News Article | May 18, 2017
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Acceleron Pharma Inc. (NASDAQ:XLRN), a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of innovative therapeutics to treat serious and rare diseases, today announced that two abstracts on luspatercept will be presented at the 22nd Congress of the European Hematology Association (EHA) in Madrid, Spain on June 22-25, 2017. Luspatercept is being developed as part of the global collaboration between Acceleron and Celgene. The oral and poster presentations will include efficacy, duration of response, and long-term safety results from the ongoing Phase 2 studies with luspatercept in myelodysplastic syndromes (MDS) and beta-thalassemia. The presentations at the conference will include updated information beyond that included in the abstracts available online on the EHA conference website. The beta-thalassemia presentation will review results updated from the ASH 2016 presentation in December and the MDS presentation will highlight results updated from the recent International Symposium on MDS earlier this month. The luspatercept clinical poster and slides from the oral presentation will be available immediately following the presentations at the conference in the “Science” section on Acceleron’s website, www.acceleronpharma.com. Luspatercept is a modified activin receptor type IIB fusion protein that acts as a ligand trap for members in the transforming growth factor-beta superfamily involved in the late stages of erythropoiesis (red blood cell production). Luspatercept regulates late-stage erythrocyte (red blood cell) precursor cell differentiation and maturation. This mechanism of action is distinct from that of erythropoiesis stimulating agents (ESAs), which stimulate the proliferation of early-stage erythrocyte precursor cells. Acceleron and Celgene are jointly developing luspatercept as part of a global collaboration. Phase 3 clinical trials are underway to evaluate the safety and efficacy of luspatercept in patients with myelodysplastic syndromes (the “MEDALIST” study) and in patients with beta-thalassemia (the “BELIEVE” study). For more information, please visit www.clinicaltrials.gov. Acceleron is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of innovative therapeutics to treat serious and rare diseases. Its pioneering research platform leverages the powerful biology behind the body’s ability to rebuild and repair its own cells and tissues. This approach to drug discovery has generated four therapeutic candidates that are currently in clinical trials. The Company’s lead therapeutic candidate, luspatercept, is being evaluated in Phase 3 studies for the treatment of the hematologic diseases myelodysplastic syndromes (MDS) and beta-thalassemia under a global partnership with Celgene Corp. Acceleron is also advancing clinical programs in the fields of oncology and neuromuscular diseases and has a comprehensive preclinical research effort targeting fibrotic and other serious diseases. For more information, please visit www.acceleronpharma.com. Follow Acceleron on social media: @AcceleronPharma and LinkedIn.
News Article | May 6, 2017
CAMBRIDGE, Mass. & SUMMIT, N.J.--(BUSINESS WIRE)--Acceleron Pharma Inc. (NASDAQ:XLRN) and Celgene Corporation (NASDAQ:CELG), today announced preliminary Phase 2 results from the ongoing three-month base and long-term extension studies with investigational drug luspatercept in patients with lower-risk myelodysplastic syndromes (MDS) at the 14th International Symposium on MDS in Valencia, Spain. Luspatercept is being developed as part of the global collaboration between Acceleron and Celgene. “These positive data presented in lower-risk MDS confirm our optimism in new opportunities for luspatercept beyond our ongoing Phase 3 trials,” said Michael Pehl, President, Hematology and Oncology for Celgene. “We are now planning a Phase 3 clinical trial to expand the development of luspatercept into this lower-risk MDS patient population.” “There is a high unmet medical need for a drug to treat patients earlier in the MDS treatment paradigm,” said Habib Dable, President and CEO of Acceleron. “We continue to be motivated to find additional opportunities for luspatercept to treat anemia due to rare blood disorders and remain on track to initiate Phase 2 trials in myelofibrosis and non-transfusion dependent beta-thalassemia by year-end.” In lower-risk, erythropoiesis-stimulating agent (ESA)-naïve MDS patients, 48% (11/23) of patients treated with luspatercept achieved red blood cell transfusion independence (RBC-TI) and 51% (20/39) of patients achieved a clinically meaningful erythroid hematological improvement (HI-E) response per the International Working Group’s (IWG) criteria. The response rates were positive in patients treated with luspatercept in both ESA-naïve and prior ESA-treated patients. In patients with baseline erythropoietin (EPO) levels ≤ 500 international units per liter (IU/L), RBC-TI and IWG HI-E response rates were positive in both ring sideroblast-positive (RS+) and –negative (RS-) patients. *Table includes both ESA refractory and ESA naïve patients. Patients treated at dose levels ≥ 0.75 mg/kg. The majority of adverse events (AEs) were grade 1 or 2. AEs at least possibly related to study drug that occurred in at least 3 patients during the studies were fatigue, headache, hypertension, diarrhea, arthralgia, bone pain, injection site erythema, myalgia, and edema peripheral. Grade 3 non-serious AEs possibly or probably related to study drug were ascites, blast cell count increase, blood bilirubin increase, hypertension, platelet count increase, and pleural effusion. Grade 3 serious AEs possibly or probably related to study drug were general physical health deterioration and myalgia. Luspatercept is an investigational product that is not approved for use in any country. The oral presentation given at the 14th International Symposium on MDS is available on Acceleron's website (www.acceleronpharma.com) under the Science tab. Acceleron will host a conference call and live webcast to discuss data presented at the MDS Symposium and its first quarter operational and financial results on May 8, 2017, at 8:00 a.m. EDT. To participate by teleconference, please dial 877-312-5848 (domestic) or 253-237-1155 (international) and refer to the Acceleron Earnings Call. To access the live webcast, please select “Events & Presentations” in the Investors/Media section on Acceleron’s website (www.acceleronpharma.com) at least 10 minutes beforehand to ensure time for any downloads that may be required. An archived webcast recording will be available on the Acceleron website beginning approximately two hours after the event. Data from two Phase 2 studies were presented at the conference: the base study in which patients received treatment with luspatercept for three months and the long-term extension study in which patients may receive treatment with luspatercept for up to an additional five years. In both the three-month base study and the long-term extension study, lower-risk MDS patients were enrolled and treated with open-label luspatercept, dosed subcutaneously once every three weeks. The outcome measures for the studies included the proportion of patients who had an erythroid response (IWG HI-E) or achieved RBC transfusion independence (RBC-TI). IWG HI-E was defined as hemoglobin increase ≥ 1.5 g/dL sustained for ≥ 8 weeks in patients with < 4 units RBC / 8 weeks transfusion burden at baseline and hemoglobin levels below 10 g/dL. For patients with a ≥ 4 units RBC / 8 weeks transfusion burden at baseline, erythroid response was defined as a reduction of ≥ 4 units RBC sustained for ≥ 8 weeks. RBC-TI was defined as no RBC transfusions for ≥ 8 weeks in patients with a ≥ 2 units RBC / 8 weeks baseline transfusion burden. Luspatercept is a modified activin receptor type IIB fusion protein that acts as a ligand trap for members in the transforming growth factor-beta superfamily involved in the late stages of erythropoiesis (red blood cell production). Luspatercept regulates late-stage erythrocyte (red blood cell) precursor cell differentiation and maturation. This mechanism of action is distinct from that of erythropoietin (EPO), which stimulates the proliferation of early-stage erythrocyte precursor cells. Acceleron and Celgene are jointly developing luspatercept as part of a global collaboration. Acceleron and Celgene are enrolling Phase 3 clinical trials that are designed to evaluate the safety and efficacy of luspatercept in patients with myelodysplastic syndromes (the “MEDALIST” study) and in patients with beta-thalassemia (the “BELIEVE” study). For more information, please visit www.clinicaltrials.gov. Acceleron is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of innovative therapeutics to treat serious and rare diseases. Its pioneering research platform leverages the powerful biology behind the body’s ability to rebuild and repair its own cells and tissues. This approach to drug discovery has generated four therapeutic candidates that are currently in clinical trials. The Company’s lead therapeutic candidate, luspatercept, is being evaluated in Phase 3 studies for the treatment of the hematologic diseases myelodysplastic syndromes (MDS) and beta-thalassemia under a global partnership with Celgene Corp. Acceleron is also advancing clinical programs in the fields of oncology and neuromuscular diseases and has a comprehensive preclinical research effort targeting fibrotic and other serious diseases. For more information, please visit http://acceleronpharma.com/. Follow Acceleron on Social Media: @AcceleronPharma and LinkedIn. Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through next-generation solutions in protein homeostasis, immuno-oncology, epigenetics, immunology and neuro-inflammation. For more information, please visit www.celgene.com. Follow Celgene on Social Media: @Celgene, Pinterest, LinkedIn, FaceBook and YouTube. This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the potential benefits of, and plans relating to the collaboration between Acceleron and Celgene; the potential of luspatercept as a therapeutic drug; and the benefit of each company’s strategic plans and focus. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “would,” “could,” “potential,” “possible,” “hope” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially from current expectations and beliefs. For example, there can be no guarantee that any product candidate will be successfully developed or complete necessary preclinical and clinical phases, or that development of any of product candidates will successfully continue. There can be no guarantee that any positive developments will result in stock price appreciation. Each company’s management's expectations and, therefore, any forward-looking statements in this press release, could also be affected by risks and uncertainties relating to a number of other important factors, including: results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. FDA and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies; the ability to obtain and maintain requisite regulatory approvals and to enroll patients in planned clinical trials; competitive factors; the ability to obtain, maintain and enforce patent and other intellectual property protection for any product candidates ; the ability to maintain key collaborations; and general economic and market conditions. These and other risks are described in greater detail under the caption "Risk Factors" included in each company’s public filings with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and neither company has any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.
News Article | February 28, 2017
Adding two blood-borne proteins associated with cancer cell migration increases the predictive ability of the current biomarker for pancreatic cancer to detect early stage disease, a research team from The University of Texas MD Anderson Cancer Center reports in the Journal of the National Cancer Institute. The trio of biomarkers, tested in three separate cohorts, including two blinded validation studies, improved the detection of patients with early stage disease compared to healthy or benign disease controls. "Adding these two biomarkers provided statistically significant improvement for all early stage cancer versus healthy controls as well as other subcohorts when used with the current gold standard biomarker, CA 19-9," said Ann Killary, Ph.D., professor of Translational Molecular Pathology. While CA 19-9 is the only biomarker approved for use by the U.S. Food and Drug Administration, and only for monitoring treatment for the disease, according to first author Seetharaman Balasenthil, Ph.D., instructor in Translational Molecular Pathology. The marker of antigens produced by pancreatic cancer has a low positive predictive value for identifying early stage disease. At early stages, pancreatic cancer can be successfully removed with surgery, but 80 percent of patients are diagnosed with either locally advanced disease (stage III) or cancer that has spread to other organs (stage IV), when surgery is no longer a curative option. Pancreatic cancer is the fourth-leading cause of deaths from cancer in the United States, with an estimated 53,070 new cases diagnosed in 2016 and 41,780 deaths, according to the National Cancer Institute. "Our goal is to identify more patients at those earlier, resectable stages, when treatment could lead to a five year survival rate of 30 percent or more, depending on stage," Killary said. Only about 7 percent of patients survive for five years following diagnosis of the disease. Additional studies in larger cohorts will be needed to validate these findings, and more biomarkers will be needed to get the completely accurate set needed to screen the general population with the long term goal of identifying precursor lesions before they become malignant. Killary and colleagues earlier identified a cluster of genes involved in cancer migration and then analyzed the proteins produced by those genes. Two, known as TFPI and tenascin C, emerged as the strongest biomarker candidates. The team first compared their predictive ability by comparing their presence in healthy volunteers and those with primarily stage IV pancreatic cancer. In the current study, deploying TFPI and an isoform of tenascin C, TNC-FN IIIC, with CA 19-9 improved performance discriminating stage I and II disease from healthy or benign disease controls. The principal measure of efficacy is called Area Under the Curve (AUC), a measure of how well biomarkers identify true cases of disease (sensitivity) while avoiding false positives (specificity). A perfect AUC would have a score of 1.0. Any biomarker test for the general public will need to be close to a perfect 1.0, Killary noted, given the infrequency of pancreatic cancer in the population at large. In the group's analysis of three cohorts of samples, AUC scores for the combination consistently outscored CA-19-9 alone. For the first cohort of samples, comparing stage I/IIA and healthy controls yielded an AUC of 0.72 for CA-19-9 alone compared to 0.84 for the combination. For stage IIB vs. controls, the combination raised CA-19-9's performance from an AUC of 0.87 to 0.98. The second blinded cohort also showed improvements in AUC over CA19-9. A third, larger blinded validation study of 252 samples of cases and controls from the Early Detection Research Network of the National Cancer Institute further confirmed those findings and also permitted the team to measure the trio's ability to detect disease in patients without a history of pancreatitis or diabetes. The AUC for those patients was 0.87 for Stage I/IIA, 0.93 for Stage IIB and 0.89 for all early stages of the disease using the combination, pointing to a potential ability to detect disease in those who lack either of those known risk-raising conditions. Killary said the team is working to use the biomarkers in MD Anderson's high-risk clinic, established through MD Anderson's Pancreatic Cancer Moon Shot™, part of the institution's Moon Shots Program™ to accelerate the development of life-saving advances based on scientific discovery. The clinic monitors people who are already at high risk of pancreatic cancer due to family history or having known risk-raising genetic mutations. "In this population, our biomarker panel might prove very useful in early detection," Killary said. Co-author Subrata Sen, Ph.D., also a professor of Molecular Translational Pathology, notes, "These findings are a significant advance considering that there's nothing else available now to detect early stage pancreatic cancer that has gone through blinded validations in multiple patient cohorts." Co-authors with Killary, Balasenthil and Sen are Nanyue Chen, M.D., Ph.D., of Translational Molecular Pathology; Suyu Liu, Ph.D., and J. Jack Lee, Ph.D., of Biostatistics; Jinyun Chen, M.D., Pharm.D., and Marsha Frazier, Ph.D. of Epidemiology; Ying Huang, Ph.D., and Tracey Marsh, of Fred Hutchinson Cancer Research Center, Seattle; Sanford Stass, M.D., and Debra KuKuruga , Ph.D., of the University of Maryland Medical Center, Baltimore; Randall Brand, M.D., University of Pittsburgh Medical Center; and Sudhir Srivastava, M.D., of the National Cancer Institute. This research was funded by Early Detection Research Network grants (U01 CA111302 and U24 CA115091-10) and by MD Anderson's Moon Shots Program.
News Article | February 15, 2017
Forty years after theorists married general relativity with supersymmetry, supergravity continues to carve out new directions in the search for a unified theory. Quarante ans après le mariage célébré par les théoriciens entre la relativité générale et la supersymétrie, la supergravité continue d’ouvrir de nouvelles voies dans la quête d’une théorie unifiée. La supergravité, qui repose sur quelques-unes des plus belles idées de la physique théorique, a dévoilé au fil des années plusieurs de ses facettes. En particulier, la supergravité s’est révélée être une manifestation à faible énergie de la théorie des cordes, et un outil essentiel pour l’étude des objets étendus appelés branes. S’il n’y a toujours pas de preuve de l’existence de la supersymétrie, la supergravité se porte toujours à merveille. The early 1970s was a pivotal period in the history of particle physics. Following the discovery of asymptotic freedom and the Brout–Englert–Higgs mechanism a few years earlier, it was the time when the Standard Model (SM) of electroweak and strong interactions came into being. After decades of empirical verification, the theory received a final spectacular confirmation with the discovery of the Higgs boson at CERN in 2012, and its formulation has also been recognised by Nobel prizes awarded to theoretical physics in 1979, 1999, 2004 and 2013. It was clear from the start, however, that the SM, a spontaneously broken gauge theory, had two major shortcomings. First, it is not a truly unified theory because the gluons of the strong (colour) force and the photons of electromagnetism do not emerge from a common symmetry. Second, it leaves aside gravity, the other fundamental force of nature, which is based on the gauge principle of general co-ordinate transformations and is described by general relativity (GR). In the early 1970s, grand unified theories (GUTs), based on larger gauge symmetries that include the SM’s “SU(3) × SU(2) × U(1)” structure, did unify colour and charge – thereby uniting the strong and electroweak interactions. However, they relied on a huge new energy scale (~1016 GeV), just a few orders of magnitude below the Planck scale of gravity (~1019 GeV) and far above the electroweak Fermi scale (~102 GeV), and on new particles carrying both colour and electroweak charges. As a result, GUTs made the stunning prediction that the proton might decay at detectable rates, which was eventually excluded by underground experiments, and their two widely separated cut-off scales introduced a “hierarchy problem” that called for some kind of stabilisation mechanism. A possible solution came from a parallel but unrelated development. In 1973, Julius Wess and Bruno Zumino unveiled a new symmetry of 4D quantum field theory: supersymmetry, which interchanges bosons and fermions and, as would be better appreciated later, can also conspire to stabilise scale hierarchies. Supersymmetry was inspired by “dual resonance models”, an early version of string theory pioneered by Gabriele Veneziano and extended by André Neveu, Pierre Ramond and John Schwarz. Earlier work done in France by Jean-Loup Gervais and Benji Sakita, and in the Soviet Union by Yuri Golfand and Evgeny Likhtman, and by Dmitry Volkov and Vladimir Akulov, had anticipated some of supersymmetry’s salient features. An exact supersymmetry would require the existence of superpartners in the SM, but it would also imply mass degeneracies between the known particles and their superpartners. This option has been ruled out over the years by several experiments at CERN, Fermilab and elsewhere, and therefore supersymmetry can be at best broken, with superpartner masses that seem to lie beyond the TeV energy region currently explored at the LHC. Moreover, a spontaneous breaking of supersymmetry would imply the existence of additional massless (“Goldstone”) fermions. Supergravity, the supersymmetric extension of GR, came to the rescue in this respect. It predicted the existence of a new particle of spin 3/2 called the gravitino that would receive a mass in the broken phase. In this fashion, one or more gravitinos could be potentially very heavy, while the additional massless fermions would be “eaten” – much as it occurs for part of the Higgs doublet in the SM. Supergravity, especially when formulated in higher dimensions, was the first concrete realisation of Einstein’s dream of a unified field theory (see diagram opposite). Although the unification of gravity with other forces was the central theme for Einstein during the last part of his life, the beautiful equations of GR were for him a source of frustration. For 30 years he was disturbed by what he considered a deep flaw: one side of the equations contained the curvature of space–time, which he regarded as “marble”, while the other contained the matter energy, which he compared to “wood”. In retrospect, Einstein wanted to turn “wood” into “marble”, but after special and general relativity he failed in this third great endeavour. GR has, however, proved to be an inestimable source of deep insights for unification. A close scrutiny of general co-ordinate transformations led Theodor Kaluza and Oskar Klein (KK), in the 1920s and 1930s, to link electromagnetism and its Maxwell potentials to internal circle rotations, what we now call a U(1) gauge symmetry. In retrospect, more general rotations could also have led to the Yang–Mills theory, which is a pillar of the SM. According to KK, Maxwell’s theory could be a mere byproduct of gravity, provided the universe contains one microscopic extra dimension beyond time and the three observable spatial ones. In this 5D picture, the photon arises from a portion of the metric tensor – the “marble” in GR – with one “leg” along space–time and the other along the extra dimensions. Supergravity follows in this tradition: the gravitino is the gauge field of supersymmetry, just like the photon is the gauge field of internal circle rotations. If one or more local supersymmetries (whose number will be denoted by N) accompany general co-ordinate transformations, they grant the consistency of gravitino interactions. In a subclass of “pure” supergravity models, supersymmetry also allows one to connect “marble” and “wood” and therefore goes well beyond the KK mechanism, which does not link Bose and Fermi fields. Curiously, while GR can be formulated in any number of dimensions, seven additional spatial dimensions, at most, are allowed in supergravity due to intricacies of the Fermi–Bose matching. Last year marked the 40th anniversary of the discovery of supergravity. At its heart lie some of the most beautiful ideas in theoretical physics, and therefore over the years this theory has managed to display different facets or has lived different parallel lives. The first instance of supergravity, containing a single gravitino (N = 1), was built in the spring of 1976 by Daniel Freedman, Peter van Nieuwenhuizen and one of us (SF). Shortly afterwards, the result was recovered by Stanley Deser and Bruno Zumino, in a simpler and elegant way that extended the first-order (“Palatini”) formalism of GR. Further simplifications emerged once the significance of local supersymmetry was better appreciated. Meanwhile, the “spinning string” – the descendant of dual resonance models that we have already met – was connected to space–time supersymmetry via the so-called Gliozzi–Scherk–Olive (GSO) projection, which reflects a subtle interplay between spin-statistics and strings in space–time. The low-energy spectrum of the resulting models pointed to previously unknown 10D versions of supergravity, which would include the counterparts of several gravitinos, and also to a 4D Yang–Mills theory that is invariant under four distinct supersymmetries (N = 4). A first extended (N = 2) version of 4D supergravity involving two gravitinos came to light shortly after. When SF visited Caltech in the autumn of 1976, he became aware that Murray Gell-Mann had already worked out many consequences of supersymmetry. In particular, Gell-Mann had realised that the largest “pure” 4D supergravity theory, in which all forces would be connected to the conventional graviton, would include eight gravitinos. Moreover, this N = 8 theory could also allow an SO(8) gauge symmetry, the rotation group in eight dimensions (see table opposite). Although SO(8) would not suffice to accommodate the SU(3) × SU(2) × U(1) symmetry group of the SM, the full interplay between supergravity and supersymmetric matter soon found a proper setting in string theory, as we shall see. The following years, 1977 and 1978, were most productive and drew many people into the field. Important developments followed readily, including the discovery of reformulations where N = 1 4D supersymmetry is manifest. This technical step was vital to simplify more general constructions involving matter, since only this minimal form of supersymmetry is directly compatible with the chiral (parity-violating) interactions of the SM. Indeed, by the early 1980s, theorists managed to construct complete couplings of supergravity to matter for N = 1 and even for N = 2. The maximal, pure N = 8 4D supergravity was also derived, via a circle KK reduction, in 1978 by Eugene Cremmer and Bernard Julia. This followed their remarkable construction, with Joel Scherk, of the unique 11D form of supergravity, which displayed a particularly simple structure where a single gravitino accounts for eight 4D ones. In contrast, the N = 8 model is a theory of unprecedented complication. It was built after an inspired guess about the interactions of its 70 scalar fields (see table) and a judicious use of generalised dualities, which extend the manifest symmetry of the Maxwell equations under the interchange of electric and magnetic fields. The N = 8 supergravity with SO(8) gauge symmetry foreseen by Gell-Mann was then constructed by Bernard de Wit and Hermann Nicolai. It revealed a negative vacuum energy, and thus an anti-de Sitter (AdS) vacuum, and was later connected to 11D supergravity via a sphere KK reduction. Regarding the ultraviolet behaviour of supergravity theories, which was vigorously investigated soon after the original discovery, no divergences were found, at one loop, in the “pure” models, and many more unexpected cancellations of divergences have since come to light. The case of N = 8 supergravity is still unsettled, and some authors still expect that this maximal theory be finite to all orders. Following the discovery of supergravity, the GSO projection opened the way to connect “spinning strings”, or string theory as they came to be known collectively, to supersymmetry. Although the link between strings and gravity had been foreseen by Scherk and Schwarz, and independently by Tamiaki Yoneya, it was only a decade later, in 1984, that widespread activity in this direction began. This followed Schwarz and Michael Green’s unexpected discovery that gauge and gravitational anomalies cancel in all versions of 10D supersymmetric string theory. Anomalies – quantum violations of classical symmetries – are very troublesome when they concern gauge interactions, and their cancellation is a fundamental consistency condition that is automatically granted in the SM by its known particle content. Anomaly cancellation left just five possible versions of string theory in 10 dimensions: two “heterotic” theories of closed strings, where the SU(3) × SU(2) × U(1) symmetry of the SM is extended to the larger groups SO(32) or E8 × E8; an SO(32) “type-I” theory involving both open and closed strings, akin to segments and circles, respectively; and two other very different and naively less interesting theories called IIA and IIB. At low energies, supergravity emerges from all of these theories in its different 10D realisations, opening up unprecedented avenues for linking 10D strings to the interactions of particle physics. Moreover, the extended nature of strings made all of these enticing scenarios free of the ultraviolet problems of gravity. Following this 1984 “first superstring revolution”, one might well say that supergravity officially started a second life as a low-energy manifestation of string theory. Anomaly cancellation had somehow connected Einstein’s “marble” and “wood” in a miraculous way dictated by quantum consistency, and definite KK scenarios soon emerged that could recover from string theory both the SM gauge group and its chiral, parity-violating interactions. Remarkably, this construction relied on a specific class of 6D internal manifolds called Calabi–Yau spaces that had been widely studied in mathematics, thereby merging 4D supergravity with algebraic geometry. Calabi–Yau spaces led naturally, in four dimensions, to a GUT gauge group E6, which was known to connect to the SM with right-handed neutrinos, also providing realisations of the see-saw mechanism. The early 1990s were marked by many investigations of black-hole-like solutions in supergravity, which soon unveiled new aspects of string theory. Just like the Maxwell field is related to point particles, some of the fields in 10D supergravity are related to extended objects, generically dubbed “p-branes” (p = 0 for particles, p = 1 for strings, p = 2 for membranes, and so on). String theory, being based at low energies on supergravity, therefore could not be merely a theory of strings. Rather, as had been strongly advocated over the years by Michael Duff and Paul Townsend, we face a far more complicated soup of strings and more general p-branes. A novel ingredient was a special class of p-branes, the D-branes, whose role was clarified by Joseph Polchinski, but the electric-magnetic dualities of the low-energy supergravity remained the key tool to analyse the system. The end result, in the mid 1990s, was the awesome, if still somewhat vague, unified picture called M-theory, which was largely due to Edward Witten and marked the “second superstring revolution”. Twenty years after its inception, supergravity thus started a third parallel life, as a deep probe into the mysteries of string theory. The late 1990s witnessed the emergence of a new duality. The AdS/CFT correspondence, pioneered by Juan Maldacena, is a profound equivalence between supergravity and strings in AdS and conformal field theory (CFT) on its boundary, which connects theories living in different dimensions. This “third superstring revolution” brought to the forefront the AdS versions of supergravity, which thus started a new life as a unique tool to probe quantum field theory in unusual regimes. The last two decades have witnessed many applications of AdS/CFT outside of its original realm. These have touched upon fluid dynamics, quark–gluon plasma, and more recently condensed-matter physics, providing a number of useful insights on strongly coupled matter systems. Perhaps more unexpectedly, AdS/CFT duality has stimulated work related to scattering amplitudes, which may also shed light on the old issue of the ultraviolet behaviour of supergravity. The reverse programme of gaining information about gravity from gauge dynamics has proved harder, and it is difficult to foresee where the next insights will come from. Above all, there is a pressing need to highlight the geometrical principles and the deep symmetries underlying string theory, which have proved elusive over the years. The interplay between particle physics and cosmology is a natural arena to explore consequences of supergravity. Recent experiments probing the cosmic microwave background, and in particular the results of the Planck mission, lend support to inflationary models of the early universe. An elusive particle, the inflaton, could have driven this primordial acceleration, and although our current grasp of string theory does not allow a detailed analysis of the problem, supergravity can provide fundamental clues on this and the subsequent particle-physics epochs. Supersymmetry was inevitably broken in a de Sitter-like inflationary phase, where superpartners of the inflaton tend to experience instabilities. The novel ingredient that appears to get around these problems is non-linear supersymmetry, whose foundations lie in the prescient 1973 work of Volkov and Akulov. Non-linear supersymmetry arises when superpartners are exceedingly massive, and seems to play an intriguing role in string theory. The current lack of signals for supersymmetry at the LHC makes one wonder whether it might also hold a prominent place in an eventual picture of particle physics. This resonates with the idea of “split supersymmetry”, which allows for large mass splittings among superpartners and can be accommodated in supergravity at the price of reconsidering hierarchy issues. In conclusion, attaining a deeper theoretical understanding of broken supersymmetry in supergravity appears crucial today. In breaking supersymmetry, one is confronted with important conceptual challenges: the resulting vacua are deeply affected by quantum fluctuations, and this reverberates on old conundrums related to dark energy and the cosmological constant. There are even signs that this type of investigation could shed light on the backbone of string theory, and supergravity may also have something to say about dark matter, which might be accounted for by gravitinos or other light superpartners. We are confident that supergravity will lead us farther once more.
News Article | March 1, 2017
Designer version 5.2 now also available with the latest SWIFT Standards Release 2017 NEW YORK, NY and LONDON, UNITED KINGDOM and DUBAI, UNITED ARAB EMIRATES and MEXICO CITY, MEXICO--(Marketwired - March 01, 2017) - Volante Technologies Inc., a global leader in the provision of software for the integration, processing and orchestration of financial messages and payments, today announced support for the technology underpinning Microservices Architecture, as well as SWIFT Standards Release 2017. Volante Designer version 5.2 provides comprehensive support for developing and deploying RESTful services - the building blocks of a microservices architecture. As the financial industry shifts towards increasing standardization and collaboration, the responsibility falls on the underlying technology to provide seamless integration of applications and services provided by various institutions such as banks, corporates, service providers and regulatory institutions. Such close coupling is also required to address the regulatory requirements for APIs such as the Open Banking APIs and PSD2. Internal applications, especially within large organizations, will also benefit from distributed RESTful services as they promote scalability, reusability and secure remote access. Volante has the ability to generate REST Client and REST server implementations for any service built using Volante Designer. Additionally, Volante provides native support to convert any standard message to JSON format and vice versa, further facilitating seamless communications using REST APIs. Using these tools, users can develop and deploy a wide range of services based on the REST architecture without writing a single line of code. Volante has been a SWIFT partner for over 15 years and has developed a level of product and standards expertise that is unmatched in the FinTech industry. In Standards Release 2017, SWIFT has introduced significant changes in the payments and securities message categories. Notably, this release includes support for the Global Payments Innovation (GPI) Initiative which provides greater transparency for cross-border payments. Volante has implemented complete support for the new standards, which have been thoroughly tested so customers can be confident of communicating SWIFT messages over the SWIFT network without worrying about rejected messages or non-compliance in the face of continuously changing standards and market practices. In addition to support for REST, JSON and SWIFT, Designer 5.2 features continuous improvement in standards support, platforms support and usability features. This includes: updated versions for standards such as NACHA, FIX, ISO 20022 and US-TCH-RTP; support for Postgres DB and other enhancements to Persistence Designer; and a new Connector for Mulesoft and updates to support for IBM Integration Bus (IIB). Venkat Malla, VP, Product Management, Volante Technologies, said, "We continue to work closely with clients and industry participants in order to understand and anticipate their needs and challenges, which in turn determines our product roadmap. By introducing comprehensive support for REST and JSON standards, clients are able to not only interface with modern infrastructure like blockchain and DLT (Distributed Ledger Technology) but also build out their own user interfaces." Fiona Hamilton, VP Europe and Asia, commented, "Being personally very active in standards groups, I continually see the ever-evolving nature of financial messaging standards. We respond by being dedicated to not only tracking and including those changes, but also offering support for those new standards quickly and efficiently. In the latest SWIFT release, firms will be able to take advantage of the benefits of GPI by enabling them to grow their international business, improve supplier relationships and achieve greater treasury efficiencies. By delivering updates within days of SWIFT publishing the final version, our clients have ample time to assess, test and incorporate the changes into their processes well ahead of the go-live deadlines." Founded in 2001, Volante Technologies is a global leader in the provision of software for the integration, processing and orchestration of payments and financial messages within financial institutions and corporate enterprises. Volante is dedicated to helping firms manage challenges in this domain with greater ease and speed so that they can focus on the business of being competitive in their marketplace. Product features such as configuration rather than coding, automated code and documentation generation and an inbuilt test harness, promise significantly accelerated project completions. Volante serves a growing client base of more than 80 financial institutions and corporate enterprises operating in 26 countries around the world, including several of the largest global financial organizations. Many clients use Volante to assist with multiple product implementations ranging from message transformation and integration, through to the processing and orchestration of transaction data and payments. Along with its products, Volante Designer, VolPay Foundation, VolPay Channel and VolPay Hub, Volante constantly maintains a growing library of over 100 domestic and international financial industry standards plugins. These standards include; SWIFT MT and MX, ISO 8583, FIX, FpML, EDIFACT, ISO 20022, SEPA, BACS, US TCH and Fedwire, and proprietary formats based on XML, CSV and Fixed Width. Volante's financial message plugins are further augmented by more than 250 prebuilt, customizable, bidirectional transformations to and from these standards. Supported by offices in Jersey City, London, Dubai, Mexico City, Hyderabad, Chennai and Pune, Volante solutions are employed by a diverse set of organizations, including buy-side and sell-side capital market institutions, banks (universal, commercial and retail), corporate treasuries, financial industry utilities, clearing houses, exchanges, systems integrators, application vendors and corporate enterprises. By working with a global and diverse client base Volante is able to encapsulate a best practice approach into all its product lines. For further information please visit: www.volantetech.com
News Article | February 15, 2017
PRINCETON, N.J., Feb. 15, 2017 /PRNewswire/ -- Signum Biosciences, Inc. ("Signum") announced today that the National Institute of Allergy and Infectious Diseases (NIAID) awarded the company a Small Business Innovation Research (SBIR) Phase IIB grant totaling $3.0 million over 3 years for t...
News Article | January 17, 2017
COEUR D’ALENE, Idaho, Jan. 17, 2017 (GLOBE NEWSWIRE) -- Jack W. Gustavel, Chairman and Chief Executive Officer of Idaho Independent Bank (“IIB” or the “Bank”) (OTC BB:IIBK), announced that the Board of Directors authorized increasing IIB's 2014 Buyback Plan ("Buyback") to $7 million of the Bank's Common Stock ("Common Stock") and extending the Buyback for a year, or earlier if the $7 million maximum has been expended. As of January 17, 2017, $4.8 million of Common Stock had been purchased. The Common Stock may be used in connection with IIB’s employee benefit plans and/or for other corporate purposes. Purchases are subject to availability, market conditions, and other factors. IIB was established in 1993 as an Idaho state-chartered, commercial bank that operates branches in Boise (3), Caldwell, Coeur d’Alene, Hayden, Meridian, Mountain Home, Nampa, Star, and Sun Valley/Ketchum, Idaho. IIB has been named to DepositAccounts.com’s Top 200 Healthiest Banks in America for the second straight year and received honorable mention from Populus for being one of the 2016 Best Places to Work in Idaho. The Bank has approximately 200 employees throughout the State of Idaho. To learn more about IIB, visit us online at www.theidahobank.com. Statements contained herein concerning future performance, developments or events, expectations for earnings, growth and market forecasts, and similar statements that are not historical facts are intended to be “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995, and as such, are subject to a number of risks and uncertainties that may cause actual results to differ materially from expectations or our stated objectives. Factors that could cause actual results to differ materially, include, but are not limited to, declines in regional and general economic conditions; changes in interest rates, deposit flows, demand for loans, real estate values, competition, and/or loan delinquency rates; changes in accounting principles, practices, policies, or guidelines; changes in legislation or regulations; changes in the regulatory environment; changes in monetary policy of the Federal Reserve Bank; changes in fiscal policy of the Federal government and the State of Idaho; changes in other economic, competitive, governmental, regulatory, and technological factors affecting operations, pricing, products, and services; material unforeseen changes in the liquidity, results of operations, or financial condition of the Bank's customers . Accordingly, these factors should be considered in evaluating forward-looking statements, and there should not be undue reliance placed on such statements. The Bank undertakes no responsibility to update or revise any forward-looking statements.
News Article | March 3, 2017
BONE THERAPEUTICS (Brussels:BOTHE) (Paris:BOTHE) (code Euronext Bruxelles et Paris : BOTHE, Eligible PEA-PME), société de thérapie cellulaire osseuse qui répond à d’importants besoins médicaux non satisfaits dans les domaines de l’orthopédie et des maladies osseuses, publiera ses résultats pour l’exercice 2016, clos au 31 décembre, le jeudi 16 mars 2017. PREOB®, produit cellulaire autologue de Bone Therapeutics est actuellement en étude clinique pivot de Phase IIB/III pour deux indications : l'ostéonécrose et les fractures au processus de guérison totalement interrompu, et en Phase II pour l'ostéoporose sévère. ALLOB®, son produit cellulaire osseux allogénique "prêt à l’emploi" est en Phase II pour le traitement des fractures avec retard de consolidation et la fusion lombaire dans les cas de maladie dégénérative de la colonne vertébrale, inclusif une thérapie mini-invasive pour des patients en échec de fusion vertébrale. La Société poursuit par ailleurs des programmes de recherche préclinique et développe de nouveaux produits candidats. Fondée en 2006, Bone Therapeutics est basée à Gosselies (sud de Bruxelles, Belgique). Les produits régénérateurs de Bone Therapeutics sont fabriqués selon les normes BPF les plus élevées et sont protégés par un important portefeuille de 9 familles de brevets. Plus d’informations sont disponibles sur www.bonetherapeutics.com/fr. Certaines déclarations, croyances ou opinions du communiqué de presse sont des déclarations prospectives, et reflètent les attentes actuelles et les projections futures relatives à des événements futurs de la Société ou, le cas échéant, de ses administrateurs. De par leur nature, les déclarations prospectives impliquent un certain nombre de risques, d'incertitudes et de suppositions qui pourraient entraîner des résultats ou événements effectifs substantiellement différents de ceux exprimés de manière explicite ou implicite dans les déclarations prospectives. Ces risques, incertitudes et suppositions peuvent affecter de manière négative les résultats et effets financiers des plans et événements décrits dans le communiqué. Une multitude de facteurs, notamment, sans s'y limiter, des modifications intervenant en matière de demande, de concurrence et de technologie, peuvent avoir pour conséquence que les événements, performances ou résultats diffèrent de manière importante des développements anticipés. Les déclarations prospectives contenues dans ce communiqué de presse qui se basent sur des tendances ou des activités passées ne constituent pas des garanties que ces tendances ou activités se poursuivront à l'avenir. En conséquence, la Société rejette expressément toute obligation ou engagement de publier des mises à jour ou révisions des déclarations prospectives de ce communiqué de presse suite à une modification des prévisions ou à une modification des événements, des conditions, des suppositions ou des circonstances sur lesquelles ces déclarations prospectives sont basées. Ni la Société ni ses conseillers ou représentants, ni aucune de ses filiales, ni aucun cadre ou employé de ces personnes ne garantit que les hypothèses sous-jacentes à ces déclarations prospectives sont exemptes d'erreurs et aucun de ceux-ci n'accepte la moindre responsabilité en ce qui concerne l'exactitude future des déclarations prospectives contenues dans ce communiqué de presse ou la survenance effective des événements prévus. Il ne faut pas placer une confiance indue dans les déclarations prospectives, qui ne concernent que la situation telle qu'elle se présente à la date de ce communiqué de presse.
News Article | March 3, 2017
BONE THERAPEUTICS (Brussels:BOTHE) (Paris:BOTHE) (Euronext Brussels and Paris: BOTHE), the bone cell therapy company addressing high unmet medical needs in orthopaedics and bone diseases, today announces it will release its full year results for the year ended 31 December 2016 on Thursday 16 March 2017. Thomas Lienard, Chief Executive Officer, and Wim Goemaere, Chief Financial Officer, will host a conference call and Q&A at 10:00 CET / 09:00 GMT to discuss the results. The call will be conducted in English and a replay will be available for 30 days via the company’s website. To access the conference call, please dial one of the appropriate numbers below quoting the conference ID: The presentation for the call will be made available on the Investors section of the Bone Therapeutics website shortly before the call. To ensure a timely connection, it is recommended that users register at least 10 minutes prior to the scheduled start timing. Bone Therapeutics is a leading biotechnology company specializing in the development of cell therapy products intended for orthopaedics and bone diseases. The current standard of care in this field involves major surgeries and long recovery periods. To overcome these problems, Bone Therapeutics is developing a range of innovative regenerative products containing osteoblastic/bone-forming cells, administrable via a minimally invasive percutaneous technique; a unique proposition in the market. PREOB®, Bone Therapeutics’ autologous bone cell product, is currently in pivotal Phase IIB/III clinical studies for two indications: osteonecrosis and non-union fractures, and in Phase II for severe osteoporosis. ALLOB®, its allogeneic “off-the-shelf” bone cell product, is in Phase II for the treatment of delayed-union fractures and lumbar fusion for degenerative disease of the spine, including a minimally invasive therapy for failed spinal fusions. The Company also runs preclinical research programs and develops novel product candidates. Founded in 2006, Bone Therapeutics is headquartered in Gosselies (South of Brussels, Belgium). Bone Therapeutics’ regenerative products are manufactured to the highest GMP standards and are protected by a rich IP estate covering 9 patent families. Further information is available at: www.bonetherapeutics.com. Certain statements, beliefs and opinions in this press release are forward-looking, which reflect the Company or, as appropriate, the Company directors’ current expectations and projections about future events. By their nature, forward-looking statements involve a number of risks, uncertainties and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, changes in demand, competition and technology, can cause actual events, performance or results to differ significantly from any anticipated development. Forward looking statements contained in this press release regarding past trends or activities should not be taken as a representation that such trends or activities will continue in the future. As a result, the Company expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this press release as a result of any change in expectations or any change in events, conditions, assumptions or circumstances on which these forward-looking statements are based. Neither the Company nor its advisers or representatives nor any of its subsidiary undertakings or any such person’s officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in this press release or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this press release.
News Article | March 3, 2017
Bone Therapeutics is een leidend biotechnologiebedrijf gespecialiseerd in de ontwikkeling van celtherapieproducten voor de orthopedie en botziektes. De huidige standaardbehandeling in dit veld houdt zware chirurgische ingrepen en lange herstelperioden in. Om die problemen aan te pakken, ontwikkelt Bone Therapeutics een waaier aan innovatieve, regeneratieve producten met osteoblastische (botvormende) cellen, die op minimaal invasieve wijze toegediend worden; een unieke aanpak in deze markt. Het autologe product van Bone Therapeutics, PREOB®, bevindt zich momenteel in een beslissende Fase IIB/III klinische studies voor de behandeling van osteonecrose en niet-helende breuken, alsook in een Fase II voor ernstige osteoporose. Het “off the shelf” allogeen celproduct, ALLOB®, bevindt zich op dit moment in Fase II voor vertraagde botheling en vertebrale artrodese. De Onderneming heeft verder nog verschillende preklinische onderzoeksprogramma’s lopen en ontwikkelt nieuwe productkandidaten. Bepaalde verklaringen, overtuigingen en meningen in dit persbericht zijn toekomstgerichte verklaringen en weerspiegelen de Vennootschap haar of, waar toepasselijk, de bestuurders van Bone Therapeutics hun, huidige verwachtingen en vooruitzichten betreffende toekomstige ontwikkelingen. Door hun aard houden toekomstgerichte verklaringen een aantal inherente risico’s, onzekerheden en veronderstellingen in die tot gevolg kunnen hebben dat de werkelijke resultaten of gebeurtenissen in aanzienlijke mate verschillen van de resultaten of gebeurtenissen die impliciet of expliciet worden weergegeven in de toekomstgerichte verklaringen. Deze risico’s, onzekerheden en veronderstellingen kunnen een negatieve weerslag hebben op de afloop en de financiële gevolgen van de in dit document beschreven plannen en gebeurtenissen. Verschillende factoren waaronder, maar niet beperkt tot, veranderingen in vraag, concurrentie en technologie, kunnen tot gevolg hebben dat de werkelijke gebeurtenissen, prestaties of resultaten in aanzienlijke mate verschillen van enige verwachte ontwikkeling. Toekomstgerichte verklaringen in dit persbericht inzake trends of activiteiten in het verleden mogen niet beschouwd worden als een verklaring dat trends en activiteiten die zich zullen voortzetten in de toekomst. Bijgevolg doet Bone Therapeutics uitdrukkelijk afstand van enige verplichting of verbintenis om toekomstgerichte verklaringen in dit persbericht bij te werken of te herzien, zij het op basis van veranderingen in verwachtingen of veranderingen in gebeurtenissen, voorwaarden, veronderstellingen of omstandigheden waarop deze toekomstgerichte verklaringen zijn gebaseerd. Noch Bone Therapeutics, noch haar adviseurs of vertegenwoordigers, noch haar dochterOndernemingen of enige met deze personen verbonden werknemers garandeert dat de veronderstellingen aan de basis van dergelijke toekomstgerichte verklaringen vrij zijn van fouten, noch aanvaarden zij verantwoordelijkheid voor de toekomstige correctheid van de toekomstgerichte verklaringen in dit persbericht of het al dan niet plaatsvinden van de voorspelde ontwikkelingen. U wordt geadviseerd behoedzaam om te gaan met toekomstgerichte verklaringen die enkel gelden op datum van dit persbericht.