On December 4, 2020, Thermo Fisher Scientific Inc. (the "Company") reported that replaced its existing $2.5 billion unsecured five-year revolving credit facility with a new $3.0 billion unsecured five-year revolving credit facility (the "Credit Facility") pursuant to a Credit Agreement (the "Credit Agreement"), among the Company, certain Subsidiaries of the Company from time to time party thereto as Designated Borrowers, Bank of America, N.A., as Administrative Agent and a syndicate of lenders from time to time party thereto (Filing, 8-K, Thermo Fisher Scientific, DEC 4, 2020, View Source [SID1234572171]). Capitalized terms used in this Form 8-K and not defined herein shall have the meanings ascribed to them in the Credit Agreement, which is attached to this Form 8-K as Exhibit 10.1.

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The Credit Facility expires December 4, 2025, subject to two one-year extensions at the request of the Company and with the consent of the lenders. The Credit Facility also contains an expansion option permitting the Company to request increases of up to an aggregate additional $1.0 billion from lenders that elect to make such increase available, upon the satisfaction of certain conditions. The proceeds of the Loans under the Credit Facility may be used for working capital purposes, capital expenditures, acquisitions, repurchases of stock, debentures and other securities, the refinancing of present and future debt and other general corporate purposes. If no Default or Event of Default has occurred, (i) each Eurocurrency Rate Loan and each Swing Line Loan denominated in Euros shall bear interest on the outstanding principal amount thereof for each Interest Period at a variable rate per annum equal to the Eurocurrency Rate for such Interest Period plus a margin of 1.025% to 1.600% based on the Company’s long-term debt credit ratings and (ii) each Base Rate Committed Loan and each Swing Line Loan denominated in Dollars shall bear interest on the outstanding principal amount thereof from the applicable borrowing date at a variable rate per annum equal to the Base Rate plus a margin of 0.025% to 0.600% based on the Company’s long-term debt credit rating. In addition, the Company has agreed to pay a facility fee equal to a variable rate between 0.100% and 0.275% per year based on the Company’s long-term debt credit rating times the actual daily amount of the Commitments, regardless of usage, quarterly in arrears on the last business day of each March, June, September and December, commencing with the first such date to occur after the Closing Date.

The Company has unconditionally and irrevocably guaranteed the obligations of each of its subsidiaries in the event a subsidiary is named a borrower under the Credit Facility. The Credit Agreement contains customary conditions precedent, representations and warranties, affirmative and negative covenants, events of default and indemnities. The negative covenants include restrictions on liens and fundamental changes. These covenants are subject to a number of important exceptions and qualifications. The Credit Agreement also requires a minimum consolidated net interest coverage ratio of 3.5 to 1.0 as at the last day of any fiscal quarter. Certain changes of control with respect to the Company would constitute an event of default under the Credit Facility. Upon the occurrence and during the continuance of an event of default, the lenders may declare the outstanding advances and all other obligations under the Credit Facility immediately due and payable. Borrowings under the Credit Facility are prepayable at the Company’s option in whole or in part without premium or penalty.

The foregoing description of the Credit Agreement does not purport to be a complete statement of the parties’ rights under such agreement and is qualified in its entirety by reference to the full text of the Credit Agreement (including exhibits), which is filed as Exhibit 10.1 and incorporated by reference herein.

In the ordinary course of business, certain of the lenders under the Credit Agreement and their affiliates have provided, and may in the future provide, investment banking, commercial banking, cash management, foreign exchange or other financial services to the Company for which they have received compensation and may receive compensation in the future.

On December 4, 2020 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported positive interim data from the Company’s dose escalation Phase 1 study of FT516 in combination with rituximab for patients with relapsed / refractory B-cell lymphoma (Press release, Fate Therapeutics, DEC 4, 2020, View Source [SID1234572170]). FT516 is the Company’s universal, off-the-shelf natural killer (NK) cell product candidate derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor, which is designed to maximize antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells.

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"We are highly encouraged by these Phase 1 data, which clearly demonstrate that off-the-shelf, iPSC-derived NK cells can drive complete responses for cancer patients and that our proprietary hnCD16 Fc receptor can effectively synergize with and enhance the mechanism of action of tumor-targeted antibodies," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "Importantly, the safety profile of FT516 continues to suggest multiple doses of iPSC-derived NK cells can be administered in the outpatient setting, and supports potential use across multiple lines of therapy, including as part of early-line CD20-targeted monoclonal antibody regimens, for the treatment of B-cell lymphoma."

As of a November 16, 2020 data cutoff, three patients in the second dose cohort of 90 million cells per dose and one patient in the third dose cohort of 300 million cells per dose were available for assessment of safety and efficacy. All four patients were heavily pre-treated, having received at least two prior rituximab-containing regimens. Each patient received two 30-day treatment cycles, with each cycle consisting of fludarabine and cyclophosphamide lympho-conditioning followed by three once-weekly doses of FT516, IL-2 cytokine support, and rituximab.

Safety Data
All four relapsed / refractory patients were administered FT516 in an outpatient setting with no requirement for inpatient monitoring. No dose-limiting toxicities, and no cases of any grade of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease, were observed. The multi-dose, two-cycle treatment regimen was well-tolerated with no FT516-related grade 3 or greater adverse events reported by investigators. In addition, no evidence of anti-product T- or B-cell mediated host-versus-product alloreactivity was detected, supporting the potential to safely administer up to six doses of FT516 in the outpatient setting without patient matching. All grade 3 or greater treatment emergent adverse events were not related to FT516 and were consistent with lympho-conditioning chemotherapy and underlying disease.

Activity Data
Three of four relapsed / refractory patients achieved an objective response, including two complete responses (CR), following the second FT516 treatment cycle as assessed by PET-CT scan per Lugano 2014 criteria. A CR was achieved in one patient with diffuse large B-cell lymphoma (DLBCL) who was most recently refractory to a rituximab-containing treatment regimen, and a CR was achieved in one patient with follicular lymphoma (FL) who had previously been treated with four rituximab-containing treatment regimens. Notably, in one patient for which an interim tumor assessment showed a partial response following the first FT516 treatment cycle, the response deepened to a CR following administration of the second FT516 treatment cycle, suggesting that additional FT516 treatment cycles can confer clinical benefit.

FT516 Dose
Cohort
Subject
#
Lymphoma
Type
Prior Systemic Therapy Protocol-defined
Response1
Rituximab-containing
Therapies Relapsed /
Refractory
90M cells
2005 DLBCL 2 Refractory CR
2006 DLBCL 2 Relapsed PR
2007 DLBCL 3 Relapsed PD
300M cells 2008 FL 4 Relapsed CR
M = million; CR = Complete Response; PR = Partial Response; PD = Progressive Disease
As of November 16, 2020 database entry. Data subject to cleaning and source document verification.
1 Day 29 of the second FT516 treatment cycle as assessed per Lugano 2014 criteria

Dose escalation is continuing in the current dose cohort of 300 million cells per dose in combination with rituximab, and a fourth dose cohort of 900 million cells per dose in combination with rituximab is planned. The Company previously reported that two patients treated in the first dose cohort of 30 million cells per dose in combination with rituximab showed a protocol-defined response assessment of progressive disease. No events of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease were observed in either patient.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 300 issued patents and 150 pending patent applications.

About FT516
FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG1 antibodies. Scientists from the Company have shown in a peer-reviewed publication (Blood. 2020;135(6):399-410) that hnCD16 iPSC-derived NK cells, compared to peripheral blood NK cells, elicit a more durable anti-tumor response and extend survival in combination with anti-CD20 monoclonal antibodies in an in vivo xenograft mouse model of human lymphoma. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in an open-label, multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071). Additionally, FT516 is being investigated in an open-label, multi-dose Phase 1 clinical trial in combination with avelumab for the treatment of advanced solid tumor resistant to anti-PDL1 checkpoint inhibitor therapy (NCT04551885).

On December 4, 2020 Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology both in vivo and ex vivo, reported the closing of an underwritten public offering of 5,513,699 shares of its common stock, including the exercise in full by the underwriters of their option to purchase an additional 719,178 shares, at the public offering price of $36.50 per share (Press release, Intellia Therapeutics, DEC 4, 2020, View Source [SID1234572169]). The gross proceeds raised in the offering, before underwriting discounts and commissions and expenses of the offering, were approximately $201 million.

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Goldman Sachs & Co. LLC, Jefferies LLC and SVB Leerink LLC acted as joint book-running managers for the offering.

The shares of common stock were offered by Intellia pursuant to a shelf registration statement that was previously filed with the U.S. Securities and Exchange Commission (SEC) and automatically became effective upon filing. A final prospectus supplement and accompanying prospectus relating to and describing the terms of the offering was filed with the SEC on December 2, 2020. The final prospectus supplement and accompanying prospectus relating to the offering may be obtained from: Goldman Sachs & Co. LLC, by mail at 200 West Street, New York, NY 10282, Attention: Prospectus Department, by telephone at (866) 471-2526, or by email at [email protected]; or Jefferies LLC, by mail at 520 Madison Avenue, 2nd Floor, New York, NY 10022, Attention: Equity Syndicate Prospectus Department, by telephone at (877) 547-6340, or by email at [email protected]; or SVB Leerink LLC, by mail at One Federal Street, 37th Floor, Boston, MA 02110, Attention: Syndicate Department, by telephone at (800) 808-7525, ext. 6132, or by email at [email protected]; or by accessing the SEC’s website at www.sec.gov.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On December 4, 2020 Y-mAbs Therapeutics, Inc. (Nasdaq: YMAB) (the "Company" or "Y-mAbs") a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer and Takeda Israel, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) ("Takeda") reported that they have entered into an exclusive license and distribution agreement for the registration and commercialization in Israel of DANYELZA for the treatment of patients with relapsed/refractory high-risk neuroblastoma and omburtamab for the treatment of pediatric patients with CNS/leptomeningeal metastasis from neuroblastoma (Press release, Y-mAbs Therapeutics, DEC 4, 2020, View Source [SID1234572168]). DANYELZA (naxitamab-gqgk) was approved by the U.S. FDA on November 25, 2020. Additionally, Y-mAbs plans to resubmit the amended BLA for omburtamab for the treatment of pediatric patients with CNS/leptomeningeal metastasis from neuroblastoma to the FDA by the end of 2020 or in early 2021.

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Under the terms of the agreement, Takeda will employ its proven platform of sales, access, marketing and regulatory expertise to distribute DANYELZA and omburtamab, if approved, in the territory. The license and distribution agreement includes the State of Israel, West Bank and Gaza Strip. All other geographies worldwide remain with the Company. Financial details were not disclosed.

"We are very pleased to enter into this license and distribution agreement with Takeda, and now expect to see a treatment cluster established in the Middle East, thereby making DANYELZA and omburtamab, if approved, available to children with unmet medical needs in the region," said Thomas Gad, founder, Chairman and President at Y-mAbs.

Arie Kramer, General Manager at Takeda further notes, "Relapsed/refractory high-risk neuroblastoma and CNS/leptomeningeal metastasis from neuroblastoma are cancers for which there are currently no approved therapies in Israel, and we are excited to partner with Y-mAbs, making these compounds available and bringing new hopes to pediatric patients suffering from these devastating conditions in Israel."

Researchers at MSK developed DANYELZA and omburtamab, which are exclusively licensed by MSK to Y-mAbs. As a result of this licensing arrangement, MSK has institutional financial interests in the compounds and in Y-mAbs.

About DANYELZA (naxitamab-gqgk)
DANYELZA (naxitamab-gqgk) is indicated, in combination with granulocyte-macrophage colony-stimulating factor ("GM-CSF"), for the treatment of pediatric patients 1 year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow who have demonstrated a partial response, minor response, or stable disease to prior therapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefits in a confirmatory trial. DANYELZA includes a Boxed Warning for serious infusion-related reactions, such as cardiac arrest and anaphylaxis, and neurotoxicity, such as severe neuropathic pain and transverse myelitis. See full Prescribing Information for complete Boxed Warning and other important safety information.

About Neuroblastoma

Neuroblastoma is a solid tumor of childhood that arises in the nervous system, outside of the brain. The clinical behavior of neuroblastoma is highly variable, with some tumors being easily treatable, but the majority being very aggressive. All patients are staged based on the International Neuroblastoma Staging System Committee ("INSS") system, ranging from stage 1 through stage 4S. All patients with stage 4 disease diagnosed after one year of age are classified in the high-risk category, where the neuroblastoma tumor cells have already metastasized to other sites in the body, such as the bone or bone marrow. Essentially all patients who have tumors with many copies, or amplification, of the MYCN oncogene also have high-risk disease, even if they do not have evidence of the tumor having spread.

On December 4, 2020 Spectrum Pharmaceuticals (NasdaqGS: SPPI), a biopharmaceutical company focused on novel and targeted oncology therapies, reported that three posters highlighting its drug development pipeline would be presented at the upcoming San Antonio Breast Cancer Conference (SABCS) to be held December 8 – 11, 2020 (Press release, Spectrum Pharmaceuticals, DEC 4, 2020, View Source [SID1234572164]).

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"We are pleased to have two scientific communications at SABCS on ROLONTIS (eflapegrastim) and the results of our Phase 2 study for Poziotinib in HER2+ metastatic breast cancer who have failed multiple lines of HER2 directed therapy," said Francois Lebel, M.D., Chief Medical Officer at Spectrum Pharmaceuticals. "We look forward to sharing these data with the medical and scientific community."

The three posters are listed below.

Poster Title: A Phase 2 study of poziotinib in patients with HER2-positive metastatic breast cancer previously treated with HER2 therapies
Authors: Adam Brufsky, M.D., Ph.D., et al.
Poster Number: PD1-07 (Spotlight Poster Discussion)
Poster Category: Breast Cancer treatment
Poster Section: Spotlight Poster Discussion 1
Poster Presentation Date/Time: December 9, 2020 4:00 PM – 5:15 PM CT

Poster Title: Pooled efficacy analysis from two Phase 3 studies in patients receiving eflapegrastim, a novel, long-acting granulocyte-colony stimulating factor, following TC for early stage breast cancer
Authors: Lee S. Schwartzberg, M.D., et al.
Poster Number: PS9-59
Poster Category: Psychosocial, Quality of Life and Educational Aspects
Poster Section: Poster Session 9
Poster Presentation Date/Time: Wednesday, December 9, 2020: 8:00 AM CT.

Poster Title: Open-label, Phase 1 study to evaluate duration of severe neutropenia after the same-day, varying dosing time schedules of eflapegrastim administration in patients with breast cancer receiving docetaxel and cyclophosphamide (NCT04187898)
Authors: Lee S. Schwartzberg, M.D., et al.
Poster Number: OT-06-01
Poster Category: Chemotherapy – Targeting Neutropenia
Poster Section: Ongoing Trial posters
Poster Presentation Date/Time: Wednesday, December 9, 2020: 8:00 AM CT

Copies of the posters will be available on the Spectrum Pharmaceuticals website following presentation at the meeting. ROLONTIS is an investigational drug not approved by the U.S. Food and Drug Administration (FDA) and the BLA is currently under review by the agency for the treatment of chemotherapy-induced neutropenia.