BBT-176 / Bridge Biotherap - LARVOL DELTA

Over 200! The largest BaF3-EGFR engineering cell lines collection, a useful platform for novel drug discovery (AACR 2025) - "Recognizing EGFR as a driver gene has accelerated the development of targeted anticancer therapies, such as monoclonal anti-EGFR antibodies (cetuximab, panitumumab) and small molecule receptor tyrosine kinase inhibitors (TKIs). The first generation of EGFR TKIs, like gefitinib and erlotinib, specifically target mutations such as L858R and exon 19 deletions. To address resistance to these early inhibitors, second-generation EGFR TKIs (afatinib, dacomitinib) were developed...Osimertinib, a third-generation TKI, was approved for use in EGFR-mutated NSCLC following the failure of first- and second-generation TKIs, although the EGFR C797S mutation limits its effectiveness. Fourth-generation EGFR TKIs, including BLU-945 and BBT-176, are under clinical evaluation but are not yet approved.We have created more than 200 Ba/F3-EGFR engineered cell lines, making this the largest in vitro and in vivo platform for drug discovery with the widest range of mutant cells. These cell lines..."

Preclinical • Brain Cancer • Breast Cancer • Colon Cancer • Colorectal Cancer • Head and Neck Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • EGFR • EPGN • ERBB3 • ERBB4 • HBEGF • HER-2 • TGFA

Targeting exon mutations in NSCLC: clinical insights into LAG-3, TIM-3 pathways, and advances in fourth-generation EGFR-TKIs. (PubMed, Med Oncol) - "Advanced inhibitors, including BBT-176, BLU-945, and BLU-701, have effectively targeted resistant mutations and reduced disease progression. Such combination regimens aim to optimize PFS, OS, and ORR while minimizing adverse effects and addressing the limitations of current therapies. This study explores the landscape of EGFR mutations, their clinical significance, and the integration of innovative fourth-generation EGFR-TKIs with immunotherapies, emphasizing the potential of precision medicine in advancing the management of EGFR-mutated NSCLC."

IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • HAVCR2 • LAG3 • PD-L1

Bridge Biotherapeutics and HitGen Initiate Research Collaboration to Advance Novel Cancer Therapeutics Program (PRNewswire) - "Bridge Biotherapeutics...announced that it has entered into a joint research agreement with HitGen Inc...This collaboration builds on successful initial hit finding and identification work from HitGen's DNA-encoded library (DEL), aiming to further develop the novel hits as promising drug candidates for cancer...Bridge plans to strengthen its existing oncology portfolio, which is centered on EGFR inhibitors for lung cancer treatment, through new anticancer drug candidates targeting undisclosed targets...With the launch of this joint research with HitGen, it is anticipated that the derivation of effective substances, optimization, and securing of lead compounds will progress rapidly within the next year."

Licensing / partnership • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

What the future holds: BBT-176, beyond third-generation EGFR tyrosine kinase inhibitors. (PubMed, Transl Lung Cancer Res) - No abstract available

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Phase 1/2 Study of BBT-176 in Advanced NSCLC With Progression After EGFR TKI Treatment (clinicaltrials.gov) - P1/2 | N=45 | Terminated | Sponsor: Bridge Biotherapeutics, Inc. | Trial completion date: Jun 2024 ➔ Nov 2023 | Active, not recruiting ➔ Terminated; Sponsor's decision considering the changing treatment landscape for NSCLC

Trial completion date • Trial termination • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Phase 1/2 Study of BBT-176 in Advanced NSCLC With Progression After EGFR TKI Treatment (clinicaltrials.gov) - P1/2 | N=45 | Active, not recruiting | Sponsor: Bridge Biotherapeutics, Inc. | Recruiting ➔ Active, not recruiting | N=168 ➔ 45

Enrollment change • Enrollment closed • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Bridge Bio presents phase 1 follow-up data for ‘4th generation lung cancer treatment’ at the World Lung Cancer Society [Google translation] (Yakup Shinmoon) - P1/2 | N=168 | NCT04820023 | Sponsor: Bridge Biotherapeutics, Inc. | "Bridge Biotherapeutics announced 'BBT-176', a 4th generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI) being developed as a treatment for non-small cell lung cancer at the 2023 International Association for Lung Cancer (IASLC 2023 WCLC)....The BBT-176 phase 1 clinical follow-up data released in Singapore through a presentation by Professor Lim Seon-min of the Lung Cancer Center at Yonsei Cancer Hospital showed the improved tolerability and medication compliance of BBT-176 due to the change in dosage from once daily to twice daily. A new case of a patient was introduced who showed ‘partial response (PR)’ in which the size of the tumor was reduced by more than 30% in the corresponding dosage group."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Discovery of BBT-176 as Fourth Generation EGFR Tyrosine Kinase Inhibitor. (AACR-NCI-EORTC 2023) - No abstract available

Oncology • EGFR

Bridge Biotherapeutics discards NSCLC drug candidate BBT-176 (Korea Biomedical Review) - "Bridge Biotherapeutics announced on Tuesday that it will discontinue the development of BBT-176, a drug candidate for non-small cell lung cancer (NSCLC)...Instead, the company stated it would focus on...BBT-207, candidates for...NSCLC, which have 'greater market potential'....Bridge Biotherapeutics also estimates that the internalization of clinical development functions will reduce costs by about 10 billion won (approximately $7.3 million) for the lung cancer project, and it is also expected to generate new cash flow through cooperation with a number of domestic companies in the bio industry."

Commercial • Discontinued • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BBT-176, a 4th Generation EGFR TKI, for Progressed NSCLC after EGFR TKI Therapy: Updated Report from a Phase 1 Study (IASLC-WCLC 2023) - P1/2 | "Early efficacy signals were shown. BID is associated with improved tolerability and compliance. Further exploration in a molecularly enriched cohort, which will be defined by the presence of EGFR C797S in plasma and sub-grouped according to the founder mutation (exon 19 del or L858R), is planned."

P1 data • Dental Disorders • Hematological Disorders • Interstitial Lung Disease • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Stomatitis

K Pharmaceutical Bio, including Yuhan Corporation, Voronoi, and Lunit, participates in large numbers at the World Lung Cancer Society [Google translation] (Money Today) - "In addition, Hanmi Pharmaceutical...announces research results on two cohorts (same group) of the phase 2 clinical trial of 'Poziotinib', a new lung cancer drug candidate. ST Cube provided some of the phase 1 clinical trial data related to the immune checkpoint inhibitor 'Nelmastobart', Bridge Bio provided follow-up data from the phase 1 clinical trial of the 4th generation lung cancer new drug candidate 'BBT-176', and Coreline Soft, a medical AI company, provided cardiac information."

P1 data • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Bridge Bio announced follow-up data of non-small cell lung cancer candidate at WCLC [Google translation] (HIT News) - P1/2 | N=168 | NCT04820023 | Sponsor: Bridge Biotherapeutics, Inc. | "Bridge Biotherapeutics...is conducting a clinical trial of BBT-176 (development code name), a candidate for the 4th generation non-small cell lung cancer treatment, at the 2023 International Association for Lung Cancer (IASLC 2023 WCLC), which will be held in Singapore on the 9th of next month. It was announced on the 30th that the announcement of the follow-up data for phase 1 was confirmed. According to the published abstract, BBT-176, which is being developed as a 4th-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI), is a follow-up data from the phase 1 clinical trial. Improvement of BBT-176 according to twice daily intake improved tolerability and medication compliance. Patient cases showing a partial response (PR) in which the tumor size was reduced by more than 30% in the changed twice-a-day regimen administration group are expected to be newly announced."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BBT-176, a Novel Fourth-Generation Tyrosine Kinase Inhibitor for Osimertinib-Resistant Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer. (PubMed, Clin Cancer Res) - P1/2 | "BBT-176 is a fourth-generation EGFR inhibitor showing promising preclinical activity against NSCLC resistant to current EGFR TKIs."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Bridge Biotherapeutics to Present at the 2023 BIO International Convention (PRNewswire) - "Bridge Biotherapeutics...is scheduled to give a company presentation on Tuesday, June 6 at the 2023 BIO International Convention taking place in Boston, Massachusetts, between June 5 - 8, 2023. Pavel Printsev, Director of Business Development, will provide an up-to-date company overview as well as an introduction to its clinical-stage assets: Oncology: BBT-176 and BBT-207 (Fourth-generation EGFR TKIs for non-small cell lung cancer active against C797S resistance mutations)."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

BBT-207, a novel, 4th generation, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with broad-spectrum activity to both treatment-emergent and drug-naïve mutants for the treatment of NSCLC (AACR 2022) - P1/2 | "Such a 4th generation EGFR TKI must also enable monotherapy, allowing precise dose adjustment in case of toxicity. Derived from BBT-176 which is under clinical evaluation (NCT04820023), we synthesized BBT-207 and other related molecules...Double mutants containing T790M (DT and LT) were inhibited effectively by BBT-207 and Osimertinib at similar concentrations, while not by Gefitinib... BBT-207 is a reversible, mutant-specific, broad-spectrum TKI, active to clinically observed mutations of EGFR and is expected to be compatible with monotherapy of QD schedule in humans. BBT-207 is well-positioned to augment the treatment of EGFR mutated NSCLC, either for acquired drug resistance or in earlier line."

Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

'Bridge Biotherapeutics committed to expanding cancer, fibrosis pipeline' (Korea Biomedical Review) - "...Bridge Biotherapeutics finished the dose escalation phase 1a study of BBT-176, an experimental non-small cell lung cancer (NSCLC) treatment, and plans to submit the U.S. IND application for BBT-207 next month. 'BBT-207’s abstract for a poster presentation at the upcoming AACR has been accepted, and we look forward to sharing our latest pre-clinical update in Orlando, Florida, in April'..."

IND • Preclinical • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

[VIRTUAL] A phase I/II, open-label study of BBT-176, a triple mutation targeting EGFR TKI, in patients with NSCLC who progressed after prior EGFR TKI therapy (ESMO 2021) - P1/2 | "Background: First- and third-generation epidermal growth factor receptor (EGFR) inhibitors such as gefitinib and osimertinib, respectively, have improved survival outcomes for patients with advanced EGFR-mutant NSCLC...Synergistic efficacy of BBT-176 with Cetuximab was also observed in animal studies...When RP2D is determined in Part 1, then Part 2 will be initiated to evaluate efficacy in molecularly selected target populations. Objective response rate, duration of response and progression-free survival will be measured in addition to safety and tolerability of BBT-176 at RP2D (NCT04820023)."

Clinical • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

BBT-176, a 4th generation EGFR TKI, for Progressed NSCLC after EGFR TKI Therapy: PK, Safety and Efficacy from Phase 1 Study (IASLC-WCLC 2022) - P1/2 | "Continuous daily dosing of BBT-176 was well-tolerated with manageable toxicities. The effectiveness of BBT-176 may be further enhanced by molecular selection of the patients and dynamic monitoring with liquid biopsy. Further exploration at RP2D is planned (NCT04820023)."

Clinical • P1 data • Dermatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pruritus • Solid Tumor • EGFR

Phase 1/2 Study of BBT-176 in Advanced NSCLC With Progression After EGFR TKI Treatment (clinicaltrials.gov) - P1/2 | N=168 | Recruiting | Sponsor: Bridge Biotherapeutics, Inc. | N=90 ➔ 168

Enrollment change • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Bridge Biotherapeutics Presents Promising Interim Clinical Study Results from Phase 1 Study of BBT-176 at WCLC 2022 (PRNewswire) - P1/2 | N=90 | NCT04820023 | Sponsor: Bridge Biotherapeutics, Inc. | "Bridge Biotherapeutics...announced promising interim clinical data from its Phase I study of BBT-176...on Lung Cancer (IASLC WCLC 2022), show promising early evidence of efficacy and favorable tolerability in patients with non-small cell lung cancer....One patient with advanced NSCLC showing C797S triple mutations, confirmed as one of the partial response (PR) cases, showed up to 53 percent decrease of EGFR mutant allele frequency compared to the baseline. Data from the five patients who had been treated with BBT-176 over 100 days suggested that circulating tumor DNA (ctDNA) analysis enabled with liquid biopsy may be useful not only in identifying those most likely to benefit from fourth-generation EGFR TKI treatments such BBT-176, but also monitoring therapeutic response with treatment of a fourth-generation EGFR TKI."

P1 data • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Bridge Biotherapeutics to Present Interim Clinical Data from Ongoing Phase 1 Study of BBT-176 at the World Conference of Lung Cancer (PRNewswire) - P1/2 | N=90 | NCT04820023 | Sponsor: Bridge Biotherapeutics, Inc. | "Bridge Biotherapeutics...announced that interim clinical data from an ongoing Phase I study of BBT-176 has been selected for a mini oral presentation at the International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer (IASLC WCLC 2022)....According to the published abstract, the presentation will cover potent anti-tumor efficacy of BBT-176 explored with radiological improvements in both target and non-target lesions from two patients harboring EGFR triple mutations of exon 19 del/T790M/C797S. One patient from the 320mg dosing cohort exhibited 30.3 percent shrinkage of the target lesion, according to the abstract. Another patient from the 480mg dosing cohort exhibited 26.3 percent shrinkage of the target lesion."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Bridge Biotherapeutics, Inc (BIO 2022) - "is a publicly traded clinical-stage biotech company based in the Republic of Korea with labs and offices in the U.S. Founded in 2015, Bridge Biotherapeutics is engaged in the discovery and development of novel therapeutics for disease indications with high unmet medical needs including cancer, ulcerative colitis, and fibrotic diseases. The company's clinical pipeline includes BBT-401, a first-in-class Pellino-1 inhibitor for the treatment of ulcerative colitis; BBT-877, a novel autotaxin inhibitor for the treatment of fibrotic diseases including idiopathic pulmonary fibrosis (IPF); and BBT-176, a potent targeted cancer therapy for non-small cell lung cancer (NSCLC) with C797S triple EGFR mutations."

Fibrosis • Gastroenterology • Gastrointestinal Disorder • Idiopathic Pulmonary Fibrosis • Immunology • Inflammatory Bowel Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Ulcerative Colitis • EGFR

Bridge Biotherapeutics to Announce Updated Data from its Phase 1 Study of BBT-176 in Advanced Non-Small Cell Lung Cancer in an Oral Presentation at IASLC 2022 World Conference on Lung Cancer (PRNewswire) - "Bridge Biotherapeutics...announced it will deliver an oral presentation highlighting the analysis data from the first-in-patient study of BBT-176 at the International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer (IASLC 2022 WCLC).....According to the company's presentation, BBT-176 has shown anti-tumor efficacy with two partial response cases, one in the 160 mg QD cohort (51 percent tumor shrinkage) and the other in the 320 mg QD cohort (30 percent tumor shrinkage)....The company's oral presentation on BBT-176 is expected to be held on August 8, during IASLC 2022 WCLC, in Vienna, Austria."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Identification of next-generation EGFR degraders to treat non-small cell lung cancer (NSCLC) patients (AACR 2022) - "A PK study of C-4383 in rats showed good exposure with moderate CL when administered intravenously (CL = 8.51 mL/min/kg, AUC = 5911 ng•h/mL).In summary, we identified heterobifunctional degraders using a 4th generation EGFR inhibitor, BBT-176, that are active in EGFR mutant NSCLC cells harboring single or C797S-containing multiple mutations. We are currently making our efforts on the improvement of physicochemical properties of EGFR mutant targeted heterobifunctional compounds."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

BridgeBio “BBT-176 enters clinical trial for capacity expansion in the fourth quarter of next year” [Google translation] (Hankyung) - "Bridge Biotherapeutics...announced on the 30th that phase 1 and 2 clinical trials for 'BBT-176', a new drug candidate for non-small cell lung cancer, are cruising. It plans to complete a capacity increase test next year and enter a capacity expansion test in the fourth quarter....From next year, clinical trials for the fifth dose group will be conducted and the maximum tolerated dose (MTD) and the recommended dose for phase 2 clinical trial (RP2D) will be confirmed....The goal is to start it in the fourth quarter of next year in Korea and the United States....Bridge Biotherapeutics is preparing for the presentation of the interim results of BBT-176 at the American Society of Clinical Oncology (ASCO) to be held on June 3-7 (local time) next year. An announcement will be made in February next year."

P1/2 data • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology