Calithera Biosciences Completes Patient Enrollment in Randomized Phase 2 ENTRATA Trial of Telaglenastat (CB-839) and Everolimus in Renal Cell Carcinoma

On February 4, 2019 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical stage biotechnology company focused on discovering and developing novel small molecule drugs directed against tumor metabolism and tumor immunology targets for the treatment of cancer, reported that it has completed patient enrollment in the ongoing Phase 2 ENTRATA trial. ENTRATA is a randomized clinical study of the glutaminase inhibitor CB-839 combined with everolimus versus placebo with everolimus for the treatment of advanced renal cell carcinoma (RCC) (Press release, Calithera Biosciences, FEB 4, 2019, View Source [SID1234535231]). CB-839 now has the International Nonproprietary Name (INN) telaglenastat, as recommended by the World Health Organization.

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"The ENTRATA trial is the first randomized trial evaluating the glutaminase inhibitor telaglenastat. There is ample evidence demonstrating the potential of glutaminase inhibition to block growth and survival of cancer cells," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera. "We are pleased that patient enrollment is now complete and look forward to learning more from ENTRATA about how this promising mechanism could help heavily pre-treated patients with advanced renal cancer."

The ENTRATA trial (NCT03163667) is a Phase 2 randomized, double blind trial designed to evaluate the safety and efficacy of telaglenastat in combination with everolimus versus placebo with everolimus in patients with advanced clear cell RCC who have been treated with at least two prior lines of systemic therapy, including a VEGFR-targeted tyrosine kinase inhibitor. The trial enrolled 69 patients at multiple centers in the United States. The primary endpoint of ENTRATA is progression-free survival (PFS). Calithera plans to report efficacy and safety data from the trial in the second half of 2019.

Telaglenastat is an investigational, novel glutaminase inhibitor specifically designed to block glutamine consumption in tumor cells. RCC tumors commonly exhibit metabolic alterations that increase their dependence on glutamine. In preclinical studies, telaglenastat produced synergistic antitumor effects when used in combination with standard-of-care RCC therapies.

Telaglenastat is also being investigated in the CANTATA trial, which will enroll approximately 400 patients and is designed with registrational intent. It is a global, randomized, double-blind trial designed to evaluate the safety and efficacy of telaglenastat in combination with cabozantinib versus placebo with cabozantinib in patients with advanced clear cell RCC who have been treated with one or two prior lines of systemic therapy. The primary endpoint is PFS by blinded independent review, and a key secondary endpoint is overall survival.

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.

INmune Bio Inc. Announces Closing of Initial Public Offering and Trading on the Nasdaq Capital Market Under the Ticker Symbol “INMB”

On February 4, 2019 INmune Bio, Inc. ("INmune" or the "Company"), an immunotherapy company focused on developing therapies that harness the patient’s innate immune system to fight disease, reported that the Company’s common stock is expected to commence trading on The Nasdaq Capital Market, on Monday, February 4, 2019 under the ticker symbol "INMB" (Press release, INmune Bio, FEB 4, 2019, View Source [SID1234533090]).

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On February 1, 2019, INmune closed its initial public offering ("IPO") of 1,020,560 shares of its common stock at of $8.00 per share for a total of $8,166,560 in gross proceeds before placement agent fees and offering expenses.

Univest Securities, LLC served as the lead placement agent for the IPO. WallachBeth Capital, LLC and WestPark Capital, Inc. were co-placement agents.

A registration statement relating to this U.S. offering was filed with the Securities and Exchange Commission ("SEC") and was declared effective by the SEC as of December 19, 2018. The offering of the securities was made only by means of a prospectus, forming a part of the registration statement. Copies of the final prospectus relating to the U.S. offering may be obtained from Univest Securities, LLC. 375 Park Avenue Unit 1502, New York, NY 10152, by telephone at +1 212 343 8888 or email at [email protected]. In addition, a copy of the prospectus relating to the offering may be obtained via the SEC’s website at www.sec.gov.

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

PRA Health Sciences to Report Fourth Quarter 2018 Earnings

On February 4, 2019 PRA Health Sciences, Inc. (NASDAQ: PRAH) reported that it will release its fourth quarter and year end 2018 results after the market closes on Wednesday, February 27, 2019 (Press release, PRA Health Sciences, FEB 4, 2019, View Source;p=RssLanding&cat=news&id=2385970 [SID1234533080]). The Company will also host a conference call on Thursday, February 28, 2019 at 9:00 a.m. (ET) to discuss the results with members of the investment community.

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To participate via telephone, investors and analysts should dial (877) 930-8062 within the United States or (253) 336-7647 outside the United States approximately 10 minutes prior to the call start time. The conference ID for the call is 8697447. An audio replay of the call will be available for one week following the call and can be accessed by dialing (855) 859-2056 within the United States or (404) 537-3406 outside the United States. The replay ID is 8697447.

A live audio broadcast will be available on the investor relations section of the PRA Health Sciences website. Following the teleconference, an audio playback of the call will be available at the same website.

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.