Frederick National Laboratory For Cancer Research

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

SOUTH SAN FRANCISCO, Calif.--( BUSINESS WIRE )--TheRas, Inc. d/b/a BridgeBio Oncology Therapeutics (“BBOT” or the “Company”), a clinical-stage biopharmaceutical company focused on RAS-pathway malignancies, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to BBO-8520, an investigational oral therapy for the treatment of adult patients with previously treated, KRAS G12C -mutated metastatic non-small cell lung cancer (NSCLC). BBO-8520 is designed to inhibit the “ON and OFF” state to provide optimal target coverage and to address KRAS G12C amplification and receptor tyrosine kinase activation – the two key mechanisms of adaptive resistance to current “OFF” state inhibitors. It drives substantial tumor growth inhibition in multiple preclinical models, even after emergence of resistance to sotorasib, an FDA approved “OFF” state inhibitor of KRAS G12C . i The discovery of BBO-8520 was the result of a collaboration between the National Cancer Institute RAS Initiative at Frederick National Laboratory for Cancer Research, Lawrence Livermore National Laboratory, and BBOT. “Receiving Fast Track designation for BBO-8520 is a significant milestone in our efforts to overcome the limitations of existing therapies for KRAS G12C -mutant cancers,” said Yong Ben, MD, Chief Medical and Development Officer of BBOT. “BBO-8520 represents a first-in-class approach with potential to address high unmet medical needs and shift the paradigm for cancer treatment. We will continue to work closely with the FDA to expedite the development of BBO-8520, which is currently being evaluated in a Phase 1 study ( NCT06343402 ) of KRAS G12C NSCLC patients pre-treated with first generation KRAS G12C “OFF” inhibitors or with no prior KRAS G12C targeted therapy experience.” Fast Track designation is intended to help rapidly advance the development and review process for promising therapeutic candidates for serious conditions that may fill an unmet medical need. About TheRas, Inc. d/b/a BridgeBio Oncology Therapeutics (BBOT) BridgeBio Oncology Therapeutics (BBOT) is a clinical-stage biopharmaceutical company advancing a next generation pipeline of novel small molecule therapeutics targeting RAS and PI3K malignancies. Initially formed as a subsidiary of BridgeBio, BBOT completed a $200M private financing with external investors in 2024 with the goal of improving outcomes for patients with cancers driven by the two most prevalent oncogenes in human tumors. For more information visit bridgebiooncology.com . i Maciag et al., Cancer Discovery. 2024

SOUTH SAN FRANCISCO, Calif.--( BUSINESS WIRE )--TheRas, Inc. d/b/a BridgeBio Oncology Therapeutics (“BBOT” or the “Company”), a clinical-stage biopharmaceutical company focused on RAS-pathway malignancies, today announced the publication of preclinical data supporting the hypothesis that targeting both “ON” and “OFF” forms of KRAS G12C results in greater potency, deeper responses, and slowed development of resistance leading to significant benefits over “OFF” only KRAS G12C inhibitors approved in non-small cell lung cancer (NSCLC). The publication, titled “ Discovery of BBO-8520, a first-in-class direct and covalent dual inhibitor of GTP-bound (ON) and GDP-bound (OFF) KRAS G12C ” was published in the peer-reviewed journal Cancer Discovery , a journal of the American Association for Cancer Research. Current KRAS G12C inhibitors work by binding to the inactive guanosine diphosphate (GDP)-bound “OFF” form of the protein, preventing its oncogenic activation. However, they do not directly target or inhibit the active guanosine triphosphate (GTP)-bound “ON” form. This limitation leaves KRAS G12C “ON” unaddressed, leading to adaptive resistance characterized by increased expression and activity of the active KRAS G12C “ON” state. The data in this manuscript demonstrate that BBO-8520, a first-in-class direct dual inhibitor, directly binds to both the “ON” and “OFF” states of KRAS G12C in the Switch-II/Helix3 pocket. There, it covalently modifies the target cysteine to disable effector binding to the “ON” state of KRAS G12C . In vivo , BBO-8520 demonstrates rapid target engagement and inhibition of downstream signaling, resulting in durable tumor regression in multiple tumor models, including those resistant to KRAS G12C “OFF” only inhibitors. “The aspiration to design a first-in-class, direct, dual inhibitor of the GTP-bound 'ON' and GDP-bound 'OFF' forms of KRAS G12C has been achieved,” said Pedro Beltran, PhD, Chief Scientific Officer of BBOT. “BBO-8520 is a dual inhibitor of KRAS G12C that provides optimal target coverage with exquisite potency, overcoming key deficiencies of 'OFF' only inhibitors, and represents a novel mechanism of action because it is the only direct inhibitor that actually blocks effector binding. Preclinical data shows that this novel mechanism delays the emergence of adaptive resistance seen with 'OFF' only inhibitors in the clinic. The potential of this approach holds significant promise for delivering enhanced clinical outcomes in patients with NSCLC.” “Using nuclear magnetic resonance (NMR) and X-ray crystallography, as well as biochemical and cell-based assays, we’ve been able to decipher the mechanism of action of this potent dual inhibitor,” said lead author Anna Maciag, PhD, Principal Scientist at Frederick National Laboratory for Cancer Research (FNLCR). “Our ability to apply the multitude of high throughput screens and assays available at FNLCR allowed for quick structure activity relationship (SAR) determination and progress.” Resistance to KRAS G12C “OFF” inhibitors primarily arises from increased KRAS G12C activity in its “ON” state. This can occur through mutant allele amplification or activation of receptor tyrosine kinases (RTKs) by growth factors. Newly synthesized KRAS is likely to bind GTP, as intracellular GTP concentrations are roughly ten times higher than GDP. As a result, upregulating the mutant protein’s transcription offers an efficient escape mechanism for cells to bypass the effects of “OFF” inhibitors. Similarly, receptor tyrosine kinase (RTK) activation can effectively overcome “OFF” only inhibitors by maintaining a high level of KRAS G12C in its “ON” state. This study shows that the presence of epidermal growth factor (EGF) and hepatocyte growth factor (HGF) significantly impairs the potency of “OFF” inhibitors in vitro , while amplification of KRAS G12C is also detrimental in vivo . In contrast, BBO-8520 maintains exquisite potency in the presence of growth factors, mutant allele amplification, as well as when mutations are engineered to maintain KRAS G12C in the “ON” form. BBO-8520 is currently being evaluated in a Phase 1 study ( NCT06343402 ) of KRAS G12C NSCLC patients pre-treated with first generation KRAS G12C “OFF” inhibitors or with no prior KRAS G12C targeted therapy experience. The discovery of BBO-8520 was the result of a collaboration between the National Cancer Institute RAS Initiative at Frederick National Laboratory for Cancer Research, Lawrence Livermore National Laboratory, and BBOT. About TheRas, Inc. d/b/a BridgeBio Oncology Therapeutics (BBOT) BridgeBio Oncology Therapeutics (BBOT) is a clinical-stage biopharmaceutical company advancing a next generation pipeline of novel small molecule therapeutics targeting RAS and PI3K malignancies. Initially formed as a subsidiary of BridgeBio, BBOT completed a $200M private financing with external investors in 2024 with the goal of improving outcomes for patients with cancers driven by the two most prevalent oncogenes in human tumors. For more information visit bridgebiooncology.com .