On August 28, 2023, Biogen Inc. (the "Company") reported to have entered into a Credit Agreement with JPMorgan Chase Bank, N.A. ("JPMorgan"), as Administrative Agent, and the lenders party thereto (the "Credit Agreement") (Filing, 8-K, Biogen, AUG 28, 2023, View Source [SID1234634831]). The Credit Agreement provides for a $1.5 billion unsecured term loan facility, comprised of a $750 million 364-day tranche ("Tranche A") and a $750 million three-year tranche ("Tranche B" and collectively, the "Term Facility").

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Borrowings under the Term Facility will be available to the Company to (a) pay a portion of the consideration for the previously announced acquisition by the Company of Reata Pharmaceuticals, Inc. ("Reata") pursuant to an Agreement and Plan of Merger among the Company, River Acquisition, Inc. ("Merger Sub") and Reata (the "Merger Agreement") pursuant to which, and upon the terms and subject to the conditions set forth therein, Merger Sub will be merged with and into Reata (the "Merger"), with Reata surviving the Merger as a wholly-owned subsidiary of the Company, (b) repay indebtedness and other amounts outstanding under certain of Reata’s existing funding agreements and (c) pay fees and expenses in connection with the transactions described in the foregoing paragraphs (a) and (b).

Loans under the Credit Agreement will be denominated in dollars and will bear interest at a rate per annum equal to (i) Term SOFR, subject to a floor of 0.00% per annum, plus an applicable margin ranging from 1.250% to 1.625% based on the ratings of the Company’s non-credit enhanced, senior unsecured long-term debt, as determined by Standard & Poor’s and Moody’s (the "Debt Ratings") or (ii) at the Company’s option, a Base Rate equal to the highest of (a) the greater of the Federal Funds Rate or a composite overnight rate determined by the Federal Reserve Bank of New York (the "NYFRB") and published on the NYFRB’s website plus, in each case, 0.50%, (b) the Prime Rate and (c) Term SOFR for a one month interest period plus 1%, subject to a floor, in each case, of 0.00% per annum (the "Base Rate"), plus an applicable margin ranging from 0.250% to 0.625% based on the Company’s Debt Ratings.

In addition to paying interest on any outstanding principal under the Term Facility, the Company will pay a commitment fee in respect of the unutilized commitments thereunder ranging from 0.100% to 0.175% per annum based on the Company’s Debt Ratings.

Loans under the Credit Agreement shall be drawn in a single drawing on the closing date of the Merger (the "Funding Date"), following which any undrawn commitments under the Term Facility shall automatically terminate. The funding of the Term Facility is contingent on the satisfaction of customary conditions, including the consummation of the Merger in accordance with the terms set forth in the Merger Agreement. The Term Facility will terminate and all amounts outstanding thereunder shall become due and payable (i) in the case of Tranche A, 364 days after the Funding Date and (ii) in the case of Tranche B, 3 years after the Funding Date. Under the Term Facility, voluntary prepayments are permitted, in whole or in part, in minimum amounts without premium or penalty, other than customary breakage costs.

The Credit Agreement contains customary representations and warranties, affirmative and negative covenants and events of default that are, in each case, substantially similar to the equivalent terms of that certain Credit Agreement, dated as of January 28, 2020 (as amended, restated, amended and restated, supplemented and/or otherwise modified prior to the date hereof) among the Company, the lenders party thereto and Bank of America, N.A., as administrative agent.

The Credit Agreement also includes a financial covenant requiring the Company to maintain, as of the end of each fiscal quarter, a maximum consolidated leverage ratio of 3.5 to 1.0 (which shall be temporarily increased (a) to 4.0 to 1.0 upon the consummation of the Merger and (b) upon notice by the Company to JPMorgan as a result of other material acquisitions from time to time, subject to customary limitations, and provided that the maximum permitted consolidated leverage ratio shall not exceed 4.0 to 1.0).

Following the Company’s entry into the Credit Agreement, JPMorgan’s commitment to provide a 364-day senior unsecured bridge loan facility in an aggregate principal amount of up to $1.5 billion (as more particularly described in the Company’s Current Report on Form 8-K dated July 31, 2023) has been terminated and canceled.

A copy of the Credit Agreement is attached hereto as Exhibit 10.1 and is incorporated herein by reference. The foregoing description of the Credit Agreement is a summary only and is qualified in its entirety by the terms of the Credit Agreement.

On August 28, 2023 Palleon Pharmaceuticals, a clinical-stage company pioneering glyco-immunology drug development to treat cancer and inflammatory diseases, reported that Fierce Biotech has recognized the company as one of its "Fierce 15" for 2023 (Press release, Palleon Pharmaceuticals, AUG 28, 2023, View Source [SID1234634733]). This annual report features the most innovative and promising biotechnology companies in the industry.

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"It is an honor to be named to the Fierce 15 and to be recognized for our work pioneering the transformational field of glyco-immunology," said Jim Broderick, M.D., Chief Executive Officer and Founder of Palleon. "As we continue to advance our therapies in the clinic, this recognition provides validation of the strength of our team, our technologies, and our strategy to bring much-needed new therapeutic options to patients across multiple disease areas."

Palleon was co-founded by Dr. Carolyn Bertozzi, recipient of the 2022 Nobel Prize in Chemistry for the invention of bioorthogonal chemistry, a technology which enabled the company’s foundational science. In April 2023, Palleon announced Phase 1 results from the GLIMMER-01 trial to evaluate its lead candidate in oncology, E-602 as a monotherapy, demonstrating proof of mechanism, including dose dependent desialylation and dose dependent immune system activation. Additionally, E-602 was found to be well tolerated across the entire dose range evaluated with no dose limiting toxicities.

For the past 21 years, the Fierce Life Sciences team has assessed hundreds of companies for inclusion in the ‘Fierce 15’ special report. To curate this list, Fierce considers a diverse range of factors, including the robustness of technology, partnerships, venture support, and competitive positioning within the market. This special report celebrates innovation and creativity in the face of intense competition.

On August 28, 2023 Novocure (NASDAQ: NVCR) reported that the phase 3 ENGOT-ov50 / GOG-3029 / INNOVATE-3 clinical trial of Tumor Treating Fields (TTFields) together with paclitaxel in patients with platinum-resistant ovarian cancer did not meet its primary endpoint of overall survival (OS) at the final analysis (Press release, NovoCure, AUG 28, 2023, View Source [SID1234634732]). Patients randomized to receive TTFields therapy plus paclitaxel (n=280) demonstrated a median OS of 12.2 months versus a median OS of 11.9 months in patients treated with paclitaxel alone (n=278) (HR: 1.008). Consistent with previously reported studies, TTFields therapy was well-tolerated with no added systemic toxicities.

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"While the final results of the ENGOT-ov50 / GOG-3029 / INNOVATE-3 trial differ from our initial expectation, these data add important context to the treatment paradigm"

"Recurrent ovarian cancer is a particularly aggressive cancer and options for patients diagnosed with platinum-resistance remain extremely limited," said Ignace Vergote, MD, PhD, Principal Investigator and Chairman of the Belgium and Luxembourg Gynaecological Oncology Group and Professor at the Catholic University of Leuven, Belgium. "We are committed to continuing research with TTFields and exploring innovative approaches to treat this area of immense unmet need, and we are extremely grateful to all the investigators and patients for their participation in these studies."

The ENGOT-ov50 / GOG-3029 / INNOVATE-3 trial enrolled patients with a maximum of five total prior lines of systemic therapy. An analysis of exploratory subgroups suggests a potential survival benefit in patients who received only one prior line of therapy. This signal could merit further exploration given the unmet need for the ~20% of ovarian cancer patients who have a limited response to frontline platinum-based treatment. Full evaluation of the data from the ENGOT-ov50 / GOG-3029 / INNOVATE-3 trial, including subgroup analyses, is ongoing.

"While the final results of the ENGOT-ov50 / GOG-3029 / INNOVATE-3 trial differ from our initial expectation, these data add important context to the treatment paradigm," said David O’Malley, MD, Professor of Obstetrics and Gynecology at The Ohio State University Wexner College of Medicine and Director of the Division of Gynecologic Oncology at The James Comprehensive Cancer Center. "We see treatment exposure and number of prior therapies are relevant and can drive outcomes, and we will leverage these data as we explore and identify new opportunities to treat this deadly disease."

"The INNOVATE-3 clinical trial set out to harness the unique mechanisms of Tumor Treating Fields to extend survival in platinum-resistant ovarian cancer," said William Doyle, Novocure’s Executive Chairman. "While today’s update is disappointing, we are encouraged by the signal identified from the exploratory analysis which suggests the potential for a clinical benefit when TTFields therapy is initiated early in a patient’s treatment journey. We are deeply grateful to the patients who participated in this clinical trial, their loved ones, and to the trial investigators."

Novocure will work with investigators to share the full results with the scientific community.

About ENGOT-ov50 / GOG-3029 / INNOVATE-3
The ENGOT-ov50 / GOG-3029 / INNOVATE-3 clinical trial was designed to evaluate the safety and effectiveness of TTFields together with paclitaxel in patients with platinum-resistant ovarian cancer. The primary endpoint of INNOVATE-3 was overall survival. Secondary endpoints include progression-free survival, objective response rate, severity and frequency of adverse events, time to undisputable deterioration in health-related quality of life or death, and quality of life. Enrollment in the trial closed in October 2021 with 540 patients enrolled, beginning the minimum 18-month follow-up period.

The European Network for Gynaecological Oncological Trial groups ("ENGOT") and The GOG Foundation, Inc. ("GOG"), third-party clinical trial networks, collaborated with Novocure on the trial. Both ENGOT and GOG were involved in the development and facilitation of the trial at leading cancer centers in Europe and the United States.

About Ovarian Cancer
In the U.S., ovarian cancer ranks fifth in cancer deaths among women, with approximately 24,000 women diagnosed each year. Ovarian cancer incidence increases with age, and the median age at time of diagnosis is 63 years old.

Physicians use different combinations of surgery and pharmacological therapies to treat ovarian cancer, depending on the stage of the disease. Surgery is usually used in early stages of the disease and is usually combined with chemotherapy, including paclitaxel and platinum-based chemotherapy. Unfortunately, the majority of patients are diagnosed at an advanced stage when the cancer has spread outside of the ovaries to include regional tissue involvement and/or metastases. Platinum-based chemotherapy remains part of the standard of care in advanced ovarian cancer, but most patients with advanced ovarian cancer will have tumor progression or, more commonly, recurrence. Almost all patients with recurrent disease ultimately develop platinum resistance, and the prognosis for this population remains poor.

About Tumor Treating Fields Therapy
Tumor Treating Fields (TTFields) are electric fields that exert physical forces to kill cancer cells via a variety of mechanisms. TTFields do not significantly affect healthy cells because they have different properties (including division rate, morphology, and electrical properties) than cancer cells. The multiple, distinct mechanisms of TTFields therapy work together to selectively target and kill cancer cells. Due to its multimechanistic actions, TTFields therapy can be added to cancer treatment modalities in approved indications and demonstrates enhanced effects across solid tumor types when used with chemotherapy, radiotherapy, immune checkpoint inhibition, or PARP inhibition in preclinical models. TTFields therapy provides clinical versatility that has the potential to help address treatment challenges across a range of solid tumors. To learn more about Tumor Treating Fields therapy and its multifaceted effect on cancer cells, visit tumortreatingfields.com.

On August 28, 2023 Agenus Inc. ("Agenus") (Nasdaq: AGEN), a leader in developing novel immunological agents to treat various cancers, reported that Dr. Garo Armen, Chairman and CEO, will participate in the following upcoming investor conferences (Press release, Agenus, AUG 28, 2023, View Source [SID1234634731]):

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2023 Wells Fargo Healthcare Conference – Fireside chat presentation will be held in-person on Thursday, September 7th, 2023, at 11:00 a.m. ET in Boston, MA. A live webcast and replay will be accessible on the company’s website at View Source

Baird 2023 Global Healthcare Conference– Fireside chat presentation will be held in person on Tuesday, September 12th, 2023, at 4:20 p.m. ET, in New York, NY. This content is for Baird clients attending the conference. There will not be a webcast replay.

HC Wainwright 25th Annual Global Investment Conference – Fireside chat presentation will be held in-person on Wednesday, September 13th, 2023, at 11:00 a.m. ET, in New York, NY. A live webcast and replay will be accessible on the company’s website at View Source

On August 28, 2023 NorthStar Medical Radioisotopes, LLC ("NorthStar"), a global innovator in the development, production and commercialization of radiopharmaceuticals used for therapeutic and medical imaging applications, reported that the first patient has been dosed in a clinical trial using NorthStar’s electron accelerator-produced Cu-67 (Press release, NorthStar Medical Radiostopes, AUG 28, 2023, View Source [SID1234634730]). Administration of the therapeutic dose took place as part of an ongoing Phase I/IIa theranostic clinical trial conducted by Clarity Pharmaceuticals to investigate the safety and efficacy of Cu-67 SARTATE in pediatric patients with high-risk neuroblastoma. The event marks a key milestone in the exclusive Cu-67 supply agreement between both companies.

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NorthStar is producing high-activity, high specific-activity and high-purity Cu-67 for use in Clarity’s clinical programs as part of an agreement to exclusively supply Cu-67 to Clarity. Clarity will use NorthStar-produced Cu-67 for its three actively recruiting theranostic clinical trials evaluating the safety and efficacy of 67Cu SARTATE, 67Cu SAR-bisPSMA and 67Cu SAR-Bombesin, as well as future commercialization of its Targeted Copper Theranostic (TCT) products.

NorthStar is the first commercial-scale supplier of this important Cu-67 therapeutic radioisotope, and Clarity leads the world in copper based theranostics. NorthStar’s Cu-67 production process uses highly efficient, environmentally preferable electron accelerator technology and the NorthStar radioisotope has proven suitable for radiolabeling of Clarity’s products using their proprietary SAR Technology platform. The platform is enabled by unique SAR chelators, that are specialized cage-like structures that securely hold copper radioisotopes. Unlike traditional chelators, SAR chelators prevent leakage of copper isotopes into the body. Once securely attached to a targeting molecule, the chelated Cu-67 delivers therapeutic doses of radiation to destroy cancer cells with limited damage to healthy tissue.

Clarity’s Executive Chairman, Dr. Alan Taylor, stated, "Large-scale manufacture of therapeutic Cu-67 from highly efficient, environmentally preferable electron accelerators is critical to overcome the widespread supply issues in the radiopharmaceutical industry, due to a heavy reliance on a small number of antiquated nuclear reactors. Clarity continues to recruit higher numbers of participants at increasingly higher activities of Cu-67 across all three of our therapeutic clinical trials."

"Reliable commercial-scale production of high specific activity Cu-67 complements our development efforts, with end-to-end production, from radioisotope through to finished product, and advantageously positions Clarity to realize the many supply and manufacturing advantages associated with TCTs. It supports a sustainable future for radiopharmaceuticals unencumbered by manufacturing, logistical and environmental issues inherent to many radiopharmaceuticals. We believe that TCTs present an efficacious, scalable, sustainable and cost-effective way to expand radiopharmaceuticals into the large, global oncology market and we look forward to continuing our collaboration with NorthStar as we realize our shared goal of improving treatment outcomes for children and adults with cancer," continued Dr. Taylor.

NorthStar Medical Radioisotopes’ President and Chief Executive Officer, Frank Scholz, Ph.D., commented, "The fact that the initial human use of NorthStar’s electron accelerator-produced Cu-67 is in a clinical trial designed to treat children with high-risk neuroblastoma underscores the importance of our work in advancing innovation to promote patient health, and we hope that we can help children and their caregivers who are affected by this serious disease. NorthStar continues to drive commercial-scale innovation solutions for our industry, to meet the needs of patients and advance clinical research.

Our efforts use the proven expertise and innovative approach demonstrated in the successful development and commercialization of our other domestically-produced, non-uranium based radioisotope. We are pleased and honored to be part of this important clinical trial, and look forward to continuing to support Clarity’s plans for further clinical development and commercialization of Cu-67-based radiopharmaceutical therapies, with the aim to improve the lives of patients with serious disease."

About Therapeutic Radioisotope Copper-67 (Cu-67)

Copper-67 (Cu-67) is an optimal-range, beta-emitting radioisotope that can be produced at commercial scale with high specific activity and without long-lived radioactive impurities. Cu-67 delivers cancer-killing radiation to target cells and is being investigated for therapeutic purposes across a wide range of adult and childhood cancers, including prostate and breast cancers. A chelator, which strongly binds Cu-67 to the targeting agent and prevents its leakage in vivo, is required to develop safe and effective targeted therapies. Clarity has successfully developed a highly specific and highly stable chelator for copper isotopes and is progressing clinical trials of a range of radiopharmaceutical products based on its proprietary SAR Technology Platform. NorthStar is rapidly advancing its proprietary process for commercial-scale production of Cu-67 to meet demand for clinical research and eventual commercial supply of TCTs.

About the CL04 Clinical Trial

The CL04 trial (NCT04023331)1 is a theranostic trial evaluating 64Cu/67Cu SARTATE for diagnosis and treatment of high-risk neuroblastoma, an aggressive childhood cancer. It is a multi-centre, dose-escalation, open label, non-randomised, Phase I/IIa clinical trial with up to 34 participants conducted across eight clinical sites in the United States.

About SARTATE

SARTATE is a next generation, highly targeted theranostic radiopharmaceutical. It is being developed for diagnosing, staging and subsequently treating cancers that express somatostatin receptor 2 (SSTR2), including neuroblastoma and neuroendocrine tumors (NETs). Like all Clarity products, the SARTATE product can be used with copper-64 (64Cu) for imaging (64Cu SARTATE) or copper-67 (67Cu) for therapy (67Cu SARTATE).

About Neuroblastoma

Neuroblastoma most often occurs in children younger than 5 years of age and presents when the tumour grows and causes symptoms. It is the most common type of cancer to be diagnosed in the first year of life and accounts for around 15% of paediatric cancer mortality2. High-risk neuroblastoma accounts for approximately 45% of all neuroblastoma cases. Patients with high-risk neuroblastoma have the lowest 5-year survival rates at 40%-50%.