Entry into a Material Definitive Agreement

On February 4, 2019 OPKO Health, Inc. (the "Company") reported that it entered into an underwriting agreement (the "Underwriting Agreement") with Jefferies LLC (the "Underwriter") to issue and sell $200 million aggregate principal amount of its 4.50% Convertible Senior Notes due 2025 (the "Notes") in a registered public offering under the Securities Act of 1933, as amended (the "Securities Act") pursuant to the Company’s effective shelf registration statement on Form S-3 (File No. 333-229400) and a related prospectus, together with the related prospectus supplements for the underwritten public offering of the Notes, filed with the Securities and Exchange Commission (Filing, 8-K, Opko Health, FEB 4, 2019, View Source [SID1234533174]).

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In addition, the Company granted the Underwriter a 30-day option to purchase up to an additional $30 million aggregate principal amount of the Notes to cover over-allotments, if any.

The Company intends to use the net proceeds received from the offering of the Notes to fund research and development to further develop and commercialize its portfolio of proprietary pharmaceutical and diagnostic products and for working capital, capital expenditures, acquisitions and other general corporate purposes, which will include the repayment or repurchase of indebtedness or debt securities outstanding from time to time, including $28.8 million principal amount and accrued but unpaid interest currently outstanding under the Company’s line of credit with an affiliate of the Company’s Chairman and Chief Executive Officer.

The Underwriting Agreement includes customary representations, warranties and covenants by the Company and customary closing conditions. Under the terms of the Underwriting Agreement, the Company has agreed to indemnify the Underwriter against certain liabilities.

The closing of the issuance of the Notes occurred on February 7, 2019.

The foregoing description of the Underwriting Agreement is qualified in its entirety by reference to the Underwriting Agreement attached as Exhibit 1.1 to this Current Report on Form 8-K and is incorporated by reference herein. A copy of the opinion of Greenberg Traurig, LLP regarding the validity of the Notes issued in this offering and the shares of the Company’s common stock, par value $0.01 per share ("Common Stock"), issuable upon conversion of the Notes is filed as Exhibit 5.1 to this Current Report on Form 8-K.

Indenture

On February 7, 2019, the Company entered into a Base Indenture (the "Base Indenture") and a First Supplemental Indenture (the "First Supplemental Indenture" and together with the Base Indenture, the "Indenture") relating to the issuance of the Notes, by and between the Company and U.S. Bank National Association, as trustee (the "Trustee").

The Notes bear interest at a rate of 4.50% per year, payable semiannually in arrears on February 15 and August 15 of each year, beginning on August 15, 2019. The Notes will mature on February 15, 2025, unless earlier converted, redeemed or purchased. Upon conversion, holders of the Notes will receive cash, shares of Common Stock, or a combination of cash and shares of Common Stock, at the Company’s election.

If the Company undergoes a Fundamental Change (as defined in the Indenture) prior to the maturity date, subject to certain conditions, holders may require the Company to repurchase for cash all or any portion of their Notes at a repurchase price equal to 100% of the principal amount of the Notes to be repurchased, plus accrued and unpaid interest to, but excluding, the Fundamental Change Repurchase Date (as defined in the Indenture).

Holders may surrender their Notes for conversion at any time prior to the close of business on the business day immediately preceding November 15, 2024 only upon the satisfaction of certain conditions relating to the closing sale price of the Common Stock, the trading price per $1,000 principal amount of Notes, if the Company calls any or all of the Notes for redemption, and specified corporate events. On or after November 15, 2024 until the close of business on the business day immediately preceding the maturity date, holders of Notes may surrender their Notes for conversion at any time, regardless of the foregoing circumstances.

The initial conversion rate will be 236.7424 shares of Common Stock for each $1,000 aggregate principal amount of Notes, which represents an initial conversion price of approximately $4.22 per share of Common Stock. The conversion rate is subject to adjustment in certain circumstances. The Company may not redeem the Notes prior to February 15, 2022, but may redeem the Notes, at its option, on or after February 15, 2022 if the last reported sale price of the Common Stock has been at least 130% of the conversion price for the Notes for at least 20 trading days (whether or not consecutive) during any 30 consecutive trading day period ending on, and including, the trading day immediately preceding the date on which the Company provides notice of redemption. The redemption price will be equal to 100% of the principal amount of the Notes to be redeemed, plus accrued and unpaid interest up to, but excluding, the redemption date.

If certain Events of Default (as defined in the Indenture) occur and are continuing, the Trustee or the holders of at least 25% in aggregate principal amount of the outstanding Notes may declare the principal amount of, and accrued but unpaid interest on, the Notes to be due and payable immediately. In the case of an Event of Default arising out of certain events of bankruptcy, insolvency or reorganization (as set forth in the Indenture), the principal amount of, and accrued but unpaid interest on, the Notes will automatically become immediately due and payable.

The Notes are senior unsecured obligations of the Company and rank (i) senior in right of payment to any indebtedness of the Company that is expressly subordinated in right of payment to the Notes; (ii) equal in right of payment to any existing and future liabilities of the Company that are not so subordinated; (iii) effectively junior in right of payment to any secured indebtedness of the Company, to the extent of the value of the assets securing such indebtedness; and (iv) structurally junior to all indebtedness and other liabilities (including trade payables) of the Company’s current and future subsidiaries.

The foregoing description of the Notes and the Indenture is qualified in its entirety by reference to the form of global Note, Base Indenture and the Supplemental Indenture attached as Exhibit 4.1, Exhibit 4.2 and Exhibit 4.3, respectively, to this Current Report on Form 8-K and are incorporated by reference.

Share Lending Agreement

On February 4, 2019, in connection with the Company’s offering of the Notes, the Company entered into a share lending agreement (the "Share Lending Agreement") with Jefferies Capital Services, LLC (the "Share Borrower"), an affiliate of the Underwriter, under which the Company will lend to the Share Borrower a total of up to 30 million shares of Common Stock. The borrowed shares are newly-issued shares issued in connection with the offering of the Notes and will be cancelled or held as treasury shares upon the expiration or early termination of the Share Lending Agreement.

Purchasers of the Notes may separately sell up to 30 million shares of Common Stock that they may borrow through the Share Borrower. The Company expects that the selling stockholders will use the short position created by such sales to establish their initial hedge with respect to their investments in the Notes. The Company will not receive any proceeds from the sale of the borrowed shares, but will receive from the Share Borrower a one-time nominal fee of $0.01 per share for each newly-issued share of Common Stock issued in connection with the Share Lending Agreement. On February 7, 2019, the Company issued 29.25 million shares of Common Stock and loaned them to the Share Borrower under the Share Lending Agreement.

The foregoing description of the Share Lending Agreement is qualified in its entirety by reference to the Share Lending Agreement attached as Exhibit 10.1 to this Current Report on Form 8-K are incorporated by reference herein. A copy of the opinion of Greenberg Traurig, LLP regarding the validity of the shares of Common Stock issued in connection with the Share Lending Agreement is filed as Exhibit 5.2 to this Current Report on Form 8-K.

Syntrix Wins $3.4M NIH Grant to Conduct Phase 1/2 Trial of SX-682 in Myelodysplastic Syndrome

On February 4, 2019 Syntrix Pharmaceuticals reported that it has been awarded a three-year grant worth $3.4 million from the National Heart Lung and Blood Institute of the National Institutes of Health to assess its investigational CXCR1/2 inhibitor SX-682 in patients with low- and high-risk myelodysplastic syndrome (MDS) who had progression or were intolerant to prior therapy (Press release, Syntrix, FEB 4, 2019, View Source [SID1234553882]). The phase 1/2 clinical trial will be carried out in collaboration with researchers at the Moffitt Cancer Center led by Dr. Rami Kamrokji.

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"Patients with low-risk MDS have an expected median survival measured in years, but suffer from hematologic deficits and related symptoms that lead to transfusion dependence," said Syntrix’s President John Zebala. "Patients with high-risk MDS have debilitating cytopenias and borderline leukemia, and can have expected survival measured in months."

Only three drugs have received regulatory approval for MDS treatment, all with suboptimal response rates (<50%) and of limited durability (1-2 years). Once these agents fail in patients, there is no second-line treatment. Prognosis after failure is dismal, with median survival estimated at <6 months for higher-risk patients, and <18 months for lower-risk patients.

The Phase 1/2 clinical trial of SX-682 builds on groundbreaking discoveries by investigators at the Moffitt Cancer Center and the Albert Einstein College of Medicine who showed CXCR1/2 is pivotal in MDS and that its inhibition is a therapeutic strategy against the disease.

This Phase 1/2 trial in MDS patients will test the hypothesis that targeting CXCR1/2 with SX-682 will be efficacious in the disease by eliminating the MDS stem cells and bone marrow MDSCs. The FDA approved the protocol for the study in an IND sponsored by Syntrix.

ABOUT SX-682: SX-682 is a clinical-stage oral allosteric small-molecule inhibitor of CXCR1 and CXCR2 (CXCR1/2). Inhibiting both human receptors is believed essential. CXCR1/2 are a combined "master switch" of the immunosuppressive tumor microenvironment. Clinical studies in melanoma, breast, ovarian, prostate and colon cancer have shown a direct correlation between serum levels of CXCR1/2 ligands and disease progression. SX-682 has been validated in all major solid tumor models, where it exhibits mono-agent anti-tumor activity, blocks metastasis, depletes immunosuppressive myeloid cells, activates tumor killing by effector cells, reverses chemo-resistance, and potently synergizes with anti-CTLA-4 and anti-PD1. SX-682 is also being evaluated in solid tumors supported by the National Cancer Institute.

Infinity Pharmaceuticals To Present At BIO CEO & Investor Conference

On February 4, 2019 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) announced today that Adelene Perkins, Infinity Pharmaceutical’s Chief Executive Officer, will present at the BIO CEO & Investor Conference on Monday, February 11, 2019, at 10:00 a.m. EST at The New York Marriott Marquis in New York, NY (Press release, Infinity Pharmaceuticals, FEB 4, 2019, View Source [SID1234533031]). A live webcast of the presentation will be available on the Investors/Media section of Infinity’s website at www.infi.com, and will be available for 30 days following the event

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Alnylam to Webcast Presentations at Upcoming February Investor Conferences

On February 4, 2019 Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, reported that management will present company overviews at the following conferences (Press release, Alnylam, FEB 4, 2019, View Source [SID1234533048]):

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21st Annual BIO CEO & Investor Conference on Monday, February 11, 2019 at 1:30 pm ET at the Marriott Marquis in New York City

8th Annual SVB Leerink Global Healthcare Conference onWednesday, February 27, 2019 at 10:30 am ET at the Lotte New York Palace Hotel in New York City

A live audio webcast of each presentation will be available on the Investors section of the Company’s website, www.alnylam.com. A replay will be available on the Alnylam website within 48 hours after each event.

Torque and Thermo Fisher Scientific Announce Collaboration to Build State-of-the-Art Facility to Manufacture Torque’s Deep-Primed T Cell Immunotherapies

On February 4, 2019 Torque, an immuno-oncology company developing first-in-class Deep Primed T Cell Therapeutics to direct immune power deep within the tumor microenvironment, and Thermo Fisher Scientific Inc. (NYSE: TMO), reported a collaboration to build a dedicated Slipstream manufacturing facility for high-efficiency production of Torque’s Deep-Primed T cell immunotherapies (Press release, Torque Therapeutics, FEB 4, 2019, View Source [SID1234553883]).

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Buildout of the Torque/Thermo Fisher manufacturing facility has begun, and the companies anticipate processing patient cells by the end of 2019. The Slipstream platform will initially be used in the clinical development of Torque’s lead Deep-Primed T cell candidate, TRQ-1501, in solid and hematologic tumors; followed by TRQ-1201, also for solid and hematologic tumors.

"Torque’s cell manufacturing technology platform is critical to achieving our goal of developing and commercializing a new class of cellular immunotherapy for cancer patients with both early and advanced disease, particularly for the large population of solid tumor patients in need of new treatments," said Bart Henderson, CEO of Torque. "We are very excited about partnering with Thermo Fisher to build this state-of-the-art manufacturing facility because of their vision and exceptional track record in building high-efficiency, globally integrated operations. This is a pioneering manufacturing partnership with the goal of dramatically improving the efficiency and scalability of producing best-in-class cellular immunotherapy products that have the potential to benefit a significant number of cancer patients."

"Thermo Fisher is dedicated to advancing precision medicine, and our collaboration with Torque is a tangible example of the progress we are making to become a recognized leader in cell therapy manufacturing," said Michel Lagarde, President of Pharma Services for Thermo Fisher Scientific. "We are pleased to partner with Torque to build and launch this unique and advanced manufacturing facility utilizing the Slipstream technology, Torque’s innovative cellular immunotherapy product, which has the potential to transform cancer treatment and patients’ lives."

The Slipstream platform technology situated in Princeton is a revolutionary design that uses a fully closed, semi-automated system that surpasses conventional cell therapy manufacturing techniques. The Slipstream process leverages advanced logistics that enable a substantially smaller manufacturing footprint that is less capital- and labor-intensive. Production capacity can be expanded modularly by adding arrays in Lego-like fashion.

About Slipstream Cell Therapy Manufacturing Technology
Slipstream is a proprietary, high-efficiency T cell manufacturing platform engineered by Torque. Currently marketed immune cell therapies are produced using open, complex, labor- and cost-intensive processes that require a substantial manufacturing facility. In contrast, Slipstream production is semi-automated and fully closed, which eliminates contamination risk between transfers and can dramatically reduce staffing requirements and the factory footprint. The cell engineering process uses a modular design that enables both large-scale and decentralized manufacturing. Slipstream has the potential to improve manufacturing efficiency beyond what is possible with currently used cell therapy manufacturing processes and to move cell therapy production closer to the point of care.

About Torque’s Deep-Primed Immune Cell Therapy Platform
Torque’s Deep-Priming platform uses advanced cell process engineering to:

prime and activate T cells to target multiple tumor antigens and
tether immune-stimulatory drugs to the surface of these multi-target T cells to direct immune activation in the tumor microenvironment
using a proprietary technology platform, without genetic engineering, for a high margin of safety.
Deep-Primed T cells both target multiple tumor antigens and pharmacologically activate an immune response with anchored cytokines. This process does not require genetic engineering of the T cells and so preserves the natural T cell receptor for delivering a regulated immune response, with the potential for a high margin of safety. In addition to antigen priming, immunomodulators are tethered to the surface of Deep-Primed T cells—initially IL-15 and IL-12 cytokines, and TLR agonists—that activate both innate and adaptive immunity. Administering these immunomodulators systemically to a patient can cause lethal toxicity by activating immune cells throughout the body. By loading precise doses of cytokines onto the surface of T cells, Deep Priming focuses the immune response to target the tumor, without systemic exposure.

In hematologic cancers, this new class of immune cell therapeutics has the potential to improve on the initial success of single-target CAR T therapeutics with expanded efficacy and also move cell therapy treatment out of the hospital with a high margin of safety. For solid tumors, Deep-Primed T cells have the potential to enable efficacy against tumors with heterogeneous antigens protected by hostile microenvironments, which are not readily addressable with the first generation of immune cell therapies.