Bicycle Therapeutics announces first patient dosed in BT8009 Phase II expansion cohorts and provides program update 

Bicycle Therapeutics plc (NASDAQ:BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle®) technology, today announced updates from the Phase I/II trial of BT8009 in patients with numerous cancer types where Nectin-4 is expressed. BT8009 is a potential first in class Bicycle Toxin Conjugate (BTC®) targeting Nectin-4, a protein located on the surface of cells that is highly expressed in urothelial cancer (UC) and other solid tumors.

“Dosing our first patient in the Phase II expansion portion of the BT8009 trial is a key development milestone for Bicycle,” said Kevin Lee, Ph.D., Chief Executive Officer. “Based on the data presented to date, we believe we are making an important step towards hopefully providing a clinically meaningful, differentiated therapy compared to what is currently available for UC as well as for other tumors that express Nectin-4, such as non-small cell lung cancer (NSCLC).”

“The results from the Phase I dose escalation portion of the BT8009 Phase I/II trial are very encouraging and we are excited to move rapidly forward with the dose expansion portion of the trial,” said Dominic Smethurst, MRCP, Chief Medical Officer of Bicycle Therapeutics. “BT8009 continues to exhibit potential best-in-class anti-tumor activity and a favorable tolerability profile, with a confirmed overall response rate from the latest cohorts consistent with previous findings from the trial, and we are pleased to see UC patients at the 5mg/m2 dose remaining on therapy and continuing to respond. We are also pleased to report a confirmed partial response in an NSCLC patient and look forward to providing additional data from the Phase I escalation cohorts at a medical meeting in the first half of 2023.”

• Phase I dose escalation portion of the Phase I/II trial is complete. Two doses have been selected as the recommended Phase II doses (RP2Ds): 5mg/m2 weekly and 7.5mg/m2 2-weeks on, 1-week off (over a 21-day cycle). Updated results from the completed escalation portion of the trial include 49 patients and the company intends to present these results at a medical meeting in the first half of 2023.
• In addition to clinical activity of BT8009 in UC as previously reported, confirmed clinical responses were observed in the 7.5mg/m2 RP2D cohort as well as in the 10mg/m2 every other week dose cohort.
  • The confirmed Response Evaluation Criteria in Solid Tumors (RECIST) overall response rate in each of the 7.5mg/m2 RP2D and 10mg/m2 every-other-week cohorts was consistent with the findings observed and previously reported from the 5mg/m2 weekly cohort.
  • At the 7.5mg/m2 RP2D, confirmed RECIST responses were observed in UC and NSCLC patients. The overall median number of prior treatments was four. This dose was selected as a second RP2D based on its clinical activity and its alternative dosing schedule, which could provide improved convenience particularly in checkpoint inhibitor (CPI) combination settings.
• All responding patients previously reported in the 5mg/m2 weekly cohort remain on therapy. The median duration of response has not yet been reached. As of the September 20, 2022 cutoff, all patients previously reported as having responses and on therapy have remained on therapy with ongoing responses.
• Confirmed RECIST response in an NSCLC patient. A confirmed partial response was observed in a 76-year-old patient with Nectin-4 positive metastatic adenocarcinoma. The patient entered the 7.5mg/m2 RP2D cohort after four prior lines of therapy, including a CPI. As of the September 20, 2022 data cutoff, the patient remains on therapy after cycle seven with an ongoing response.
• First patient dosed in Phase II expansion cohort. The Phase II multi-center, open label trial will evaluate BT8009 administered at the RP2Ds of 5mg/m2 and 7.5mg/m2.
• First-line metastatic UC in cisplatin ineligible patients in combination with a CPI is a priority for fast-to-market development.
  • This is an indication with high unmet need as many patients have limited access to chemotherapy, often due to renal impairment.
    The ongoing dose expansion includes cohorts evaluating the activity of BT8009 in CPI combination cohorts as well as in cohorts of patients with renal impairment.
  • Additionally, a Phase II study enrolling over 100 patients in combination with a CPI is being planned to start in 2023. The trial will include interim analyses that could be used to engage with regulatory authorities.
• The company also intends to rapidly pursue multiple indications for BT8009, including in combination with a CPI. These include the following:
  • Peri-operative muscle invasive UC in combination with a CPI
  • Second and third-line metastatic UC in patients who have been exposed to enfortumab vedotin as well as naïve patients as a monotherapy
    Tumors outside of UC (NSCLC, triple negative breast cancer, and ovarian cancer) in combination with a CPI and as a monotherapy