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Breast cancer is a heterogeneous disease, encompassing various subtypes defined by distinct molecular profiles, behaviors, and responses to treatment. This diversity has led to a complex treatment landscape, with companies adopting different approaches and targets to tackle breast cancer.
Approximately 75% of breast cancers are estrogen receptor-positive (ER+), meaning the tumor cells rely on estrogen for growth. Often co-expressed with ER, progesterone receptor (PR) positivity signals a functional estrogen signaling pathway and provides additional prognostic information that can influence treatment decisions. These cancers, collectively referred to as hormone receptor-positive (HR+), are typically responsive to endocrine therapies.
Additionally, about 25% of breast cancers overexpress the human epidermal growth factor receptor 2 (HER2), a protein that promotes aggressive tumor growth. HER2-positive (HER2+) cancers respond well to HER2-targeted therapies like trastuzumab. Conversely, tumors that lack HER2 overexpression (HER2-negative, HER2-) may not benefit from these treatments but can often be managed with alternative therapeutic strategies.
Breast cancer subtypes are typically categorized by their combinations of HR+ or HR- and HER2+ or HER2-, making molecular profiling essential for tailoring effective treatment. In this article, we take a look at eight biotech companies developing new therapies for breast cancer.
Table of contents
Arvinas
- Lead candidate in breast cancer: ARV-471 in phase 2 clinical trials
- Technology: PROTAC (proteolysis targeting chimera)
- Recent news: $350 million fundraise
Arvinas, headquartered in New Haven, Connecticut, is a public biotech company specializing in the development of therapies based on targeted protein degradation. Arvinas utilizes its proprietary PROTAC (proteolysis targeting chimera) technology, which represents a novel approach to tackling disease-causing proteins.
Traditional drugs typically work by inhibiting the activity of a target protein, but this approach can leave the problematic protein intact. PROTACs, on the other hand, are small molecules designed to guide unwanted proteins to the cell’s natural disposal system, the proteasome. They achieve this by forming a “bridge” between the target protein and an E3 ubiquitin ligase, an enzyme responsible for tagging proteins with ubiquitin, marking them for degradation. This process effectively removes the harmful protein entirely, rather than just blocking its function, potentially leading to more durable therapeutic effects.
ARV-471 is Arvinas’ lead candidate for the treatment of ER+ breast cancer. It is an oral PROTAC protein degrader designed to specifically target and degrade the estrogen receptor, aiming to overcome resistance mechanisms associated with current therapies.
Arvinas has established a global collaboration with Pfizer to develop and commercialize ARV-471. This partnership aims to position ARV-471 as a leading endocrine therapy across the breast cancer treatment spectrum.
ARV-471 is currently undergoing phase 2 clinical trials. A year ago, Arvinas and Pfizer announced interim data from a phase 1b trial evaluating ARV-471 in combination with palbociclib, showing promising results in patients with ER+/HER2- metastatic breast cancer.
Last November, Arvinas completed a $350 million fundraise, securing financial resources to support its operations and clinical development programs through at least 2027.
BioNTech
- Lead candidate in breast cancer: BNT323 in phase 3
- Technology: ADC
- Recent news: FDA hold lifted for another cancer candidate, BNT326/YL202
Based in Mainz, Germany, BioNtech is a public biotech specializing in the development of immunotherapies for cancer and infectious diseases.
BioNTech employs a diverse array of platforms, including mRNA-based therapies, engineered cell therapies, antibodies, and small molecule immunomodulators, to create individualized treatment options.
BNT323 is an antibody-drug conjugate (ADC) targeting HER2-expressing cancers, including HER2-low metastatic breast cancer. ADCs combine the specificity of monoclonal antibodies with the potency of chemotherapy. In the case of BNT323, the monoclonal antibody binds selectively to the HER2 protein on cancer cells, acting as a delivery vehicle for the cytotoxic agent. Once the ADC is internalized by the cancer cell, the cytotoxic payload is released, disrupting the cell’s function and leading to its death.
BioNTech is collaborating with DualityBio to advance the development of BNT323. The two companies initiated a pivotal phase 3 trial in early 2024 to assess the efficacy and safety of BNT323 in patients with hormone receptor-positive (HR+) and HER2-low metastatic breast cancer progressing on hormone therapy.
Besides BNT323, in August 2024, the U.S. Food and Drug Administration (FDA) lifted a partial hold on an early-stage trial of another BioNTech’s experimental cancer drug, BNT326/YL202, an ADC targeting HER3-expressing tumors. BioNTech has multiple assets in breast cancer, and with the FDA lifting the hold on BTN326/YL202, BioNTech can proceed with further trials.
Carrick Therapeutics
- Lead candidate in breast cancer: Samuraciclib (CT7001) in phase 2
- Technology: Oral cyclin-dependent kinase 7 (CDK7) inhibitor
- Recent news: Clinical trial collaboration with Pfizer and Arvinas
Carrick Therapeutics, headquartered in Dublin, Ireland, is a private biotech specializing in the development of cancer therapies, including breast cancer.
The company focuses on targeting key mechanisms that drive aggressive and resistant forms of cancer. Its lead candidate, samuraciclib (CT7001), is an oral cyclin-dependent kinase 7 (CDK7) inhibitor. CDK7 is a key regulator of the cell cycle, which controls the process of cell growth and division. In many cancers, including HR+, HER2-negative breast cancer, dysregulated CDK7 activity contributes to uncontrolled tumor growth and resistance to existing endocrine therapies. By inhibiting CDK7, samuraciclib aims to halt cancer cell proliferation and restore sensitivity to hormone therapies, offering a potential solution for patients who have progressed on standard treatments.
CT7001 is in phase 2b clinical trials and the first patient was dosed in December 2023. A year before, In December 2022, Carrick announced a $35 million investment from Pfizer to support the rapid development of samuraciclib in HR+, HER2-negative breast cancer. This collaboration includes Pfizer providing global development capabilities and expertise to support Carrick’s phase 2 study of samuraciclib in combination with fulvestrant for CDK4/6 inhibitor-resistant HR+, HER2-negative advanced breast cancer.
In December 2022, Carrick closed a $25 million series C financing round. Combined with Pfizer’s $35 million investment, Carrick raised a total of $60 million to advance its oncology pipeline that year.
Recently, the company announced a clinical trial collaboration and supply agreement with Arvinas and Pfizer to evaluate the combination of samuraciclib and vepdegestrant (ARV-471) that we mentioned earlier, in patients with ER+/HER2- advanced breast cancer.
Context Therapeutics
- Lead candidate in breast cancer: ONA-XR in phase 1/2
- Technology: selective antagonist of the progesterone receptor
- Recent news: $100 million private placement funding
Context Therapeutics, headquartered in Philadelphia, Pennsylvania, develops treatments for hormone-driven cancers, with a particular focus on breast cancer.
The company’s lead candidate, onapristone extended release (ONA-XR), is an orally administered, selective antagonist of the progesterone receptor (PR), which plays a key role in the progression of certain hormone-driven cancers such as breast cancer. The PR is a transcription factor activated by progesterone, a hormone that can promote the growth and survival of cancer cells in HR+, HER2-negative breast cancer.
ONA-XR works by binding to the PR and preventing its activation, thereby blocking tumor growth and survival. ONA-XR is currently being evaluated in multiple clinical trials. Context Therapeutics is conducting phase 2 studies to assess the efficacy of ONA-XR in combination with other therapies for HR+, HER2-negative breast cancer. The drug is also in phase 1/2 in combination elacestrant (ORSERDU) in patients with advanced or metastatic ER+, PR+, HER2-negative breast cancer.
In May 2024, Context Therapeutics announced the completion of a $100 million private placement financing. The proceeds are expected to extend the company’s cash runway into 2028, supporting the ongoing development of ONA-XR and other pipeline programs.
Hummingbird Bioscience
- Lead candidate in breast cancer: HMBD-001 in phase 1/2
- Technology: monoclonal antibody
- Recent news: Positive phase 1 data
Hummingbird Bioscience, based in Singapore and Houston, Texas, is a clinical-stage biotechnology company.
The company’s lead candidate, HMBD-001, is a monoclonal antibody specifically designed to target human epidermal growth factor receptor 3 (HER3) – HER3 is often overexpressed or activated in various cancers, including breast cancer, where it contributes to resistance to standard therapies and supports tumor growth and survival.
Unlike other HER3-targeting therapies, HMBD-001 binds to a unique epitope on HER3, effectively locking the receptor in an inactive state. This prevents its activation by neuregulin-1 (NRG1), the natural ligand of HER3, and disrupts pathways critical for cancer cell proliferation and survival.
HMBD-001 is currently in phase 1/2 clinical trials for HER3-positive cancer. In October 2023, the company reported that HMBD-001 was safe and well-tolerated, with a disease control rate of 43% among evaluable patients.
Hummingbird Bioscience’s latest funding round was a $125 million series C round led by Novo Holding in 2021.
Oncolytics Biotech
- Lead candidate in breast cancer: Pelareorep in phase 2 clinical trial
- Technology: immuno-oncolytic virus
- Recent news: Favorable trial data
Based in Calgary, Canada, Oncolytics Biotech is a clinical-stage biotechnology company specializing in the development of immuno-oncolytic viruses for cancer treatment, including breast cancer. The company’s lead candidate, pelareorep, is an intravenously delivered immuno-oncolytic virus derived from the naturally occurring, unmodified reovirus.
Pelareorep exploits a key vulnerability in cancer cells: many tumors lack the ability to defend against viral infections due to defective antiviral signaling pathways. The virus selectively infects and replicates within these cancer cells, causing them to burst and die. This process releases tumor-associated antigens into the microenvironment, effectively “flagging” the cancer cells for recognition by the immune system.
In addition to directly killing tumor cells, pelareorep stimulates an anti-tumor immune response by activating dendritic cells and T-cells, helping the body recognize and attack cancer more effectively.
Pelareorep is currently being evaluated in multiple clinical trials. The BRACELET-1 trial is a phase 2 study assessing pelareorep in combination with paclitaxel in patients with hormone receptor-positive (HR+), HER2-negative metastatic breast cancer. Interim results have shown promising improvements in overall response rates and progression-free survival.
The AWARE-1 trial is evaluating pelareorep in combination with letrozole and trastuzumab in early-stage HR+/HER2- breast cancer patients. The trial aims to assess the virus’s ability to remodel the tumor microenvironment and enhance anti-tumor immunity.
In September 2024, Oncolytics Biotech announced favorable results from the BRACELET-1 study, reinforcing the path to funding a registration-enabling study for pelareorep in metastatic breast cancer. The company is moving forward to secure funding for this pivotal trial.
Olema Pharmaceuticals
- Lead candidate in breast cancer: OP-1250
- Technology: small molecule
- Recent news: New data presented at ESMO Breast Cancer Annual Congress
This company, headquartered in San Francisco, California, is dedicated to developing targeted therapies for women’s cancers, with a primary focus on breast cancer.
Olema’s lead candidate, OP-1250, is an orally available small molecule that functions as both a complete estrogen receptor antagonist (CERAN) and a selective estrogen receptor degrader. This dual mechanism is designed to inhibit and degrade the estrogen receptor, aiming to effectively block estrogen signaling pathways that drive the growth of ER-positive, HER2-negative breast cancer cells.
OP-1250 is currently undergoing phase 1/2 clinical trials. In May 2023, Olema shared favorable interim clinical data demonstrating that OP-1250 exhibited favorable pharmacokinetics, tolerability, and preliminary anti-tumor activity in patients with recurrent, locally advanced, or metastatic ER-positive, HER2-negative breast cancer.
This year, Olema presented promising new data on OP-1250 at the European Society for Medical Oncology (ESMO) Breast Cancer Annual Congress, showing its potential as a monotherapy and in combination with other agents for the treatment of ER-positive, HER2-negative breast cancer.
Relay Therapeutics
- Lead candidate in breast cancer: RLY-2608 in phase 2
- Technology: PI3Kα inhibitor
- Recent news: Clinical trial collaboration with Pfizer
Relay Therapeutics, headquartered in Cambridge, Massachusetts, specializes in precision medicine through the integration of computational technologies.
The company’s lead candidate in breast cancer, RLY-2608, is a selective inhibitor of mutant phosphoinositide 3-kinase alpha (PI3Kα), a critical enzyme involved in cancer cell growth and survival. Mutations in the PIK3CA gene, which encodes the PI3Kα enzyme, are among the most common genetic alterations in HR+, HER2-negative metastatic breast cancer. These mutations lead to hyperactivation of the PI3K pathway, driving tumor proliferation and resistance to standard therapies.
RLY-2608 is designed to specifically target and inhibit only the mutant form of PI3Kα, sparing the normal enzyme. This selectivity minimizes off-target effects, potentially reducing toxicity while delivering treatment for patients with PIK3CA-mutated breast cancer.
In September 2024, Relay Therapeutics reported interim data of RLY-2608’s phase 2 trials in combination with fulvestrant demonstrating a median progression-free survival of 9.2 months in heavily pre-treated patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer. The company plans to initiate phase 3 clinical trials in 2025.
Moreover, RLY-2608 is being explored in combination with Novartis’ CDK4/6 inhibitor ribociclib in addition to fulvestrant. This triplet combination is on track to initiate clinical trials by the end of 2024 according to the company. The company has also announced a clinical trial collaboration with Pfizer to test a similar combination with the investigational CDK4 inhibitor, atirmociclib.
Breast cancer treatment: A diverse, established market
Breast cancer treatment has seen remarkable advancements over the years, with several therapies now forming the cornerstone of care. Targeted treatments like trastuzumab (Herceptin), developed by Roche, have transformed outcomes for patients with HER2-positive breast cancer. Similarly, Pfizer’s palbociclib (Ibrance), a CDK4/6 inhibitor, has become a standard for managing HR+, HER2-negative advanced breast cancer.
Meanwhile, AstraZeneca’s olaparib (Lynparza), a poly ADP-ribose polymerase (PARP) inhibitor, offers an option for patients with inherited breast cancer gene (BRCA) gene mutations. These mutations impair the ability of cancer cells to repair their DNA, and olaparib takes advantage of this weakness by further blocking DNA repair mechanisms.
Despite these achievements, significant challenges remain. Resistance to endocrine, targeted, and chemotherapy continues to limit long-term efficacy for many patients. Additionally, triple-negative breast cancer (TNBC) remains a critical unmet need due to the lack of hormone or HER2 targets, making it a more aggressive and difficult-to-treat subtype.
While there are already several FDA-approved treatments for breast cancer, the molecular profile diversity of the disease calls for research to keep progressing and bring new solutions to market.
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