BridgeBio Pharma Announces First Publication of Preclinical Data for its Potentially Best-in-Class SHP2 Inhibitor Designed for Treatment of Resistant Cancer, Showing Response in Established Non-small Cell Lung Cancer Models

Rhea-AI Summary

BridgeBio Pharma (Nasdaq: BBIO) announced promising preclinical data for its SHP2 inhibitor, BBP-398, targeting non-small cell lung cancer (NSCLC). The data, presented at the AACR-NCI-EORTC Conference, reveals BBP-398's potential as a combination agent with KRAS and EGFR inhibitors. The company is advancing a Phase 1 trial for patients with solid tumors with MAPK pathway mutations. The anticipated continuous once-daily dosing and strong preclinical efficacy could position BBP-398 as a leading treatment option for RAS-driven cancers. Further insights will be shared at the virtual R&D Day on October 12, 2021.

Positive

• Promising preclinical results for BBP-398 in NSCLC; potential for combination therapy.
• Ongoing Phase 1 trial indicates progress in targeting solid tumors with MAPK mutations.
• Collaboration with renowned MD Anderson Cancer Center enhances development credibility.

Negative

• None.

PALO ALTO, Calif., Oct. 7, 2021 /PRNewswire/ -- BridgeBio Pharma, Inc. (Nasdaq: BBIO), a commercial-stage biopharmaceutical company that focuses on genetic diseases and cancers, today announced preclinical findings for its SHP2 inhibitor, BBP-398, in non-small cell lung cancer (NSCLC). The results are featured in a poster presentation titled 'BBP-398, a potent, small molecule inhibitor of SHP2, enhances the response of established NSCLC xenografts to KRAS^G12C and EGFR^mut inhibitors' at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics taking place virtually on October 7 – 10, 2021.

"We are excited to share our promising preclinical data in non-small cell lung cancer models, which provides a critical step in understanding the potential that BBP-398 has for patients with tumors driven by RAS or other MAPK-pathway activating mutations," said Eli Wallace, Ph.D., chief scientific officer at BridgeBio Oncology. "For patients with this type of progressive cancer, there is a serious need for more innovative medicines to be accessible as quickly as possible. Our potentially best-in-class SHP2 inhibitor could be an ideal combination agent for certain cancer patients given its promising profile of preclinical results and potential for once daily dosing."

BBP-398, developed in collaboration with the University of Texas MD Anderson Cancer Center's Therapeutics Discovery division, exhibits preclinical monotherapy efficacy in RTK/KRAS-driven xenograft models as well as synergy in combination with both sotorasib and osimertinib. The predicted human steady-state plasma concentration-time profiles suggest continuous once daily oral dosing of BBP-398 may achieve the desired therapeutic index for patients.

BridgeBio is currently advancing its Phase 1 dose escalation clinical trial with its SHP2 inhibitor, BBP-398, in patients with solid tumors driven by mutations in the MAPK signaling pathway, including RAS and receptor tyrosine kinase genes. More than 30% of all human cancers – including 95% of pancreatic cancers and 45% of colorectal cancers — are driven by mutations of the RAS family of genes.

BridgeBio's precision oncology programs are driven by the Company's molecular dynamics and RAS structural biology platforms, which are enabled by our broad partnerships with the Lawrence Livermore National Laboratory and National RAS Initiative, respectively.

BridgeBio's SHP2 inhibitor, BBP-398, is one of the Company's 14 programs that are in the clinic or commercial setting for patients living with genetic diseases and genetically-driven cancers.

Learn more about the preclinical data for BBP-398 at BridgeBio's upcoming virtual R&D Day on Tuesday, October 12, 2021 at 8:30 am ET. The event will be webcast and registration information can be found here.

BridgeBio will unveil new programs, share new information about its pipeline and discuss how it is broadening the scope of its R&D engine. It will also cover the Company's most significant near-term catalysts with a focus on the upcoming topline results for acoramidis, BridgeBio's investigational therapy for transthyretin (TTR) amyloidosis (ATTR). ATTR is a rare heart condition with a progressive and debilitating impact on quality of life likely affecting more than 400,000 patients worldwide.

Topline acoramidis results from Part A are expected in late 2021 and from Part B in 2023. The primary endpoint at Part A is the change from baseline in a 6-minute walk distance (6MWD) in trial participants receiving acoramidis or placebo after 12 months. If the change from baseline in 6MWD in Part A is highly statistically significant, BridgeBio expects to submit an application for regulatory approval of acoramidis in 2022 to the U.S. Food and Drug Administration.

The R&D Day program importantly and additionally will highlight BridgeBio's broader efforts in cardiorenal, progress in its KRAS portfolio, and advancements in its previously disclosed early-stage Mendelian programs. The Company will also be unveiling new investigational programs in gene therapy.

About SHP2
SHP2 is a protein-tyrosine phosphatase that links growth factor, cytokine and integrin signaling with the downstream RAS/ERK MAPK pathway to regulate cellular proliferation and survival. Overactivity of the SHP2 pathway, often driven by distinct genetic mutations, is a critical contributor to many forms of cancer, and is a mechanism of resistance to several targeted therapies. Estimated to affect approximately 500,000 patients in the United States and the European Union, cancers that are driven by hyperactive MAPK signaling, including certain RAS mutations such as KRAS^G12C, may be sensitive to SHP2 inhibition.

About BBP-398
BBP-398 is a potent, selective, orally bioavailable SHP2 inhibitor that demonstrates pathway inhibition across a panel of cell lines with active MAPK signaling. The therapy is designed to be optimized for continuous once daily dosing through its pharmacokinetic profile. The inhibitor was developed through a collaboration with the University of Texas MD Anderson Cancer Center's Therapeutics Discovery division. BridgeBio has a non-exclusive, co-funded clinical collaboration with Bristol Myers Squibb to evaluate the combination of BBP-398 with OPDIVO® (nivolumab) in patients with advanced solid tumors with KRAS mutations. The collaboration will also include the initiation of a Phase 1/2 study to evaluate the safety and preliminary efficacy of BBP-398 in combination with both OPDIVO as doublet therapy, and OPDIVO plus a KRAS^G12C inhibitor as triplet therapy in non-small cell lung cancer (NSCLC) with KRAS mutations, as first- and second-line treatment options. Additionally, BridgeBio previously entered into a strategic collaboration with LianBio for clinical development and commercialization of BBP-398 in combination with various agents in solid tumors such as non-small cell lung cancer, colorectal and pancreatic cancer, in mainland China and other major Asian markets.

About BridgeBio Pharma, Inc.
BridgeBio Pharma, Inc. (BridgeBio) is a 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 over 30 development programs ranges from early science to advanced clinical trials and its commercial organization is focused on delivering the Company's two approved therapies. 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 we make 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," "estimates," "expects," "intends," "may," "plans," "projects," "seeks," "should," "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 and are making this statement for purposes of complying with those safe harbor provisions.  These forward-looking statements, including statements relating to expectations, plans, and prospects regarding preclinical study results for our SHP2 inhibitor, BBP-398, being indicative of future clinical trial results, the potential for BBP-398 to be a best-in-class SHP2 inhibitor as a once daily dose to treat patients with tumors driven by RAS or other MAPK-pathway activating mutations, the continuing success of our collaboration with the University of Texas MD Anderson Cancer Center's Therapeutics Discovery division, the timing and success of a Phase 1 dose escalation clinical trial of BBP-398 in patients with solid tumors driven by mutations in the MAPK signaling pathway, including RAS and receptor tyrosine kinase genes , the ability of our SHP2 inhibitor's ability to enhance immuno-oncology and other targeted therapies to potentially provide options for patients with difficult-to-treat cancers as quickly and safely as possible, the incidence of KRAS mutations and the promise of targeted therapies for patients with such mutations, the success of current and future relationships with third-party collaborators and academic partners, and the potential ability of our product candidates to treat genetically driven diseases and cancers with clear genetic drivers, reflect our current views about our plans, intentions, expectations, strategies and prospects, and are based on the information currently available to us and on assumptions we have made and are not forecasts, promises nor guarantees. Although we believe that our plans, intentions, expectations, strategies and prospects as reflected in or suggested by these 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, the success of our product candidates to treat genetically driven diseases and cancers with clear genetic drivers, the success of our collaboration with the University of Texas MD Anderson Cancer Center's Therapeutics Discovery division and preclinical study results being indicative of future clinical trial results as well as those risks set forth in the Risk Factors section of BridgeBio's most recent Annual Report on Form 10-K and BridgeBio's other SEC filings. Moreover, we operate in a very competitive and rapidly changing environment in which new risks emerge from time to time. 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.

¹ Maurer, M., Schwartz, J., Gundapaneni, B., et al. "Tafamidis treatment for patients with transthyretin Amyloid cardiomyopathy". New England Journal of Medicine 379.11 (2018): 1007–16.
²Enright, M., Duanel, S. "Reference equations for the six-minute walk in healthy adults". American Journal of Respiratory and Critical Care Medicine 158.5 (1998): 1384–7.

BridgeBio Media Contact:
Grace Rauh
Grace.rauh@bridgebio.com
(917) 232-5478

BridgeBio Investor Contact:
Katherine Yau
katherine.yau@bridgebio.com
(516) 554-5989

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FAQ

What are the preclinical findings for BBP-398 in non-small cell lung cancer?

BBP-398 shows promising efficacy in established NSCLC models, enhancing responses to KRAS and EGFR inhibitors.

What is the focus of the Phase 1 trial for BBP-398?

The trial targets solid tumors with mutations in the MAPK signaling pathway, including RAS and receptor tyrosine kinases.

When will BridgeBio share more about BBP-398's development?

Further insights will be provided during the virtual R&D Day on October 12, 2021.

What is the significance of BBP-398 in cancer treatment?

BBP-398 could be a best-in-class SHP2 inhibitor, ideal for patients with RAS-driven tumors.

What are the expected results from the trial for acoramidis?

Topline results from Part A are anticipated in late 2021, with regulatory submission planned for 2022 if results are favorable.