PRESENTATION SESSIONS - TECHNOMARKET / LICENSING OPPORTUNITIES START-UP SLAMS - LILLE - BioFIT 2018
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LILLE
30TH NOVEMBER & 1ST DECEMBER
PRESENTATION
SESSIONS
The one-stop shop to engage new partnerships
for life sciences innovative projects
TECHNOMARKET /
LICENSING OPPORTUNITIES
START-UP SLAMS
LILLE
www.biofit-event.com
CONTENT
INTRODUCTION TECHNOMARKET / 4
LICENSING OPPORTUNITIES
INTRODUCTION START-UP SLAMS 5
AGENDA 6
TECHNOMARKET / LICENSING OPPORTUNITIES 9
ONCOLOGY 10
NEUROLOGY/CARDIOLOGY 22
INFECTIOLOGY AND VACCINES 35
RESEARCH TOOLS 43
START-UP SLAMS 47
3
TECHNOMARKET / LICENSING OPPORTUNITIES
To foster alliances and business development opportunities on innovative projects,
SATT Network (the association of the French TTOs) & BioFIT joint their initiatives
to organise the TechnoMarket and Licensing Opportunity Presentations.
Let’s discover the latest innovations in:
• RESEARCH TOOLS
• ONCOLOGY
• NEUROLOGY/CARDIOLOGY
• INFECTION AND VACCINES
During the two-day event, you can discover 30 licensing opportunities selected by
a jury of experts in the poster area in the Innovation area and listen to their pitches
in Van Gogh 3 room.
ORGANISED BY
4
S TA R T- U P S L A M S
The Start-up Slams are dedicated to young entrepreneurs (≤ 5 years) who are thin-
king about creating or have created an innovative company and having an overall
strategy to present.
During the presentations, the selected candidates will present their overall strategy
to potential partners and investors who could support their company and receive
feedback and advice by experienced pharmas and VCs on how to advance it.
PA N E L O F A DV I S O R S
• Sarah HOLLAND,
BD&L Business Partner, General Medicines and Emerging Markets
Business Unit (FR)
• Esther LANGE,
Industry Liaison Manager, ASCENION (DE)
• Cécile THÉARD-JALLU,
Partner Attorney, DE GAULLE FLEURANCE & ASSOCIÉS (FR)
• Sara NUNEZ GARCIA,
Principal, SOFINNOVA PARTNERS (FR)
• Stephan LENSKY,
COO and CBO, EPIMAB BIOTHERAPEUTICS (DE)
• Nicolas CARBONI,
President and CEO, CONECTUS ALSACE (FR)
• Guy HÉLIN,
Chief Executive Officer, SYNGULON (BE)
• Christian POLICARD
Member of the board and Chairman of the Business Development
Sub-Committee, FRANCE BIOTECH (FR)
ORGANISED BY
5
LILLE
AG E N DA
3 0 TH N O V E M B E R
VA N G O G H 3 R O O M
TECHNOMARKET / LICENSING OPPORTUNITIES
ONCOLOGY
• Diagnostic and stratification of colorectal cancer for a better
management of patient care protocol - SATT
• New peptide-based drug with anti-angiogenic properties - SATT
9. 4 5 A M
• Poly(2-oxazoline)s for a new generation of Cancer Drug Delivery
11 .0 0 A M
• Potent blocker of HER2 receptor for treatment of metastatic breast cancer - SATT
• Kinase Inhibitors & Cancer - SATT
• Small molecule lead compounds for colorectal cancer treatment through
TNIK modulation
• ProNGF: New target to counter resistance mechanisms in breast cancer - SATT
• Dual PI3K and mTOR inhibitors as promising drugs to treat cancer - SATT
S TA R T- U P S L A M S
• APTEEUS
2.30 PM • VitamFero S.A.
4 .0 0 P M • ViroVet
• Sencet
• Kangstem Biotech Co., Ltd.
• NOVAPTECH
TECHNOMARKET / LICENSING OPPORTUNITIES
NEUROLOGY - CARDIOLOGY
• A Preventing neuropathic pain induced by mastectomy - SATT
• Neuropain and chronic pain prevention - SATT
• DIVE: Dopaminergic stimulation by continuous intracerebro ventricular
4.30 PM delivery of anaerobic dopamine in Parkinson’s disease - SATT
6 .0 0 P M • Biomarkers for the diagnosis of dementia with Lewy bodies
• New generation of neuroprotectants: an original way to treat and prevent
acute and chronic neurological diseases - SATT
• Preventing neuropathic pain induced by chemotherapy - SATT
6 • CARMIDO - SATT
• Therapeutic potential of a molecule that modulates platelet function
and thrombosis - SATTAG E N DA
1 ST D E C E M B E R
VA N G O G H 3 R O O M
TECHNOMARKET / LICENSING OPPORTUNITIES
I N F E C T I O L O G Y A N D VA C C I N E S
• Bioactive Prosthesist - SATT
9. 45 A M • First effective vaccine against chlamydia infection - SATT
11.0 0 A M • Influenza antivirals - SATT
• Adenoviral coat protein delivery vehicles for use as a vaccine platform
• FibroCOPD - SATT
• New antibody fragments to treat ocular toxoplasmosis - SATT
• New small molecules to purge HIV reservoirs - SATT
S TA R T- U P S L A M S
• e-Zyvec
11.3 0 A M
• Spectralys Biotech
1.00 P M
• CEFO Co., Ltd
• Immune InsighT
• 1CryoBio AG
TECHNOMARKET / LICENSING OPPORTUNITIES
RESEARCH TOOLS
2. 30 P M • A rapid NTP-transporter as a tool for staining DNA in living cells
3.15 P M • MAGIA - SATT
• Disruptive mixed in vitro-in-silico approach for protein engineering
and screening
• iBodies: Modular Polymer-Based Synthetic Antibodies
7TECHNOMARKET / LICENSING OPPORTUNITIES
ON COLOGY
Diagnostic and stratification of colorectal
cancer for a better management of patient
care protocol
Key words lorectal cancer recurrence risk in order to
• Colorectal cancer select the best therapy to treat it. It gives
• Cancer stem cells the pathologist new data, a cancer stem
• Cancer aggressiveness cell scoring, that could be associated to
cancer aggressiveness indicator and a
Technology predictor of cancer recurrence.
The product is a new diagnostic kit with This new diagnostic tool is particularly
a high capacity to stratify colorectal interesting for early stages of colorectal
cancer. cancer (stage I or II) for which a chemo-
This is an immunohistochemistry test therapy treatment may not be indicated,
that can be easily added to standard although a real recurrence risk exists.
anatomopathological procedures. This
new product is selective of cancer stem Market
cells and based on their occurrence that Colorectal cancer is the second leading
provide data on cancer aggressiveness cause of mortality among cancer patients
and potential recurrence rate. This test in the world and is the third most dia-
uses markers that recognize biomarkers gnosed cancer globally. Populations are
expressed only on colorectal cancer stem aging and colorectal incident case rates
cells surface. are increasing in all the markets covered.
The product has already been successful- Overall, across the 7 major markets (US,
ly tested in a retrospective clinical study 5EU (France, Germany, Italy, Spain, the
using biopsies and patient survival rates UK), Japan), the incidence of colorec-
at 5 years. The results show a strong sta- tal is expected to increase by an Annual
tistical correlation between the specific Growth Rate (AGR) of 1.5% from 2013-
biomarker titer and the patient survival 2023.
rate. In that way, this new immunohisto- The market size for our technology in-
chemistry test will provide the patholo- cludes in particular population with stage
gist with a new aggressiveness score for I or II colorectal cancers.
colorectal cancer. The goal is to improve
Partnership sought
patient care protocol and treatment and
decrease the risk of cancer recurrence. Available for co-development and/or
licensing out: Diagnosis company.
Applications
The newly developed kit will be useful
and beneficial to assess the level of co-
10
SATT GRAND CENTRE
Magali Granger
magali.granger@sattgc.comON COLOGY
New peptide-based drug
with anti-angiogenic properties
Key words Market
• New peptide-based drug According to a new report released by
• Anti-angiogenic properties the IMS Institute for Healthcare Informa-
• Interaction TSP-1:CD47 tics, total global spending on oncology
medicines – including therapeutic treat-
Technology
ments and supportive care – reached the
Thrombospondin-1 (TSP-1) is a large $100 billion threshold in 2014. Oncology
matricellular glycoprotein found to be drug spending has risen slightly as a
overexpressed within tumor stroma in percentage of total drug spending over
several cancer types.TSP-1 binding to the past five years in all regions, most
CD47 is widely reported to regulate notably in the EU5 countries where onco-
cardiovascular function as it promotes logy now represents 14.7 percent of total
vasoconstriction and angiogenesis limi- drug spending.
tation. Therefore, many studies focused
on targeting TSP-1:CD47 interaction, ai- Competitors
ming for up-regulation of physiological This important therapeutic domain is
angiogenesis to enhance post-ischemia attractive and a lot of biopharmas are in
recovery or to facilitate engraftment. competition… The top 10 pharma compa-
Thus, we sought to identify an innova- nies by oncology sales are Roche, Novar-
tive selective antagonist for TSP-1:CD47 tis, Celgene, Johnson & Johnson, Bristol-
interaction. Protein-protein docking and Myers Squibb, Lilly, Takeda, AstraZeneca,
molecular dynamics simulations were Merck & Co. and Amgen. Nevertheless, a
conducted to design this drug peptide. lot of biotechs are also developing per-
TAX2 binds TSP-1 to prevent TSP-1:CD47 tinent approaches, tools, molecules, bio-
interaction, as revealed by ELISA and co- logics to tackle the cancer progression.
immunoprecipitation experiments. TAX2
Partnership sought
peptide molecular targets (TSP-1, CD47
and CD36) are overexpressed within Partnerships to achieve the development
human pancreatic and ovarian tumors. in the best therapeutic application and/
or out-licensing: Biotechs, Big Pharms.
Applications
Design and validation of a new mole-
cular agent able to disrupt TSP-1:CD47
molecular interaction and exhibiting
robust anti-angiogenic, anti-tumor and
anti-metastatic properties for new inno-
vative therapeutic approaches against
malignant diseases.
11
SATT NORD
Anthony Daccache
anthony.daccache@sattnord.frON COLOGY
LILLE
Poly(2-oxazoline)s for a new generation
of Cancer Drug Delivery
Technology drug release and high drug loading.
The combination of polymers and phar- The inclusion of these features in the
maceuticals is enabling the development current polymer systems is cumbersome,
of advanced drug delivery systems pro- and has triggered the search for alterna-
viding high efficacy while minimizing tive polymer platforms better suited for
side-effects. Polymers enhance drug polymer therapeutics.
solubilization, stability, bioavailability and Our technology: The versatile polymer
pharmacokinetics, while also allowing the platform for the new generation chemo-
introduction of targeting units, thereby therapy Poly(2-oxazoline)s (abbreviated
dramatically improving the pharmaceu- as PAOx, POx or POZ), set themselves
tical value of the active pharmaceutical ahead as they display all the required
ingredient (API). Due to their specificity, features for the ideal polymer platform
new generation chemotherapy is the for novel biomedical applications. Due
medical discipline that can most bene- to their structural analogy to natural
fit from the conjugation of APIs and polypeptides, PAOx are biocompatible,
polymers. exhibit the so-called stealth behavior
Polymer conjugation is applicable to (they are not recognized by the immune
either low molecular weight drugs, system), and benenfit from tunable
peptides or proteins. A water soluble properties and high functionalization
polymer can confer several properties to possibilities (Bioconjugate Chem. 2011,
the linked molecules: i) increased half- 22, 976-986, Macromol. Rapid Commun.
life due to reduced kidney clearance, ii) 2012, 33, 1613-1631, J. Mater. Sci.: Mater.
protection against degrading enzymes Med. 2014, 25, 1211-1225).
or reduced uptake by reticulo-endothe- At Ghent University, Belgium, we have
lial system (RES), thanks to the polymer developed methods to produce defi-
steric hindrance iii) augmentation of ned PAOx with tunable physicochemical
water solubility, particularly relevant for properties (from more hydrophilic than
some anticancer drugs with low solubi- PEG to thermoresponsive), very nar-
lity, iv) prevention of immunogenicity of row molar mass distribution (dispersity
proteins and v) selective tumor accu- < 1.10, WO2016/008817), and high purity
mulation (Adv. Drug Deliv. Rev. 2009, 61, (> 99 %).
1177–1188, Special issue: Advanced func- As with other polymers, PAOx allow the
tional polymers for medicine. Macromol introduction of functionality in the poly-
Biosci. 2011, 11, 1613–768). mer chain-ends, an ideal place to locate
Since the development of the first po- targeting units for targeted drug release
lymer-protein conjugates 25 years ago and/or labels for monitoring. Importantly,
(Adagen), polyethylene glycol (PEG) has PAOx also allow the introduction of mul-
been widely used in the clinic. The suc- tiple reactive handles along the polymer
12 cess of PEG has paved the way for the chain, enabling the conjugation of mul-
current development of the next gene- tiple APIs. This key feature grants PAOx
ration of polymer-drug systems, so-cal- with the ability to overcome the current
led polymer therapeutics which incor- limitation of polymer therapeutics, their
porate stimuli-responsiveness, targeted low drug loading capacity, and facilitatesON COLOGY
LILLE
to develop combination therapies as one gressive manner. Followed by one single
individual chain can carry different APIs. subcutaneous injection, this conjugate
We have developed proprietary linking provided sustained plasma levels of the
technology (WO2013/103297) to connect API during a period of seven days, hi-
multiple APIs to the polymer chain with ghly increasing the quality of life of the
the ability to provide controlled release. patient.
Polymer hydrophilicity, chain length, and In the field of cancer treatment, antibo-
the number and nature of the functional dy-drug conjugates (ADCs) hold a great
groups incorporated can be precisely promise as they have the ability to reco-
tuned to obtain the optimal drug carrier. gnize low receptor density targets in the
As such, our PAOx technology consti- cancer cell. Unlike conventional treat-
tutes an ideal platform to be broadly ments that damage healthy cells upon
applied for the development of highly dose escalation, ADCs specifically bind
effective cancer treatments. to the tumor tissue to deliver the che-
motherapeutic agent. This extremely
Applications
efficacious class of cancer therapy has
Our technology serves as a platform bloomed in the recent years with dozens
to highly increase the pharmaceutical of new ADCs entering the clinical pipeline
value of APIs, therefore opening a range (Biosci. Rep. 2015, 35, e00225, Pharma-
of applications as wide as the APIs used col. Rev. 2016, 68, 3-19).
in combination with our polymers (J. Ma- Most current ADCs are based on direct
ter. Sci.: Mater. Med. 2014, 25, 1211-1225). connection of the drug to the antibody,
As previously discussed, highly potent limiting the antibody to drug ratio (DAR)
but highly hydrophobic drugs can greatly to approximately 4, before interfering
benefit from our technology, as the poly- with the antibody activity. Conjugation
mer increases the solubility of the drug. of the antibody as targeting unit to one or
The ability of carrying numerous drug several PAOx chains enables the prepara-
molecules per polymer chain also enables tion of high capacity ADCs that can not
the use of PAOx as a drug depot for sus- only improve current treatments but also
tained release and the development of enable successful targeting of more spe-
highly effective targeted therapies. Both cific antigens with lower expression in the
these fields of application are current- cancer cell (Eur. Polym. J., 2016, in press,
ly being explored and will lead to first DOI: 10.1016/j.eurpolymj.2016.09.052).
FDA-approved PAOx-based therapy to In all, the synergy of PAOx and suitable
date (Eur. Polym. J., 2016, in press, DOI: APIs and targeting units presents itself
10.1016/j.eurpolymj.2016.09.052). In par- as a great opportunity to develop a new
ticular, Serina therapeutics has developed generation of chemotherapeutics.
a polymer therapeutic for the treatment
of Parkinson’s disease that, when appro- Market 13
ved, will provide a major advancement in Since our technology is a technology
the field. In this work, PAOx was conjuga- platform for a wide variety of applica-
ted with multiple rotigotine units along tions it is not possible to give a speci-
the polymer chain via cleavable linkers fic market size or number of customers.
that release the drug in a controlled, pro- The total global oncology drug deliveryON COLOGY
LILLE
market was >$95 billion in 2014 domi- with 50 unique ADCs. Analysis expects
nated by 5 major cancer drug manufac- the overall ADC-market to be worth $10
turers (Roche, Novartis, Eli Lilly, J&J and billion annually by 2024 with 7-10 new
Merck) together having a market share > commercial launches. PAOx-technolo-
75%. Although the oral drug prescriptions gy allows higher DARs (Drug Antibody
are increasing, intravenous infusion drug Ratio) easily up to 10 or 20 drug units
delivery is expected to keep dominating per antibody via conjugation on the poly-
the market. mer chain. We believe that PAOx has a
Nano vehicles (drug carriers) have be- high added value in the more advanced
come a hot topic of research in industry polymeric therapeutics as the side-chain
to make oral forms of drugs more effec- drug loading and easy tunability are strong
tive. The last decades of research are assets of PAOx that are lacking in current
focused on exploring the treatment of technologies.
cancer at its molecular level and polymer
Competitors
therapeutics is establishing as an innova-
tive and reliable approach for its ability to Polyethylene glycol (PEG) constitutes
create synergies with proteins, enzymes, the gold standard in polymer therapeu-
nanoparticles, liposomes and low mole- tics and, in addition to one commercial
cular weight drugs. In this regard, polye- product –Doxil-, several PEGylated anti-
thylene glycol (PEG) is the gold standard cancer drugs are currently undergoing
and has been effectively employed to clinical trials. However, PEG has some
achieve better therapeutic index of anti- important drawbacks and limitations.
cancer drugs: this includes PEGylated PEG can only be functionalized at the
protein or antibody fragments, PEGyla- chain ends, highly limiting its capacity
ted cytokines, PEGylated low molecular as drug carrier (J. Control. Release, 2008,
weight anticancer drugs, PEGylated na- 25, 87-95). This feature constrains PEG
noparticles, PEGylated smart polymers, mainly to micellar systems and prevents
and PEGylated polymeric micelles. The its broader application in polymer thera-
global PEG-market has growth expecta- peutics and antibody-drug conjugates.
tions towards $16 billion in 2020 to $27 PEG has also limitations in the develop-
billion in 2030. We believe PAOx has the ment of the so-called smart or stimuli-
potential to take a considerable share of responsive systems. Developing novel
this market in the future, especially as thermoresponsive systems based on
it can open new development avenues PEG is not possible unless it is coupled to
unattainable by PEG, but only from the other thermoresponsive polymers, such
moment it receives FDA approval. as low temperature-sensitive liposomes,
In the war against cancer, Antibody Drug introducing undesirable complexity in the
Conjugates will be a game changer. system.
14 At present, two ADCs (Adcetris® and Kad- Most importantly, the observation
cyla®) are on the market. Stimulated by of anti-PEG antibodies in 25% of the
these successful examples, the number of population never treated with PEG, due to
companies entering the field of ADC the- its ubiquity in cosmetics and food addi-
rapeutics has risen enormously. Currently tives, constitutes a risk to the efficacy of
there are over 200 ongoing clinical trials future PEG-based therapies (Cancer, 2007,ON COLOGY
LILLE
110, 103-111). research projects. For instance, PAOx for
Technical limitations aside, the profuse peptide and protein conjugation (e.g. PA-
number of patents protecting a variety Oxylation as alternative to PEGylation),
of compositions and applications of for instance conjugation of multiple small
PEG-based formulations hinders fur- molecules or combination therapy, for de-
ther research and development on novel velopment of polymeric micelle delivery
therapies. systems, for targeted delivery systems
The improved properties and tremen- and antibody drug conjugates with high
dous versatility of PAOx make them not loading via PAOx conjugation.
only a strong competitor for PEG-based Pharmaceutical companies, biotech or
bioconjugates but also suitable for new academic research teams that:
advances in cancer medicine. PAOx can • are looking for advanced drug delivery
fill the requirements in high drug loading, systems
responsiveness, controlled drug delivery, • want to enhance the retention time
novel drug formulations or next genera- and therapeutic potential of their thera-
tion antibody-drug-conjugation (Macro- peutics such as proteins, enzymes, small
mol. Rapid Commun. 2012, 33, 1648, Eur. molecules, liposomes or nanoparticles
Polym. J., 2016, in press, DOI: 10.1016/j. • are looking for alternatives to PEG
eurpolymj.2016.09.052). Although today and PEGylation (called PAOxylation or
PAOx has no FDA approval, the success POZylation)
of the ongoing clinical trials (Phase • are looking for delivery vehicles with
I, https://clinicaltrials.gov/ ct2/show/ higher drug loadings
NCT02579473) will certainly trigger • are looking for polymer linkers in ADC-
many companies to enter the PAOx field development in order to obtain high
and realize the enormous clinical benefits DARs
of targeted drug delivery. • are looking for smart (responsive) poly-
mers to develop new methodologies to
Partnership sought
treat cancer
We are seeking collaboration partners • are looking for a reliable source of high
(pharma, biotech, academic) to explore quality, ultra-defined poly(2-oxazoline)s
the potential of PAOx in cancer drug
delivery and beyond. We offer the design,
synthesis, characterization and study of
tailor made PAOx, specifically adjusted to
your API and drug delivery needs.
We are looking for potential licencing
opportunities and/or we can provide
ultra-defined PAOx material for your
15
GHENT UNIVERSITY
An Van Den Bulcke
a.vandenbulcke@ugent.beON COLOGY
Potent blocker of HER2 receptor
for treatment of metastatic breast cancer
Key words blood-brain barrier and, therefore, to
• HER2 target brain metastases.
• Breast Cancer
Applications
• Targeted Therapy
Treatment of breast cancer’s brain metas-
• Small Molecule
tases; Treatment of HER2+ breast cancers
• Brain Metastasis
Resistance; Potential treatment of other
Technology HER2+ cancers (ovarian, gastric, salivary,
The offer relates to two families of selec- neuroblastoma etc.).
tive compounds targeting a new HER2 in-
Market
tracellular domain for treatment of breast
1.67 million of new breast cancer
cancer’s brain metastases and drug resis-
diagnosed every year; about 20% HER2+
tant breast cancer. Two hits have been
HER2+ resistant breast cancer, HER2+
selected and one has been tested on
metastatic breast cancer.
orthotopic inoculation of human breast
cancer cell lines in a mouse model. Competitors
20 to 30% of breast cancers are related Two commercialized antibodies (trastu-
to an overexpression of HER2 and among zumab and pertuzumab) target HER2
them, 20 to 40% express p95HER2, a extracellular domain but cannot reach the
truncated version of the receptor belie- brain metastases, one commercialised
ved to play a role in cancer resistance. (lapatinib) and two in-clinical-develop-
Despite the benefits of the recent thera- ment (neratinib and ONT380) small mo-
pies targeting HER2 (Herceptin®, Perjeta® lecules target the tyrosine kinase domain.
and Tykerb®), a large part of patients’
relapses because of treatment failure due Partnership sought
to cancer resistance or toxicity issues. License: SME specialized in cancer
Notably, 20% to 50% of HER2 metas- therapy development; big pharma that
tatic breast cancer patients die of brain wishes to enrich its early asset pipeline.
metastases.
It was recently found that targeting a
new domain of HER2 prevents the acti-
vation of HER2 signalization and may
constitute a novel therapeutic approach.
The present offer proposes two com-
pound families targeting this domain and
inhibiting specifically HER2 downstream
signaling pathways in breast cancer.
The compounds are able to cross the
16
IDF INNOV
Davide D’Alia
dda@idfinnov.comON COLOGY
Kinase Inhibitors & Cancer
Key words Ongoing hit-to-lead optimization, target
• Non-canonical NF-k-B pathway validation and preclinical validation on
• Ezh2 melanoma tumors and metastases mouse
• Anti-programmed death-1 models.
• Metastasic melanoma
Applications
• Colorectal cancer
Treatment of Melanoma and Metastatic
Technology melanoma.
The project deals with multi-kinase inhibi- Treatment of other solid tumors including
tors having intrinsic anti-cancer activity and colorectal, pancreas and non-small cell lung
potentiating anti-PD1 immunotherapy for cancers.
cancer treatment, in particular melanomas.
Market
The hit compound (DMPB5) show same
effects than the ones induced by gene Single-agent antibodies blocking the PD-1
silencing of NF-kappa-B non-canonical pathway have already shown their worth.
pathway (siRNA): However, many patients still do not respond
• Restores in vitro a strong senescence in to immunotherapy.
melanoma (not dependent of the B-Raf By treating with multiple therapies with
mutations), colorectal, breast and lung can- mechanistically different modes of action,
cer cells by decreasing the transcription of a more powerful anticancer effect might
the oncogene EZH2 be obtained with minimized toxicity/side
• Triggers or potentiates in vitro and in vivo effects.
the tumor immune surveillance: increases Competitors
production of a key cytokine that attracts A lot of ongoing trials combining PD-1
immune cells (macrophages M1, dendritic inhibitors with other therapies: combina-
cells, T-cells and NK cells). tion of anti-CTLA-4 and anti-PD1 gives the
• Leads to a dramatic reduction in tumor best response rate but with significant side
size in vivo with complete regression in effects.
some cases when combined with anti-PD-1 Some 40 separate novel small molecules
treatments. being combined with anti-PD-1/PD-L1 anti-
Results: bodies across 44 active clinical trials (mela-
In vitro: high potency on melanoma cells, noma, metastatic melanoma, solid tumors,
metastatic melanoma primary cells from NSCLC, colorectal, pancreas). A particularly
patient, non-small cell lung and colorectal popular combo links immunotherapy with
cancer cells. a B-Raf and/or Mek inhibitor: Novartis’s
In vivo activity at 10mg/kg, i.p., on colorec- marketed Tafinlar® and Mekinist®, Roche/
tal cancer cells injected subcutaneously Exelixis’s Zelboraf® and cobimetinib, and
into syngeneic mice; greater activity for AstraZeneca/Array’s selumetinib.
combination DMBP5/PD-1.
No clinical signs of preliminary toxicity in Partnership sought 17
mice treated with DMBP5. We are currently looking for an industrial
partner interested for licensing-in the tech-
SATT SUD-EST nology and/or R&D collaboration (possible
Rémi Picard co-funding): Pharmaceutical companies
remi.picard@sattse.com and Biotechs.ON COLOGY
LILLE
Small molecule lead compounds for colorectal
cancer treatment through TNIK modulation
Key words TNIK is involved in other type of tumor,
• Colorectal cancer treatment including pancreatic cancer, the expan-
• TNIK(Traf2- and Nck-Interacting sion of indication is also possible.
Kinase) modulator Also, recent research results suggest that
• Cancer stemnee by prosthetic inhibition of TNIK activity,
one can achieve tumor formation pre-
Technology
vention. Thus, a well-optimized TNIK
KY-08341 and closely related analogues inhibitor with excellent safety profile
are Novel TNIK modulators w/ excellent can serve as a tumor preventive agent
biochemical efficacy, good in vivo effi- for colorectal cancer, especially patients
cacy and profile. The team led by Dr. with polyps. Besides these applications,
Hyuk Lee of KRICT and Dr. Sang Joon TNIK inhibitors can be developed as
Shin of Yonsei Univ. Hospital has disco- EMT modulators for tumor metastasis
vered a series of small molecules that can blocking. Recent studies suggest that
potently inhibit the activity of TNIK (IC50 by inhibiting TNIK, the TGF- ß mediated
value of less than 10 nM). The binding EMT phenomenon can be down-regula-
mode of these compounds to TNIK is ted. Thus, KRICT/Yonsei TNIK modulators
confirmed by X-ray crystallography stu- can be applied as an EMT modulation for
dies. These compounds can inhibit the cancer treatment.
activity of TNIK in colorectal cancer cells
and also inhibit the growth of colorec- Market
tal cancer cell line such as SW480 and The total market size for colorectal can-
SW620. These TNIK inhibitors also can cer treatment is estimated to be about
show synergistic effects when combined 7 billion USD annually by the end of
with traditional colorectal cancer treat- 2014. The market is slowly but conti-
ments, such as Irinotecan. In mice xeno- nuously growing with CAGR of 1.3% and
graft experiments with subcutaneously is expected to grow further. Due to the
injected SW620 colorectal cancer cells, fact that gradual increase of patients is
KY-08331, a lead compound for TNIK expected due to the change of life style,
inhibition, has shown strong growth including the increased uptake of red
inhibition as a single treatment or com- meats, the market is expected to grow
bination with Irinotecan. KRICT/Yonsei gradually also. The specific sub-segment
Univ. Hospital TNIK modulators possess for the application of TNIK inhibitor is the
good drug-like profiles. Most of the com- treatment of 4th grade colorectal cancer
pounds possess small molecular weight patients. The targeted agents, Bevacizu-
(270 – 350), sparing rooms for further mab, Cetuximab, Regorafenib, are also
optimization. used to treat 4th grade colorectal cancer
patients, which is about 11% of the total
18 Applications
colorectal cancer patients (however, the
The primary application of TNIK modula- market portion of these patients are as
tors is to treat colorectal cancer. As a Wnt high as 80% of total colorectal cancer
signal blocker, TNIK inhibitors can find treatment market, due to the high price
applicatins in the treatment of colorec- of novel drugs). For these patients, the
tal cancer treatment. Additionally, since development of targeted therapeuticsON COLOGY
LILLE
or immunotherapy is very hard due to Partnership sought
several reasons. Thus, the development of KRICT and Yonsei Univ. Hospital are
TNIK inhibitor is a unique chance that can now looking for a pharma or a biotech
meet patients’ unmet needs and market partner for the licensing out of TNIK modu-
needs at the same time. Combining these lator technology. Most preferred form of
information, one can conclude that the partnership is to license out the entire
estimated value of TNIK inhibitor market technology. However, collaborative
might reach billion USD market. research is also possible.
Pharmaceutical company, Biotech
Competitors venture with preclinical/clinical develop-
ment capacity.
The most prominent potential market
competitors are other modulators of Wnt
signalling pathway. Inhibitors modulating
many other components of Wnt pathway
are now being developed. However, as
described above, TNIK inhibitor has a
merit of being down-stream modulator
that can overcome potential resistance
problems and potential expansion of ap-
plication. Other targeted therapeutics or
immunotherapies can be other competi-
tors. However, since most of the previous
approach to treat colorectal cancer using
targeted therapeutics have failed and it
is very difficult to find target oncogenes
detected in a significant number of pa-
tients, the potential competition from tar-
geted therapeutics will be not so high. In
addition, it is expected that only minority
(ON COLOGY
ProNGF: New target to counter resistance
mechanisms in breast cancer
Key words Competitors
• Chemotherapy Tyrosine Kinases specific
• Resistance • Medimmune (main competitor)
• Companion Test • Cephalon (K252A Þ TEVA)
• Astra Zeneca
Technology
• Novartis
The proposed technology can overcome • Roche
the development of resistance to treat-
ment in the case of breast cancer therapy Partnership sought
failure (30% of cases) by blocking a newly License or Cooperation: Biotech
identified tumor escape. or Pharma.
This treatment strategy could be applied
to other types of cancers:
• ENT
• Prostate
A companion test was developed to
orient and monitor treatment.
Applications
Treatment of Breast Cancer
Potential treatment of other cancers
(ENT, prostate...)
Companion test on different types of
cancers
Market
Target Market: Monoclonal Antibodies
Market Size: ~60 Billion Dollars with a
trend of high growing
Some of these monoclonal antibodies
can generate a turnover of 7 billion
dollars per a year…
20
SATT NORD
François-Xavier Denimal
francois-xavier.denimal@sattnord.frON COLOGY
Dual PI3K and mTOR inhibitors
as promising drugs to treat cancer
Key words Applications
• Antitumoral activity Main therapeutic applications:
• Dual Inhibitors • Solid Cancer: Colorectal cancer, Renal
• Library of small molecules Cell Carcinoma, Breast Cancer including
Triple Negative Breast Cancer (TNBC),
Technology
brain cancer, lung and ovarian cancer,
The phosphatidylinositol-3-kinase
• Hematologic Cancer: Through our enzy-
(PI3K)/Akt and the mammalian target of
matic assay, some of our inhibitors exhibit
rapamycin (mTOR) signaling pathways
better nanomolar range inhibition toward
are both crucial to many aspects of cell
PI3Kŏ isoform against four clinical stage
growth and survival, in physiological
molecules.
as well as in pathological conditions.
Alternative applications:
The PI3K/Akt pathway is a key regulator
• Anti-inflammatory treatment some of
of survival during cellular stress. Since
our molecules have nanomolar range
tumors exist in an intrinsically stressful
inhibition of PI3Kß and PI3Kŏ (systemic
environment, the role of this pathway in
lupus erythematous, rheumatoid arthri-
cancer appears
tis, allergic asthma, cardiovascular and
to be crucial.
systemic anaphylaxis),
Synthesis, and screening of dual PI3K/
• Fibroadipose hyperplasia, an orphan
mTOR inhibitors have been used to
disease caused by somatic activating
create a portfolio of small molecules with:
mutations in PIK3CA.
• Novel and IP protected family of
compounds: They have both PI3K and Market
mTOR targets. This combined activity The two main addressed markets are the
should lead to a strongest inhibition of triple negative breast cancer and colorec-
the whole PI3K/Akt/mTOR pathway, tal cancer treatments based on no avai-
• Optimized synthesis, lable very efficient solution on the market
• Nanomolar range of enzymatic and and the positive results of our product for
cellular activities exhibiting specifity on the first one and the high rate of tumor
both targets (PI3K and mTOR) with an regression of our lead for the second one.
acceptable kinase selectivity profile,
• A wide spectrum of indication, Competitors
• Low toxicity and good stability relative Pharma companies.
to compounds under clinical develop-
Partnership sought
ment,
• Proven in vivo efficacy versus molecule Available for licensing out: pharma
under clinical development. companies.
21
SATT GRAND CENTRE
Magali Granger
magali.granger@sattgc.comN EUROLOGY - C A R DI O LO GY
Preventing neuropathic pain induced
by mastectomy
Key words better well-being of patients for at least
• Neuropathic pain six months after treatment suggests
• Mastectomy that Memantine could be an interesting
• Memantine therapeutic option to diminish the burden
of breast cancer therapy.
Technology In conclusion, this innovative trial shows
The product is a repositioning of Meman- for the first time that pre-surgery Meman-
tine, a NMDA receptor antagonist usually tine may prevent the occurrence of pain
prescribed for Alzheimer’s disease, as a three months after mastectomy, and sug-
preventing solution to avoid neuropathic gests that it may also reduce dysesthesia
pain following mastectomy. and paresthesia induced by chemothe-
Neuropathic pain following surgical treat- rapy.
ment for breast cancer with or without
chemotherapy is a clinical burden and Applications
patients frequently report cognitive, By definition pain is highly unpleasant
emotional and quality of life impairment. and often motivates individuals to seek
A preclinical study recently showed that healthcare. Patients suffering from breast
Memantine administered before surgery cancer sometimes undergo mastectomy
may prevent neuropathic pain develop- but this surgical treatment may induce
ment and cognitive dysfunction. A clinical neuropathic pain. In the course of breast
trial with a translational approach sup- surgery, 20–68% of patients report bur-
ports these preclinical results. Indeed, a ning and shooting pain with numbness
randomized, pilot clinical trial included and pressure sensation. Mastectomy is
40 women undergoing mastectomy in known to generate neuropathic pain
the Oncology Department, University in 30.7% patients at 3 months, 25.7%
Hospital, Clermont-Ferrand, France. at 6 months, 42% at 5 years and 37%
Memantine (5 to 20mg/ day; n=20) or at 9 years post-mastectomy. Cancer
placebo (n=20) was administered for four chemotherapy is also well known to
weeks starting two weeks before surgery. induce pain with neuropathic characte-
The primary endpoint was pain intensity ristics in 25–50% of patients. However,
measured on a (0–10) numerical rating a sizeable proportion of these patients
scale at three months post-mastecto- with neuropathic pain go untreated, even
my. Compared with placebo, patients though the majority of them report the
receiving Memantine showed at three pain to their physician.
months a significant reduction in post- Our technology represents a promising
mastectomy pain intensity, less rescue to and innovative strategy for the thera-
analgesic and a better emotional state. peutic management of post-surgical and
An improvement of pain symptoms in- chemotherapic neuropathic pains that
22 duced by cancer chemotherapy was also have currently no disease-modifying or
reported. Data show the beneficial effect curative therapies. It offers an analgesic
of Memantine to prevent post-mastec- solution that is specifically effective in
tomy pain development and to diminish controlling the key disturbance of neuro-
chemotherapy-induced pain symptoms. pathic pain symptoms induced by breast
The lesser analgesic consumption and surgery.N EUROLOGY - C A R DI O LO GY
Market the neuropathy market in recent years by
According to the World Health Orga- introducing novel drugs in these classes
nization (WHO), breast cancer is the that improve upon the safety and efficacy
second most common cancer in the profile of predecessors in the same class
world and the most common cancer in (Pfizer’s Lyrica and Eli Lilly’s Cymbalta),
women worldwide, accounting for 16% or by offering a convenient drug deli-
of all female cancers, making the disease very system (Endo Health’s Lidoderm).
exceedingly prevalent. In 2013, the 6 ma- Although many of the available drugs
jor markets (France, Germany, Italy, Spain, offer some degree of efficacy in terms
and UK, US, Japan and China) had 853 of pain relief, there still remains vast room
902 diagnosed incident cases of breast for improvement in efficacy, safety, drug
cancer. The US had the highest number delivery, and dosing convenience.
of cases at 260 971, and accounted for Furthermore, all three market-leading
30.56% of all diagnosed incident cases drugs will lose patent protection over
in these markets. The total number the forecast period and will face intense
of diagnosed incident cases of breast generic erosion. Future players will also
cancer in the 8 major markets is expected join the market like Daiichi-Sankyo and
to grow to 1,214,776 cases in 2023 at the Convergence. There are seven promising
rate of 4.23% per year. All markets will drugs in clinical development for neuro-
see a substantial increase in the number pathies, which are project to enter the
of diagnosed incident cases. market before the end of the forecast
The target market of our product period in 2022, and will lead to some
could be the same as the breast cancer growth in a market that will be largely
market according to that neuropathic generic. Sales of these pipeline drugs
pain following surgical treatment for will account for 23.8% of global neuro-
breast cancer with or without chemo- pathy sales in 2022. At the moment, these
therapy is a clinical burden and patients are all drugs in Phase II and Phase III of
frequently report cognitive, emotional development for post-diabetic neuropa-
and quality of life impairment. thies, post herpetic neuralgia, and trige-
minal neuropathy but not post-surgery-
Competitors
induced neuropathic pain.
The main classes of drugs used in the
treatment of neuropathic pain are widely Partnership sought
available under generic form. Licensing out: Pharma
However, some big pharmas (Pfizer,
Eli Lilly, and Endo Health) have esta-
blished themselves as the key players in
23
SATT GRAND CENTRE
Magali Granger
magali.granger@sattgc.comN EUROLOGY - C A R DI O LO GY
Neuropain and chronic pain prevention
Key words • Post-operative pain treatment
• Chronic pain • Early diagnosis of risk for developing
• Inflammatory pain post-operative chronic pains
• Neuropathic pain
Market
• Genetic marker
Neuropathic pain (NP) affects about
• Companion test
19% of the world’s population. Although
• Peripheral nervous system
there are several drugs in the NP pipeline,
• Analgesic drugs
what is still lacking is the ability to match
• Protein
patients to these once they are on the
Technology market.
A first-in-class treatment for preventing, Post-operative pain market is estimated
alleviating or treating neuropathic and at $ 21.6 billion in 2022. Overall incidence
inflammatory pains (possible associa- of moderate to severe Post-Operative
tion with very low amount of pregaba- Chronic Pain after major surgery: 30%
lin) using the endogenous TAFA4 protein.
Competitors
TAFA4 is a human endogenous short pro-
tein (100 amino acids) with high affinity Existing classes of NP drugs contains
for PRF-1 on macrophages. The binding several established drugs that are widely
of TAFA4 to peripheral nervous system available in generic form. There are se-
(dorsal root ganglia) reverses pain more veral products in development that may
than 4 hours after injection. TAFA 4 is address some of the unmet clinical needs,
an original endogenous molecule (not but the level of unmet need will still be
yet investigated) and doesn’t’ need to relatively high (safety, efficacy). Clini-
cross blood brain barrier for function. cal trials: 40% of patients get only 30%
No observed adverse effects in vivo and pain relief. High demand of drugs with
no immunogenicity. novel mechanisms of action. No sensory
markers associated with particular pa-
TAFA4 has strong analgesic effects
thophysiological pain mechanisms are
against carrageenan- and Spared Nerve
available.
Injury-induced mechanical hypersensiti-
vity in mice, similar to Pregabalin with a Partnership sought
100 fold lower dose. We are currently looking for an indus-
Researchers develop also a companion trial partner interested for licensing-in
test based on the first genetic biomarker the technology and/or R&D collaboration
predicting chronic pains occurring after (possible co-funding): Pharmaceutical
surgery. companies and biotech.
Applications
• Neuropathic pain treatment
• Inflammatory pain treatment
24
SATT SUD-EST
Rémi Picard
remi.picard@sattse.comN EUROLOGY - C A R DI O LO GY
DIVE: Dopaminergic stimulation by
continuous intracerebro ventricular delivery
of anaerobic dopamine in Parkinson’s disease
Key words Partnership sought
• Anaerobic Dopamine License: Pharmaceutical Company in the
• Parkinson’s disease field of CNS and specially Parkinson
• Intracerebro ventricular delivery
Technology
New therapeutic concept for Parkinson’s
disease based upon a continuous intra-
ventricular administration of a specific
dopamine delivered in the third ventricle
directly close to bilateral striatum.
Applications
Parkinson’s disease.
Market
6.5 million people worldwide suffer from
Parkinson’s disease representing 1.5% of
the population over 65 years, the class
of the most affected age group being
80-84 years old.
The global market for treatment of
Parkinson’s disease is estimated at
2,751 billion. All patients are not eligible
for treatment with DIVE technology, their
number is estimated at 14 000 per year
worldwide. Considering the cost of the
pump and the cost of dopamine, the
market at 10 years could be estimated at
634 million euros.
Competitors
L-Dopa, apomorphine pump, lévodopa +
carbidopa, subthalamic stimulation.
25
SATT NORD
François-Xavier Denimal
francois-xavier.denimal@sattnord.frN EUROLOGY - C A R DI O LO GY
LILLE
Biomarkers for the diagnosis of dementia
with Lewy bodies
Key words can be applied for the patients carrying
• Dementia with Lewy bodies those alleles or genotypes responsible
• Diagnosis for that phenotype.
• SNPs and mRNA transcripts
Applications
Technology Dementia with Lewy bodies (DLB)
“Biomarker 1” consists of the determi- belongs together with Parkinson’s di-
nation of various transcripts of certain sease (PD) to the group of Lewy body
gene (gene A) in blood of patients with diseases and is after Alzheimer disease
possible DLB. For this purpose, blood is (AD) the second cause of dementia. DLB
collected in PAXgene blood RNA tubes. is characterized by an aggressive disease
After RNA purification and reverse trans- course and overall elevated mortality
cription, relative expression levels are de- and survival of 6 years. These facts turn
termined by real-time PCR. Diminished an early and accurate diagnosis of this
levels of at least two of the transcripts will disease to a need.
be indicative for DLB, allowing its correct Due to overlapping features between
diagnosis. DLB and AD, the clinical diagnosis of DLB
“Biomarker 2” consists of the determi- is still very difficult to achieve and the
nation of 6 polymorphic sites within the use of complementary diagnostic tools
regulatory region of another gene (gene such as neuroimaging techniques are too
B). A defined genotype combination will expensive for their routine use.
be consistent with the diagnosis of those Moreover, due to DLB heterogeneity,
DLB patients who show diminished levels different subgroups develop disease by
of certain protein in the brain. their own molecular mechanisms each.
Diminished levels of “Biomarker 1” may Thus more than one biomarker (one
reflect increased protein aggregation for each of the various subgroups) will
rates in the brain that represent a charac- be needed to identify all DLB patients.
teristic feature for the very first stages of Only such working strategies will permit
Lewy body disorders. Signaling to the pe- to tackle the challenges of personalized
riphery (e.g. through miRNAs) may result medicine.
in the diminution of gene A transcripts in To address both, heterogeneity of the
blood. By substrate exhaustion at later disease on one hand and difficult dia-
disease stages, protein aggregation rate gnosis on the other, we have developed
slows down cancelling the signaling and two different biomarkers for the early
normalizing mRNA expression levels. and differential diagnosis of DLB that will
About 40% of DLB patient develop substantially improve clinical diagnosis
disease as a result of diminished le- success.
26 vels of certain protein in the brain. We
Market
have identified six polymorphic sites as
Estimation of potential direct avec in-
“Biomarker 2” within the regulatory re-
direct beneficiaries: The national mar-
gion of gene B, responsible for this dimi-
ket includes about 30.000 new DLB
nution. Future treatments directed to the
cases per year, and about 150.000 new
increase those protein levels in the brain
AD cases. Worldwide, in 2016 aboutN EUROLOGY - C A R DI O LO GY
LILLE
46,8 million people lived with dementia.
Of them, around 60% (28,1 million) had
AD and 20% (9,35 million) DLB. Since inci-
dence of both AD and DLB increases with
age, being of 10-15% for AD and of 2-3%
for DLB for people aged over 65 years
and of 30% for AD and of 10% for DLB
for people over 80 years. With ageing
of the world population, these numbers
are raising constantly and with improving
prevention and health care, mortality by
conditions like HIV and heart disease is
decreasing. In contrast, AD is becoming
a more common cause of death and has
increased in USA by 68% between 2000
and 2010.
Partnership sought
We are open to any kind of partnership
with pharmaceutical and biotech industry
that lead us to achieve final development
and/or for licensing out the technology.
27
Institut de Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP)
Katrin Beyer
kbeyer@igtp.catN EUROLOGY - C A R DI O LO GY
New generation of neuroprotectants:
an original way to treat and prevent acute
and chronic neurological diseases
Key words mic strokes in main markets is estimated
• Acute ischemic Stroke at 1 500 000 (Datamonitor).
• Traumatic brain injury • Post-traumatic epilepsy
• Neuroprotectants Traumatic brain injury (TBI) is one of
Technology the major causes of acquired epilepsy
today. In the United States alone approxi-
TThe team has developped a new ge-
mately 1.4 million people sustain a TBI
neration of neuroprotectants that are
each year, 200 000 are hospitalized and
selective kinase inhibitors (CDK inhibi-
50 000 die. TBI is estimated to cause
tors) to treat and prevent acute and chro-
10-20% of all symptomatic epilepsy. A
nic neurological diseases, such as stroke,
clear relationship exists between the se-
traumatic brain injury, post-traumatic epi-
verity of injury and the likelihood of deve-
lepsy, and amyotrophic lateral sclerosis
loping epilepsy. The 30-year cumulative
(ALS). Misregulation of CDKs appears
incidence of epilepsy is 2.3% for mild,
to play a key role within the molecular
4.2% for moderate, and 16.7% for severe
pathways leading to neuronal death. It
TBI1.
is the first molecule which are able to
modulate specific CDKs in the brain. • Amyotrophic lateral sclerosis (ALS)
During an acute neuronal damage, two Amyotrophic lateral sclerosis is a pro-
deleterious mechanisms take place: gressive disease of the nervous system.
neuronal death (astrocytes and oligoden- ALS occurs when specific nerve cells in
drocytes) and inflammation (proliferation the brain and spinal cord that control vo-
of immune and microglial cells). These luntary movement gradually deteriorate.
two mechanisms participate in the da- The loss of these so-called motor neurons
mage of cerebral tissue. Similar mecha- causes the muscles under their control
nisms are known to be involved in chronic to weaken and waste away, leading to
neurological damage. paralysis and death.
The candidates target simultaneously • Niemann-Pick disease
degenerating and proliferating cells. Niemann–Pick diseases are inherited in
an autosomal recessive pattern. They are
Applications
genetic diseases which are classified in
The compound could be used in different
a subgroup of LSDs called sphingolipi-
therapeutic domains:
doses or lipid storage disorders, in which
• Acute ischemic Stroke harmful quantities of lipid, accumulate
Stroke is classified into two major cate- in the spleen, liver, lungs, bone marrow,
gories: ischemic stroke (90%) and hae- and brain. Sphingomyelin accumulation
28 morrhagic stroke (10%). Risk factors in the central nervous system results in
are age (75% of strokes occur after unsteady gait, slurring of speech and
65), hypertension, smoking, diabetes dysphagia. Abnormal posturing of the
and hypercholesterolemia. In western limbs, trunk and face and upper brainstem
countries incidence of ischemic stroke is disease results in impaired voluntary
120/100 000 and the number of ische- rapid eye movements. More widespreadN EUROLOGY - C A R DI O LO GY
disease involving the cerebral cortex and leading cause of disability for adults and
subcortical structures is responsible up to 50% of surviving patients remain
for gradual loss of intellectual abilities disabled. In the US, the cost associated
causing dementia and seizures. with stroke has been estimated at 58MM$
in 2006 (AHA).
Market
The global acute ischemic stroke
Stroke is classified into two major
therapeutics market was 250 M$ in
categories: ischemic stroke (90%) and
2010 and is expected to have growth of
hemorrhagic stroke (10%). Risk factors
16 % over the next eight years to reach
are age (75% of strokes occur after
approximately $880m by 2018. This
65), hypertension, smoking, diabetes
low figure considering the incidence
and hypercholesterolemia. In western
of the disease reflects the absence of
countries incidence of ischemic stroke is
efficacious drugs. Given themedical
120/100 000 and the number of ischemic
needs, a successful neuroprotective agent
strokes in main markets is estimated at
would open the market and rapidly reach
1 500 000 (Datamonitor).
multiMM$ sales.
Stroke is the second leading cause of
death in the western world. In 2008, the Competitors
World Stroke Congress reported that Alteplase (tPA, Activase®, Genentech)
20 million stroke events occur globally
Partnership sought
each year and account for 5.7 million
deaths. 10% of ischemic stroke leads to License: Big Pharma
death within 30 days and 50% in the next
6 months. Stroke is also the first
29
OUEST VALORISATION
Hervé Le Deit
herve.le-deit@ouest-valorisation.frN EUROLOGY - C A R DI O LO GY
Preventing neuropathic pain induced
by chemotherapy
Key words allodynia in rats. Interestingly, Donepezil
• Neuropathic pain also reduces the depression-like pheno-
• Oxaliplatin type induced by oxaliplatin.
• Donepezil Intracerebral microdialysis revealed
a lower level of acetylcholine in the
Technology
posterior insular cortex (pIC) of oxali-
Our product is a repositioning of Done- platin-treated rats, which was signifi-
pezil, a centrally active acetylcholineste- cantly increased by Donepezil. Finally,
rase inhibitor prescribed in Alzheimer’s the analgesic effect of Donepezil was
disease, as a solution to prevent and cure markedly reduced by a microinjection of
neuropathic pains induced by platinum the M2 antagonist, methoctramine, wit-
compounds used in chemotherapies. hin the pIC in both oxaliplatin-treated
Chemotherapy-induced peripheral rats and spared nerve injury rats. These
neuropathy (CIPN) represents a dose findings highlight the crucial role of corti-
limiting adverse effect of specific neuro- cal cholinergic neurotransmission as a cri-
toxic anticancer drugs such as platinum tical mechanism of neuropathic pain, and
salts for which no preventive or curative suggest that targeting insular M2 recep-
treatment are available yet. Oxalipla- tors using central cholinomimetics could
tin, a platinum compound used in the be used for neuropathic pain treatment.
treatment of several solid tumors such
as colorectal cancer, induces an acute Applications
sensory neuropathy which can lead to Our technology provides a promising and
limit dosage, to changes in treatment to innovative strategy for the therapeutic
non-neurotoxic agents with the risk of management of neuropathic pain that
limiting the effective clinical outcome. has currently no disease-modifying or
A chronic cumulative sensorimotor neu- curative therapies. It offers an analgesic
ropathy is also frequently developed solution that is specifically effective in
and greatly alters the quality of life of controlling the key disturbance of neu-
survivors. Hence, a better understanding ropathic pain symptoms induced by
of its pathophysiological mechanisms is chemotherapies responsible for incapa-
necessary to identify new pharmacolo- citating and dose-limiting neurotoxicity.
gical targets. Repeated oxaliplatin admi- Donepezil regimen resulted in significant
nistration in a mouse model of chronic reduction of overall neuropathic pain
oxaliplatin-induced peripheral neuropa- symptom and anxiety depression for
thy, induces both cephalic and extrace- both platinum salts, taxanes and Vinca
phalic mechanical and cold hypersensi- alkaloids. The most targeted cancers are
tivity as soon as after the first injection, advanced and metastatic colorectal can-
as well as delayed sensorimotor deficits cers but could be also ovarian, prostate
30 and a depression-like phenotype. Syste- and head and neck cancers. Donepezil
mic treatment with Donepezil (Aricept®), repositioning is highly attractive because
a centrally active acetylcholinesterase of its potential to speed up the process of
inhibitor, prevents and reversed both drug development, hence reducing costs
sensory and motor deficits induced by in addition to providing new treatments
oxaliplatin such as cold and mechanical for unmet pain needs.You can also read
