On February 15, 2019 Nektar Therapeutics presented the corporate presentation (Presentation, Nektar Therapeutics, FEB 15, 2019, View Source [SID1234533358]).

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On February 15, 2019 Eli Lilly and Company (NYSE:LLY) reported the successful completion of its acquisition of Loxo Oncology, Inc. (NASDAQ:LOXO) (Press release, Eli Lilly, FEB 15, 2019, View Source [SID1234533343]). The acquisition broadens the scope of Lilly’s oncology portfolio into precision medicines through the addition of a pipeline of highly selective potential medicines for patients with genomically defined cancers.

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Lilly’s tender offer for all outstanding shares of common stock of Loxo Oncology, at a price of $235.00 per share in cash, expired as scheduled at one minute past 11:59 p.m., Eastern time, on Thursday, February 14, 2019. As of the expiration of the tender offer, 26,043,820 shares of Loxo Oncology common stock were validly tendered and not properly withdrawn, representing approximately 84.6 percent of the shares of Loxo Oncology common stock outstanding, and have been accepted for payment under the terms of the tender offer. Following completion of the tender offer, Lilly completed the acquisition of Loxo Oncology through the previously-planned second-step merger.

"We are pleased to announce the completion of our acquisition of Loxo Oncology, which will expand the breadth of our portfolio into precision medicines and target cancers that are caused by specific gene abnormalities," said Anne White, president of Lilly Oncology. "We look forward to working with the Loxo Oncology team and continuing to rapidly advance this pioneering scientific innovation and improve the lives of people with cancer."

"The Loxo Oncology team has always been relentless and unified around the common goal of bringing highly selective medicines to patients with genomically defined cancers," said Josh Bilenker, M.D., chief executive officer of Loxo Oncology. "With the acquisition now complete, we look forward to realizing the full value of our pipeline with the ongoing support of our teams in Connecticut, Colorado and California."

The acquisition of Loxo Oncology provides Lilly with a promising pipeline of investigational medicines, including:

LOXO-292, a first-in-class oral RET inhibitor that has been granted Breakthrough Therapy designation by the FDA for three indications, with an initial potential launch in 2020. LOXO-292 targets cancers with alterations to the rearranged during transfection (RET) kinase. RET fusions and mutations occur across multiple tumor types, including certain lung and thyroid cancers as well as a subset of other cancers.
LOXO-305, an oral BTK inhibitor currently in Phase 1/2. LOXO-305 targets cancers with alterations to the Bruton’s tyrosine kinase (BTK), and is designed to address acquired resistance to currently available BTK inhibitors. BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas.
In November 2017, Loxo Oncology and Bayer Consumer Care AG entered into a global collaboration for the development and commercialization of the TRK inhibitors Vitrakvi (larotrectinib) and LOXO-195. The Bayer/Loxo agreement provides that Bayer may elect to convert the co-exclusive license to an exclusive license in the U.S. and Puerto Rico in the event of a change of control of Loxo Oncology. Bayer exercised its election under the Bayer/Loxo agreement to convert its co-exclusive license to an exclusive license in the U.S. and Puerto Rico, pending clearance under the Hart-Scott-Rodino Antitrust Improvements Act. When the new exclusive licensing arrangement takes effect, Lilly will receive royalties from Bayer on future sales of Vitrakvi and LOXO-195 both in the U.S. and in international markets.

Lilly has reaffirmed its current 2019 financial guidance. The expected financial impact of Lilly’s acquisition of Loxo Oncology has been previously communicated and is reflected in Lilly’s current 2019 financial guidance, as announced on February 6, 2019.

The Offer and the Merger
The tender offer for all of the outstanding shares of common stock of Loxo Oncology at a price of $235.00 per share, net to the seller in cash, without interest and less any required tax withholding (the "Offer"), expired as scheduled at one minute past 11:59 p.m., Eastern time, on Thursday, February 14, 2019. Computershare Trust Company, N.A., the depositary and paying agent for the Offer, has advised Lilly that 26,043,820 shares of Loxo Oncology common stock were validly tendered and not properly withdrawn in the Offer, representing approximately 84.6 percent of the shares of Loxo Oncology common stock outstanding. All of the conditions to the Offer have been satisfied and on February 15, 2019, Lilly and its wholly-owned subsidiary, Bowfin Acquisition Corporation, accepted for payment, and will promptly pay for, all shares validly tendered and not properly withdrawn in the Offer.

Following completion of the Offer, Lilly completed the acquisition of Loxo Oncology through the merger of Bowfin Acquisition Corporation with and into Loxo Oncology, without a vote of Loxo Oncology’s stockholders pursuant to Section 251(h) of the General Corporation Law of the State of Delaware, with Loxo Oncology surviving the merger as a wholly-owned subsidiary of Lilly. In connection with the merger, each share of common stock of Loxo Oncology not validly tendered into the Offer (other than (1) shares owned by Loxo Oncology immediately prior to the effective time of the merger, (2) shares owned by Lilly or Bowfin Acquisition Corporation at the commencement of the Offer and owned by Lilly or Purchaser immediately prior to the effective time of the merger or (3) shares held by any stockholder that was entitled to and has properly demanded statutory appraisal of its shares) has been converted into the right to receive the same $235.00 per share in cash, without interest and less applicable tax withholding, as will be paid for all shares that were validly tendered and not properly withdrawn in the Offer. Loxo Oncology’s common stock will be delisted from the NASDAQ Stock Market.

On February 15, 2020 Oncoceutics, Inc. reported the outlicense of the rights to the company’s lead compound, ONC201, for Japan to Ohara Pharmaceutical Co., Ltd (Press release, Oncoceutics, FEB 15, 2019, View Source [SID1234558361]). In addition, Ohara will receive a right of first refusal on the license of ONC201 for additional areas, including most of Asia and West Africa, and a right of first refusal for the company’s next generation compound, ONC206, in these territories.

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In return for the license and future rights, Ohara will make a multi-part payment to Oncoceutics including upfront payments, milestone payments, payment for purchase of the drug for re-sale, and royalties. In addition, Ohara will make a significant equity investment into Oncoceutics. Ohara will also be responsible for the execution of clinical trials required to obtain Marketing Authorization in Japan and the commercialization of ONC201 in the Japanese market.

ONC201 is a novel small molecule with a unique mechanism of action that has demonstrated anti-cancer activity and safety in preclinical models and in several ongoing clinical trials, including clinical trials in adult and pediatric patents with high-grade gliomas. The trials focus on gliomas that harbor a H3 K27M mutation that can be identified by immunohistochemistry or gene sequencing, including the FDA-approved companion diagnostic FoundationOne CDx. H3 K27M-mutant glioma is a molecularly-defined disease with a dismal prognosis.

Oncoceutics’ clinical trials are being carried out at numerous leading cancer centers across the United States, including: Massachusetts General Hospital, Dana Farber Cancer Institute, NYU Langone, MD Anderson Cancer Center, Levine Cancer Institute, Miami Cancer Institute, University of California San Francisco, and the University of Michigan. In addition, Emory University, University California Los Angeles, Columbia University and several other institutions are in the process of joining the program. Recently, the FDA granted Fast Track Designation to ONC201 for the Treatment of Adult Recurrent H3 K27M-mutant High-Grade Glioma.

"We are delighted to be partnering with Ohara Pharmaceutical Co., Ltd. whose mission and focus set them apart in the Japanese market and make them the ideal collaborators to bring ONC201 to Japanese patients with H3 K27M-mutant gliomas and other indications," said Wolfgang Oster, MD, PhD, Chief Executive Officer and Chairman of Oncoceutics. "This agreement sets the stage for developing ONC201 towards entry into global markets and providing a therapeutic option to patients in Japan who are affected by a serious disease. Oncoceutics will work closely with Ohara to expand the use of ONC201 into other cancers that are similarly responsive to the pathways engaged by ONC201. We are thrilled by the shared vision between the two companies to introduce a truly novel therapeutic paradigm to a broad selection of tumors that abuse dopamine signaling to promote their growth."

"We are excited to be working with the exceptional team at Oncoceutics to bring this novel medicine and medical concept to Japan for patients with cancer for whom there are no other options," said Seiji Ohara, President of Ohara Pharmaceuticals., Ltd. "The introduction of new treatment paradigms have often led to breakthroughs in diseases that have no therapeutic standards. The anticipated market entry for ONC201 in Japanese pediatric and adult oncology patients is consistent with Ohara’s strategy to challenge and address unmet medical needs. We are excited with the opportunity of the two companies to collaborate and develop ONC201 to address a broad selection of cancers responsive to ONC201."

On February 14, 2019 Alkermes plc (Nasdaq: ALKS) reported financial results for the year ended Dec. 31, 2018 and provided financial expectations for 2019 (Press release, Alkermes, FEB 14, 2019, View Source [SID1234533306]).

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"Our strong financial results in 2018 were driven by the growth of our proprietary commercial products and the continued strength and diversity of our royalty and manufacturing business," commented James Frates, Chief Financial Officer of Alkermes. "As we enter 2019, our financial expectations reflect the continued growth of our proprietary products, VIVITROL and ARISTADA, as well as important investments in the future growth drivers of the company including our advancing development pipeline and commercial capabilities to support our expanding presence in schizophrenia."

Quarter Ended Sept. 30, 2018 Financial Highlights

Total revenues for the quarter were $315.8 million. This compared to $275.4 million for the same period in the prior year, representing an increase of 15%. Proprietary product net sales for VIVITROL and ARISTADAi were $132.7 million for the quarter, reflecting a 28% increase compared to the same period in the prior year.

Net loss according to generally accepted accounting principles in the U.S. (GAAP) was $9.7 million for the quarter, or a basic and diluted GAAP net loss per share of $0.06. This compared to GAAP net loss of $9.8 million, or a basic and diluted GAAP net loss per share of $0.06, for the same period in the prior year.

Non-GAAP net income was $54.8 million for the quarter, or a non-GAAP basic earnings per share of $0.35 and non-GAAP diluted earnings per share of $0.34. This compared to non-GAAP net income of $50.3 million, or a non-GAAP basic earnings per share of $0.33 and non-GAAP diluted earnings per share of $0.31, for the same period in the prior year.

The launch of ARISTADA INITIOii continues to gain traction as payers and providers recognize the value proposition of this important new offering, particularly in combination with the ARISTADA two-month dose which provides the unique ability to fully dose a patient on day one for up to two monthsiii. With this offering, we are supporting continuity of care which is critically important for this patient population. We also continue to build the customized commercial capabilities necessary to navigate this complex treatment environment, including recent expansions of our field- and hospital-based teams," stated Jim Robinson, President and Chief Operating Officer of Alkermes. "VIVITROL results for 2018 were in-line with our expectations and we are encouraged by solid growth trends across many states. As we enter 2019, we remain committed to increasing access to VIVITROL and driving increased adoption in order to meet the needs of patients with opioid and alcohol dependence."

Quarter Ended Dec. 31, 2018 Financial Results

Revenues

Net sales of VIVITROL were $83.8 million, compared to $75.6 million for the same period in the prior year, representing an increase of approximately 11%.

Net sales of ARISTADA were $48.8 million, compared to $28.3 million for the same period in the prior year, representing an increase of approximately 72%.

Manufacturing and royalty revenues from RISPERDAL CONSTA, INVEGA SUSTENNA/XEPLION and INVEGA TRINZA/TREVICTA were $81.4 million, compared to $78.2 million for the same period in the prior year.

Manufacturing and royalty revenues from AMPYRA/FAMPYRAiv were $38.8 million, compared to $38.1 million for the same period in the prior year, which was above our expectations given generic entry into the market in 2018.

Manufacturing and royalty revenues included $26.7 million from Alkermes’ share of proceeds from the sale of certain royalty streams by Zealand Pharma A/S, related to products using Alkermes’ technology, to Royalty Pharma.

Research and development revenues were $15.6 million, of which $14.4 million related to R&D reimbursement from the company’s collaboration with Biogen for diroximel fumarate, or BIIB098.

Costs and Expenses

Operating expenses were $315.7 million, compared to $269.5 million for the same period in the prior year, primarily reflecting increased investment in the commercialization of ARISTADA and VIVITROL.

Calendar Year 2018 Financial Highlights

Total revenues increased 21% to $1.09 billion in 2018, which included VIVITROL net sales of $302.6 million and ARISTADA net sales of $147.7 million. This compared to total revenues of $903.4 million for 2017, which included VIVITROL net sales of $269.3 million and ARISTADA net sales of $93.5 million. Please see the tables at the end of this press release for a detailed breakdown of the revenues from our key commercial products.

GAAP net loss was $139.3 million, or a basic and diluted GAAP loss per share of $0.90, for 2018. This compared to a GAAP net loss of $157.9 million, or a basic and diluted GAAP loss per share of $1.03, for 2017.

Non-GAAP net income was $97.8 million, or a non-GAAP basic earnings per share of $0.63 and non-GAAP diluted earnings per share of $0.61, for 2018. This compared to non-GAAP net income of $27.8 million, or a non-GAAP basic earnings per share of $0.18 and non-GAAP diluted earnings per share of $0.17, for 2017.

At Dec. 31, 2018, Alkermes recorded cash, cash equivalents and total investments of $620.0 million, compared to $590.7 million at Dec. 31, 2017. At Dec. 31, 2018, the company’s total debt outstanding was $279.3 million, compared to $281.4 million at Dec. 31, 2017.

"Alkermes is defined by our commitment to making medicines that help address critical public health challenges, using our scientific insights to develop medicines that are designed with the real-world needs of patients in mind. Following the positive results of the ALKS 3831 ENLIGHTEN-2 pivotal study and the increasing traction of ARISTADA in the market, we continue to establish our emerging leadership position in the treatment of schizophrenia," said Richard Pops, Chief Executive Officer of Alkermes. "2019 will be an important year for our late-stage pipeline highlighted by the planned submission of the

ALKS 3831 New Drug Application and the regulatory review of the recently submitted New Drug Application for diroximel fumarate for multiple sclerosis, with expected action in the fourth quarter. As development activities surrounding our ALKS 4230 immuno-oncology program gain momentum, we expect to have our first indications of ALKS 4230’s anti-tumor response activity this year, and we look forward to updating you on our progress."

Recent Events:

ALKS 3831

In November 2018, Alkermes announced positive topline results from ENLIGHTEN-2, a pivotal phase 3 study of ALKS 3831 compared to olanzapine in patients with stable schizophrenia. In the study, ALKS 3831 met the pre-specified co-primary endpoints, demonstrating both a lower mean percent weight gain from baseline at six months compared to the olanzapine group and a lower proportion of patients who gained 10% or more of their baseline body weight at six months compared to the olanzapine group.

Diroximel fumarate (BIIB098)

In December 2018, Alkermes and Biogen announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for diroximel fumarate, a novel oral fumarate in development for the treatment of relapsing forms of multiple sclerosis. If approved, Biogen intends to market diroximel fumarate under the brand name VUMERITYTM. This name has been conditionally accepted by the FDA and will be confirmed upon approval.

ALKS 4230

In November 2018, Alkermes presented initial clinical data from the ongoing dose-escalation stage of the phase 1 study for ALKS 4230 at the 2018 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting.

ALKS 5461

In January 2019, Alkermes received a Complete Response Letter from the FDA regarding the NDA for ALKS 5461 for the adjunctive treatment of major depressive disorder.

Financial Expectations for 2019

The following outlines the company’s financial expectations for 2019, which include planned investments in the company’s pipeline of development candidates and commercial infrastructure to support the company’s expanding presence in schizophrenia.

Revenues: The company expects total revenues to range from $1.14 billion to $1.19 billion, driven by expected growth of our proprietary products and an expected $150 million milestone payment from Biogen in the fourth quarter related to the potential FDA approval of diroximel fumarate. Included in this total revenue expectation, Alkermes expects VIVITROL net sales to range from $330 million to $350 million, and ARISTADA net sales to range from $210 million to $230 million.

Cost of Goods Manufactured and Sold: The company expects cost of goods manufactured and sold to range from $180 million to $190 million.

Research and Development (R&D) Expenses: The company expects R&D expenses to range from $450 million to $480 million.

Selling, General and Administrative (SG&A) Expenses: The company expects SG&A expenses to range from $590 million to $620 million.

Amortization of Intangible Assets: The company expects amortization of intangibles to be approximately $40 million.

Net Interest Expense: The company expects net interest expense to range from $5 million to $10 million.

Income Tax Expense: The company expects income tax expense to range from $10 million to $15 million.

GAAP Net Loss: The company expects GAAP net loss to range from $135 million to $165 million, or a basic and diluted loss per share of $0.87 to $1.06, based on a weighted average basic and diluted share count of approximately 156 million shares outstanding.

Non-GAAP Net Income: The company expects non-GAAP net income to range from $40 million to $70 million, or a non-GAAP basic earnings per share of $0.26 to $0.45, based on a weighted average basic share count of approximately 156 million shares outstanding and a non-GAAP diluted earnings per share of $0.25 to $0.43, based on a weighted average diluted share count of approximately 161 million shares outstanding.

Share-Based Compensation: The company expects share-based compensation of approximately $120 million.

Capital Expenditures: The company expects capital expenditures to range from $90 million to $100 million.

Conference Call

Alkermes will host a conference call and webcast presentation with accompanying slides at 8:30 a.m. ET (1:30 p.m. BST) on Thursday, Feb. 14, 2019, to discuss these financial results and provide an update on the company. The webcast may be accessed on the Investors section of Alkermes’ website at www.alkermes.com. The conference call may be accessed by dialing +1 877 407 2988 for U.S. callers and +1 201 389 0923 for international callers. In addition, a replay of the conference call will be available from 11:00 a.m. ET (4:00 p.m. BST) on Thursday, Feb. 14, 2019, through Thursday, Feb. 21, 2019, and may be accessed by visiting Alkermes’ website or by dialing +1 877 660 6853 for U.S. callers and +1 201 612 7415 for international callers. The replay conference ID is 13687392.

On February 14, 2019 Bayer reported Results from the pivotal Phase III ARAMIS trial in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) showed a statistically significant improvement in metastasis-free survival (MFS) with the investigational drug darolutamide plus androgen deprivation therapy (ADT) compared to placebo plus ADT (HR=0.41, 95% CI 0.34-0.50; P<0.001) (Press release, Bayer, FEB 14, 2019, View Source [SID1234533327]).2 This translates to a 59 percent reduction in the risk of metastasis or death.1 The median MFS was 40.4 months in the darolutamide arm compared with 18.4 months for the placebo arm – an overall difference in median MFS of 22 months.1

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The incidence of adverse events (AEs) was generally similar in the darolutamide and placebo arms; only fatigue occurred in more than 10 percent of patients (15.8 percent with darolutamide plus ADT versus 11.4 percent with placebo plus ADT).2 The most common grade 3-4 AEs for darolutamide and placebo were 24.7 percent and 19.5 percent, respectively.2 Grade 3-4 AEs occurring in greater than or equal to 2 percent of patients were hypertension (3.1 percent versus 2.2 percent) and urinary retention (1.6 percent versus 2.0 percent) for darolutamide and placebo, respectively.2

These data were 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.

"These data are exciting for the prostate cancer community, as they show darolutamide’s potential to treat asymptomatic nmCRPC patients and delay spread of the disease," said Karim Fizazi, M.D., Ph.D., Professor of Medicine at the Institut Gustave Roussy, University of Paris Sud, France.

"These data demonstrate that darolutamide may be an option for men with nmCRPC and can potentially fulfill an unmet need for these patients," said Matthew Smith, M.D., Ph.D., Director of the Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center.

"Bayer is working diligently to bring treatments to patients in need," said Scott Z. Fields, M.D., senior vice president and head of Oncology Development at Bayer’s Pharmaceutical Division. "With the positive results of the ARAMIS trial, we are one step closer to our goal of bringing darolutamide to patients and physicians."

Bayer plans to discuss the data from the ARAMIS trial with health authorities regarding the submission of new drug applications. Bayer has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA) for darolutamide in men with nmCRPC. Darolutamide is being developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company.

Detailed study results
The ARAMIS trial also included several key secondary endpoints.2 At the time of the first interim analysis, median OS had not yet been reached in either treatment arm.1 However, these interim results demonstrated a trend in favor of darolutamide plus ADT (HR=0.71, 95% CI 0.50-0.99; P=0.045).1 Median time to pain progression was 40.3 months in the darolutamide arm compared to 25.4 months in the placebo arm (HR=0.65, 95% CI 0.53-0.79; P<0.001).1 Median time to cytotoxic chemotherapy was not reached yet in the darolutamide arm compared to 38.2 months in the placebo arm (HR=0.43, 95% CI 0.31-0.60; P<0.001).1 Median time to first symptomatic skeletal event (SSE) was also not reached yet in either treatment arm; however, these interim results demonstrated a trend in favor of darolutamide plus ADT (HR=0.43, 95% CI 0.22-0.84; P<0.001).1 SSE was defined as external beam radiation therapy (EBRT) to relieve skeletal symptoms, new symptomatic pathologic bone fracture, or occurrence of spinal cord compression or tumor-related orthopedic surgical intervention, whichever occurs first.2

Time-to-event exploratory endpoints included progression-free survival (PFS) and time to prostate-specific antigen (PSA) progression.2 Median PFS was 36.8 months in the darolutamide arm compared to 14.8 months in the placebo arm (HR=0.38, 95% CI 0.32-0.45; P<0.001).1 Time to PSA progression was 33.2 months in the darolutamide arm versus 7.3 months in the placebo arm (HR=0.13, 95% CI 0.11-0.16; P<0.001).2

Exploratory PRO-based endpoints (based on the Functional Assessment of Cancer Therapy-Prostate; FACT-P, European Organisation for Research and Treatment of Cancer quality of life; EORTC-QLQ-PR25, and EQ-5D-3L questionnaires) were also evaluated in the ARAMIS trial.1

About the ARAMIS trial design
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 as standard of care 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.

The primary endpoint of this trial is MFS defined as time between randomization and evidence of metastasis or death. The secondary endpoints of this trial are OS, time to pain progression, time to initiation of first cytotoxic chemotherapy, time to first SSE, and characterization of the safety and tolerability of darolutamide.

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 effective treatment options for CRPC patients who have rising PSA levels while on ADT and no detectable metastases. In men with progressive nmCRPC, a short PSA doubling time has been consistently associated with reduced time to first metastasis and death.8

About darolutamide
Darolutamide is an investigational, non-steroidal androgen receptor antagonist with a chemical structure that binds to the receptor and exhibits antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. 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.