Sacituzumab govitecan-hziy

FOSTER CITY, Calif.--( BUSINESS WIRE )--Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to Trodelvy ® (sacituzumab govitecan-hziy) for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease has progressed on or after platinum-based chemotherapy. The Breakthrough Therapy Designation is based on results from the global Phase 2 TROPiCS-03 study ES-SCLC cohort, which showed encouraging results with Trodelvy as a second-line treatment for ES-SCLC. As recently presented at the IASLC 2024 World Conference on Lung Cancer, Trodelvy demonstrated promising antitumor activity in both platinum-resistant (PR) and platinum-sensitive (PS) disease, and the safety profile was consistent with previous Trodelvy studies. These data support further investigation of Trodelvy in ES-SCLC and Gilead plans to initiate a Phase 3 clinical trial in this patient population. Lung cancer is the second most diagnosed cancer in the U.S., and the leading cause of cancer-related deaths. Approximately 15% of lung cancer cases are SCLC, with nearly 70% of patients with SCLC diagnosed at extensive-stage, which occurs when the cancer has spread to both lungs or beyond the lungs to lymph nodes or other organs. For people with ES-SCLC whose disease does not respond to current first-line standard of care (platinum-based chemotherapy or immunotherapy), the prognosis is often poor, and treatment options are limited. There is an urgent need for new and more effective approaches to care that can improve survival and slow the progression of the disease. Breakthrough Therapy Designation is designed to expedite the development and regulatory review of investigational treatments for serious or life-threatening conditions that, based on preliminary clinical evidence, have the potential to substantially improve clinical outcomes compared with available therapy. This is the second Breakthrough Therapy Designation for Trodelvy. Trodelvy is the first and only approved Trop-2-directed antibody-drug conjugate (ADC) that has demonstrated meaningful survival advantages in two different types of metastatic breast cancers. Across Phase 3 trials, we are exploring Trodelvy alone or in combination with other agents across many diverse tumor types and stages of disease. This includes collaborations with partners in academia, industry and the global cancer community. About Trodelvy Trodelvy ® (sacituzumab govitecan-hziy) is a first-in-class Trop-2-directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and lung cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the tumor microenvironment through a bystander effect. Trodelvy is currently approved in more than 50 countries for second-line or later metastatic triple-negative breast cancer (TNBC) patients and in more than 40 countries for certain patients with pre-treated HR+/HER2- metastatic breast cancer. Trodelvy is being investigated for use in other TNBC and HR+/HER2- breast cancer populations, as well as a range of tumor types where Trop-2 is highly expressed, including small cell lung cancer and first-line metastatic non-small cell lung cancer where Trodelvy has shown clinical activity through the TROPiCS-03 proof-of-concept study and the EVOKE-02 proof-of-concept study, respectively. Trodelvy is also being studied in head and neck cancer and gynecological cancers. U.S. Indications for Trodelvy In the United States, Trodelvy is indicated for the treatment of adult patients with: Unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. Unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH–) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. U.S. Important Safety Information for Trodelvy BOXED WARNING: NEUTROPENIA AND DIARRHEA Severe or life-threatening neutropenia may occur. Withhold Trodelvy for absolute neutrophil count below 1500/mm 3 or neutropenic fever. Monitor blood cell counts periodically during treatment. Consider G-CSF for secondary prophylaxis. Initiate anti-infective treatment in patients with febrile neutropenia without delay. Severe diarrhea may occur. Monitor patients with diarrhea and give fluid and electrolytes as needed. At the onset of diarrhea, evaluate for infectious causes and, if negative, promptly initiate loperamide. If severe diarrhea occurs, withhold Trodelvy until resolved to ≤Grade 1 and reduce subsequent doses. CONTRAINDICATIONS Severe hypersensitivity reaction to Trodelvy. WARNINGS AND PRECAUTIONS Neutropenia: Severe, life-threatening, or fatal neutropenia can occur and may require dose modification. Neutropenia occurred in 64% of patients treated with Trodelvy. Grade 3-4 neutropenia occurred in 49% of patients. Febrile neutropenia occurred in 6%. Neutropenic colitis occurred in 1.4%. Withhold Trodelvy for absolute neutrophil count below 1500/mm 3 on Day 1 of any cycle or neutrophil count below 1000/mm 3 on Day 8 of any cycle. Withhold Trodelvy for neutropenic fever. Administer G-CSF as clinically indicated or indicated in Table 1 of USPI. Diarrhea: Diarrhea occurred in 64% of all patients treated with Trodelvy. Grade 3-4 diarrhea occurred in 11% of patients. One patient had intestinal perforation following diarrhea. Diarrhea that led to dehydration and subsequent acute kidney injury occurred in 0.7% of all patients. Withhold Trodelvy for Grade 3-4 diarrhea and resume when resolved to ≤Grade 1. At onset, evaluate for infectious causes and if negative, promptly initiate loperamide, 4 mg initially followed by 2 mg with every episode of diarrhea for a maximum of 16 mg daily. Discontinue loperamide 12 hours after diarrhea resolves. Additional supportive measures (e.g., fluid and electrolyte substitution) may also be employed as clinically indicated. Patients who exhibit an excessive cholinergic response to treatment can receive appropriate premedication (e.g., atropine) for subsequent treatments. Hypersensitivity and Infusion-Related Reactions: Serious hypersensitivity reactions including life-threatening anaphylactic reactions have occurred with Trodelvy. Severe signs and symptoms included cardiac arrest, hypotension, wheezing, angioedema, swelling, pneumonitis, and skin reactions. Hypersensitivity reactions within 24 hours of dosing occurred in 35% of patients. Grade 3-4 hypersensitivity occurred in 2% of patients. The incidence of hypersensitivity reactions leading to permanent discontinuation of Trodelvy was 0.2%. The incidence of anaphylactic reactions was 0.2%. Pre-infusion medication is recommended. Have medications and emergency equipment to treat such reactions available for immediate use. Observe patients closely for hypersensitivity and infusion-related reactions during each infusion and for at least 30 minutes after completion of each infusion. Permanently discontinue Trodelvy for Grade 4 infusion-related reactions. Nausea and Vomiting: Nausea occurred in 64% of all patients treated with Trodelvy and Grade 3-4 nausea occurred in 3% of these patients. Vomiting occurred in 35% of patients and Grade 3-4 vomiting occurred in 2% of these patients. Premedicate with a two or three drug combination regimen (e.g., dexamethasone with either a 5-HT3 receptor antagonist or an NK 1 receptor antagonist as well as other drugs as indicated) for prevention of chemotherapy-induced nausea and vomiting (CINV). Withhold Trodelvy doses for Grade 3 nausea or Grade 3-4 vomiting and resume with additional supportive measures when resolved to Grade ≤1 . Additional antiemetics and other supportive measures may also be employed as clinically indicated. All patients should be given take-home medications with clear instructions for prevention and treatment of nausea and vomiting. Increased Risk of Adverse Reactions in Patients with Reduced UGT1A1 Activity: Patients homozygous for the uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)*28 allele are at increased risk for neutropenia, febrile neutropenia, and anemia and may be at increased risk for other adverse reactions with Trodelvy. The incidence of Grade 3-4 neutropenia was 58% in patients homozygous for the UGT1A1*28, 49% in patients heterozygous for the UGT1A1*28 allele, and 43% in patients homozygous for the wild-type allele. The incidence of Grade 3-4 anemia was 21% in patients homozygous for the UGT1A1*28 allele, 10% in patients heterozygous for the UGT1A1*28 allele, and 9% in patients homozygous for the wild-type allele. Closely monitor patients with known reduced UGT1A1 activity for adverse reactions. Withhold or permanently discontinue Trodelvy based on clinical assessment of the onset, duration and severity of the observed adverse reactions in patients with evidence of acute early-onset or unusually severe adverse reactions, which may indicate reduced UGT1A1 function. Embryo-Fetal Toxicity: Based on its mechanism of action, Trodelvy can cause teratogenicity and/or embryo-fetal lethality when administered to a pregnant woman. Trodelvy contains a genotoxic component, SN-38, and targets rapidly dividing cells. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Trodelvy and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Trodelvy and for 3 months after the last dose. ADVERSE REACTIONS In the pooled safety population, the most common (≥ 25%) adverse reactions including laboratory abnormalities were decreased leukocyte count (84%), decreased neutrophil count (75%), decreased hemoglobin (69%), diarrhea (64%), nausea (64%), decreased lymphocyte count (63%), fatigue (51%), alopecia (45%), constipation (37%), increased glucose (37%), decreased albumin (35%), vomiting (35%), decreased appetite (30%), decreased creatinine clearance (28%), increased alkaline phosphatase (28%), decreased magnesium (27%), decreased potassium (26%), and decreased sodium (26%). In the ASCENT study (locally advanced or metastatic triple-negative breast cancer), the most common adverse reactions (incidence ≥25%) were fatigue, diarrhea, nausea, alopecia, constipation, vomiting, abdominal pain, and decreased appetite. The most frequent serious adverse reactions (SAR) (>1%) were neutropenia (7%), diarrhea (4%), and pneumonia (3%). SAR were reported in 27% of patients, and 5% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the ASCENT study were reduced neutrophils, leukocytes, and lymphocytes. In the TROPiCS-02 study (locally advanced or metastatic HR-positive, HER2-negative breast cancer), the most common adverse reactions (incidence ≥25%) were diarrhea, fatigue, nausea, alopecia, and constipation. The most frequent serious adverse reactions (SAR) (>1%) were diarrhea (5%), febrile neutropenia (4%), neutropenia (3%), abdominal pain, colitis, neutropenic colitis, pneumonia, and vomiting (each 2%). SAR were reported in 28% of patients, and 6% discontinued therapy due to adverse reactions. The most common Grade 3-4 lab abnormalities (incidence ≥25%) in the TROPiCS-02 study were reduced neutrophils and leukocytes. DRUG INTERACTIONS UGT1A1 Inhibitors: Concomitant administration of Trodelvy with inhibitors of UGT1A1 may increase the incidence of adverse reactions due to potential increase in systemic exposure to SN-38. Avoid administering UGT1A1 inhibitors with Trodelvy. UGT1A1 Inducers: Exposure to SN-38 may be reduced in patients concomitantly receiving UGT1A1 enzyme inducers. Avoid administering UGT1A1 inducers with Trodelvy. Please see full Prescribing Information , including BOXED WARNING. About Gilead Sciences Gilead Sciences, Inc. is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis, COVID-19, cancer, and inflammation. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, Calif. Forward-Looking Statement This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including Gilead’s ability to initiate, progress or complete clinical trials or studies within currently anticipated timelines or at all, and the possibility of unfavorable results from ongoing and additional clinical trials or studies, including those involving Trodelvy (such as TROPiCS-03); uncertainties relating to regulatory applications and related filing and approval timelines, including potential applications for programs and/or indications currently under evaluation; the possibility that Gilead may make a strategic decision to discontinue development of these programs and, as a result, these programs may never be successfully commercialized for the indications currently under evaluation; and any assumptions underlying any of the foregoing. These and other risks, uncertainties and factors are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, as filed with the U.S. Securities and Exchange Commission. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. All statements other than statements of historical fact are statements that could be deemed forward-looking statements. The reader is cautioned that any such forward-looking statements are not guarantees of future performance and involve risks and uncertainties and is cautioned not to place undue reliance on these forward-looking statements. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation and disclaims any intent to update any such forward-looking statements. Trodelvy, Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc., or its related companies. U.S. Prescribing Information for Trodelvy, including BOXED WARNING , is available at www.gilead.com . For more information about Gilead, please visit the company’s website at www.gilead.com , follow Gilead on X/Twitter (@GileadSciences) and LinkedIn (@Gilead-Sciences).

CAMBRIDGE, England & BOSTON--( BUSINESS WIRE )--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 data showing the enhanced anti-tumor activity of zelenectide pevedotin monotherapy in breast cancer patients with NECTIN4 gene amplification at the 2024 San Antonio Breast Conference Symposium (SABCS) in San Antonio, Texas. The company also announced topline combination data for zelenectide pevedotin plus pembrolizumab in previously untreated (first-line) cisplatin-ineligible patients with metastatic urothelial cancer (mUC), provided an enrollment and timeline update for the company’s Phase 2/3 Duravelo-2 trial and shared topline monotherapy data for zelenectide pevedotin in non-small cell lung cancer (NSCLC) patients with NECTIN4 gene amplification. Bicycle Therapeutics will host a conference call and webcast tomorrow, Dec. 13, at 8 a.m. ET to review the data updates for zelenectide pevedotin and discuss its development strategy leveraging NECTIN4 gene amplification. Management will be joined by oncology experts Sherene Loi, M.D., Ph.D., from the Peter MacCallum Cancer Centre in Melbourne, Australia, and Niklas Klümper, M.D., from the University Hospital Bonn in Germany. “ The totality of the data shared today builds on the breadth of previously reported data for zelenectide pevedotin that we believe, when combined with our ambitious development strategy leveraging NECTIN4 gene amplification, position Bicycle as a leader in addressing Nectin-4 associated cancers,” said Bicycle Therapeutics CEO Kevin Lee, Ph.D. “ We are encouraged by the topline zelenectide pevedotin data in combination with pembrolizumab in first-line mUC patients, which demonstrate zelenectide pevedotin’s response data are in line with other drug conjugates used to treat mUC while its safety and tolerability profile continues to be differentiated. Additionally, we are very pleased with our progress in enrolling our Duravelo-2 registrational trial for zelenectide pevedotin in mUC and look forward to providing dose selection and topline data in the second half of next year.” Dr. Lee continued: “ While early, the zelenectide pevedotin monotherapy data in breast cancer and NSCLC patients with NECTIN4 gene amplification underscore its promising anti-tumor activity and solidify our next steps for the therapy’s development. By leveraging NECTIN4 gene amplification, we expect to be able to identify the patients who may most benefit from zelenectide pevedotin and accelerate development for solid tumor indications beyond bladder cancer. Over the course of 2025, we plan to initiate Phase 1/2 trials evaluating zelenectide pevedotin in NECTIN4 gene-amplified breast cancer, lung cancer and multiple other cancers.” Topline Zelenectide Pevedotin Plus Pembrolizumab Combination Data in First-line mUC Highlights Zelenectide pevedotin is a Bicycle ® Toxin Conjugate (BTC ® ) targeting Nectin-4, a well-validated tumor antigen. Topline results from the ongoing Phase 1/2 Duravelo-1 trial evaluating zelenectide pevedotin 5 mg/m 2 weekly plus pembrolizumab 200 mg once every three weeks in 22 first-line cisplatin-ineligible patients with mUC showed: 60% overall response rate (ORR) (12/20) among efficacy-evaluable patients. Of the responses, 5 were confirmed and 7 were unconfirmed at the time of the data cut. Fifteen patients remained on treatment at the time of the data cut. Safety and tolerability profile was broadly consistent with late-line Duravelo-1 monotherapy and combination cohorts. Adverse events of clinical interest such as peripheral neuropathy, skin reactions and eye disorders were primarily low grade. There was one report of Grade 3 sensory peripheral neuropathy and one report of Grade 3 rash, both of which were transient and reverted to Grade 1 upon dose interruption. More detailed data from this study will be presented at a future medical meeting. Bicycle Therapeutics is currently conducting the Phase 2/3 Duravelo-2 trial evaluating zelenectide pevedotin plus pembrolizumab versus chemotherapy in first-line mUC (Cohort 1), and zelenectide pevedotin monotherapy and in combination with pembrolizumab in late-line mUC (Cohort 2). In each cohort, two doses of zelenectide pevedotin – 5 mg/m 2 weekly and 6 mg/m 2 two weeks on, one week off – are being initially assessed. Based on enrollment progress, the company plans to report dose selection and topline data for both cohorts in the second half of 2025. Zelenectide Pevedotin Monotherapy Data in Breast Cancer Patients with NECTIN4 Gene Amplification Highlights (Presented at 2024 SABCS) Gene amplification is a common mechanism by which cancer cells gain function. Bicycle Therapeutics identified that the NECTIN4 gene sits on a commonly amplified chromosomal site in cancer, creating more copies of the gene and often translating to more protein expression. Since zelenectide pevedotin binds to Nectin-4, it was hypothesized that NECTIN4 gene amplification may predict response and could serve as a biomarker for therapy stratification. The company conducted a post-hoc analysis of 38 heavily pretreated breast cancer patients enrolled in Duravelo-1, of which 32 were confirmed to have triple-negative breast cancer (TNBC). The majority of patients were treated with zelenectide pevedotin 5 mg/m 2 weekly. Of the 38 breast cancer patients enrolled, 35 patients were efficacy evaluable. Additionally, 23 breast cancer patient samples were available for NECTIN4 testing, of which 8 demonstrated NECTIN4 gene amplification or harbored NECTIN4 polysomy. Results showed: 62.5% ORR (5/8) among breast cancer patients with NECTIN4 gene amplification or polysomy, compared to 14.3% ORR (5/35) among all efficacy-evaluable breast cancer patients. Of the 5 partial responses, 4 were confirmed and 1 was unconfirmed. No responses in non-amplified or non-polysomy patients. Of the 32 TNBC patients enrolled, 30 patients were efficacy evaluable. Additionally, 19 TNBC patient samples were available for NECTIN4 testing, of which 7 demonstrated NECTIN4 gene amplification or harbored a NECTIN4 polysomy. Results showed: 57.1% ORR (4/7) among TNBC patients with NECTIN4 gene amplification or polysomy, compared to 13.3% ORR (4/30) among all efficacy-evaluable TNBC patients. Of the 4 partial responses, 3 were confirmed and 1 was unconfirmed. All 3 TNBC patients with NECTIN4 gene amplification who responded to zelenectide pevedotin had prior treatment with sacituzumab govitecan. No responses in non-amplified or non-polysomy patients. In this study of heavily pretreated breast cancer patients, zelenectide pevedotin was generally well tolerated, and its safety and tolerability profile was consistent with data from other Duravelo-1 cohorts. Low rates of Grade ≥3 treatment-related adverse events (TRAEs) (34.2%) and Grade ≥3 treatment-related serious adverse events (TRSAEs) (10.5%) occurred. The most common TRAEs were fever (pyrexia), nausea and diarrhea. TRAEs of clinical interest, including peripheral neuropathy (any kind) and skin reactions, were low grade. “ Although the sample size was limited, this post-hoc analysis highlights the encouraging anti-tumor activity of zelenectide pevedotin in breast cancer patients with NECTIN4 gene amplification, particularly among those with TNBC who urgently need new treatment options,” said Professor Sherene Loi, M.D., Ph.D., consultant medical oncologist in the Breast Unit and group leader at the Peter MacCallum Cancer Centre in Melbourne, Australia. “ As innovative and genomically targeted therapies for breast cancer continue to emerge, these findings position zelenectide pevedotin as a promising potential new therapy and NECTIN4 gene amplification as a novel target for breast cancer drug development.” The poster presentation, “ Enhanced anti-tumor activity of zelenectide pevedotin in triple-negative breast cancer (TNBC) patients with NECTIN4 gene amplification” is available in the Publications section of the Bicycle Therapeutics website. Topline Zelenectide Pevedotin Monotherapy Data in NSCLC Patients with NECTIN4 Gene Amplification Highlights The company conducted a post-hoc analysis of 40 pretreated patients with NSCLC enrolled in Duravelo-1. The majority of patients received zelenectide pevedotin 5 mg/m 2 weekly. Of the 40 patients enrolled, 34 patients were efficacy evaluable. Additionally, 19 patient samples were available for NECTIN4 testing, of which 6 demonstrated NECTIN4 gene amplification. Five out of 6 patients with NECTIN4 gene amplification were efficacy evaluable. Results showed: 40.0% ORR (2/5) among patients with NECTIN4 gene amplification, compared to 8.8% ORR (3/34) among all efficacy-evaluable patients. Of the 3 partial responses, 2 were confirmed and 1 was unconfirmed. Out of 19 patients tested for NECTIN4 gene amplification, none of the non-amplified patients responded. The safety and tolerability profile of zelenectide pevedotin was broadly consistent with data from other Duravelo-1 monotherapy cohorts. More detailed data from this study will be presented at a future medical meeting. Overview of Development Strategy Leveraging NECTIN4 Gene Amplification Bicycle Therapeutics plans to advance development of zelenectide pevedotin in broader indications outside of mUC utilizing a NECTIN4 gene amplification strategy to target patients who have the potential for significantly deeper responses. Over the course of 2025, Bicycle Therapeutics plans to initiate several additional Phase 1/2 trials to assess zelenectide pevedotin in NECTIN4 gene-amplified breast cancer, lung cancer and multiple other cancers. Through this strategy, the company believes it has the opportunity to become the leader in addressing Nectin-4 associated cancers and potentially transform the treatment landscape for thousands of patients in the United States. Conference Call Details Bicycle Therapeutics will host a conference call and webcast on Friday, Dec. 13, at 8 a.m. ET to review the data updates for zelenectide pevedotin. The company’s management team will be joined by Sherene Loi, M.D., Ph.D., Peter MacCallum Cancer Centre, and Niklas Klümper, M.D., University Hospital Bonn. To access the call, please dial +1-833-816-1408 (U.S.) or +1-412-317-0501 (international) and ask to join the Bicycle Therapeutics call. A live webcast and replay of the conference call will be accessible in the Investor section of the Company’s website at www.bicycletherapeutics.com . 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 zelenectide pevedotin (formerly BT8009), a Bicycle ® Toxin Conjugate (BTC ® ) targeting Nectin-4, a well-validated tumor antigen; BT5528, a BTC molecule targeting EphA2, a historically undruggable target; and BT7480, a Bicycle Tumor-Targeted Immune Cell Agonist ® (Bicycle TICA ® ) targeting Nectin-4 and agonizing CD137, in company-sponsored clinical trials. Additionally, the company is developing Bicycle Radionuclide Conjugates (BRC ® ) for radiopharmaceutical use and, through various partnerships, is exploring the use of Bicycle ® technology to develop therapies for diseases beyond oncology. Bicycle Therapeutics is headquartered in Cambridge, UK, with many key functions and members of its leadership team located in Cambridge, Mass. For more information, visit www.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’s development of zelenectide pevedotin, BT5528 and BT7480 as well as potential radiopharmaceutical product candidates; the company’s plans to utilize a NECTIN4 gene amplification strategy in the clinical development of zelenectide pevedotin; expectations with respect to Bicycle’s ability to identify the patients who may most benefit from zelenectide pevedotin, to advance or accelerate development of this product candidate for broader indications, including solid tumor cancers beyond bladder cancer, and to become a leader in addressing Nectin-4 associated cancers; the planned initiation of clinical trials of zelenectide pevedotin in breast cancer, lung cancer, and other cancers; the timing and manner of announcement of data and program updates from clinical trials for zelenectide pevedotin, including reporting of dose selection and topline data from the Duravelo-2 trial; and the use of Bicycle’s technology through various partnerships to develop potential therapies in diseases beyond oncology. Bicycle 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’s product candidates; the risk that Bicycle may not realize the intended benefits of its technology, partnerships or NECTIN4 gene amplification strategy; 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’s product candidates; and other important factors, any of which could cause Bicycle’s 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’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on October 31, 2024, as well as in other filings Bicycle 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 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.