Mar 10, 2017 - ... to constitute, and should not be construed as an offer to sell or a solicitation of an offer to buy o
Teaching regulatory T cells to treat your disease
Corporate Presentation March 2017
FR0010127662 – TXCL
Disclaimer References herein to this presentation (the “Presentation”) shall mean and include this document, any oral presentation accompanying this document provided by TxCell (the “Company”) and any further information that may be made available in connection with the subject matter contained herein. The disclosure, distribution and publication of this Presentation may be restricted by law in certain jurisdictions and persons into whose possession any document or other information referred to herein comes should inform themselves about and comply with any such restrictions. The Company takes no responsibility for any violation of any restrictions by any person. This Presentation has been prepared by the Company and is provided for information purposes only. This document does not purport to contain comprehensive or complete information about the Company and is qualified in its entirety by the business, financial and other information that the Company is required to publish in accordance with the rules, regulations and practices applicable to companies listed on Euronext Paris, including the risk factors described in the Company’s Document de Référence (registration document) for the year ended December 31, 2015 as filed with the French financial market authority (the Autorité des marchés financiers – the “AMF”) on May 24, 2016 under number R.16048 and in the update of the registration document filed with the AMF on January 24, 2107 under number D.16-0346-A01, available on the Company’s website (www.txcell.com), in particular in Chapter 4 “Risk factors”. Information and other data appearing in such publications, and certain figures and numbers appearing in this document have been rounded. Consequently, the total amounts and percentages appearing in tables and elsewhere may not necessarily equal the sum of the individually rounded figures, amounts or percentages. No representation, warranty or undertaking, express or implied, is made as to the accuracy, completeness or appropriateness of the information and opinions contained in this Presentation, or its use for any purpose, and no reliance should be placed on any information or opinions contained herein. The Company and its representatives accept no responsibility for and shall not, under any circumstance, be held liable for any loss or damage that may arise from the use of this document or the information or opinions contained in it. In particular, this document contains information on the Company’s markets and competitive position, and more specifically, on the size of its markets. This information has been drawn from various sources or from the Company’s own estimates which may not be accurate and thus no reliance should be placed on such information. The information and opinions contained in this document are provided as of the date of this document only and may be updated, supplemented, revised or amended, and thus such information is subject to change at any time. The Company is not under any obligation to update the information, statements or opinions contained in this Presentation. This Presentation contains certain forward-looking statements relating to the business of the Company, including the Company’s ability to develop, market, commercialize and achieve market acceptance for its products, estimates for future performance and estimates regarding anticipated operating losses, future revenues, capital requirements, and needs for additional financing. Even if the actual results or development of the Company are consistent with the forward-looking statements contained in this Presentation, those results or developments of the Company may not be indicative of future results or developments. In some cases, you can identify forward-looking statements by words such as “could,” “should,” “may,” “expects,” “anticipates,” “believes,” “intends,” “estimates,” “aims,” “targets,” or similar words. Although the management of the Company believes that these forward-looking statements are reasonably made, they are based largely on the current expectations of the Company as of the date of this Presentation and are subject to a number of known and unknown risks and uncertainties and other factors that may cause actual results, performance or achievements to be materially different from any future results, performance or achievement expressed or implied by these forward-looking statements. In particular, the expectations of the Company could be affected by, among other things, uncertainties involved in the development of the Company’s products, which may not succeed, the ability to manufacture product, the outcome of clinical trials and the delivery of regulatory authorizations necessary for clinical trials, manufacturing and marketing of the Company’s products and, in general, any factor that could affects the Company’s capacity to commercialize the products it develops, as well as any other risk and uncertainties developed or identified in any public documents described above. In light of these risks and uncertainties, there can be no assurance that the forward-looking statements made in this Presentation will in fact be realized. Notwithstanding the compliance with article 223-1 of the General Regulation of the AMF (the information disclosed must be “accurate, precise and fairly presented“), the Company is providing the information in these materials as of the date of this Presentation, and disclaims any intention or obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise. All persons accessing this document are deemed to agree to all the limitations and restrictions set out above. This Presentation and the information it contains are not intended to constitute, and should not be construed as an offer to sell or a solicitation of an offer to buy or subscribe to any the Company securities, in any jurisdiction. 2
Teaching regulatory T cells to treat your disease
Introduction
A unique positioning TxCell develops cellular immunotherapies based on regulatory T cells (Treg) for the treatment of autoimmune diseases as well as transplantation-related inflammatory disorders.
4
A highly experienced management team
Stéphane BOISSEL Chief Executive Officer •
25 years of experience, 15 of them in the biopharma industry
•
MBA from the University of Chicago
François MEYER Head of Research • •
35 years in pharma & biotech R&D, including gene & cell therapy Graduated from the Swiss Federal Institute of Technology (ETHZ) and PhD from the Institute for Molecular Biology of Zurich
Raphael FLIPO Chief Financial Officer
•
12 years in corporate finance and auditing
•
Master in Law and graduated from EDHEC Business School
5
Cell therapy: potential to be a game changer in the treatment of autoimmune and inflammatory diseases T cell type
Therapeutic strategy
Therapeutic field
T Effector Cells
Stimulate the immune system to attack the tumor
Cancer
(Teffs)
Selected companies
T cell IP
Multiple CAR-Teffs product patents
T Regulatory Cells (Tregs)
Control the immune system that has turned against the patient
Autoimmunity Inflammation Transplantation
Exclusive license on Weizmann Institute CAR-Treg patent — >150 TxCell patents
CELL THERAPY IS RAPIDLY BECOMING A MAINSTREAM TECHNOLOGY TXCELL UNIQUELY POSITIONED IN THIS EMERGING SPACE CAR: Chimeric Antigen Receptor 6
Key dates in the history of Teffs and Tregs First clinical trial with non-modified Teffs (Rosenberg, 1998)
Teffs Discovery of Teffs antigen specificity in the 1970’s
1970
First clinical trial with genetically modified Teffs
1990
2000
Discovery of Tregs (Sakagushi, 1995)
Discovery of Type 1 Tregs by TxCell’s scientific founder (Groux, Nature 1997)
2010
First clinical data with non-modified Tregs (Trzonkowski,2009)
First rolling BLA for CAR-T candidate in cancer
2016
Preclinical POC with CAR-Tregs (Eshhar, 2014)
First clinical data with TxCell’s Treg drugcandidate Ovasave in Crohn’s disease (Desreumaux, 2012)
Increasing number of publications on Tregs since the end of the 1990s1
Preclinical POC with human CAR-Tregs (Levings, 2016)
1998 2000 2002 2004 2006 2008 2010 2012 2014
Tregs
First proof of efficacy of CAR-Ts in clinical trials
Tregs: a recent discovery rapidly gaining momentum in the scientific community 1. Source : « Treg cells » research on PubMed, Medline extraction. 7
A considerable body of scientific and medical evidence
Natural role evidenced: • •
Cells specialized in immune tolerance induction Prevention of hypersensitivity to allergens and autoimmunity to self
Key function in inflammation and autoimmunity demonstrated:
T Regulatory Cells (Treg)
• • • •
Absence of Treg cells leads to multi-organ autoimmune syndrome Defects of Treg cells are observed in chronic inflammation and autoimmunity Decreased Treg cells specific for allergens is observed in allergic patients Treg cells increase in patients with treatment induced remission
Confirmed therapeutic potential: • • •
Tolerance and activity demonstrated in early clinical studies in Crohn’s Multiple mode of actions acting in synergy to reduce inflammation Great potential for therapeutic efficacy in humans
8
Large potential market opportunities NEUROLOGY Primary focus: Multiple Sclerosis Other possible indication: neuromyelitis optica
TRANSPLANTATION GASTROINTESTINAL Primary focus: Crohn’s disease Other possible indications: Ulcerative colitis, celiac disease, autoimmune hepatitis
Primary focus: Solid organ transplantation Other possible indication: Graft-versus-Host Disease
DERMATOLOGY Primary focus: Bullous pemphigoid Other possible indications: psoriasis, pemphigus vulgaris
RHEUMATIC Primary focus: Lupus Other possible indications: Rheumatoid arthritis, spondylarthritis, psoriatic arthritis
▪ 100+ diseases ▪ Business opportunity > 100Bn$1 with CAGR > 5%2
1. 2.
Company estimate. During the period 2016-2020. Source : Global Autoimmune Diseases Drugs Market 2016-2020, Market Research Reports, March 18, 2016. 9
A pragmatic strategy to deliver strong product & partnership potential 1/ Unmet medical need • • •
Large market with refractory sub-population, e.g. Crohn’s disease, multiple sclerosis Rare diseases, e.g. bullous pemphigoid Indications with no “game changing” pipeline, e.g. lupus nephritis
2/ Scientific relevance of Tregs •
Can a Treg work in this indication, in the targeted sup-population? • Strong inflammatory component • Relevance of the Treg mechanism of action
3/ Feasibility • • •
Adequate set of possible targets Preclinical feasibility (available model, tools & reagents) Freedom to operate / IP
Suitable targets for Treg-based therapy development Targets for large and competitive diseases TxCell to partner-out to pharmas
Targets for rare or orphan diseases TxCell to keep rights as long as possible 10
Teaching regulatory T cells to treat your disease
Technology platforms
Two complementary platforms: ASTrIA and ENTrIA ASTrIA
ENTrIA
ASTrIA is TxCell’s original platform, based on naturally antigen-specific Tregs
ENTrIA is TxCell’s new platform, based on genetically modified CAR-Tregs
• Antigen specificity comes from the natural T cell receptor (TCR)
Antigen specificity
• Antigen specificity comes from a CAR (Chimeric Antigen Receptor)
Antigen Presenting Cell
(Genetically-modified Tregs)
Contrary to conventional approaches based on non-specific polyclonal Tregs, TxCell is exclusively developing antigen-specific Tregs. 12
Two complementary platforms: ASTrIA and ENTrIA ASTrIA
ENTrIA
ASTrIA is TxCell’s original platform, based on naturally antigen-specific Tregs
ENTrIA is TxCell’s new platform, based on genetically modified CAR-Tregs
Mechanism of action
13
Strong IP position in therapeutic Tregs • TxCell’s solid patent portfolio: •
Over 150 granted patents applicable to either ASTrIA or ENTrIA or both platforms
•
Various populations of Tregs and CAR-Tregs •
Type 1 Tregs (Tr1)
•
CD4+Foxp3+ Tregs
•
CD8+ Tregs
•
Various production methods for both non-modified and genetically-modified Tregs
•
Numerous therapeutic applications in autoimmunity, inflammation and transplantation
• Additional strategic in-licensing agreements in place •
Exclusive worldwide license on key CAR-Treg patent from Weizmann Institute (Rehovot, Israel)
•
Exclusive worldwide license on CD8+ Treg patents from CRTI (Nantes, France)
•
Additional in-licensing options as part of R&D collaborations with OSR (Italy) and UBC (Canada)
Proactive and efficient IP strategy to help maintain first-mover advantage in the field of therapeutic Tregs 14
A first clinical POC with an antigen-specific approach •
20 patient-study in 4th line, refractory Crohn’s disease
•
Good tolerability of Ovasave® (autologous ovalbumin-specific Tregs)
•
High response and remission rate with dose related efficacy at 5 to 8 weeks after single injection
Ovasave® CATS1 study Percentage of patients receiving 106 cells in Response or Remission on CDAI (Crohn’s Disease Activity Index) 100 (n=8)
75%
80
75%
60
•
Biomarkers for identification of patient responses
38%
40
• •
Physicians’ assessments lead to repeated injections for up to 1 year
25% 20
Phase I/II retreatments document feasibility and tolerability of multiple injection
0 Week 5
Week 8
Response Delta CDAI ≥ 100
Full study results published in Gastroenterology and featured in Nature Reviews of Gastroenterology (2012)
•
Strong set of data - First clinical proof-of-concept
Remission ≤150 CDAI points
CDAI* change from baseline – Dose 106 (n=8) 50
Moyenne ± ESM
•
0 -50 -100 -150 -200 0
2
4
6
8
10
12
Weeks
15
Product pipeline Product(s)
Indication(s)
Research
Preclinical
Clinical
Next catalysts
ENTrIA (CAR-Treg) CAR-Tregs Transplantation
CAR-Tregs Autoimmunity & Inflammation
ENTX#SOT
Transplantation
ENTX#LN
Lupus nephritis
ENTX#BP
Bullous pemphigoid
ENTX#MS
Multiple sclerosis
2017: In vivo PoC
2018: First-in-man study
2017: In vivo PoC
2018-2019: At least one first-in-man study
ASTrIA Ag-Tregs Autoimmunity & Inflammation
Ovasave® * (Ova-Treg)
Crohn’s disease, IBD
Col-Treg*
Non-infectious uveitis
Validation of new process 2017 & Potential new clinical study 2018
*Development on hold pending (i) GMP validation of the improved manufacturing process and (ii) appropriate funding to finance the clinical development. PoC: proof of concept 16
Teaching regulatory T cells to treat your disease
CAR-Treg transplantation program ENTX#SOT (ENTrIA)
17
The unmet medical need in transplant rejection Key transplantation figures •
>60,000 solid organ transplant procedures performed per year (US, EU)1
•
Significant risk of organ rejection
•
•
Only 50% graft survival at 10 years for kidney2
•
High mortality rates associated with lung transplants (40-55% at 5 years)3
>160,000 patients on waiting lists4 •
Increased transplantation procedures with tissues from cadaveric donors
Specific unmet needs in solid organ transplantation (SOT) •
Need for alternatives to current treatments Adverse events (nephrotoxicity, cardiovascular toxicity) notably in the context of chronic, long-term use
•
Improve prevention or treatment of chronic antibody-mediated rejection with strategies that are more effective and less toxic
•
Treat high-risk immunologic patients presenting HLA-reactive antibodies
1. Sources : US Department of Health & Human Services. ‘More than 30,000 transplants performed annually for first time in United States’ January 9, 2016. European Commission, Journalist workshop on organ donation and transplantation, November 26, 2014. 2. Gondos A , Döhler B, Brenner H, Opelz G. Transplantation. 2013 Jan 27;95(2):267-74 3. Hartert M, Senbaklavaci O, Gohrbandt B, Fischer BM, Buhl R, Vahl CF. Dtsch Arztebl Int 2014; 111(7): 107–16. 4. Sources : UNOS, European Commission 18
CAR-Tregs in transplantation •
Regulatory T cells are essential for the establishment and maintenance of immune tolerance
•
Polyclonal (non-specific) Tregs have already demonstrated good safety profile and signs of efficacy in open-label non-controlled clinical studies
•
CAR-Tregs have recently demonstrated efficacy in transplantation models •
•
CAR-Tregs have shown high superiority over polyclonal (non-specific) approaches
CAR-Treg-based treatments could offer numerous advantages over existing options: •
Specificity to graft tissues without direct impact on recipient’s cells
•
Local inhibition of inflammation
•
Potential for long-term cell persistence potentially leading to long-term control of graft maintenance
19
TxCell’s approach in Solid Organ Transplantation
•
Autologous cells ensuring absence of immunogenicity
•
Donor tissue specificity
ensuring local, graft CAR-Tregs designed to
restricted activity
specifically recognize the HLA-A2+ graft and induce local immune tolerance
Kidney transplantation is just used as an example and may not be the final indication
Local, graft specific inhibition of inflammation and induction of tolerance 20
First in vivo proof-of-concept with CAR-Tregs in transplantation model The first preclinical POC with human CAR-Tregs in transplantation was published in March
20161 by the University of British Columbia (UBC), TxCell’s academic partner •
Human CAR-engineered Treg cells specific for the molecule HLA-A2 are significantly more effective than polyclonal (non-specific) Tregs in reducing GvHD-related inflammation Graft-versus-host disease (GvHD) model Immunodéficient mice
Inflammation caused to the recipient/host by the donor/graft’s immune cells
INFLAMMATION
Human white blood cells
Survival curve
GvHD score Score GvHD
Survie (%)
CAR-Treg
Control Treg No Treg
PBMC: peripheral blood mononuclear cells PBS: phosphate buffered saline
Temps après injection (jrs) 1.
Temps après injection (jrs)
MacDonald KG, Hoeppli RE, Huang Q, Gillies J, Luciani DS, Orban PC, Broady R, Levings MK. J Clin Invest. 2016, 126(4):1413-1424. 21
UBC: a strategic academic collaboration with a leading research team in CAR-Tregs
•
•
Strategic R&D collaboration signed in October 2016 with the University of British Columbia (UBC), in Vancouver (Canada)
•
Development and commercialization rights exclusively optioned-out to TxCell
•
TxCell and UBC are conducting non-clinical pharmacology studies with CAR-Treg cells
Upcoming milestones: •
2017: Deliver additional sets of preclinical proof-of-concept data
•
2017: Develop CAR-Treg manufacturing process and transfer manufacturing process to CMO
TxCell aims at being the 1st company in the world to start a clinical trial with a CAR-Treg, in 2018
22
Teaching regulatory T cells to treat your disease
CAR-Treg programs for autoimmunity and inflammation (ENTrIA)
23
A strong rationale to use CAR-Treg cells for autoimmunity and inflammation •
Tregs are naturally involved in the prevention of autoimmunity
•
Defect of Treg cells have been identified as one of the cause of deregulated immunity in autoimmune diseases (Skin inflammatory diseases, SLE, Multiple Sclerosis, etc.) •
Initial targets:
Medical need & Relevance of CAR-Tregs
• • •
Bullous pemphigoid Multiple sclerosis Lupus Nephritis CAR construction and characterization
In vitro CAR-Treg validation in targeted Treg cells subtypes
In vivo Proof-of-concept
Current status ✓ We have initiated the development of lead candidates in all 3 indications (Bullous pemphigoid, Multiple sclerosis & Lupus Nephritis) ✓ We have established the in vitro validation of several CAR-Treg cells ➢ We expect to deliver one (possibly more) in vivo proof-of-concepts throughout 2017
Promising results already obtained with wide range of CAR-Treg programs Further in vivo POCs expected throughout 2017 24
Two CAR-Treg programs in collaboration with leading academic institutions ENTX#LN
Lupus Nephritis
Ospedale San Raffaele (OSR) Milan, Italy European expert in cell and gene therapy Contributed to the development of Strimvelis
• Lupus Nephritis is one of the most serious complications of Lupus, a chronic systemic autoimmune disease affecting over 5 million people worldwide1
• Pharmacology and toxicology studies conducted in Lupus Nephritis • Development and commercialization rights exclusively optioned-out to TxCell
ENTX#BP
Bullous Pemphigoid
Lübeck Institute of Experimental Dermatology (LIED) Lübeck, Germany Leading institution in translational research on skin blistering diseases
• Bullous pemphigoid is a rare, potentially fatal autoimmune disease characterized by tense inflammatory skin blisters • Pharmacology and toxicology studies conducted in bullous pemphigoid • Development and commercialization rights retained by TxCell
1. Source: Lupus Foundation of America 25
Teaching regulatory T cells to treat your disease
Manufacturing & Economic Model
From blood sample to medicinal product Major improvement identified in 2016
2
•
Latest improvements now being leveraged to develop the ENTrIA manufacturing process
Natural presence • of Treg ( )
5
Off the shelf 5-year stability data2
3
Industrial expansion of antigen-specific Tregs
New isolation method allowing 50% reduction of manufacturing costs & time for the ASTrIA process
Blood collection
1
Drug1
•
4
Antigen-specific Tregs
GMP validation of both processes expected in 2017 and 2018
ASTrIA
ENTrIA
Stimulation with antigen ( )
Cell sorting
Cell sorting
1. 2.
CAR transduction
ATMP in Europe Internal data on ASTrIA drug-candidates
One blood sample, one processing, multiple years of personalized treatment 27
Viable commercial model
First generation
Next generation – Target Product Profile
Autologous cell therapy
Hybrid autologous and allogeneic therapy
Gross Margin
Production cost Revenues
Year N
Year N+1
Year N+2
Total for 3 years
Autologous Model GM ~40-60%
Hybrid Autologous Model GM ~80-85%
Hybrid autologous model – Gross Margin target ~80-85% in line with biological products 28
Teaching regulatory T cells to treat your disease
Financials & Outlook
Key financials P&L *
Cash flow * In million of euros
12/31/2016 2.9 (10.5) (4.5) (0.6) (12.7) (13.6)
Revenue Other income Research and development expenses General and administrative expenses Expenses related to share-based payments Current operating profit / (loss) Net profit / (loss) *
In million of euros Net cash flows from operating activities Net cash flows from investing activities Net cash flows from financing activities Net cash flows as of December 31, 2016 Cash position as of December 31, 2015 Cash position as of December 31, 2016 *
12/31/2016 (10.4) (0.5) 5.2 (5.7) 9.2 3.2
IFRS data
IFRS data
2016 current operating expenses (excl. expenses related to-share based payments)
Research and development expenses
30%
Cash position In million of euros
Date
Amount
Cash position
06/30/2016
3.2
Cash position
09/30/2016
4.6
Cash position as of December 31, 2016 ABSA capital increase (gross amount)
General and administrative expenses
70%
Proforma cash position
3.5 24/02/2017
11.1 14.6
Cash burn guidance 2017 On the basis of the Company's development plan
Cash burn estimation Around €13M
30
Stock information Main shareholders as of February 24, 2017
To the best knowledge of TxCell as of February 24, 2017
Number of shares (as of Feb. 24, 2017): 19,422,552
Fully diluted capital as of February 24, 2017 As of February 24, 2017 (post operation)
Number of shares
Basic shares outstanding pre operation
13 873 252
New shares
5 549 300
Basic shares outstanding (non diluted capital) Incentive plans (management) Convertible notes with attached warrants (Yorkville) Listed warrants (shareholders)
Fully diluted capital **
19 422 552
Liquidity TxCell share: average volume before and after the capital increase of February 24, 2017 180000
140000
1 992 602
120000
2 226 036 *
100000
4 161 975
80000
27 803 165
60000
* Including outstanding warrants and theoretical number of shares to be issued by conversion of outstanding convertible Notes (i.e excluding unexercised warrants giving access to convertible Notes with share subscription warrants attached), based on 93% of the lowest daily VWAP over the ten days preceding December 31, 2016 (i.e. 2,15€). ** Excluding impact related to the PACEO equity line and the remaining drawdown of €15M of warrants giving access to Notes with share subscription warrants attached.
153k
160000
75k
40000 20000 0 Before transaction (3 mo.)
Post transaction
31
Capital increase completed in February 2017 • Capital increase successfully completed with support from existing shareholders and international investors • Offer subscribed at 100% • Issue of 5,549,300 new shares with warrants attached • Gross proceeds: €11.1 million
• Warrants attached to new shares • Warrants are listed on a separate line: FR0013231792 • 75% coverage: 4 equity warrants give the right to subscribe to 3 new shares • Strike price: €2.60 per new share upon exercise of the warrants • 12-month maturity: Can be exercised at any time until February 26, 2018
• In the event of a full exercise of warrants • Additional €10.8m gross product (4,161,975 new shares) • Would finance TxCell up until IND approval to start first-in-man CAR-Treg study, in 2018 32
Strategy & Outlook Transplantation • 2017
Generate additional preclinical POC data sets
• 2018
Launch first-in-man study First-ever clinical study with a CAR-Treg worldwide
Autoimmunity • 2017
Generate additional preclinical POC data sets
• 2018-2019
Launch at least one first-in-man study
Process development • 2017
Confirm & GMP-prove process development improvement with ASTrIA platform
• 2017
Develop manufacturing process for ENTrIA & Transfer to CMO
Business development • Corporate objective: sign pharma/biotech deals regularly
33
Key highlights • Innovative and unique technology platform
• Addressing significant unmet medical needs • Large markets: >100 Bn$ in annual sales and >5% CAGR • First mover with unparalleled IP position • Major short-term and mid-term catalysts • A real status of publicly-listed company following the recent financing
Strategic refocusing
2016
Multiple preclinical POCs
2017
First-ever first-in-man CAR-Treg study
2018
2019
Clinical POC
2020
34
Teaching regulatory T cells to treat your disease
TxCell
Thank you
www.txcell.com @TxCellSA
Teaching regulatory T cells to treat your disease
Back-up slides
Target antigen selection 1/ Antigen distribution • Local or Systemic: • Local: tissue-specific antigen (not necessarily linked to the pathology) • Systemic: disease-specific antigen OR antigen present in secondary lymphoid tissues
2/ Specificity • Antigen expression should be specific of the targeted tissue
3/ No cross-reactivity of CAR ligand binding domain • Target Structure: avoid strong similarities with other proteins • Target absence of homology with Infectious pathogens: avoid side effects due to Treg activation
4/ Cross-linking availability • Cross-linking is necessary to really activate CAR-Tregs • Various options: • Surface antigen CAR-Treg • Macromolecule • Polymer CAR
Macromolecule or polymer with repeated epitope
Surface antigen
CAR-Treg CAR
37
Key collaborations with leading scientists worldwide
Dr. Bernard MALISSEN
Research Director, Immunology Center of Luminy, Marseille, FRANCE
Dr. Megan LEVINGS Head, Immunity in Health and Disease, Child & Family Research Institute, University of British Columbia, Vancouver CANADA
Dr. Olivier DANOS
VP, Cell & Gene Therapy Biogen, Boston UNITED STATES
Dr. Ralf LUDWIG Head of the LIED Model Systems of Inflammatory Skin Diseases, Institute of Experimental Dermatology, Lübeck GERMANY
Pr. Chiara BONINI
Head of Unit, Experimental Hematology San Raffaele Hopital, Milan ITALY
Dr. Attilio BONDANZA Assistant Professor and Immunotherapy Group Leader, Institute San Rafaelle, Milan ITALY
Pr. Zelig ESHHAR Prof. of Immunology, Chair of Immunology Research Weizmann Institute of Science, Rehovot ISRAEL
38
Exclusive worldwide license on key CAR-Treg patent
REDIRECTED, GENETICALLY-ENGINEERED T REGULATORY CELLS AND THEIR USE IN SUPPRESSION OF AUTOIMMUNE AND INFLAMMATORY DISEASE (EP2126054)
Patent family Europe Patent granted by EPO in June 2016
United States Patent under review by USPTO
Inventors : Zelig Eshhar, Eran Elinav Applicant : Yeda Research and Development Co. Ltd., Rehovot, Israel (technology transfer arm of the Weizmann Institute of Science)
Exclusive worldwide license granted to TxCell in June 2016
TxCell’s exclusive access to key umbrella CAR-Treg patent enhances first mover advantage • Licence covers claims that include all redirected regulatory T cells (Tregs) comprising a Chimeric Antigen Receptor
(CAR) and actively equipped with specificity towards a selected antigen • CAR-Tregs have great potential for the treatment of autoimmune and inflammatory disorders in the likes of the ongoing groundbreaking results obtained with CAR-T cells in hematological cancers • Patent further strengthens TxCell’s position as a leading company in the Treg therapeutic field • Patent reinforces and enables TxCell’s ambitious business development strategy
39
Our expertise and strengths
International regulatory expertise (FDA, EMA, PMDA)
Unique expertise in the biology of all Treg subtypes
Antigenic target selection
Technology transfer to third parties (CMO etc.)
▪
Partner-out assets when relevant
Cell engineering
▪
Scout academic & industry works on Tregs in view of inlicensing
Design & optimization of CAR constructs
▪
When needed, partner with best academic teams for early development
▪
Educate industry on Tregs
What do our labs & people do? Process development expertise
Development of functional & analytical assays
Vector engineering & optimization scFV optimization
40
Ovasave® CATS1 CDAI assessment at weeks 5 and 8 Response rate (% patients)
Remission rate (% patients)
100%
100%
80%
75%
80%
75%
60%
40%
60% 40%
40% 33%
38%
40%
33%
25% 17%
20%
17%
0%
0%
20%
15% 10%
0%
0% 0% 0%
0%
Week 5
Week 8 All (n=20)
106 (n=8)
Week 5 107 (n=3)
Response: Delta CDAI ≥ 100
All (n=20)
0% 0% 0%
108 (n=3)
Week 8 109 (n=6)
Remission: ≤ 150 CDAI points
CDAI Week -2
CDAI Week 0
CDAI Week 5
Delta CDAI W0 vs W5
CDAI Week 8
Delta CDAI W0 vs W8
377 ± 81.8
363.7 ± 80.5
281.5 ± 116.1
-82.2 ± 95.4
292.0 ± 108.1
-63.0 ± 87.9
p=0.003 106 (n=8)
400.9 ± 101.2
395.1 ± 91.7
251.8 ± 157.9
-143.4 ± 105.0 p=0.039
p=0.006 244.6 ± 130.1
-131.6 ± 65.4 p=0.031
Source:, Gastroenterology 2012;1207-1217
41
Ovasave® CATS1 consistent results across multiple measures
Reduction in Crohn’s disease activity
Moyenne ± ESM
CDAI* change from baseline – Dose 106 (n=8) 50 0 -50 -100 -150 -200
Weeks
0
2
4
6
8
10
12
10
12
Improvement in patient quality of life
Average ± ESM
IBDQ* change from baseline – Dose 106 (n=7) 80 40 0 -40 -80
Weeks
0
2
4
6
8
CRP* change from baseline – Dose 106 (n=8) 20
Decrease in inflammation
Average ± ESM
10
0 -10 -20
Weeks
0
2
4
6
8
10
12
OVA* proliferation change from baseline – Dose 106 (n=8)
Proliferative response of cells to antigen biomarker of response
Average ± ESM
0.0 0.0 0.0 -0.1 Source: Company, Gastroenterology 2012;1207-1217
Weeks
0
2
4
6
8
10
12
*Notes: CDAI: Crohn's disease activity index, indice d'activité de la maladie de Crohn; IBDQ: inflammatory bowel disease questionnaire, questionnaire pour les maladies intestinales inflammatoires; CRP: C reactive protein/protéine C réactive, OVA: ovalbumin (antigen)/ovalbumine (antigène)
42
