NRG融合 - 競争情勢（2025年）

レポートのハイライト

• 2024年12月、米国FDAは成人に対するzenocutuzumab-zbco（商品名、Bizengri）について、全身療法前または全身療法後に病勢進行した、ニューレグリン1遺伝子融合を有する切除不能または転移性の進行性非小細胞肺がん、または全身療法前または全身療法後に病勢進行した、ニューレグリン1遺伝子融合を有する切除不能または転移性の進行性膵臓腺がんを適応症とする早期承認を与えました。
• 2024年12月、Merus N.V.とPartner Therapeutics, Inc.は、NRG1融合遺伝子陽性（NRG1+）がん治療薬zenocutuzumab（Zeno）の米国における商業化権をMerusがPTxに独占的にライセンスする契約を締結したと発表しました。
• 2024年11月、FDAは、NRG1陽性非小細胞肺がん（NSCLC）と膵臓がん患者の治療におけるzenocutuzumab（MCLA-128）の承認を求める生物製剤承認申請（BLA）のPrescription Drug User Fee Act（PDUFA）に基づく目標措置期日を延長しました。新しいPDUFA目標実施日は2025年2月4日です。
• 2024年5月、Merus N.V.は、米国食品医薬品局（FDA）が、NRG1融合遺伝子陽性の非小細胞肺がん（NSCLC）と膵管腺がん（PDAC）患者の治療薬として、zenocutuzumabの生物製剤承認申請（BLA）に優先審査を付与し、BLA申請を受理したと発表しました。

当レポートでは、NRG融合の競合情勢について調査分析し、企業と医薬品の包括的な考察を提供しています。また、製品タイプ、段階、投与経路、分子タイプごとに治療薬を評価し、休止中のパイプライン製品も取り上げています。

目次

イントロダクション

エグゼクティブサマリー

NRG融合：概要

• イントロダクション
• NRG1の構造と機能
• NRG1を介したシグナル伝達
• NRG1タンパク質の受容体
• 臨床的意義

NRG融合 - 分析的視点：徹底的な商業の評価

• NRG融合の提携の分析：企業別

競合情勢

• 企業の比較評価：治療法別、開発段階別、技術別

治療薬の評価

• 評価：製品タイプ別
• 評価：段階別、製品タイプ別
• 評価：投与経路別
• 評価：段階別、投与経路別
• 評価：分子タイプ別
• 評価：段階別、分子タイプ別

NRG融合：企業と製品のプロファイル（上市済みの治療薬）

Merus

• 企業の概要

BIZENGRI（R）

• 製品の説明
• 研究開発活動
• 製品開発活動

NRG融合：企業と製品のプロファイル（パイプライン治療薬）

後期段階の製品（フェーズIII）

• 比較分析

中期段階の製品（フェーズII）

• 比較分析

初期段階の製品（フェーズI/II）

• 比較分析

Hummingbird Bioscience

• 企業の概要

HMBD-001

• 製品の説明
• 研究開発活動
• 製品開発活動

前臨床・創薬段階の製品

• 比較分析

休止中の製品

• 比較分析

NRG融合 - アンメットニーズ

NRG融合 - 市場の促進要因と障壁

List of Tables

• Table 1 Total Products for NRG Fusion
• Table 2 Late Stage Products
• Table 3 Mid Stage Products
• Table 4 Early Stage Products
• Table 5 Pre-clinical & Discovery Stage Products
• Table 6 Assessment by Product Type
• Table 7 Assessment by Stage and Product Type
• Table 8 Assessment by Route of Administration
• Table 9 Assessment by Stage and Route of Administration
• Table 10 Assessment by Molecule Type
• Table 11 Assessment by Stage and Molecule Type
• Table 12 Inactive Products

List of Figures

• Figure 1 Total Products for NRG Fusion
• Figure 2 Late Stage Products
• Figure 3 Mid Stage Products
• Figure 4 Early Stage Products
• Figure 5 Preclinical and Discovery Stage Products
• Figure 6 Assessment by Product Type
• Figure 7 Assessment by Stage and Product Type
• Figure 8 Assessment by Route of Administration
• Figure 9 Assessment by Stage and Route of Administration
• Figure 10 Assessment by Molecule Type
• Figure 11 Assessment by Stage and Molecule Type
• Figure 12 Inactive Products

DelveInsight's, "NRG Fusion - Competitive landscape, 2025," report provides comprehensive insights about 3+ companies and 3+ drugs in NRG Fusion Competitive landscape. It 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

NRG Fusion: Understanding

NRG Fusion: Overview

NRG1 Fusion is a genetic rearrangement involving the NRG1 gene, where it fuses with another gene, leading to the production of abnormal proteins that can drive tumor growth. These fusions activate the ERBB2/ERBB3 (HER2/HER3) signaling pathway, promoting cancer cell proliferation and survival. NRG1 fusions are rare but have been identified in various cancers, including Non-small cell lung cancer (NSCLC), Pancreatic cancer, Breast cancer, Colorectal cancer. NRG1 fusions are considered actionable mutations because they respond to targeted therapies such as HER2/HER3 inhibitors (e.g., afatinib, neratinib).

Neuregulin 1 (NRG1), also referred to as ARIA, HRG, GGF, or NDF, is a 44 kDa protein belonging to the epidermal growth factor (EGF) family. The NRG1 protein comprises several structural features, including an intracellular region, a transmembrane segment, a proximal membrane sequence, an extracellular EGF-like domain, an immunoglobulin-like domain, and specific amino acid sequences. The NRG1 gene has four main isoforms, designated as Type I through Type VI NRG1. All isoforms share two EGF-like domains, a and B, with the EGF-like receptor-binding domain located near the extracellular domain's proximal region, essential for activating ERBB receptor tyrosine kinases.

NRG1 is predominantly expressed in glial cells and neurons, as well as in organs like the mammary gland, heart, lungs, kidneys, and liver. It plays a vital role in the development of the nervous system, heart, and mammary tissue. Notably, NRG1B is highly expressed in the nervous system and cardiomyocytes, whereas NRG1a is more prevalent in mammary glands. Increasing evidence indicates that NRG1 fusions are strongly linked to the progression of various cancers.

NRG1 activates multiple intracellular signaling pathways, including ERK, PI3K/AKT, MAPK, PKC, and JAK-STAT, through interactions with ERBB receptors. This signaling cascade regulates cell proliferation, differentiation, and anti-apoptotic processes. In Schwann cells, NRG1 binds ERBB3/ERBB2 heterodimers, triggering pathways like Ras-ERK, PI3K/AKT, and PKC/NFAT, which influence cell survival, proliferation, migration, and differentiation.

NRG1 plays a critical role in neurological and cardiac functions, with abnormal expression and fusions linked to related disorders. The NRG1 fusion antibody drug JK07, developed by Salubris, is in Phase II clinical trials for chronic heart failure. While antibody drugs are expanding into non-traditional areas like cardiovascular and neurological diseases, no anti-NRG1 antibodies are currently in clinical development, presenting significant market potential. NRG1 fusions, although rare oncogenic drivers, have become a focus for targeted therapies. Zenocutuzumab (MCLA-128), a bispecific antibody, has shown promising results in pancreatic cancer patients with NRG1 fusions and received FDA Fast Track designation. With increasing research on NRG1 mechanisms, the development of NRG1-targeted therapies offers a promising future, especially in China, where the antibody drug market is rapidly growing.

Report Highlights:

• In December 2024, The US FDA granted accelerated approval to zenocutuzumab-zbco (brand name Bizengri) for adults with the following advanced, unresectable, or metastatic non-small cell lung cancer harboring a neuregulin 1 gene fusion with disease progression on or after prior systemic therapy, or advanced, unresectable, or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 gene fusion with disease progression on or after prior systemic therapy.
• In December 2024, Merus N.V. and Partner Therapeutics, Inc. announced they had entered into an agreement in which Merus has exclusively licensed to PTx the right to commercialize zenocutuzumab (Zeno) for the treatment of NRG1 fusion-positive (NRG1+) cancer in the United States (U.S.).
• In November 2024, The FDA has extended the target action date under the Prescription Drug User Fee Act (PDUFA) for the biologics license application (BLA) seeking the approval of zenocutuzumab (MCLA-128) in the treatment of patients with NRG1-positive non-small cell lung cancer (NSCLC) and pancreatic cancer. The new PDUFA target action date is February 4, 2025.
• In May 2024, Merus N.V. announced that the U.S. Food and Drug Administration (FDA) had granted Priority review to a biologics license application (BLA) and accepted the BLA application for zenocutuzumab as a treatment for patients with NRG1 fusion-positive non-small cell lung cancer (NSCLC) and pancreatic ductal adenocarcinoma (PDAC).

NRG Fusion: Company and Product Profiles (Marketed Therapies)

1. Company Overview: Merus

Merus is a clinical-stage oncology company developing innovative full-length human bispecific and trispecific antibody therapeutics, referred to as Multiclonics(R). Multiclonics(R) are manufactured using industry standard processes and have been observed in preclinical and clinical studies to have several of the same features of conventional human monoclonal antibodies, such as long half-life and low immunogenicity

Product Description: OPZELURA

Zeno is an antibody-dependent cell-mediated cytotoxicity (ADCC)-enhanced Biclonics(R) that utilizes the Merus Dock & Block(R) mechanism to inhibit the neuregulin/HER3 tumor-signaling pathway in solid tumors with NRG1 fusions (NRG1+ cancer). Through its unique mechanism of binding to HER2 and potently blocking the interaction of HER3 with its ligand NRG1 or NRG1-fusion proteins, Zeno has the potential to be particularly effective against NRG1+ cancer. In preclinical studies, Zeno potently inhibits HER2/HER3 heterodimer formation thereby inhibiting oncogenic signaling pathways, leading to inhibition of tumor cell proliferation and blocking tumor cell survival. The drug was granted accelerated approval by US FDA for the treatment of adults with advanced unresectable or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.

NRG Fusion: Company and Product Profiles (Pipeline Therapies)

1. Company Overview: Hummingbird Bioscience

Hummingbird Bioscience is a precision bio therapeutics company discovering and developing transformative biologics for hard-to-treat diseases. To address key challenges with current antibody-drug conjugate (ADC) therapies, Hummingbird Bioscience is building a pipeline of next-generation ADCs using its proprietary antibody discovery and linker/payload platforms. The company approach combines computational and systems biology with wet lab drug discovery in a multi-disciplinary, collaborative environment spanning initial discovery through clinical development. The company harnesses this integrated approach across target identification and patient selection, enabling the team to increase the efficiency of translating novel scientific insights while reducing the inherent risk in drug discovery and development.

Product Description: HMBD-001

HMBD-001 is an IgG1 antibody designed to target HER3, discovered using Hummingbird Bioscience's proprietary Rational Antibody Discovery (RAD) platform. The company believe HMBD-001 is the only anti-HER3 antibody in development that has the potential to fully block both ligand-dependent and -independent HER3 activation and oncogenic signaling, by targeting a key epitope located at the interface where HER3 forms heterodimers with HER2 or EGFR. In preclinical models evaluating HMBD-001, superior affinity and more potent tumor growth inhibition compared to existing anti-HER3 antibodies were observed. Currently the drug is in Phase I/II stage of its development for the treatment of sqNSCLC and mCRPC.

NRG Fusion Analytical Perspective by DelveInsight

• In-depth Commercial Assessment: NRG Fusion Collaboration Analysis by Companies

The Report provides in-depth commercial assessment of drugs that have been included, which comprises collaboration, agreement, licensing and acquisition - deals values trends. The sub-segmentation is described in the report which provide company-company collaboration (licensing/partnering), company academic collaboration and acquisition analysis in tabulated form.

• NRG Fusion Competitive Landscape

The report comprises of comparative assessment of Companies (by therapy, development stage, and technology).

NRG Fusion Report Assessment

• Company Analysis
• Therapeutic Assessment
• Pipeline Assessment
• Inactive drugs assessment
• Unmet Needs

Key Questions:

Current Treatment Scenario and Emerging Therapies:

• How many companies are developing NRG Fusion drugs?
• How many NRG Fusion drugs are developed by each company?
• How many emerging drugs are in mid-stage, and late-stage of development for the treatment of NRG Fusion?
• What are the key collaborations (Industry-Industry, Industry-Academia), Mergers and acquisitions, licensing activities related to the NRG Fusion 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 NRG Fusion and their status?
• What are the key designations that have been granted to the emerging and approved drugs?

Key Players

• Zensun (Shanghai) Sci & Tech
• Salubris Biotherapeutics Inc
• Hummingbird Bioscience
• Minerva Neurosciences

Key Products

• Neucardin
• JK07
• HMBD-001
• MIN-301

Table of Contents

Introduction

Executive Summary

NRG Fusion: Overview

• Introduction
• Structure and Function of NRG1s
• NRG1-Mediated Signal Transduction
• Receptors for NRG1 Protein
• Clinical Significance

NRG Fusion -Analytical Perspective: In-depth Commercial Assessment

• NRG Fusion Collaboration Analysis by Companies

Competitive Landscape

• Comparative Assessment of Companies (by therapy, development stage, and technology)

Therapeutic Assessment

• Assessment by Product Type
• Assessment by Stage and Product Type
• Assessment by Route of Administration
• Assessment by Stage and Route of Administration
• Assessment by Molecule Type
• Assessment by Stage and Molecule Type

NRG Fusion: Company and Product Profiles (Marketed Therapies)

Merus

• Company Overview

BIZENGRI(R)

• Product Description
• Research and Development Activities
• Product Developmental Activities

NRG Fusion: Company and Product Profiles (Pipeline Therapies)

Late Stage Products (Phase III)

• Comparative Analysis

Company Name

• Company Overview

Drug Name

• Product Description
• Research and Development Activities
• Product Developmental Activities

Mid Stage Products (Phase II)

• Comparative Analysis

Company Name

• Company Overview

Drug Name

• Product Description
• Research and Development Activities
• Product Developmental Activities

Early Stage Products (Phase I/II)

• Comparative Analysis

Hummingbird Bioscience

• Company Overview

HMBD-001

• Product Description
• Research and Development Activities
• Product Developmental Activities

Preclinical and Discovery Stage Products

• Comparative Analysis

Company Name

• Company Overview

Product Name

• Product Description
• Research and Development Activities
• Product Developmental Activities

Inactive Products

• Comparative Analysis

NRG Fusion- Unmet needs

NRG Fusion - Market drivers and barriers