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.

Start Date15 Jun 2024

Sponsor / Collaborator

National Center for Advancing Translational Sciences

[+1]

NCT06136117 / RecruitingNot ApplicableIIT

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.

Start Date22 May 2023

Sponsor / Collaborator

Instituut voor Tropische Geneeskunde

[+6]

NCT04301154 / Active, not recruitingPhase 1IIT

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

Start Date18 Feb 2022

Sponsor / Collaborator

The Henry M. Jackson Foundation

[+11]

100 Clinical Results associated with Leidos Biomedical Research, Inc.

0 Patents (Medical) associated with Leidos Biomedical Research, Inc.

153

Literatures (Medical) associated with Leidos Biomedical Research, Inc.

21 Sep 2024·Cancer Epidemiology, Biomarkers & Prevention

Abstract C022: Pathomics-based classifiers for inferring breast cancer genomic assays and prognosis in sub-Saharan Africa: Results from the Ghana Breast Health Study

Author: Aitpillah, Francis ; Clegg-Lamptey, Joe-Nat ; Lawrence, Scott M. ; Abubakar, Mustapha ; Nyarko, Kofi ; Wiafe, Seth ; Wiafe-Addai, Beatrice ; Adjei, Ernest ; Troester, Melissa A. ; Ansong, Daniel ; Edusei, Lawrence ; Butler, Ebonee N. ; Hurson, Amber N. ; Hewitt, Stephen ; Yarney, Joel ; Duggan, Maire A. ; Brinton, Louise A. ; Hamilton, Alina M. ; Garcia-Closas, Montserrat ; Figueroa, Jonine D. ; Titiloye, Nicolas ; Awuah, Baffour ; Ahearn, Thomas U.

AbstractBackground: Although several gene expression-based assays are validated for informing prognosis and treatment decision-making for breast cancer (BC) patients, their uptake has been hampered by technical complexities and cost, particularly in underrepresented and low-resource settings. Here, we explored whether machine learning-based features on standard hematoxylin and eosin (H&E)-stained images can be used in conjunction with routinely available pathology data (pathomics) to infer clinically relevant tumor genomic assays among BC patients from a sub-Saharan African population. Methods: This study comprised 563 BC patients with diagnostic H&E-stained images, clinicopathological data, and Nanostring gene expression data from the Ghana Breast Health Study (GBHS), a population-based case-control study that recruited BC patients between 2013 and 2015. H&E images were analyzed using high-accuracy machine learning algorithms to extract data on several, prospectively selected, human interpretable imaging features. The assessed features encompassed characteristics of the tumor (e.g., average nuclear size, nuclear optical density, nuclear roundness, etc.) and stroma (e.g., degree of stromal cellularity, stromal cell phenotype, extent of stromal desmoplasia, remodeling, necrosis, etc.). Nanostring technology was used to generate data on PAM50 subtype [luminal (A and B), non-luminal (HER2-enriched and Basal), normal-like], 21-gene recurrence score (RS), and TP53 pathway function. Multivariable logistic regression models were fitted to luminal (vs other subtypes), non-luminal (vs other subtypes), TP53 mutant-like (vs wildtype-like), and RS (4th vs 1st quartile) data to develop predictive classifiers in a discovery set (60% of the data). The performance of the classifiers was then tested in a held-out internal validation set (40% of the data). Results: In the discovery set, the pathomics-based classifiers achieved varying but excellent discriminatory accuracy [AUROC = 0.90 (0.86-0.94), 0.94 (0.91-0.97), 0.95 (0.91-0.98), and 0.96 (0.94-0.99) for TP53, non-luminal, RS, and luminal classification, respectively]. In the held-out (validation) set, the corresponding AUROC values were 0.82 (0.75-0.88), 0.87 (0.81-0.92), 0.85 (0.77-0.92), and 0.88 (0.83-0.93) for TP53, non-luminal, RS, and luminal classification. The TP53 classifier was correlated with the luminal (R=-0.73), non-luminal (R=0.80), and RS (R=0.77) classifiers. The distribution of the pathomics-based TP53 probability score varied considerably between PAM50 subtypes (P<0.0001), and according to RS categories within both ER+ (P=0.009) and ER- (P=0.006) BC subtypes in the validation set. Conclusion: H&Es are cost-effective and routinely performed as part of the diagnostic workup for BC patients. Accordingly, the results open promising avenues for the use of interpretable, machine learning-based, H&E imaging and pathology data to infer breast tumor genomic signatures and prognosis in low-resource settings. Further work is required to validate findings in independent populations.:Citation Format: Mustapha Abubakar, Amber N. Hurson, Thomas U. Ahearn, Ebonee N. Butler, Alina M. Hamilton, Maire A. Duggan, Scott M. Lawrence, Ernest Adjei, Joe-Nat Clegg-Lamptey, Joel Yarney, Beatrice Wiafe-Addai, Baffour Awuah, Seth Wiafe, Kofi Nyarko, Francis Aitpillah, Daniel Ansong, Stephen Hewitt, Louise A. Brinton, Melissa A. Troester, Lawrence Edusei, Nicolas Titiloye, Jonine D. Figueroa, Montserrat Garcia-Closas. Pathomics-based classifiers for inferring breast cancer genomic assays and prognosis in sub-Saharan Africa: Results from the Ghana Breast Health Study [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C022.

27 Apr 2024·Archives of Pathology & Laboratory Medicine

Notable Histologic Findings in a “Normal” Cohort: The National Institutes of Health Genotype-Tissue Expression (GTEx) Project

Article

Author: Vaught, Jim ; Engel, Kelly B ; Branton, Philip A ; Greytak, Sarah R ; Moore, Helen M ; Barcus, Mary ; Guan, Ping ; Sobin, Leslie

Context.—The National Institutes of Health (NIH) Genotype-Tissue Expression (GTEx) project was designed to evaluate how genetic variation and epigenetic effects influence gene expression in normal tissue.Objective.—To ensure that the grossly normal-appearing tissues collected were free from disease, each specimen underwent histologic evaluation.Design.—In total, nearly 30 000 tissue aliquots collected from almost 1000 postmortem donors underwent histologic review by project pathologists, and detailed observations of any abnormalities or lesions present were recorded.Results.—Despite sampling of normal-appearing tissue, in-depth review revealed incidental findings among GTEx samples that included neoplastic, autoimmune, and genetic conditions; the incidence of some of these conditions among GTEx donors differed from those previously reported for other populations. A number of age-related abnormalities observed during histologic review of tissue specimens are also described.Conclusions.—Histologic findings from the GTEx project may serve to improve populational awareness of several conditions and present a unique opportunity for others to explore age- and gender-influenced conditions. Resources from the study, including histologic image and sequencing data, are publicly available for research.

22 Mar 2024·Cancer Research

Abstract 3948: HPV45 and HPV52 prevalence, within-type variants, and precancer/cancer risks differ by race/ethnicity

Author: Koestler, Aimee J. ; Chen, Zigui ; Schiffman, Mark ; Mirabello, Lisa ; Dean, Michael ; Nelson, Chase W. ; Suh-Burgmann, Elizabeth ; Lorey, Thomas ; Yeager, Meredith ; Mishra, Sambit K. ; Burdett, Laurie ; Castle, Phillip E.

AbstractIntroduction: Persistent infection with a high-risk HPV (HR-HPV) type causes cervical cancer and many other cancers in both men and women. Our published data have shown that the distribution of specific HPV16/35 sublineages and genetic variants differ around the world and confer greater risk of cervical precancer/cancer in the populations where the virus is thought to have originated and coevolved. More studies are needed to evaluate the relationship between race/ethnicity, HR-HPV genetic variation, and precancer/cancer risk.Objective: To evaluate HPV45 and HPV52 genetic variation, and how it relates to a woman’s race/ethnicity and cervical precancer/cancer risk, using HPV whole-genome sequencing of 774 HPV45+ and 719 HPV52+ women in the NCI-Kaiser Permanente Northern California (KPNC) HPV Persistence and Progression cohort; and compared to HPV16/35.Methods: We viral genome sequenced 557 HPV45+ and 345 HPV52+ controls (women with benign infections [≤CIN1]), and 94 HPV45+ and 227 HPV52+ precancer/cancer cases (CIN3+). We evaluated HPV45 and HPV52 prevalence for each type by a woman’s self-reported race/ethnicity, and compared them to HPV16 and HPV35 using existing comparable NCI-KPNC data. To assess associations between HPV45 and HPV52 genetic variation (viral sublineages and SNPs) and infection outcome, we used Fisher’s Exact Tests and logistic regression to estimate the OR and 95% CI.Results: For HPV45, we determined that sublineages have varying histology-specific precancer/cancer risk (ORs ranged from 2-14), and that the sublineage distribution significantly varied by race/ethnicity (p < 0.001). By race, the HPV45 A2 sublineage was most prevalent in Asian/PI women and was associated with the highest risk of CIN3+ in these women compared to other races/ethnicities (OR=5.7, 95% CI=1.5-29.4), while the B2 sublineage was associated with increased risk of CIN3+ in Black women only (OR=6.1, 95% CI=1.2-33.6). The prevalence of each HR-HPV type (HPV16/35/45/52) significantly varied by race/ethnicity (p < 0.001). For each type, White was the most reported race/ethnicity; however, Black women were a greater proportion of the HPV35+ cases compared to other types (15% vs 8-10%), and Asian/PIs were a greater proportion of HPV52+ cases (26% vs 10-13%). HPV52 genome analyses are still underway; we will present the complete study results (i.e., sublineage risk by race) at AACR.Conclusions: We conducted the largest studies of HPV45 and HPV52 genome variation to date. We demonstrate that specific HPV45 sublineages vary by race and are associated with an increased risk of precancer/cancer for specific races/ethnicities, and that HPV52 infection has a greater prevalence in Asian/PI women compared to other racial groups. Our data suggest that certain HR-HPV types and specific sublineages of these types are more common in specific racial/ethnic groups and potentially linked to differing risks by race.Citation Format: Aimee J. Koestler, Chase W. Nelson, Meredith Yeager, Zigui Chen, Laurie Burdett, Sambit K. Mishra, Michael Dean, Elizabeth Suh-Burgmann, Thomas Lorey, Phillip E. Castle, Mark Schiffman, Lisa Mirabello. HPV45 and HPV52 prevalence, within-type variants, and precancer/cancer risks differ by race/ethnicity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3948.

News (Medical) associated with Leidos Biomedical Research, Inc.

04 Sep 2024

·www.globenewswire.com

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

02 May 2024

·www.fiercebiotech.com

BridgeBio taps VCs for $200M, fueling oncology spinout's push to surpass KRAS class

Funding will support BridgeBio Oncology Therapeutics and "significant clinical inflection points over the next 18-24 months." BridgeBio Pharma has spun its Rolodex to fund a subset of its sprawling list of opportunities. Busy with launch and late-phase activities, BridgeBio has secured $200 million to equip a cancer-focused offshoot to push a pipeline led by a KRAS inhibitor through early-phase tests. In 2017, TheRas, which is now doing business as BridgeBio Oncology Therapeutics (BBOT), struck a deal with Leidos Biomedical Research that led to the licensing of a KRAS G12C inhibitor and two other assets. TheRas was a wholly owned subsidiary of BridgeBio for years but required limited funding, with R&D expenses related to the Leidos agreements totaling $3.6 million in 2023. Now, with one asset in the clinic and two approaching human testing, BridgeBio has decided to spin the molecules out to create BBOT and bring outside investors on board. The funding gives BBOT the “runway to achieve significant clinical inflection points over the next 18-24 months,” BridgeBio said. BBOT began a phase 1 trial of KRAS G12C inhibitor BBO-8520 in non-small cell lung cancer last month. The start date of the study, which will test the molecule as a single agent and in combination with Keytruda, puts the program years behind approved KRAS drugs sold by Amgen and Bristol Myers Squibb. But BBOT and its backers contend a feature of BBO-8520 could lead to better efficacy. KRAS cycles between an “on” and “off” state. Amgen’s Lumakras and BMS' Krazati target the off state, as does Roche’s challenger divarasib. BBOT believes molecules also need to inhibit KRAS in its on state to achieve optimal target coverage and prevent adaptive mechanisms of resistance. BBOT’s preclinical tests suggest BBO-8520 has advantages over Amgen, BMS and Roche’s molecules. And the biotech's researchers saw responses when the molecule was administered after the development of resistance to Lumakras. The spinout is working to generate human data on BBO-8520 while preparing to move two other assets into the clinic. BBO-10203 is designed to block an interaction between RAS and PI3Ka. In doing so, the molecule may inhibit a tumor signaling pathway without causing the high blood sugar that affects people on PI3Kα inhibitors. BBOT is aiming to start enrolling patients in a clinical trial this year. A pan-KRAS inhibitor, BBO-11818, is following close behind. Like Lumakras and Krazati, BBOT’s lead drug candidate only targets a subset of patients with KRAS mutations. BBO-11818 is designed to target the on and off states of multiple forms of KRAS, potentially making it effective in more patients. BBOT is aiming to file to study the molecule in humans next year. Eli Wallace, Ph.D., and Pedro Beltran, Ph.D., will oversee the programs as BBOT’s CEO and chief scientific officer, respectively. Wallace joined BridgeBio as CSO in residence for oncology in 2019. Beltran arrived the following year to work with Wallace on programs targeting RAS biology. The financing round was led by Cormorant Asset Management and co-led by Omega Funds. Affiliates of Deerfield Management, GV, EcoR1 Capital, Wellington Management, Enavate Sciences, Surveyor Capital, Aisling Capital, Casdin Capital and Longwood Fund also participated. Securing outside investment frees BridgeBio to spend its cash on launching acoramidis and enrolling patients in a clutch of phase 3 studies.

Phase 1License out/inExecutive Change

02 May 2024

·www.biospace.com

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.

Executive Change

100 Deals associated with Leidos Biomedical Research, Inc.

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Pipeline Snapshot as of 20 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

Iotivibart ( CD4 x HIV envelope protein gp120 )	HIV Infections More	Preclinical
KRAS G12C inhibitors (Leidos Biomedical Research) ( KRAS G12C )	Neoplasms More	Preclinical
BBO-8520 ( KRAS G12C )	KRAS G12C mutation Solid Tumors More	Preclinical
KRAS G12D inhibitors (Leidos Biomedical Research) ( KRAS G12D )	Neoplasms More	Preclinical
UPCDC-30766 ( VCP )	Neoplasms More	Preclinical

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