tovecimig (CTX-009) / ABL Bio, Compass Therap, Handok, Elpiscience - LARVOL DELTA

Safety and Efficacy of CTX-009 With or Without CTX-471 for Recurrent Glioblastoma (clinicaltrials.gov) - P1/2 | N=54 | Not yet recruiting | Sponsor: Washington University School of Medicine

Monotherapy • New P1/2 trial • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

The bispecific antibody ABL001 (tovecimig), which ABL Bio out-licensed, has reached a turning point. Key readouts from global phase 2 and 3 trials of the candidate, which partner Compas Therapeutics is developing as a second-line treatment for cholangiocarcinoma, are expected to be released next month. (Chosun Biz) - "Based on the results, Compas Therapeutics plans to submit a biologics license application (BLA) to the U.S. Food and Drug Administration (FDA) in the second half of this year. It is said to have already completed a preliminary meeting with the FDA."

FDA filing • P2/3 data • Cholangiocarcinoma

CTX-009 (ABL001), a bispecific antibody targeting DLL4 and VEGF A, in combination with paclitaxel in patients with advanced biliary tract cancer (BTC): A phase 2 study. (ASCO-GI 2023) - P1b/2a | "A phase 1b study assessed the safety, tolerability, pharmacokinetics and efficacy of CTX-009 in combination with paclitaxel or irinotecan in patients (pts) with advanced solid tumors. This Phase 2 study has shown promising efficacy in BTC pts treated in 2L or 3L setting. TRAE rate based on mode of action was high, but DLL4/VEGF targeting in BTC has a potential of development. Further investigation of safety and efficacy of this regimen is warranted."

Clinical • Combination therapy • Metastases • P2 data • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • NOTCH1

COMPANION-002 A clinical trial of investigational drug CTX-009 plus paclitaxel vs paclitaxel in second line advanced BTC. (PubMed, Future Oncol) - P2/3 | "Described here is the design of and rationale for COMPANION-002, a randomized phase II/III study, which will evaluate the safety and efficacy of CTX-009 in combination with paclitaxel versus paclitaxel alone as second-line treatment for patients with advanced biliary tract cancer. The primary end point is ORR, and crossover is allowed.Clinical Trial Registration: NCT05506943 (ClinicalTrials.gov)."

Journal • Metastases • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor

Results of a phase 2 study of a novel DLL4-VEGF, a bispecific antibody, tovecimig (CTX-009), as a monotherapy in patients with refractory metastatic colorectal cancer (COMPANION-003). (ASCO-GI 2026) - P2 | "Eligible patients had metastatic CRC with primary tumor resection and had progressed after receiving two or three prior systemic therapies, which must have included oxaliplatin, irinotecan, a fluoropyrimidine, an anti-VEGF therapy, and, if indicated, an anti-EGFR therapy. The results from the Phase 2 COMPANION-003 study demonstrated clinically meaningful anti-tumor activity with a manageable safety profile, which supports further development of tovecimig in patients with advanced, metastatic CRC."

Clinical • Metastases • Monotherapy • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • DLL4 • KRAS

ABL Bio (CEO Sang-Hoon Lee) announced on the 9th that Compass Therapeutics, the technology transfer partner of ABL001 (Tovecimig), will be presenting at the JPM Healthcare Conference 2026, which will be held from the 12th to the 15th (local time). [Google translation] (HIT News) - "Clinical results from COMPANION-002, including overall survival (OS) and progression-free survival (PFS), are scheduled to be announced in the first half of this year."

P2/3 data • Biliary Tract Cancer • Cholangiocarcinoma

HANDOK plans to continue expanding its anticancer pipeline (Chosun Biz) - "In 2027, it plans to launch in Korea as its own new drug the cholangiocarcinoma treatment 'HDB001A (generic name tovecimig),' which is being developed through open-innovation R&D. Tobesimig met the primary endpoint based on objective response rate (ORR) in key results from phase 2/3 in April this year. Results from analyses of the secondary endpoints overall survival (OS) and progression-free survival (PFS) are scheduled to be released in the first quarter of next year."

Launch non-US • P2/3 data • Cholangiocarcinoma

ABL001 aims for US approval next year…[Google translation] (HIT News) - "The full data from the US Phase 2/3 clinical trial of ABL001 is expected to be released in the first quarter of next year, and Compass is expected to submit a BLA (Biologics License Application) to the US FDA based on the data. It is understood that preliminary meetings have already been held."

FDA filing • P2/3 data • Biliary Tract Cancer • Cholangiocarcinoma

Tovecimig (DLL4 and VEGF-A bispecific antibody) (GlobeNewswire) - "Analyses of key secondary endpoints from the COMPANION-002 Phase 2/3 randomized study, including OS and PFS, are triggered by a pre-specified number of pooled OS events (80%). Based on a continued trend of decreased mortality in the study, top-line data are expected in late Q1 2026....Preparations for the Phase 2 basket study of tovecimig in a broader set of patients with DLL4+ cancers (potentially including gastric, ovarian, renal, hepatocellular, and colorectal cancers) are underway. The study is expected to begin following a comprehensive analysis of the complete data set from the COMPANION-002 BTC trial."

New P2 trial • P2/3 data • Biliary Tract Cancer • Colorectal Cancer • Gastric Cancer • Hepatocellular Cancer • Ovarian Cancer • Renal Cell Carcinoma

ABL Bio and partner Compass confirmed a lower-than-expected mortality rate in Phase 2/3 trials of their ABL001 trial. [Google translation] (BioTimes) - "The combination therapy of ABL001 (tovesimig) and paclitaxel achieved the primary endpoint in the phase 2/3 clinical trial COMPANION-002 for patients with biliary tract cancer, confirming an ORR of 17.1%, showing a statistically significant improvement compared to the ORR of 5.3% for paclitaxel monotherapy (P=0.031)....Secondary endpoints of the phase 2/3 clinical trial, including PFS and OS, are expected to be analyzed in the first quarter of 2026."

P2/3 data • Biliary Tract Cancer • Cholangiocarcinoma

COMPANION-003: A Study of CTX-009 in Adult Patients With Metastatic Colorectal Cancer (clinicaltrials.gov) - P2 | N=49 | Completed | Sponsor: Compass Therapeutics | Active, not recruiting ➔ Completed | N=84 ➔ 49

Enrollment change • Trial completion • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • BRAF • HER-2 • MSI

Compass Therapeutics Presents Data on Enhanced Efficacy of CTX-471 in Combination with Tovecimig in Checkpoint-Refractory Models at the American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "CTX-471 monotherapy demonstrated efficacy in multiple murine models, including models highly resistant to immune checkpoint inhibitors; Combining CTX-471 with tovecimig (CTX-009) markedly increased anti-tumor efficacy in these models; Tovecimig in combination with CTX-471 showed evidence of enhanced innate and adaptive anti-tumor immunity ranging from increased tumor cell killing to increased antigen presentation and interferon signaling; The combination of tovecimig and CTX-471 has the potential to be an effective therapeutic regimen in patients where checkpoint inhibitors have failed, including anti-PD-1 and anti-PD-L1 antibodies."

Preclinical • Oncology

Enhanced efficacy of CTX-471, a CD137 agonist antibody, in models of immune checkpoint failure via simultaneous blockade of neo-angiogenesis (AACR 2025) - "Coupling VEGF-A/Dll4 targeting with CD137 agonism markedly increased the anti-tumor efficacy of the individual treatments alone in the MC38B2m-/-, MC38H-2k1-/-, CT26B2m-/- models as well as in the highly IO resistant CT26B2m-/-E model. Tumor growth inhibition was accompanied by pharmacodynamic evidence consistent with decrease of vascular bed density and enhancement of cellular cytotoxic immunity. CTX-471 monotherapy was still efficacious, albeit blunted, in these IO resistant models."

Clinical • IO biomarker • Colorectal Cancer • Oncology • Solid Tumor • B2M

Compass Therapeutics Announces First Patient Dosed in an Investigator Sponsored Trial of Tovecimig in the First-Line Setting for Patients with Biliary Tract Cancer (GlobeNewswire) - "Compass Therapeutics...announced the first patient has been dosed in an Investigator Sponsored Trial (IST) to evaluate tovecimig (CTX-009, a DLL4 x VEGF-A bispecific antibody) for the first time in the front-line setting for patients with biliary tract cancer (BTC). The IST is being conducted at The University of Texas MD Anderson Cancer Center....In the MD Anderson-led, open-label trial, tovecimig is being added to a standard first-line regimen of gemcitabine, cisplatin, and durvalumab in an estimated 50 patients with unresectable or metastatic BTC. The study will have a standard safety run-in phase in 12 patients followed by an expansion phase in which 38 additional patients will be treated."

Trial status • Biliary Tract Cancer

ABL Bio faces pivotal moment as biliary tract cancer trial data could define its future (Korea Biomedical Review) - P2/3 | N=150 | COMPANION-002 (NCT05506943) | Sponsor: Compass Therapeutics | "At 10 p.m. KST, topline results will drop from the phase 2/3 U.S. trial of ABL001 (also known as CTX-009), a bispecific antibody co-developed with Compass Therapeutics for second-line biliary tract cancer (BTC). It’s the company’s first major readout from a partnered program and, by all accounts, its make-or-break moment....The company’s early hopes rest on performance signals already indicated in Korea, where ABL001 showed a 62 percent objective response rate (ORR) as a monotherapy in advanced solid tumors, including BCT....Compass' latest update pegs the ORR for CTX-009 plus paclitaxel at 37.5 percent in 24 patients, with a median progression-free survival of 9.4 months and overall survival at 12.5....A 17-patient interim update is expected this summer. Full enrollment could stretch into 2026."

P2/3 data • Trial status • Biliary Tract Cancer

COMPANION-003: A Study of CTX-009 in Adult Patients With Metastatic Colorectal Cancer (clinicaltrials.gov) - P2 | N=84 | Active, not recruiting | Sponsor: Compass Therapeutics | Trial completion date: Dec 2024 ➔ Jun 2025 | Trial primary completion date: Jun 2024 ➔ Mar 2025

Trial completion date • Trial primary completion date • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • BRAF • HER-2 • MSI

Compass Therapeutics Reports 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "Fully enrolled the third dosing cohort in the Phase 1 dose-escalation study of CTX-8371 (PD-1 x PD-L1 bispecific antibody), with preliminary data expected in the second half of 2025...In 2024, initiated dosing of the Phase 1 dose-escalation study of CTX-8371. As of February 2025, we have enrolled the third dosing cohort of the dose escalation study with no dose limiting toxicities (DLTs) observed to date....R&D expenses were $42.3 million for the year ended December 31, 2024, as compared to $38.1 million for the same period in 2023, an increase of $4.2 million or 11%. This increase was primarily attributable to additional program spending on tovecimig of $2.4 million and $1.3 million on CTX-471."

Commercial • P1 data • Trial status • Biliary Tract Cancer • Hematological Malignancies

CTX-009 with Gemcitabine, Cisplatin, and Durvalumab As First-line Therapy in Patients with Unresectable or Metastatic Biliary Tract Cancers (clinicaltrials.gov) - P1/2 | N=50 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Biliary Cancer • Biliary Tract Cancer • Oncology • Solid Tumor

A Study of CTX-009 (ABL001) in Combination With Irinotecan or Paclitaxel in Advanced or Metastatic Solid Tumor Patients (clinicaltrials.gov) - P1/2 | N=41 | Terminated | Sponsor: Handok Inc. | N=92 ➔ 41 | Trial completion date: Jul 2025 ➔ Jan 2025 | Active, not recruiting ➔ Terminated; Change of Development Plan

Enrollment change • Trial completion date • Trial termination • Biliary Cancer • Biliary Tract Cancer • Cholangiocarcinoma • Gallbladder Cancer • Hepatology • Oncology • Solid Tumor

Compass Therapeutics Provides Corporate Update (GlobeNewswire) - "Top-line data readout in the U.S. on track for the end of Q1 2025 for COMPANION-002, the Company’s Phase 2/3 randomized trial of tovecimig in combination with paclitaxel in patients with advanced BTC; Continuing to design and plan a Phase 2 study in patients with DLL4-positive colorectal cancer in the second-line setting in combination with chemotherapy, which is expected to initiate in mid-2025; An IST (investigator sponsored study) of tovecimig in patients with BTC in the first-line setting at The University of Texas MD Anderson Cancer Center is being initiated in Q1 2025. Tovecimig will be added to the standard first-line regimen of gemcitabine, cisplatin, and durvalumab"

New P2 trial • P2/3 data • Biliary Tract Cancer • Colorectal Cancer

Compass Therapeutics Reports 2024 Third Quarter Financial Results and Provides Corporate Update (GlobeNewswire) - "Fully enrolled the Phase 2/3 trial of lead asset CTX-009 (DLL4 and VEGF-A bispecific antibody) in patients with biliary tract cancers (BTC); top-line data readout is on track for the end of the first quarter of 2025. Designing a Phase 2 trial of CTX-009 in combination with chemotherapy in patients with DLL4-positive colorectal cancer (CRC) treated in the second-line setting; trial initiation expected in mid-2025. Identified neural cell adhesion molecule (NCAM or CD56) as a potential biomarker of response to CTX-471 based on data from the Phase 1 trial; planning a Phase 2 trial in patients with tumors expressing NCAM for mid-2025."

New P2 trial • P2/3 data • Biliary Cancer • Biliary Tract Cancer • Colorectal Cancer • Oncology • Solid Tumor

Population pharmacokinetic model of ABL001/CTX-009 (anti-VEGF/DLL4) in adult cancer patients with solid tumor. (PubMed, Cancer Sci) - P1/2 | "In conclusion, the model well described the plasma concentrations of ABL001/CTX-009 in patients with solid tumors. The simulation suggested that weight-based dose and fixed dose can provide equivalent systemic exposure."

Journal • PK/PD data • Oncology • Solid Tumor

ABL Bio’s ’ABL001’ to Seek FDA Accelerated Approval Next Year [Google translation] (WikiLeaks Korea) - "ABL Bio plans to announce topline data from phase 2/3 clinical trials for ABL001, a bile duct cancer treatment, next year and pursue accelerated approval from the FDA...After announcing the results of Phase 2/3 in the first half of next year and applying for FDA accelerated approval in 2025, sales are expected to begin in 2026."

Commercial • P2/3 data • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

Compass Therapeutics and ABL Bio Announce Presentation of CTX-009 Clinical Data as a Plenary Session of the 2021 AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics (Businesswire) - "Compass Therapeutics, Inc...and ABL Bio, Inc...announced today that the Phase 1 monotherapy dose escalation and expansion study data for CTX-009 (ABL001/ES104), a bispecific dual angiogenesis inhibitor targeting DLL4 and VEGF-A, has been selected for an oral plenary presentation at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics, being held virtually on October 7-10, 2021. The oral presentation will include single agent safety, tolerability, exploratory DLL4 expression analysis, and clinical activity data for CTX-009 in heavily pre-treated patients with metastatic, anti-VEGF-resistant solid tumors, mainly of colorectal and gastric origin."

P1 data • Colorectal Cancer • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

'Clinical Trial Cruise'...Domestic Pharmaceuticals, Commercialization of New Bile Duct Cancer Drugs at a Speed [Google translation] (Daily Pharm) - P2 | N=24 | "Handok confirmed the efficacy and safety of HDB001A in the phase 2 clinical trial conducted in Korea...The trial compared HDB001A plus paclitaxel with paclitaxel monotherapy in 24 adults with previously treated advanced, metastatic, or recurrent biliary tract cancer...After a median follow-up of 12 months, the objective response rate (ORR), which refers to a decrease in tumor size, with the combination therapy was 37.5%. The median overall survival (OS) was 12.5 months, the median duration of response (DOR) was 9.4 months, and the median progression-free survival (PFS), which refers to the period without disease worsening, was 9.4 months....Handok plans to apply for domestic approval once it confirms efficacy and good safety data in the US clinical trial."

P2 data • Biliary Cancer • Biliary Tract Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor