BBO-10203 / BridgeBio, BridgeBio Oncology Therap - LARVOL DELTA

BBO-8520, a first-in-class direct dual inhibitor of GTP-bound (ON) and GDP-bound (OFF) KRASG12C, exhibits robust efficacy in non-small cell lung cancer preclinical models (AACR 2025) - P1 | "Sotorasib and adagrasib, allele-specific KRASG12C covalent inhibitors that only target KRASG12C in the inactive GDP-bound (OFF) state, have been approved for patients with KRASG12C locally advanced or metastatic non-small cell lung cancer (NSCLC)...BBO-8520 also exhibits strong combination benefit in vivo in the KRASG12 CDX model NCI-H2122 when combined with either BBO-10203, a selective RAS:PI3Kα breaker that blocks RAS-mediated activation of AKT in clinical development (NCT06625775), or the anti-EGFR antibody cetuximab. In summary, BBO-8520 is a first in class, potent and selective KRASG12C dual GTP-bound (ON) and GDP-bound (OFF) inhibitor that exhibits robust efficacy and may improve upon approved, KRASG12C GDP-bound (OFF)-only inhibitors in NSCLC. BBO-8520 has entered phase 1 clinical trials in patients with KRASG12C NSCLC that are either naïve or have experienced first-generation KRASG12C (OFF) inhibitors (NCT06343402)."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS • PIK3CA

BBO-11818, an orally bioavailable, highly potent and non-covalent pan-KRAS inhibitor demonstrates robust anti-tumor activity in KRAS-mutant preclinical models (AACR 2025) - "In combination with either BBO-10203, a selective RAS:PI3Kα breaker that blocks RAS-mediated activation of AKT; or cetuximab, an anti-EGFR monoclonal antibody, BBO-11818 shows significantly enhanced efficacy in models harboring KRASG12D or KRASG12V mutations. BBO-11818 also shows a combination benefit with anti-PD-1 treatment, resulting in complete tumor regressions in the CT-26 syngeneic tumor mouse model. BBO-11818 is a potent pan-KRAS inhibitor with activity against both GTP and GDP forms of KRAS, presenting the opportunity to address, as monotherapy or combination, a large fraction of KRAS mutant tumors currently lacking targeted therapeutic options."

IO biomarker • Preclinical • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • BRAF • KRAS • NRAS • PIK3CA

BridgeBio Oncology Therapeutics (BBOT) and Helix Acquisition Corp. II Announce Business Combination Agreement to Create Publicly Listed Biotechnology Company Advancing a Pipeline of RAS and PI3Kα-Targeting Medicines (Businesswire) - "TheRas, Inc. d/b/a BridgeBio Oncology Therapeutics...and Helix Acquisition Corp...announced that they have entered into a definitive business combination agreement. Upon closing of the transaction, the combined company will be renamed 'BridgeBio Oncology Therapeutics, Inc.'...In addition to approximately $196 million held in Helix Acquisition Corp. II’s trust account (assumed as of the closing and assuming no redemptions by Helix’s public shareholders), the transaction also includes commitments for an approximately $260 million PIPE from a group of premier institutional investors...Net proceeds from the transaction are expected to provide BBOT with the capital needed to accelerate the development of three lead programs: BBO-8520, BBO-10203, and BBO-11818....BBOT expects to dose the first patient with BBO-11818 in the first half of 2025."

M&A • New trial • Colorectal Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Non Small Cell Lung Cancer • Solid Tumor

BBO-10203, a first-in-class, orally bioavailable, selective blocker of the PI3Kα:RAS interaction inhibits tumor growth alone and in combination with standard of care therapies in breast cancer models without inducing hyperglycemia. (SABCS 2024) - "In vitro and in vivo studies show that BBO-10203 significantly enhances the anti-tumor activity of the HER2-targeted antibody trastuzumab in the BT-474 (ER+, HER2amp, and PIK3CAK111N) and MDA-MB-453 (ER-, HER2+, and PIK3CAH1047R) breast cancer models. In addition, BBO-10203 also significantly enhances the anti-tumor activity of the SERD fulvestrant or the CDK4/6 inhibitor palbociclib in the MCF7 (ER+, HER2-, and PIK3CAE545K) breast cancer model...In conclusion, BBO-10203 blocks RAS-mediated activation of PI3Kα and strongly inhibits pAKT signaling in tumor cells without affecting glucose metabolism. BBO-10203 has entered phase 1 clinical trials and may provide clinical benefit without the limiting toxicities that have restricted the use of PI3Kα inhibitors."

Combination therapy • Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HRAS • IR • KRAS • NRAS • PIK3CA

BridgeBio Oncology Therapeutics (BBOT) Announces First Patient Dosed with First-in-Class BBO-10203, a RAS:PI3Kα Breaker, in the Phase 1 BREAKER-101 Trial for Advanced Solid Tumors (Businesswire) - "TheRas, Inc. d/b/a BridgeBio Oncology Therapeutics...has announced that the first patient has been dosed with BBO-10203 in the BREAKER-101 trial. BBO-10203 is a first-in-class orally bioavailable RAS:PI3Ka breaker that blocks the interaction between RAS and PI3Kα to inhibit PI3Kα-AKT signaling in tumors, without directly inhibiting the catalytic activity of PI3Kα....The BREAKER-101 trial will enroll patients globally with locally advanced or metastatic HER2-positive breast cancer, HR-positive/HER2-negative breast cancer, KRAS mutant advanced colorectal cancer, and KRAS mutant advanced non-small cell lung cancer."

Trial status • Colorectal Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Non Small Cell Lung Cancer

BBO-10203, an orally bioavailable small molecule that disrupts the RAS-PI3K interaction leading to pAKT and tumor growth inhibition in models of breast, lung and colorectal cancer (EORTC-NCI-AACR 2024) - "Even though BBO-10203 does not inhibit the kinase activity of PI3Ka, its effects on cancer cell signaling inhibition and transcriptional regulation highly resemble those of alpelisib...Combinations with trastuzumab, fulvestrant, palbociclib, KRASG12C inhibitor, and irinotecan results in significantly better efficacy than either agent alone in HER2amp, ER+ Breast, KRASG12C mutant NSCLC and KRAS mutant CRC, respectively... We have identified a novel pharmacological approach to inhibit the PI3Ka signaling pathway by blocking its interaction with, and activation by RAS proteins. This approach can achieve strong pAKT inhibition in tumor cells without changes in glucose metabolism. Clinical investigation of BBO-10203 alone and in combination with multiple standard of care therapeutics is warranted."

Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • IR • KRAS

Dose Escalation and Expansion of BBO-10203 in Advanced Solid Tumors (BREAKER-101) (clinicaltrials.gov) - P1 | N=153 | Recruiting | Sponsor: TheRas, Inc., d/b/a BridgeBio Oncology Therapeutics | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Oncology • Solid Tumor • KRAS

Dose Escalation and Expansion of BBO-10203 in Advanced Solid Tumors (BREAKER-101) (clinicaltrials.gov) - P1 | N=153 | Not yet recruiting | Sponsor: TheRas, Inc., d/b/a BridgeBio Oncology Therapeutics

New P1 trial • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Oncology • Solid Tumor • KRAS

BridgeBio launches BridgeBio Oncology Therapeutics (BBOT) with $200M of private external capital to accelerate the development of its novel precision oncology pipeline (GlobeNewswire) - "BridgeBio Pharma, Inc...has announced the completion of a $200M private financing of its former subsidiary, TheRas, Inc. d/b/a BridgeBio Oncology Therapeutics (BBOT), to accelerate the development of its oncology portfolio....BBOT will be advancing three initial programs: BBO-8520, a direct inhibitor of KRASG12C that binds to both the ON and OFF states of the protein....BBOT expects to file an Investigational New Drug application (IND) for BBO-10203 in Q2 2024 and, subject to clearance of the IND, will begin enrolling patients later this year. BBO-11818, a pan-KRAS inhibitor that targets both the ON and OFF states of KRASG12X for which BBOT expects to file an IND in early 2025."

Financing • IND • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BridgeBio Pharma Reports First Quarter 2023 Financial Results and Business Update (GlobeNewswire) - "BridgeBio is continuing to develop the three main programs of its RAS franchise: BBO-8520, an investigational, next-generation small molecule direct KRASG12C(ON) inhibitor candidate that is designed to directly bind and inhibit KRASG12C in both its ON (GTP-bound) and OFF (GDP-bound) conformations, which remains on track to file an IND and enter the clinic in the second half of 2023. A PI3Kα:RAS breaker program...The Company remains on track to select a development candidate in 2023, with IND filing to follow in 2024. The Company’s pan-KRAS program, which targets multiple KRAS mutants including KRASG12D and KRASG12V, which are present in a large percentage of colorectal, pancreatic, and non-small cell lung cancer tumors. Development candidate selection for this program is planned for late 2023 or early 2024."

IND • New trial • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor

BridgeBio Pharma Reports Fourth Quarter and Full Year 2022 Financial Results and Business Update (GlobeNewswire) - "BridgeBio is continuing to progress the three main programs of its RAS franchise: BBO-8520, an investigational, next-generation small molecule KRAS G12C dual inhibitor candidate that is designed to directly bind and inhibit KRAS G12C in both its active (GTP bound) and inactive (GDP bound) conformations, which remains on track to file an IND and enter the clinic in the second half of 2023. A PI3Kα:RAS breaker program...The Company remains on track to select a development candidate in 2023, with IND filing to follow in 2024. The Company’s pan-KRAS program, which targets multiple KRAS mutants including KRASG12D and KRASG12V, which are present in a large percentage of colorectal, pancreatic, and non-small cell lung cancer tumors. Development candidate selection for this program is planned for late 2023 or early 2024."

IND • New trial • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor