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UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section
13 or 15(d) of the Securities Exchange Act of 1934
April 20, 2026
Date of Report (Date of earliest event reported)
Bicycle
Therapeutics plc
(Exact name of registrant as specified in its
charter)
| England
and Wales |
|
001-38916 |
|
Not
applicable |
(State or other jurisdiction
of incorporation) |
|
(Commission
File Number) |
|
(IRS Employer
Identification No.) |
Blocks
A & B, Portway Building,
Granta
Park Great Abington, Cambridge
United Kingdom |
CB21
6GS |
| (Address of principal
executive offices) |
(Zip Code) |
Registrant’s telephone number, including area code: +44
1223 261503
Check the appropriate box below if the Form 8-K
filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
| ¨ | Written
communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| | |
| ¨ | Soliciting
material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| | |
| ¨ | Pre-commencement
communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| | |
| ¨ | Pre-commencement
communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b)
of the Act:
| Title
of each class |
Trading
Symbol (s) |
Name
of each exchange on which registered |
| Ordinary
shares, nominal value £0.01 per share |
n/a |
The
Nasdaq
Stock Market LLC* |
| American
Depositary Shares, each representing one ordinary share, nominal value £0.01 per share |
BCYC |
The
Nasdaq
Stock Market LLC |
* Not
for trading, but only in connection with the listing of the American Depositary Shares on The Nasdaq Stock Market LLC.
Indicate
by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405
of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company ¨
If an emerging
growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any
new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨
On April 20, 2026, Bicycle
Therapeutics plc (the “Company”) issued a press release providing updates on its nuzefatide pevedotin program and the Company’s
EphA2 pipeline. 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.
| Item 9.01. |
Financial Statements and Exhibits |
(d) Exhibits
| Exhibit No. |
|
Description |
| 99.1 |
|
Press Release issued April 20, 2026 |
| 104 |
|
Cover Page Interactive Data File (formatted in Inline XBRL) |
SIGNATURES
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.
| Date: April 20, 2026 |
BICYCLE THERAPEUTICS PLC |
| |
|
| |
By: |
/s/ Travis Thompson |
| |
Name: Travis Thompson |
| |
Title: Chief Financial Officer |
Exhibit 99.1
Bicycle Therapeutics
Provides Update on Nuzefatide Pevedotin and EphA2 Pipeline at the AACR Annual Meeting 2026
Phase 1 combination
data of 6.5mg/m2 Q2W nuzefatide pevedotin plus nivolumab demonstrate an encouraging preliminary efficacy profile with a differentiated
tolerability profile in previously treated metastatic urothelial cancer
Nuzefatide pevedotin
demonstrates potent preclinical anti-tumor activity across a broad range of pancreatic ductal adenocarcinoma (PDAC) and head and neck
squamous cell carcinoma xenograft models
Dose range finding
studies identify 8mg/m2 Q2W as the preferred dose for monotherapy and first patient dosed in 2L+ PDAC Phase 2 trial
Human imaging
data provides further evidence of the potential of EphA2 as a novel cancer target and the positive properties of Bicycle®
radioligand molecules for radiopharmaceutical use
CAMBRIDGE, England & BOSTON, April
20, 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 updates from its EphA2 pipeline at the
American Association for Cancer Research (AACR) Annual Meeting 2026.
“EphA2 is a potentially high value
target that is widely expressed in cancer and has been considered undruggable following the failure of multiple antibody-based approaches
due to toxicity or insufficient efficacy. Encouraging results presented at AACR demonstrate the potential of our Bicycle platform to
drug this target with a generally well tolerated and differentiated safety profile and enhances our understanding of how best to deploy
EphA2-targeted therapeutics,” said Bicycle Therapeutics CEO Kevin Lee, Ph.D. “Nuzefatide pevedotin has demonstrated an emerging
differentiated safety profile as a monotherapy and in combination with a checkpoint inhibitor, in over 150 patients to date. Consequently,
using a combination of expression analysis, preclinical patient-derived xenograft efficacy studies, and human patient imaging, we have
identified significant opportunities for this molecule in a number of cancers, including pancreatic cancer.”
Dr. Lee added: “We have now identified
8mg/m2 Q2W as the preferred dose for monotherapy. Our strategy is to initially develop nuzefatide in pancreatic cancer where
patients have limited available treatment options, and in parallel, to bring forward the next generation of EphA2-targeted radiotherapeutics
to build on our foundational work in bladder and other EphA2-expressing tumors. Following this strategy, I am very pleased to announce
that the first patient in our 2L+ pancreatic ductal adenocarcinoma Phase 2 study has been successfully dosed.”
AACR Annual Meeting 2026 Data Highlights
| · | Nuzefatide
pevedotin (nuzefatide), formerly BT5528, a potentially first-in-class EphA2 targeting Bicycle®
Drug Conjugate (BDC®), Phase 1/2 data in combination with nivolumab in metastatic
urothelial cancer (mUC) patients. As of the February 9, 2026 data cutoff, results from
the Phase 1/2 trial evaluating nuzefatide 6.5mg/m2 once every two weeks (Q2W)
plus nivolumab 480mg once every four weeks (Q4W) in 14 patients with mUC who had previously
progressed on a checkpoint inhibitor (10 while on enfortumab vedotin) showed: |
| o | 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. |
| o | Patients
who achieved a partial response (PR) or at least 16 weeks of stable disease (SD) were on
treatment for a minimum of 56 weeks and most continued on treatment at the time of the data
cut-off. |
| o | Nuzefatide
in combination with nivolumab was generally well tolerated with no Grade ≥3 treatment-related
adverse events (TRAEs) of clinical interest and no TRAEs of haemorrhage observed. Only one
dose-limiting toxicity of Grade 3 fatigue that lasted for five days was reported and improved
to Grade 1 without dose reduction. |
In contrast to other EphA2-targeted
agents, nuzefatide has demonstrated a positive emerging efficacy and safety profile in over 150 patients with hard-to-treat tumors to
date. 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).
| · | Additional
human imaging data of a Bicycle® Imaging Agent (BIA) targeting EphA2 in patients
with PDAC. The German Cancer Consortium (DKTK), part of a cooperative network with the
German Cancer Research Center (DKFZ), presented human imaging data conducted with a Bicycle
molecule targeting EphA2 labelled with gallium-68 (EphA2 BIA). Seven patients with histologically
confirmed PDAC underwent PET/CT imaging up to three hours post injection of the EphA2 BIA.
Data demonstrated rapid tumor uptake and excretion primarily via the kidneys in six out of
seven patients. EphA2 BIA PET imaging successfully detected multiple liver, bone, lymph node,
and peritoneal metastases. |
These data are representative
of the results seen in 15 out of 18 patients with PDAC who have undergone EphA2 BIA imaging to date. Bicycle Therapeutics believes these
data validate the potential of EphA2 as a novel target in the treatment of cancer, demonstrate the translatability of preclinical data
and highlight the potential of Bicycle® molecules for targeted radioligand therapies and radiopharmaceutical imaging.
| · | Preclinical
assessment of nuzefatide anti-tumor activity in patient-derived xenograft (PDX) models of
PDAC. 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. |
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.
| · | Preclinical
assessment of nuzefatide anti-tumor activity in cell-line-derived xenograft (CDX) models
of head and neck squamous cell carcinoma (HNSCC). Nuzefatide demonstrated potent preclinical
anti-tumor activity in EphA2-expressing CDX models of HNSCC. |
The presentations are available in the
Publications section of the Bicycle Therapeutics website.
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: the potential therapeutic
benefit of nuzefatide pevedotin, including the reproducibility and durability of any favorable results initially seen in patients dosed
to date in clinical trials, and the potential development of nuzefatide pevedotin in a number of cancers, including pancreatic cancer;
the progress of Bicycle Therapeutics’ clinical trials, reporting data from Bicycle Therapeutics’ clinical trials, including
for nuzefatide pevedotin, the timing of EphA2 human imaging data and updates on future clinical development plans for nuzefatide
pevedotin; the potential of EphA2 as a novel cancer target and the positive properties of Bicycle® radioligand molecules for radiopharmaceutical
use; the potential of the Bicycle platform to drug EphA2 and to enhance understanding of how best to deploy EphA2 targeted therapeutics;
and the development of the Bicycle® radioligands pipeline, including BRCs and BIAs. 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: the recently announced workforce reduction may
take longer or result in more significant charges or cash expenditures than anticipated or otherwise negatively impact Bicycle Therapeutics’
and its business plans during and after the period during which the proposed workforce reduction is being executed; uncertainties related
to the benefits of the recently announced strategic reprioritization; 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 realize the intended benefits of its technology or partnerships; 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; the risk that Bicycle Therapeutics’
projections regarding its expected cash runway are inaccurate or that its conduct of its business requires more cash than anticipated;
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’
Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on March 17, 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
