On March 8, 2019 Bayer reported that it has submitted a marketing authorization application (MAA) to the European Medicines Agency (EMA) for darolutamide for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) (Press release, Bayer, MAR 8, 2019, View Source [SID1234534165]).

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"Men are typically asymptomatic at this stage of prostate cancer. Therefore, it is critical that they have treatment options, which not only delay the development of metastases, but also limit burdensome side effects of therapy, so that these men can continue with their day-to-day lives," said Scott Z. Fields, M.D., senior vice president and head of Oncology Development of Bayer AG’s Pharmaceutical Division. "With this submission, we are taking an important step toward providing patients, caregivers, and physicians with a potential new treatment option for nmCRPC."

The submission to the EMA is based on data from the Phase III ARAMIS trial in men with nmCRPC, which were recently presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) in San Francisco and published simultaneously in The New England Journal of Medicine, showing a statistically significant improvement in metastasis-free survival (MFS) for darolutamide plus androgen deprivation therapy (ADT).(1)

Bayer recently completed the rolling submission of a New Drug Application to the United States Food and Drug Administration (FDA) and submitted an application to the Ministry of Health, Labor and Welfare (MHLW) in Japan. Bayer is also in discussions with other health authorities regarding submissions.

The compound is being developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company.

About ARAMIS
The ARAMIS trial is a randomized, Phase III, multi-center, double-blind, placebo-controlled trial evaluating the safety and efficacy of oral darolutamide in patients with nmCRPC who are currently being treated with ADT and are at high risk for developing metastatic disease. 1,509 patients were randomized in a 2:1 ratio to receive 600 mg of darolutamide twice a day or placebo along with ADT.

About darolutamide
Darolutamide is a non-steroidal androgen receptor (AR) antagonist with a distinct chemical structure that binds to the receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. In preclinical studies, darolutamide demonstrated lower blood-brain barrier penetration compared to other currently available AR antagonists.(2)

In addition to the Phase III trial ARAMIS in men with nmCRPC, darolutamide is also being investigated in a Phase III study in metastatic hormone-sensitive prostate cancer (ARASENS). Information about these trials can be found at www.clinicaltrials.gov.

Darolutamide is not approved by the U.S. FDA, the European Medicines Agency or any other health authority.

About castration-resistant prostate cancer (CRPC)
Prostate cancer is the second most commonly diagnosed malignancy in men worldwide.(3) In 2018, an estimated 1.2 million men were diagnosed with prostate cancer, and about 358,000 died from the disease worldwide.(3) Prostate cancer is the fifth leading cause of death from cancer in men.(3) Prostate cancer results from the abnormal proliferation of cells within the prostate gland, which is part of a man´s reproductive system.(4) It mainly affects men over the age of 50, and the risk increases with age.(5) Treatment options range from surgery to radiation treatment to therapy using hormone-receptor antagonists, i.e., substances that stop the formation of testosterone or prevent its effect at the target location.(6) However, in nearly all cases, the cancer eventually becomes resistant to conventional hormone therapy.(7)

CRPC is an advanced form of the disease where the cancer keeps progressing even when the amount of testosterone is reduced to very low levels in the body. The field of treatment options for castration-resistant patients is evolving rapidly, but until recently, there have been no approved treatment options for CRPC patients who have rising prostate-specific antigen (PSA) levels while on ADT and no detectable metastases. In men with progressive nmCRPC, a rapid PSA doubling time has been consistently associated with reduced time to first metastasis and death.(8)

On March 8, 2019 Conatus Pharmaceuticals Inc. (Nasdaq:CNAT) reported financial results for the fourth quarter and full year ended December 31, 2018, and provided updates on its development programs (Filing, 8-K, Conatus Pharmaceuticals, MAR 8, 2019, View Source [SID1234534163]).

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Program Updates
The company is conducting three double-blind, placebo-controlled Phase 2b clinical trials in collaboration with Novartis – the EmricasaN, a Caspase inhibitOR, for Evaluation (ENCORE) trials, designed to evaluate emricasan, a first-in-class pan-caspase inhibitor, in patients with liver fibrosis or cirrhosis caused by nonalcoholic steatohepatitis (NASH).

The ENCORE-NF (for NASH Fibrosis) clinical trial, initiated in the first quarter of 2016, has enrolled approximately 330 patients with baseline NASH Clinical Research Network (CRN) fibrosis scores of F1 (up to 20% of enrolled patients), F2, and F3. The primary endpoint is a biopsy-based one point or greater improvement in NASH CRN fibrosis score compared with placebo at week 72, with no worsening of steatohepatitis. The primary endpoint will be evaluated and can be achieved in either of two prospectively defined patient populations – the F1/F2/F3 population or the F2/F3 population. Either of these populations may be used in a future Phase 3 trial. The company believes that the ENCORE-NF analysis plan has the potential to facilitate discussions with regulatory authorities regarding its use as a study to support regulatory approval. Top-line results from ENCORE-NF are expected in the first half of 2019.

The ENCORE-LF (for Liver Function) clinical trial, initiated in the second quarter of 2017, has enrolled approximately 210 patients with stable decompensated NASH cirrhosis. The primary endpoint is event-free survival, which is a composite of all-cause mortality, new decompensation events, or ≥4 points progression in Model for End-stage Liver Disease (MELD) score. Enrollment was completed in the first quarter of 2019. Top-line results triggered by reaching a prespecified number of events are expected in mid-2019.

The ENCORE-PH (for Portal Hypertension) clinical trial, initiated in the fourth quarter of 2016, enrolled 263 patients with compensated or early decompensated NASH cirrhosis and severe portal hypertension. The trial’s primary endpoint was change in mean hepatic venous pressure gradient (HVPG) from baseline to Week 24 in any of three emricasan dosing groups compared with placebo. Top-line results were reported in December 2018 showing HVPG trends consistently favoring emricasan compared with placebo in the overall population but not meeting the primary endpoint. Post hoc analyses showed clinically meaningful treatment effects for emricasan compared with placebo and a trend toward clinical benefit in the prespecified subpopulation of compensated patients, with the greatest improvement in compensated patients with baseline HVPG ≥16 mmHg. Patients had the option to continue on their assigned doses of treatment or placebo in a double-blind 24-week extension period to evaluate longer term safety, liver function and clinical outcomes. Results following the extension period are expected in mid-2019.
In its internal development program, the company has assembled a proprietary portfolio of orally active molecules that inhibit the NLRP3 inflammasome pathway and the activation of the potent inflammatory cytokine IL-1b. Inhibition of IL-1b is a clinically validated approach to treating inflammatory diseases, with several injectable biologic products using that mechanism of action already on the market. The NLRP3 inflammasome pathway is dependent upon caspase 1, which activates IL-1b. Caspase 1 occupies a uniquely central position in the inflammasome pathway, and the company has leveraged its scientific expertise in caspase research and development to design potent, selective and orally bioavailable inhibitors of caspase 1. Excess IL-1b has been linked to a variety of diseases including rare genetic inflammatory diseases, cancer, liver and other gastrointestinal diseases, and cardiovascular diseases.

The company is announcing today the selection of its first internally developed product candidate, CTS-2090, based on its preclinical profile, including high selectivity for caspase 1, and drug-like properties. CTS-2090 is currently in preclinical development and IND-enabling studies, with an initial clinical trial expected to begin by the first half of 2020. Additional details will be discussed in the conference call and webcast scheduled for 4:30 p.m. ET today (information below).

Financial Results
The net loss for the fourth quarter of 2018 was $3.9 million compared with $4.4 million for the fourth quarter of 2017. The net loss for the full year 2018 was $18.0 million compared with $17.4 million for the full year 2017.

Total revenues were $7.4 million for the fourth quarter of 2018 compared with $8.8 million for the fourth quarter of 2017, and $33.6 million for the full year 2018 compared with $35.4 million for the full year 2017. Total revenues consisted of collaboration revenues related to the Novartis agreement. The decreases in revenues for both periods were primarily due to lower emricasan-related research and development expenses resulting in corresponding lower revenues related to the Novartis agreement, partially offset by the effects of adopting the ASC 606 revenue recognition standard.

Research and development expenses were $8.9 million for the fourth quarter of 2018 compared with $10.9 million for the fourth quarter of 2017. Research and development expenses were $41.4 million for the full year 2018 compared with $43.2 million for the full year 2017. The decreases in both periods were primarily due to lower costs related to the ENCORE clinical trials, as well as lower costs related to emricasan manufacturing activities, partially offset by higher costs related to new product candidate development.

General and administrative expenses were $2.5 million for the fourth quarter of 2018 compared with $2.3 million for the fourth quarter of 2017. General and administrative expenses were $10.5 million for the full year 2018 compared with $9.7 million for the full year 2017. The increases in general and administrative expenses for both periods were primarily due to higher personnel costs and recognition of deferred collaboration costs due to adoption of the new revenue recognition standard.

In December 2018, the company, at its option, converted the outstanding principal plus accrued and unpaid interest of the Novartis note into shares of the company’s common stock. Cash, cash equivalents and marketable securities were $40.7 million at December 31, 2018, compared with $74.9 million at December 31, 2017, and a projected year-end 2019 balance, without including any potential milestone payments under the Novartis collaboration, of between $10 million and $15 million.

Conference Call and Audio Webcast
Conatus will host a conference call and audio webcast at 4:30 p.m. ET today to discuss the financial results and provide a corporate update. To access the conference call, please dial 877-312-5857 (domestic) or 970-315-0455 (international) at least five minutes prior to the start time and refer to conference ID 3249458. A live and archived audio webcast of the call will also be available in the Investors section of the Conatus website at www.conatuspharma.com.

On March 8, 2018 Bausch Health Companies Inc. (NYSE/TSX: BHC) ("Bausch Health," the "Company" or the "Offeror") reported the results to date of its pending cash tender offers (collectively, the "Tender Offers," and each offer to purchase a series of notes individually, a "Tender Offer") to purchase up to $1,500,000,000 aggregate purchase price (the "Aggregate Maximum Purchase Amount") of its outstanding notes listed in the table below (collectively, the "Notes"), as well as the anticipated early settlement date for the Tender Offers on March 11, 2019 (the "Early Settlement Date") (Press release, Valeant, MAR 8, 2019, View Source [SID1234534161]).

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In conjunction with the Tender Offers, the Company also commenced a solicitation of consents (the "Solicitation," and, together with the Tender Offers, the "Tender Offers and Solicitation") to certain proposed amendments to the indenture governing its 5.625% Senior Notes due 2021 (the "2021 Notes") to eliminate substantially all of the restrictive covenants and events of default and related provisions contained in the indenture under which the 2021 Notes were issued (the "Proposed Amendments"). No amendments to the indentures governing the 5.50% Senior Notes due 2023 (the "5.50% Notes") and 5.875% Senior Notes due 2023 (the "5.875% Notes" and, together with the 5.50% Notes, the "2023 Notes") are being sought. The terms and conditions of the Tender Offers and the Solicitation are described in an Offer to Purchase and Consent Solicitation Statement dated Feb. 22, 2019 (as it may be amended or supplemented from time to time, the "Statement") and the related Letter of Transmittal and Consent. All terms and conditions of the Tender Offers and the Solicitation, as amended by the Company’s news release dated Feb. 22, 2019, announcing the upsize of the Tender Offers, remain unchanged as set forth in the Statement.

The following table sets forth the aggregate principal amounts of each series of Notes and related consents that were tendered and not withdrawn on or prior to 5:00 p.m., New York City time, on March 7, 2019 (such date and time with respect to a Tender Offer and the Solicitation, as it may be extended for such Tender Offer and the Solicitation, the "Early Tender Date"), the aggregate principal amount of Notes expected to be accepted for purchase on the Early Settlement Date and the approximate proration factor with respect to the 2023 Notes.

On March 8, 2019 Bausch Health Companies Inc. (NYSE/TSX: BHC) ("Bausch Health" or the "Company") reported that it has closed its previously announced offering of $500,000,000 aggregate principal amount of 5.750% senior secured notes due 2027 (the "Secured Notes") and that Bausch Health Americas, Inc. (f/k/a Valeant Pharmaceuticals International) ("BHA"), the Company’s wholly owned indirect subsidiary, has closed its previously announced offering of $1,000,000,000 aggregate principal amount of 8.500% senior unsecured notes due 2027 (the "Unsecured Notes" and, together with the Secured Notes, the "Notes") (Press release, Valeant, MAR 8, 2019, View Source [SID1234534160]). The Unsecured Notes are additional notes and form part of the same series as BHA’s existing 8.500% senior notes due 2027. Bausch Health intends to use the net proceeds from the offerings of the Notes, along with cash on hand, to repurchase $1,500 million aggregate purchase price of outstanding notes pursuant to its previously announced tender offers, including the Company’s outstanding 5.625% Senior Notes due 2021 (the "2021 Notes") and up to $800,000,000 principal amount across the Company’s outstanding 5.50% Senior Notes due 2023 (the "5.50% Notes") and 5.875% Senior Notes due 2023 (the "5.875% Notes" and, together with the 2021 Notes and the 5.50% Notes, the "Existing Notes"), and to pay related fees and expenses. The Company expects the after-tax impact of these transactions to be neutral to 2019 adjusted net income. This announcement does not constitute an offer to purchase or the solicitation of an offer to sell the Existing Notes.

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The Company issued today an irrevocable notice of redemption for any and all outstanding 2021 Notes to the extent not tendered and accepted for purchase pursuant to the previously announced tender offers. The Company will use a portion of the net proceeds from the offerings of the Notes to fund the aggregate redemption price for any 2021 Notes to be redeemed. On March 8, 2019, a copy of the irrevocable notice of redemption with respect to the 2021 Notes was issued to record holders. Payment of the redemption price and surrender of the 2021 Notes for redemption will be made through the facilities of the Depository Trust Company in accordance with the applicable procedures of the Depository Trust Company on April 8, 2019. The name and address of the paying agent are as follows: The Bank of New York Mellon Trust Company, N.A., c/o The Bank of New York Mellon Trust Company, N.A.; 111 Sanders Creek Parkway, East Syracuse, N.Y. 13057; Attn: Redemption Unit; Tel: (800) 254- 2826.

On March 8, 2019 Leap Therapeutics, Inc. (Nasdaq: LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, reported the Company will be presenting at the Society of Gynecologic Oncology 2019 Annual Meeting on Women’s Cancer, being held March 16-19, 2019 in Honolulu, HI (Press release, Leap Therapeutics, MAR 8, 2019, View Source [SID1234534150]).

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About the DKN-01 P204 clinical trial
The P204 study is a Phase 2 basket study of DKN-01 as both a monotherapy and in combination with paclitaxel in patients with advanced endometrioid unterine (EEC) and endometrioid ovarian (EOC) cancers. These malignancies have a percentage of patients with mutations in the Wnt pathway. The study consists of four dosing groups and will enroll up to 94 patients using a Simon 2-Stage design in each group. The primary objective in each independent study group is to determine the overall response. Secondary objectives include measures of efficacy such as overall survival and progression free survival, and to evaluate the safety of the treatment regimen.

Leap Presentation Details:
Abstract Number: 65
Title: Safety and efficacy of a DKK1 inhibitor (DKN-01) as monotherapy or in combination with paclitaxel in patients with Wnt activated recurrent gynecologic malignancies
Session Title: Oral Featured Poster Session II: Trials, Basic Science and Translational Science
Date: Monday, March 18
Time: 6:00 – 7:00 PM GMT
Location: Hawaii Convention Center 313AB