A Phase 1, Double-Blind, Placebo-Controlled, Randomized, Single Ascending Dose, Multiple Ascending Dose, and Food Effect Study to Assess the Safety, Tolerability, and Pharmacokinetics of GS-441524 in Healthy Subjects

The goal of this clinical trial is to evaluate the safety, tolerability, and pharmacokinetics of GS-441524 in healthy subjects. The main questions to answer are: 1) What dosage of GS-441524 is required for adequate therapeutic plasma levels? 2) Does fed or fasted state produce variability in plasma levels? 3) How is GS-441524 eliminated from the body.
Participants will receive varying levels of GS-441524 or placebo to evaluate AEs and plasma levels.

开始日期2024-06-15

申办/合作机构

National Center for Advancing Translational Sciences

[+2]

NCT06136117

/ CompletedN/AIIT

Mpox, Biology, Outcome, Transmission and Epidemiology - Prospective Follow-up of High-risk Contacts

With the MBOTE-CONTACT study, a detailed follow-up study of high-risk contacts of mpox patients will be done. The MBOTE-CONTACT study will be nested in the NIH-Funded PALM-007 clinical trial (NCT05559099) and the MBOTE project on mpox transmission. The study will take place in Maniema Province, Democratic Republic of Congo (DRC). Participants will be recruited among high-risk contacts of mpox patients included in the PALM-007 trial. Consenting contacts will be either followed daily at the central study site or visited weekly by an outreach team in the community. They will be examined daily for signs and symptoms and asked to provide daily saliva and weekly blood samples for polymerase chain reaction (PCR) and/or serology. If participants develop mpox, they are offered treatment and enrollment in the PALM-007 trial.

开始日期2023-05-22

申办/合作机构

University of California, Los Angeles

[+4]

NCT04301154

/ Active, not recruiting临床1期IIT

Phase I, Proof of Concept, Open-Label, Randomized Clinical Trial to Evaluate the Safety and Effects of Using Prime-boost HIVIS DNA and MVA-CMDR Vaccine Regimens With or Without Toll-like Receptor 4 Agonist on HIV Reservoirs in Perinatally HIV Infected Children and Youth

Phase I, Proof of Concept, Open-Label, Randomized Clinical Trial to Evaluate the Safety and Effects of Using Prime-boost HIVIS DNA and MVA-CMDR Vaccine Regimens with or without Toll-like Receptor 4 Agonist on HIV Reservoirs in Perinatally HIV Infected Children and Youth

开始日期2022-02-18

申办/合作机构

The Henry M. Jackson Foundation

[+11]

100 项与 Leidos Biomedical Research, Inc. 相关的临床结果

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项与 Leidos Biomedical Research, Inc. 相关的文献（医药）

2025-08-04·JOURNAL OF EXPERIMENTAL MEDICINE

Immunopathological and microbial signatures of inflammatory bowel disease in partial RAG deficiency

Article

作者: Pasic, Srdjan ; Villa, Anna ; Yilmaz, Melis ; Riley, Deanna ; Smith, Grace ; Corsino, Cristina ; Lim, Ai Ing ; Lionakis, Michail S. ; Oguz, Cihan ; Dimitrova, Dimana ; Segre, Julia A. ; Belkaid, Yasmine ; Pala, Francesca ; Licciardi, Francesco ; Delmonte, Ottavia M. ; Freeman, Alexandra F. ; Bohrnsen, Eric ; Brigatti, Karlla W. ; Holland, Steven M. ; Alva-Lozada, Guisela ; Subramanian, Poorani ; Brett, Ana ; Potts, David E. ; Kimzey, Cole D. ; Pittaluga, Stefania ; Vujkovic-Cvijin, Ivan ; Bergerson, Jenna R.E. ; Daley, Stephen R. ; Ale, Hanadys ; Sharapova, Svetlana O. ; Marseglia, Gian Luigi ; Burns, Andrew S. ; Ward, Brant R. ; Strauss, Kevin A. ; Fontana, Elena ; Dos Santos Dias, Lucas ; Poskitt, Laura E. ; Ott de Bruin, Lisa ; Fink, Danielle ; Kuhns, Douglas B. ; Schwarz, Benjamin ; Dasso, Joseph F. ; Kong, Heidi H. ; Bosticardo, Marita ; Dutmer, Cullen M. ; Castagnoli, Riccardo ; Walter, Jolan E. ; Notarangelo, Luigi D. ; Oikonomou, Vasileios ; Angelova, Angelina ; Kenney, Heather

Partial RAG deficiency (pRD) can manifest with systemic and tissue-specific immune dysregulation, with inflammatory bowel disease (IBD) in 15% of the patients. We aimed at identifying the immunopathological and microbial signatures associated with IBD in patients with pRD and in a mouse model of pRD (Rag1w/w) with spontaneous development of colitis. pRD patients with IBD and Rag1w/w mice showed a systemic and colonic Th1/Th17 inflammatory signature. Restriction of fecal microbial diversity, abundance of pathogenic bacteria, and depletion of microbial species producing short-chain fatty acid were observed, which were associated with impaired induction of lamina propria peripheral Treg cells in Rag1w/w mice. The use of vedolizumab in Rag1w/w mice and of ustekinumab in a pRD patient were ineffective. Antibiotics ameliorated gut inflammation in Rag1w/w mice, but only bone marrow transplantation (BMT) rescued the immunopathological and microbial signatures. Our findings shed new light in the pathophysiology of gut inflammation in pRD and establish a curative role for BMT to resolve the disease phenotype.

2025-05-13·PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Activity and structure of human (d)CTP deaminase CDADC1

Article

作者: Slyvka, Anton ; Rathore, Ishan ; Skowronek, Krzysztof ; Kanai, Tapan ; Bochtler, Matthias ; Gewartowska, Olga ; Wlodawer, Alexander ; Yang, Renbin ; Lountos, George T. ; Czarnocki-Cieciura, Mariusz

Vertebrates have evolved an understudied protein termed CDADC1 (NYD-SP15) that contains an inactive N-terminal and active C-terminal DCTD-like domain. Here, we show that human CDADC1 is a (d)CTP-specific deaminase, with a roughly 2-fold in vitro preference for dCTP over CTP. We determined high-resolution cryo-EM structures of CDADC1 in the absence of substrate and in complex with dCTP and 5-methyl-dCTP. The structures show that CDADC1 forms trimers and dimers of trimers in solution. The (d)CTP substrate is selected by a narrow pocket for the cytosine base and multiple lysine and arginine contacts to the triphosphate. Substrate binding promotes the association of trimers into hexamers and the transition of the hexamers from a loose to a tighter arrangement. Genetic experiments in mice show that loss of Cdadc1 is surprisingly well tolerated, even in the absence of the dCMP deaminase Dctd that is considered as the main source of dUMP, the precursor of dTTP.

2025-05-01·JAMA Dermatology

Treatment of Cutaneous Neurofibromas in Neurofibromatosis Type 1 With MEK Inhibitor Selumetinib

Article

作者: Steinberg, Seth M. ; Choo-Wosoba, Hyoyoung ; Pichard, Dominique C. ; Gross, Andrea M. ; Baldwin, Lauren A. ; Widemann, Brigitte C. ; Wolters, Pamela L. ; Cannon, Ashley ; Dombi, Eva ; Derdak, Joanne ; Reid, Olivia H. ; Korf, Bruce R. ; Tibery, Cecilia M. ; Lobbous, Mina

Importance:

Cutaneous neurofibromas (cNFs) can cause itching, disfigurement, pain, and emotional difficulties in people with neurofibromatosis type 1 (NF1).

Objective:

To determine the impact of the mitogen-activated protein kinase kinase inhibitor selumetinib on cNF including change in tumor volume and patient-reported outcome measures.

Design, Setting, and Participants:

Adults with NF1 and 9 or more measurable cNFs were enrolled in this nonrandomized pilot trial at the National Cancer Institute and the University of Alabama at Birmingham, which spanned from August 26, 2017, to August 21, 2023.

Intervention:

Participants received selumetinib for up to 24 cycles (1 cycle = 28 days) with restaging visits after every 4 cycles.

Main Outcomes and Measures:

Photography and volumetric measurements of cNFs using calipers were used to evaluate the number and volume of tumors. Participants completed the Skindex-29 Quality of Life assessment to quantify the effect of treatment on symptoms, functioning, emotions, itching, and pain.

Results:

Among the 11 participants who enrolled, the median (range) age was 54 (28-75) years, and 6 were female. The median (IQR) best response across all participants and tumors was a −28.5% (−40.9% to −12.5%) decrease in cNF volume from baseline. Some participants showed a visible improvement in cNF burden while receiving treatment in standardized photographs. The median (range) duration of treatment was 9 cycles (1-24), with only 4 participants completing the full 24 cycles of treatment. Two of these participants continued treatment beyond the original 24 cycles due to perceived clinical benefit. All participants experienced at least 1 reversible drug-related adverse event (AE), with cutaneous AEs such as dry skin and rash being the most common. Two participants were removed from treatment due to concern for drug reaction with eosinophilia and systemic symptoms. While the Skindex-29 assessment showed improvement in emotion scores after cycle 1, there were no other significant or durable changes in scores.

Conclusions and Relevance:

In this nonrandomized pilot trial, selumetinib resulted in some decrease in cNF volume; however, there was no sustained improvement in patient-reported outcome measures. Study enrollment was incomplete, in part due to the COVID-19 pandemic, and highlights the challenges of treating patients with cNF with a drug that often leads to dermatologic AEs. Future larger studies using other measurement techniques, such as 3-dimensional photography, could help to yield results that are more generalizable to the phenotypically diverse NF1 population.

Trial Registration:

ClinicalTrials.gov Identifier: NCT02839720

项与 Leidos Biomedical Research, Inc. 相关的新闻（医药）

2025-02-18

·PRNewswire

The Inner Circle acknowledges, Elizabeth Roulette Baseler as a 2025 Pinnacle Professional Member

UNION BRIDGE, Md., Feb. 18, 2025 /PRNewswire/ -- Prominently featured in The Inner Circle, Elizabeth Roulette Baseler is acknowledged as a 2025 Pinnacle Professional Member Inner Circle of Excellence for her contributions in Healthcare and Research. Continue Reading Elizabeth Roulette Elizabeth Roulette Baseler, a distinguished leader in healthcare and clinical research with over 46 years of experience, currently serves as a Senior Clinical Project Manager at Manpower, a position she has held since 2023. Ms. Baseler's illustrious career includes a notable tenure with Leidos Biomedical Research Inc., where she advanced from 1978 to 2022 to become the Director of Clinical Monitoring for the Research Program Directorate at the Frederick National Laboratory for Cancer Research. In her role, she has been instrumental in establishing clinical infrastructure and ensuring regulatory compliance for clinical trials conducted by the National Institutes of Health, both in the United States and internationally. Ms. Baseler has traveled to over 29 countries, setting up clinical trials and managing teams in diverse and challenging environments. Her work includes significant contributions to the Ebola outbreak response in West Africa (2014-2016). A graduate of McDaniel College with a Bachelor's degree in Biology and Hood College with a Master of Science in Administration and Management, Ms. Baseler is affiliated with several professional organizations, including the Society of Clinical Research Associates and the Regulatory Affairs Professionals Society. She is also an active volunteer mentor at Woman to Woman Mentoring and contributes to Blessings in a Backpack and the Ocean City Reef Foundation. Her career has been marked by prestigious recognitions, including the Directors Award from the NIH and accolades from the National Institute of Allergy and Infectious Diseases. As she looks to the future, Ms. Baseler aims to continue her growth in clinical research, expand her involvement in mentoring and women's leadership, and share her experiences through writing. Ms. Baseler values the support of her family and mentors, remains passionate about biology and clinical research, and believes in the importance of networking, seeking advice, and effective public speaking. Contact: Katherine Green, 516-825-5634, [email protected] SOURCE The Inner Circle WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

高管变更

2024-09-04

·GlobeNewswire-Health Care

Nanocarry Therapeutics' Brain Penetrating Nanoplatform Selected by the NCI Nanotechnology Characterization Laboratory for its Preclinical Characterization Program

Program Will Facilitate Filing an IND Application Toward Human Clinical TrialsNESS ZIONA, Israel, Sept. 04, 2024 (GLOBE NEWSWIRE) -- Nanocarry Therapeutics, a pioneering biopharmaceutical company focused on advancing treatments for brain diseases through its innovative AxS nanoparticle platform, announced the selection of its lead product, AxS007, by the U.S. National Cancer Institute’s (NCI’s) Nanotechnology Characterization Laboratory (NCL) for comprehensive preclinical characterization. The NCL is located at the Frederick National Laboratory for Cancer Research, operated for NCI by Leidos Biomedical Research, Inc. Over 400 million people globally suffer from brain diseases that remain insufficiently treated due to the Blood-Brain Barrier (BBB) blocking most therapeutics. Nanocarry's AxS technology utilizes an insulin-based nanoplatform to cross the BBB, enabling the delivery of multiple copies and combinations of antibodies, small molecules, and other therapeutics to the brain, thus targeting various central nervous system disorders. AxS007 specifically targets brain metastases of HER2+ breast cancer, which affects 50% of metastatic breast cancer patients and represents a significant unmet need. The NCL was established to advance the use of nanotechnology in cancer research and accelerate the development of promising nanomedicine-based therapeutics. The NCI partners with the National Institute of Standards and Technology (NIST) and the FDA, offering preclinical testing and services on a competitive acceptance basis, to expedite the transition of nanomedicines from early-stage development to clinical applications. Through this collaboration, the NCL will conduct detailed preclinical evaluations of AxS007. These studies will support the advancement of AxS007 towards filing an Investigational New Drug (IND) application with the FDA and facilitate future clinical development. This partnership will also strengthen collaborations focused on utilizing AxS technology with diverse therapeutic agents to treat various brain diseases. "We are very pleased and honored that AxS007 has been selected for the NCL program, marking a pivotal moment for Nanocarry Therapeutics," said Revital Mandil-Levin, Co- founder and CEO of Nanocarry Therapeutics. "The detailed characterization by the NCL will significantly accelerate the development of AxS007 towards clinical trials. Our lead product addresses breast cancer brain metastases, a severe complication of HER2+ metastatic breast cancer in which current treatments often fail due to the BBB, drastically reducing survival rates. Our mission is to replicate the prominent success of HER2+ therapeutic antibodies and extend it to the brain, aiming to improve outcomes for the 1 in 8 women who will develop breast cancer in their lifetime.” About Nanocarry Therapeutics Nanocarry Therapeutics is a biopharmaceutical company dedicated to transforming brain disease treatment through an advanced insulin-based nano delivery system that crosses the blood-brain barrier. Founded in 2021 and rooted in the nano-bioengineering lab at Bar Ilan University, the company's lead product targets HER2+ breast cancer brain metastases and is now entering IND-enabling studies. The early pipeline also includes neurodegenerative diseases. Nanocarry Therapeutics aims to improve patient outcomes by delivering innovative therapies to previously unreachable areas of the brain. For more information about Nanocarry Therapeutics, visit www.nanocarry.com. Nanocarry contact:Michal Roytman Chief Business Officer Tel: +972-50-8460424michal@nanocarry.com

2024-05-02

·BioSpace

BridgeBio Spins Out Oncology Company with $200M in Financing

Pictured: 3D image of a KRAS oncogene iStock/Gilnature BridgeBio announced Thursday that it has secured $200 million in financing to spinout a former subsidiary to develop a KRAS-focused oncology portfolio. Called BridgeBio Oncology Therapeutics (BBOT), the company was initially formed as a subsidiary of BridgeBio known as TheRas. According to an SEC filing, the subsidiary has existed since 2016 and formed a research and development agreement with Leidos Biomedical Research in 2017. BBOT’s mission now is to generate a pipeline of small molecule therapeutics targeting RAS and PI3K malignancies. The company aims to advance three programs, including BBO-8520, a direct inhibitor of KRAS that seeks to bind to the protein’s “on” and “off” states. The spinout is enrolling patients with mutant non-small cell lung cancer in a Phase Ia/Ib trial. A second asset that BBOT will be advancing is BBO-10203, a PI3Kα:RAS breaker that blocks the interaction between RAS and PI3Ka to inhibit the PI3Kα/AKT effector signaling in tumors. The company plans to IND application sometime in the second quarter of 2024 and enroll patients later this year. The other asset is BBO-11818, a pan-KRAS inhibitor that is going after the “on” and “off” states of KRASG12X, and BBOT plans to IND sometime in early 2025. The company is also pursuing a discovery-stage research program focused on developing assets that target additional oncogenic drivers within the RAS and PI3K pathways. “We believe the launch of BBOT better aligns investors with an opportunity that was being hidden in our pipeline, and our partnership with these new investors enables us to prosecute these oncology programs more quickly and with higher fidelity,” BridgeBio CEO Neil Kumar said in a statement. The spinout secured its $200 million financing in an oversubscribed round led by Cormorant Asset Management and co-led by Omega Funds. There was also participation from GV (Google Ventures), Deerfield Management, EcoR1 Capital, Wellington Management, Enavate Sciences, Surveyor Capital, Casdin Captial, Aisling Capital, and Longwood Fund. BBOT will headed by Eli Wallace, BridgeBio’s CEO of oncology R&D. Wallace joined BridgeBio in 2019 after serving as the chief scientific officer at Peloton Therapeutics. Kumar will also serve as a director of BBOT. “In conjunction with BridgeBio and an amazing suite of investors, we look forward to seeing all three of our programs progress into the clinic over the next 12 months,” Wallace said in a statement. BridgeBio has gone down the spinout path before, launching QED Therapeutics in 2018. The company secured $65 million and aimed to develop infigratinib, a cancer asset that Novartis abandoned. Infigratinib was given accelerated approval by the FDA in 2021. Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.

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100 项与 Leidos Biomedical Research, Inc. 相关的药物交易

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