Bicycle Therapeutics reports fourth quarter and full year 2022 financial Results and provides corporate update 

• Significant progress across pipeline including advancing BT8009, BT5528, and BT7480 in ongoing clinical trials
• BT8009 granted Fast Track Designation by the U.S. Food and Drug Administration; completed Phase I results presented at ASCO GU Cancers Symposium
• Cash position of $339.2 million at December 31, 2022 expected to provide financial runway into 2025

“We have made continued clinical progress across our pipeline, including advancing BT8009 and BT5528 into the ongoing dose expansion cohorts and are encouraged by the progress of BT7480 in the ongoing dose escalation portion of its clinical trial,” said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. “We are pleased to have a balance sheet that has supported the advancement and expansion of our clinical portfolio, with an anticipated financial runway into 2025. We believe we are well-positioned ahead of multiple potential inflection points as we pursue our goal of demonstrating the true therapeutic potential of Bicycle Toxin Conjugates® and Bicycle tumor-targeted immune cell agonists.”

Fourth Quarter 2022 and Recent Highlights

• Presented Completed BT8009 Phase I Dose Escalation Results from Ongoing Phase I/II Study of BT8009 at the 2023 American Society for Clinical Oncology (ASCO) Genitourinary (GU) Cancers Symposium. In February 2023, Bicycle presented monotherapy Phase I dose escalation results of the ongoing Phase I/II trial of BT8009, a novel Bicycle Toxin Conjugate targeting Nectin-4, at the ASCO GU Cancers Symposium. BT8009 demonstrated anti-tumor activity in heavily pre-treated urothelial, lung and breast cancer patients with signs of differentiation compared to antibody-based approaches. Bicycle announced that it had dosed its first patient in the Phase II expansion portion of the trial and established RP2Ds of 5 mg/m2 weekly and 7.5 mg/m2 administered two-weeks on, one-week off over a 21-day cycle in November 2022. Enrollment in the clinical trial remains ongoing. The company expects to provide an update on the program by the end of 2023.
• BT8009 granted Fast Track Designation (FTD) by the U.S. Food and Drug Administration (FDA). In January 2023, Bicycle announced that the FDA granted BT8009 FTD as a monotherapy for the treatment of adult patients with previously treated locally advanced or metastatic urothelial cancer.
• Presented Five Posters at the Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting in November 2022. Posters featured preclinical data from Bicycle tumor-targeted immune cell agonist® (Bicycle TICA™) programs.
• Continue to Advance BT5528 and BT7480 in Clinical Trials.
  • BT5528, a novel Bicycle Toxin Conjugate® targeting EphA2, continues in the dose expansion portion of the ongoing Phase I/II clinical trial. In September 2022, Bicycle announced results from the Phase I dose escalation portion of the ongoing Phase I/II trial in patients with advanced solid tumors. Bicycle observed anti-tumor activity in patients with EphA2-postive heavily pre-treated ovarian and urothelial cancers.
  • BT7480, a novel, fully synthetic Bicycle tumor-targeted immune cell agonist® (Bicycle TICA™) targeting Nectin-4 and agonizing CD137 is currently in the Phase I dose escalation portion of a company-sponsored Phase I/II trial. The company expects to provide an update later this year from the dose escalation portion of the trial.

Financial Results

• Cash and cash equivalents were $339.2 million as of December 31, 2022, compared to $438.7 million as of December 31, 2021. The decrease in cash is primarily due to cash used in operating activities.
• Research and development expenses were $24.7 million for the three months ended December 31, 2022 and $81.6 million for the year ended December 31, 2022, compared to $13.0 million for the three months ended December 31, 2021 and $44.9 million for the year ended December 31, 2021. The increase in expense of $11.8 million and $36.7 million for the three months and year ended December 31, 2022, respectively, was primarily due to increased clinical program expenses for BT5528 and BT8009, Bicycle TICA program development expenses, and other discovery and platform related expenses, as well as increased personnel-related expenses, including incremental non-cash share-based compensation expense of $1.3 million and $5.4 million for the three months and year ended December 31, 2022, respectively, offset by incremental UK research and development tax credit reimbursements.
• General and administrative expenses were $10.7 million for the three months ended December 31, 2022 and $49.5 million for the year ended December 31, 2022, compared to $8.8 million for the three months ended December 31, 2021 and $32.4 million for the year ended December 31, 2021. The increase of $1.8 million for the three months ended December 31, 2022 as compared to the same period in the prior year was primarily due an increase in personnel-related costs, including $1.2 million of incremental non-cash share-based compensation expense, offset by a decrease in professional- and consulting-related expenses. The increase of $17.1 million for the year ended December 31, 2022 as compared to the same period in the prior year was primarily due to an increase in personnel-related costs, including $9.3 million of incremental non-cash share-based compensation expense.
• Net loss was $30.0 million, or $(1.01) basic and diluted net loss per share, for the three months ended December 31, 2022, and net loss was $112.7 million, or $(3.80) basic and diluted net loss per share, for the year ended December 31, 2022, compared to net loss of $18.0 million, or $(0.63) basic and diluted net loss per share, for three months ended December 31, 2021, and net loss of $66.8 million, or $(2.67) basic and diluted net loss per share, for the year ended December 31, 2021.