On June 6, 2025 Arvinas, Inc. (Nasdaq: ARVN), reported the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) with its partner Pfizer Inc. (NYSE: PFE), for vepdegestrant for the treatment of patients with ER-positive (ER+)/human epidermal growth factor receptor 2 (HER2)-negative (ER+/HER2-) ESR1-mutated advanced or metastatic breast cancer previously treated with endocrine-based therapy (Press release, Arvinas, JUN 6, 2025, View Source [SID1234653759]). This submission is based on results from VERITAC-2 (NCT05654623), a global, randomized Phase 3 trial evaluating vepdegestrant versus fulvestrant.

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"This milestone comes after an exciting presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s annual meeting," said John Houston, Ph.D., Chairperson, Chief Executive Officer and President at Arvinas. "We look forward to the NDA review and to the first ever FDA-approved PROTAC ER degrader potentially being available to patients who could benefit from a much needed, new treatment option."

Vepdegestrant is being jointly developed by Arvinas and Pfizer for the treatment of patients with advanced or metastatic ER+/HER2- breast cancer and was granted fast track designation as a monotherapy by the FDA. Results from the VERITAC-2 study were recently presented in a late-breaking oral presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2025 Annual Meeting and were selected for the ASCO (Free ASCO Whitepaper) press briefing and for Best of ASCO (Free ASCO Whitepaper). Detailed results were also simultaneously published in the New England Journal of Medicine.

About the VERITAC-2 Clinical Trial
The Phase 3 VERITAC-2 clinical trial (NCT05654623) is a global, randomized trial evaluating the efficacy and safety of vepdegestrant (ARV-471) as a monotherapy compared to fulvestrant in patients with ER+/HER2- advanced or metastatic breast cancer. The trial enrolled 624 patients at sites in 25 countries who had previously received treatment with a CDK4/6 inhibitor plus endocrine therapy.

Patients were randomized 1:1 to receive either vepdegestrant once daily, orally on a 28-day continuous dosing schedule, or fulvestrant, administered intramuscularly on Days 1 and 15 of Cycle 1 and then on Day 1 of each 28-day cycle starting from Day 1 of Cycle 2. In the trial, 43% of patients (n=270) had ESR1 mutations detected. The primary endpoint was progression-free survival (PFS) in the ESR1-mutation and intent-to-treat populations as determined by blinded independent central review. Overall survival is the key secondary endpoint.

About Vepdegestrant
Vepdegestrant is an investigational, orally bioavailable PROTAC (PROteolysis TArgeting Chimera) protein degrader designed to specifically target and degrade the estrogen receptor (ER). Vepdegestrant is being developed as a potential monotherapy for ER+/HER2- advanced or metastatic breast cancer with estrogen receptor 1 (ESR1) mutations in the second line-plus setting.

In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will share worldwide development costs, commercialization expenses, and profits.

The U.S. Food and Drug Administration (FDA) has granted vepdegestrant Fast Track designation as a monotherapy in the treatment of adults with ER+/HER2- advanced or metastatic breast cancer previously treated with endocrine-based therapy.

On June 6, 2025 AstraZeneca reported a fixed-duration regimen of Calquence (acalabrutinib) in combination with venetoclax, with or without obinutuzumab, has been approved in the European Union (EU) for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL) (Press release, AstraZeneca, JUN 6, 2025, View Source [SID1234653743]).

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The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and was based on positive results from the pivotal AMPLIFY Phase III trial, presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2024 Annual Meeting and published in The New England Journal of Medicine.1

Results from the AMPLIFY trial showed 77% of patients treated with Calquence plus venetoclax and 83% of patients treated with Calquence plus venetoclax and obinutuzumab were progression free at three years, versus 67% of patients treated with standard-of-care chemoimmunotherapy (investigator’s choice of fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab).1 Median progression-free survival (PFS) was not reached for either experimental arm versus 47.6 months for chemoimmunotherapy.1 Calquence plus venetoclax reduced the risk of disease progression or death by 35% compared to chemoimmunotherapy (hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.49-0.87; p=0.0038). Calquence plus venetoclax with obinutuzumab demonstrated a 58% reduction in the risk of disease progression or death compared to chemoimmunotherapy (HR 0.42; 95% CI 0.30-0.59; p<0.0001).2

CLL is the most common type of leukaemia in adults. An estimated 27,000 people were diagnosed with CLL in the UK, France, Germany, Spain and Italy in 2024.3

Barbara Eichhorst, MD, University Hospital Cologne, Cologne, Germany and investigator for the AMPLIFY trial, said: "For patients diagnosed with chronic lymphocytic leukaemia, this approval provides a new option in the first-line setting that may help to minimize long-term side effects and reduce drug resistance as they may occur with continuous treatment. A fixed-duration regimen is appealing to patients and helps with adherence during the treatment period."

Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: "Today’s approval brings a new fixed-duration treatment option to patients with previously untreated chronic lymphocytic leukaemia across Europe. Calquence plus venetoclax is the first and only all-oral combination treatment option with a second-generation BTK inhibitor approved in the EU and provides patients and their physicians more flexibility in managing this incurable blood cancer."

The safety and tolerability of Calquence was consistent with its known safety profile, and no new safety signals were identified.

Regulatory applications for these regimens are currently under review in several countries based on the AMPLIFY results.

Notes

Chronic lymphocytic leukaemia (CLL)
CLL is the most prevalent type of leukaemia in adults, with an estimated 40,000 people being treated for CLL in the first line in the US, UK, France, Germany, Spain, Italy, Japan and China in 2024.3 Although some people with CLL may not experience any symptoms at diagnosis, others may experience symptoms, such as weakness, fatigue, weight loss, chills, fever, night sweats, swollen lymph nodes and abdominal pain.4 In CLL, there is an accumulation of abnormal lymphocytes within the blood, bone marrow and lymph nodes. As the number of abnormal cells increases, there is less room within the marrow for the production of normal white blood cells, red blood cells and platelets.5 This could result in infection, anaemia and bleeding. B-cell receptor signalling through BTK is one of the essential growth pathways for CLL.

AMPLIFY
AMPLIFY is a randomised, global, multi-centre, open-label Phase III trial evaluating the efficacy and safety of Calquence in combination with venetoclax, with or without obinutuzumab, compared to investigator’s choice of chemoimmunotherapy (fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab) in adult patients with previously untreated CLL without del(17p) or TP53 mutation.6 Patients were randomised 1:1:1 to receive either Calquence plus venetoclax, or Calquence plus venetoclax with obinutuzumab for a fixed duration, or standard-of-care chemoimmunotherapy.6 Both the Calquence containing arms were administered for a fixed duration of 14 cycles (each 28 days), and the standard-of-care chemoimmunotherapy was for 6 cycles.6

The primary endpoint is PFS in the Calquence and venetoclax arm as assessed by an Independent Review Committee, and PFS in the Calquence plus venetoclax with obinutuzumab arm is a key secondary endpoint.6 Other key secondary endpoints include overall survival (OS) and undetectable measurable residual disease.6 The trial includes 27 countries across North and South America, Europe, Asia and Oceania.6

The AMPLIFY trial enrolled patients from 2019 to 2021, continuing through the COVID-19 pandemic.6

Calquence
Calquence (acalabrutinib) is a second-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.8 In B-cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.

Calquence is approved for the treatment of chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) in the US, Japan and China, and approved for CLL in the EU and many other countries. Calquence is also approved in combination with venetoclax, with or without obinutuzumab, as a fixed-duration treatment for CLL in the EU. Calquence is also approved for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) in the US, Europe and other countries. It is also approved for the treatment of adult patients with MCL who have received at least one prior therapy in China and several other countries. Calquence is not currently approved for the treatment of MCL in Japan.

As part of an extensive clinical development programme, Calquence is currently being evaluated as a single treatment and in combination with standard-of-care chemoimmunotherapy for patients with multiple B-cell blood cancers, including CLL, MCL and diffuse large B-cell lymphoma.

On June 5, 2025 Avenzo Therapeutics, Inc. ("Avenzo"), a clinical-stage biotechnology company developing next-generation oncology therapies, reported initiation of a Phase 1/2 clinical study of its potential best-in-class cyclin-dependent kinase 4 (CDK4) selective inhibitor, AVZO-023, in patients with advanced or metastatic hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer and select other advanced solid tumors (Press release, Avenzo Therapeutics, JUN 5, 2025, View Source [SID1234653735]).

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"CDK4 is a key driver in HR+/HER2- breast cancer, and selective inhibition has emerged as a promising strategy to improve efficacy and minimize toxicity," said Antonio Giordano, M.D., Ph.D., Clinical Director, Center for Cancer Therapeutic Innovation, Dana-Farber Cancer Institute. "Preclinically, AVZO-023 demonstrates best-in-class selectivity and potency, potentially enabling rational combinations with not only endocrine therapy but also CDK2 inhibitors to address emerging resistance."

The Phase 1/2 first-in-human, open-label clinical study is designed to assess the safety, tolerability, and preliminary clinical activity of AVZO-023 as a single agent and in combination with endocrine therapy and with AVZO-021, Avenzo’s potential best-in-class CDK2 inhibitor. AVZO-021 is currently being studied in HR+/HER2- metastatic breast cancer and other advanced solid tumors.

"We are excited to have initiated our third clinical trial – and our second study in a week – ahead of our anticipated timeline," said Mohammad Hirmand, M.D., Co-founder and Chief Medical Officer of Avenzo Therapeutics. "We look forward to investigating the potential of AVZO-023, including in combination with AVZO-021, as we believe AVZO-023 and AVZO-021 both have the potential to make a difference in the lives of patients with HR+/HER2- breast cancer."

On June 5, 2025 Signify Bio, a pioneering biotechnology company harnessing the human body for the production of in situ protein therapeutics, reported an oversubscribed $15 million initial financing (Press release, Signify Bio, JUN 5, 2025, View Source [SID1234653757]). The round was led by Actium Group with participation from the Gates Foundation Strategic Investment Fund, Danaher Ventures LLC, a subsidiary of Danaher Corporation, Eli Lilly and Company, and BrightEdge, the American Cancer Society’s (ACS) venture capital arm.

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Signify Bio is built on three proprietary and novel platforms encompassing both nucleic acid payloads and non-viral delivery systems designed to control the production, secretion and localization of protein therapeutics directly within the human body. The first is its modular Signal peptide Engineered Nucleic acid Design (SEND) platform, which enables control over the secretion and localization of any nucleic acid encodable protein of interest. The second platform, iPhos, is a novel lipid nanoparticle delivery system based on ionizable phospholipid (iPhos) lipid nanoparticles (iPLNPs) engineered to maximize endosomal escape and tissue specificity. The third utilizes Signify’s computational methods for design and discovery of novel signal peptides sequences. Together, these platforms drive innovation in personalized protein therapeutics by combining the promise of signal peptide engineering with the speed and power of mRNA encoded design.

Originally conceived in the Siegwart Lab at University of Texas Southwestern Medical Center (UTSW), Signify Bio has access to a world class team of scientists and cutting-edge technology through a strategic partnership with the university. This collaboration provides access to scalable LNP manufacturing and nucleic acid generation, broad expertise ranging from chemical synthesis to pre-clinical models and a core competency in chemistry and engineering all situated at UT Southwestern.

"Signify Bio’s modular platforms offer an unprecedented opportunity to engineer personalized protein therapeutics directly within the body, addressing long-standing challenges in drug production, delivery, and efficacy," said Daniel J. Siegwart, Ph.D., Co-founder and Chief Scientific Advisor at Signify Bio, and Director of the Program in Genetic Drug Engineering at UT Southwestern Medical Center. "With its versatility and adaptability, the company lays the groundwork for a new generation of precision medicine across a wide range of chronic and genetic disorders."

"The quality and diversity of our investor syndicate underscores the agility, flexibility, and broad applications for our proprietary platforms," said RA Session II, Co-founder and Chief Executive Officer at Signify Bio. "The SEND platform and iPhos LNP system represent a groundbreaking step forward in nucleic acid therapeutics, transforming the human body into a biofactory for precise, targeted protein production."

Signal peptides enable secretion and localization of nucleic acid-encoded proteins, replicating natural protein trafficking pathways. The SEND platform supports modular control over the secretion of proteins into systemic circulation and their localization to cellular organelles including the cell membrane, nucleus, lysosome, mitochondria, synapse among others. The iPhos LNP system allows for dose-dependent protein secretion from diverse cell types with compatibility across multiple routes of administration including subcutaneous (SQ), intramuscular (IM) and intravenous (IV).

"We are thrilled to support Signify Bio in their mission to create personalized medicines that will revolutionize therapeutic protein delivery," said Jun Il Kwun, Managing Director of Actium Group and Chair of the Board of Directors at Signify Bio. "The exceptional team at Signify Bio, with their deep expertise in nucleic acid engineering, is uniquely positioned to bring these technologies to patients. Their groundbreaking innovations and commitment to addressing unmet medical needs will transform the field of genetic medicine."

Signify Bio is led by a management team with deep industry expertise and is founded by pioneers in chemistry and nucleic acid engineering including:

Daniel J. Siegwart, Ph.D., Co-founder and Chief Scientific Advisor, Director of the Program in Genetic Drug Engineering at UT Southwestern, Professor and W. Ray Wallace Distinguished Chair in Molecular Oncology Research, Departments of Biomedical Engineering and Biochemistry at UT Southwestern, Co-founder of ReCode Therapeutics;
RA Session II, Co-founder, President, and Chief Executive Officer, former President, CEO, and Founder of Taysha Gene Therapies and former Chief Business Officer of the gene therapy subsidiaries of BridgeBio, former Board Member of ReCode Therapeutics;
Lukas J. Farbiak, Ph.D., Co-founder and Chief Technology Advisor, Assistant Professor, Departments of Biomedical Engineering and Biochemistry at UT Southwestern;
David Morrissey, Ph.D., Chief Scientific Officer, former Vice President, Head RNA Accelerator at Pfizer and Senior Vice President, Platform & Delivery Technology at Intellia Therapeutics; and
Morag Stewart, Ph.D., Vice President of Translational Biology, former Senior Director, RNA Medicines at Pfizer Centers for Therapeutic Innovation and Head of Exploratory Biology at Flagship Pioneering.
Chardan Capital served as Strategic Advisor to Signify Bio.

On June 5, 2025 Scholar Rock (NASDAQ: SRRK), a late-stage biopharmaceutical company focused on developing and commercializing apitegromab for patients with spinal muscular atrophy (SMA) and other severe and debilitating neuromuscular diseases, reported that David L. Hallal, Chief Executive Officer, and members of management will participate in a fireside chat at the 46th Annual Goldman Sachs Global Healthcare Conference on Wednesday, June 11 at 9:20 a.m. ET in Miami, Florida (Press release, Scholar Rock, JUN 5, 2025, View Source [SID1234653756]).

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A live webcast of the events may be accessed by visiting the Investors & Media section of the Scholar Rock website at View Source Archived replays of the webcasts will be available on the Company’s website for approximately 90 days.