The bispecific antibody ABL001 (toveshimig), 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.
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.
If approval and commercialization succeed, toveshimig will become the first product for which ABL Bio recognizes sales royalties. The company expects to receive up to 200 billion won in royalties annually. Compas Therapeutics CEO Thomas Schuetz previously put the U.S. market potential at $1 billion (about 1.45 trillion won) per year.
◇ Toveshimig awaits OS and PFS…knocks on the FDA's door in the second half
Cholangiocarcinoma is considered a hard-to-treat cancer with limited options after first-line therapy. According to market research firm Research Nester, the global cholangiocarcinoma therapeutics market is expected to expand to $2.42 billion (about 3.5 trillion won) by 2035, with a compound annual growth rate (CAGR) of 15.3% from this year through 2035.
Toveshimig is a bispecific antibody that simultaneously blocks the DLL4 and VEGF-A signaling pathways involved in tumor angiogenesis. Compas Therapeutics in-licensed the molecule and, since 2022, has been conducting a phase 2/3 trial under the name CTX-009 comparing a combination regimen with the chemotherapy paclitaxel against paclitaxel monotherapy.
In an interim analysis, the objective response rate (ORR) in the combination arm was 17.1%, surpassing by threefold that of the competing drug FOLFOX (4.9%) and the monotherapy arm (5.3%). Complete response (CR) and partial response (PR) were observed in 1 and 18 patients, respectively. The rate of progressive disease (PD) was also much lower in the combination arm at 16.2%, compared with 42.1% in the monotherapy arm.
Expectations are growing for the not-yet-disclosed overall survival (OS) and progression-free survival (PFS) endpoints. The company had planned to analyze and release the data at the end of last year when the cumulative death rate reached 80%, but the timeline was delayed as patient survival lasted longer than expected.
Conditions for an expedited approval are seen as being in place. Toveshimig was designated for the FDA's Fast Track in 2024. Fast Track-designated drugs may be eligible for another FDA support pathway, Accelerated Approval, if they meet separate criteria.
Investigator-sponsored trials (ISTs) are also being conducted alongside to supplement the phase 2 and 3 studies. Led by the University of Texas MD Anderson Cancer Center, this research is testing a combination strategy with the standard first-line regimen of gemcitabine, cisplatin and durvalumab.
◇ "First running royalties" in sight…will ABL Bio's fundamentals change?
ABL Bio expects that if toveshimig receives FDA approval, it could begin receiving royalties as early as next year. Based on that, the company plans to expand its research workforce and broaden clinical trials for its pipeline.
With a revenue source that recurs annually secured, its earnings structure is also expected to become more stable. ABL Bio has so far had high reliance on upfront and milestone payments from technology transfers, leading to large volatility in sales and operating profit.
Hur Hye-min, an analyst at Kiwoom Securities, said, "There is effectively no standard second-line therapy for cholangiocarcinoma at present," adding, "If the OS and PFS data to be released this time are positive, meaningful royalty revenue inflows will be possible." The estimated price for toveshimig was revised upward from the previous $22,000 (about 31.9 million won) to $66,000 (about 95.7 million won).
The industry is also watching the possibility that the ORR could improve to around 30% in this announcement. Handok, which holds domestic rights to ABL001, previously said that the ORR of the paclitaxel combination arm reached 37.5% in a phase 2 trial in Korea.
An ABL Bio official said, "Depending on the clinical results, we are leaving open the possibility of applying for FDA Accelerated Approval," adding, "The initial launch region is likely to be the United States." Compas Therapeutics is said to have recently hired a head of commercial to prepare for direct sales in the United States.