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Anyone following OSE (OSE.PA) ? I was in since the CD47 deal with Boehringer. They also seem to have an interesting SAR-COV-2 vaccine
CoVepiT is a SARS-COV-2 vaccine activating T cell defenses through CD8 T-cell multi-epitope* responses.
CoVepiT epitopes are selected from 11 viral protein targets and designed to cover all initial and new emerging SARS-CoV-2 variants.
CoVepiT, as second-generation vaccine, potentially provides long-term cellular immunity with memory T cells.
https://ose-immuno.com/wp-content/uploads/2021/04/EN_210104_CoVepiT-Ph1_VF.pdf
Roughly 60% infected aboard the French aircraft carrier https://en.wikipedia.org/wiki/COVID-19_pandemic_on_Charles_de_Gaulle
210144 (and counting) tests were performed in South Korea
CLLS Update on UCART 19 from ebmt2018
OS10-4 - FIRST-IN-HUMAN STUDY WITH UCART19, AN ALLOGENEIC ANTI-CD19 CAR T-CELL PRODUCT, IN HIGH RISK ADULT PATIENTS WITH CD19+ R/R B-CELL ALL: PRELIMINARY RESULTS OF CALM STUDY
Charlotte Graham1,2, Deborah Yallop1, Agnieszka Jozwik2, Piers Patten1,2, Alan Dunlop1, Rose Ellard1, Orla Stewart1, Victoria Potter1, Victoria Metaxa1, Shireen Kassam1, Farzin Farzaneh2, Stephen Devereux1, Antonio Pagliuca1, Amina Zinai3, Florence Binlich3, Sandra Dupouy3, Anne Philippe3, Svetlana Balandraud3, Camille Poirot3, Flavie Simon3, Cyril Konto4, Candy Bermingham4, Ghulam Mufti1,2, Reuben Benjamin1,2 1King's College Hospital NHS Foundation Trust, London, United Kingdom; 2King's College London, London, United Kingdom; 3Institut de Recherches Internationales Servier, Paris, France; 4Pfizer Inc, San Francisco, CA, United States Background: UCART19 (anti-CD19 scFv- 41BB- CD3?) is a genetically modified CAR T-cell product manufactured from healthy donor cells, in which TRAC and CD52 genes have been knocked out to allow its administration in non-HLA matched patients. We report preliminary results of the CALM trial, a first-in-human phase 1 dose finding study of UCART19 in adult patients with relapsed/refractory (R/R) B-ALL.
Methods: Adult R/R B-ALL patients (age ≥16 years) with morphological disease or minimal residual disease (MRD) level ≥1x10-3 and who had exhausted available treatment options were eligible for the study. A lymphodepletion regimen combining cyclophosphamide and fludarabine, with or without alemtuzumab was administered prior to UCART19 single dose infusion. Safety and anti-leukemic activity were assessed as primary and secondary objectives, respectively. Exploratory objectives included evaluation of the proportion of patients who proceeded to a transplant as well as the time to transplant following UCART19 treatment.
Results: As of early December 2017, 7 patients have been treated in the dose escalation phase (6 at dose level 1 (DL1) and 1 at DL2 with 6x106 and 8x107 UCART19 respectively). Median age was 23 years (range 18-49). Patients received a median of 4 prior treatment lines (range 1-5). 6 patients had undergone a previous MUD allogeneic SCT (allo-SCT) and had relapsed at a median of 7.8 months post transplant (range 4-11).
All patients experienced cytokine release syndrome (CRS): 1 G1, 5 G2 and 1 G4. The patient with CRS G4 also developed neutropenic sepsis leading to multiple organ failure and death at Day(D)15. Tociluzumab was administered in 4/7 patients. Median time to onset of CRS was 8 days (range 5-12). CRS correlated with serum cytokine increase (IL-6; IL-10 and IFNg) and UCART19 expansion in blood. One patient developed a G1 skin GvHD. G1 neurotoxicity was observed in 2 patients. Asymptomatic viral reactivations (CMV and/or adenovirus) were seen in 3 patients and resolved with antiviral therapy. 3/7 patients developed prolonged G4 cytopenia.
5 out of 7 patients achieved molecular remission (MRD-ve) at D28, 1 had refractory disease at D28 and 1 died at D15. Of the 5 patients who achieved MRD negativity, 1 relapsed with CD19+ve disease at D61, received a 2nd identical dose of UCART19 and became MRD-ve again. All 5 patients who achieved MRD negativity proceeded to a subsequent allo-SCT at a median of 66 days (range 51-140) post UCART19 treatment with all but one transplanted with a different MUD donor.
Post allo-SCT, 4 patients remain alive and 1 early death occurred at D17 from transplant related infections. 2/4 patients became MRD+ve at 52 and 100 days respectively but reverted to MRD negativity following withdrawal of immunosuppression. Currently 3 patients remain in MRD-ve remission and 1 relapsed with CD19+ extramedullary disease.
Conclusions: Allogeneic CAR-T product UCART19 shows an acceptable safety profile and promising results with 5 over 7 patients achieving molecular remission and proceeding to a second stem cell transplant. Recruitment is on-going at DL2.
Clinical Trial Registry: NCT 02746952
OS18-5 - GENE-EDITED ALLOGENEIC CAR19 T CELLS (UCART19) INDUCE MOLECULAR REMISSION AHEAD OF ALLO-SCT IN HIGH RISK PEDIATRIC PATIENTS WITH CD19+ RELAPSED/REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA
Waseem Qasim1, Oana Ciocarlie1, Stuart Adams1, Sarah Inglott1, Claire Murphy1, Christine Rivat1, Gary Wright1, Giovanna Lucchini1, Juliana Silva1, Kanchan Rao1, Amina Zinaï2, Florence Binlich2, Sandra Dupouy2, Jeanne Pauly2, Svetlana Balandraud2, Flavie Simon2, Cyril Konto3, Candy Bermingham3, Robert Chiesa1, Sujith Samarasinghe1, Havinder Hara1, Alayna Boyle1, Jan Chu1, Danielle Pinner1, Persis J Amrolia1, Ajay Vora1, Anupama Rao1, Philip Ancliffe1, Paul Veys1 1Great Ormond Street Hospital NHS Trust, London, United Kingdom; 2Institut de Recherches Internationales Servier, Suresnes, France; 3Pfizer Inc, San Francisco, CA, United States Background: UCART19 (anti-CD19 scFv- 41BB- CD3?) is a genetically modified CAR T-cell product manufactured from healthy donor cells, in which TRAC and CD52 genes have been disrupted to allow administration in non-HLA matched patients. Preliminary results of an ongoing Phase I study in CD19+ R/R B-ALL pediatric pts (PALL) are presented.
Methods: Pediatric pts (≥ 6 months to < 18 years) who had exhausted treatment options and exhibited morphological disease or minimal residual disease (MRD) ≥1x10-3 were lymphodepleted using a regimen comprising high-intensity fludarabine-cyclophosphamide, and alemtuzumab. A fixed dose of UCART19 (2x107 total cells or 1.1 to 2.3x106 cells/kg) in 4 different weight-bands was infused on Day 0. Safety and ability of UCART19 to achieve molecular remission at Day 28 were assessed as primary and secondary objectives, respectively.
Results: As of October 13 2017, 5 children (3 males and 2 females) between 10 months and 16.4 years have been treated. Of the 5 pts, two had previously undergone allo-SCT but had relapsed with CD19+ B-ALL. Prior to lymphodepletion, 4 patients exhibited < 10% blasts and 1 had 80% blasts, albeit with a hypoplastic marrow. All pts experienced reversible cytokine release syndrome (CRS) between D4-D8 (1 grade (G) 1, 3 G2, 1 G3). CRS G3 required 2 doses of tocilizumab. Acute skin GvHD G1 was confirmed by biopsy and recovered with topical steroids in one patient. Four children experienced viral reactivation (CMV, ADV, BK, Metapneumovirus) after lymphodepletion and 2/5 pts remained neutropenic by D28.
All patients achieved a CRi at D28-D42 with 5/5 confirmed MRD negative (< 0.01%) by flow cytometry and 3/5 MRD negative by PCR. All underwent a subsequent allo-SCT, between 49 and 62 days after UCART19 infusion with conditioning incorporating TBI (2-14.4Gy), fludarabine, +/- cyclophosphamide with or without ATG. All pts also received a single dose of rituximab, to target any remaining UCART19 cells. Two children relapsed 3 months after transplantation (one CD19- and one CD19+; both MRD positive by PCR prior to SCT), and died 7 and 8 months after UCART19 infusion, respectively. One patient died 2.5 months after MSD allo-SCT from transplant-related complications (thrombotic microangiopathy, BK hemorrhagic cystitis and nephritis). Two children remain in CR > 5 months post-transplant and continue to be monitored.
Conclusions: In addition to the two patients successfully treated under special access scheme before the trial and now followed for > 24 months, a further five children with high risk R/R B-ALL have been treated in this study with UCART19 before proceeding to allo-SCT. Preliminary safety data were within expectations, and 2/5 trial patients are in remission. The study is open and recruiting at multiple sites.
Clinical Trial Registry: NCT02808442
SAN takes ABLX for 45 euros
http://hugin.info/137912/R/2164257/832585.pdf
NVO & ABLX
Offer @EUR 30.5. Not enough says ABLX
http://ih.advfn.com/p.php?pid=nmona&article=76423840
CLLS, PFE, Servier PR on CALM and PALL studies. Nothing really new unless I am wrong, but I thing PFE and Servier did not issue PR previously
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an investigational allogeneic anti-CD19 CAR T-cell product, in adult and pediatric patients with relapsed or refractory (R/R) CD19-positive B-cell acute lymphoblastic leukemia (B-ALL). These first-in-human data demonstrated the safety and tolerability of UCART19, resulting in an 83% complete remission rate across the adult and pediatric patient population.
Results from the CALM (UCART19 in Advanced Lymphoid Malignancies) Trial
The CALM study (UCART19 in Advanced Lymphoid Malignancies) is an open label, dose-escalation study designed to evaluate the safety, tolerability and anti-leukemic activity of UCART19 in adult patients with R/R B-ALL. Five out seven patients treated achieved molecular remission at Day 28 post UCAR19. Molecular remission is defined by negative minimal residual disease (MRD). MRD is a measurement of the number of residual leukemic cells that remain after treatment.
“These early results for UCART19 are very encouraging both in terms of manageable safety and the impressive complete molecular remission rate in these hard-to-treat adult patients with R/R B-ALL,” said Reuben Benjamin, Principal Investigator of the CALM Study and Consultant Hematologist at King’s College Hospital, United Kingdom. “This first cohort explored a lower dose of UCART19 that is approximately one tenth of that used in most autologous CAR-T trials. These results support additional evaluation of UCART19 at varying doses.”
Only one Grade 1 cutaneous acute graft versus host disease (GvHD) occurred. No severe neurotoxicity was observed. Cytokine release syndromes (CRS) were mild and manageable except in one patient treated with UCART19 at the first dose level, who developed CRS Grade 4 and neutropenic sepsis leading to death at Day 15.
Results from the PALL (Pediatric Acute Lymphoblastic Leukemia) Trial
The PALL (Pediatric Acute Lymphoblastic Leukemia) study is a phase 1, open label study designed to evaluate the safety and ability of UCART19 to induce molecular remission defined by MRD negativity at Day 28 to enable allogeneic stem cell transplantation in pediatric patients with high-risk R/R B-ALL. Results showed all five children achieved MRD negativity, enabling them to proceed to allogeneic stem cell transplant. Only one Grade 1 cutaneous acute GvHD occurred. No severe neurotoxicity was observed. Cytokine release syndromes were mild in the majority of cases and were all manageable.
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You are fully right! The threshold must have been 12 years, which does not concern Mr. Jimenez.
Are you sure of that? I believe he left in 2010 and became CEO in 1999 or 2010. (I may be wrong)
At one point Novartis had bylaws putting an eight year threshold for a top management tenure. (Vasella did overstep by one or two years) Maybe it has something to do with this move ?
Not unhappy to see a MD coming back at the helm.
CLLS
CD123 study has started recruiting
NCT03190278
Lirilumab (IPH.PA) misses in AML
PR
ADOC.PA
Downgraded by analyst ODDO from 80 to 40. This follows an PR (Jan 19) where ADOC said they now intent to partner only Phase III projects.
CC today at 7:30PM
(see http://www.adocia.fr/WP/news-pressreleases/)
CLLS IND for UCART 123 in AML and BPDCN
PR
Pending regulatory clearance, Cellectis plans to initiate Phase 1 clinical trials in the first half of 2017.
The RAC committee meeting can be watched here https://videocast.nih.gov/Summary.asp?File=21061&bhcp=1%E2%80%A6
with the CLLS part starting at 52' and the very recommendations list at the very end.
CLLS
A webcast for French speakers
http://bit.ly/2fragCe
I believe this this a transfer done in December. Mr. Bastid already had the shares and transferred them from Belgium to Luxembourg. Tax regulation changed in Belgium January 1st.
L. Olanoff was also head of Clinical Research at Novartis while Exelon (rivastigmin) was being developed. If memory serves, he left well before the launch.
IPO expecting date is March 26th $36.83
http://www.nasdaq.com/markets/ipos/activity.aspx?tab=upcoming
http://www.nasdaq.com/markets/ipos/company/cellectis-sa-958510-77689
Not bad, PFE will pay for a big part of their early development, so they have some cushion with this.
This is a good map
http://www.centerforda.com/HepC2013b/HepMap.html
Indeed!
In its december 4th issue, the NEJM had an article on Crizotinib first line vs Chemo. The most common adverse events with crizotinib were vision disorders, diarrhea, nausea, and edema. Do we also have vision disorders AE with Briga ?
On the topic stem cell & heart failure
http://www.presstv.ir/Detail/2015/01/16/393403/Stemcell-therapy-works-for-patient
Here is the list for 2015 ( I believe the threshold is a market value > 1B at the end of the previous year)
A Accor
Aéroports De Paris (ADP)
Air France - KLM
Air Liquide
Alcatel-Lucent
Alstom
Altarea
Alten
Altran
Areva
Arkema
Artois
Atos
Axa
B Bic
BioMérieux
BNP Paribas
Boiron
Bolloré
Bourbon
Bouygues
Bureau Veritas
Burelle
C Capgemini
Carrefour
Casino
CFAO
CGG
Christian Dior
CIC
CNP Assurances
Coface
Colas
Compagnie du Cambodge
Crédit Agricole SA
D Danone
Dassault Aviation
Dassault Systèmes
E Edenred
EDF
Eiffage
Elior
Eramet
Essilor International
Euler Hermès Group
Eurazeo
Eurosic
Eutelsat Communications
F Faurecia
FFP
Fimalac
Financière de l'Odet
Foncière des Murs
Foncière des Régions
Foncière Lyonnaise
Fromageries Bel
G GazTransport Technigaz (GTT)
GDF Suez
Gecina
Groupe Eurotunnel
H Havas
Hermès International
I Icade
Iliad
Imerys
Ingenico
Ipsen
Ipsos
J JC Decaux
K Kering
Klépierre
Korian-Medica
L Lafarge
Lagardère
LDC
Legrand
Lisi
L'Oréal
LVMH
M M6 Metropole TV
Mercialys
Michelin
Moncey Financière
N Natixis
Neopost
Nexans
Nexity
Norbert Dentressangle
Numericable-SFR
O Orange
Orpea
P Paris-Orléans
Pernod-Ricard
Peugeot SA
Plastic Omnium
Publicis
R Rallye
Rémy Cointreau
Renault
Rexel
Rubis
S Safran
Saint-Gobain
Sanofi
Sartorius Stedim Biotech
Schneider Electric
Scor
Seb
Société Générale
Sodexo
Somfy
Sopra Steria Group
Suez Environnement
T Tarkett
Technicolor
Technip
Teleperformance
TF1
Thalès
Total
U Ubisoft Entertainment
Unibail-Rodamco
Unibel
V Valeo
Vallourec
Veolia Environnement
Vicat
Vilmorin & Cie
Vinci
Virbac
Vivendi
W Wendel
Worldline
Z Zodiac Aerospace
At the end of the French article, "2 molecules under license" are mentioned ?????
--->
sans compter deux molécules qui seront développées sous licences…
<---
Greece and Italy ?
http://www.oecd.org/els/health-systems/Obesity-Update-2014.pdf
BR, Otsuka is Abilify the biggest selling drug in the US http://www.drugs.com/stats/abilify (before the HCV launch)
Far, far from being a 4th tier pharma
Thanks for the advice. Their concept does not seem totally outrageous though!
Not exactly gene therapy, but you might be interested in Cardio3 BioSciences
http://www.c3bs.com/en/product-pipeline
BR, I will give you a hint, look for Abilify.
For the rest I tend to agree with you
Why BS, we are stuck with the patient killing dose thus lower we go.
http://cen.acs.org/articles/92/i40/Immune-System-Fights-Back.html
Read the end, weep and cry. Berger sold this for peanuts. 2da, BR and the others are 100% correct, Berger must go and the faster the better.
Pfizer And Cellectis Enter Into Global Strategic Cancer Immunotherapy Collaboration
Collaboration to Utilize Cellectis’ Proprietary Allogeneic CAR-T Platform Technology to Develop Immunotherapies Against Select Targets in the Field of Oncology
Wednesday, June 18, 2014 - 1:00am EDT
Pfizer Inc. (NYSE:PFE) and Cellectis (Paris:ALCLS) today announced that they have entered into a global strategic collaboration to develop Chimeric Antigen Receptor T-cell (CAR-T) immunotherapies in the field of oncology directed at select targets. Cellectis’ CAR-T platform technology provides a proprietary, allogeneic approach (utilizing engineered T-cells from a single donor for use in multiple patients) to developing CAR-T therapies that is distinct from other autologous approaches (engineering a patient’s own T-cells to target tumor cells).
Under the terms of the agreement, Pfizer has exclusive rights to pursue development and commercialization of CAR-T therapies, in the field of oncology, directed at a total of fifteen targets selected by Pfizer. Both companies will work together on preclinical research and Pfizer will be responsible for the development and potential commercialization of any CAR-T therapies for the Pfizer-selected targets. In addition, the agreement provides for a total of twelve targets selected by Cellectis. Both companies will work together on preclinical research on four Cellectis-selected targets and Cellectis will work independently on eight additional targets. Cellectis will be responsible for clinical development and commercialization of CAR-T therapeutics for the Cellectis-selected targets. Pfizer has right of first refusal to the four Cellectis-selected targets.
Cellectis will receive an upfront payment of $80 million, as well as funding for research and development costs associated with Pfizer-selected targets and the four Cellectis-selected targets within the collaboration. Cellectis is eligible to receive development, regulatory and commercial milestone payments of up to $185 million per Pfizer product. Cellectis is also eligible to receive tiered royalties on net sales of any products that are commercialized by Pfizer.
Additionally, Pfizer will be entering into an equity agreement to purchase approximately 10% of the Cellectis capital through newly issued shares at 9.25 Euro per share, pending Cellectis shareholder approval. Approval by two-thirds of the votes cast by voting Cellectis shareholders is required for the issuance. Shareholders of Cellectis representing 52.8% of its voting rights have already undertaken to vote in favor of the issuance. In the event the sale of equity is not approved by the Cellectis shareholders, Pfizer has the option to terminate the collaboration agreement.
Cellectis expects to open a site in the United States to work more closely with scientists at Pfizer.
“We believe our CAR-T platform technology has the potential to offer a real advantage over other approaches to T-cell receptor engineering and this collaboration with Pfizer is an important step towards realizing the full potential of this technology in harnessing the body’s own immune system to fight cancer,” said Andre Choulika, PhD, Chairman and Chief Executive Officer at Cellectis. “This alliance provides access to Pfizer’s state-of-the-art therapeutic development capabilities and provides a unique opportunity to advance this innovative work with the goal of developing best-in-class CAR-T therapeutics. We look forward to working closely with the team at Pfizer on researching and developing novel CAR-T therapies that could potentially change the way cancer is treated.”
“This leading immuno-oncology collaboration aimed at delivering immunotherapies is built upon Cellectis’ advanced genome editing and cell engineering capability and Pfizer’s cutting-edge biotherapeutic cancer therapy platform," said Mikael Dolsten, MD, PhD, President of R&D at Pfizer. "Combining the innovation and scientific expertise of Cellectis with Pfizer’s deep oncology and immunology experience creates a world-class partnership designed to deliver a new generation of CAR-T immunotherapies for cancer patients with urgent medical needs."
About CAR-Ts
Allogeneic CAR-Ts are “off-the-shelf” products which have the potential to be industrialized and thereby standardized, with consistent pharmaceutical release criteria, over time and from batch to batch. Each potential future patient may thus be treated by immediately receiving a single dose of a standard product with consistent quality. In addition, it is expected that such allogeneic products may be shipped in advance and would be accessible to any cancer center in the world without the need to invest in a local CAR-T processing facility.
GLPG.BR
Charles River Laboratories to acquire Galapagos' Argenta and BioFocus service operations for up to €134 million
· Total cash consideration of up to €134 million
o €129 million cash payment
o earnout of €5 million upon achievement of revenue target after 12 months
· Proceeds to be used to progress Galapagos' pipeline
o four Phase 2 patient data readouts expected over next 15 months
o delivery of multiple Phase 1 studies and candidates in 2014
· Galapagos retains target discovery capabilities for its R&D and alliance operations
· Management guidance for 2014 Group revenues (including Argenta and BioFocus revenues Q1) of €125 million and year end cash of €170 million
Objectives
Anaplastic lymphoma kinase (ALK) rearrangement is a validated predictive marker to define patients with non-small cell lung cancer (NSCLC) who can benefit from selective ALK inhibitors. Therefore, accurate assessment of its prevalence and clinical characteristics is increasingly important in the treatment of NSCLC. Also, this ALK rearrangement was previously reported to be more common in patients with no smoking history or those with adenocarcinoma.
Patients and methods
Never-smokers with completely resected pulmonary adenocarcinoma were screened for ALK rearrangements using Nanostring's gene expression platform. Clinicopathologic data, such as information about epidermal growth factor receptor (EGFR) and KRAS mutation status were retrospectively reviewed.
Results
Of 231 tumors screened, 20 (9%) had an ALK rearrangement and all were confirmed to be positive with immunohistochemical and fluorescent in situ hybridization analysis. Of the tumors with available data on the EGFR/KRAS mutation status, EGFR and KRAS mutation rates were 64% (69/108) and 5% (5/102), respectively. Amongst the tumors that were free of EGFR and KRAS mutations, the proportion of ALK rearrangements reached up to 33%. At the time of data cut-off, total 68 tumors recurred. Although the recurrence rate was similar between the ALK-positive and negative groups (30% vs. 29%), there was a tendency for ALK-positive tumors to recur more frequently in the pleural space (15% vs. 5%). The five-year disease-free survival (61%) and overall survival rates (79%) in the ALK-positive group were similar to those in the ALK-negative group (51% and 83%, respectively). Even after excluding two patients treated with crizotinib after disease recurrence, overall survival was similar between the two groups.
Conclusion
In an NSCLC subpopulation based on smoking history, histology, and EGFR and KRAS mutation status, the prevalence of ALK rearrangements is considerably high. However, ALK rearrangement status itself has no prognostic relevance in patients with completely resected NSCLC.
Lung Cancer
Clinical Characteristics Associated With ALK Rearrangements in Never-Smokers With Pulmonary Adenocarcinoma
Lung Cancer 2013 Nov 20;[EPub Ahead of Print], J-M Suna, M Lirab, K Pandyab, Y-L Choic, JS Ahna, M Maob, J Hanc, M-J Ahna, J Kimd