Molecular Targeted Maintenance Therapy Versus Standard of Care in Advanced Biliary Cancer: an International, Randomised, Controlled, Open-label, Platform Phase 3 Trial
The object of this trial is to evaluate whether the introduction of a targeted therapy after 4 cycles of the current standard-of-care treatment for advanced biliary cancer is superior to continuing with the standard treatment. The trial is composed of two phases: (i) An initial screening phase to identify a suitable patient population, during which a molecular profile of the patient's tumour will be obtained, and (ii) a randomised comparative trial in which patients with disease control after 4 cycles of standard treatment, and whose tumour harbours a targetable molecular alteration, will be randomised (2:1) to receive either a matched targeted therapy or to continue with the standard treatment.
An Integrated Pharmacokinetic and Safety Open-label Basket Trial of Daprodustat for the Treatment of Anemia Associated with Chronic Kidney Disease in Male and Female Children and Adolescents Aged 3 Months to Under 18 Years Requiring or Not Requiring Dialysis. - ASCEND-P
A Phase 2, Single-Arm, Open-Label Study with Dostarlimab Monotherapy in Participants with Untreated Stage II/III dMMR/MSI-H Locally Advanced Rectal Cancer - Phase 2 Study of Dostarlimab in Untreated dMMR/MSI-H Locally Advanced Rectal Cancer
100 项与 GlaxoSmithKline Research & Development Ltd. 相关的临床结果
0 项与 GlaxoSmithKline Research & Development Ltd. 相关的专利（医药）
项与 GlaxoSmithKline Research & Development Ltd. 相关的文献（医药）
2019-08-22·Journal of Medicinal Chemistry1区 · 医学
A Qualified Success: Discovery of a New Series of ATAD2 Bromodomain Inhibitors with a Novel Binding Mode Using High-Throughput Screening and Hit Qualification
1区 · 医学
作者: Bamborough, Paul ; Chung, Chun-wa ; Demont, Emmanuel H. ; Bridges, Angela M. ; Craggs, Peter D. ; Dixon, David P. ; Francis, Peter ; Furze, Rebecca C. ; Grandi, Paola ; Jones, Emma J. ; Karamshi, Bhumika ; Locke, Kelly ; Lucas, Simon C. C. ; Michon, Anne-Marie ; Mitchell, Darren J. ; Pogany, Peter ; Prinjha, Rab K. ; Rau, Christina ; Roa, Ana Maria ; Roberts, Andrew D. ; Sheppard, Robert J. ; Watson, Robert J.
The bromodomain of ATAD2 has proved to be one of the least-tractable proteins within this target class. Here, we describe the discovery of a new class of inhibitors by high-throughput screening and show how the difficulties encountered in establishing a screening triage capable of finding progressible hits were overcome by data-driven optimization. Despite the prevalence of nonspecific hits and an exceptionally low progressible hit rate (0.001%), our optimized hit qualification strategy employing orthogonal biophysical methods enabled us to identify a single active series. The compounds have a novel ATAD2 binding mode with noncanonical features including the displacement of all conserved water molecules within the active site and a halogen-bonding interaction. In addition to reporting this new series and preliminary structure-activity relationship, we demonstrate the value of diversity screening to complement the knowledge-based approach used in our previous ATAD2 work. We also exemplify tactics that can increase the chance of success when seeking new chemical starting points for novel and less-tractable targets.
2018-08-25·International Journal of Pharmaceutics (Amsterdam, Netherlands)2区 · 医学
Multivariate monitoring for the industrialization of a continuous wet granulation tableting process
2区 · 医学
作者: Zomer, Simeone ; Zhang, Jun ; Talwar, Sameer ; Chattoraj, Sayantan ; Hewitt, Christopher
The pharmaceutical industry is undergoing a significant change in product development and manufacturing strategies with the progressive shift from batch to continuous processes. These typically feature vast volumes of data generated by the numerous sensors connected to several unit operations running over the period of several hours or even days and that demand the application of increasingly efficient tools for process understanding, monitoring and control. This paper describes the use of multivariate statistical process modeling by means of chemometric methods to monitor the continuous wet granulation tableting process for a drug product currently under development. Models are tailored to the different units that make up the continuous tableting line, from material feeding and granulation up to tablet compression, where the solutions devised reflect the different dynamics of each unit and are used as maintenance and intervention tools to optimise manufacturing and associated operations retrospectively as well as in real-time, as part of the product industrialisation programme.
2,4-Diamino-8-quinazoline carboxamides as novel, potent inhibitors of the NAD hydrolyzing enzyme CD38: Exploration of the 2-position structure-activity relationships
3区 · 医学
作者: Deaton, David N. ; Haffner, Curt D. ; Henke, Brad R. ; Jeune, Michael R. ; Shearer, Barry G. ; Stewart, Eugene L. ; Stuart, J. Darren ; Ulrich, John C.
Starting from 4-amino-8-quinoline carboxamide lead 1a and scaffold hopping to the chemically more tractable quinazoline, a systematic exploration of the 2-substituents of the quinazoline ring, utilizing structure activity relationships and conformational constraint, resulted in the identification of 39 novel CD38 inhibitors. Eight of these analogs were 10-100-fold more potent human CD38 inhibitors, including the single digit nanomolar inhibitor 1am. Several of these molecules also exhibited improved therapeutic indices relative to hERG activity. A representative analog 1r exhibited suitable pharmacokinetic parameters for in vivo animal studies, including moderate clearance and good oral bioavailability. These inhibitor compounds will aid in the exploration of the enzymatic functions of CD38, as well as furthering the study of the therapeutic implications of NAD enhancement in metabolic disease models.
项与 GlaxoSmithKline Research & Development Ltd. 相关的新闻（医药）
It’s once again open season for biotech IPOs, as the summer drought has given way to an autumn flood.
Five companies filed to go public on Friday, including four penciling in $100 million fundraises: Evotec, Entrada Therapeutics, Aura Biosciences and Vaxxinity. The fifth biotech, Blue Water Vaccines, is estimating a more modest $24 million.
The combined industry raise surpassed $14 billion last week after two more biotechs priced, per the
tally, and the sector remains on pace to eclipse last year’s record of $16.5 billion. It could come down to the wire, however, after a third quarter lull that
the lowest levels of IPO numbers since the start of 2020.
German biotech Evotec has racked up a veritable stable of biopharma partners, and now it’s taking its talents to Nasdaq.
Evotec has made its name with its range of platform plays aimed at helping its collaborators develop drugs. The biotech has, over the last 25 years, built a suite of five different technologies that it utilizes in partnerships covering small molecules, omics, biologics, cell therapy and gene therapy.
Some of Evotec’s more prominent recent deals come from Takeda,
for the first small molecule ligand for RNA in a March partnership, and Novo Nordisk, which
to shell out nearly $180 million per kidney disease program. Additionally, Evotec has spent time building out its manufacturing capabilities,
a former GlaxoSmithKline R&D site in Italy over the summer after
a French plant in April.
Novo Holdings and T. Rowe Price are the big winners from the IPO, holding 11% and 10% stakes in Evotec, respectively, according to the
. Mubadala Investment Company, the UAE’s sovereign wealth fund that purchased $236 million worth of shares last October, also nets a 5.6% stake pre-offering.
The biotech also says its pipeline contains more than 130 drug candidates. Most of the IPO funds will be directed toward continued manufacturing expansion.
When Evotec starts trading, it will do so under the ticker
Half a year after locking down a hefty $116 million
, Entrada Therapeutics says it’s ready for its public debut.
The Boston-based biotech filed its S-1 papers on Friday, penciling in a $100 million raise, which has become the standard for companies that often go on to raise much more.
The platform, based on Dehua Pei’s lab research at Ohio State University, involves a new technology Entrada calls endosomal escape vehicles. EEVs are essentially cyclic peptides that trigger a process enabling cell membranes to take in biologic conjugates, CEO Dipal Doshi told
back in March.
Priority number one is neuromuscular diseases like Duchenne muscular dystrophy. In such diseases, patients have mutations that prevent the translation of RNA into proteins — in Duchenne’s case, dystrophin.
Oligonucleotides connected to the EEVs force the cells to skip these mutations in their genetic code, Doshi said, allowing for the creation of dystrophin. Through this method, the dystrophin can then get into the appropriate muscles.
Entrada’s lead candidate, ENTR-601-44, is expected to enter the clinic in DMD next year — and some of the IPO funds will be used to help get it there.
Before pivoting to oligonucleotides, Entrada’s main focus was enzyme replacement therapies, with a primary target of the mitochondrial disease known as MNGIE. While the startup has completed IND-enabling studies, it’s now looking for another company to take the program into the clinic.
“We continue to believe that the program will have an important role in the future treatment of patients with MNGIE,” the company said in the
, noting that it’s still exploring potential partnerships.
MPM Capital and 5AM Ventures, which have been around since the launch round, hold a considerable proportion of shares, with 20.74% and 19.94% pieces of the pie, respectively. Doshi, on the other hand, has a 5.14% stake, according to the S-1.
The company plans to trade under the ticker
Aura Biosciences CEO Elisabet de los Pinos hinted at a forthcoming IPO after securing a
Series E round
back in March.
That day has apparently come, as the company submitted its S-1 papers last Friday, penciling in a $100 million raise.
Aura’s platform centers around virus-like particles, which can be conjugated with drugs or loaded with nucleic acids to create virus-like drug conjugates, or VDCs. The viral nanoparticles — modeled after the human papillomavirus — are light-activated, meaning they selectively destroy the membrane of cancer cells upon activation with an ophthalmic laser.
AU-011, Aura’s first VDC candidate, is being developed for primary choroidal melanoma, an eye cancer for which no other drugs exist. The current approach to treatment is radioactivity, which can cause irreversible damage to the retina and lead to blindness.
“The cytotoxic payload for the drug in the clinic is activated with light, so it’s very safe,” de los Pinos told
in March. “And because of the cell activity of the virus-like particles, not binding to retina, it preserves vision.”
Aura plans to present six- to 12-month data from a Phase II dose escalation trial in 2022, and if all goes well, launch a pivotal trial in the second half of 2022, according to the
. There’s also an IND coming in the second half of 2022 for choroidal metastases, the company said.
Matrix Capital Management and Medicxi, which led Aura’s Series E and D rounds, respectively, each hold 10.1% of the company’s shares. De los Pinos has a 3% stake.
Aura will trade under the ticker
Dallas vaccine biotech Vaxxinity, rebranded from the consolidation of COVAXX and United Neuroscience in April, is shooting for a quick IPO.
The biotech centers its efforts around developing peptide-based vaccines for chronic diseases, arguing the current vaccine market struggles to ward off persistent conditions. Vaxxinity also believes this approach can capture some of the market share from monoclonal antibodies, saying its candidates can be manufactured more cheaply.
As its former name implies, the company has a Covid-19 vaccine candidate in development and has secured $2.8 billion worth of advance purchase commitments with Brazil, Ecuador, Peru and other countries to deliver more than 140 million doses of its vaccine. There are also pipeline programs for Alzheimer’s and Parkinson’s diseases, as well as migraines.
Most of the IPO funds will go toward clinical trials for the neurodegenerative indications, according to the
. Vaxxinity did not spell out the stakes of its principal shareholders but said there had been investment from United Biomedical and Prime Movers Lab.
When Vaxxinity goes public, it will trade under the ticker
Blue Water Vaccines is penciling in $24 million to take its flu shot programs public.
Everything is preclinical so far, but the biotech is working on a universal flu vaccine as well as what it calls an “H1 pre-pandemic shot” that it hopes will provide long-lasting protection. Both programs are licensed from the University of Oxford.
Preclinical proof of concept studies are slated to begin for the universal shot in the first half of next year, while the pre-pandemic shot will launch IND-enabling studies in the same time period. Blue Water also has two norovirus vaccine candidates under its belt, in addition to a vaccine program for the bacteria
When the offering is completed, the company will hire a new CEO in Joseph Hernandez, who pre-offering owns about 37% of shares. Cincinnati Cornerstone Investors owns the highest stake, however, at about 41%.
Once Blue Water goes public, it will trade under the ticker
ST. LOUIS & BUDE, England--(BUSINESS WIRE)--Jan. 25, 2006--
New Deals With CeNeS, Gemin X Biotechnologies, Genzyme, GlaxoSmithKline Research and Development, and Schering-Plough Research Institute Underscore Tripos' Commitment to Chemistry Services Business
Tripos, Inc. (Nasdaq:TRPS), a leading provider of drug discovery chemistry and informatics products and services, today announced new collaborations with several prominent pharmaceutical and life science organizations across Europe and North America to provide knowledge-driven customized chemistry services. These agreements encompass a combination of new partnerships and extensions with CeNeS Ltd., Gemin X Biotechnologies Inc., Genzyme Corp., GlaxoSmithKline Research and Development Ltd., and Schering-Plough Research Institute. Terms of the agreements, which were all finalized in the fourth quarter of 2005, were not disclosed.
100 项与 GlaxoSmithKline Research & Development Ltd. 相关的药物交易