DLL3-Targeted Immunotherapy: a Competitor Analysis

This competitive intelligence report about DLL3-Targeted Immunotherapies provides a competitor evaluation in the field of product candidates in research and development targeting DLL3. This report will be prepared on demand within one working day upon order placement. The report lists DLL4-targeted R&D programs by R&D phase in a tabular format and describes in brief the profile of DLL3-targeted immunotherapies by drug modality. The report will be provided in pdf format and sent by e-mail to the customer.

As an example of this category of on demand reports please see our free sample report of “Pipeline of 5T4-Targeted Immunotherapies”.

DLL3 is a clinically validated target for treatment of small cell lung cancer which recently started commercialization. Delta-like canonical Notch ligand 3 (DLL3) is minimally expressed in normal tissue but expressed in 80-85% of (small cell lung cancer) SCLC tumors, and approximately 77% of neuroendocrine carcinomas (NECs)1 making DLL3 an ideal therapeutic target for these two indications of high unmet medical need.

Upregulated DLL3 functions as a Notch ligand and has been a target for cancer therapy. DLL3 is fundamental in the downstream cellular signaling for proliferation and apoptosis. DLL3 is an atypical member of the Notch receptor ligand family that is able to inhibit activation of the Notch receptors. DLL3 contains different functional domains (such as a Delta-Serrate-Lag2 [DSL] domain, epidermal growth factor [EGF] repeats, and a transmembrane domain). Aberrant DLL3 expression has been found in neuroendocrine cancers and also high-grade serous ovarian cancer.

SCLC is an aggressive neuroendocrine tumor; response to initial chemotherapy and radiotherapy is often followed by recurrence, rapid progression, and resistance to current therapies. New data show that >75% of castration-resistant small-cell neuroendocrine prostate cancers (CRPC-NE) express the Notch ligand delta-like protein 3 (DLL3). None of the benign and only 0.52% of localized prostate cancer samples were DLL3⁺. By contrast, 12.5% of CRPC adenocarcinomas and 76.6% of CRPC-NE expressed DLL3, and 10.37% and 63.95% of cells in these samples were DLL3⁺, respectively.

The DLL3 target validated by the T-cell engaging antibody tarlatamab-dlle has attracted competitors developing novel anti-DLL3 product candidates with further enhanced effector functions including mono- and bispecific antibody drug, conjugates, radioligand therapies, CAR T- and NK cell therapies, T-cell engaging trispecific antibodies incorporating an immunostimulatory domain and other bispecific antibodies. The field still is in mid-stage clinical development without clear leader in the competition.