BridgeBio announces FDA clearance of IND application for BBO-8520, a first-in-class direct inhibitor of KRASG12C (ON)
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Insights
The recent FDA clearance of the IND application for BridgeBio Pharma's BBO-8520 marks a significant advancement in the oncology field, particularly for targeted cancer therapies. BBO-8520's mechanism, targeting both the GTP-bound (ON) and GDP-bound (OFF) states of KRASG12C, represents a novel approach compared to first-generation inhibitors that primarily target the OFF state. This dual binding could potentially overcome the adaptive resistance mechanisms that often limit the efficacy of current treatments.
As an inhibitor that acts on the ON state, BBO-8520 may prove to be a more effective treatment option for patients with KRASG12C-driven malignancies. These malignancies are notoriously difficult to treat due to the KRAS gene's role in cell signaling pathways that promote cancer growth and survival. By addressing the limitations of first-generation inhibitors, BBO-8520 could significantly improve patient outcomes.
Furthermore, the preclinical models have shown substantial tumor growth inhibition, even in cases where resistance to current treatments like sotorasib has emerged. This suggests that BBO-8520 could be a valuable addition to the oncology treatment arsenal, potentially extending the lives of patients and improving their quality of life.
BridgeBio Pharma's progress with BBO-8520 is a testament to the collaborative efforts in drug discovery and development. The partnership between the RAS Initiative at Frederick National Laboratory for Cancer Research, Lawrence Livermore National Laboratory and BridgeBio underscores the importance of cross-disciplinary collaboration in advancing medical research. This collaboration leverages the expertise of national laboratories and private sector agility to accelerate the development of promising therapies.
With the expected initiation of the ONKORAS-101 trial in the first half of 2024, the research community will be keenly observing the clinical efficacy and safety profile of BBO-8520. The trial's results will have implications not only for the future of KRASG12C inhibitor therapies but also for the broader landscape of precision oncology. A successful trial could pave the way for more targeted small molecule therapies and bolster the investment in precision medicine.
The FDA's clearance of the IND for BBO-8520 could have a positive impact on BridgeBio Pharma's market position and investor confidence. As a first-in-class therapy with a novel mechanism of action, BBO-8520 has the potential to capture a significant share of the market for KRASG12C-driven cancers, which includes prevalent forms such as non-small cell lung cancer.
Investors will likely monitor the progress of the ONKORAS-101 trial closely, as positive clinical data could lead to an increase in BridgeBio's stock value. However, it is essential to consider the inherent risks associated with drug development, including potential safety concerns, regulatory hurdles and competition from other pharmaceutical companies developing similar therapies.
It is also important to note that the commercial success of BBO-8520 will depend on various factors, including the drug's efficacy, safety profile, pricing and reimbursement policies. If BBO-8520 demonstrates a significant clinical benefit over existing treatments, it could command premium pricing and potentially disrupt the current treatment paradigm for KRASG12C-driven malignancies.
- The United States Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application for BBO-8520, a first-in-class orally bioavailable and potentially highly potent small molecule direct inhibitor of KRASG12C that binds to the Switch II pocket in both the GTP-bound (ON) and GDP-bound (OFF) state conformations of KRASG12C
- BBO-8520 is expected to significantly improve outcomes for patients with KRASG12C driven malignancies by providing optimal target coverage and addressing mechanisms of adaptive resistance to first generation KRASG12C (OFF) state inhibitors
- BridgeBio expects to initiate enrollment of patients with KRASG12C mutant non-small cell lung cancer in the ONKORAS-101 trial in the first half of 2024
PALO ALTO, Calif., Jan. 03, 2024 (GLOBE NEWSWIRE) -- BridgeBio Pharma, Inc. (Nasdaq: BBIO) (“BridgeBio” or the “Company”), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, has announced that the United States Food and Drug Administration (FDA) has cleared the investigational new drug (IND) application for BBO-8520, a first-in-class orally bioavailable and highly potent small molecule direct inhibitor of KRASG12C (ON) state. BBO-8520 binds covalently to the Switch II pocket in both the GTP-bound (ON) and GDP-bound (OFF) state conformations of KRASG12C, leading to rapid and robust inhibition of KRASG12C activity.
BBO-8520’s ability to inhibit the (ON) state should provide optimal target coverage and address KRASG12C amplification and receptor tyrosine kinase activation - the two key mechanisms of adaptive resistance to current (OFF) state inhibitors. BBO-8520 drives substantial tumor growth inhibition in multiple preclinical models, even after emergence of resistance to sotorasib, an FDA approved (OFF) state inhibitor of KRASG12C.
“Clinical results from the first generation of KRASG12C inhibitors suggest that compounds with better potency and the ability to target the ON state are likely to lead to better outcomes,” said Frank McCormick, Ph.D., Chairman of Oncology at BridgeBio, David A. Wood Distinguished Professor of Tumor Biology and Cancer Research at UCSF and advisor to the National Cancer Institute’s RAS Initiative at Frederick National Laboratory for Cancer Research (FNL). “BBO-8520 is the most potent G12C inhibitor with an IND, and the only compound that directly binds and targets the ON state. We hope that this drug will bring significantly improved benefit for patients suffering from KRASG12C cancers.”
BBO-8520’s discovery was the result of a collaboration between the RAS Initiative FNL, Lawrence Livermore National Laboratory and BridgeBio. It is specifically designed to provide patients afflicted with KRASG12C mutant cancers with a best-in-class, oral small molecule therapy that directly targets the tumor at its source - oncogenic KRASG12C GTP-bound (ON) signaling. Enrollment of patients with KRASG12C mutant non-small cell lung cancer into the ONKORAS-101 trial is expected to begin in H1 of this year.
About BridgeBio Pharma, Inc.
BridgeBio Pharma, Inc. is a commercial-stage biopharmaceutical company founded to discover, create, test, and deliver transformative medicines to treat patients who suffer from genetic diseases and cancers with clear genetic drivers. BridgeBio’s pipeline of development programs ranges from early science to advanced clinical trials. BridgeBio was founded in 2015 and its team of experienced drug discoverers, developers and innovators are committed to applying advances in genetic medicine to help patients as quickly as possible. For more information visit bridgebio.com and follow us on LinkedIn and Twitter.
BridgeBio Pharma, Inc. Forward-Looking Statements
This press release contains forward-looking statements. Statements in this press release may include statements that are not historical facts and are considered forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended (the Securities Act), and Section 21E of the Securities Exchange Act of 1934, as amended (the Exchange Act), which are usually identified by the use of words such as “anticipates,” “believes,” “hopes,” “estimates,” “expects,” “intends,” “may,” “plans,” “projects,” “seeks,” “should,” “continue,” “will,” and variations of such words or similar expressions. We intend these forward-looking statements to be covered by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act and Section 21E of the Exchange Act. These forward-looking statements, including statements relating to the clinical and therapeutic potential of BBO-8520, including the expectation that BBO-8520 will significantly improve outcomes for patients with KRASG12C driven malignancies by providing optimal target coverage and addressing mechanisms of adaptive resistance to first generation KRASG12C (OFF) state inhibitors, our clinical development program for BBO-8520, including the expected timeline to initiate enrollment of patients with KRASG12C mutant non-small cell lung cancer in the ONKORAS-101 trial in the first half of 2024, the statements regarding the potency and potential benefit of BBO-8520 and of our clinical trial in the quotes of Dr. McCormick, and the timing of these events, reflect our current views about our plans, intentions, expectations and strategies, which are based on the information currently available to us and on assumptions we have made. Although we believe that our plans, intentions, expectations, and strategies as reflected in or suggested by those forward-looking statements are reasonable, we can give no assurance that the plans, intentions, expectations, or strategies will be attained or achieved. Furthermore, actual results may differ materially from those described in the forward-looking statements and will be affected by a number of risks, uncertainties and assumptions, including, but not limited to, initial and ongoing data from our clinical trials not being indicative of final data, the design and success of ongoing and planned clinical trials, difficulties with enrollment in our clinical trials, adverse events that may be encountered in our clinical trials, the FDA or other regulatory agencies not agreeing with our regulatory approval strategies, components of our filings, such as clinical trial designs, conduct and methodologies, or the sufficiency of data submitted, potential adverse impacts due to the global COVID-19 pandemic such as delays in regulatory review, manufacturing and supply chain interruptions, adverse effects on healthcare systems and disruption of the global economy, the impacts of current macroeconomic and geopolitical events, including changing conditions from the COVID-19 pandemic, hostilities in the Middle East and Ukraine, increasing rates of inflation and rising interest rates, on our overall business operations and expectations, as well as those risks set forth in the Risk Factors section of our Annual Report on Form 10-K for the year ended December 31, 2022 and our other filings with the U.S. Securities and Exchange Commission. Moreover, we operate in a very competitive and rapidly changing environment in which new risks emerge from time to time. These forward-looking statements are based upon the current expectations and beliefs of our management as of the date of this press release and are subject to certain risks and uncertainties that could cause actual results to differ materially from those described in the forward-looking statements. Except as required by applicable law, we assume no obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise.
BridgeBio Contact:
Vikram Bali
contact@bridgebio.com
(650)-789-8220
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