On December 12, 2024 INOVIO Pharmaceuticals, Inc. (Nasdaq: INO), a biotechnology company focused on developing and commercializing DNA medicines to help treat and protect people from HPV-related diseases, cancer, and infectious diseases, reported that it intends to offer and sell shares of its common stock and accompanying warrants to purchase shares of its common stock, in an underwritten public offering (Press release, Inovio, DEC 12, 2024, View Source [SID1234649075]). All of the securities in the proposed offering will be sold by INOVIO. The proposed offering is subject to market conditions, and there can be no assurance as to whether or when the offering may be completed, or the actual size or terms of the offering.

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Oppenheimer & Co. Inc. and Citizens JMP are acting as joint book-running managers for the offering. Stephens Inc. is acting as lead manager for the offering.

A shelf registration statement relating to the shares of common stock and accompanying warrants offered in the offering described above was filed with the Securities and Exchange Commission (SEC) on November 9, 2023 and declared effective by the SEC on January 31, 2024. The offering will be made only by means of a written prospectus and prospectus supplement that form a part of the registration statement. A preliminary prospectus supplement and accompanying prospectus relating to and describing the terms of the proposed offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. Copies of the preliminary prospectus supplement and the accompanying prospectus, when available, may also be obtained by contacting: Oppenheimer & Co. Inc., Attention: Syndicate Prospectus Department, 85 Broad Street, 26th Floor, New York, NY 10004, by telephone at (212) 667-8055, or by email at [email protected]; or Citizens JMP Securities, LLC, 600 Montgomery Street, Suite 1100, San Francisco, California 94111, by telephone at (415) 835-8985, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy the securities being offered, nor shall there be any sale of the securities being offered in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

On December 12, 2024 Immuneering Corporation (Nasdaq: IMRX), a clinical-stage oncology company seeking to develop and commercialize universal-RAS/RAF medicines for broad populations of cancer patients, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for its lead clinical-stage program, IMM-1-104, as a treatment for patients with unresectable or metastatic NRAS-mutant melanoma who have progressed on or are intolerant to PD-1/PD-L1 based immune checkpoint inhibitors (Press release, Immuneering, DEC 12, 2024, View Source [SID1234649074]). IMM-1-104 is currently being evaluated in a Phase 2a clinical trial in patients with advanced solid tumors, including melanoma.

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"Immune checkpoint inhibitors play a vital role in the treatment of melanoma, yet patients who progress on or are intolerant to them have limited options," said Ben Zeskind, Ph.D., Co-Founder and CEO of Immuneering. "Targeted therapies including MEK and RAF inhibitors have shown promise in melanoma but historically are severely limited by toxicity. As we presented at the European Society for Medical Oncology 2024 congress, IMM-1-104 is a new kind of MEK inhibitor that was observed to be uniquely well tolerated in our Phase 1 trial, relative to MEK inhibitors currently used to treat melanoma. We believe this creates opportunities for IMM-1-104 to benefit melanoma patients both alone and in combination with RAF inhibitors and/or immune checkpoint inhibitors. Against this backdrop, we are pleased with the FDA’s decision to grant Fast Track designation for IMM-1-104 in advanced melanoma, an area of significant unmet need. Melanoma patients are actively enrolling in one of the five arms of our Phase 2a clinical trial, and this designation follows our announcements earlier this year that IMM-1-104 has also been granted Fast Track designations for the treatment of both first and second-line pancreatic cancer."

Fast Track designation is a program designed to facilitate the development and expedite the review of medicines with the potential to treat serious conditions and fulfill an unmet medical need. An investigational medicine that receives Fast Track designation may be eligible for more frequent interactions with the FDA to discuss the candidate’s development plan and, if relevant criteria are met, may be eligible for accelerated approval and priority review.

About IMM-1-104

IMM-1-104 aims to achieve universal-RAS activity that selectively impacts cancer cells to a greater extent than healthy cells, through Deep Cyclic Inhibition of the MAPK pathway with once-daily dosing. IMM-1-104 is currently being evaluated in a Phase 1/2a study in patients with advanced solid tumors harboring RAS mutations (NCT05585320).

On December 12, 2024 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) reported that the Center for Drug Evaluation of China’s National Medical Products Administration ("NMPA") has granted Breakthrough Therapy Designation ("BTD") to the combination of ORPATHYS (savolitinib) and TAGRISSO (osimertinib) for the treatment of patients with locally advanced or metastatic epidermal growth factor receptor ("EGFR") mutation-positive non-small cell lung cancer ("NSCLC") with MET amplification after disease progression on EGFR inhibitor therapy (Press release, HUTCHMED, DEC 12, 2024, View Source [SID1234649073]). ORPATHYS is an oral, potent and highly selective MET tyrosine kinase inhibitor ("TKI"). TAGRISSO is a third-generation, irreversible EGFR TKI.

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This treatment combination is being evaluated in China in the ongoing multi-center, open-label, randomized, controlled, Phase III SACHI trial. The study is investigating the efficacy and safety of a combination of ORPATHYS and TAGRISSO compared to platinum-based doublet-chemotherapy (pemetrexed plus cisplatin or carboplatin), the standard-of-care treatment option, in patients with locally advanced or metastatic NSCLC with MET amplification after failure of EGFR inhibitor therapy. The primary endpoint of the study is progression-free survival ("PFS") as assessed by investigators. Other endpoints include PFS assessed by an independent review committee, overall survival (OS), objective response rate (ORR), duration of response (DoR), disease control rate (DCR), time to response (TTR), and safety (NCT05015608).

NMPA grants BTD to new drugs that treat life-threatening diseases or serious conditions for which there are no effective treatment options, and where clinical evidence demonstrates significant advantages over existing therapies. Drug candidates with BTD may be considered for conditional approval and priority review when submitting an NDA. This indicates that the development and review of the therapy for this disease indication may be expedited, to address patients’ unmet needs more quickly.

About NSCLC and MET aberrations

Lung cancer is the leading cause of cancer death, accounting for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.2 The majority of NSCLC patients (approximately 75%) are diagnosed with advanced disease, and approximately 10-15% of NSCLC patients in the US and Europe and 30-40% of patients in Asia have EGFR-mutated ("EGFRm") NSCLC.3,4,5,6

MET is a tyrosine kinase receptor that has an essential role in normal cell development.7 MET overexpression and/or amplification can lead to tumor growth and the metastatic progression of cancer cells, and is one of the mechanisms of acquired resistance to EGFR TKI for metastatic EGFR-mutated NSCLC.7,8 Approximately 2-3% of NSCLC patients have tumors with MET exon 14 skipping alterations, a targetable mutation in the MET gene.9 MET aberration is a major mechanism for acquired resistance to both first/second-generation EGFR TKIs as well as third-generation EGFR TKIs like osimertinib. Among patients who experience disease progression post-osimertinib treatment, approximately 15-50% present with MET aberration.10,11,12,13,14 The prevalence of MET aberration depends on the sample type, detection method and assay thresholds used.15

About ORPATHYS and TAGRISSO Combination Development in EGFR mutation-positive NSCLC

The combination of ORPATHYS and TAGRISSO has been studied extensively in patients with EGFR mutation-positive NSCLC, including the TATTON (NCT02143466) and SAVANNAH (NCT03778229) studies. The encouraging results from these studies led to the initiation of three Phase III trials with this combination: SACHI (NCT05015608) and SANOVO (NCT05009836) were initiated in China in 2021, and the global, pivotal Phase III SAFFRON (NCT05261399) study started enrollment in 2022. In comparison to other treatment options, this combination treatment is chemotherapy-free, biomarker-specific and orally administered, aiming for a balanced efficacy, safety and quality-of-life profile for lung cancer patients.

SAVANNAH is a global Phase II study in patients who have progressed following osimertinib due to MET amplification or overexpression, and recruitment completed earlier in 2024. The evaluation of savolitinib in combination with osimertinib was designated as a Fast Track development program by the US Food and Drug Administration (FDA) in 2023.

SAFFRON is a multi-center, randomized, controlled, open-label, global Phase III trial in patients with EGFR mutation-positive NSCLC with MET overexpression and/or amplification after disease progression on osimertinib.

SACHI is a multi-center, randomized, controlled, open-label, China Phase III trial in patients with EGFR mutation-positive NSCLC with MET amplification after disease progression on any EGFR inhibitor therapy, including third-generation EGFR-TKIs such as osimertinib.

SANOVO is a multi-center, randomized, controlled, blinded, China Phase III trial in treatment-naïve patients with EGFR mutation-positive NSCLC with MET-positive tumors.

About ORPATHYS Approval in China

ORPATHYS was granted conditional approval in China for the treatment of patients with locally advanced or metastatic NSCLC with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy. ORPATHYS is the first selective MET inhibitor approved in China. It has been included in the National Reimbursement Drug List of China (NRDL) since March 2023. A supplementary NDA is under review which, if approved, could expand this indication to include treatment-naïve adult patients in China. More than a third of the world’s lung cancer patients are in China and, among those with NSCLC globally, approximately 2-3% have tumors with MET exon 14 skipping alterations.

About ORPATHYS (savolitinib)

ORPATHYS is an oral, potent and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression.

ORPATHYS is marketed in China and is currently under clinical development for multiple tumor types, including lung, kidney and gastric cancers, as a single treatment and in combination with other medicines.

In 2011, AstraZeneca and HUTCHMED entered a global licensing and collaboration agreement to jointly develop and commercialize ORPATHYS. Joint development of ORPATHYS in China is led by HUTCHMED, while AstraZeneca leads development outside of China. HUTCHMED is responsible for the marketing authorization, manufacturing and supply of ORPATHYS in China. AstraZeneca is responsible for the commercialization of ORPATHYS in China and worldwide. Sales of ORPATHYS are recognized by AstraZeneca.

About TAGRISSO

TAGRISSO (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system (CNS) metastases. TAGRISSO (40mg and 80mg once-daily oral tablets) has been used to treat nearly 800,000 patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO as a treatment for patients across multiple stages of EGFRm NSCLC.

There is an extensive body of evidence supporting the use of TAGRISSO as standard of care in EGFRm NSCLC. TAGRISSO improved patient outcomes in early-stage disease in the ADAURA Phase III trial, locally advanced disease in the LAURA Phase III trial, late-stage disease in the FLAURA Phase III trial, and with chemotherapy in the FLAURA2 Phase III trial.

On December 12, 2024 Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, reported the nomination of EO-1022 as its HER3 ADC development candidate (Press release, Elevation Oncology, DEC 12, 2024, View Source;utm_medium=rss&utm_campaign=elevation-oncology-expands-pipeline-with-nomination-of-eo-1022-a-her3-adc-for-the-treatment-of-her3-expressing-solid-tumors [SID1234649071]). EO-1022 is currently progressing through preclinical development, and Elevation Oncology expects to file an investigational new drug (IND) application in 2026.

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HER3 is a protein expressed across several types of solid tumors, including breast cancer, EGFR-mutant non-small cell lung cancer and pancreatic cancer, and often associated with poor clinical outcomes. EO-1022 is a differentiated ADC containing seribantumab, an anti-HER3 monoclonal antibody (mAb), and a monomethyl auristatin E (MMAE) payload, with site-specific conjugation to the glycan. EO-1022 is being developed for the treatment of patients living with solid tumors that express HER3.

"The nomination of our HER3-ADC development candidate marks a key milestone for Elevation Oncology in bolstering our ADC pipeline. EO-1022 combines the seribantumab antibody and state-of the-art ADC site-specific technology. We believe seribantumab is ideally-suited to be used in an ADC due to its selectivity in delivering cytotoxic payload to HER3-expressing cancer cells and its well-tolerated safety profile demonstrated in over 900 patients in multiple studies," said Joseph Ferra, President and Chief Executive Officer of Elevation Oncology. "This program is another step forward in leveraging our ADC and oncology drug development expertise to develop innovative, selective cancer therapies that address significant unmet needs. We look forward to sharing preclinical data for EO-1022 in the first half of 2025, as we continue to advance this asset toward the clinic."

Also today, Elevation Oncology announced that it has entered into a licensing agreement with Synaffix B.V. (Synaffix). This licensing agreement gives Elevation Oncology global access to Synaffix’s clinical stage, site-specific ADC technology platform, including GlycoConnect antibody conjugation technology, HydraSpace polar spacer technology, as well as the toxSYN linker-payload, SYNstatin E. The license granted to GlycoConnect and HydraSpace technologies is exclusive to HER3 as a single target in combination with SYNstatin E linker-payload.

"HER3 is broadly expressed in various cancer types, making it a compelling target for innovative therapeutic strategies. We believe an ADC approach is uniquely positioned to fully unlock the clinical potential of HER3," said David Dornan, Ph.D., Chief Scientific Officer of Elevation Oncology. "We are excited to nominate EO-1022, which leverages Synaffix’s state-of-the art site-specific conjugation and differentiated linker-payload for a potentially best-in-class profile. We look forward to advancing our pipeline, as we work towards transforming the care and treatment of patients living with solid tumors that overexpress HER3."

"As a dedicated partner in the ADC space, Synaffix is excited to collaborate with Elevation Oncology to push the boundary of ADC innovation," said Peter van de Sande, Head of Synaffix. "With our state-of-the-art ADC technology platform and established supply chain, Elevation is well-positioned to accelerate the development of its differentiated HER3 ADC."

On December 12, 2024 Bicycle Therapeutics plc (NASDAQ: BCYC), a pharmaceutical company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported 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 (Press release, Bicycle Therapeutics, DEC 12, 2024, View Source [SID1234649070]). 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.

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"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/m2 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/m2 weekly and 6 mg/m2 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/m2 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/m2 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.