On January 20, 2019 Samsung Bioepis Co., Ltd. reported that the U.S. Food and Drug Administration (FDA) has approved ONTRUZANT (trastuzumab-dttb), a biosimilar referencing HERCEPTIN 1 (trastuzumab), across all eligible indications, namely adjuvant treatment of HER2-overexpressing breast cancer, metastatic breast cancer and metastatic gastric cancer or gastroesophageal junction adenocarcinoma in patients who have not received prior treatment for metastatic disease (Press release, Samsung Bioepis, JAN 20, 2019, View Source [SID1234532794]). Please see Boxed Warnings and Important Safety Information for ONTRUZANT below.

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ONTRUZANT is Samsung Bioepis’ first oncology biosimilar to receive FDA approval, and will be marketed and distributed in the United States (US) by Merck, which is known as MSD outside of the US and Canada.

"For many cancer patients in the US, battling cancer has not only been a health issue, but a considerable financial burden brought on by cancer treatment. Biosimilars are intended to be lower cost, high-quality treatment options that have the potential to alleviate such burden. We sincerely hope our trastuzumab biosimilar will do exactly that," said Sang-Jin Pak, Senior Vice President and Head of Commercial Division, Samsung Bioepis. "At Samsung Bioepis, we will continue to demonstrate our enduring commitment to biosimilars by further strengthening our pipeline and widening the availability of approved treatments for cancer patients across the US."

ONTRUZANT was also approved by the European Commission (EC) in November 2017, and has since been launched in a growing number of European countries.

About ONTRUZANT (trastuzumab-dttb)
ONTRUZANT is indicated for adjuvant treatment of HER2-overexpressing node-positive or node-negative (ER/PR-negative or with one high-risk feature*) breast cancer:

As part of a treatment regimen containing doxorubicin, cyclophosphamide and either paclitaxel or docetaxel
With docetaxel and carboplatin
As a single agent following multi-modality anthracycline-based therapy
Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product.
* High-risk is defined as ER/PR positive with one of the following features: tumor size >2 cm, age <35 years, or tumor grade 2 or 3.
ONTRUZANT is indicated:

In combination with paclitaxel for the first line treatment of HER2-overexpressing metastatic breast cancer
As a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease
Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product.
ONTRUZANT is indicated, in combination with cisplatin and capecitabine or 5-fluorouracil, for the treatment of patients with HER2 overexpressing metastatic gastric or gastroesophageal junction adenocarcinoma, who have not received prior treatment for metastatic disease.
Select patients for therapy based on an FDA-approved companion diagnostic for a trastuzumab product

Select Important Safety Information

Cardiomyopathy

ONTRUZANT administration can result in sub-clinical and clinical cardiac failure manifesting as congestive heart failure and decreased left ventricular ejection fraction with greatest risk when administered concurrently with anthracyclines. Evaluate cardiac function prior to and during treatment. Discontinue ONTRUZANT for cardiomyopathy.
Infusion Reactions; Pulmonary Toxicity

Administration can result in serious and fatal infusion reactions and pulmonary toxicity. Symptoms usually occur during or within 24 hours of administration. Discontinue ONTRUZANT for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome.
Embryo-Fetal Toxicity

Exposure to ONTRUZANT during pregnancy can result in oligohydramnios in some cases complicated by pulmonary hypoplasia, skeletal abnormalities, and neonatal death. Advise patients of these risks and the need for effective contraception
Exacerbation of Chemotherapy-Induced Neutropenia

In randomized, controlled clinical trials, the per-patient incidences of NCI-CTC Grade 3-4 neutropenia and of febrile neutropenia were higher in patients receiving trastuzumab products in combination with myelosuppressive chemotherapy as compared to those who received chemotherapy alone. The incidence of septic death was similar among patients who received trastuzumab and those who did not
Most Common Adverse Reactions

The most common adverse reactions for trastuzumab products in breast cancer were fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, dyspnea, rash, neutropenia, anemia, and myalgia
The most common adverse reactions for trastuzumab products in metastatic gastric cancer were neutropenia, diarrhea, fatigue, anemia, stomatitis, weight loss, upper respiratory tract infections, fever, thrombocytopenia, mucosal inflammation, nasopharyngitis, and dysgeusia
These are not all of the risks associated with ONTRUZANT. For additional information on ONTRUZANT indications, as well as Important Safety Information related to its use, including Boxed WARNINGS, please see the ONTRUZANT Prescribing Information HERE

On January 16, 2019 Precision BioSciences ("Precision" or the "Company"), a genome editing company dedicated to improving life (DTIL) through its proprietary ARCUS genome editing platform, reported that it has entered into an agreement for the issuance and sale of convertible promissory notes in a private placement transaction in the aggregate principal amount of approximately $40 million, which will bring the Company’s total capital generated in the last year to over $150 million and total funding since inception to over $300 million (Press release, Precision Biosciences, JAN 16, 2019, View Source [SID1234534181]). Contributors to this financing were largely first-time investors in the Company.

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Investors in Precision now include ArrowMark Partners, Franklin Templeton, Cowen Healthcare Investments, venBio, F-Prime, RA Capital Management, Brace Pharma Capital, Pontifax AgTech, OCV Partners, DSAM, Adage Capital Management, Cormorant Asset Management, Gilead Sciences, Laurion Capital Management, Vivo Capital, Lilly Asia Ventures, Alexandria Venture Investments, Ridgeback Capital, Ditch Plains Capital Management, Agent Capital, entities affiliated with Leerink Partners, Amgen Ventures, Osage University Partners, DUMAC and the Longevity Fund.

On January 19, 2019 On January 19, 2019, Shanghai Cellular Biopharmaceutical Group Ltd. ("CBMG Shanghai"), a controlled entity of Cellular Biomedicine Group, Inc. (the "Company"), reported that it has entered into a credit agreement (the "Credit Agreement") with China Merchants Bank, Shanghai Branch (the "Merchants Bank") (Filing, 8-K, Cellular Biomedicine Group, JAN 19, 2019, View Source [SID1234532905]). Pursuant to the Credit Agreement, the Merchants Bank agreed to extend credit of up to RMB 100 million (approximately $14.7 million) to CBMG Shanghai via revolving and/or one-time credit lines. The types of credit available under the Credit Agreement, include, but not limited to, working capital loans, trade financing, commercial draft acceptance, letters of guarantee and derivative transactions. The credit period under the Credit Agreement runs until December 30, 2019. As of the date of this Current Report on Form 8-K, no amounts had been drawn down under the Credit Agreement.

Pursuant to the Credit Agreement, CBMG Shanghai will enter into a supplemental agreement with the Merchants Bank prior to the applicable drawdown that will set forth the terms of each borrowing thereunder (except for working capital loans), including principal, interest rate, term of loan and use of borrowing proceeds. With regard to working capital loans to be provided pursuant to the Credit Agreement, CBMG Shanghai shall submit a withdrawal application that includes the principal amount needed, purposes of the loan and a proposed quarterly interest rate and term of the loan for the Merchants Bank’s review and approval. The terms approved by the bank will govern such working capital loans. The bank has the right to adjust the interest rate for working capital loans from time to time based on changes in national policy, changes in interest rate published by the People’s Bank of China, credit market conditions and the bank’s credit policies. Upon CBMG Shanghai’s non-compliance with the agreed use of loan proceeds, the interest rate for the amount of loan proceeds improperly used will be the original rate plus 100% starting on the first day of such use. If CBMG Shanghai fails to pay a working capital loan on time, an extra 50% interest will be charged on the outstanding balances starting on the first day of such default.

Under the Credit Agreement, CBMG Shanghai has the obligation to notify the Merchants Bank prior to certain corporate actions and assist the bank in taking measures to ensure repayment of the loans provided under the Credit Agreement upon occurrence of such events. Such corporation actions include: (i) major financial losses and assets losses, (ii) loans to or guarantees for third parties or mortgages on its properties, (iii) revocation or cancellation of business license or applications for bankruptcy, (iv) major operational or financial crises of its controlling shareholder or other related entities that affect its business operations, (v) related party transactions that involve 10% or more of CBMG Shanghai’s net assets and (vi) legal proceeding that have material adverse effects on its operations or financial condition. Pursuant to the Credit Agreement, CBMG Shanghai cannot enter into a merger, an acquisition or a joint venture, transfer its equity interest or consummate a reorganization or share ownership restructuring without prior written consent of the Merchants Bank. The Credit Agreement also contains a covenant requiring that CBMG Shanghai maintain or improve its existing operations and preserve or increase the value of its existing assets.

Events of default under the Credit Agreement include, among other matters, CBMG Shanghai’s failure to perform its obligations thereunder, untrue or inaccurate representations, use of loan proceeds for purposes that are inconsistent with the Credit Agreement or related agreements. Additionally, a default under any other loan agreement of CBMG Shanghai that is not cured within three months of such default shall be deemed an event of default under the Credit Agreement. Upon the occurrence of an event of default, the Merchant Bank has the right to reduce the credit available under the Credit Agreement, suspend the use of the remaining credit by CBMG Shanghai and declare all outstanding balance to become immediately due and payable.

Pursuant to a pledge agreement which became enforceable upon execution of the Credit Agreement, Cellular Biomedicine Group Ltd. (HK), a wholly owned subsidiary of the Company ("CBMG HK"), provided a guarantee of CBMG Shanghai’s obligations under the Credit Agreement. In connection with such guarantee, CBMG HK deposited $17,000,000 into its account at the Merchants Bank for a 12-month period starting January 7, 2019 and also granted the Merchants Bank a security interest in the cash deposited.

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Schedule your 30 min Free 1stOncology Demo!
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On January 18, 2019, Bristol-Myers Squibb Company ("Bristol-Myers Squibb") reported that it has entered into a Term Loan Agreement (the "Term Loan Agreement") with the lenders party thereto and Morgan Stanley Senior Funding, Inc., as administrative agent (Filing, 8-K, Bristol-Myers Squibb, JAN 18, 2019, View Source [SID1234532805]). The Term Loan Agreement provides for total term loan commitments in an aggregate principal amount of $8.0 billion and reduces the $33.5 bridge facility commitments previously described in the Current Report on Form 8-K filed by Bristol-Myers Squibb with the Securities and Exchange Commission (the "SEC") on January 4, 2019 (the "January 4 Current Report") by such principal amount. The Term Loan Agreement was entered into in connection with the previously announced proposed merger (the "Merger") of a wholly owned subsidiary of Bristol-Myers Squibb with Celgene Corporation ("Celgene"), pursuant to the Agreement and Plan of Merger, dated as of January 2, 2019 (the "Merger Agreement"), among Bristol-Myers Squibb, Celgene and Burgundy Merger Sub, Inc., a wholly-owned subsidiary of Bristol-Myers Squibb, described in the January 4 Current Report.

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The lenders party to the Term Loan Agreement will be obligated to make loans under the Term Loan Agreement upon the satisfaction or waiver of several limited conditions, including but not limited to completion of the Merger, the non-occurrence of a material adverse effect (as such term is defined in the Term Loan Agreement) on Celgene, the accuracy in all material respects of certain representations and warranties related to both Bristol-Myers Squibb and Celgene, the absence of certain defaults by Bristol-Myers Squibb, the delivery of certain financial statements of Bristol-Myers Squibb and Celgene and other customary conditions to completion more fully set forth in the Term Loan Agreement. The date such limited conditions are satisfied or are waived in accordance with the terms of the Term Loan Credit Agreement and the loans thereunder are funded is referred to herein as the "Closing Date."

The term loan facility under the Term Loan Agreement consists of a $1 billion 364-day tranche, a $4 billion three-year tranche and a $3 billion five-year tranche. Borrowings under the Term Loan Agreement will be unsecured. The term loans are pre-payable without premium or penalty (but subject to breakage costs, if applicable). The term loans under the $1 billion 364-day and the $4 billion three-year tranche do not amortize. The five-year tranche amortizes in equal quarterly amounts equal to (i) 0.0% from after the Closing Date to, and including, the third anniversary of the Closing Date and (ii) 10% per annum from after the third anniversary to, and including, the five-year anniversary of the Closing Date. The $1 billion tranche of the term loan facility will mature and be payable on the 364-day anniversary of the Closing Date. The $4 billion tranche of the term loan facility will mature and be payable on the third anniversary of the Closing Date. The $3 billion tranche of the term loan facility will mature and be payable (to the extent not amortized) on the fifth anniversary of the Closing Date.

At the option of Bristol-Myers Squibb, borrowings under the Term Loan Agreement will bear interest at either a base rate or at the Eurodollar rate, plus, in each case, an applicable margin. The applicable margin will range from (i) with respect to the $1 billion 364-day tranche, 0.0 – 0.125% with respect to base rate borrowings, and 0.75 – 1.125% with respect to Eurodollar rate borrowings, (ii) with respect to the $4 billion three-year tranche, 0.0 – 0.25% with respect to base rate borrowings, and 0.875 – 1.25% with respect to Eurodollar rate borrowings, and (iii) with respect to the $3 billion five-year tranche, 0.0 – 0.375% with respect to base rate borrowings, and 1.00 – 1.375% with respect to Eurodollar rate borrowings in each case, based on the public ratings of Bristol-Myers Squibb’s non-credit enhanced senior unsecured long-term debt, as set forth in the Term Loan Agreement. The base rate will be, for any day, a fluctuating rate per annum equal to the highest of (i) the rate last quoted by The Wall Street Journal as the "Prime Lending Rate" (if more than one rate is published as the Prime Lending Rate, then the highest of such rates), (ii) the Federal Funds effective rate plus 0.5% and (iii) the one-month reserve adjusted Eurodollar Rate plus 1% (provided, that the reserve adjusted Eurodollar Rate shall not be less than zero). The Eurodollar rate will be an annual rate equal to the London Interbank Offered Rate. Pursuant to the base rate option, interest will be calculated on the basis of the actual number of days elapsed in a year of 365 or 366 days and will be payable quarterly in arrears. Alternatively, under the Eurodollar rate option, interest will be determined based on interest periods to be selected by Bristol-Myers Squibb of one, two, three or six months, will be calculated on the basis of the actual number of days elapsed in a year of 360 days and will be payable at the end of each interest period (and at the end of every three months, in the case of interest periods longer than three months).

The Term Loan Agreement contains certain covenants relating to the following subjects: legal existence; business and properties; delivery of financial statements, reports, etc.; maintenance of insurance; obligations and payment of taxes; litigation and other notices; books and records; maintenance of ratings; compliance with laws; limitations on mergers, sales of assets and consolidations; limitations on liens; limitations on sale and leaseback transactions; and sanctions, anti-corruption laws and guaranties.

The Term Loan Agreement also contains certain events of default, limited to nonpayment of principal when due; nonpayment of interest, fees or other amounts after a three business day grace period; material inaccuracy of representations and warranties; violation of covenants (subject, in the case of certain affirmative covenants, to certain grace periods); cross-payment default and cross-acceleration; bankruptcy events; material judgments; change of control; certain ERISA events; and to the extent there are any guarantees of the term facility then in effect, actual or asserted invalidity of such guarantees under the Term Loan Agreement.

The description of the Term Loan Agreement contained in this item 1.01 does not purport to be complete and is qualified in its entirety by reference to the full text of the Term Loan Agreement, a copy of which is filed hereto as Exhibit 10.1 to this Current Report on Form 8-K, and the terms of which are incorporated herein by reference.
The representations, warranties and covenants contained in the Term Loan Agreement were made only for purposes of such agreement and as of the dates specified therein, were solely for the benefit of the parties thereto and may be subject to standards of materiality applicable to the contracting parties that differ from those applicable to investors. Investors should not rely on the representations, warranties and covenants or any descriptions thereof as characterizations of the actual state of facts or condition of Bristol-Myers Squibb and its subsidiaries. Moreover, information concerning the subject matter of any representations, warranties and covenants may change after the dates of the Term Loan Agreement, which subsequent information may or may not be fully reflected in public disclosures by Bristol-Myers Squibb.

Certain of the financial institutions party to the Term Loan Agreement, either directly or through affiliates, have performed, and may in the future perform, various commercial banking, investment banking and other financial advisory services in the ordinary course of business for Bristol-Myers Squibb and in connection with the Merger for which they have received, and will receive, customary fees and commissions.