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BioXcel Therapeutics Announces Addition of Merck KGaA, Darmstadt, Germany, and Pfizer to Clinical Collaboration with Nektar for Development of Triple-combination Therapy in Pancreatic Cancer

On March 4, 2019 BioXcel Therapeutics, Inc. ("BTI") (BTAI) reported the addition of Merck KGaA, Darmstadt, Germany, which operates its biopharmaceutical business as EMD Serono in the USA and Canada, and Pfizer Inc. (PFE) to its Nektar Therapeutics (NKTR) clinical collaboration to evaluate a novel triple combination therapy in pancreatic cancer (Press release, BioXcel Therapeutics, MAR 4, 2019, View Source [SID1234533993]). The collaboration now includes avelumab*, BXCL701 and NKTR-214 as a potential combination therapy for pancreatic cancer. Avelumab is a human anti-programmed death ligand (PD-L1) co-developed and co-commercialized by Merck KGaA Darmstadt, Germany and Pfizer. BXCL701 is an orally-available systemic innate-immune activator that inhibits dipeptidyl peptidase (DPP) 8/9 and FAP developed by BTI. NKTR-214 is a CD122-biased agonist developed by Nektar. BTI is a clinical stage biopharmaceutical development company utilizing novel artificial intelligence approaches to identify the next wave of medicines across neuroscience and immuno-oncology.

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Under the collaboration, BTI will be responsible for initiating and managing the clinical program, with Merck KGaA, Darmstadt, Germany and Pfizer supplying avelumab and Nektar supplying NKTR-214. BTI and Nektar will equally share all development costs. The primary objectives of the study are to evaluate safety and efficacy of the triple combination of BXCL701, NKTR-214 and avelumab for the treatment of patients with pancreatic cancer. Additionally, correlative immune activation markers will be evaluated in blood and tumor tissue.

"We are excited to welcome Merck KGaA, Darmstadt, Germany and Pfizer as partners for the development of this novel triple combination regimen with Nektar," said Vimal Mehta, Chief Executive Officer of BTI. "We believe that the expansion of this clinical collaboration provides clear evidence of industry enthusiasm toward BXCL701. We look forward to working closely with Merck KGaA, Darmstadt, Germany and Pfizer as well as Nektar to leverage their clinical and regulatory expertise as we establish the development plan for the triple combination in pancreatic cancer."

"We believe it is essential to target multiple dimensions of the immune system in parallel to address the multi-faceted etiologies underlying cancer cell growth in difficult-to-treat tumors such as pancreatic cancer," said Jonathan Zalevsky, Chief Scientific Officer of Nektar Therapeutics. "This experimental triple combination regimen of BXCL701, NKTR-214 and avelumab is designed to leverage multiple mechanisms of action to better fight pancreatic cancer while potentially generating long-term cancer immunity. We’re pleased to be working with BTI as well as Merck KGaA, Darmstadt, Germany and Pfizer on this program."

*Avelumab is under clinical investigation for the treatment of pancreatic cancer and has not been demonstrated to be safe and effective for these uses. There is no guarantee that avelumab will be approved for pancreatic cancer by any health authority worldwide.

About BXCL701

BXCL701 is an orally-available systemic innate-immune activator with dual mechanisms of action. It has demonstrated single agent activity in melanoma, with an established safety profile from 700 healthy subjects and cancer patients. Designed to stimulate both the innate and acquired immune systems, BXCL701 works by inhibiting dipeptidyl peptidase (DPP) 8/9 and blocking immune evasion by targeting Fibroblast Activation Protein (FAP). Preclinical combination data evaluating BXCL701, a checkpoint inhibitor and other immuno-oncology agents has demonstrated encouraging anti-tumor activity in multiple tumor types and formation of functional immunological memory. BXCL701’s primary mechanism of action has recently been highlighted in multiple peer reviewed journals, providing an important validation of the scientific rationale behind BXCL701.

About NKTR-214

NKTR-214 preferentially binds to the CD122 receptor on the surface of cancer-fighting immune cells in order to stimulate their proliferation. In clinical and preclinical studies, treatment with NKTR-214 resulted in expansion of these cells and mobilization into the tumor micro-environment. NKTR-214 has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines.

About Avelumab

Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab has been shown in preclinical models to engage both the adaptive and innate immune functions. By blocking the interaction of PD-L1 with PD-1 receptors, avelumab has been shown to release the suppression of the T cell-mediated antitumor immune response in preclinical models.(1)-(3) Avelumab has also been shown to induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity (ADCC) in vitro.(3)-(5) In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a strategic alliance to co-develop and co-commercialize avelumab.

Approved Indications

The US Food and Drug Administration (FDA) granted accelerated approval for avelumab (BAVENCIO) for the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or following platinum-containing chemotherapy, or have disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. These indications are approved under accelerated approval based on tumor response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.

Avelumab is currently approved for patients with MCC in more than 45 countries globally, with the majority of these approvals in a broad indication that is not limited to a specific line of treatment.

Important Safety Information from the US FDA-Approved Label

The warnings and precautions for avelumab (BAVENCIO) include immune-mediated adverse reactions (such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction and other adverse reactions), infusion-related reactions and embryo-fetal toxicity.

Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO for mMCC and patients with locally advanced or metastatic UC include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary tract infection and rash.

For full prescribing information and medication guide for BAVENCIO, please see www.BAVENCIO.com.

Medtronic Announces Pricing of €7.0 Billion of Senior Notes

On March 4, 2019 Medtronic plc (NYSE:MDT) reported that its wholly-owned subsidiary, Medtronic Global Holdings S.C.A. ("Medtronic Luxco"), has priced an offering of €500,000,000 principal amount of floating rate senior notes due 2021, €1,500,000,000 principal amount of 0% senior notes due 2021, €1,500,000,000 principal amount of 0.375% senior notes due 2023, €1,500,000,000 principal amount of 1.125% senior notes due 2027, €1,000,000,000 principal amount of 1.625% senior notes due 2031, and €1,000,000,000 principal amount of 2.250% senior notes due 2039 (collectively, the "Notes") (Press release, Medtronic, MAR 4, 2019, View Source;p=RssLanding&cat=news&id=2390014 [SID1234533988]). All of Medtronic Luxco’s obligations under the Notes will be fully and unconditionally guaranteed by Medtronic plc and Medtronic, Inc., a wholly-owned indirect subsidiary of Medtronic Luxco, on a senior unsecured basis.

The net proceeds of the offering will be used to fund the previously announced tender offers for several series of outstanding notes issued by Medtronic, Inc. and Covidien International Finance S.A., a wholly-owned indirect subsidiary of Medtronic plc, and to pay accrued and unpaid interest, premiums, fees and expenses in connection with those tender offers. Any remaining net proceeds of the offering will be used for repayment of Medtronic Luxco’s 1.700% senior notes due 2019 at maturity on March 28, 2019 plus accrued and unpaid interest thereon, repayment of other indebtedness and general corporate purposes. The offering is expected to close on March 7, 2019, subject to customary closing conditions. The joint book-running managers for the offering are Barclays Bank PLC and Merrill Lynch International.

The offering is being made only by means of a prospectus dated February 3, 2017 and prospectus supplement (together, the "Prospectus"). You may get these documents for free by visiting EDGAR on the Securities and Exchange Commission website at www.sec.gov. Alternatively, copies of the Prospectus for each offering may be obtained by contacting Barclays Bank PLC, toll free at +1-888-603-5847 and Merrill Lynch International, toll-free at +1-800-294-1322.

Alder BioPharmaceuticals, Inc. Announces Closing of Public Offering and Private Placement of Common Stock and Exercise in Full of Option to Purchase Additional Shares

On March 4, 2019 Alder BioPharmaceuticals, Inc. (NASDAQ: ALDR), a biopharmaceutical company focused on developing novel therapeutic antibodies for the treatment of migraine, reported the closing of its previously announced underwritten public offering of 13,000,000 shares of common stock, including 1,695,652 shares sold pursuant to the underwriters’ exercise in full of their option to purchase additional shares, at a public offering price of $11.50 per share (Press release, Alder Biopharmaceuticals, MAR 4, 2019, View Source [SID1234533964]).

Concurrent with the public offering, Alder sold, in a private placement exempt from the registration requirements of the Securities Act of 1933, as amended (the "Securities Act"), 1,739,130 shares of common stock to certain institutional and other accredited investors affiliated with or managed by Redmile Group, LLC at a sale price equal to $11.50 per share.

The gross proceeds to Alder from the public offering and concurrent private placement, before deducting underwriting discounts and commissions, placement agent fees, and offering expenses payable by Alder, were approximately $169.5 million. Alder intends to use the net proceeds from the public offering and the concurrent private placement, together with other available funds, for the commercialization of eptinezumab up to and through launch and the manufacture of commercial supply for eptinezumab, and may also use net proceeds for future eptinezumab clinical trials, the development of ALD1910 and for working capital and general corporate purposes.

J.P. Morgan, SVB Leerink and Wells Fargo Securities acted as joint book-running managers for the public offering. RBC Capital Markets acted as co-manager for the public offering.

A shelf registration statement relating to the public offering was filed with the Securities and Exchange Commission (SEC), and was effective on filing on February 23, 2017. A prospectus supplement and the accompanying prospectus related to the public offering have been filed with the SEC and are available on the SEC’s website, located at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus relating to the public offering may be obtained from J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, or by telephone at (866) 803-9204, or by email at [email protected]; from SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, or by phone at (800) 808-7525, ext. 6132, or by email at [email protected]; or from Wells Fargo Securities, LLC, Attention: Equity Syndicate Department, 375 Park Avenue, New York, New York 10152 at (800) 326-5897 or email a request to [email protected].

The shares of common stock sold in the concurrent private placement have not been registered under the Securities Act or under any state securities laws and, unless so registered may not be offered or sold in the United States except pursuant to an exemption from, or in a transaction not subject to, the registration requirements of the Securities Act and applicable state securities laws.

This press release shall not constitute an offer to sell or a 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.

Horizon Pharma plc Announces Proposed Public Offering of Ordinary Shares

On March 4, 2019 Horizon Pharma plc (Nasdaq: HZNP) reported that it is offering to sell $300,000,000 of its ordinary shares in an underwritten public offering (Press release, Horizon Pharma, MAR 4, 2019, View Source [SID1234533961]). The Company also expects to grant the underwriters a 30-day option to purchase up to an additional $45,000,000 of ordinary shares in the public offering solely to cover over-allotments.

Citigroup, Morgan Stanley, Goldman Sachs & Co. LLC and Cowen are acting as joint book-running managers for the offering.

The Company intends to use the net proceeds from this offering, together with cash on hand, to redeem or repay approximately $550 million of outstanding debt, consisting of a portion of the outstanding principal amount of term loans under the Company’s Credit Agreement and a portion of the outstanding principal amount of the Company’s 6.625% Senior Notes due 2023, as well as to pay the related premiums, accrued interest and fees and expenses associated with the planned redemption or repayment.

A registration statement relating to the ordinary shares described above was previously filed with and became effective by rule of the Securities and Exchange Commission ("SEC"). A preliminary prospectus supplement related to the offering will be filed with the SEC and will be available on the SEC’s website located at View Source Copies of the preliminary prospectus supplement and related prospectus, when available, may be obtained by contacting Citigroup Global Markets Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by email at [email protected] or by phone at 800-831-9146; Morgan Stanley & Co. LLC, 180 Varick Street, 2nd Floor, New York, NY 10014, Attention: Prospectus Department; Goldman Sachs & Co. LLC, c/o: Prospectus Department, 200 West Street, New York, NY 10282, by email at [email protected] or by phone at 866-471-2526; or Cowen and Company, LLC, c/o Broadridge Financial Services, 1155 Long Island Avenue, Edgewood, NY, 11717, Attn: Prospectus Department or by phone at 631-274-2806.

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

Anixa Biosciences to Present Cchek™ Technology and Data at the Molecular Medicine Tri-Conference

On March 4, 2019 Anixa Biosciences, Inc. (NASDAQ: ANIX), a biotechnology company focused on using the body’s immune system to fight cancer, reported that it will present its Cchek artificial intelligence (AI) based liquid biopsy for the early detection of cancer technology and its most recent data in an oral presentation at the 26th International Molecular Medicine Tri-Conference (Press release, Anixa Biosciences, MAR 4, 2019, View Source [SID1234533952]). Cchek utilizes flow cytometry of white blood cells and AI to identify tumor-bearing patients. Dr. Kumar, President and CEO of Anixa, will make his presentation at 12:15 pm on March 14, 2019. The symposium in which the presentation will be made is focused on early cancer detection (View Source).

"The Molecular Medicine Tri-Conference is one of the largest commercial conferences addressing the latest advances in biotechnology, diagnostics and life sciences," said Dr. Kumar. "I am pleased to be telling people about our technology, how it works, and the latest performance data on the detection of prostate cancer, breast cancer and several other types of cancer. This is a timely conference as we approach the commercial launch of our Cchek Prostate Cancer Confirmation test later this year."