Delta-like Ligand 3 (DLL3)-targeted Therapies - Target Population, Competitive Landscape, and Market Forecast - 2034

Key Highlights:

• Delta-like Ligand 3 (DLL3) is an atypical Notch ligand overexpressed in Small Cell Lung Cancer (SCLC) and other Neuroendocrine Carcinomas/Tumors (NECs/NETs), linked to tumor growth, metastasis, and poor prognosis, making it a promising therapeutic target.
• In 2024, nearly 30,330 incident cases of NETs were observed in the US. Whereas, SCLC, which represents nearly 14% of all lung cancers, accounted for approximately 33,000 incident cases in the US.
• The approval of the first DLL3-targeted Bispecific T-cell Engager therapy, IMDELLTRA by the US Food and Drug Administration (FDA) in May 2024, marked a pivotal moment for patients battling Extensive-stage Small Cell Lung Cancer (ES-SCLC).
• The current pipeline is dominated with early-stage DLL-3 targeted therapies like peluntamig (Phanes Therapeutics), MK-6070/ HPN328-4001/ DS3280 (Merck / Daiichi Sankyo), LB2102/ DLL3-targeted CAR Ts (Legend Biotech and Novartis), 225Ac-ABD147 (Abdera Therapeutics), BI 764532 (Boehringer Ingelheim), ALPS12/ RG6524 (Chugai Pharmaceutical and Roche), ZL-1310 (Zai Lab), and others.
• Zai Lab is planning to submit Biologics License Applications (BLA) of ZL-1310 for the treatment of SCLC in or after 2026.
• DLL3-targeted therapies represent a promising frontier in SCLC and NEC treatment, offering new hope for patients facing this aggressive malignancy.

DelveInsight's "Delta-like Ligand 3 (DLL3)-targeted Therapies - Target Population, Competitive Landscape, and Market Forecast - 2034" report delivers an in-depth understanding of the DLL3-targeted therapies, historical and competitive landscape as well as its market trends in the United States, EU4 (Germany, France, Italy, and Spain) and the United Kingdom, and Japan.

The DLL3-targeted therapies' market report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted DLL3-targeted therapies' 7MM market size from 2020 to 2034. The report also covers current DLL3-targeted therapies' 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

Delta-like Ligand 3 (DLL3)-targeted Therapies Understanding and Treatment Algorithm

Delta-like Ligand 3 (DLL3)-targeted Therapies Overview

DLL3 is an atypical ligand of the Notch signaling pathway that, when overexpressed, contributes to the growth, migration, and invasiveness of SCLC cells. It also plays a role in driving the development of metastatic and treatment-resistant features in NECs, promoting both tumor cell proliferation and resistance to platinum-based chemotherapy. In normal cells, DLL3 expression is low and primarily localized to the Golgi apparatus and cytoplasmic vesicles. This restricted localization is maintained by the transmembrane domain and adjacent sequences in the DLL3 protein, which act as retention signals. However, in SCLC, DLL3 is significantly overexpressed and mislocalized to the cell surface, a feature present in up to 85% of human SCLC tumors. Although the precise mechanisms responsible for this overexpression and abnormal trafficking in malignant cells remain unclear, its distinct expression pattern makes DLL3 a notable marker and potential therapeutic target in SCLC.

In addition to SCLC, DLL3 is also broadly expressed in various other NECs, including certain molecular subtypes of pulmonary Large Cell NEC (LCNEC), as well as NECs of the gastroenteropancreatic system, bladder, prostate, and cervix. Elevated DLL3 expression in these malignancies has been associated with more advanced stages of disease and reduced overall survival, indicating a link between DLL3 levels and poor clinical prognosis.

Delta-like Ligand 3 (DLL3)-targeted Therapies' Market Overview

The differential expression and localization profiles of DLL3 in normal and tumor cells render DLL3 an attractive, tumor-selective therapeutic target. DLL3-targeted therapies include Antibody-drug Conjugates (ADCs), bispecific antibodies, cell therapies, antibody radionuclide conjugates, and photoabsorber conjugates. These diverse platforms reflect innovative strategies to exploit DLL3 as a therapeutic target.

Delta-like Ligand 3 (DLL3)-targeted Therapies' Epidemiology

The epidemiology chapter of DLL3-targeted therapies' in the report provides historical as well as forecasted epidemiology segmented as total cases in selected indications for DLL3-targeted therapies, total eligible patient pool in selected indications for DLL3-targeted therapies, and total treated cases in selected indications for DLL3-targeted therapies in the 7MM covering the United States, EU4 (Germany, France, Italy, and Spain), and the United Kingdom, and Japan from 2020 to 2034.

• In general, about 10-15% of all lung cancers are SCLC.
• Approximately 250,000 patients are diagnosed with SCLC each year globally, of which approximately 200,000 succumb to the disease.
• Each year nearly 30,000 cases of SCLC are diagnosed in the US.
• Around 12,000 people in the United States are diagnosed with NETs (sometimes called carcinoid tumors) each year.

The list is indicative and not exhaustive...

Delta-like Ligand 3 (DLL3)-targeted Therapies Drug Chapters

The drug chapter segment of the DLL3-targeted therapies report encloses a detailed analysis of approved DLL3-targeted therapies, late-, mid-, and early-stage DLL3-targeted therapies. It also helps understand the clinical trial details of DLL3-targeted therapies, expressive pharmacological action, agreements and collaborations, approval, and patent details, advantages and disadvantages of each included drug, and the latest news and press releases.

Marketed Delta-like Ligand 3 (DLL3)-targeted Therapies

IMDELLTRA (tarlatamab-dlle): Amgen

IMDELLTRA is a first-in-class immunotherapy engineered by Amgen researchers that binds to both DLL3 on tumor cells and CD3 on T cells, activating T cells to kill DLL3-expressing SCLC cells. This results in the formation of a cytolytic synapse with lysis of the cancer cell.

In May 2024, the US FDA approved IMDELLTRA for the treatment of adult patients with Extensive-stage SCLC (ES-SCLC) with disease progression on or after platinum-based chemotherapy. IMDELLTRA has received accelerated approval based on the encouraging response rate and duration of response (DoR) observed in clinical studies.

Emerging Delta-like Ligand 3 (DLL3)-targeted Therapies

Peluntamig (PT217): Phanes Therapeutics

Peluntamig (PT217), a first-in-class native IgG-like bispecific antibody targeting DLL3 and CD47, is being developed for the treatment of patients with SCLC and NEC, including Neuroendocrine Prostate Cancer (NEPC). The FDA has already granted peluntamig two Orphan Drug Designations (ODDs) for the treatment of SCLC and NEC, as well as two Fast Track Designations (FTDs) for the treatment of ES-SCLC with disease progression following treatment with platinum chemotherapy with or without a checkpoint inhibitor, and metastatic de novo or treatment-emergent neuroendocrine prostate cancer (NEPC), respectively. Currently, the therapy is in Phase I/II SKYBRIDGE trial (NCT05652686) for SCLC and NEC.

MK-6070/ HPN328-4001/ DS3280: Merck/ Daiichi Sankyo

MK-6070 is an investigational DLL3-directed tri-specific T-cell engager currently being evaluated in a Phase I/II clinical trial as a monotherapy in certain patients with advanced cancers associated with expression of DLL3 and in combination with atezolizumab in certain patients with SCLC. The US FDA granted ODD to MK-6070 for the treatment of SCLC in March 2022. In March 2024, Merck announced the completion of the acquisition of Harpoon Therapeutics.

In August 2024, Daiichi Sankyo and Merck, expanded their existing global co-development and co-commercialization agreement for three investigational DXd antibody-drug conjugates to include Merck's MK-6070. The companies will jointly develop and commercialize MK-6070 worldwide, except in Japan where Merck will maintain exclusive rights. Merck will be solely responsible for manufacturing and supply for MK-6070. The companies are planning to evaluate MK-6070 in combination with ifinatamab deruxtecan (I-DXd) in certain patients with SCLC, as well as other potential combinations.

Delta-like Ligand 3 (DLL3)-targeted Therapies Market Outlook

While ES-SCLC remains the primary focus, ongoing research is exploring DLL3-targeted therapies in other neuroendocrine cancers, including large cell neuroendocrine carcinoma, neuroendocrine prostate cancer, gastroenteropancreatic neuroendocrine tumors, and others. This expansion is expected to drive further market growth and diversify therapeutic applications.

Several key players, including Phanes Therapeutics, Merck, Abdera Therapeutics, and others, are involved in developing drugs for DLL3-targeted therapies. Overall, this is an exciting new class with great potential for development. The maturation of current studies over the next few years will lead to a better understanding of DLL3-targeted therapies and define their role in autoimmune indications.

Delta-like Ligand 3 (DLL3)-targeted Therapies Drugs Uptake

The launch of IMDELLTRA, the first DLL3-targeted therapy, has garnered widespread attention and marked a major milestone in DLL3-directed treatment, generating around USD 115 million in revenue in 2024 in the US. This DLL3-targeting therapy in ES-SCLC comprises a transformative option demonstrating long-lasting responses in pretreated patients. This approval further demonstrates our commitment to addressing aggressive cancers through our second FDA-approved BiTE molecule. IMDELLTRA offers these patients who are in urgent need of new innovative therapies hope, and we're proud to deliver this long-awaited effective treatment to them.

This section focuses on the uptake rate of potential approved and emerging DLL3-targeted therapies expected to be launched in the market during 2025-2034.

Delta-like Ligand 3 (DLL3)-targeted Therapies Pipeline Development Activities

The report provides insights into different therapeutic candidates. It also analyzes key players involved in developing targeted therapeutics.

The presence of numerous drugs under different stages is expected to generate immense opportunity for DLL3-targeted therapies' market growth over the forecast period.

Pipeline Development Activities

The report covers information on collaborations, acquisitions and mergers, licensing, and patent details for DLL3-targeted therapies.

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 DLL3-targeted therapies' evolving treatment landscape, patient reliance on conventional therapies, patient therapy switching acceptability, drug uptake, along challenges related to accessibility.

DelveInsight's analysts connected with 20+ KOLs to gather insights; however, interviews were conducted with 10+ KOLs in the 7MM. Centers such as Emory University and others.

Their opinion helps understand and validate current and emerging therapy treatment patterns or DLL3-targeted therapies' 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, Continuing Medical Education (CME) program, 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 Delta-like Ligand 3 (DLL3)-targeted Therapies

• In February 2025, Phanes Therapeutics announced that the first patient was dosed in the clinical study of peluntamig (PT217) in combination with chemotherapy.
• In September 2024, Abdera Therapeutics announced that the US FDA granted ODD to ABD-147 for the treatment of NEC.
• In August 2024, Daiichi Sankyo and Merck expanded their existing global co-development and co-commercialization agreement for Merck's MK-6070 for the treatment of SCLC.

The abstract list is not exhaustive, will be provided in the final report

Scope of the Report:

• The report covers a segment of key events, an executive summary, and a descriptive overview of the DLL3-targeted therapies, explaining its mechanism, and therapies (current and emerging).
• 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 DLL3-targeted therapies 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 DLL3-targeted therapies market.

Delta-like Ligand 3 (DLL3)-targeted Therapies Report Insights

• DLL3-targeted Therapies Patient Pool
• Therapeutic Approaches
• DLL3-targeted Therapies' Pipeline Analysis
• DLL3-targeted Therapies Market Size and Trends
• Existing and future Market Opportunities

Delta-like ligand 3 (DLL3)-targeted Therapies Report Key Strengths

• 10 years Forecast
• The 7MM Coverage
• Key Cross Competition
• Drugs Uptake and Key Market Forecast Assumptions

Delta-like ligand 3 (DLL3)-targeted Therapies Report Assessment

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

Key Questions:

• What was the total market size of DLL3-targeted therapies, 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 therapy is going to be the largest contributor in 2034?
• Which is the most lucrative market for DLL3-targeted therapies?
• What are the pricing variations among different geographies for approved therapies?
• How has the reimbursement landscape for DLL3-targeted therapies evolved since the first one was approved? Do patients have any access issues that are driven by reimbursement decisions?
• What are the risks, burdens, and unmet needs of treatment with DLL3-targeted therapies? What will be the growth opportunities across the 7MM for the patient population of DLL3-targeted therapies?
• What are the indications for which recent novel therapies and technologies have been developed to overcome the limitations of existing treatments?
• What key designations have been granted to the therapies for DLL3-targeted therapies?
• What is the cost burden of approved therapies on the patient?
• Patient acceptability in terms of preferred therapy options as per real-world scenarios?
• What are the country-specific accessibility issues of expensive, recently approved therapies?

Reasons to buy:

• The report will help develop business strategies by understanding the latest trends and changing dynamics driving the DLL3-targeted therapies 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.