On January 13, 2025 Century therapeutics presented its corporate presenation (Presentation, Century Therapeutics, JAN 13, 2025, View Source [SID1234649644]).

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!

On January 13, 2025 Caribou Biosciences, Inc. (Nasdaq: CRBU), a leading clinical-stage CRISPR genome-editing biopharmaceutical company, reported initiation of the GALLOP Phase 1 clinical trial evaluating CB-010 in patients with lupus nephritis (LN) and extrarenal lupus (ERL) (Press release, Caribou Biosciences, JAN 13, 2025, View Source [SID1234649643]). In addition, Caribou highlighted successful execution across its three clinical-stage allogeneic CAR-T cell therapy programs in hematologic malignancies over the past year and provided an outlook on multiple clinical data catalysts planned for 2025.

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!

"We are excited to share we have initiated the GALLOP Phase 1 trial. This milestone is a testament to the significant momentum we achieved across all four clinical programs throughout 2024," said Rachel Haurwitz, PhD, Caribou’s president and chief executive officer. "In the first half of 2025, we plan to report clinical data from our lead program, CB-010, in second-line and CD19 relapsed large B cell lymphoma patients as well as dose escalation data from our second program, CB-011, in relapsed or refractory multiple myeloma. Pending confirmation of our HLA matching strategy, we plan to initiate a pivotal Phase 3 trial for CB-010 in second-line large B cell lymphoma in the second half of 2025. We are excited to be on the forefront of a new era for allogeneic CAR-T cell therapies, which offer broad access and rapid availability to patients and healthcare systems."

2024 clinical highlights and corporate accomplishments

Clinical highlights
CB-010, a clinical-stage allogeneic anti-CD19 CAR-T cell therapy for B cell non-Hodgkin lymphoma
•At the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, Caribou presented clinical data from the ongoing ANTLER Phase 1 clinical trial that indicated a single dose of CB-010 has the potential to be on par with the safety, efficacy, and durability of approved autologous CAR-T cell therapies.
•A retrospective analysis of all patient data demonstrated that patients who received a dose of CB-010 manufactured from a donor with ≥4 matching human leukocyte antigen (HLA) alleles showed improved progression free survival (PFS).

•To confirm the HLA matching strategy, Caribou is enrolling approximately 20 additional second-line large B cell lymphoma (2L LBCL) patients in the ongoing ANTLER Phase 1 clinical trial.
•Caribou also began enrolling a proof-of-concept cohort of up to 10 patients who have relapsed following any prior CD19-targeted therapy in this population of unmet need.
•Caribou plans to present data from both the additional 2L and prior CD19 relapsed LBCL patient cohorts in H1 2025. The company plans to initiate a pivotal Phase 3 trial of CB-010 in the second half of 2025, should data from the additional 2L LBCL patients confirm the initial observation that partial HLA matching of patient to the donor results in outcomes on par with autologous CAR-T cell therapies. The Phase 3 trial would be initiated after agreement with the FDA on a pivotal trial design.

CB-010, a clinical-stage allogeneic anti-CD19 CAR-T cell therapy for lupus
•Caribou expanded the CB-010 program following clearance of its Investigational New Drug (IND) application by the U.S. Food and Drug Administration (FDA) for CB-010 in LN and ERL.
•The FDA granted Fast Track designation to CB-010 for refractory systemic lupus erythematosus (SLE).
•Caribou has initiated the GALLOP Phase 1 clinical trial, an open-label, multicenter clinical trial designed to evaluate a single infusion of CB-010 in adult patients with LN and ERL.

CB-011, a clinical-stage allogeneic anti-BCMA CAR-T cell therapy for multiple myeloma
•In the dose escalation portion of the CaMMouflage Phase 1 clinical trial for relapsed or refractory multiple myeloma (r/r MM), Caribou implemented a lymphodepletion regimen that includes a deeper dose of cyclophosphamide (increased from 300 to 500 mg/m2/day together with the same fludarabine dose of 30 mg/m2/day for 3 days). Following observations of efficacy, Caribou is enrolling additional patients as backfill at active dose levels with the deeper lymphodepletion regimen.
•No DLTs have been observed in CaMMouflage.
•Caribou plans to present dose escalation data on a minimum of 15 patients at active doses from the ongoing CaMMouflage Phase 1 clinical trial in H1 2025.

CB-012, a clinical-stage allogeneic anti-CLL-1 CAR-T cell therapy for acute myeloid leukemia
•The FDA granted Fast Track and Orphan Drug designations to CB-012 for relapsed or refractory acute myeloid leukemia (r/r AML).
•Caribou is enrolling patients with r/r AML in the dose escalation portion of the ongoing AMpLify Phase 1 clinical trial. Enrollment has concluded for dose level 3 (150×106 CAR-T cells, N=3) and no DLTs were observed. Patients are being enrolled at dose level 4 (300×106 CAR-T cells).

Corporate updates
Appointed experienced executive leaders and expanded the scientific advisory board (SAB)
•In January 2024, Tim Kelly was appointed chief technology officer and he leads Caribou’s process development and manufacturing organizations.
•In August 2024, Tina Albertson, MD, PhD, was appointed chief medical officer and she leads Caribou’s clinical programs and the clinical, regulatory, and medical affairs functions.
•In January 2025, Sri Ryali was appointed chief financial officer and he leads Caribou’s corporate finance, investor relations, and corporate communications functions.

•Terri Laufer, MD, was appointed to Caribou’s SAB. She is a leading rheumatologist known for her extensive research into immune cell regulation and dysfunction that leads to autoimmune diseases.
$281M in cash, cash runway into H2 2026
•Caribou previously reported $281 million in cash, cash equivalents, and marketable securities as of September 30, 2024, which is expected to fund the current operating plan into H2 2026.

2025 Anticipated milestones
•CB-010 ANTLER: Caribou plans to present data from both the additional 2L and prior CD19 relapsed LBCL patient cohorts in H1 2025. Caribou plans to initiate a pivotal Phase 3 clinical trial in H2 2025 should data confirm the initial observation that partial HLA matching drives outcomes that are on par with autologous CAR-T cell therapies.
•CB-010 GALLOP: Caribou plans to provide updates as the GALLOP Phase 1 clinical trial in LN and ERL advances.
•CB-011 CaMMouflage: Caribou plans to present dose escalation data from the ongoing CaMMouflage Phase 1 clinical trial in r/r MM in H1 2025.
•CB-012 AMpLify: Caribou plans to provide updates on dose escalation as the AMpLify Phase 1 clinical trial in r/r AML advances.

Caribou to present at the 43rd Annual J.P. Morgan Healthcare Conference
Dr. Haurwitz is scheduled to present a corporate update at the 43rd Annual J.P. Morgan Healthcare Conference on Thursday, January 16, 2025 at 10:30 am PST.

A live webcast of the presentation will be accessible via Caribou’s website on the Events page. The archived webcast will be available on the Caribou website for 30 days after the event.

About CB-010
CB-010 is the lead clinical-stage product candidate from Caribou’s allogeneic CAR-T cell therapy platform, and it is being evaluated in patients with relapsed or refractory B cell non-Hodgkin lymphoma (r/r B-NHL) in the ongoing ANTLER Phase 1 clinical trial and in patients with lupus nephritis (LN) and extrarenal lupus (ERL) in the GALLOP Phase 1 clinical trial. To Caribou’s knowledge, CB-010 is the first allogeneic CAR-T cell therapy in the clinic with a PD-1 knockout, a genome-editing strategy designed to improve CAR-T cell activity by limiting premature CAR-T cell exhaustion. The FDA granted CB-010 Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug designations for B-NHL and Fast Track designations for both B-NHL and refractory systemic lupus erythematosus (SLE). Additional information on the ANTLER trial (NCT04637763) and GALLOP trial (NCT06752876) can be found at clinicaltrials.gov.

About CB-011
CB-011 is a product candidate from Caribou’s allogeneic CAR-T cell therapy platform and is being evaluated in patients with relapsed or refractory multiple myeloma (r/r MM) in the CaMMouflage Phase 1 trial. CB-011 is an allogeneic anti-BCMA CAR-T cell therapy engineered using Cas12a chRDNA genome-editing technology. To Caribou’s knowledge, CB-011 is the first allogeneic CAR-T cell therapy in the clinic that is engineered to improve antitumor activity through an immune cloaking strategy with a B2M knockout and insertion of a B2M–HLA-E fusion protein to blunt immune-mediated rejection. CB-011 has been granted Fast Track and Orphan Drug designations by the FDA. Additional information on the CaMMouflage trial (NCT05722418) can be found at clinicaltrials.gov.

About CB-012
CB-012 is a product candidate from Caribou’s allogeneic CAR-T cell therapy platform and is being evaluated in the AMpLify Phase 1 clinical trial in patients with relapsed or refractory acute myeloid leukemia (r/r AML). CB-012 is an anti-CLL-1 CAR-T cell therapy engineered with five genome edits, enabled by Caribou’s patented next-generation CRISPR technology platform, which uses Cas12a chRDNA genome editing to significantly improve the specificity of genome edits. To Caribou’s knowledge, CB-012 is the first allogeneic CAR-T cell therapy with both checkpoint disruption, through a PD-1 knockout, and immune cloaking, through a B2M knockout and B2M–HLA-E fusion protein insertion; both armoring strategies are designed to improve antitumor activity. Caribou has exclusively in-licensed from Memorial Sloan Kettering Cancer Center (MSKCC) in the field of allogeneic CLL-1-targeted cell therapy a panel of fully human scFvs targeting CLL-1, from which the company has selected a scFv for the generation of the company’s CAR. CB-012 was granted Fast Track and Orphan Drug designations by the FDA. Additional information on the AMpLify trial (NCT06128044) can be found at clinicaltrials.gov.

On January 13, 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 recent successes across the Company’s viral immunotherapy portfolio and provided an update on the Company’s cash position and upcoming 2025 milestones (Press release, Candel Therapeutics, JAN 13, 2025, View Source [SID1234649642]).

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!

"I am incredibly proud of the Candel team for their successful execution of our 2024 priorities," said Paul Peter Tak, MD, PhD, FMedSci, President and Chief Executive Officer of Candel. "We demonstrated substantial clinical activity for our investigational medicines and delivered strong results across our pipeline, including positive and pivotal topline phase 3 data for CAN-2409 in intermediate-to-high risk localized prostate cancer, positive topline overall survival data from the phase 2a randomized controlled clinical trial of CAN-2409 in borderline resectable PDAC, as well as topline overall survival data from the open label phase 2a clinical trial of CAN-2409 in patients with stage III/IV NSCLC. We have also reported initial clinical and biomarker activity after repeated injection of CAN-3110 in the ongoing phase 1b clinical trial in rHGG and encouraging data demonstrating CAN-3110’s potential in a second indication, in a model of melanoma. In 2024, we also presented data on two novel experimental assets generated using Candel’s enLIGHTEN Discovery Platform. During the 2024 American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, we reported preclinical data for the first-in-class, tertiary lymphoid structure (TLS) inducer viral immunotherapy, and during the 2024 International Oncolytic Virotherapy Conference (IOVC), we presented data on a multimodal immunotherapy that delivers interleukin-12 (IL-12) and interleukin-15 (IL-15) to the tumor microenvironment."

Dr. Tak continued, "We are entering 2025 with clear momentum. Our primary focus will be achieving BLA readiness for CAN-2409 in prostate cancer. If approved, we believe that CAN-2409 has the potential to become a first-line treatment, as an addition to radiation therapy to reduce the risk of recurrence of prostate cancer, and to redefine the current standard-of-care for prostate cancer patients. In the upcoming months we look forward to collaborating closely with the FDA to ensure alignment in preparation for our BLA submission which, if approved, would enable us to deliver this much-needed therapy to patients."

2024 Accomplishments

•
CAN-2409 – Prostate Cancer
•
In December, the Company reported positive topline data from its multicenter phase 3 clinical trial evaluating CAN-2409 in intermediate-to-high-risk localized prostate cancer patients. The study met its primary endpoint by demonstrating statistically significant improvement in disease-free survival (DFS) in patients who received CAN-2409 plus valacyclovir (prodrug) combined with standard of care (SoC) external beam radiation therapy (n=496) compared to standard of care alone (n=249) in the intent to treat population.
•
The data showed a 30% reduction in the risk for prostate cancer recurrence or death due to any cause for the CAN-2409 treatment arm compared to placebo control arm (p=0.0155), and 80.4% pathological complete responses in 2-year post-treatment biopsies after CAN-2409 administration compared to 63.6% in the control arm (p=0.0015). The safety profile of CAN-2409 was generally consistent with previous studies, with no new safety signals identified.
•
This study was conducted under a Special Protocol Assessment (SPA) with U.S. Food and Drug Administration (FDA) agreement on key aspects of study design, meaning that safety and efficacy data generated from the study could be sufficient for the Company to seek regulatory approval for CAN-2409 in this indication.

•
FDA previously granted Fast Track Designation for CAN-2409 for the treatment of prostate cancer.
•
CAN-2409 – Pancreatic Cancer
•
In April 2024, the Company announced positive updated survival data, from the phase 2a randomized controlled clinical trial of CAN-2409 plus valacyclovir (prodrug), together with SoC chemoradiation, in borderline resectable PDAC (n=13). The data showed notable improvements in estimated median overall survival (mOS) of 28.8 months after experimental treatment with CAN-2409 versus 12.5 months in control group. At 24 months, the survival rate was 71.4% in CAN-2409-treated patients versus 16.7% in the control group. At 36 months, estimated survival was 47.6% in the CAN-2409 group versus 16.7% in the control group.
•
FDA previously granted Fast Track Designation for CAN-2409 in borderline resectable PDAC.
•
FDA granted Orphan Drug Designation for CAN-2409 in borderline resectable PDAC in April 2024.
•
CAN-2409 – Non-Small Cell Lung Cancer
•
At the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, the Company presented topline overall survival data from the phase 2a clinical trial of CAN-2409 plus valacyclovir in combination with continued immune checkpoint inhibitor (ICI) therapy in patients with stage III/IV NSCLC inadequately responding to ICI therapy. The data (as of April 1, 2024) showed mOS of 20.6 months in patients with progressive disease (n=41) despite ICI treatment compared to published results of less than 12 months with SoC docetaxel-based chemotherapy in similar patient populations.
•
As of the data cut-off date, CAN-2409 treatment in NSCLC continued to exhibit a favorable safety and tolerability profile.
•
FDA previously granted Fast Track Designation for CAN-2409 for the treatment of NSCLC.
•
CAN-3110 – Recurrent High-Grade Glioma
•
Presented a Trial-in-Progress poster at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting on the ongoing phase 1b clinical trial exploring multiple doses of CAN-3110 in patients with rHGG.
•
Presented updated clinical and biomarker activity data at the IOVC in October 2024. Investigators reported ongoing improved survival compared to historical controls, with 3 out of 6 patients still alive after more than one year (12.2, 13.0, and 18.7 months, respectively) after initiation of experimental treatment with repeated CAN-3110 injections
•
FDA granted Orphan Drug Designation for CAN-3110 for treatment of rHGG in May 2024.
•
FDA granted Fast Track Designation for CAN-3110 for the treatment of rHGG in February 2024.
•
CAN-3110 – Melanoma
•
Presented preclinical results on the therapeutic potential of CAN-3110 in the Ras-Raf pathway altered melanoma model at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2024 Annual Meeting. CAN-3110 exhibited potent, tumor-specific cytotoxicity in human and murine melanoma cell lines with varied CDKN2A pathway alterations and Nestin expression. In vivo mouse studies showed dose-dependent inhibition of tumor growth, with regression observed in a subset (3 of 8) of tumors treated with a high dose of CAN-3110. The therapy was well-tolerated in preclinical mouse models based on body weight and histopathological analysis following intra-tumoral administration.
•
enLIGHTEN Discovery Platform
•
Presented data on a new multimodal viral therapeutic candidate encoding IL-12 and IL-15 at the 2024 IOVC. Data showed the ability of the asset to induce expansion and activation of natural killer and CD8+ T cell populations, resulting in significant tumor growth inhibition and tumor regression in two different models.
•
Presented data at the AACR (Free AACR Whitepaper) 2024 Annual Meeting describing a first-in-class, multimodal immunotherapy candidate for the induction of tertiary lymphoid structures, being developed as a novel therapeutic strategy for solid tumors. Delivery of two unique payload combinations, predicted in silico using the enLIGHTEN Advanced Analytics suite, was shown to induce TLS formation, inhibit tumor growth, and improve response to ICI therapy in preclinical models of cancer.
2025 Anticipated Milestones and Key Catalysts

•
CAN-2409 – Pancreatic Cancer
•
Updated overall survival data from phase 2a clinical trial, expected in Q1 2025
•
Preparations underway for potential phase 2b, randomized clinical trial
•
CAN-2409 – Non-Small Cell Lung Cancer
•
Updated overall survival data from phase 2a clinical trial, expected in Q1 2025

•
Preparations underway for potential phase 2b, randomized clinical trial
•
CAN-2409 – Prostate Cancer
•
Presentation of the phase 3 clinical trial data at upcoming scientific conference
•
Publication of the phase 3 clinical trial data in a scientific journal
•
BLA submission on track for Q4 2026
•
CAN-3110 – Recurrent High-Grade Glioma
•
Overall survival data from ongoing phase 1b clinical trial evaluating multiple doses, expected in Q4 2025

Cash Position

Cash and cash equivalents, as of December 31, 2024, were $102.9 million (unaudited), as compared to $35.4 million (audited) as of December 31, 2023. Based on current plans and assumptions, the Company expects that its existing cash and cash equivalents will support the preparation and submission of a BLA for CAN-2409 in prostate cancer, as well as fund its current operating plan into Q1 2027.

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 NSCLC, and borderline resectable PDAC, in ongoing clinical trials, and has recently completed phase 2b and phase 3 clinical trials in localized, non-metastatic prostate cancer. CAN-2409 plus prodrug (valacyclovir) 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 primary prostate cancer. Candel’s pivotal phase 3 clinical trial in prostate cancer was conducted under a Special Protocol Assessment agreed with the FDA. The FDA has also granted Orphan Drug Designation to CAN-2409 for the treatment of PDAC.

About CAN-3110

CAN-3110 is a first-in-class, replication-competent herpes simplex virus-1 (HSV-1) oncolytic viral immunotherapy candidate designed with dual activity for oncolysis and immune activation in a single therapeutic. CAN-3110 is being evaluated in a phase 1b clinical trial in patients with rHGG. In October 2023, the Company announced that Nature published results from this ongoing clinical trial. CAN-3110 was well tolerated with no dose-limiting toxicity reported. In the clinical trial, the investigators observed improved median overall survival compared to historical controls after a single CAN-3110 injection in this therapy-resistant condition.1 The Company and academic collaborators are currently evaluating the effects of multiple CAN-3110 injections in rHGG, supported by the Break Through Cancer foundation. CAN-3110 has previously received FDA Fast Track Designation and Orphan Drug Designation for the treatment of rHGG.

About the enLIGHTEN Discovery Platform

The enLIGHTEN Discovery Platform is a systematic, iterative herpes simplex virus (HSV)-based discovery platform leveraging human biology and advanced analytics to create new multimodal biological immunotherapies for solid tumors. The enLIGHTEN Discovery Platform has been designed to deconvolute the characteristics of the tumor microenvironment related to clinical outcomes. These characteristics are rapidly translated into optimized multi-gene payloads of tumor modulators that can be delivered to the tumor microenvironment for specific indications, disease stages, and rationally designed therapeutic combinations. In 2022, the Company announced a discovery partnership with the University of Pennsylvania Center for Cellular Immunotherapies to create new viral immunotherapies that could enhance the efficacy of chimeric antigen receptor T cell (CAR-T) therapy in solid tumors. During the SITC (Free SITC Whitepaper) 2023 Annual Meeting and the 2023 IOVC meeting, Candel presented encouraging data on the first candidate from this platform, Alpha 201-macro-1, which was designed to interfere with the CD47/SIRP1α pathway, in mouse models of breast cancer and lung cancer. During the AACR (Free AACR Whitepaper) Annual Meeting 2024, Candel presented preclinical data, unveiling the second candidate from the enLIGHTEN Discovery Platform, a first-in-class multimodal immunotherapy candidate to induce TLS, being developed as a novel therapeutic for solid tumors. Candel presented data at the 2024 IOVC meeting. The presentation focused on a multimodal viral therapeutic candidate encoding IL-12 and IL-15, the latest asset from the platform.

On January 13, 2025 Bristol-Myers Squibb presented its corporate presenteation (Presentation, Bristol-Myers Squibb, JAN 13, 2025, View Source [SID1234649641]).

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!

On January 13, 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 updated topline Phase 1 combination data for zelenectide pevedotin plus pembrolizumab in previously untreated (first-line) cisplatin-ineligible patients with metastatic urothelial cancer (mUC) (Press release, Bicycle Therapeutics, JAN 13, 2025, View Source [SID1234649640]). The company also announced recent accomplishments and outlined strategic priorities and anticipated milestones for 2025.

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!

"Bicycle Therapeutics made significant advances across all aspects of our business in 2024. Notably, we drove important clinical progress of our targeted therapeutics in solid tumors, including greatly expanding the number of patients who could potentially benefit from our lead therapy zelenectide pevedotin, advanced our emerging pipeline of novel radiopharmaceuticals and strengthened our financial position and operational capabilities to advance our strategic priorities," said CEO Kevin Lee, Ph.D. "We are encouraged by our updated topline Phase 1 combination data for zelenectide pevedotin plus pembrolizumab in first-line cisplatin-ineligible patients, which we believe continue to demonstrate a differentiated safety profile and encouraging response rates in patients with poor prognosis and limited treatment options. We believe we are well-positioned to continue our strong momentum of execution over the course of 2025, which will be another year of important data milestones across our pipeline as we work to develop potentially transformative treatments that will help patients live longer and live well."

Updated Topline Zelenectide Pevedotin Plus Pembrolizumab Combination Data in First-Line mUC Highlights

Zelenectide pevedotin, a Bicycle Toxin Conjugate (BTC), has significant potential to treat Nectin-4 cancers. 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 three weeks in 22 first-line cisplatin-ineligible patients with mUC showed:

· 65% overall response rate (ORR) (13/20) among all efficacy-evaluable patients, and a 50% ORR (10/20) among patients with confirmed responses. Of the 3 unconfirmed responses, 1 patient remained on treatment at the time of the data cut.
· Median duration of response (mDOR) is not yet mature, with 12 patients still on treatment at the time of the data cut.
· 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. Notably, no patients withdrew from the study due to zelenectide TRAEs.

Altogether, these updated data continue to position zelenectide pevedotin as a potentially promising best-in-class therapy for mUC.

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 initially being assessed before a final dose is selected.

2024 Key Accomplishments

· Initiated the global Phase 2/3 Duravelo-2 trial for zelenectide pevedotin in mUC, providing multiple opportunities for potential accelerated approval.
· Presented updated monotherapy data for zelenectide pevedotin showing a promising 45% ORR in patients with late-line mUC who had not previously been treated with enfortumab vedotin. The data continue to support zelenectide pevedotin’s emerging differentiated profile as a potential treatment for mUC.
· Presented updated monotherapy data for BT5528, a BTC targeting EphA2, and BT7480, a Bicycle Tumor-Targeted Immune Cell Agonist (Bicycle TICA), in advanced solid tumors. The data support each molecule’s emerging differentiated safety and tolerability profile and provide important information for continued dose selection exploration.
· Presented first human imaging data validating the potential of MT1-MMP as a novel target in the treatment of cancer and highlighting the potential of Bicycle molecules for targeted radionuclide therapy. The company also selected EphA2 as its second radiopharmaceutical target.
· Reported monotherapy data for zelenectide pevedotin showing an enhanced response in late-line breast cancer and non-small cell lung cancer (NSCLC) patients with NECTIN4 gene amplification and/or polysomy. Based on these data, the U.S. Food and Drug Administration granted Fast Track designation to zelenectide pevedotin for the treatment of adult patients with previously treated, NECTIN4-amplified, advanced or metastatic triple-negative breast cancer and NSCLC.
· Raised $555 million to help advance research and development and strategic priorities. As of Sept. 30, 2024, the company had $890.9 million in cash and cash equivalents, with expected financial runway into 2H 2027.

2025 Strategic Priorities and Anticipated Milestones

Seek to transform treatment across multiple Nectin-4 associated cancers with zelenectide pevedotin

· Report additional Phase 1 Duravelo-1 combination data with pembrolizumab in first-line cisplatin-ineligible mUC in 2H 2025.
· Report longer-term follow-up Phase 1 Duravelo-1 monotherapy data in late-line mUC in 2H 2025.
· Report Phase 2/3 Duravelo-2 Cohort 1 and Cohort 2 dose selection data in 2H 2025.
· Initiate Phase 1 trials in NECTIN4 gene-amplified breast cancer (Duravelo-3) in 1H 2025 and NECTIN4 gene-amplified lung cancer (Duravelo-4) and multi-tumor (Duravelo-5) in 2H 2025.

Advance emerging Bicycle Radionuclide Conjugates (BRC) pipeline and progress strategy for leadership in next-generation radiopharmaceuticals

· Report additional MT1-MMP human imaging data in mid-2025.
· Report initial EphA2 human imaging data in 2H 2025.

Advance targeted therapeutics pipeline addressing novel targets that have historically been challenging to treat

· Report Phase 1 combination data for BT5528 plus nivolumab in 4Q 2025.
· Report Phase 1 combination data for BT7480 plus nivolumab in 4Q 2025.

J.P. Morgan Healthcare Conference Presentation and Webcast

Bicycle Therapeutics will highlight these updates and strategic priorities in a corporate presentation at the 43rd Annual J.P. Morgan Healthcare Conference on Tuesday, Jan. 14, 2025, at 5:15 p.m. PT, followed by a question-and-answer breakout session at 5:35 p.m. PT.

A live webcast of the presentation 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.