Multicenter, Rising, Multiple-Dose, Placebo-Controlled, Dose-Response Study to Evaluate the Safety, Tolerability, and Anti-Viral Activity of 4 Weeks of Treatment With 200-800 Mg Fozivudine Tidoxil in Patients With HIV-1 Infection (MF4314).
To identify doses of fozivudine tidoxil that are well tolerated and produce measurable antiviral activity. To identify the adverse event profile that defines the maximum tolerated dose. To characterize the single- and multiple-dose pharmacokinetics of fozivudine and its metabolites. To correlate the adverse event profile and antiviral activity of fozivudine with pharmacokinetic parameters.
Impact of Self-Management of Oral Anticoagulation in the Elderly in Terms of Mortality and Morbidity: a Randomized Controlled Trial - SPOG 60+
Self-management is safe and reliable in patients with long-term oral anticoagulation (OAC). However, no study has yet assessed the safety and efficacy of OAC self-management in elderly patients with major thromboembolic and haemorrhagic complications as primary outcomes. In this multi-centre, open, randomised controlled trial, patients aged 60 years or will be randomised into a self-management or routine care group and followed up for at least two years. The primary hypothesis of the study is that self-management of oral anticoagulation is superior compared to routine control in terms of reducing thromboembolic events requiring hospitalisation and all major bleeding complications as the primary endpoint.
Transgenic mice expressing a human apolipoprotein[a] allele
2区 · 生物学
作者: Acquati, Francesco ; Hammer, Robert ; Ercoli, Barbara ; Mooser, Vincent ; Tao, Ruixan ; Ronicke, Volker ; Michalich, Alessandra ; Chiesa, Giulia ; Taramelli, Roberto ; Hobbs, Helen H. ; Muller, Hans-Joachim
The most important determinant of plasma levels of Lp[a] are sequence differences at the highly polymorphic apolipoprotein[a] (apo[a]) locus. To define the sequences that mediate the regulation of apo[a] expression, we cloned a 370 kb DNA fragment that included a 130 kb apo[a] gene, and 40 kb 5'- and 200 kb 3'-flanking region from an individual with high plasma levels of Lp[a] using a YAC vector. This genomic clone was used to generate transgenic mice. In the YAC-apo[a] transgenic mouse, apo[a] was only expressed in the liver, as it is in humans. The mean serum level of apo[a] in 4-week-old YAC-apo[a] transgenic mice was 20 mg/dl. In the female mice the levels of apo[a] varied over a 1.5-fold range during the 4-day estrus cycle and the levels correlated directly with serum progesterone levels. The serum levels of apo[a] decreased to almost undetectable level in male mice after puberty and this decrease was reversed by castration. Ingestion of a high-fat diet resulted in a approximately 100-fold fall in hepatic apo[a] mRNA levels and >60-fold decrease in serum apo[a] levels. To delimit the control elements that mediate tissue-specific and sex hormone-responsive apo[a] transcription, we derived a reporter YAC in which 40 kb of 5' flanking sequences from the cloned apo[a] allele were linked to a luciferase reporter gene. Analysis of four independent transgenic lines revealed no hepatic luciferase expression, suggesting that important cis -acting elements located outside the apo[a] 5'-flanking region are necessary for in vivo expression of apo[a].
Improved procedures for large scale preparation of 6- and 7-oxy-substituted isoquinolines and a convenient work-up protocol for titanium supported reactions
作者: Kucznierz, Ralf ; Dickhaut, Joachim ; Leinert, Herbert ; Von Der Saal, Wolfgang
Improved procedures for large scale preparation of oxy-substituted isoquinolines are reported. Moreover, a simple and convenient protocol for alk. work-up of titanium containing reaction mixtures is given, which is expected to be of general interest even for reactions on a tech. scale.
1999-02-28·Anticancer Research4区 · 医学
Identification of URIM, a novel gene up-regulated in metastasis
4区 · 医学
作者: Hildebrandt, Tobias ; Preiherr, Josef ; Klostermann, Stefan ; Kaul, Sepp ; Zendman, Albert J. W. ; Van Muijen, Goos N. P. ; Weidle, Ulrich H.
URIM (Up-Regulated In Metastasis) was identified as a new gene by Differential Display Technique during investigation of the transcriptional pattern of a metastasizing (NMCL-1) and a non-metastasizing (530) human melanoma cell line. The protein is encoded by 206 amino acids with an isoelectric point of 10.4. In addition, URIM displays a putative nuclear localization signal and a putative leucine zipper suggesting that URIM may function as a nuclear protein. Expression of URIM in several normal tissues and tumor cell lines was studied by Northern blotting. Surprisingly, 17 fold increased steady-state mRNA levels for URIM were detected in three cell lines derived from bone marrow micrometastasis of mammary carcinoma and one mammary carcinoma cell line derived from ascites fluid compared to normal epithelial cells from mammary gland and two cell lines derived from primary mammary carcinoma. These findings indicate that expression of URIM might be deregulated in metastases of different types of tumors.
WALTHAM, Mass., Feb. 09, 2023 (GLOBE NEWSWIRE) -- Repligen Corporation (NASDAQ:RGEN) today announced the appointment to its Board of Directors of life sciences tools industry leader Martin D. Madaus.
Dr. Madaus brings to the Repligen board over 25 years of industry experience, including five years as Chairman, President and Chief Executive Officer of Millipore Corporation, where he was integral to the company’s transformation into a life science leader, and its acquisition by Merck KGaA in 2010. He is an active board leader, currently serving two public companies; as Lead Director for precision health technology company Quanterix Corporation and as Board member for mass cytometry player Standard BioTools, Inc. (previously Fluidigm Corporation).
Karen A. Dawes, Chairperson of the Board of Directors for Repligen, said, “We are thrilled to welcome Dr. Madaus to the Repligen board, as the company continues to drive innovation in bioprocessing and expand into new markets. Martin’s exceptional career demonstrates his success as a leader and his aptitude for guiding growth. We are certain to benefit from his involvement as we continue to set new standards in bioprocessing and scale our product portfolio.”
Tony J. Hunt, President and Chief Executive Officer said, “I’m excited for this opportunity to work more closely with Martin. He is a terrific addition to the Board, bringing extensive bioprocessing and biopharmaceutical industry experience, especially in the areas of strategy, M&A and commercial. Martin will be a key asset to the Board as we move forward on our journey of transforming bioprocessing through cutting edge innovation.”
Dr. Madaus’ executive pro his aforementioned leadership of Millipore Corporation, in addition to his earlier role as President and Chief Executive Officer, N.A., with Roche Diagnostics Corp., and his more recent position as Chairman and Chief Executive Officer at Ortho Clinical Diagnostics. He is currently a senior operating executive at The Carlyle Group.
In addition to his current public company board positions, Dr. Madaus currently leads the boards of three private companies - Unchained Labs, Emulate, Inc. and UltiVue Inc. Dr. Madaus previously served on the Board at Covidien, Ltd. and Mettler-Toledo International Inc.
Dr. Madaus began his career as a veterinarian, before joining Boehringer Mannheim Corporation, where he worked in sales and marketing roles from 1989-1996, until his move into general management coincident with the company’s acquisition by Roche Holdings, AG. He holds a D.V.M. from the University of Munich and a Ph.D. in veterinary medicine from the University of Veterinary Medicine Hannover in Germany.
About Repligen Corporation
Repligen Corporation is a global company that develops and commercializes highly innovative bioprocessing technologies and systems that enable efficiencies in the process of manufacturing biological drugs. We are inspiring advances in bioprocessing for the customers we serve; primarily biopharmaceutical drug developers and contract development and manufacturing organizations (CDMOs) worldwide. Our focus areas are Filtration, Chromatography, Process Analytics, Fluid Management and Proteins. Our corporate headquarters are located in Waltham, Massachusetts, with additional administrative and manufacturing operations worldwide. The majority of our manufacturing sites are located within the U.S. (California, Massachusetts, New Hampshire, New Jersey and New York), and we also have sites in Estonia, France, Germany, Ireland, the Netherlands and Sweden. For more information about the company, including Repligen news releases, see our website at . Follow us on LinkedIn and Twitter.
This press release may contain forward-looking statements within the meaning of the federal securities laws. Investors are cautioned that statements in this press release which are not strictly historical statements including, without limitation, statements identified by words like “believe,” “expect,” “may,” “will,” “should,” “seek,” or “could” and similar expressions, constitute forward-looking statements. Such forward-looking statements are subject to a number of risks and uncertainties that could cause actual results to differ materially from those anticipated, including risks discussed from time to time in our filings with the Securities and Exchange Commission. We expressly disclaim any responsibility to update any forward-looking statements, except as required by law.
Sondra S. Newman
Global Head of Investor Relations
A photo accompanying this announcement is available at
Repligen Appoints Martin Madaus to Board of Directors
Karuna Therapeutics is looking to compete with Boehringer Ingelheim on depression and anxiety with a new
to Goldfinch Bio’s assets, starting with $15 million to the shuttered biotech.
Karuna steps into an arena already being tested by Boehringer in multiple Phase II studies — the two are targeting transient receptor potential canonical 4 and 5, or TRPC4/5, which is thought to have a role in neuroscience indications. Goldfinch’s asset went through a
Phase II in kidney diseases
, but Karuna’s sights are set on mood and anxiety disorders for now.
At the forefront of the deal stands GFB-887, with preclinical candidates also in the package.
Based on what Karuna saw out of Boehringer and the literature, the biotech was looking for a new mechanism to treat depression and anxiety, CSO Steve Paul said in an interview. It follows the thesis of Karuna, similar to its approach in schizophrenia and Alzheimer’s psychosis, which
paid out big time
Phase III data
Before signing the deal, which could balloon by $520 million in biobucks for each candidate, Karuna did a materials transfer agreement to test out Goldfinch’s GFB-887 and also investigate BI’s compound, Paul said. The results were promising and Karuna was “just persistent enough and hung around long enough” to beat out other potential dealmakers, the executive added.
Boehringer is investigating its TRPC4/5 inhibitor, dubbed BI 1358894, in Phase II studies in
borderline personality disorder
major depressive disorder
post-traumatic stress disorder
“Hopefully that’ll help de-risk us a little bit,” Paul said, referring to the BI studies, noting Karuna doesn’t have an interest in testing GFB-887 in borderline personality disorder. Karuna’s compound has a longer half-life, Paul noted, meaning they’ll look to test once-daily dosing rather than BI’s twice-daily strategy.
Karuna will announce more development plans in the second half of this year, Paul said. The executive, who swapped C-suite roles last year, is well-versed in CNS by way of decades at NIH, Eli Lilly and as co-founder of Sage Therapeutics and Voyager Therapeutics.
For Goldfinch, the news means a “happy ending,” CEO Tony Johnson said in an interview. Karuna gets GFB-887 and the “full program,” including a “constellation of key molecules” associated with TRPC4/5, Johnson said.
The money will go to an “assignment estate” of Goldfinch, as the Third Rock-launched biotech recently entered an assignment for the benefit of the creditors (ABC), an alternative to bankruptcy, Johnson told Endpoints last week. Thursday morning, Johnson said Goldfinch went through with the ABC because “you just can’t guarantee that a deal will be signed.”
“They had identified TRPC4/5 as one of those exciting targets” in psychiatry, CFO and COO Kyle Kuvalanka said in an interview. “They had contacted us a while ago knowing that we had these backup compounds, and so this early interaction enabled them to move very quickly when we decided to stop developing ‘887 in kidney disease, but we had been talking to many other CNS and kidney companies.”
Goldfinch was founded with support from kidney specialists, nephrologists and scientists steeped in that area, so the biotech set its sights on that space, Johnson said, noting while they were in Phase II, other opportunities came to light in neuroscience.
“This is a very happy ending and maybe not where we started more than five years ago, but a happy ending nonetheless and a real opportunity for a different collection of patients who are also in need of new mechanisms and molecules,” Johnson said.
Boehringer Ingelheim (BI) has reported positive results from its phase 2b trial of spesolimab, demonstrating that the anti-interleukin-36 receptor antibody can prevent flares in adolescent and adult patients with generalised pustular psoriasis (GPP) for up to 48 weeks.
The EFFISAYIL 2 trial, which evaluated maintenance treatment with subcutaneous spesolimab for the prevention of GPP flares and sustained control of GPP symptoms, met its primary and key secondary endpoint and reinforced previous positive results in the EFFISAYIL clinical programme.
Spesolimab, sold under the brand name Spevigo, is already approved in major markets for GPP flares in adults.
The antibody was most recently approved by the European Commission in December 2022 for this indication, a decision supported by results from the phase 2 EFFISAYIL 1 trial.
In EFFISAYIL 1, after one week, 54% of patients treated with a single dose of Spevigo showed no visible pustules, compared to 6% of patients in the placebo group.
After 12 weeks, more than four out of five Spevigo-treated patients had no visible pustules and clear/almost clear skin.
“These results support positive results from the previous phase 2 study in the EFFISAYIL clinical trial programme, which formed the basis of spesolimab approvals as the first specific treatment for GPP flares in adults in major markets including the US, Japan, Mainland China and the EU,” said Carinne Brouillon, member of the board of managing directors, responsible for human pharma at BI.
GPP is a rare, heterogenous and potentially life-threatening neutrophilic skin disease, which is clinically distinct from plaque psoriasis. GPP is caused by neutrophils – a type of white blood cell – accumulating in the skin, causing painful, sterile pustules all over the body.
Despite the varying severity of GPP flares, if left untreated they can be life-threatening due to complications such as sepsis and multisystem organ failure, and the unpredictability and severity of these flares greatly affects quality of life.
“Painful GPP flares can occur suddenly, escalate quickly and may require urgent hospital care leaving people anxious and uncertain about what the future might hold,” Brouillon said.
BI reports that there is a ‘high unmet need’ for treatments with an acceptable safety profile that can rapidly resolve the symptoms of GPP flares and prevent their reoccurrence.