On February 25, 2025 Day One Biopharmaceuticals, Inc. (Nasdaq: DAWN) ("Day One" or the "Company"), a biopharmaceutical company dedicated to developing and commercializing targeted therapies for people of all ages with life-threatening diseases, reported its fourth quarter and full year 2024 financial results and highlighted recent corporate achievements (Press release, Day One, FEB 25, 2025, View Source [SID1234650523]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"The approval of OJEMDA was the catalyst for our next stage of growth and I am proud that our team was able to offer OJEMDA to so many relapsed or refractory pediatric low-grade glioma (pLGG) patients in our first months of launch," said Jeremy Bender, Ph.D., chief executive officer of Day One. "With OJEMDA as our foundation and a strong balance sheet, we believe we are on a path to long-term, durable growth and to the realization of Day One’s mission."

Program Highlights

•
OJEMDA net product revenues were $29.0 million and $57.2 million for the fourth quarter and full year ended December 31, 2024, respectively.
o
OJEMDA net product revenues increased 44% from the third to fourth quarter of 2024.
o
In approximately eight months since launch in April 2024, more than 1,600 OJEMDA prescriptions have been written.
•
OJEMDA received the Exclusively Pediatric designation by the Centers for Medicare & Medicaid Services in the fourth quarter ended December 31, 2024, reducing its Medicaid and 340B minimum rebate percentage from 23.1% to 17.1%.
•
DAY301, our PTK7-targeted ADC, cleared the first dose cohort (a single-patient accelerated titration cohort) in the Phase 1a portion of the Phase 1a/b clinical trial.
•
Day One advanced enrollment in the global, pivotal Phase 3 FIREFLY-2 clinical trial, with full enrollment expected in the first half of 2026.

Corporate Highlights

•
Chief executive officer Dr. Jeremy Bender presented preliminary 2024 OJEMDA net product revenue and 2025 corporate priorities at the 43rd Annual J.P. Morgan Healthcare Conference. An archived audio webcast of the discussion is available by visiting the Events Presentations section of the Company’s website.

Fourth Quarter and Full Year 2024 Financial Highlights

•
Product Revenue, Net: OJEMDA net product revenues were $29.0 million and $57.2 million for the fourth quarter and full year ended December 31, 2024, respectively.

•
License Revenue: License revenue from the sale of ex-U.S. commercial rights for tovorafenib were $0.2 million and $73.9 million for the fourth quarter and full year ended December 31, 2024, respectively.

•
R&D Expenses: Research and development expenses were $61.8 million and $227.7 million for the fourth quarter and full year ended December 31, 2024, respectively, as compared to $37.3 million and $130.5 million for the same periods in 2023. The increase was primarily due to the DAY301 upfront license payment of $55.0 million in the third quarter 2024 and initiation of the DAY301 dose escalation study milestone of $20.0 million in the fourth quarter 2024.

•
SG&A Expenses: Selling, general and administrative expenses were $29.8 million and $115.5 million for the fourth quarter and full year ended December 31, 2024, respectively, as compared to $22.2 million and $75.6 million for the same periods in 2023. The increase was primarily due to employee compensation costs and professional service expenses to support the launch of OJEMDA.

•
Net Loss: Net loss totaled $65.7 million and $95.5 million for the fourth quarter and full year ended December 31, 2024, respectively, with non-cash stock-based compensation expense of $11.0 million and $48.3 million for the same periods. Net loss totaled $54.5 million and $188.9 million for the fourth quarter and full year ended December 31, 2023, respectively, with non-cash stock-based compensation expense of $10.8 million and $39.3 million for the same periods.

•
Cash Position: The Company’s cash, cash equivalents and short-term investments totaled $531.7 million on December 31, 2024.

Upcoming Events

•
44th Annual TD Cowen Health Care Conference
o
Management will participate in a fireside chat on Tuesday, March 4 at 1:10 p.m. ET. A live and archived audio webcast of the discussion will be available by visiting the Events Presentations section of the Company’s website.

Conference Call

Day One will host a conference call and webcast today, February 25 at 4:30 p.m. Eastern Time. To access the live conference call by phone, dial 877-704-4453 (domestic) or 201-389-0920 (international), and provide the access code 13745150. Live audio webcast will be accessible from the Day One Media & Investors page. To ensure a timely connection to the webcast, it is recommended that participants register at least 15 minutes prior to the scheduled start time. An archived version of the webcast will be available for replay on the Events & Presentations section of the Day One Investors & Media page for 30 days following the event.

About OJEMDA

OJEMDA (tovorafenib) is a Type II RAF kinase inhibitor of mutant BRAF V600, wild-type BRAF, and wild-type CRAF kinases.

OJEMDA is indicated for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Tovorafenib was granted Breakthrough Therapy and Rare Pediatric Disease designations by the FDA for the treatment of patients with pLGG harboring an activating RAF alteration, and it was evaluated by the FDA under priority review. Tovorafenib has also received Orphan Drug designation from the FDA for the treatment of malignant glioma and from the European Commission for the treatment of glioma.

For more information, please visit www.ojemda.com.

On February 25, 2025 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported a business update and announced financial results for the fourth quarter and full year of 2024 (Press release, Cogent Biosciences, FEB 25, 2025, View Source [SID1234650522]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Cogent is preparing to report data from three bezuclastinib pivotal clinical trials this year," said Andrew Robbins, the company’s President and Chief Executive Officer. "Given our strong cash balance, and emerging pipeline of potential best-in-class targeted therapies, we are poised for a transformational year culminating with the planned submission of Cogent’s first NDA for bezuclastinib by the end of 2025."

Q4 2024 and Recent Business Highlights

In December 2024, announced updated clinical results from SUMMIT, showcasing dramatic symptomatic improvement in nonadvanced systemic mastocytosis (NonAdvSM) patients and positive updated data from the APEX trial evaluating bezuclastinib in patients with advanced systemic mastocytosis (AdvSM) at the American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting. In both trials, bezuclastinib continued to demonstrate an encouraging safety and tolerability profile. Highlights include:

In SUMMIT, a registration-directed, global, randomized, placebo-controlled trial in patients with NonAdvSM, treatment with 100 mg bezuclastinib demonstrated:
56% mean improvement in Total Symptom Score (TSS) at 24 weeks with 76% of patients achieving at least a >50% reduction from baseline in TSS
89% of patients had >50% decrease in serum tryptase levels by four weeks of treatment
In APEX, a registration-directed, global, open-label trial in patients with AdvSM, treatment with various doses of bezuclastinib demonstrated:
52% ORR per mIWG criteria, including 83% ORR for patients receiving 100 mg BID
88% ORR per PPR criteria, including 100% ORR for patients receiving 100 mg BID
2.2 months median time-to-response with median duration-of-response and median PFS not yet reached with at least 20 months follow-up
In October 2024, announced the addition of a potent and selective KRAS inhibitor to Cogent’s pipeline at the 2024 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) International Symposium on Molecular Targets and Cancer Therapeutics.
Cogent’s internally-developed pan-KRAS(ON) inhibitor demonstrated picomolar (pM) activity across KRAS mutations with selectivity over H/NRAS leading to potential advantages versus other molecules in the class. Following oral administration, CGT6737 demonstrated robust PK/PD and tumor growth inhibition with 90% PD inhibition in mouse xenograft models. Lead optimization of the program is ongoing.
In October 2024, shared progress on Cogent’s clinical candidate CGT6297, a potent allosteric inhibitor of PI3Kα, with 25-fold selectivity over PI3Kα WT. In a poster at the 2024 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) International Symposium on Molecular Targets and Cancer Therapeutics, CGT6297 showed high oral bioavailability and low clearance across species, providing robust inhibition of downstream signaling and efficacy in animal models. Importantly, when compared to a clinically relevant dose of a currently approved therapy in a mouse tumor model, CGT6297 demonstrated superior efficacy with no increase in insulin.
Projected Near-Term Milestones

Bezuclastinib – Systemic Mastocytosis (SM)

Poster presentation focused on symptomatic performance of patients from SUMMIT Part 1 who have received 100 mg bezuclastinib for at least 48 weeks at the 2025 American Academy of Allergy Asthma & Immunology Annual Meeting (AAAAI).
Report top-line results in July 2025 from the SUMMIT trial.
Report top-line results during the second half of 2025 from the APEX trial.
Submit the first bezuclastinib New Drug Application (NDA) by the end of 2025.
Bezuclastinib – Gastrointestinal Stromal Tumors (GIST)

Report top-line results by the end of 2025 from the pivotal Phase 3 PEAK trial. PEAK is a global, blinded, randomized clinical trial studying the combination of bezuclastinib and sunitinib versus sunitinib alone in patients with imatinib-resistant gastrointestinal stromal tumors (GIST).
Bezuclastinib – Expanded Access Program

In Q1, initiate Expanded Access Programs (EAP) in the U.S. for SM and GIST patients to receive investigational bezuclastinib after meeting certain eligibility criteria.
CGT4859 (FGFR2 inhibitor)

Enroll patients in the ongoing Phase 1 trial with CGT4859, a reversible, selective FGFR2 inhibitor in patients with documented FGFR mutations, including advanced cholangiocarcinoma. The trial is designed to explore the safety, tolerability and clinical activity of escalating doses of CGT4859 with a goal of selecting an active and well-tolerated dose for further clinical investigation.
Preclinical Pipeline

Submit an IND application in 2025 for CGT4255, a potent, selective ErbB2 inhibitor, highlighted by potential best-in-class brain-penetrant properties.
Submit an IND application in 2025 for CGT6297, a potent allosteric inhibitor of PI3Kα, with 25-fold selectivity over PI3Kα WT.
Upcoming Investor Conference

Leerink Healthcare Conference on Wednesday, March 12 at 10:00 a.m. ET.

A live webcast can be accessed on the Investors & Media page of Cogent’s website at investors.cogentbio.com/events. A replay will be available approximately two hours after completion of the event and will be archived for up to 30 days.
Fourth Quarter and Full Year 2024 Financial Results

Cash and Cash Equivalents: As of December 31, 2024, Cogent had cash, cash equivalents and marketable securities of $287.1 million. Cogent believes this year-end balance, together with the $25.0 million gross proceeds from shares sold under the Company’s at-the-market (ATM) stock offering in February 2025, will be sufficient to fund its operating expenses and capital expenditure requirements into late 2026, including through clinical readouts from the ongoing SUMMIT, PEAK and APEX registration-directed trials.

R&D Expenses: Research and development expenses were $62.0 million for the fourth quarter of 2024 and $232.7 million for the year ended December 31, 2024, as compared to $48.7 million for the fourth quarter of 2023 and $173.8 million for the year ended December 31, 2023. The increase was driven by the development of bezuclastinib, including costs associated with the accelerated completion of enrollment of the SUMMIT and PEAK trials and ongoing cost of the APEX trial, and the continued progression of our research pipeline. R&D expenses include non-cash stock compensation expense of $5.0 million for the fourth quarter of 2024 and $19.0 million for the year ended December 31, 2024, as compared to $4.1 million for the fourth quarter of 2023 and $14.6 million for the year ended December 31, 2023.

G&A Expenses: General and administrative expenses were $11.7 million for the fourth quarter of 2024 and $43.3 million for the year ended December 31, 2024, as compared to $9.5 million for the fourth quarter of 2023 and $34.4 million for the year ended December 31, 2023. The increase was primarily due to the growth of the organization. G&A expenses include non-cash stock compensation expense of $5.0 million for the fourth quarter of 2024 and $20.8 million for the year ended December 31, 2024, as compared to $4.8 million for the fourth quarter of 2023 and $16.0 million for the year ended December 31, 2023.

Net Loss: Net loss was $67.9 million for the fourth quarter of 2024 and $255.9 million for the year ended December 31, 2024, as compared to a net loss of $54.4 million for the fourth quarter of 2023 and $192.4 million for the year ended December 31, 2023.

Inducement Grants Under Nasdaq Listing Rule 5635(c)(4)
Cogent also announced today that, on February 12, 2025 and February 24, 2025, the Compensation Committee of Cogent’s Board of Directors, made up entirely of independent directors, approved the grants of "inducement" equity awards to five new employees under the company’s 2020 Inducement Plan with grant dates of February 12, 2025, February 19, 2025 and February 24, 2025. The awards were approved in accordance with Listing Rule 5635(c)(4) of the corporate governance rules of the Nasdaq Stock Market. The employees received, in the aggregate, nonqualified options to purchase 78,500 shares of Cogent common stock. Each option has a 10-year term, an exercise price equal to the closing price of Cogent’s common stock on the grant date, and a 4-year vesting schedule with 25% vesting on the 1-year anniversary of the grant date and the remainder vesting in equal monthly installments over the subsequent 36 months, provided such employee remains employed through each such vesting date.

On February 25, 2025 Candel Therapeutics, Inc. (Candel or the Company) (Nasdaq: CADL), a clinical stage biopharmaceutical company focused on developing multimodal biological immunotherapies to help patients fight cancer, reported final overall survival data from the completed randomized controlled phase 2 clinical trial of CAN-2409 plus valacyclovir (prodrug), together with standard of care (SoC) chemoradiation, followed by resection, in patients with borderline resectable PDAC (Press release, Candel Therapeutics, FEB 25, 2025, View Source [SID1234650521]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Final data of the randomized controlled clinical trial, updated with an additional nine months of follow-up, confirmed a durable improvement in survival for patients treated with CAN-2409 plus SoC therapy (n=7) compared to SoC alone (n=6). Notably, long-term survivors in the CAN-2409 arm, remaining alive at 66.0, 63.6, and 35.8-months post-enrollment experienced disease recurrence but, in contrast to patients in the control arm with disease recurrence, responded to salvage chemotherapy and have experienced extended and ongoing post-progression survival at the time of the data cutoff (February 20, 2025), further highlighting the sustained benefit of CAN-2409 in this aggressive disease setting.

"Pancreatic cancer remains one of the most difficult to treat diseases," said W. Garrett Nichols, MD, MS, Candel’s Chief Medical Officer. "Patients with borderline resectable PDAC often have undetectable metastases that are not cleared with current standard of care neoadjuvant chemoradiation and surgery. CAN-2409 is a first-in-class multimodal immunotherapy candidate designed for in situ vaccination against the patient’s tumor, which offers the potential to control this disease and to prolong survival, thus improving outcomes following this dismal prognosis."

Data highlights:

•
Prolonged and sustained survival was observed in this randomized controlled clinical trial after experimental treatment with CAN-2409 compared to the control group in patients with borderline resectable PDAC

o
Estimated median overall survival after enrollment was 31.4 months in the CAN-2409 group (n=7) versus only 12.5 months in the control group (n=6).

o
Median survival post-progression was 21.2 months in patients who received CAN-2409 compared to 7.2 months in the control arm.
o
Importantly, three out of seven patients who received CAN-2409 were still alive at the time of data cut-off with a survival of 66.0, 63.6, and 35.8 months, respectively, after enrollment; survival from the time of diagnosis for these patients was 73.5, 68.8, and 41.3 months, respectively. Of these, the first patient had stage IV metastatic disease detected during surgery, the second had residual tumor present at the resection margin, and the third had adenocarcinoma with negative resection margins. In contrast, only one out of six patients randomized to SoC chemotherapy arm remained alive at the data cut-off (61.2 months from enrollment and 65.5 months from diagnosis); histologic analysis at resection showed intraepithelial neoplasia (without evidence of residual invasive adenocarcinoma) in this patient, which is associated with improved prognosis.

o
Previous analysis at 24 months showed survival rates of 71.4% in patients treated with CAN-2409 compared to 16.7% in the control group.

•
Previous analysis of blood and resected tumors showed consistent and robust activation of the immune response after experimental treatment with CAN-2409

o
In pancreatic tissue of patients treated with CAN-2409 plus prodrug, together with SoC (but not SoC alone), dense aggregates of CD8+ granzyme B+ cytotoxic tumor infiltrating lymphocytes, dendritic cells, and B cells were observed in the tumor microenvironment.

o
Increased levels of soluble granzymes B and H, along with pro-inflammatory cytokines, including IFN-γ, were detected in peripheral blood following CAN-2409 treatment, but not in the control arm, supporting CAN-2409’s ability to drive a potent systemic anti-tumoral immune response.

•
CAN-2409 continued to be associated with a favorable safety/tolerability profile

o
The addition of CAN-2409 regimen to SoC was generally well-tolerated, with no dose-limiting toxicities, including no cases of pancreatitis.

"The notable benefits observed with CAN-2409 in this clinical trial, including evidence of a long tail of survival, highlights the transformative potential of this biological multimodal immunotherapy in difficult to treat cancers", said Paul Peter Tak, MD, PhD, FMedSci, CEO and President of Candel. "Recently, the Company announced positive, statistically significant topline data for CAN-2409 based on a large, randomized, placebo-controlled clinical trial in localized prostate cancer. The data presented today support the potential of CAN-2409 across various solid tumors, by showing its potential to alter the balance between the pancreatic tumor and the anti-tumor immune response, even in patients with residual tumor, improving long-term survival in a subset of the patients. Based on these promising findings, the Company has decided to prepare for a larger, late-stage randomized controlled clinical trial of CAN-2409 in PDAC."

The FDA previously granted Fast Track Designation and Orphan Drug Designation to the Company for CAN-2409 in combination with valacyclovir for the treatment of patients with PDAC.

About CAN-2409

CAN-2409, Candel’s most advanced multimodal biological immunotherapy candidate, is an investigational, off-the-shelf, replication-defective adenovirus designed to deliver the herpes simplex virus thymidine kinase (HSV-tk) gene to a patient’s specific tumor and induce an individualized, systemic immune response against the tumor. HSV-tk is an enzyme that locally converts orally administered valacyclovir into a toxic metabolite that kills nearby cancer cells. Together, this regimen is designed to induce an individualized and specific CD8+ T cell-mediated response against the injected tumor and uninjected distant metastases for broad anti-tumor activity, based on in situ vaccination against a variety of tumor antigens. Because of its versatility, CAN-2409 has the potential to treat a broad range of solid tumors. Encouraging monotherapy activity, as well as combination activity with standard of care radiotherapy, surgery, chemotherapy, and immune checkpoint inhibitors, have previously been shown in several preclinical and clinical settings. More than 1,000 patients have been dosed with CAN-2409 with a favorable tolerability profile to date, supporting the potential for combination with other therapeutic strategies.

Currently, Candel is evaluating CAN-2409 in non-small cell lung cancer (NSCLC), PDAC, and localized, non-metastatic prostate cancer. In December 2024, Candel announced that CAN-2409 achieved its primary endpoint in a pivotal phase 3 clinical trial in men with intermediate-to-high-risk, localized prostate cancer, demonstrating statistically significant improvement in disease-free survival when added to SoC radiation therapy +/- androgen deprivation therapy. CAN-2409 plus prodrug has been granted Fast Track Designation by the FDA for the treatment of PDAC, stage III/IV NSCLC in patients who are resistant to first line PD-(L)1 inhibitor therapy and who do not have activating molecular driver mutations or have progressed on directed molecular therapy, and localized prostate cancer. The FDA has also granted Orphan Drug Designation to CAN-2409 for the treatment of PDAC. Candel’s pivotal phase 3 clinical trial in localized prostate cancer was conducted under a Special Protocol Assessment (SPA) agreed with the FDA.

On February 25, 2025 Bristol Myers Squibb (NYSE: BMY) reported that the company will participate in two upcoming investor conferences in March 2025 (Press release, Bristol-Myers Squibb, FEB 25, 2025, View Source [SID1234650520]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The company will participate in a fireside chat at the TD Cowen 45th Annual Health Care Conference on March 4, 2025, at 2:30 p.m. ET. In addition, the company will take part in a fireside chat at the Leerink Partners 2025 Global Healthcare Conference on March 12, 2025, at 11:20 a.m. ET.

Investors and the general public are invited to listen to both sessions at their respective times by visiting View Source An archived edition of each session will be available following its conclusion.

On February 25, 2025 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 financial results for the fourth quarter and full year ended December 31, 2024, and provided recent corporate updates (Press release, Bicycle Therapeutics, FEB 25, 2025, View Source [SID1234650519]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"In 2024, the significant progress across our pipeline and business continued to validate our approach to developing next-generation precision-guided therapeutics. We believe that zelenectide pevedotin’s promising anti-tumor activity and differentiated safety profile could transform the treatment landscape not only for patients with metastatic urothelial cancer but also NECTIN4 gene-amplified solid tumors. Additionally, our encouraging first human imaging data for MT1-MMP demonstrates the potential of our technology platform to produce radiopharmaceutical medicines to novel targets," said Bicycle Therapeutics CEO Kevin Lee, Ph.D. "With a clear strategy to build on this foundation and financial runway into the second half of 2027, we are strongly positioned for another year of execution across our research and development pipeline of oncology, radiopharmaceuticals and partnered programs as we work to bring innovative therapies to cancer patients."

Fourth Quarter 2024 and Recent Events

Announced updated topline combination data for zelenectide pevedotin plus pembrolizumab in first-line metastatic urothelial cancer (mUC). As of Jan. 3, 2025, updated topline results from the ongoing Phase 1 Duravelo-1 trial evaluating zelenectide pevedotin 5 mg/m2 weekly plus pembrolizumab 200 mg once every 3 weeks in 22 first-line cisplatin-ineligible patients with mUC continued to show promising anti-tumor activity and a differentiated safety profile.
Among 20 efficacy evaluable patients, a 65% overall response rate (ORR) (13/20) was achieved, and a 50% ORR (10/20) was reached among patients with confirmed responses. Of the 3 unconfirmed responses, 1 patient remained on treatment at the time of the reported clinical results.
Median duration of response (mDOR) is not yet mature, with 12 patients still on treatment at the time of the reported clinical results.
The safety and tolerability profile continues to be broadly consistent with other Phase 1 zelenectide pevedotin monotherapy and combination cohorts. Adverse events of clinical interest such as peripheral neuropathy, skin reactions and eye disorders were primarily low grade. All cases of Grade 3 treatment-related adverse events (TRAEs) of clinical interest were reversible, and there were no Grade 4 or Grade 5 TRAEs of clinical interest.
Bicycle Therapeutics is currently conducting the Phase 2/3 Duravelo-2 registrational 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 assessed before a planned final dose selection in 2H 2025.

Announced development strategy leveraging NECTIN4 gene amplification for zelenectide pevedotin in breast cancer, lung cancer and multiple tumor types. During the 2024 San Antonio Breast Conference Symposium, Bicycle Therapeutics presented data from post-hoc analyses of late-line breast cancer and lung cancer patients enrolled in the Phase 1/2 Duravelo-1 trial evaluating zelenectide pevedotin 5 mg/m2 weekly. Results showed enhanced anti-tumor activity of zelenectide pevedotin monotherapy in patients with NECTIN4 gene amplification and/or polysomy.
Among 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 a 62.5% ORR (5/8) in patients with NECTIN4 gene amplification and/or polysomy versus 14.3% ORR (5/35) in efficacy-evaluable patients. All responses were seen in patients with NECTIN4 gene amplification and/or polysomy.
Among 32 triple-negative breast cancer (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 a 57.1% ORR (4/7) in patients with NECTIN4 gene amplification and/or polysomy versus 13.3% ORR (4/30) in efficacy-evaluable patients. All responses were seen in patients with NECTIN4 gene amplification and/or polysomy. Notably, all 3 patients with NECTIN4 gene amplification who responded to zelenectide pevedotin had prior treatment with sacituzumab govitecan.
Among 40 non-small cell lung cancer (NSCLC) patients enrolled, 34 patients were efficacy evaluable. Additionally, 19 NSCLC 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 a 40.0% ORR (2/5) in patients with NECTIN4 gene amplification versus 8.8% ORR (3/34) among efficacy-evaluable patients. Of the 3 partial responses, 2 were confirmed and 1 was unconfirmed. Two out of 3 responses were seen in patients with NECTIN4 gene amplification.
Zelenectide pevedotin was generally well tolerated, demonstrating a safety and tolerability profile consistent with data from other Duravelo-1 cohorts, and TRAEs were primarily low grade, further supporting the potential for NECTIN4 gene amplification to serve as a biomarker for therapy stratification. Based on these data, the U.S. Food and Drug Administration (FDA) granted Fast Track designation to zelenectide pevedotin for the treatment of adult patients with previously treated, NECTIN4 gene-amplified, advanced or metastatic TNBC and NSCLC.

Bicycle Therapeutics has continued to build a robust patent estate related to the use of NECTIN4 gene amplification as a biomarker for patient selection. The company plans to initiate several additional Phase 1/2 trials evaluating zelenectide pevedotin in NECTIN4 gene-amplified cancer, including breast cancer (Duravelo-3) in 1H 2025 and lung cancer (Duravelo-4) and multi-tumor (Duravelo-5) in 2H 2025.

Announced first human imaging data for a Bicycle Radionuclide Conjugate (BRC) targeting MT1-MMP and outlined strategy for leadership in next-generation radiopharmaceuticals. Data presented at the European Association of Nuclear Medicine 2024 Congress validate the potential of MT1-MMP as a novel target in the treatment of cancer, demonstrate the translatability of BRC preclinical data and highlight the potential of Bicycle molecules for targeted radionuclide therapy.
In an oral presentation, the German Cancer Consortium (DKTK) shared results of fluorine-18-labelled FDG-PET/CT imaging and gallium-68-labelled BRC MT1-MMP PET/CT imaging in a 65-year-old male diagnosed with advanced pulmonary adenocarcinoma, the most common type of NSCLC, in the lung and lymph nodes. MT1-MMP imaging demonstrated tracer uptake in the primary tumor in the lung and lymph node and bone metastases, consistent with FDG imaging. Additionally, the MT1-MMP BRC tracer showed renal excretion, with all other organs showing only a negligible tracer uptake.
Preclinical data presented by Bicycle Therapeutics demonstrated the suitability of Bicycle molecules to deliver indium to tumors in vivo due to their favorable properties, including specific tumor uptake, rapid tumor penetration and rapid renal elimination. Additionally, imaging showed how the biodistribution profile of BRCs can be optimized to maintain high tumor uptake and retention while significantly reducing kidney levels.
Bicycle Therapeutics continues to advance its emerging BRC pipeline, with additional MT1-MMP human imaging data anticipated in mid-2025 and initial EphA2 human imaging data expected in 2H 2025. The company is targeting clinical trials for its first radiotherapeutic program to begin in 2026.

Expanded Clinical Advisory Board with the appointment of three distinguished oncology experts to further support the advancement of the company’s clinical programs. Bicycle Therapeutics welcomed Howard A. "Skip" Burris, III, M.D., president and chief medical officer of Sarah Cannon Research Institute; Markus Eckstein, M.D., a board-certified senior consultant pathologist at the University Hospital Erlangen (FAU Erlangen-Nürnberg); and Niklas Klümper, M.D., senior consultant for Urology & Genitourinary Oncology at the University Hospital Bonn.
Participation in Upcoming Investor Conferences

Bicycle Therapeutics management will participate in a fireside chat at the TD Cowen 45th Annual Health Care Conference on Tuesday, March 4, at 9:50 a.m. ET. A live webcast of the fireside chat will be accessible from the Investor section of the company’s website at www.bicycletherapeutics.com. A replay of the webcast will be archived and available following the event.

Fourth Quarter and Year End 2024 Financial Results

Cash and cash equivalents were $879.5 million as of December 31, 2024, compared to $526.4 million as of December 31, 2023. The increase in cash and cash equivalents is primarily due to net proceeds from the company’s private investment in public equity (PIPE) financing in May 2024 and share option exercises, offset by the repayment of the company’s debt facility with Hercules Capital, Inc. in July 2024 and cash used in operating activities.
Research and development (R&D) expenses were $49.8 million for the three months ended December 31, 2024, and $173.0 million for the year ended December 31, 2024, compared to $44.7 million for the three months ended December 31, 2023, and $156.5 million for the year ended December 31, 2023. The increases in expense of $5.1 million and $16.5 million for the three months and year ended December 31, 2024, respectively, were primarily due to increased clinical program expenses for zelenectide pevedotin development and increased personnel-related expenses, including incremental share-based compensation expense of $2.2 million and $3.8 million for the three months and year ended December 31, 2024, respectively, offset by decreased clinical program expenses for Bicycle Tumor-Targeted Immune Cell Agonist molecule development, lower discovery, platform and other expenses, and higher U.K. R&D tax credits period over period.
General and administrative expenses were $21.6 million for the three months ended December 31, 2024, and $72.2 million for the year ended December 31, 2024, compared to $14.9 million for the three months ended December 31, 2023, and $60.4 million for the year ended December 31, 2023. The increases of $6.7 million and $11.8 million for the three months and year ended December 31, 2024, respectively, were primarily due to increased personnel-related expenses, including incremental share-based compensation expense $0.3 million and $1.8 million for the three months and year ended December 31, 2024, respectively, as well as increased professional and consulting fees.
Net loss was $51.9 million, or $(0.75) basic and diluted net loss per share, for the three months ended December 31, 2024, and net loss was $169.0 million, or $(2.90) basic and diluted net loss per share, for the year ended December 31, 2024, compared to net loss of $49.1 million or $(1.16) basic and diluted net loss per share, for three months ended December 31, 2023, and net loss of $180.7 million or $(5.08) basic and diluted net loss per share, for the year ended December 31, 2023.