BT1718 / Bicycle Therap - LARVOL DELTA

CRUKD/17/009: BT1718 in Patients With Advanced Solid Tumours. (clinicaltrials.gov) - P1/2 | N=72 | Completed | Sponsor: Cancer Research UK | Active, not recruiting ➔ Completed

Trial completion • Esophageal Cancer • Gastrointestinal Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • MMP14

CRUKD/17/009: BT1718 in Patients With Advanced Solid Tumours. (clinicaltrials.gov) - P1/2 | N=72 | Active, not recruiting | Sponsor: Cancer Research UK | Recruiting ➔ Active, not recruiting | N=130 ➔ 72

Enrollment change • Enrollment closed • Metastases • Esophageal Cancer • Gastrointestinal Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • MMP14

Preliminary pharmacokinetic assessment of BT1718: A phase I/IIa trial of BT1718 (a first in class Bicycle Toxin Conjugate) in patients with advanced solid tumours (EORTC-NCI-AACR 2018) - P1/2; "The preliminary PK data confirm the expected PK profile based on preclinical data. Updated clinical PK data from the ongoing study will be discussed along with further preclinical tumor and plasma data illustrating mechanism of action of this new treatment modality"

Clinical • P1/2 data • PK/PD data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • Thoracic Cancer • Triple Negative Breast Cancer

CRUKD/17/009: BT1718 in Patients With Advanced Solid Tumours. (clinicaltrials.gov) - P1/2 | N=130 | Recruiting | Sponsor: Cancer Research UK | Trial completion date: Mar 2022 ➔ Dec 2024 | Trial primary completion date: Mar 2022 ➔ Dec 2024

Trial completion date • Trial primary completion date • Esophageal Cancer • Gastrointestinal Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • MMP14

Pharmacokinetic (PK) assessment of BT1718: A phase I/II a study of BT1718, a first in class bicycle toxin conjugate (BTC), in patients (pts) with advanced solid tumours (ESMO 2019) - P1/2; "BT1718 is a first in class BTC which is generally well tolerated at the present dose level. Current plasma and tumor PK data are consistent with proposed preclinical mechanism of tumor targeted toxin delivery. Clinical trial identification: NCT03486730."

Clinical • P1/2 data • PK/PD data

Bicycle Therapeutics Reports Fourth Quarter and Full Year 2020 Financial Results and Provides Corporate Update (Businesswire) - “BT1718: Additional sites expected to begin enrolling patients during the first half of 2021…BT5528: additional sites expected to begin enrolling patients in 2021…BT8009: The first clinical trial site outside of the United States opened in the first quarter of 2021…”

Clinical • Enrollment status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Development of a LC-MS/MS method for the quantification of toxic payload DM1 cleaved from BT1718 in a Phase I study. (PubMed, Bioanalysis) - " The method was fully validated over a linear range of 200-50,000 ng/ml BT1718, with overall precision ≤10% and accuracy 89-102%. A novel method for quantifying DM1 yielded from BT1718 has been validated and is now being utilized clinically."

Journal • P1 data • Oncology

Bicycle Therapeutics Announces Pipeline Progress Update (Businesswire) - “BT1718: Enrollment is ongoing at four clinical sites, with additional sites expected to begin enrolling patients during the first half of 2021….Depending on results from these first two cohorts, Cancer Research UK may initiate up to two additional cohorts….Enrollment in the Phase I/II trial of BT5528 remains on track and additional sites are expected to begin enrolling patients in 2021…Further clinical updates for all three BTC programs - BT1718, BT5528, and BT8009 – are expected during 2021…IND preparation for BT7480, a novel TICA, remains on track, for a potential clinical start during the second half of 2021.”

Clinical • Enrollment status • IND • Pipeline update • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Bicycle Therapeutics Announces Settlement of Patent Dispute with Pepscan Systems B.V. (Businesswire) - "The companies have agreed to settle all intellectual property disputes worldwide. Under the terms of the settlement, Bicycle has been granted a license to use CLIPS peptide technology in the development of its product candidates BT1718 and THR-149. Bicycle will pay €3 million upfront, will pay €1 million on the first anniversary of the date of settlement, and will make potential additional payments to Pepscan based on achievement of specified clinical, regulatory and commercial milestones."

Corporate lawsuit • Oncology

[VIRTUAL] BT1718 (AACR-NCI-EORTC 2020) - "Abstract not received."

Oncology

Bicycle Therapeutics Announces Gross Proceeds of $50.0 Million from its At-the-Market Offering Program and Enters into Debt Financing from Hercules Capital (Bicycle Therapeutics Press Release) - "Bicycle plans to use the proceeds of the financings to advance its oncology pipeline of Bicycle Toxin Conjugates and immuno-oncology candidates through multiple clinical milestones expected in 2021, including interim updates from the ongoing Phase IIa trial of BT1718, Phase I/II trial of BT5528 and Phase I/II trial of BT8009, as well as the initiation of a Phase I/II trial of BT7480 and advancement of IND-enabling studies for BT7455."

New P1/2 trial • Preclinical • Trial status • Oncology

Bicycle Therapeutics Announces First Patient Dosed in Phase IIa Trial of Bicycle Toxin Conjugate BT1718 (Businesswire) - "Bicycle Therapeutics plc…announced that the first patient has been dosed in the Phase IIa expansion portion of the Phase I/IIa trial sponsored by Cancer Research UK, the world’s leading cancer charity dedicated to saving lives through research. The trial is evaluating BT1718 in patients with MT1-MMP-positive squamous non-small cell lung cancer (NSCLC) and a basket of other MT1-MMP-positive solid tumors."

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

[VIRTUAL] Integrative surfaceome profiling identifies MMP14, MRC2 and CD276 as candidate immunotherapeutic target in osteosarcomas (AACR-II 2020) - "Multiple preclinical tests including CD276 CAR-T cells, MRC2 ADC and MMP14 Bicycle Drug Conjugate (BT1718) are planned to further validate the therapeutic potential of these targets. Our current findings have not been previously reported in OS. The results might warrant further development of ADC and CAR-T cell therapy for osteosarcomas against these targets."

IO Biomarker • Oncology • Osteosarcoma • Sarcoma • Solid Tumor

The discovery of BT1718: A novel bicyclic peptide drug conjugate drug conjugate for the treatment of solid tumors expressing MT1-MMP (AACR 2018) - "There is no abstract associated with this presentation."

Oncology • Solid Tumor

Bicycle Therapeutics reports first quarter 2020 financial results and provides corporate update (Businesswire) - "The Company continues to expect that Cancer Research UK will initiate the Phase IIa portion of the Phase I/IIa study of BT1718 in 2020…[for BT5528] The combination arm opened in the second quarter of 2020, and the monotherapy escalation continues toward clinically relevant doses; In 2020, Bicycle expects to initiate a Phase I/II trial of BT8009, a second-generation BTC targeting Nectin-4, in patients with advanced solid tumors…IND-enabling activities for BT7480 are ongoing and on track to a potential initiation of clinical development in 2021…"

IND • New P1/2 trial • Trial status • Oncology • Solid Tumor

Bicycle Therapeutics announces pipeline progress update (Businesswire) - “BT1718, a potential first-in-class BTC targeting key tumor antigen MT1-MMP: The Company anticipates that Cancer Research UK will initiate the Phase IIa portion of the Phase I/IIa study of BT1718 in 2020, although timing may be dependent on the ongoing COVID-19 pandemic; BT5528, a BTC targeting EphA: Bicycle expects the first patient in the combination arm will be dosed in 2020, subject to potential timing and other impacts of the ongoing COVID-19 pandemic; Phase I/II Trial of BT8009 Currently On Track to Initiate in 2020: The Company plans to initiate a Phase I/II study of BT8009 in patients with advanced solid tumors in indications associated with Nectin-4 expression this year...IND Preparation for BT7480 On Track, Enabling Potential Clinical Start in 2021”

Enrollment status • IND • New P1/2 trial • Trial status • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer

Bicycle Therapeutics reports fourth quarter and full year 2019 financial results and corporate updates (Businesswire) - “Anticipated Key Events in 2020: Initiation of Phase IIa trial of BT1718, a BTC targeting MT1-MMP, in patients with solid tumors expressing MT1 (trial sponsored by Cancer Research UK); Interim BT5528 Phase I data readout from the ongoing Phase I/II trial; Initiation of nivolumab arm in BT5528 Phase I portion of the ongoing Phase I/II trial; Initiation of a Phase I/II trial of BT8009, a second-generation BTC targeting Nectin-4, a tumor antigen shown to be overexpressed in tumor cells, in patients with solid tumors.”

New P1/2 trial • New P2 trial • P1/2 data • Trial status

"@Physiomics #PYC partner with BT1718 hopefully @Bicycle_tx can pass on good vibes to @Genentech" (@Kidlington)

MT1-MMP Immunohistochemistry (IHC) analysis of tumor microarrays (TMAs) using a novel scoring system guides patient selection for BT1718 expansion cohorts (AACR-NCI-EORTC 2019) - "Based on these analyses; squamous lung, squamous esophageal, and an all comers high MT1-MMP basket were selected (using a TM cut-off of at least H-score ≥100) as the three proposed BT1718 expansion cohorts."

Clinical

Bicycle Therapeutics to present new translational data for BT1718 and preclinical data for other bicycle toxin conjugates at AACR-NCI-EORTC 2019 (Businesswire) - P1, N=130; NCT03486730; "Bicycle Therapeutics plc...announced that new translational data for BT1718 and preclinical data for BT5528 and BT8009 will be presented during poster sessions at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics on October 26-30, 2019 in Boston, MA....New translational data will be presented for BT1718, the Company’s lead Bicycle® Toxin Conjugate (BTC) product candidate, which define enrollment criteria for identifying expansion cohorts in the Phase IIa part of the ongoing Phase I/IIa trial with BT1718."

P2a data • Preclinical

"$BCYC #ESMO19 BT1718 poster, via Natalie Cook" (@JacobPlieth)

Bicycle Therapeutics announces presentation of updated data from phase I/IIa Trial evaluating BT1718 in patients with advanced solid tumors at ESMO 2019 Annual Congress (Businesswire) - PI/IIa, N=130; NCT03486730; “Based on data from patients in cohorts across dose levels tested, many of which are below the predicted therapeutic range, 13 of 24 evaluable patients (54%) had stable disease at the eight-week timepoint, including a patient who experienced a 45% reduction in a target lesion. With once-weekly dosing, which is the expected schedule for the Phase IIa portion of the study, BT1718 has appeared tolerable, with manageable adverse events.”

P1/2 data

Bicycle Therapeutics to present updated data from phase I/IIa trial evaluating lead asset BT1718 in patients with advanced solid tumors at ESMO 2019 Annual Congress (Businesswire) - P1/2a, N=130; NCT03486730; “Bicycle Therapeutics plc…announced that updated data from the Phase I dose escalation portion of the Phase I/IIa trial evaluating the Company’s lead asset BT1718 in patients with advanced solid tumors will be presented at the European Society of Medical Oncology (ESMO) 2019 Annual Congress, September 27 – October 1 in Barcelona, Spain.”

P1/2 data