Entry into a Material Definitive Agreement

On November 15, 2023, Alkermes plc (the "Company") reported the previously announced separation of its oncology business into Mural Oncology plc ("Mural"), a new, independent, publicly-traded company (the "Separation") (Filing, Alkermes, NOV 15, 2023, View Source [SID1234639963]). The Separation was effected by means of a distribution of all of the outstanding ordinary shares of Mural to the Company’s shareholders (the "Distribution"), in which each of the Company’s shareholders received one ordinary share, nominal value $0.01 per share, of Mural for every ten ordinary shares, par value $0.01 per share, of the Company (the "Distribution Ratio") held by such shareholder as of the close of business on November 6, 2023, the record date for the Distribution (the "Record Date"). The effective time of the Distribution was 12:01 a.m. Eastern time on November 15, 2023.

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Separation Agreement

In connection with the Separation, the Company entered into a separation agreement with Mural, dated as of November 13, 2023, that, among other things, sets forth the Company’s agreements with Mural regarding the principal actions to be taken in connection with the Separation, including the Distribution. The separation agreement identifies assets to be transferred to, liabilities to be assumed by and contracts to be assigned to Mural, including the operating lease for 850 and 852 Winter Street in Waltham, Massachusetts, as part of the Separation, and it provides for when and how such transfers, assumptions and assignments occur. The purpose of the separation agreement is to provide Mural and the Company with those assets necessary to operate their respective businesses and to retain or assume the respective liabilities related to those assets. Under the terms of the separation agreement, the Company granted Mural a perpetual, worldwide, non-exclusive, royalty-free, fully paid-up license (or, as the case may be, sublicense) to intellectual property controlled by the Company as of the date of the Distribution to allow Mural to use such intellectual property for the oncology business, and Mural granted the Company a perpetual, worldwide, non-exclusive, royalty-free, fully paid-up license (or, as the case may be, sublicense) to intellectual property transferred to Mural as part of the Separation for the Company’s use outside of the oncology business. Each of Mural and the Company agreed to releases with respect to pre-Distribution claims, and cross-indemnities with respect to post-Distribution claims, that are principally designed to place financial responsibility for the obligations and liabilities allocated to Mural under the separation agreement with Mural, and financial responsibility for the obligations and liabilities allocated to the Company under the separation agreement with the Company. The Company and Mural are also each subject to mutual six-month employee non-solicitation and non-hire restrictions, subject to certain customary exceptions, and certain confidentiality restrictions and information sharing obligations.

Tax Matters Agreement

In connection with the Separation, the Company also entered into a tax matters agreement with Mural, dated as of November 13, 2023. The tax matters agreement governs the Company’s and Mural’s respective rights, responsibilities and obligations with respect to taxes (including taxes arising in the ordinary course of business and taxes, if any, incurred as a result of any failure of the Distribution, together with certain related transactions, to qualify as tax-free for U.S. federal income tax purposes), tax attributes, the preparation and filing of tax returns, the control of audits and other tax proceedings, and assistance and cooperation in respect of tax matters.

In addition, the tax matters agreement imposes certain restrictions on Mural and its subsidiaries (including restrictions on share issuances, business combinations, sales of assets and similar transactions) and on the Company and its subsidiaries that are designed to prevent the taking of any actions that would adversely affect, or could reasonably be expected to adversely affect, the tax-free status of the Distribution, together with certain related transactions. The tax matters agreement provides special rules that allocate tax liabilities in the event that the Distribution, together with certain related transactions, is not tax-free. In general, under the terms of the tax matters agreement, if the Distribution, together with certain related transactions, were to fail to qualify as a transaction that is tax-free for U.S. federal income tax purposes, under Sections 355 and 368(a)(1)(D) of the Internal Revenue Code of 1986, as amended (the "Code"), and if and to the extent that such failure results from certain actions, omissions or failures to act by the Company, including a prohibited change of control in the Company under Section 355(e) of the Code or an acquisition of shares or assets of the Company, then the Company will bear any resulting taxes, interest, penalties and other costs. If and to the extent that such failure results from certain actions, omissions or failures to act by Mural, including a prohibited change of control in Mural under Section 355(e) of the Code or an acquisition of shares or assets of Mural, then Mural will indemnify the Company for any resulting taxes, interest, penalties and other costs. If such failure does not result from a prohibited change of control in the Company or Mural under Section 355(e) of the Code and both the Company and Mural are responsible for such failure, liability will be shared according to relative fault. If neither Mural nor the Company is responsible for such failure, the Company will bear any resulting taxes, interest, penalties and other costs.

Employee Matters Agreement

In connection with the Separation, the Company also entered into an employee matters agreement with Mural, dated as of November 13, 2023. The employee matters agreement governs the Company’s, Mural’s and their respective subsidiaries’ and affiliates’ rights, responsibilities and obligations after the Separation with respect to, employment, benefits and compensation matters relating to employees and former employees (and their respective dependents and beneficiaries) who are or were associated with the Company, including those who became employees of Mural in connection with the Separation; the allocation of assets and liabilities generally relating to employees, employment or service-related matters and employee benefit plans; other human resources, employment and employee benefits matters; and the treatment of equity-based awards granted by the Company prior to the Separation.

Transition Services Agreements

Alkermes, Inc., a wholly-owned subsidiary of the Company ("Company Subsidiary"), and Mural Oncology, Inc., a wholly-owned subsidiary of Mural ("Mural Subsidiary"), entered into a transition services agreement on November 13, 2023, pursuant to which the Company and its subsidiaries will provide, on an interim, transitional basis, various services to Mural and its subsidiaries, including services related to corporate functions such as finance, human resources, internal audit, research and development, financial reporting, and information technology, each for a term of two years, unless earlier terminated in accordance with the terms of such agreement.

Company Subsidiary and Mural Subsidiary also entered into a second transition services agreement on November 13, 2023, pursuant to which Mural and its subsidiaries will provide certain services to the Company and its subsidiaries, each for a term of two years, unless earlier terminated in accordance with the terms of such agreement.

The foregoing descriptions of the separation agreement, the tax matters agreement, the employee matters agreement, and the transition services agreements do not purport to be complete, provide only summaries of the material terms of such agreements and are qualified in their entirety by reference to each of the agreements, which are filed as Exhibit 2.1, Exhibit 10.1, Exhibit 10.2, Exhibit 10.3, and Exhibit 10.4, respectively, to this Current Report on Form 8-K and are incorporated herein by reference.

Mural Oncology Launches to Advance Pipeline of Novel Engineered Cytokine Immunotherapies

On November 20, 2023 Mural Oncology plc (Nasdaq: MURA) reported to have launched as an independent, publicly traded, clinical-stage immuno-oncology company leveraging its core competencies in immune cell modulation and protein engineering to develop novel, investigational engineered cytokine therapies designed to address areas of unmet need for patients with a variety of cancers (Press release, Mural Oncology, NOV 15, 2023, View Source [SID1234637844]). Mural’s ordinary shares will begin trading on the Nasdaq Global Market tomorrow, November 16th, under the ticker symbol "MURA".

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"Immunotherapies have made a tremendous impact on the treatment of cancers over the past decade," said Caroline Loew, Ph.D., the Company’s chief executive officer. "Unfortunately, many patients either do not respond or do not have durable responses. We believe Mural Oncology can lead the future of immunotherapies for patients. Our protein engineering expertise allows us to reimagine the development of pro-inflammatory cytokine-based therapeutics that could address the key limitations with current cancer immunotherapies. I am thrilled to lead this company and am energized by the enormous potential of our lead clinical candidate, our preclinical programs, and our underlying protein engineering capabilities."

Mural Oncology’s pipeline is built to address difficult-to-treat tumor types where checkpoint inhibitors are not effective. The Company’s lead product candidate, nemvaleukin alfa (nemvaleukin), is an investigational, engineered interleukin-2 (IL-2) cytokine designed to capture and expand the therapeutic benefits of high-dose recombinant human IL-2 (rhIL-2), while mitigating the hallmark toxicities of native IL-2 in difficult-to-treat cancers with high unmet need. Nemvaleukin is currently in two potentially registrational studies: one for the treatment of mucosal melanoma as a monotherapy and one for the treatment of platinum-resistant ovarian cancer (PROC) in combination with pembrolizumab.

In addition to nemvaleukin, Mural Oncology has discovery-stage programs in IL-18 and IL-12, focused on proinflammatory cytokines that leverage the Company’s immune cell modulation expertise and protein engineering capabilities. This multi-faceted approach to cytokine engineering is aimed at maximizing the utility of identified cytokines and includes binding selectivity, tumor-targeting, half-life modification, and stable fusion proteins.

"We believe nemvaleukin has the potential to reduce native IL-2’s toxicities, potentially allowing greater tolerability and efficacy than other IL-2 molecules have shown in the past," Dr. Loew continued. "We plan to report top-line results in each of mucosal melanoma and PROC in the first quarter of 2025 and declare product candidates across both of our other discovery-stage programs in 2024. We are building on years of foundational work from which our engineered cytokines may lead to new therapies for significant patient populations where checkpoint inhibitors either failed to achieve a response or produced a limited response. We believe these new therapies could be effective either as monotherapies or in combination with a range of other therapeutics."

To advance the Company’s pipeline and capitalize on its protein engineering capabilities, Mural has assembled an experienced and highly accomplished executive team and board of directors.

Mural Oncology’s executive officers:

Caroline Loew, Ph.D., chief executive officer, was previously president and chief executive officer of Glympse Bio. Prior to Glympse, she was vice president, head of R&D strategy and planning at Bristol-Myers Squibb (BMS). Dr. Loew joined BMS following leadership roles at Merck and PhRMA, where she led teams responsible for commercial portfolio management, market access, and regulatory policy.
Adam Cutler, chief financial officer, was previously chief financial officer of both Q32 Bio and Molecular Templates. Prior to that, he was senior vice president of corporate affairs at Arbutus Biopharma.
Vicki Goodman, M.D., chief medical officer, was previously executive vice president, product development & medical affairs, and chief medical officer of Exelixis. Previously, she was vice president, clinical research and therapeutic area head, late-stage oncology at Merck where she oversaw the company’s late-stage development portfolio, including pembrolizumab. Prior to Merck, she was a member of BMS’s oncology senior leadership team, managing a team developing nivolumab and ipilimumab.
Maiken Keson-Brookes, chief legal officer, previously served as chief legal officer and corporate secretary of Rubius Therapeutics. Prior to joining Rubius, she served as General Counsel at Synlogic, uniQure, and Forum Pharmaceuticals.

Nykode Therapeutics – Quarterly report Q3 2023

On November 15, 2023 Nykode Therapeutics reported its third quarter 2023 financial results (Presentation, Nykode Therapeutics, NOV 15, 2023, View Source [SID1234637726]).

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Seneca Therapeutics Announces Publication of TEM8 Review Article “TEM8 in Oncogenesis” in Cells Journal

On November 15, 2023 Seneca Therapeutics, Inc., reported the publication of "TEM8 in Oncogenesis" in Cells (Press release, Seneca Therapeutics, NOV 15, 2023, View Source [SID1234637723]). The authors are Dr. Samuel Kareff and Dr. Aman Chauhan from Sylvester Cancer at University of Miami, Dr. Virginia Corbett from Mt. Sinai Tisch Cancer Center and Dr. Paul Hallenbeck from Seneca Therapeutics.

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"In the article, we underline TEM8’s prognostic and predictive abilities in various solid tumors by (1) highlighting its association with more aggressive disease biology and poor clinical outcomes and (2) assessing its associated clinical trial landscape," said Dr. Aman Chauhan. "Finally, we offer future directions for clinical studies involving TEM8, including incorporating preclinical agents into clinical trials and combining previously tested oncologic therapies with currently available treatments, such as immunotherapy."

"The evidence of TEM8’s abilities and role in a broad range of solid tumors continues to grow," said Dr. Paul Hallenbeck. "This review article provides an excellent update on both TEM8, ANTXR1 – the gene that encodes TEM8 – and SVV-001 which targets TEM8. This update provides a foundation for upcoming publications and clinical trials for SVV-001 and TEM8."

Seneca Therapeutics is developing SVV-001, a number of SVV-001 armed constructs and a multiple IV option for SVV-001 sensitive solid tumors. SVV-001 sensitivity is defined as high ANTXR1 (TEM8) expression and a microtumor environment which permits replication of SVV-001 in the tumor. Seneca has developed an SVV-001 Companion Diagnostic and received FDA clearance to use it in clinical trials to identify patients that would benefit from SVV-001.

Foundation Medicine Announces Collaboration with Pierre Fabre Laboratories to Develop Companion Diagnostics in Non-Small Cell Lung Cancer

On November 15, 2023 Foundation Medicine, Inc., and Pierre Fabre Laboratories reported a collaboration to develop Foundation Medicine’s high-quality genomic tests, FoundationOneCDx and FoundationOneLiquid CDx, as companion diagnostics for new targeted therapies to treat patients with non-small cell lung cancer (NSCLC) (Press release, Foundation Medicine, NOV 15, 2023, View Source [SID1234637722]). The companies will work collaboratively to seek the regulatory approval for Foundation Medicine assays which detect mutations including BRAFV600E to identify patients for potential treatment with Pierre Fabre Laboratories’s BRAF/MEK inhibitor combination regimen, BRAFTOVI (encorafenib) and MEKTOVI (binimetinib), in the European Union. This combination therapy is currently under evaluation by the European Medicines Agency for patients with BRAFV600-mutant advanced NSCLC and was evaluated in a clinical trial sponsored by Pfizer and supported by Pierre Fabre.

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Lung cancer – the number one cause of cancer deaths worldwide – remains an area of high unmet need notably for those people living with BRAFV600E mutations, which occur in approximately 2% of all non-small cell lung cancer.1 FoundationOne CDx and FoundationOne Liquid CDx are U.S. Food and Drug Administration (FDA) approved in-vitro diagnostics used to identify potentially targetable mutations, including BRAF, in blood- and tissue-based solid tumor samples.

"Today, as the number of indications and approvals in oncology grow rapidly, companion diagnostics provide information that is critical for the safe and effective use of targeted therapies. And that’s why we are excited to work with Foundation Medicine," said Núria Perez-Cullell, Head of Medical and Patient Consumer Department, Pierre Fabre Laboratories. "Thanks to those companion diagnostics, physicians will have comprehensive, reliable information about what is driving a patient’s cancer, such as BRAFV600E mutations, so they can make personalized treatment decisions."

Foundation Medicine has the only FDA-approved portfolio of comprehensive genomic profiling tests offering physicians both blood- and tissue-based testing options for detecting genomic alterations like BRAFV600E to help guide personalized treatment decisions. Foundation Medicine has demonstrated initial success in navigating the new In Vitro Diagnostics Regulation (IVDR) in Europe through activation of dozens of global clinical studies or using patient samples from over 20 European Union member states in compliance with IVDR Authorization and Notification pathways.2

"High-quality companion diagnostics play a crucial role in helping physicians match their patients with targeted treatment options," said Troy Schurr, Chief Biopharma Business Officer at Foundation Medicine. "We are excited to support Pierre Fabre Laboratories in offering more treatment options for cancer patients, and to increase access to precision therapies in the European Union."