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On May 21, 2026, Bicycle Therapeutics plc (the
“Company”) issued a press release announcing initial Duravelo-2 data for metastatic urothelial cancer at the
2026 American Society of Clinical Oncology (“ASCO”) Annual Meeting. A copy of the press release is attached as Exhibit 99.1
to this Current Report on Form 8-K and is incorporated into this Item 8.01 by reference.
Pursuant to the requirements
of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto
duly authorized.
Exhibit 99.1
Bicycle Therapeutics to Present Initial Duravelo-2
Data at 2026 ASCO Annual Meeting
In the dose optimization stage of the randomized
Phase 2 trial (Duravelo-2), zelenectide pevedotin at its optimal dose in combination with pembrolizumab demonstrated response rates comparable
to published data for standard of care (SOC) in patients with previously untreated metastatic urothelial cancer (mUC)
The optimal dose of zelenectide demonstrated
a potentially differentiated safety profile with incidence rates approximately four-fold lower for skin reactions and half that for peripheral
neuropathy as published for SOC
Further data from the randomized Phase 2 trial
are expected in 2H 2026
In a separate Phase 1 trial (Duravelo-1) in
previously untreated, cisplatin-ineligible mUC, zelenectide in combination with pembrolizumab demonstrated a clinically
meaningful median progression-free survival comparable to published data for SOC
These data provide further validation of the
potential of Bicycle® technology to deliver oncology therapeutics with improved benefit/risk profiles compared to existing modalities
CAMBRIDGE, England & BOSTON, May 21, 2026 – Bicycle
Therapeutics plc (NASDAQ: BCYC), a pharmaceutical company pioneering a new and differentiated class of therapeutics based on its proprietary
bicyclic peptide (Bicycle®) technology, today announced the presentation of initial data from the randomized Phase 2 trial
(Duravelo-2) evaluating zelenectide pevedotin (zelenectide) in previously untreated patients with metastatic urothelial cancer (mUC),
demonstrating encouraging response rates and a potentially differentiated safety profile both as a monotherapy and in combination with
pembrolizumab. In addition, updated data from the Phase 1 trial (Duravelo-1) in previously untreated, cisplatin-ineligible mUC patients
demonstrated encouraging median progression-free survival (PFS) comparable to published data for standard of care (SOC). The data announced
today will be presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 29 - June 2
in Chicago.
“Despite recent advances for the treatment
of bladder cancer, there remains an urgent need for more tolerable therapies. For instance, published clinical data for the current SOC
for mUC demonstrate a significant number of tolerability-related drug discontinuations, and high rates of neuropathy and skin toxicities.
In contrast, the initial Duravelo-2 data shared today demonstrate that zelenectide in combination with pembrolizumab continues to show
response rates comparable to published data for SOC for mUC, while potentially offering substantially lower toxicity and improved tolerability
for patients. We have now tested zelenectide as a monotherapy or in combination with pembrolizumab in more than 600 patients and have
consistently observed lower rates and severity of neuropathy and skin toxicities,” said Bicycle CEO Kevin Lee, Ph.D. “We
believe that the extensive data we have generated in patients continue to demonstrate the unique nature of Bicycle molecules as targeting
agents that offer a potentially differentiated tolerability profile to antibody-based approaches. We are excited to continue to explore
these advantages with novel targets and novel payloads in our mission to help patients not only live longer but live well. Meanwhile,
the Duravelo-2 trial has been converted into a randomized Phase 2 trial and we look forward to sharing further results in the second
half of 2026.”
Initial Duravelo-2 Data Results
Zelenectide is a Bicycle® Drug
Conjugate (BDC®) targeting Nectin-4, a well-validated tumor antigen. The Duravelo-2 trial evaluated two doses of zelenectide
– 5mg/m2 weekly (5mg dose) and 6mg/m2 (6mg dose) two weeks on, one week off – in combination with 200mg
of pembrolizumab once every three weeks in previously untreated patients with mUC (Cohort 1). Bicycle reached regulatory alignment on
the zelenectide 6mg dose as optimal both in combination with pembrolizumab and as a monotherapy. Cohort 1 data were extracted for the
interim analysis at Week 27, on July 23, 2025. At the time of the data cut, the median PFS was not mature, and the results at the
optimal dose showed:
| · | 65%
(17/26) overall response rate (ORR) regardless of confirmation and blinded independent central
review (BICR) confirmed ORR of 58% (15/26) at the 27-week cutoff. Subsequent to the 27-week
cutoff, an additional confirmed BICR response was observed, which would result in an ORR
of 62% (16/26). |
| · | Median
duration of treatment (mDOT) was 6.3 months (0.7-10.6). |
| · | 65%
of patients remain on treatment. |
| · | Median
relative dose intensity in patients receiving the optimal dose was 97%. |
| · | Low
rates of zelenectide-related adverse events (AEs) of clinical interest were observed, including
peripheral neuropathy, sensory (33%); skin reactions (17%); eye disorders (10%). There were
no reported instances of zelenectide-related hyperglycemia. |
| · | No
zelenectide-related severe skin reactions of any grade were reported. |
| · | The
single Grade 3 zelenectide-related AE of clinical interest, peripheral neuropathy, resolved
to Grade ≤1. There were no Grade 4 or Grade 5 zelenectide-related AEs of clinical interest. |
| · | Notably,
only one patient at the optimal dose discontinued therapy due to a zelenectide-related AE
at the time of the data cut in Cohort 1. |
The Duravelo-2 trial also evaluated the 5mg dose
and 6mg dose regimens of zelenectide as a monotherapy in mUC patients with one or more prior lines of systemic therapy (Cohort 2). Cohort
2 data were extracted for the interim analysis at Week 27, on June 14, 2025. At the time of the data cut, the median PFS was not
mature, and the results at the optimal dose showed:
| · | 37%
(10/27) ORR regardless of confirmation and 30% confirmed ORR (8/27) was achieved among efficacy-evaluable
patients. Of the confirmed responses, 3 (11%) were complete responses (CRs) and 5 (19%) were
partial responses (PRs). |
| · | mDOT
was 4.8 months (1.3-10.1). |
| · | 31%
of patients remain on treatment. |
| · | Median
relative dose intensity in patients receiving the optimal dose was 86%. |
| · | Low
rates of zelenectide-related AEs of clinical interest were observed, including peripheral
neuropathy (38%); skin reactions (28%); eye disorders (10%); and hyperglycemia (3%). |
| · | There
were no Grade 4 or Grade 5 zelenectide-related AEs of clinical interest. |
| · | Notably,
no zelenectide-related severe skin reactions of any grade were reported, and no treatment
discontinuations occurred at the optimal dose. |
The company plans to share additional Duravelo-2
data from the randomized Phase 2 trial in the second half of 2026.
Updated Duravelo-1 Data Results
The company also announced the presentation of
updated Phase 1 Duravelo-1 data evaluating zelenectide in mUC, including monotherapy data in enfortumab vedotin (EV)-naïve patients
and in combination with 200mg of pembrolizumab once every three weeks in previously untreated cisplatin-ineligible patients. Both cohorts
evaluated zelenectide at the 5mg dose.
Updated results as of the August 1, 2025
data cutoff evaluating zelenectide in combination with pembrolizumab in previously untreated cisplatin-ineligible patients, 45% of whom
were classified as Eastern Cooperative Oncology Group (ECOG) performance status of 2, showed:
| · | 59%
(13/22) ORR regardless of confirmation, 50% confirmed ORR (11/22), and a disease control
rate (DCR) of 82%. Of the confirmed responses, 5 (23%) were CRs and 6 (27%) were PRs. |
| · | Median
PFS was 13.0 months and median duration of response (mDOR) was not mature at the time of
the data cutoff. |
Updated results as of the August 1, 2025
data cutoff evaluating zelenectide as a monotherapy in EV-naïve recurrent, unresectable mUC patients who had prior anti-programmed
death-1/programmed death ligand-1 (PD-1/PD-L1), had disease progression after or were ineligible for platinum-based chemotherapy showed:
| · | 38%
(20/53) ORR regardless of confirmation, 32% confirmed ORR (17/53) and a DCR of 66%. Of the
confirmed responses, 2 (4%) were CRs and 15 (28%) were PRs. |
| · | Median
PFS was 5.4 months and mDOR was 10.0 months (5.3-16.6) among patients with confirmed responses. |
Across all patients, the safety and tolerability
profile was consistent with other zelenectide data to date. No new safety signals were observed and there were no Grade 4 or Grade 5
zelenectide-related AEs of clinical interest reported.
The presentations will be made available in the
Publications sections of the Bicycle Therapeutics website following each presentation.
About Bicycle Therapeutics
Bicycle Therapeutics is a clinical-stage
pharmaceutical company developing a novel class of medicines, referred to as Bicycle® molecules, for diseases that
are underserved by existing therapeutics. Bicycle molecules are fully synthetic short peptides constrained with small molecule scaffolds
to form two loops that stabilize their structural geometry. This constraint facilitates target binding with high affinity and selectivity,
making Bicycle molecules attractive candidates for drug development. The company is evaluating nuzefatide pevedotin, formerly BT5528,
a Bicycle® Drug Conjugate (BDC®) targeting EphA2, a historically undruggable target; a pipeline of
other bicycle-based conjugate molecules, including Bicycle® Radioconjugates (BRC®) for radiopharmaceutical
use; zelenectide pevedotin (formerly BT8009), a BDC® targeting Nectin-4, a well-validated tumor antigen; BT7480, a Bicycle
Tumor-Targeted Immune Cell Agonist® (Bicycle TICA®) targeting Nectin-4 and agonizing CD137; and, through
various partnerships, is exploring the use of Bicycle® technology to develop therapies for diseases in additional
therapeutic areas.
Bicycle Therapeutics is headquartered in Cambridge,
UK, with many key functions and members of its leadership team located in Lexington, Mass. For more information, visit bicycletherapeutics.com.
Forward Looking Statements
This press release may contain forward-looking
statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may
be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,”
“expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,”
“potential,” “seeks,” “will” and variations of these words or similar expressions that are intended
to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in
this press release include, but are not limited to, statements regarding: Bicycle Therapeutics’ ability to explore the advantages
of Bicycle molecules, and develop Bicycle molecules, with novel targets and novel payloads; the timeline for Bicycle Therapeutics’
clinical trials, including for zelenectide pevedotin, and the release of data therefrom. Bicycle Therapeutics may not actually achieve
the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these
forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in
these forward-looking statements as a result of various factors, including: uncertainties inherent in research and development and in
the initiation, progress and completion of clinical trials and clinical development of Bicycle Therapeutics’ product candidates;
the risk that Bicycle Therapeutics may not achieve any of its clinical development strategies; timing of results from clinical trials;
whether the outcomes of preclinical studies and prior clinical trials will be predictive of future clinical trial results; the risk that
trials may have unsatisfactory outcomes; potential adverse effects arising from the testing or use of Bicycle Therapeutics’ product
candidates; and other important factors, any of which could cause Bicycle Therapeutics’ actual results to differ from those contained
in the forward-looking statements, are described in greater detail in the section entitled “Risk Factors” in Bicycle Therapeutics’
Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on April 30, 2026, as well as in other
filings Bicycle Therapeutics may make with the SEC in the future. Any forward-looking statements contained in this press release speak
only as of the date hereof, and Bicycle Therapeutics expressly disclaims any obligation to update any forward-looking statements contained
herein, whether because of any new information, future events, changed circumstances or otherwise, except as otherwise required by law.
###
Investors:
Matthew DeYoung
Argot Partners
ir@bicycletx.com
212-600-1902
Media:
Argot Partners
media@bicycletx.com
