On December 7, 2018 Arvinas Inc. (Nasdaq: ARVN), a biotechnology company creating a new class of drugs based on targeted protein degradation, reported its positive preclinical data on the company’s lead clinical candidate, ARV-471, for advanced or metastatic ER-positive/HER2-negative breast cancer at the 2018 San Antonio Breast Cancer Symposium (SABCS), taking place December 4-8 in San Antonio, Texas (Poster P5-04-18; Session 5: Tumor Cell and Molecular Biology: Endocrine Therapy and Resistance) (Press release, Arvinas, DEC 7, 2018, View Source [SID1234531969]). In this study, orally administered ARV-471 demonstrated improved potency and anti-tumor activity both as a monotherapy and in combination with a CDK4/6 inhibitor, compared to current standard of care treatment regimens.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We believe that ARV-471 has the potential to be the first oral protein degrader for the treatment of patients with metastatic ER-positive/HER2-negative breast cancer, when used either as a single-agent or in combination with other routinely used anti-cancer agents," said John Houston, Ph.D., President and CEO of Arvinas. "This data reinforces our growing confidence that our PROTAC protein degraders have the potential to provide distinct advantages over existing approaches across a broad range of disease targets and to improve clinical outcomes over current standard of care. We continue to expect to initiate our Phase 1 clinical trial of ARV-471 in mid-2019."

Key highlights from the poster "ARV-471, an oral estrogen receptor PROTAC degrader for breast cancer":

Orally bioavailable ARV-471 demonstrated potent ERa degradation in wild-type and mutant ERa-expressing cell lines.
Oral administration of ARV-471 caused near-complete ERa degradation and resulted in tumor shrinkage in an orthotopic MCF7/estradiol breast cancer preclinical model; ARV-471 demonstrated superior tumor growth inhibition and ERa degradation compared to standard-of-care agent, fulvestrant.
Combination of ARV-471 and a CDK4/6 inhibitor demonstrated superior tumor growth inhibition when compared to the combination of fulvestrant and a CDK4/6 inhibitor.
ARV-471 inhibited growth of tamoxifen-resistant and ERa gene (ESR1) mutant tumors while also reducing tumor ERa levels.
ARV-471 displayed no ER agonist activity.

On December 7, 2018 The board of directors of Medtronic plc (NYSE:MDT) reported the fiscal year 2019 third quarter cash dividend of $0.50 per ordinary share, representing a 9 percent increase over the prior year (Press release, Medtronic, DEC 7, 2018, View Source;p=RssLanding&cat=news&id=2379925 [SID1234531967]). This quarterly declaration is consistent with the dividend announcement made by the company in June 2018. Medtronic is a constituent of the S&P 500 Dividend Aristocrats index, having increased its annual dividend payment for the past 41 consecutive years. The dividend is payable on January 18, 2019, to shareholders of record at the close of business on December 28, 2018.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On December 7, 2018 Amgen (NASDAQ:AMGN) reported that its Board of Directors declared a $1.45 per share dividend for the first quarter of 2019 (Press release, Amgen, DEC 7, 2018, View Source;p=RssLanding&cat=news&id=2379993 [SID1234531966]). The dividend will be paid on March 8, 2019, to all stockholders of record as of the close of business on Feb. 15, 2019. This represents a 10 percent increase from that paid in each of the previous four quarters.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On December 7, 2018 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported that on December 6, it received a letter from the U.S. Food and Drug Administration (FDA) indicating that a partial clinical hold has been placed on its Phase 1 monotherapy study of MGD009, a B7-H3 × CD3 bispecific DART molecule, as well as on a combination study of MGD009 and MGA012 (anti-PD-1) (Press release, MacroGenics, DEC 7, 2018, View Source [SID1234531963]). Under the partial clinical hold, no new patients will be enrolled in either study until the partial hold is lifted by the FDA. Current study participants may continue to receive drug at their pre-assigned dose.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The partial clinical hold was initiated following MacroGenics’ reporting of hepatic adverse events on the MGD009 monotherapy trial to the FDA, including reversible elevations of transaminases with or without concurrent elevations of bilirubin. Although these events have been otherwise uncomplicated and short-lived in duration, MacroGenics also communicated to the FDA the company’s plans to amend the existing MGD009 studies with additional supportive care to mitigate these events. The FDA has placed the trials on partial clinical hold, pending review of additional details regarding these events, and satisfactory review of the planned amendments to the monotherapy and combination study protocols and related documents. MacroGenics will be working closely with the FDA to review these events and seek to resolve this clinical hold.

"MacroGenics’ top concern in conducting clinical trials is the safety of study participants," said Scott Koenig, M.D., Ph.D. "As we’ve identified to the FDA, we believe that transaminitis observed in patients administered MGD009 was likely a cytokine-mediated event. We are working with the FDA and will provide an update when we have additional information. This partial clinical hold does not impact ongoing clinical studies for enoblituzumab and MGC018, our other B7-H3-targeted molecules."
About MGD009
MGD009 is a humanized, bispecific DART molecule that recognizes both B7-H3 and CD3 and has a prolonged serum half-life. B7-H3 is a member of the B7 family of molecules involved in immune regulation and is over-expressed on a wide variety of cancer cells, including cancer stem cells, as well as on the supporting tumor vasculature and underlying tissues, or stroma. The intended mechanism of action of MGD009 is its ability to redirect T cells, via their CD3 component, to kill B7-H3-expressing cells.

In addition to MGD009, MacroGenics’ comprehensive B7-H3 franchise includes enoblituzumab, an Fc-optimized monoclonal antibody, as well as MGC018, an antibody-drug conjugate (ADC). These clinical molecules target B7-H3. MacroGenics retains worldwide rights to its franchise of three B7-H3-based molecules.

On December 7, 2018 Sophiris Bio Inc. (the "Company") reported that entered into an Controlled Equity OfferingSM Sales Agreement (the "Sales Agreement") with Cantor Fitzgerald & Co., as sales agent ("Cantor Fitzgerald"), pursuant to which the Company may offer and sell, from time to time, through Cantor Fitzgerald, common shares of the Company having an aggregate offering price of up to $20.0 million (Press release, Sophiris Bio, DEC 7, 2018, View Source [SID1234531962]). The shares will be offered and sold pursuant to the Company’s shelf registration statement on Form S-3 (File No. 333-219887).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The Company is not obligated to sell any shares under the Sales Agreement. Subject to the terms and conditions of the Sales Agreement, Cantor Fitzgerald will use commercially reasonable efforts, consistent with its normal sales and trading practices, applicable state and federal law, rules and regulations and the rules of the Nasdaq Capital Market, to sell shares from time to time based upon the Company’s instructions, including any price, time or size limits specified by the Company. Under the Sales Agreement, Cantor Fitzgerald may sell shares in privately negotiated transactions or by any other method or payment permitted by law deemed to be an "at-the-market" offering as defined in Rule 415 under the Securities Act of 1933, as amended. The Company will pay Cantor Fitzgerald a commission of 3.0% of the aggregate gross proceeds from each sale of shares, reimburse certain legal fees and disbursements and provide Cantor Fitzgerald with customary indemnification and contribution rights. The Sales Agreement may be terminated by Cantor Fitzgerald or the Company at any time upon notice to the other party, or by Cantor Fitzgerald at any time in certain circumstances, including the occurrence of a material and adverse change in the Company’s business or financial condition that makes it impractical or inadvisable to market the shares or to enforce contracts for the sale of the shares.

The foregoing description of the Sales Agreement does not purport to be complete and is qualified in its entirety by reference to the full text of the Sales Agreement, a copy of which is filed as Exhibit 10.1 to this Current Report on Form 8-K. The legal opinion of Fasken Martineau DuMoulin LLP relating to the common shares being offered pursuant to the Sales Agreement is filed as Exhibit 5.1 to this Current Report on Form 8-K.

This Current Report on Form 8-K shall not constitute an offer to sell or the solicitation of an offer to buy any shares under the Sales Agreement, nor shall there be any sale of such shares in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.