HER2 Positive Breast Cancer - Pipeline Insight, 2024

This “HER2 Positive Breast Cancer- Pipeline Insight, 2024” report provides comprehensive insights about 60+ companies and 65+ pipeline drugs in HER2 Positive 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

HER2 Positive Breast Cancer: Understanding

HER2 Positive Breast Cancer: Overview

Breast cancer is not a single disease but a group of diseases. Scientists discovered human epidermal growth factor receptor 2 (HER2)-positive breast cancer when searching for genes that cause cancer. On the most basic level, cancer is the result of normal cells growing unchecked, an observation that led researchers to speculate that specific genes or gene mutations enable this to occur. Resistance to anti-HER2 therapies may occur via multiple mechanisms, some of which appear to be shared between different agents. A common reason for trastuzumab treatment failure is incomplete inhibition of the HER family of receptors, which can be overcome by dual HER2-targeted therapy or ADCs with potent payloads that have activity even with lower HER2 expression. Effective inhibition of HER2 may also be thwarted by the emergence of HER2-activating mutations. Other resistance mechanisms include generation of p95HER2, a truncated form of HER2 that lacks the ECD that is recognized by anti-HER2 antibodies and Δ16HER2, a splice variant lacking the ECD encoded by exon 16, which leads to stabilization of homo dimers and constitutive activation of downstream signaling.

There are no specific HER2 breast cancer symptoms, but HER2 breast tumors share similar symptoms with other breast cancer types. However, it is important to remember that many people show no symptoms when breast cancer is first diagnosed, which is why breast awareness and attending regular mammograms after age 50 is essential. For all breast cancers, including HER2 positive breast cancer, symptoms may include New lump/s or thickening in the breast, especially if only in one breast, changes in the shape or appearance of the nipple, including turning-in or inversion of the nipple, crusting sores and redness.

The definition of HER2 positivity according to American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) guidelines, includes tumours that have 3+ positive staining by immunohistochemistry (IHC) in ≥10% of tumour cells, or HER2 gene amplification detected by fluorescence in situ hybridization (FISH)15,16 (Box 2). Recent research has identified a subset of patients with ‘HER2-low’ (HER2low) BC that is responsive to novel HER2-targeted ADCs. HER2low is defined as HER2 IHC 1+ by itself or 2+ in the absence of HER2 gene amplification by ISH (in situ hybridization). The cut-off for the level of HER2 expression by IHC is only a crude estimation of those who may actually benefit from anti-HER2 therapies. With the introduction of the new HER2low definition, additional diagnostic tools may need to be considered. There are several tests used to find out if breast cancer is HER2-positive. Two of the most common tests are IHC test and Fluorescence in Situ Hybridization test.

Since HER2-positive breast cancer is dependent on HER2 gene amplification or overexpression, researchers wanted a way to stop the HER2 protein from exerting its effect on the breast cancer cells. The introduction of anti-HER2 therapies to the treatment of patients with HER2-positive breast cancer has led to dramatic improvements in survival in both early and advanced settings. Despite this breakthrough, nearly all patients with metastatic HER2-positive breast cancer eventually progress on anti-HER2 therapy due to de novo or acquired resistance. A better understanding not only of the underlying mechanisms of HER2 therapy resistance but of tumor heterogeneity as well as the host and tumor microenvironment is essential for the development of new strategies to further improve patient outcomes. One strategy has focused on inhibiting the HER2 signaling pathway more effectively with dual-blockade approaches and developing improved anti-HER2 therapies like antibody-drug conjugates, new anti-HER2 antibodies, bispecific antibodies, or novel tyrosine kinase inhibitors that might replace or be used in addition to some of the current anti-HER2 treatments. Combinations of anti-HER2 therapy with other agents like immune checkpoint inhibitors, CDK4/6 inhibitors, and PI3K/AKT/mTOR inhibitors are also being extensively evaluated in clinical trials.

Report Highlights

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

HER2 Positive Breast Cancer Emerging Drugs Chapters

This segment of the HER2 Positive Breast Cancer report encloses its detailed analysis of various drugs in different stages of clinical development, including phase 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.

HER2 Positive Breast Cancer Emerging Drugs

SHR-A1811: Jiangsu HengRui Medicine Co., Ltd.

SHR-A1811 is an innovative HER2-targeted antibody-drug conjugate with a topoisomerase I payload conjugated to an anti-HER-2 mAb by a cleavable linker. Once bound to HER2 expressing tumor cells, the ADC is internalized and the linker releases the toxin, leading to tumor cell death. It can bind to the cell membrane surface of HER2 expressing cells, and then enter the cells to reach the lysosome to release small Molecular toxins eventually induce tumor cell apoptosis, combining the high targeting of antibodies and the powerful killing power of cytotoxic drugs on target cells.

Preclinical research results show that SHR-A1811 has good anti-tumor activity, safety, tolerability and pharmacokinetic characteristics, or can further improve drug resistance, enhance efficacy, meet clinical needs, and provide more cancer patients multiple choice. Currently, the drug is in the Phase III stage of its development for the treatment of

HER2 Positive Breast Cancer.

HLX11: Shanghai Henlius Biotech

HLX11 is a pertuzumab biosimilar developed by Henlius independently in line with relevant regulations and guidelines on biosimilars in China and the European Union (EU), which can be potentially used in combination with trastuzumab and chemotherapy as neoadjuvant or adjuvant treatment for HER2-positive early breast cancer and in combination with trastuzumab and docetaxel in patients with HER2-positive metastatic or unresectable locally recurrent breast cancer patients. HLX11 can specifically bind with the subdomain II of HER2 extracellular domain and inhibit the heterodimerisation of HER2 and other HER family receptors, i.e., EGFR, HER3, and HER4. This will inhibit signal transduction of relevant pathways and lead to the stop of growth and apoptosis of tumour cells. In the meantime, HLX11 can also enhance the tumour-killing activity of immune cells via antibody-dependent cell cytotoxicity. Currently, the drug is in the Phase III stage of its development for the treatment of HER2 Positive Breast Cancer.

MCLA-128: Merus N.V.

MCLA-128 is an antibody-dependent cell-mediated cytotoxicity (ADCC) -enhanced Biclonics® that utilizes Merus Dock & Block® mechanism and inhibits the neuregulin/HER3 tumor-signaling pathway in solid tumors. MCLA-128 is believed to target the HER3 signaling pathway and to overcome the resistance of tumor cells to HER2-targeted therapies using two mechanisms: blocking growth and survival pathways to stop tumor expansion and recruitment and enhancement of immune effector cells to eliminate the tumor. The therapeutic candidate is a full-length IgG bi-specific antibody that acts by targeting HER2 and HER3. It is an antibody-dependent cellular cytotoxicity (ADCC)-enhanced Biclonic, which is developed based on Biclonics ENGAGE platform. Currently the drug is in the Phase II stage of clinical trial evaluation for the treatment of HER2-positive metastatic breast cancer.

GQ1001: GeneQuantum

GQ1001 is a novel HER2-targeted antibody-drug conjugate (ADC) that was developed using innovative conjugation technologies coined intelligent Ligase-Dependent Conjugation (iLDC), that can significantly improves homogeneity and biostability of ADC. In preclinical studies, GQ1001 showed a robust anti-tumor response in multiple HER2+ models alone or in combination with HER2 TKIs and chemotherapeutics, and excellent pharmacokinetics and safety profiles in rats and monkeys due to low level of payload release. GQ1001 has already received Clinical Trial approval from the Therapeutic Goods Administration (TGA) in Australia and IND from FDA in USA. Currently the drug is in the Phase I stage of clinical trial evaluation for the treatment of HER2-positive metastatic breast cancer.

HER2 Positive Breast Cancer: Therapeutic Assessment

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

Major Players in HER2 Positive Breast Cancer

• There are approx. 60+ key companies which are developing the therapies for HER2 Positive Breast Cancer. The companies which have their HER2 Positive Breast Cancer drug candidates in the most advanced stage, i.e. phase III include, Jiangsu HengRui Medicine Co., Ltd.

Phases

DelveInsight’s report covers around 65+ 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

HER2 Positive 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.

HER2 Positive Breast Cancer: Pipeline Development Activities

The report provides insights into different therapeutic candidates in phase II, I, preclinical and discovery stage. It also analyses HER2 Positive 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 HER2 Positive Breast Cancer drugs.

HER2 Positive Breast Cancer Report Insights

• HER2 Positive Breast Cancer Pipeline Analysis
• Therapeutic Assessment
• Unmet Needs
• Impact of Drugs

HER2 Positive 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 HER2 Positive Breast Cancer drugs?
• How many HER2 Positive 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 HER2 Positive Breast Cancer?
• What are the key collaborations (Industry-Industry, Industry-Academia), Mergers and acquisitions, licensing activities related to the HER2 Positive 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 HER2 Positive Breast Cancer and their status?
• What are the key designations that have been granted to the emerging drugs?

Key Players

• Byondis
• Tanvex Biopharma
• Prestige BioPharma
• EirGenix
• AMbrx
• CSPC ZhongQi Pharmaceutical Technology Co., Ltd. 
• Roche
• Jiangsu Alphamab Oncology Co., Ltd.
• Jiangsu HengRui Medicine Co., Ltd.
• RemeGen
• Shanghai Henlius Biotech
• Merus N.V.
• Hangzhou DAC Biotech
• Lepu Biopharma
• Zymeworks
• Klus Pharma Inc.
• Bolt Biotherapeutics
• GeneQuantum Healthcare
• ALX Oncology
• Precirix
• BriaCell Therapeutics Corporation
• Bliss Biopharmaceutical
• BioInvent International
• Incyte Corporation
• Triumvira Immunologics, Inc.
• Horizon Therapeutics

Key Products

• SYD-985
• TX-05
• HD201
• EG-12014
• ARX788
• DP303c
• Inavolisib
• KN026
• SHR-A1811
• RC48-ADC
• HLX11
• MCLA-128
• DX126 262
• MRG002
• Zanidatamab
• A166
• BDC 1001
• GQ1001
• ALX-148
• CAM-H2
• SV-BR-1-GM
• BB-1701
• BI-1607
• Ruxolitinib
• TAC01-HER2
• Interferon-gamma

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