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

BBOT expects the following data catalysts over the next 12 months (GlobeNewswire) - "(i) BBO-11818 and BBO-10203 monotherapy data update in the fourth quarter of 2026; (ii) Expanded BBO-8520 plus pembrolizumab dataset in 2L+ KRASG12C inhibitor-experienced NSCLC expected in mid-2027; (iii) Data from BBO-11818 and BBO-10203 internal and standard-of-care combination cohorts in colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) expected in mid-2027."

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

Strategic Prioritization (GlobeNewswire) - "BBOT is focusing its capital and resources on opportunities that offer the highest probability of success and greatest potential benefit for patients: (i) BBO-8520 in combination with pembrolizumab in 2L+, KRASG12C inhibitor-experienced NSCLC patients; (ii) BBO-11818 and BBO-10203 internal combination and independent combinations with standard of care agents in KRAS-mutant cancers....BBO-11818 and BBO-10203 combination cohorts enrolling in KRAS-mutant CRC and PDAC."

Clinical • Enrollment status • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

Key Program Highlights and Updates (GlobeNewswire) - "(i) BBO-8520: Initiated BBO-8520 plus BBO-10203 combination in patients with G12C NSCLC; (ii) BBO-11818: Continued to enroll BBO-11818 monotherapy across multiple dose levels; Initiated dosing of BBO-11818 in combination with cetuximab; Subsequent to the end of the quarter, initiated dosing of BBO-11818 in combination with BBO-10203."

Trial status • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

Evolution of KRAS molecular glues: from allele-selective to Pan-RAS and protein-protein interaction modulators. (PubMed, Acta Pharmacol Sin) - "Molecular glues, such as the RMC macrocyclic series (e.g., RMC-6291 as a G12C-selective MG, RMC-6236 as a pan-MG), function by recruiting endogenous chaperone proteins to form ternary complexes that sterically block KRAS-effector interactions or allosterically restore GTPase activity...Complementarily, PPI inhibitors (e.g., BBO-10203, VVD-699) disrupt critical oncogenic interfaces between KRAS and PI3Kα, offering a strategy to inhibit oncogenic signaling with fewer side effects. Collectively, balancing broad-spectrum versus selective targeting of KRAS, attaining optimal drug-like properties and establishing rational combination therapies with other modalities remain key challenges. The ongoing evolution of MGs and PPI modulators heralds a major expansion of the therapeutic frontier for KRAS-driven cancers and is redrawing the boundaries of precision oncology."

Journal • Review • Oncology • Targeted Protein Degradation • KRAS • LZTR1 • NEDD4 • PIK3CA

BBO-11818 in Adult Subjects With KRAS Mutant Cancer (clinicaltrials.gov) - P1 | N=665 | Recruiting | Sponsor: TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics) | N=387 ➔ 665

Enrollment change • First-in-human • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

BREAKER-101: Open-Label Study of BBO-10203 in Subjects With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=392 | Recruiting | Sponsor: TheRas, Inc., d/b/a BBOT (BridgeBio Oncology Therapeutics) | N=91 ➔ 392

Enrollment change • First-in-human • Breast Cancer • Colorectal Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CDK4 • KRAS • PIK3CA

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 2026) - P1 | "Combination treatment with BBO-10203, a clinical-stage (NCT06625775), selective RAS:PI3Kα breaker that blocks RAS-mediated activation of the PI3Kα-AKT pathway, 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 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

The RAS: PI3Kα breaker BBO-10203 inhibits PI3Kα/AKT activity in HER2+ models through non-canonical RAS signaling blockade (AACR 2026) - P1 | "Treatment with the panRAS inhibitor RMC-6236 showed little effect on pAKT, suggesting that canonical RAS (K-, H- and N-RAS) may not be important players in pAKT signaling. Indeed, BBO-10203 enhanced the anti-tumor activity of HER2-targeted therapies (tucatinib, trastuzumab, or Enhertu) in vivo, leading to tumor regression, even in the trastuzumab-resistant JIMT-1 model. BBO-10203 has entered phase 1 clinical trials (NCT06625775) and is being evaluated in HER2+ breast cancers, both as a monotherapy and in combination with trastuzumab."

Breast Cancer • Esophageal Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ERBB3 • HER-2 • IR • KRAS • PIK3CA • RRAS2

BBO-10203 is being evaluated in the Phase 1 BREAKER-101 trial (NCT06625775) for patients with locally advanced or metastatic HER2+ breast cancer, HR+/HER2- breast cancer, KRAS-mutant colorectal cancer, and KRAS-mutant non-small cell lung cancer (GlobeNewswire) - "Updated Phase 1 clinical data are expected in the second half of 2026."

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

BBOT Presents Preclinical Data Showing RAS:PI3Kα Breaker BBO-10203 Inhibits PI3Kα/AKT Signaling in HER2AMP Models at the AACR Annual Meeting 2026 (GlobeNewswire) - "BBO-10203 physically and allosterically disrupts the interaction between RAS and PI3Kα, leading to signaling inhibition without inhibiting the kinase activity of PI3Kα. BBO-10203 induces tumor regressions at 30 mg/kg QD and no hyperglycemia observed at 100 mg/kg QD....Non-canonical RAS signaling appears to be the dominant driver of pAKT in HER2AMP cell lines. BBO-10203 displays strong in vivo combination effects with HER2 inhibitors tucatinib or trastuzumab in HER2AMP models."

Preclinical • Solid Tumor

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-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

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

BBOT Announces Multiple Presentations at the American Association for Cancer Research (AACR) Annual Meeting 2026 (GlobeNewswire)

Preclinical • Solid Tumor

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

BBO-10203 (RAS:PI3Kα Breaker) (GlobeNewswire) - "As of December 10, 2025, the BBO-10203 safety profile has demonstrated the potential to be highly differentiated compared to previously reported data on other PI3Ka-targeting agents. No DLTs. No grade ≥3 TRAEs except for one incidence of asymptomatic hypokalemia (lab abnormality)​; no dose reductions​; no TRSAEs.​...​BBO-10203 achieved target systemic exposure and rapid full target engagement."

P1 data • Colorectal Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • 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

BREAKER-101: a phase 1a/1b open-label study evaluating the safety, tolerability, pharmacokinetics, and efficacy of BBO-10203 in patients with advanced solid tumors (SABCS 2025) - P1 | "At recommended dose(s) for expansion, additional safety, PK, and antitumor activity will be evaluated for BBO-10203 monotherapy and in combination with trastuzumab in HER2+ aBC, as well as in combination with fulvestrant ± ribociclib in HR+/HER2- aBC, and with FOLFOX + bevacizumab in aCRC...BBO-10203 will be taken orally, once daily, in a 21-day or 28-day treatment cycle depending on the cohort. This study is currently open for enrollment."

Clinical • Metastases • P1 data • PK/PD data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • KRAS • PIK3CA

BBO-10203, a first-in-class breaker of the RAS:PI3Kα interaction, inhibits tumor growth alone and in combination with fulvestrant or ribociclib in breast cancer models without inducing hyperglycemia (SABCS 2025) - P1 | "In the EFM-19 CDX model, which harbors a kinase domain PIK3CA mutation, the combination of BBO-10203 and fulvestrant show the same activity as the combination of STX-478 and fulvestrant. In conclusion, BBO-10203 blocks RAS-mediated activation of PI3Kα, strongly inhibits pAKT signaling in tumor cells without affecting glucose metabolism, and shows robust tumor activity alone or in combination with standard of care therapies in mutant or wild-type PIK3CA breast cancer models. BBO-10203 has entered phase 1 clinical trials (NCT06625775) 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 • KRAS • NRAS • PIK3CA

Trial in Progress Poster (GlobeNewswire) - "The data is being presented today at the San Antonio Breast Cancer Symposium (SABCS)....BREAKER-101 (NCT06625775) is a first-in-human, multicenter, open-label, Phase 1a/1b study evaluating the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of BBO-10203....Key endpoints include safety and tolerability, anti-tumor activity, and pharmacokinetics. Intracranial activity of BBO-10203 will also be evaluated as an exploratory endpoint. The study is currently enrolling patients in the United States and Australia, and initial Phase 1 clinical data are expected in the first half of 2026."

First-in-human • P1 data • Trial status • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer

BBOT Announces Late-Breaking Preclinical Data on BBO-10203, a First-in-Class RAS:PI3Kα Breaker, at the San Antonio Breast Cancer Symposium (SABCS) (GlobeNewswire) - "Preclinical data demonstrate BBO-10203 blocks RAS-mediated activation of PI3Kα, strongly inhibits pAKT signaling in tumor cells without inducing hyperglycemia, and shows robust anti-tumor activity both as monotherapy and in combination with standard of care therapies in mutant or wild-type PIK3CA breast cancer models."

Late-breaking abstract • Preclinical • Breast 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

BridgeBio Oncology Therapeutics…announced two poster presentations featuring BBO-10203, a first-in-class, orally bioavailable, selective breaker of the RAS:PI3Kα interaction, at the San Antonio Breast Cancer Symposium (SABCS)… (GlobeNewswire)

Late-breaking abstract • Preclinical • Trial status • Breast Cancer

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