BBO-8520 / BridgeBio, BridgeBio Oncology Therapeutics - LARVOL DELTA

Onkoras-101: Open-label Study of BBO-8520 in Adult Subjects With KRASG12C Non-small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=350 | Recruiting | Sponsor: TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics) | N=250 ➔ 350 | Trial completion date: Feb 2028 ➔ Sep 2031 | Trial primary completion date: Aug 2027 ➔ Apr 2031

Enrollment change • First-in-human • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

TBBO8520-101: A Phase 1a/1b Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of BBO-8520 in Subjects with Advanced KRASG12C Mutant Non-Small Cell Lung Cancer - The ONKORAS-101 Study (clinicaltrialsregister.eu) - P1 | N=45 | Not yet recruiting | Sponsor: Theras Inc.

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

TBBO8520-101: A Phase 1a/1b Open-Label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of BBO-8520 in Subjects with Advanced KRASG12C Mutant Non-Small Cell Lung Cancer - The ONKORAS-101 Study (clinicaltrialsregister.eu) - P1 | N=5 | Not yet recruiting | Sponsor: Theras Inc.

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

Upcoming Milestones (GlobeNewswire) - "(i) BBO-8520:...Updated clinical data are expected in the second half of 2026 and internal combination with BBO-10203 is anticipated to open later in 2026...; (ii) BBO-11818:...Updated clinical data are expected in the second half of 2026. Combination with BBO-10203 is anticipated to open later in 2026...; (iii) BBO-10203:...Updated clinical data are expected in the second half of 2026 and internal combinations, including with BBO-8520 and BBO-11818, are anticipated to open later in 2026."

New trial • P1 data • Colorectal Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

Onkoras-101: A phase 1a/1b open-label study evaluating the safety, tolerability, pharmacokinetics, and efficacy of BBO-8520 in subjects with advanced KRASG12C mutant non-small-cell lung cancer. (ASCO 2025) - P1 | "BBO-8520 will also be evaluated in combination with pembrolizumab in an expansion cohort of patients with advanced NSCLC and no prior treatment with immune checkpoint or KRASG12C inhibitors. The primary objective of Phase 1b is to verify safety and tolerability of BBO-8520 monotherapy and in combination with pembrolizumab and evaluate antitumor activity (objective response rate evaluation)."

Clinical • Metastases • P1 data • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

BBO-8520 (Direct KRAS^G12C ON/OFF) (GlobeNewswire) - "As of November 15, 2025, a 65% (11/17) objective response rate (ORR) was observed in NSCLC patients with a KRASG12C mutation across all dose levels, including 10 partial responses (PRs) and one complete response (CR). Responses appear durable with a 6-month progression-free survival (PFS) of 66% and with 83% of patients remaining on study for ≥6 months. In this interim readout, BBO-8520 demonstrated a generally well-tolerated and manageable monotherapy safety profile with a meaningfully differentiated liver toxicity profile."

P1 data • Non Small Cell Lung Cancer

BBO-8520 Upcoming Catalysts (GlobeNewswire) - "BBOT plans to provide additional data updates, including additional pembrolizumab combination efficacy and safety data, in the second half of 2026. Combination studies with BBO-10203 are expected to open later in 2026."

New trial • P1 data • Non Small Cell Lung Cancer

BBO-10203 Upcoming Catalysts (GlobeNewswire) - "BBOT plans to provide additional data updates, which will include combination data in HER2+ BC, HR+/HER2- PIK3CA mutant BC and KRAS mutant CRC, in the second half of 2026. Combination studies with BBO-8520 and BBO-11818 are expected to open later in 2026."

New trial • P1 data • Colorectal Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Non Small Cell Lung Cancer

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

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-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

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 Oncology Therapeutics (BBOT) Granted U.S. FDA Fast Track Designation for BBO-8520 for KRASG12C-Mutated Metastatic Non-Small Cell Lung Cancer (Businesswire) - "TheRas, Inc. d/b/a BridgeBio Oncology Therapeutics...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, KRASG12C-mutated metastatic non-small cell lung cancer (NSCLC)."

Fast track • Non Small Cell Lung Cancer

BBO-8520 Preclinical Data Published in Cancer Discovery Supports the Potential for the First-in-Class Molecule to Provide Therapeutic Benefit in KRASG12C Mutant Tumors (Businesswire) - "Data demonstrates BBO-8520 binds directly to both the 'ON' and 'OFF' states of KRASG12C, leading to rapid and complete inhibition of KRASG12C activity. In murine models, BBO-8520 treatment results in greater potency, deeper responses, and slowed development of resistance compared to approved, 'OFF' only KRASG12C inhibitors."

Preclinical • Non Small Cell Lung Cancer

TBBO8520-101: Study of BBO-8520 in Adult Subjects with KRASG12C Non-small Cell Lung and Colorectal Cancer (clinicaltrials.gov) - P1 | N=229 | Recruiting | Sponsor: TheRas, Inc., d/b/a BridgeBio Oncology Therapeutics | N=160 ➔ 229

Combination therapy • Enrollment change • Metastases • Monotherapy • Colon Cancer • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

BridgeBio Oncology Therapeutics announces first patient dosed with BBO-8520 in the Ph. 1 ONKORAS-101 trial for KRASG12C NSCLC (Businesswire) - "TheRas, Inc. d/b/a BridgeBio Oncology Therapeutics...has announced that the first patient has been dosed in the ONKORAS-101 trial for its lead program, BBO-8520....The ONKORAS-101 study will enroll patients pre-treated with first generation KRASG12C (OFF) inhibitors as well as patients with no prior KRASG12C targeted therapy experience. The trial will enroll across the US, Australia, Canada, and the EU."

Trial status • Non Small Cell Lung Cancer

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

Study of BBO-8520 in Adult Subjects With KRASG12C Non-small Cell Lung Cancer (clinicaltrials.gov) - P1 | N=160 | Recruiting | Sponsor: TheRas, Inc

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

BridgeBio announces FDA clearance of IND application for BBO-8520, a first-in-class direct inhibitor of KRASG12C (ON) (GlobeNewswire) - "BridgeBio Pharma, Inc...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....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."

IND • New trial • 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

BridgeBio Pharma Highlights its RAS Precision Oncology Portfolio and Shares Compelling Data from Next-generation G12C Inhibitor and Novel PI3Kα:RAS Breaker Mechanism at the Fourth RAS Initiative Symposium (GlobeNewswire) - "BridgeBio Pharma...presented preclinical data for its two lead RAS programs – a next-generation KRASG12C dual inhibitor program and a novel PI3Kα:RAS breaker program – in an oral presentation at the Fourth RAS Initiative Symposium....BridgeBio has selected a next-generation KRASG12C dual inhibitor development candidate, BBO-8520, and plans to enter the clinic in 2023....BBO-8520 shows strong efficacy in KRASG12C models, including deep regressions in an NSCLC model and differentiated activity vs a first-generation KRASG12C GDP-only inhibitor in a patient-derived xenograft model."

New trial • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

BridgeBio Pharma to Present New Data on its Novel Approaches to RAS-driven Cancers at the Fourth RAS Initiative Symposium (GlobeNewswire) - "BridgeBio Pharma, Inc...announced that preclinical data for its two lead RAS programs – a next-generation KRAS G12C dual inhibitor program and a PI3Kα:RAS breaker program – will be featured in an oral presentation on Monday, October 17th at the Fourth RAS Initiative Symposium. The Symposium will take place in Frederick, MD on October 17-19, 2022....KRAS G12C dual inhibitor: BridgeBio has selected a next-generation KRAS G12C dual inhibitor development candidate and plans to enter the clinic in 2023."

Clinical • Preclinical • Oncology