ROR Inhibitors - Target Population, Competitive Landscape, and Market Forecast - 2034

Key Highlights:

• Receptor Tyrosine Kinases (RTKs) are transmembrane proteins that relay growth-factor signals to sustain a diverse set of biological responses from cell proliferation to apoptosis and differentiation. A distinct subfamily of RTKs comprises Wnt receptors, such as receptor tyrosine kinase orphan-like receptors 1 and 2 (ROR1/2).
• ROR1 is highly expressed in a variety of cancers, including hematological cancers such as chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and solid tumors (ovarian, breast, prostate, lung, melanoma, colorectal cancers, and others).
• ROR1 is a highly expressed cell surface antigen present on many aggressive solid tumors, including approximately 60% of patients with Triple-negative Breast Cancer (TNBC) and 40% of patients with Non-small Cell Lung Cancer (NSCLC).
• Several key companies, including Merck (Zilovertamab vedotin), Novalgen (NVG-111, NVG-222, NVG-333), BioAtla (Ozuriftamab vedotin), CStone Pharmaceuticals (CS5001), and others, are involved in developing ROR inhibitors.

DelveInsight's "ROR Inhibitors - Target Population, Competitive Landscape, and Market Forecast - 2034" report delivers an in-depth understanding of the ROR inhibitors, historical and competitive landscape as well as the ROR inhibitors market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.

The ROR inhibitors market report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted 7MM ROR inhibitors market size from 2020 to 2034. The report also covers current ROR inhibitors treatment practices/algorithms and unmet medical needs to curate the best opportunities and assess the market's potential.

Geography Covered:

• The United States
• EU4 (Germany, France, Italy, and Spain) and the United Kingdom
• Japan

Study Period: 2020-2034

ROR Inhibitors Understanding and Treatment Algorithm

ROR Inhibitors Overview

The ROR-family proteins, ROR1 and ROR2, act as receptors or co-receptors for non-canonical Wnt ligands such as Wnt5a, thereby regulating cell polarity, migration, proliferation, and differentiation that are required for proper developmental morphogenesis and tissue-/organo-genesis. In the RORs subfamily, there are three members: RORa, RORB, and ROR?, encoded by RORA, RORB, and RORC, respectively. All of these receptors are transcription factors that are ligand-dependent.

ROR1 and ROR2 are tyrosine kinase-like orphan receptors that play critical roles in embryogenesis. Aberrant expression of ROR1 has been observed in a range of cancers compared to its limited expression in healthy adult tissue, which makes it a candidate target for treating these cancers. ROR1 has been demonstrated to play an oncogenic role in many tumor types and has been broadly linked with cell proliferation, stemness, Epithelial-mesenchymal Transition (EMT), and other metastatic abilities. In contrast, the role of ROR2 in carcinogenesis remains controversial, as it acts as either a tumor suppressor or a tumor promoter in different cancers.

The ROR inhibitor family of proteins includes ROR1 and ROR2, receptor tyrosine kinases. ROR1 is especially interesting to pharmacologists as it has only been observed in cancerous and embryonic cells, and never in healthy adult tissue. This makes it a strong therapeutic target for the treatment of several types of cancer. ROR1 and ROR2 are implicated in age-related diseases, including tissue fibrosis, atherosclerosis (or arteriosclerosis), neurodegenerative diseases, and cancers.

ROR Inhibitors Epidemiology

The ROR inhibitors epidemiology chapter in the report provides historical as well as forecasted epidemiology segmented as total cases of selected indication for ROR inhibitors, total eligible patient pool for ROR inhibitors in selected indication, total treated cases in selected indication for ROR inhibitors in the 7MM covering the United States, EU4 (Germany, France, Italy, and Spain), and the United Kingdom, and Japan from 2020 to 2034.

• According to DelveInsight's estimates, the incident cases in the 7MM for DLBCL were ~77,000 in 2024. Among EU4 and the UK, Germany accounted for the highest incident cases of DLBCL, while Spain accounted for the lowest incident cases of DLBCL.
• In the United States, the maximum number of DLBCL patients lies in the age group of 65-74 years, and the least number of patients lies in the age group of 0-19 years.
• As per DelveInsight's estimates, the incident cases in the US for NSCLC were ~203,000 in 2024. Cases of NSCLC were higher among those aged =65 years than those aged <65 years.
• Among EU4 countries, the highest number of incident cases of TNBC was found in Germany with ~11,000 cases in 2024, followed by France.

ROR Inhibitors Drug Chapters

The drug chapter segment of the ROR inhibitors report encloses a detailed analysis of ROR inhibitors in different stages of development. It also helps understand the ROR inhibitors' clinical trial details, expressive pharmacological action, agreements and collaborations, approval and patent details, advantages and disadvantages of each included drug, and the latest news and press releases.

Emerging Drugs

Zilovertamab Vedotin (MK-2140): Merck

Zilovertamab vedotin is an investigational ADC that targets ROR1. ROR1 is a transmembrane protein that is overexpressed in multiple hematologic malignancies. Merck is committed to research with zilovertamab vedotin across B-cell malignancies and is establishing a robust program of clinical trials under the name waveLINE.

In June 2025, Merck presented the data from the Phase II/III waveLINE-003 study evaluating zilovertamab vedotin, an investigational ADC that targets ROR1, plus standard of care as a treatment for patients with relapsed or refractory DLBCL at the ASCO 2025 annual meeting.

In February 2025, Merck announced the initiation of waveLINE-010, a pivotal Phase III clinical trial evaluating zilovertamab vedotin in combination with rituximab plus cyclophosphamide, doxorubicin, and prednisone (R-CHP) compared to rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) alone, for the treatment of patients with previously untreated DLBCL.

According to the JP Morgan Healthcare Conference data readout, the Phase II NCT05144841 (waveLINE-004) trial of zilovertamab vedotin for R/R DLBCL is expected by 2025. The Phase II/III NCT05139017 (waveLINE-003) trial for R/R DLBCL is anticipated between 2026 and 2027, while the Phase III NCT06717347 (waveLINE-010) trial for DLBCL is projected beyond 2028.

Ozuriftamab vedotin (BA3021): BioAtla/ Bristol-Myers Squibb

Ozuriftamab vedotin is a Conditionally Active Biologic (CAB) anti-ROR2 ADC consisting of a CAB anti-ROR2 humanized IgG1 monoclonal antibody conjugated to monomethyl auristatin E (MMAE) using a cleavable linker. Ozuriftamab vedotin is designed to specifically and reversibly bind to ROR2 in conditions found within the tumor microenvironment, thus conferring a selective binding advantage for tumors over normal cells. Upon binding of ozuriftamab vedotin to ROR2 on the surface of tumor cells, it is internalized, and the MMAE cytotoxin is released, thus killing the cancer cell. Ozuriftamab vedotin has shown promising overall response rates in SCCHN, and the FDA has granted Fast-Track designation (FTD) for ozuriftamab vedotin in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).

According to BioAlta's Q1 2025 financial highlights, the company is utilizing FTD for additional discussions with the US FDA in treatment-refractory, metastatic HPV-positive SCCHN for guidance on a proposed Phase III study.

In May 2025, BioAlta announced a poster presentation of the Phase II trial of ozuriftamab vedotin (BA3021), a conditionally binding ROR2-ADC, in patients with heavily pretreated SCCHN at ASCO 2025.

ROR Inhibitors Market Outlook

ROR1/2 are putative druggable targets increasing in significance in translational oncology. Increasing evidence emerging from functional and structural studies points toward Wnt-binding receptor pseudokinases having a key role in regulating functional processes in normal and pathological conditions, despite their lack of catalytic activity. Overexpression of ROR1 and ROR2 has been detected in numerous cancers. For instance, in hematological cancers, the reactivation of ROR1 signaling in CLL, MCL, and B-ALL is linked to advanced disease stage and activation of AKT signaling in ROR1-high positive cells. ROR2 expression was also shown to activate AKT signaling in multiple myeloma.

ROR1 is considered an ideal druggable target for oncology because of its demonstrated pro-tumourigenic actions, cancer-specific expression, cell surface expression, and availability of drugs that can regulate ROR1 action. ROR2 is also under clinical evaluation as a drug target, with several clinical trials in progress, including one of Bioatla BA3021, a CAB ROR2-targeted ADC.

Several key companies, including Merck (Zilovertamab Vedotin), Octernal Therapeutics (ONCT-808), Novalgen (NVG-111, NVG-222, NVG-333), BioAtla (Ozuriftamab vedotin), CStone Pharmaceuticals (CS5001), and others, are involved in developing ROR inhibitors.

ROR Inhibitor Drugs Uptake

This section focuses on the uptake rate of potential approved and emerging ROR inhibitors expected to be launched in the market during 2025-2034.

ROR Inhibitors Pipeline Development Activities

The report provides insights into different therapeutic candidates in Phase III, Phase II, and Phase I. It also analyzes key players involved in developing targeted therapeutics.

The presence of numerous drugs at different stages is expected to generate immense opportunities for the ROR inhibitors market growth over the forecasted period.

Pipeline development activities

The report covers information on collaborations, acquisitions and mergers, licensing, and patent details for ROR inhibitors emerging therapies.

The increasing strategic collaborations among major market players to enhance the growth of their pipeline products are anticipated to drive market expansion.

KOL Views

To keep up with current and future market trends, we take Industry Experts' opinions working in the domain through primary research to fill the data gaps and validate our secondary research. Industry experts were contacted for insights on ROR's evolving treatment landscape, patient reliance on conventional therapies, patient therapy switching acceptability, drug uptake, along challenges related to accessibility.

DelveInsight's analysts connected with 25+ KOLs to gather insights; however, interviews were conducted with 10+ KOLs in the 7MM. Centers such as Penn Medicine's Hematologic Malignancies Translational Center of Excellence, UC Davis Comprehensive Cancer Center, University of Texas MD Anderson Cancer Center, etc. were contacted.

Their opinion helps understand and validate current and emerging therapy treatment patterns or ROR inhibitors market trends. This will support the clients in potential upcoming novel treatments by identifying the overall scenario of the market and the unmet needs.

Qualitative Analysis

We perform Qualitative and market Intelligence analysis using various approaches, such as SWOT analysis. In the SWOT analysis, strengths, weaknesses, opportunities, and threats in terms of disease diagnosis, patient awareness, patient burden, competitive landscape, cost-effectiveness, and geographical accessibility of therapies are provided. These pointers are based on the analyst's discretion and assessment of the patient burden, cost analysis, and existing and evolving treatment landscape.

Market Access and Reimbursement

Reimbursement may be referred to as the negotiation of a price between a manufacturer and payer that allows the manufacturer access to the market. It is provided to reduce the high costs and make the essential drugs affordable. Health Technology Assessment (HTA) plays an important role in reimbursement decision-making and recommending the use of a drug. These recommendations vary widely throughout the seven major markets, even for the same drug.

In the US healthcare system, both Public and Private health insurance coverage are included. Also, Medicare and Medicaid are the largest government-funded programs in the US. The major healthcare programs including Medicare, Medicaid, the Children's Health Insurance Program (CHIP), and the state and federal health insurance marketplaces are overseen by the Centers for Medicare & Medicaid Services (CMS). Other than these, Pharmacy Benefit Managers (PBMs), and third-party organizations that provide services, and educational programs to aid patients are also present.

The report further provides detailed insights on the country-wise accessibility and reimbursement scenarios, cost-effectiveness scenario of approved therapies, programs making accessibility easier and out-of-pocket costs more affordable, insights on patients insured under federal or state government prescription drug programs, etc.

Key Updates on ROR Inhibitors

• In June 2025, Merck presented the data from the Phase II/III waveLINE-003 study evaluating zilovertamab vedotin, an investigational ADC that targets ROR1, plus standard of care as a treatment for patients with relapsed or refractory DLBCL at the ASCO 2025 annual meeting.
• In February 2025, Merck announced the initiation of waveLINE-010, a pivotal Phase III clinical trial evaluating zilovertamab vedotin in combination with rituximab plus cyclophosphamide, doxorubicin, and prednisone (R-CHP) compared to rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) alone, for the treatment of patients with previously untreated DLBCL.
• According to BioAlta's Q1 2025 financial highlights, the company is utilizing FTD for additional discussions with the US FDA in treatment-refractory, metastatic HPV-positive SCCHN for guidance on a proposed Phase III study.
• In May 2025, BioAlta announced a poster presentation of the Phase II trial of ozuriftamab vedotin (BA3021), a conditionally binding ROR2-ADC, in patients with heavily pretreated SCCHN at ASCO 2025.

Scope of the Report:

• The report covers a segment of key events, an executive summary, and a descriptive overview of the ROR Inhibitor, explaining its mechanism, and emerging ROR inhibitors.
• Comprehensive insight into the competitive landscape, and forecasts, the future growth potential of treatment rate, drug uptake, and drug information have been provided.
• Additionally, an all-inclusive account of the current and emerging therapies and the elaborative profiles of late-stage and prominent therapies will impact the current landscape.
• A detailed review of the ROR Inhibitor market, historical and forecasted market size, market share by therapies, detailed assumptions, and rationale behind our approach is included in the report, covering the 7MM drug outreach.
• The report provides an edge while developing business strategies, by understanding trends, through SWOT analysis, expert insights/KOL views, and treatment preferences that help shape and drive the 7MM ROR Inhibitor market.

ROR Inhibitors Report Insights

• ROR Inhibitors Targeted Patient Pool
• Therapeutic Approaches
• ROR Inhibitors Pipeline Analysis
• ROR Inhibitors Market Size and Trends
• Existing and Future Market Opportunity

ROR Inhibitors Report Key Strengths

• Ten-Year Forecast
• The 7MM Coverage
• Key Cross Competition
• Drug Uptake and Key Market Forecast Assumptions

ROR Inhibitors Report Assessment

• Current Treatment Practices
• Unmet Needs
• Pipeline Product Profiles
• Market Attractiveness
• Qualitative Analysis (SWOT)
• Conjoint Analysis

Key Questions:

• What was the ROR inhibitor total market size, the market size by therapies, market share (%) distribution, and what would it look like in 2034? What are the contributing factors for this growth?
• Which drug is going to be the largest contributor in 2034?
• Which is the most lucrative market for ROR Inhibitors?
• What are the pricing variations among different geographies?
• What are the risks, burdens, and unmet needs of treatment for ROR inhibitors? What will be the growth opportunities across the 7MM for the patient population of ROR inhibitors?
• What are the key factors hampering the growth of the ROR inhibitors market?
• What key designations have been granted to ROR inhibitors?
• Patient acceptability in terms of preferred therapy options as per real-world scenarios?

Reasons to buy:

• The report will help develop business strategies by understanding the latest trends and changing dynamics driving the ROR inhibitors market.
• Understand the existing market opportunities in varying geographies and the growth potential over the coming years.
• Distribution of historical and current patient share based on real-world prescription data along with reported sales of approved products in the US, EU4 (Germany, France, Italy, and Spain) the United Kingdom, and Japan.
• Identifying strong upcoming players in the market will help devise strategies to help get ahead of competitors.
• Detailed analysis and ranking of indication-wise current and emerging therapies under the conjoint analysis section to provide visibility around leading indications.
• Highlights of Access and Reimbursement policies of approved therapies, barriers to accessibility of expensive off-label therapies, and patient assistance programs.
• To understand Key Opinion Leaders' perspectives around the accessibility, acceptability, and compliance-related challenges of existing treatment to overcome barriers in the future.
• Detailed insights on the unmet needs of the existing market so that the upcoming players can strengthen their development and launch strategy.