BBO-11818 / BridgeBio, BridgeBio Oncology Therapeutics - LARVOL DELTA

BBO-10203, a first-in-class, orally bioavailable, selective breaker of the RAS:PI3Kα interaction inhibits tumor growth alone and in combination with KRAS inhibitors in KRAS mutant models without inducing hyperglycemia (AACR-NCI-EORTC 2025) - P1 | "In vitro cellular studies and in vivo CDX, PDX, and GEM model studies show that BBO-10203 significantly enhances the anti-tumor activity of the dual GTP-bound (ON) and GDP-bound (OFF) KRASG12C and pan-KRAS inhibitors BBO-8520 (NCT06343402) and BBO-11818 (NCT06917079), respectively...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 (NCT06625775) and is being evaluated in KRAS mutant CRC and NSCLC, both as a monotherapy and in combination with KRAS inhibitors."

Combination therapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HRAS • KRAS • NRAS • PIK3CA

Preclinical Data Presented at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics Support Potential of BBO-10203, a First-in-Class RAS:PI3Kα Breaker That Inhibits KRAS-Mutant Tumor Growth without Inducing Hyperglycemia (GlobeNewswire) - "Data demonstrate BBO-10203 blocks RAS-mediated activation of PI3Kα and strongly inhibits pAKT signaling in tumor cells without affecting glucose metabolism. Robust monotherapy activity, as well as combination activity with BBOT’s KRASG12C ON/OFF inhibitor, BBO-8520, and panKRAS inhibitor, BBO-11818, was observed at well-tolerated dose levels in a panel of KRAS-mutant models."

Preclinical • Solid Tumor

BBO-11818: an orally bioavailable, highly potent and selective non-covalent pan-KRAS(ON) and (OFF) inhibitor with robust anti-tumor activity in KRAS-mutant preclinical models (AACR-NCI-EORTC 2025) - P1 | "Combination treatment with BBO-10203, a selective RAS:PI3Kα breaker that blocks RAS-mediated activation of the PI3K-AKT pathway (NCT06625775), results in decreased cellular proliferation, increased apoptosis, and enhanced efficacy in CDX and PDX models harboring KRASG12D or KRASG12V mutations. Similarly, combination treatment with BBO-11818 and cetuximab, an approved anti-EGFR monoclonal antibody, results in enhanced anti-tumor activity in a KRASG12D CDX model...BBO-11818 is a potent pan-KRAS inhibitor with activity against both the GTP- and GDP-bound states of KRAS, presenting the opportunity to address, as monotherapy or combination, a large fraction of KRAS mutant tumors currently lacking targeted therapeutic options. BBO-11818 has entered Phase 1 clinical trials for patients with various KRAS mutations in colorectal, pancreatic, and lung cancers (NCT06917079)."

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

BBO-11818 is currently being evaluated in the Phase 1 KONQUER-101 trial in patients with KRAS mutant pancreatic, non-small cell lung, and colorectal cancer with initial Phase 1 clinical data expected in the second half of 2026 (GlobeNewswire)

P1 data • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Cancer

BBOT Presents Preclinical Data Demonstrating Potential of BBO-11818 as a Potent panKRAS Inhibitor at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (GlobeNewswire) - "Data demonstrate potent suppression of MAPK signaling and viability in KRAS mutant cell lines, as well as anti-tumor activity across multiple KRASG12D and KRASG12V cell-derived xenograft (CDX) models....Efficacy of the combination with BBOT’s RAS:PI3K⍺ breaker, BBO-10203, is driven by a robust decrease in tumor cell proliferation and increase in apoptosis..."

Preclinical • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Cancer

BBOT Announces Poster Presentations at the 2025 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (GlobeNewswire)

Preclinical • Solid Tumor

BBOT Debuts as a Publicly Traded Company Focused on RAS-Pathway Malignances with a Potential to Realize the Full Promise of KRAS and PI3K Inhibition (GlobeNewswire) - "BridgeBio Oncology Therapeutics...announced the closing of its previously announced business combination with Helix Acquisition Corp. I....The combined business is expected to have approximately $490 million in cash....BBOT will use the net proceeds to accelerate the development of its pipeline of RAS-targeted oncology drug candidates, including: BBO-8520..., BBO-10203..., BBO-11818...."

Commercial • Breast Cancer • Colorectal Cancer • Non Small Cell Lung Cancer

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

BBO-11818 in Adult Subjects With KRAS Mutant Cancer (clinicaltrials.gov) - P1 | N=287 | Recruiting | Sponsor: TheRas, Inc., d/b/a BridgeBio Oncology Therapeutics

New P1 trial • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

BBOT Announces First Patient Dosed with BBO-11818, a PanKRAS Dual Inhibitor, in the Phase 1 KONQUER-101 Trial for Advanced Solid Tumors (Businesswire) - "TheRas, Inc. d/b/a BridgeBio Oncology Therapeutics...announced that the first patient has been dosed with BBO-11818 in the Phase 1 KONQUER-101 trial for advanced solid tumors. BBO-11818 is an orally bioavailable small molecule dual inhibitor that directly binds to both the 'ON' and 'OFF' states of KRAS. KONQUER-101 will enroll patients globally with certain KRAS mutations."

Trial status • Solid Tumor

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

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