ER positive, HER2 negative Breast Cancer Pipeline Summary

DelveInsight’s, “ER positive, HER2 negative Breast Cancer - Pipeline Insight, 2026” report provides comprehensive insights about 70+ companies and 75+ pipeline drugs in ER positive, HER2 negative Breast Cancer pipeline landscape. It covers the pipeline drug profiles, including clinical and nonclinical stage products. It also covers the therapeutics assessment by product type, stage, route of administration, and molecule type. It further highlights the inactive pipeline products in this space.

Geography Covered

• Global coverage

ER positive, HER2 negative Breast Cancer: Understanding

ER positive, HER2 negative Breast Cancer: Overview

Breast cancer is the most common cancer in women worldwide and comprises biologically diverse subtypes, with ER+/HER2? disease accounting for approximately 60–70% of cases. Although generally associated with a more favorable prognosis than HER2-positive and triple-negative disease, ER+/HER2? tumors exhibit substantial heterogeneity in hormone receptor expression, histologic grade, proliferation, genomic alterations, and molecular subtype (luminal A or B), leading to differences in prognosis and treatment response. These features guide the use of endocrine therapy, chemotherapy, and targeted agents, while the risk of late recurrence highlights the need for long-term surveillance and strategies to overcome endocrine resistance.

ER+/HER2? breast cancer may be asymptomatic in early stages or present with localized breast changes, while advanced disease can cause systemic symptoms depending on tumor burden and metastatic involvement. Common clinical features include a palpable breast lump, which may be hard and associated with nipple inversion; fatigue and weakness, ranging from persistent tiredness to significant functional limitations; generalized or bone-related pain, which may occur with metastatic disease; and shortness of breath, particularly with exertion or in advanced disease involving the lungs or pleura.

ER+/HER2? breast cancer is driven primarily by estrogen receptor signaling, with tumors typically expressing ER and often PR while lacking HER2 overexpression or amplification. Its pathophysiology involves interconnected pathways, particularly PI3K/AKT/mTOR, MAPK, and CDK4/6–cyclin D1, which promote tumor-cell proliferation and survival and can enable endocrine resistance when alternative signaling pathways compensate for estrogen blockade. Genomic alterations, including PIK3CA, ESR1, CCND1, and TP53 abnormalities, further contribute to treatment resistance, disease progression, and metastatic potential, particularly in luminal B–like and relapsed disease. Interactions with the tumor microenvironment, including stromal, immune, and bone components, additionally support tumor survival and metastatic colonization, with bone being a common site of metastasis. Although ER+/HER2? tumors generally exhibit slower disease progression than HER2-positive or TNBC, dormant micrometastatic cells can persist for years and drive late recurrence. These mechanisms underpin treatment strategies combining endocrine therapy with targeted agents such as CDK4/6, PI3K, and mTOR inhibitors to delay or overcome endocrine resistance and prolong disease control.

Diagnosis of ER+/HER2? breast cancer involves a systematic evaluation combining clinical assessment, imaging, tissue biopsy, biomarker testing, and disease staging. Initial evaluation includes medical and family history and physical examination, although early disease may be asymptomatic and detected through screening. Mammography is the primary imaging modality, supplemented by ultrasound for lesion characterization and biopsy guidance, while MRI may be used in selected high-risk or complex cases. Core needle biopsy confirms malignancy and establishes histologic subtype and grade, while immunohistochemical testing determines ER, PR, and HER2 status to classify the tumor and guide treatment selection. In selected early-stage patients, multigene assays such as Oncotype DX or MammaPrint may further assess recurrence risk and the potential benefit of chemotherapy. Following diagnosis, staging evaluates regional lymph-node involvement and, when clinically indicated, distant metastases using modalities such as CT, PET-CT, or bone scans, thereby informing treatment planning and prognosis.

For ER+/HER2? breast cancer, endocrine therapy remains the cornerstone of treatment by blocking estrogen receptor signaling or reducing estrogen production. Selective estrogen receptor modulators (SERMs) such as tamoxifen (Soltamox) inhibit estrogen signaling in breast tissue, while aromatase inhibitors (AIs) such as anastrozole (Arimidex), exemestane (Aromasin), and letrozole (Femara) suppress estrogen synthesis, particularly in postmenopausal women. GnRH agonists, including goserelin (Zoladex) and leuprolide (Lupron Depot), suppress ovarian estrogen production and are primarily used in premenopausal women, with ovarian ablation as an alternative. For patients requiring additional targeted therapy, CDK4/6 inhibitors such as abemaciclib (Verzenio), ribociclib (Kisqali), and palbociclib (Ibrance) inhibit cell-cycle progression and are commonly combined with endocrine therapy. In advanced HER2-low disease, trastuzumab deruxtecan (Enhertu), a HER2-directed antibody–drug conjugate, selectively delivers a cytotoxic payload to HER2-expressing tumor cells and provides an additional treatment option despite the absence of HER2-positive status.

"ER positive, HER2 negative Breast Cancer- Pipeline Insight, 2026" report by DelveInsight outlays comprehensive insights of present scenario and growth prospects across the indication. A detailed picture of the ER positive, HER2 negative Breast Cancer pipeline landscape is provided which includes the disease overview and ER positive, HER2 negative Breast Cancer treatment guidelines. The assessment part of the report embraces, in depth ER positive, HER2 negative Breast Cancer commercial assessment and clinical assessment of the pipeline products under development. In the report, detailed description of the drug is given which includes mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, ER positive, HER2 negative Breast Cancer collaborations, licensing, mergers and acquisition, funding, designations and other product related details.

Report Highlights

• The companies and academics are working to assess challenges and seek opportunities that could influence ER positive, HER2 negative Breast Cancer R&D. The therapies under development are focused on novel approaches to treat/improve ER positive, HER2 negative Breast Cancer.

ER positive, HER2 negative Breast Cancer Emerging Drugs Chapters

This segment of the ER positive, HER2 negative Breast Cancer report encloses its detailed analysis of various drugs in different stages of clinical development, including Phase III, II, I, Preclinical and Discovery. It also helps to understand clinical trial details, expressive pharmacological action, agreements and collaborations, and the latest news and press releases.

ER positive, HER2 negative Breast Cancer Emerging Drugs

PF-07248144: Pfizer

PF-07248144 is a selective catalytic inhibitor of KAT6 (KAT6A/B), members of the histone lysine acetyltransferase family of enzymes that are involved in regulating gene expression. In certain cancers, KAT6A/B gene activity is dysregulated promoting cancer cell growth. PF-07248144 suppresses this abnormal gene activity and thereby suppresses cancer growth. Previous clinical trials have shown promise for treating advanced or metastatic hormone receptor positive, HER2-negative breast cancer. Currently the drug is in Phase III stage of development for the treatment of HR+ HER2- breast cancer.

Palazestrant: Olema Pharmaceuticals

Palazestrant (OP-1250) is a novel, orally available small molecule with dual activity as both a complete estrogen receptor antagonist (CERAN) and selective estrogen receptor degrader (SERD). It is currently being investigated in patients with recurrent, locally advanced or metastatic ER-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. In clinical studies, palazestrant completely blocks ER-driven transcriptional activity in both wild-type and mutant forms of metastatic ER+ breast cancer and has demonstrated anti-tumor efficacy along with attractive pharmacokinetics and exposure, favorable tolerability, central nervous system penetration, and combinability with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors. Palazestrant has been granted US Food and Drug Administration (FDA) Fast Track designation for the treatment of ER+/HER2- metastatic breast cancer that has progressed following one or more lines of endocrine therapy with at least one line given in combination with a CDK4/6 inhibitor. Currently the drug is in Phase III stage of development for the treatment of HR+ HER2- breast cancer.

STAR0602: Marengo Therapeutics

STAR0602 (invikafusp alfa), developed by Marengo Therapeutics, is a first-in-class, clinical-stage bi-functional fusion protein immunotherapy that uniquely targets specific variable (V?) regions of the T cell receptor (TCR) found on defined T cell subsets. Its novel mechanism of action involves simultaneous binding to the TCR V? region and delivering a co-stimulatory activation signal within the same T cell, leading to the selective expansion and activation of effector memory V? T cells capable of generating durable, tumor-directed immune responses. Unlike conventional T cell therapies that rely on clonal expansion or antigen-specific targeting, STAR0602 employs a non-clonal activation strategy, enabling it to bypass mechanisms of resistance to PD-1 inhibitors. According to the company’s pipeline, the drug is in Phase II stage of its development for the treatment of HR+, HER2-, Advanced Breast Cancer.

PCS6422: Processa Pharmaceuticals

PCS6422 is an oral, potent, selective, and irreversible inhibitor of dihydropyrimidine dehydrogenase (DPD), the enzyme that rapidly metabolizes 5-FU to inactive metabolites, such as ?-fluoro-?-alanine (F-Bal). F-Bal is thought to cause the neurotoxicity and Hand–Foot Syndrome associated with 5-FU while greater formation of F-Bal has been associated with a decrease in the antitumor activity of 5-FU. Inhibition of DPD by PCS6422 is expected to significantly increase the cancer exposure to the 5-FU cytotoxic metabolites, potentially improving tumor response while reducing side effects. Currently the drug is in Phase II stage of its development for the treatment of HR+/HER2- breast cancer.

AVZO-023: Avenzo Therapeutics, Inc. / Allorion Therapeutics

AVZO-023 is an investigational, highly potent and selective CDK4 inhibitor being developed by Avenzo Therapeutics for the treatment of HR-positive/HER2-negative breast cancer. It is designed to precisely target CDK4-driven cell-cycle dysregulation, a key mechanism underlying tumor growth in hormone receptor–positive disease. The drug aims to provide a next-generation, more selective CDK-targeted therapy to improve outcomes in endocrine-resistant disease. AVZO-023 is currently being evaluated in a Phase I/II clinical study, including combination regimens for patients with advanced or metastatic HR+/HER2- breast cancer.

TOS-358: Totus Medicines

TOS-358 is an investigational, highly selective, covalent small-molecule inhibitor of PI3K? (phosphatidylinositol 3-kinase alpha), targeting tumors with PIK3CA mutations or amplifications, including HR+/HER2- (ER+/HER2-) breast cancer, administered orally once or twice daily. It achieves durable near-100% inhibition of mutant PI3K? with minimal off-target effects on wild-type PI3K isoforms, reducing common toxicities like hyperglycemia seen with prior PI3K inhibitors, while demonstrating potent antitumor activity in preclinical patient-derived xenograft models of breast cancer and early clinical signals of efficacy in Phase I. The drug is currently being evaluated under Phase I clinical trial.

MRT-51443: Monte Rosa Therapeutics

MRT-51443 is a next-generation CDK2-directed molecular glue degrader being developed by Monte Rosa Therapeutics as a novel therapy for hormone receptor-positive (HR-positive), HER2-negative breast cancer. Designed to selectively degrade the CDK2 protein, a key driver of cancer cell proliferation, MRT-51443 has shown in preclinical models that, when combined with standard CDK4/6 inhibitors and anti-estrogen therapies, it can induce deeper tumor regressions and delay resistance compared with current standard-of-care regimens. Preclinical data also suggest improved target selectivity and a favorable drug-like profile that may help reduce off-target toxicities compared to less selective CDK2 inhibitors. Currently, it is in the preclinical stage of development for the treatment of HR-positive/HER2-negative Breast Cancer.

Further product details are provided in the report……..

ER positive, HER2 negative Breast Cancer: Therapeutic Assessment

This segment of the report provides insights about the different ER positive, HER2 negative Breast Cancer drugs segregated based on following parameters that define the scope of the report, such as:

• Major Players in ER positive, HER2 negative Breast Cancer
• There are approx. 70+ key companies which are developing the therapies for ER positive, HER2 negative Breast Cancer. The companies which have their ER positive, HER2 negative Breast Cancer drug candidates in the most advanced stage, i.e. Phase III include, Pfizer.

• Phases

DelveInsight’s report covers around 75+ products under different phases of clinical development like

• Late stage products (Phase III)
• Mid-stage products (Phase II)
• Early-stage product (Phase I) along with the details of
• Pre-clinical and Discovery stage candidates
• Discontinued & Inactive candidates

• Route of Administration

ER positive, HER2 negative Breast Cancer pipeline report provides the therapeutic assessment of the pipeline drugs by the Route of Administration. Products have been categorized under various ROAs such as

• Oral
• Intravenous
• Subcutaneous
• Parenteral
• Topical

• Molecule Type

Products have been categorized under various Molecule types such as

• Recombinant fusion proteins
• Small molecule
• Monoclonal antibody
• Peptide
• Polymer
• Gene therapy

• Product Type

Drugs have been categorized under various product types like Mono, Combination and Mono/Combination.

ER positive, HER2 negative Breast Cancer: Pipeline Development Activities

The report provides insights into different therapeutic candidates in Phase III, II, I, preclinical and discovery stage. It also analyses ER positive, HER2 negative Breast Cancer therapeutic drugs key players involved in developing key drugs.

Pipeline Development Activities

The report covers the detailed information of collaborations, acquisition and merger, licensing along with a thorough therapeutic assessment of emerging ER positive, HER2 negative Breast Cancer drugs.

ER positive, HER2 negative Breast Cancer Report Insights

• ER positive, HER2 negative Breast Cancer Pipeline Analysis
• Therapeutic Assessment
• Unmet Needs
• Impact of Drugs

ER positive, HER2 negative Breast Cancer Report Assessment

• Pipeline Product Profiles
• Therapeutic Assessment
• Pipeline Assessment
• Inactive drugs assessment
• Unmet Needs

Key Questions

Current Treatment Scenario and Emerging Therapies:

• How many companies are developing ER positive, HER2 negative Breast Cancer drugs?
• How many ER positive, HER2 negative Breast Cancer drugs are developed by each company?
• How many emerging drugs are in mid-stage, and late-stage of development for the treatment of ER positive, HER2 negative Breast Cancer?
• What are the key collaborations (Industry–Industry, Industry–Academia), Mergers and acquisitions, licensing activities related to the ER positive, HER2 negative Breast Cancer therapeutics?
• What are the recent trends, drug types and novel technologies developed to overcome the limitation of existing therapies?
• What are the clinical studies going on for ER positive, HER2 negative Breast Cancer and their status?
• What are the key designations that have been granted to the emerging drugs?

Key Players

• Pfizer
• Olema Pharmaceuticals
• Marengo Therapeutics
• Processa Pharmaceuticals
• Avenzo Therapeutics, Inc.
• Allorion Therapeutics
• Totus Medicines
• Monte Rosa Therapeutics
• Relay Therapeutics
• Daiichi Sankyo Company
• Merck
• Eli Lilly and Company
• Risen (Suzhou) Pharma Tech
• Jiangsu Simcere Pharmaceutical
• Tolmar
• Oncolytics Biotech
• Shanghai Henlius Biotech
• Edgewood Oncology
• BicycleTx Limited
• Carrick Therapeutics Limited
• SynDevRx, Inc.
• Ellipses Pharma
• Hinova Pharmaceuticals
• Accutar Biotechnology, Inc.
• BridgeBio Pharma
• BeOne Medicines
• Kind Pharmaceuticals LLC

Key Products

• PF-07248144
• Palazestrant
• STAR0602
• PCS6422
• AVZO-023
• TOS-358
• MRT-51443
• RLY-2608
• Patritumab deruxtecan
• LY4064809
• JS105
• SIM0270
• TOL2506
• Pelareorep
• HLX22
• BTX-A51
• Belzutifan
• BT8009
• Samuraciclib
• Evexomostat
• Vosilasarm (EP0062)
• HP568
• AC699
• BBO-10203
• BGB-21447
• AND019