expansion
stand-alone
• Tumor debulking
Multiple Treatment THINK
Cycles in Expansion
First FOCUS ON AML
Standard CAR-T
in Hematological Enhance
preconditioning AML
Tumors engraftment and
regimen to induce preconditioning
proliferation
lymphodepletion
Increase potency Combination with 2nd line
through debulking AML SoC
standard of care
chemotherapy regimen
Broaden patient Donor-derived CYAD-01
SIBLINK
population infused in patients in
remission post allo-graft
13Secondary Endpoint: Early readout: Signals of activity in Colorectal
Cancer and Ovarian Cancer
• Two out of four metastatic colorectal cancer patients treated at per-
protocol dose reported as “stable disease” up to 3-months follow-up*+
• No toxicity signals to date
➢ Next anticipated steps: Higher dose, longer follow-up + SHRINK and
LINK
* Median progression free survival in these patients under standard of care is between 1.9 and 3.2 months
(e.g. regorafinib or trifluridine/tipiracil).
+ Fifth CRC patient treated at a dose lower then per-protocol dose did not show signs of clinical activity
Sources: Grothey et al., 2013 Lancet. 381(9863):303-12; Li et al., 2015. Lancet Oncol. 16(6):619-29;
Moriwaki et al., 2017. Oncologist. 2017 Sep 11. 14CYAD-01 clinical development plan in CRC
Boosting potency through:
Prolong durability as • Expansion
stand alone • Tumor debulking
• Homing
Multiple Treatment
THINK
Cycles in Expansion
Standard CAR-T
Enhance CRC pre-
preconditioning regimen
engraftment and conditioning
proliferation
First FOCUS ON
1st line standard of care
CRC in Solid Increase potency chemotherapy regimen SHRINK SOC
Tumors through debulking for metastatic CRC (FOLFOX)
Local infusion in hepatic
artery for primary liver
Favor tumor homing LINK
metastasis of CRC
15Intensely Focused on Manufacturing Improvements in Anticipation
of Commercial Ready Product
• Evolution from drug product manufactured in academic setting (DFCI) towards a
commercial-ready process that is reproducible and scalable, with attractive COGs
• Legacy method (LY process) failed to consistently yield drug product with target T cell
numbers
• Of 15 patients treated at December 31, 2017, 10 were dosed at per-protocol intended dose and 5 were
treated at lower doses
• New manufacturing process is currently being used in the clinic
• mAb manufacturing process inhibits NKG2D expression on the T cell surface during production
• Enables significantly higher cell numbers than the legacy process
• Validated in both in vivo and ex vivo models
• CMC amendments to THINK protocol are in effect with applicable regulators
• First patient treated January 2018
• Continued focus on next-generation process improvements, including automated
and closed system approach
16Clinical Development Plan
Product Indication Clinical Study Preclinical Phase 1 Next Anticipated
Milestones
THINK Complete Dose Escalation
Pre-conditioning File IND
AML
Standard of Care File IND
SIBLINK File IND
CYAD-01
THINK Complete Dose Escalation
SHRINK First Patient First Visit
CRC
LINK First Patient Dosing
Pre-Conditioning File IND
CYAD-101
CRC SHRINK Allo File IND
(Allogeneic)
17CYAD-101: Non gene edited allogeneic option
• Engineered for CYAD-01 (NKG2D-based CAR-T cell)
• Alloreactivity controlled through co-expression of an inhibitory peptide (termed a T cell
receptor inhibitory molecule – TIM) to reduce TCR-signaling and thereby reduce Graft
versus Host Disease (GvHD).
01/02/2018 18Impact on GvHD off the expression of TIM8 in allogeneic T cells
The expression of TIM8 inhibits Tumor growth (orthotopic colorectal tumor in NSG mice)
xGvHD in the NSG mouse is decreased following treatment with CYAD-101
10 11 C o n tro l
100
(p h o to n s / s e c / m m )
tC D 1 9 T c e lls
2
B io lu m in e s c e n c e
10 10 CYAD-101
T IM 8 .N KR2
S u r v iv a l ( % )
**
9
50 10
D o n o r T c e lls
8
D o n o r T IM 8 T c e lls 10
N o T c e lls
0 7
TIM8.
0 20 40 60
10 Vehicle tCD19
0 5 10 15 20 25 CYAD-101
D a y s p o s t in fu s io n D a y s p o s t in fu s io n
19Summary: Towards CAR-T leadership
NKG2D platform;
Autologous Cell
Leveraging Stress Ligands Allogeneic CAR T Cell Therapy
Manufacturing Paradigm shift
based CAR-T
Building on early signals Process Development Strong IP position
Improving outcomes Improved yields and CoGs Patents concerning TCR knockdown
in CAR T cell therapy providing
broad coverage in the field
Initial focus on AML and CRC Automation
Execution Making Autologous Cell Therapies
feasible and cost effective Allogeneic NKG2D Platform
Development of TIM8-CYAD 01
(CYAD-101)
Continuing Development Plan
Broaden indications beyond AML Towards Point of Care Processing Allogeneic TIM Platform
and CRC Enabling large indications Developing broad based Allogeneic
CAR –T products
20Corporate collaborations
• May 2nd, 2017: Celyad grants to Novartis a non-
exclusive license for its allogeneic TCR-deficient
CAR-T cells patents for two undisclosed targets
• July 11th 2016: Celyad grants exclusive license to
ONO for the development and commercialization of • Deal value: $96 million. Celyad to receive
allogeneic CYAD-01 T-cell immunotherapy in Japan, upfront, and potential development and
Taiwan and Korea commercial milestones payments and single
digit royalties
• License in exchange for $12.5M upfront, $300M in
potential milestones and double-digit royalties • Celyad retains all rights to grant further licenses
to third parties for the use of allogeneic CAR-T
cells. Deal can be turned into exclusive license
21Financial snapshot
Cash Position:
• Approximately €34 million as of December 31, 2017*
• Enabling company’s activities through first half of 2019
Ticker: Nasdaq (CYAD), Euronext Paris & Euronext Brussels (CYAD.BB)
* Preliminary estimate abd unaudited
22Management team
1. Christian Homsy, CEO
2. Patrick Jeanmart, CFO
3. Jean-Pierre Latere, COO
4. Frédéric Lehmann, VP Clinical Development & Medical Affairs
5. David Gilham, VP R&D
6. Georges Rawadi, VP Business Development & IP
1 2 3 7. Philippe Dechamps, CLO
8. Philippe Nobels, Global Head Of Human Resources
4 5 6
6
7 8
7 8
01/02/2018 23Thank you
Contact: investors@celyad.com
BELGIUM USA
Celyad SA Celyad Inc.
Axis Business Park Seaport East
Rue Edouard Belin, 2 2 Seaport Lane
B-1435 Mont-Saint-Guibert Boston, MA. 02210
+32(0) 10 39 41 00 +1 857-990-6900
www.celyad.comYou can also read
