Sanofi : Isatuximab Phase 3 trial meets primary endpoint of prolonging progression free survival in patients with relapsed/refractory multiple myeloma

On February 5, 2019 Sanofi reported that the pivotal Phase 3 trial of isatuximab in patients with relapsed/refractory multiple myeloma met the primary endpoint of prolonging progression free survival in patients treated with isatuximab in combination with pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone alone (standard of care) (Press release, Sanofi, FEB 5, 2019, View Source [SID1234533065]).

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Results will be submitted to an upcoming medical meeting and are anticipated to form the basis of regulatory submissions planned for later this year.

"We are excited by these results, which represent significant progress in our ambition to extend the lives of multiple myeloma patients," said John Reed, Head of Research and Development at Sanofi. "We look forward to engaging with regulatory authorities with the goal of bringing this potential new treatment to patients as quickly as possible."

Multiple myeloma is the second most common hematologic malignancy[1], with more than 138,0002 new cases worldwide each year. Multiple myeloma remains incurable in the vast majority of patients, resulting in significant disease burden.

The randomized, multi-center, open label Phase 3 study, known as ICARIA-MM, enrolled 307 patients with relapsed/refractory multiple myeloma across 96 centers spanning 24 countries. All study participants received two or more prior anti-myeloma therapies, including at least two consecutive cycles of lenalidomide and a proteasome inhibitor given alone or in combination. During the trial, isatuximab was administered through an intravenous infusion at a dose of 10mg/kg once weekly for four weeks, then every other week for 28-day cycles in combination with standard doses of pomalidomide and dexamethasone for the duration of treatment. The safety profile was evaluated as a secondary endpoint.

About isatuximab clinical development program

Isatuximab targets a specific epitope of CD38 capable of triggering multiple, distinct mechanisms of action that are believed to promote programmed tumor cell death (apoptosis) and immunomodulatory activity. CD38 is highly and uniformly expressed on multiple myeloma cells and is a cell surface receptor target for antibody-based therapeutics in multiple myeloma and other malignancies. The clinical significance of these findings is under investigation.

ICARIA-MM is one of four ongoing Phase 3 clinical trials evaluating isatuximab in combination with currently available standard treatments for people with relapsed/refractory or newly-diagnosed multiple myeloma.

Isatuximab received orphan designation for relapsed/refractory multiple myeloma by the U.S. Food and Drug Administration and the European Medicines Agency. Isatuximab is an investigational agent and the safety and efficacy has not been evaluated by the U.S. Food and Drug Administration, the European Medicines Agency, or any other regulatory authority. Isatuximab is also under investigation for the treatment of other hematologic malignancies and solid tumors.

Surface Oncology Retains Worldwide Rights for its First-in-Class Antibody Targeting IL-27, SRF388

On February 4, 2019 Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, reported the retention of worldwide rights for its novel antibody, SRF388, targeting IL-27 (Press release, Surface Oncology, FEB 4, 2019, View Source [SID1234533066]). This program was previously subject to Surface’s collaboration with Novartis. IL-27 is a novel target in immuno-oncology, believed to play a significant and broad role in tumor-related immunosuppression via the regulation of checkpoint protein expression.

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"SRF388 is an ideal program for Surface Oncology. We have conducted significant preclinical and translational work to understand IL-27’s role in specific tumor types and have a focused translational strategy as we advance this program into clinical development," said Jeff Goater, chief executive officer of Surface Oncology. "We are pursuing an aggressive development timeline for SRF388, with an IND filing planned for the fourth quarter of this year."

Based on the terms of the 2016 agreement with Novartis, IL-27 was one of a set of predefined targets for which Novartis had a right to purchase an option, subject to certain financial conditions. Novartis has elected to not purchase an option for SRF388 and as a result full rights remain with Surface Oncology.

Currently, Surface Oncology is conducting IND-enabling studies for both SRF388 and its wholly owned CD39 program, SRF617, and anticipates submission of both INDs in Q4 of 2019.

ABOUT SRF388

SRF388 is a fully human anti-IL-27 antibody. In preclinical studies, treatment with SRF388 was observed to block IL-27 signaling and its downstream immunosuppressive effects. Preclinical combination with a PD-1 inhibitor increased the production of key inflammatory cytokines. SRF388 also demonstrates preclinical anti-metastatic tumor activity.

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.

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.