nuzefatide pevedotin (BT5528) / Bicycle Therap - LARVOL DELTA

Phase 2 Study of Nuzefatide Pevedotin, an EphA2-targeting Bicycle Drug Conjugate (BDC), in Patients (Pts) With Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) (ESMO 2026) - No abstract available

Clinical • Metastases • P2 data • Oncology • Pancreatic Ductal Adenocarcinoma

Results From First-in-Human Phase I Dose-Escalation Study of a Novel Bicycle Toxin Conjugate Targeting EphA2 (BT5528) in Patients With Advanced Solid Tumors. (PubMed, J Clin Oncol) - "BT5528 was well tolerated and demonstrated favorable and preliminary antitumor activity. We believe these data provide preliminary validation of a Bicycle Toxin Conjugate approach to EphA2 tumor antigen. The study is ongoing and is evaluating BT5528 as monotherapy at a RP2D of 6.5 mg/m2 once every 2 weeks."

Journal • Metastases • P1 data • Fatigue • Hematological Disorders • Neutropenia • Oncology • Solid Tumor

EphA2 targeting bicycle® peptides for precision guided cancer therapy via multiple approaches | Poster Board #1441 (ACS-Fall 2026) - "For example, EphA2-targeting BDC®, BT5528, delivers MMAE rapidly into tumours to provide persistent cytotoxin exposure, whilst rapid renal elimination prevents prolonged exposure elsewhere.2 Bicycle® peptides can be the ideal vector for radiopharmaceutical payloads, wherein the cytotoxin payload of a BDC may be replaced with a chelating group for site-specific radiolabelling with isotopes such as Ga-68 or Lu-177 and subsequently optimised to yield Bicycle® Radioligands, designed to deliver radioisotopes for both diagnostic imaging and targeted radiotherapy...This approach offers another strategy to target EphA2-positive cancers through tumour-localised immune response. This robust discovery and optimisation process for Bicycle® conjugates has the potential to deliver a pipeline of best-in-class diagnostic and therapeutic agents across a range of high value cancer targets to address critical unmet needs across a breadth of cancer indications."

Oncology • TNFRSF9

Bicycle Continued Access Protocol (BiCAP) for Participants Receiving a Bicycle Investigational Product (clinicaltrials.gov) - P2 | N=16 | Not yet recruiting | Sponsor: BicycleTx Limited

New P2 trial • Oncology • Solid Tumor

Study BT5528-100 in Patients With Advanced Solid Tumors Associated With EphA2 Expression (clinicaltrials.gov) - P1/2 | N=288 | Recruiting | Sponsor: BicycleTx Limited | Trial completion date: Oct 2026 ➔ Oct 2025

Metastases • Trial completion date • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • CD4 • EPHA2

Study BT5528-100 in Patients With Advanced Solid Tumors Associated With EphA2 Expression (clinicaltrials.gov) - P1/2 | N=288 | Recruiting | Sponsor: BicycleTx Limited | Trial completion date: Dec 2024 ➔ Oct 2026

Trial completion date • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer • CD4 • EPHA2

Study BT5528-100 in Patients With Advanced Solid Tumors Associated With EphA2 Expression (clinicaltrials.gov) - P1/2 | N=312 | Recruiting | Sponsor: BicycleTx Limited | N=166 ➔ 312 | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • Cervical Cancer • Gastric Cancer • Gastrointestinal Cancer • Gastrointestinal Disorder • Genito-urinary Cancer • Head and Neck Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer • CD4 • EPHA2

The journey of targeted drug conjugates in solid tumors: moving beyond antibody drug conjugates. (PubMed, Expert Opin Investig Drugs) - "We expect promising preclinical and clinical data emerging for SMDCs, PDCs, and BDC molecules will translate into approvals, such as BDC molecules that are under pivotal randomized phase II clinical investigation. These novel treatments will increase survival and quality of life for patients with solid tumors."

Journal • Review • Oncology • Solid Tumor

Bicycle Therapeutics initiated a strategic reprioritization in order to focus its resources on its promising pipeline of next-generation therapeutics, including nuzefatide, as well as its emerging Bicycle conjugate pipeline, including BRCs. (Bicycle Therapeutics Press Release)

Pipeline update • Pancreatic Ductal Adenocarcinoma • Urothelial Cancer

Preclinical assessment of BT5528 anti-tumor activity in patient-derived xenograft (PDX) models of pancreatic ductal adenocarcinoma (PDAC) (AACR 2026) - "Expression of EphA2 was found in all PDAC PDX models. Most models were sensitive to BT5528 treatment, which was not affected by the degree of desmoplasia or membrane EphA2 TPS. These results may reflect a lack of truly EphA2-negative models in this analysis."

Preclinical • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • EPHA2

An EphA2-targeting Bicycle Drug Conjugate (BDC), BT5528, in combination with nivolumab in patients (pts) with advanced solid tumors: Results from a Phase 1/2 study (AACR 2026) - P1/2 | "All 14 pts in the 6.5 mg/m2 cohort had metastatic urothelial carcinoma (mUC) and had previously progressed on a checkpoint inhibitor and 10 while on enfortumab vedotin. BT5528 + nivo demonstrated a generally well-tolerated safety profile across doses, with no new safety signals, in contrast to prior attempts to target EphA2, with no PK drug-drug interactions. Preliminary anti-tumor activity was demonstrated in pts with mUC at a dose of BT5528 6.5 mg/m2 once every 2 wks + nivo 480 mg once every 4 wks, especially in MMAE-naive pts with EphA2+ tumors."

Clinical • Combination therapy • Metastases • P1/2 data • Oncology • Solid Tumor • Urothelial Cancer • EPHA2

Preclinical assessment of BT5528 anti-tumor activity in cell-line-derived xenograft (CDX) models of head and neck squamous cell carcinoma (HNSCC) (AACR 2026) - "BT5528 has shown potent preclinical anti-tumor activity in EphA2-expressing CDX models of HNSCC at clinically relevant doses. These data support the potential to further evaluate BT5528 in HNSCC.1. Bennett et al."

Preclinical • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EPHA2

Bicycle Therapeutics Provides Update on Nuzefatide Pevedotin...at the AACR Annual Meeting 2026 (PharmiWeb) - "40% confirmed overall response rate (ORR) (4/10) among patients with EphA2+ tumors and 100% confirmed ORR (3/3) among patients with EphA2+ tumors that were monomethyl auristatin E (MMAE)-naïve; Patients who achieved a partial response (PR) or at least 16 weeks of stable disease (SD) were on treatment for a minimum of 56 week....Further work has led Bicycle Therapeutics to determine 8mg/m2 Q2W as the preferred dose for the Phase 2 trial in patients with recurrent pancreatic ductal adenocarcinoma (PDAC)....In March 2026, Bicycle Therapeutics began enrolling patients in a Phase 2 clinical trial to evaluate efficacy, safety, and pharmacokinetics of nuzefatide in adult patients with recurrent PDAC, and the first patient was successfully dosed in April 2026."

P1/2 data • Trial status • Pancreatic Ductal Adenocarcinoma • Urothelial Cancer

Preclinical assessment of nuzefatide anti-tumor activity in patient-derived xenograft (PDX) models of PDAC. (PharmiWeb) - "Expression of EphA2 was found in all 16 PDAC PDX models. Of the 14 PDAC PDX models assessed for anti-tumor activity, 10 models were sensitive to nuzefatide, six of which showed high sensitivity. These data support the potential for nuzefatide to offer a novel option for the treatment of patients with PDAC."

Preclinical • Pancreatic Ductal Adenocarcinoma

Preclinical assessment of nuzefatide anti-tumor activity in cell-line-derived xenograft (CDX) models of head and neck squamous cell carcinoma (HNSCC). (PharmiWeb) - "Nuzefatide demonstrated potent preclinical anti-tumor activity in EphA2-expressing CDX models of HNSCC."

Preclinical • Squamous Cell Carcinoma of Head and Neck

Study BT5528-100 in Patients with Advanced Solid Tumors Associated with EphA2 Expression (clinicaltrialsregister.eu) - P1/2 | N=63 | Active, not recruiting | Sponsor: Bicycletx Limited | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Solid Tumor

Bicycle Therapeutics…announced an oral presentation and multiple poster presentations of five abstracts at the American Association for Cancer Research (AACR) Annual Meeting 2026 (Businesswire)

P1/2 data • Preclinical • Bladder Cancer • Pancreatic Ductal Adenocarcinoma • Squamous Cell Carcinoma of Head and Neck

BT5528, a potential first-in-class EphA2 targeting BDC molecule (Businesswire) - "Bicycle Therapeutics announced nuzefatide pevedotin (nuzefatide) as the International Nonproprietary Name for BT5528. Phase 1 nuzefatide combination data with nivolumab in mUC patients will be presented at a scientific conference in the first half of 2026. In March 2026, Bicycle Therapeutics began enrolling a Phase 2 clinical trial to evaluate efficacy, safety, and pharmacokinetics of nuzefatide in adult patients with recurrent pancreatic ductal adenocarcinoma (PDAC). Additional information regarding this indication will be presented at a scientific conference in the first half of 2026."

Clinical data • Commercial • Trial status • Pancreatic Ductal Adenocarcinoma • Urothelial Cancer

A Study of BT5528 in Patients With Metastatic Pancreatic Ductal Adenocarcinoma (PDAC) (clinicaltrials.gov) - P2 | N=39 | Recruiting | Sponsor: BicycleTx Limited

New P2 trial • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • KRAS

Unlocking the potential of EphA2 with precision-guided cancer therapy: bicycle drug conjugates. (PubMed, J Transl Med) - No abstract available

Journal • Review • Oncology • Solid Tumor

EphA2 Pipeline (BT5528, EphA2 imaging) (Businesswire) - "(i) Report Phase 1 BT5528 combination data with nivolumab in mUC patients at a scientific conference in the first half of 2026; (ii) Provide an update on future clinical development plans for BT5528 in the first half of 2026; (iii) Report additional EphA2 human imaging data in the first half of 2026."

Clinical data • Pipeline update • Urothelial Cancer

Study BT5528-100 in Patients With Advanced Solid Tumors Associated With EphA2 Expression (clinicaltrials.gov) - P1/2 | N=288 | Active, not recruiting | Sponsor: BicycleTx Limited | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2025 ➔ Jul 2027 | Trial primary completion date: Oct 2025 ➔ Jul 2026

Enrollment closed • Trial completion date • Trial primary completion date • Breast Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Head and Neck Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • Triple Negative Breast Cancer • Urothelial Cancer • CD4 • EPHA2

Phase 1 BT5528 combination data with nivolumab in mUC patients will now be presented at a scientific conference in the first half of 2026. (Businesswire)

P1 data • Urothelial Cancer

Innovative Peptide Therapeutics in the Pipeline: Transforming Cancer Detection and Treatment. (PubMed, Int J Mol Sci) - "Innovative peptide platforms now enable three transformative applications: (1) precision molecular diagnostics (e.g., 18F-PSMA-1007 for prostate cancer detection), (2) targeted therapies (e.g., BT5528 and SAR408701 targeting tumour-specific antigens), and (3) theranostic systems (e.g., RAYZ-8009 and 177Lu-FAP-2286 integrating imaging and radiotherapy). By overcoming current limitations, peptide drugs are poised to redefine cancer management, offering safer, more effective alternatives to conventional therapies. Their integration into clinical practice could mark a critical milestone in achieving precision oncology."

IO biomarker • Journal • Review • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

Multimodal targeting of Ephrin A2 in solid tumors using bi-cyclic drug conjugates (EACR 2025) - "The Bicycle Platform enables the development of a multimodal therapeutic approach for solid tumor treatment, including the targeting of previously intractable proteins for other agents such as ADCs, therefore offering the opportunity to develop both best and first in class therapies. This approach is exemplified herein with EphA2 targeting Bicycle® containing molecules, with BT5528 currently in Phase 1/2 clinical trials"

Oncology • Solid Tumor • EPHA2 • TNFRSF9