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San Francisco, CA, United States

ACT Biotech Inc is a San Francisco-based, privately held biopharmaceutical company focused on the development and commercialization of targeted cancer drugs.The Company's clinical stage pipeline includes :Telatinib, an oral kinase inhibitor for the first-line treatment of advanced gastric cancer. It has been granted Orphan Drug status by the U.S. Food and Drug Administration . It has reported encouraging interim results from a phase II trial.ACTB1003, an oral kinase inhibitor that targets cancer cells through multiple modes of action. It inhibits cancer cell growth by targeting the FGF receptor family, which are mutated in a number of human cancer types. ACTB1003 also directly induces apoptosis by targeting kinases downstream of the PI3K pathway, all at low nanomolar concentrations.Other pipeline products include an oral Aurora A and B kinase inhibitor at the pre-IND stage, and an ABL tyrosine kinase inhibitor targeting the T315I mutant enzyme in pre-clinical development. Wikipedia.


Namouchi A.,Institute Pasteur Paris | Didelot X.,University of Oxford | Schock U.,ACT Biotech | Gicquel B.,Institute Pasteur Paris | And 2 more authors.
Genome Research | Year: 2012

Many of the most virulent bacterial pathogens show low genetic diversity and sexual isolation. Accordingly, Mycobacterium tuberculosis, the deadliest human pathogen, is thought to be clonal and evolve by genetic drift. Yet, its genome shows few of the concomitant signs of genome degradation. We analyzed 24 genomes and found an excess of genetic diversity in regions encoding key adaptive functions including the type VII secretion system and the ancient horizontally transferred virulence-related regions. Four different approaches showed evident signs of recombination in M. tuberculosis. Recombination tracts add a high density of polymorphisms, and many are thus predicted to arise from outside the clade. Some of these tracts match Mycobacterium canettii sequences. Recombination introduced an excess of non-synonymous diversity in general and even more in genes expected to be under positive or diversifying selection, e.g., cell wall component genes. Mutations leading to non-synonymous SNPs are effectively purged in MTBC, which shows dominance of purifying selection. MTBC mutation bias toward AT nucleotides is not compensated by biased gene conversion, suggesting the action of natural selection also on synonymous changes. Together, all of these observations point to a strong imprint of recombination and selection in the genome affecting both non-synonymous and synonymous positions. Hence, contrary to some other pathogens and previous proposals concerning M. tuberculosis, this lineage may have come out of its ancestral bottleneck as a very successful pathogen that is rapidly diversifying by the action of mutation, recombination, and natural selection. © 2012 by Cold Spring Harbor Laboratory Press. Source


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.1.2-1 | Award Amount: 3.93M | Year: 2012

Lung transplantation (LT) is the standard of care for selected patients with chronic respiratory failure. Chronic lung allograft dysfunction (CLAD) (i.e. Bronchiolitis obliterans syndrome (BOS) and Restrictive Allograft Syndrome (RAS)) represents a major health risk for LT recipients, requiring the use of heavy treatments and possible retransplantation. Observed in almost 50% of patients after 5 years post LT, it is currently impossible to predict the appearance of CLAD before the onset of first symptoms. This project aims to develop the SysCLAD model which will allow to predict, within the 1st year post LT, the recipients at risk of developing CLAD by 3 years post LT. Building upon available data from the cohort of lung transplantation (COLT, recruited since mid-2009), this project will integrate new LT recipients to form the European cohort of lung transplantation (ECOLT). The SysCLAD prediction tool will be based on a mathematical model developed through a system biology approach integrating both clinical and biological data collected from a total of 400 LT recipients. The model will be validated on the first 200 LT recipients (3 years follow-up at project start) and refined using the new set of 200 LT data with 3 years follow-up by 2014. The aim is to identify and validate the signature of CLAD both at the clinical and molecular levels to allow for an early recognition and specific interventions in patients at risk of CLAD. The implementation of the model is expected to significantly improve the cost-effectiveness of post-LT treatments, limit the risk of graft rejection in LT recipients and, ultimately lead to an improved quality of life and a prolonged life expectancy of patients following LT. Finally, the SysCLAD model holds further great promises in the context of other chronic bronchial inflammatory diseases of major incidence such as severe asthma and Chronic Obstructive Pulmonary Disease (COPD) to predict decline in lung function.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.1.2-1 | Award Amount: 7.65M | Year: 2012

CLINICAL NEED Every year in the EU ~45,300 and 330,000 women are diagnosed with ovarian and breast cancer respectively & 28,800 and 90,000 of these two groups of women will die as a consequence of these diseases. Currently there are no tools available that allow for: a) Effective screening of ovarian and/or breast cancer of sufficient sensitivity and specificity to avoid potential over-diagnosis, or; b) Stratification of patients into optimal personalised therapy regimes in ovarian/breast cancer. EpiFemCare ADVANCES Progress in personalised cancer medicine will only be possible with the development of bioassays involving the analysis of easy accessible biomaterials that contain stable target molecules reflective of disease. We will establish and clinically validate a series of blood tests based upon DNA methylation technology that will facilitate both early detection and prediction of therapeutic outcome in breast and ovarian cancer. CONSORTIUM Our pan-European academic-industrial consortium demonstrates diverse clinical, scientific & industrial expertise. We have access to the latest state of the art technologies and, integrally, the best available cohort and clinical trial sample sets required to ensure the success of the EpiFemCare program. GATC-Biotech and Genedata are Europes leading providers of DNA sequencing and bioinformatics for biomarker development and have developed serum DNA based prenatal tests. The clinical partners have access to unique cohort and clinical samples collected from >200,000 women well in advance of disease (UK Collaborative Trial of Ovarian Cancer Screening) or before and during treatment (SUCCESS Trial). IMPACT As a result of refined and improved patient stratification, EpiFemCare will: - Reduce the late stage presentation of ovarian & breast cancer by 50% - Reduce the requirement for 50% of breast cancer patients to have adjuvant therapies - Reduce female cancer related fatalities as well as treatment-related morbidity by 20%


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2010.1.4-1 | Award Amount: 15.80M | Year: 2010

Primary immune deficiencies (PID) are inherited disorders of the adaptive and innate immune system marked by severe infections, autoimmunity and high risk of cancer. Treatment entails hematopoietic stem cell (HSC) transplantation from allogeneic donors, however in the absence of an HLA compatible donor, HSCT outcome is limited by delayed or suboptimal reconstitution and complications. SCID-X1 and ADA-SCID have been successfully treated with autologous gene corrected HSC, however, associated with safety issues inherent to first generation retroviral vectors. This project utilizes genetically modified HSC and their descendants as immunotherapeutic cells to build a healthy immune system in PID patients, and is carried out by clinical centres, scientists and industrial partners pioneering in the field of advanced therapies and aiming at broad clinical application of safe cell-based therapeutic products. Multicentre phase I/II clinical trials for SCID-X1 and WAS are ready to start. Disease targeted technology to cure ADA-SCID, V(D)J recombination defects and CGD by gene corrected HSC and novel approaches in IPEX and HLH to gene modify already committed cells will be investigated. Based on rigorous preclinical efficacy and toxicology evaluation, flanked by basic studies aimed at improving HSC homing capacity and thymic epithelium regeneration, new clinical trials will be implemented. The consortium will establish a technology platform to implement, harmonize and run controlled, standardized multicentre preclinical studies using state-of-the-art advanced therapy. Strict observance of good practice quality guidelines and regulation of medicinal product development will be ensured. The successful completion of the project will be instrumental to accomplish and broaden clinical application of medicinal products able to rebuild and modulate the immune system with an anticipated impact that extends beyond PID to acquired immune disorders, allogeneic HSCT and cancer treatment.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-05-2014 | Award Amount: 7.99M | Year: 2015

While prevention of most female specific cancers (ovarian, breast, endometrial) has not progressed substantially in recent years, significant progress has been made with cervical cancer due to accessibility of the cell of origin (cervical smear) and availability of a test for the causal agent (human papilloma virus); together these enable identification of high risk individuals and interventions to prevent infection or halt progression to invasive cancer. Our consortium has developed an exciting opportunity to utilise clinically abundant cervical cells in tandem with a multi-omics enabled (genome, epigenome, metagenome) analysis pipeline to understand an individuals risk of developing a female specific cancer and to direct a personalised screening and prevention strategy. Cervical cells currently collected within cervical cancer screening provide an ideal window into other female specific cancers because they are (i) an excellent non-invasive source of high quality DNA, (ii) provide a readout for environmental exposure, (iii) are part of the Mllerian tract and (iv) are hormone sensitive, recording (via the epigenome) various hormonal conditions over a lifetime that trigger cancer development. The FORECEE project is aligned with the novel concept of P4 Medicine (predictive, preventive, personalized, and participatory): it aims to translate the risk prediction tools output into personalised recommendations for screening and prevention of female cancers. Our consortium comprises a multi-disciplinary team of experts in clinical oncology, risk-benefit communication, omics technologies, decision analysis, health economics and public health. We will examine the effectiveness of the proposed cervical cell omics analysis method and investigate the legal, social, ethical and behavioural issues related to implementation of the risk prediction tool, through direct interaction with stakeholder groups, to ensure its rapid translation into clinical practice across Europe.

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