Bicycle Therapeutics (NasdaqGS:BCYC) 2025 Conference November 18, 2025 05:30 AM ET Company ParticipantsJennifer Perry - Chief Strategy OfficerAlethia Young - CFOKevin Lee - CEOConference Call ParticipantsClara Dong - Biotech AnalystClara DongAll right, good morning. Thank you, everyone, for joining Jefferies Healthcare Conference in London. My name is Clara Dong, one of the biotech analysts here at Jefferies. For this session, it's my pleasure to welcome the Bicycle Therapeutics team. We have the Chief Exec ...

Zelenectide Pevedotin (Nectin-4 Targeting Bicycle Drug Conjugate) - Zelenectide pevedotin targets Nectin-4, which is highly expressed in many tumors, and is being studied as a potential treatment for multiple solid tumors including mUC, TNBC, and NSCLC[19, 20] - In the Duravelo-1 Ph1 study, zelenectide has shown a promising response and differentiated safety profile in 2L+ EV-naïve mUC, with an ORR of 45% (17/38 patients)[22, 26] - In the Duravelo-1 Ph1 study, zelenectide + pembrolizumab has shown an encouraging response in 1L cisplatin-ineligible mUC, with an ORR of 65% (13/20 patients) including a Complete Response of 25% (5/20 patients)[36, 38] - Patients with NECTIN4 gene amplification show an enhanced response to zelenectide in 2L+ TNBC and NSCLC, with ORRs of 57% (4/7) and 40% (2/5) respectively in NECTIN4-amplified patients[49, 55] - The company initiated the Duravelo-3 trial in March 2025 in NECTIN4-amplified breast cancer and plans to initiate Duravelo-4 and Duravelo-5 trials in 2H 2025 in NECTIN4-amplified NSCLC and multi-tumor respectively[60, 62] Bicycle Radioconjugates (BRC) - BRC molecules show selective tumor uptake and ideal PK across a range of targets and tumor models, including MT1-MMP, EphA2, and CD38[71, 72] - Early MT1-MMP-targeting BRC molecules show high tumor enrichment in PET imaging studies, with first human MT1-MMP imaging representative of data seen in 12 patients with various solid tumors[80, 83] - EphA2 is a tumor antigen that is widely expressed in many cancers, with 60% of pancreatic cancer and 58% of bladder cancer cases testing positive[101, 93] BT5528 (EphA2 Targeting BDC Molecule) - BT5528 demonstrated anti-tumor activity in patients with advanced solid tumors, particularly in mUC, with an ORR of 34% (10/29 patients) in all monotherapy dose escalation and expansion[119] - BT5528 delivers 10x more drug to the tumor compared to plasma in patients, demonstrating efficient and durable tumor MMAE delivery[112, 113] - In clinical trials, treatment-related adverse events of interest were of low frequency and severity, with peripheral neuropathy occurring in 20% (26/128) of patients and neutropenia in 10% (13/128) of patients[131] BT7480 (Bicycle TICA Molecule) - BT7480 was generally well-tolerated, with any grade treatment-related AEs occurring in 49% (19/39) of patients, the most common being fatigue (23%)[157, 159] - BT7480 showed preliminary antitumor activity in patients with advanced Nectin-4–associated solid tumors, with a clinical benefit rate of 38% (15/40 patients)[160, 161]

Zelenectide Pevedotin (Nectin-4 Targeting Bicycle Drug Conjugate) - In the Duravelo-1 Ph1 study, 45% ORR (17/38) was observed in 2L+ EV-naïve mUC patients treated with zelenectide [26] - In the Duravelo-1 Ph1 study, 65% ORR (13/20) was observed in 1L cisplatin-ineligible mUC patients treated with zelenectide + pembrolizumab [38] - In TNBC patients with NECTIN4 gene amplification, 57% ORR (4/7) and 100% DCR (7/7) were observed with zelenectide monotherapy [56] - In NSCLC patients with NECTIN4 gene amplification, 40% ORR (2/5) and 100% DCR (5/5) were observed with zelenectide monotherapy [56] - The company plans to initiate the Duravelo-4 trial in NECTIN4-amplified NSCLC and the Duravelo-5 trial in NECTIN4-amplified multi-tumor in 2H 2025 [63] BT5528 (EphA2 Targeting Bicycle Drug Conjugate) - In all cancers, 12% ORR (14/113) was observed with BT5528 monotherapy at 6.5 mg/m2 Q2W dose esc+exp [120] - In urothelial cancer, 34% ORR (10/29) was observed with BT5528 monotherapy at 6.5 mg/m2 Q2W dose esc+exp [120] - BT5528 delivers 10x more drug to the tumor compared to plasma in patients [114] BT7480 (Tumor-Targeted Immune Cell Agonist) - 49% of patients experienced any grade treatment-related AEs (TRAEs) with BT7480, the most common being fatigue (23%) and headache (10%) [159] - 5% ORR (2/40) was observed with BT7480 in all patients [161] Financial Position - The company had $793 million in cash and cash equivalents as of March 31, 2025, with expected financial runway into 2H 2027 [6]