On June 9, 2025 Axio BioPharma Inc., a next-generation biomanufacturing company using AI to transform mammalian protein production, and Likarda Inc., a leader in advanced drug delivery and formulation technologies, reported a strategic partnership to accelerate innovation in biologic drug development (Press release, Likarda, JUN 9, 2025, View Source [SID1234653786]). This collaboration will integrate Likarda’s proprietary delivery technologies with Axio’s manufacturing capabilities, creating a more efficient and scalable path to clinical manufacturing for clients across the biopharmaceutical sector.

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Through this collaboration, Axio BioPharma will incorporate Likarda’s proprietary delivery platforms— including its Core-Shell Spherification (CSS) hydrogel technology for encapsulation, stability, and controlled release —into its service offering, enhancing workflows for monoclonal antibodies (mAbs), bispecifics, and Fc-fusions. Likarda will also offer Axio’s discovery-to-GMP manufacturing capabilities to its client base, supporting programs in need of high-quality protein production and scalable manufacturing solutions.

"This partnership brings delivery innovation directly into the development process, helping our clients move faster and make better decisions," said Justin Byers, CEO of Axio BioPharma. "By aligning earlier on both delivery and manufacturing, we reduce friction, shorten timelines, and provide integrated solutions that truly support our clients’ goals."

"At Likarda, we believe that delivery should never be an afterthought—it should be part of the development strategy from day one," said Dr. Stella Vnook, CEO of Likarda Inc. "Partnering with Axio allows us to integrate our encapsulation and formulation technologies earlier in the drug development process, where they can have the greatest impact on stability, efficacy, and patient experience. Importantly, it provides seamless integration to scaled manufacturing for our clients. Together, we’re creating a smarter, more connected path from discovery to clinic."

This collaboration strengthens Axio’s mission of transforming biologic manufacturing through predictive science and digital-first process development. At the same time, it enables Likarda to apply its proprietary delivery technologies earlier in the development cycle, giving clients new efficiencies and expanded therapeutic applications.

On June 8, 2025 Samsung Bioepis Co., Ltd. ("Samsung Bioepis") reported that the company has entered into a license, development and commercialization agreement with NIPRO Corporation ("NIPRO") for multiple biosimilar candidates including SB17, ustekinumab biosimilar candidate, in Japan (Press release, Nipro, JUN 8, 2025, View Source [SID1234653771]).

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Under the terms of the agreement, Samsung Bioepis will be responsible for the development, manufacture and supply of the medicines, while NIPRO will be responsible for commercialization of the medicines in Japan.

"This partnership marks an important step towards expanding our footprint in Japan. Biosimilars have a great potential to bring cost savings and widen access to treatments for healthcare systems, providers, and patients in Japan. We look forward to collaborating with NIPRO, a company renowned for its high-quality medical devices and healthcare solutions, to accelerate access to treatments in the Japanese market," said Kyung-Ah Kim, President and Chief Executive Officer of Samsung Bioepis. "We will continue to advance our development platform and innovate access to treatments for healthcare systems, payers, physicians, and patients around the world."

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 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, Integra LifeSciences Holdings Corporation (the "Company") reported to have entered into an amendment (the "Amendment") to the Seventh Amended and Restated Credit Agreement, dated as of March 24, 2023, among the Company, a syndicate of lending banks, Bank of America, N.A., as Administrative Agent, Swing Line Lender and L/C Issuer, Citibank N.A., JPMorgan Chase Bank, N.A., Morgan Stanley MUFG Loan Partners, LLC, PNC Bank, N.A., Truist Bank and Wells Fargo Bank, N.A., as Co-Syndication Agents, and The Bank of Nova Scotia, BMO Harris Bank N.A., BNP Paribas, Capital One, National Association, Citizens Bank, N.A., DNB Bank ASA, New York Branch, Santander Bank, N.A. and TD Bank, N.A., as Co-Documentation Agents (as amended, restated, modified and supplemented from time to time prior to the date hereof, the "Credit Agreement") (Filing, 8-K, Integra LifeSciences, JUN 6, 2025, View Source [SID1234653775]). The Credit Agreement was filed as Exhibit 10.1 to the Company’s Current Report on Form 8-K, filed with the SEC on March 24, 2023.

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The Amendment amends the financial covenant requiring the Company to maintain a particular consolidated total leverage ratio. In particular, the Amendment increases the maximum permitted consolidated total leverage ratio from the currently applicable 5.00 to 1.00 (which reflects an increase from 4.25 to 1.00 taken by the Company in connection with the closing of a permitted acquisition and which is applicable through the fiscal quarter ending September 30, 2025) to (a) 5.00 to 1.00 for the fiscal quarters ending March 31, 2025 through June 30, 2026, (b) 4.75 to 1.00 for the fiscal quarter ending September 30, 2026, (c) 4.50 to 1.00 for the fiscal quarter ending December 31, 2026, and (d) 4.00 to 1.00 for the fiscal quarter ending March 31, 2027 and the last day of each fiscal quarter thereafter. During the period commencing on the effective date of the Amendment and ending on the date of delivery of the financial statements and related compliance certificate for the fiscal year ending December 31, 2026 (the "Covenant Relief Period"), the Company will not be permitted to temporarily increase the applicable maximum consolidated total leverage ratio in connection with a permitted acquisition.

In addition to the foregoing, the Amendment, among other things, also: (i) temporarily establishes, during the Covenant Relief Period, a revised applicable rate schedule; (ii) temporarily limits, during the Covenant Relief Period, the Company’s ability to make certain investments; (iii) temporarily restricts, during the Covenant Relief Period, the Company’s ability to incur incremental indebtedness under the Credit Agreement, create certain liens, make certain restricted payments and incur or guarantee indebtedness of excluded subsidiaries; and (iv) temporarily prohibits, during the Covenant Relief Period, the Company from selling, transferring or exclusively licensing material intellectual property to a subsidiary of the Company that is not a loan party under the Credit Agreement or designating any subsidiary that owns or exclusively licenses any material intellectual property as an excluded subsidiary under the Credit Agreement.

The Amendment does not increase the Company’s total indebtedness.

A copy of the Amendment is attached as Exhibit 4.1 to this Current Report on Form 8-K and is incorporated by reference into this Item 1.01. The foregoing summary does not purport to be complete and is qualified in its entirety by reference to the full text of the Amendment and the Credit Agreement.