On July 30, 2019 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported financial results for the three and six months ended June 30, 2019, and provided an operating forecast and program updates (Press release, Ligand, JUL 30, 2019, View Source [SID1234537897]). Ligand management will host a conference call today beginning at 9:00 a.m. Eastern time to discuss this announcement and answer questions.

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!

"During the quarter we reported positive top-line results from our Phase 1 trial with CE-Iohexol. Sage Therapeutics launched ZULRESSO, and in doing so added another key commercial asset to Ligand’s portfolio. We purchased a synthetic royalty from Novan on SB206, and Novan launched a Phase 3 trial with that compound for the treatment of molluscum contagiosum. Finally, our business development team has been very active in licensing, with two new partnerships from our OmniAb technology, two from our VDP technology and five new or advanced Captisol deals. In addition, this month we closed an acquisition of an antigen discovery company," said John Higgins, Chief Executive Officer of Ligand. "The sources of potential growth within our existing pipeline are rich and diversified, and we anticipate additional positive news flow throughout the remainder of the year. Over the longer term, we expect Ligand’s pipeline to be a significant source of meaningful and diversified cash flow."

Second Quarter 2019 Financial Results

Total revenues for the second quarter of 2019 were $25.0 million, compared with $90.0 million for the same period in 2018. Royalties were $6.6 million, compared with $31.4 million for the second quarter of 2018 and primarily consisted of royalties from Kyprolis and EVOMELA. Royalties in the second quarter of 2018 include royalties from Promacta, which was sold to Royalty Pharma as of March 6, 2019, for $827 million; Ligand did not receive any Promacta royalties in the second quarter of 2019 and will not receive any Promacta royalties going forward. Material sales were $8.5 million, compared with $7.6 million for the same period in 2018 due to the timing of Captisol purchases for use in clinical trials and commercial products. License fees, milestones and other revenues were $9.8 million, compared with $51.0 million for the same period in 2018, which included a $47 million payment from WuXi Biologics to amend its OmniAb platform license agreement.

Cost of material sales was $2.4 million for the second quarter of 2019, compared with $1.1 million for the same period in 2018, due to the timing and mix of Captisol sales. Amortization of intangibles was $3.5 million, compared with $3.3 million for the same period in 2018. Research and development expense was $12.2 million, compared with $6.1 million for the same period of 2018, due to costs associated with the VDP research team acquired recently and non-cash amortization of the upfront investments in the Palvella and Novan programs. General and administrative expense was $11.0 million, compared with $9.3 million for the same period in 2018.

Net loss for the second quarter of 2019 was $14.4 million, or $0.74 per diluted share, compared with net income of $73.2 million, or $2.99 per diluted share, for the same period in 2018. The second quarter of 2019 net loss was affected by a non-cash change in the value of Ligand’s investment in Viking Therapeutics of $12.4 million. Adjusted net income for the second quarter of 2019 was $13.9 million, or $0.68 per diluted share, compared with $60.6 million, or $2.59 per diluted share, for the same period in 2018.

As of June 30, 2019, Ligand had cash, cash equivalents and short-term investments of $1.3 billion, after having spent approximately $105 million on share repurchase and taxes, principally associated with taxes related to the $827 million sale of Promacta.

Year-to-Date Financial Results

Total revenues for the six months ended June 30, 2019 were $68.5 million, compared with $146.2 million for the same period in 2018. Royalties were $26.2 million, compared with $52.2 million for the six months ended June 30, 2018. Royalties for the six months ended June 30, 2019 primarily consisted of royalties from Promacta, Kyprolis and EVOMELA and do not include contribution from Promacta after March 6, 2019, whereas 2018 royalties included a full six months of Promacta royalties. Material sales were $17.5 million, compared with $12.0 million for the same period in 2018, due to the timing of Captisol purchases for use in clinical trials and commercial products. License fees, milestones and other revenues were $24.8 million, compared with $82.0 million for the same period in 2018, which included a $47 million payment from WuXi Biologics to amend its OmniAb platform license agreement as well as a $20 million upfront payment upon the licensing of Ligand’s GRA program.

Cost of material sales was $6.3 million for the six months ended June 30, 2019, compared with $1.9 million for the same period in 2018 due to the timing and mix of Captisol sales. Amortization of intangibles was $7.0 million, compared with $6.6 million for the same period in 2018. Research and development expense was $23.5 million, compared with $13.5 million for the same period of 2018, due to costs associated with recent acquisitions. General and administrative expense was $22.1 million, compared with $16.9 million for the same period in 2018, due to costs associated with recent acquisitions and non-cash stock-based compensation expense.

Net income for the six months ended June 30, 2019 was $651.9 million, or $31.34 per diluted share, compared with $118.4 million, or $4.81 per diluted share, for the same period in 2018. Net income for the six months ended June 30, 2019 was impacted by an after-tax gain of approximately $640 million on the sale of Ligand’s assets and royalty for Promacta to Royalty Pharma. Adjusted net income from continuing operations for the six months ended June 30, 2019 was $38.6 million, or $1.86 per diluted share, compared with $96.2 million, or $4.14 per diluted share, for the same period in 2018.

2019 Financial Guidance

Ligand is affirming its revenue guidance for 2019 with total revenues expected to be approximately $118 million. Ligand is also affirming its existing adjusted earnings per share guidance of approximately $3.20.

Second Quarter 2019 and Recent Business Highlights

OmniAb Platform Updates

Acquisition and New Licenses

Ligand announced the acquisition of Ab Initio Biotherapeutics for $12 million in cash. Ab Initio is a privately held antigen-discovery company based in South San Francisco, California.
Ligand entered into an OmniAb license agreement with Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Under the license, Takeda and its affiliates will be able to use OmniAb platform rodents and chickens in campaigns to discover fully human mono- and bispecific antibodies, as well as therapies using engineered cells and OmniAb-derived binders.
Ligand entered into an OmniAb license agreement with GigaGen, Inc., a South San Francisco-based biotherapeutics company, under which GigaGen will be able to use OmniAb platform rodents and chickens to discover fully human mono- and bispecific-antibodies.
Partner Updates

CStone Pharmaceuticals announced dosing of the first patient in a Phase 3 clinical trial assessing OmniAb-derived CS1001 in combination with chemotherapy for the treatment of gastric adenocarcinoma or gastro-esophageal junction adenocarcinoma.
CStone Pharmaceuticals announced the company has entered into a collaboration with Bayer to evaluate CS1001 in combination with Bayer’s regorafenib as a treatment for multiple cancers including gastric cancer.
OmniAb-derived DuoBody-PD-L1x4-1BB was highlighted in GenMab’s U.S. IPO Form S-1 filing and on clintrials.gov.
Immunovant announced presentation of detailed findings in healthy subjects for IMVT-1401 (formerly RVT-1401) in a poster session at the 2019 American Academy of Neurology Annual Meeting and initiated dosing in ASCEND-GO 1, an open-label, single-arm Phase 2a clinical trial evaluating IMVT-1401 in patients with moderate-to-severe active Graves’ ophthalmopathy.
Aptevo Therapeutics provided an update on OmniAb-derived APVO436 and announced that Phase 1 data is anticipated in the fourth quarter of 2019. New preclinical data for APVO436 was also presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2019 Annual Meeting.
OmniAb partner xCella Biosciences presented high-throughput functional screening of antibody libraries, highlighting OmniRat and OmniChicken, at the 2019 Protein Engineering Summit (PEGS).
Publications and Presentations

At PEGS 2019, Ligand scientists announced the launch of OmniClic, a novel next-generation common light chain OmniChicken-based antibody discovery technology focused on bispecific antibodies.
Ligand highlighted OmniChicken in a presentation titled "High Throughput SPR Demonstrates that V-lambda Expressing OmniChickens Exhibit Broad Epitope Coverage and Picomolar Affinity" and highlighted OmniClic in a presentation titled "Fixed Light Chain Transgenic Chicken for Bispecific Antibody Discovery" at Antibody Engineering and Therapeutics-Europe conference.
Other Licensing and Acquisition Events

Ligand announced the acquisition of economic rights to SB206 from Novan, Inc. SB206 is a Phase 3 topical antiviral gel for the treatment of skin infections, including molluscum contagiosum. Ligand paid $12 million to Novan and in return is entitled to receive a tiered royalty of 7% to 10%, as well as up to $20 million in regulatory and commercial milestones.
Ligand entered a worldwide license agreement granting Cumulus Oncology exclusive rights to develop and commercialize VER250840, a novel, oral, selective, preclinical Chk1 Kinase Inhibitor discovered using Ligand’s Vernalis Design Platform (VDP). Ligand received an upfront license fee and is eligible to receive more than $76 million of milestone payments, as well as tiered royalties in the mid-to-high single digits and an additional fee based on Cumulus achieving specified financing-related events.
Ligand entered an exclusive commercial license and supply agreement with SQ Innovation AG for use of Ligand’s Captisol technology in the formulation of high-concentration furosemide for the treatment of edema in patients with heart failure. Ligand is eligible to receive potential milestone payments and royalties, as well as revenue from materials sales of Captisol.
Ligand entered a VDP research collaboration agreement with PhoreMost Limited, a private UK-based biotech, on an undisclosed novel oncology target. Ligand and PhoreMost will share revenues from any future out-licenses. Based on Ligand’s contribution and stage of development at the time of licensing, Ligand will be entitled to a scaling interest in license economics.
Ligand recently entered into new Captisol clinical use or commercial license and supply agreements with Millennium/Takeda, Bexon Biomedical, Valanbio Therapeutics and BendaRx Corporation.
Additional Pipeline and Partner Developments

Sage Therapeutics launched ZULRESSO (brexanolone) injection. With this launch, ZULRESSO is the 11th U.S. Food and Drug Administration (FDA)-approved drug to use Ligand’s patented Captisol technology.
Novan announced that the company had exceeded 50% of expected patient enrollment in the company’s ongoing "B-SIMPLE" Phase 3 program evaluating topical nitric oxide product candidate SB206 for the treatment of molluscum contagiosum.
Viking Therapeutics presented new results from the company’s 12-week Phase 2 study of VK2809 in patients with non-alcoholic fatty liver disease and elevated low-density lipoprotein cholesterol at the International Liver Congress 2019.
Metavant has been working with FDA to determine a path forward for the glucagon receptor antagonist or GRA program now known as RVT-1502 in diabetes. Ligand believes that continued development of RVT-1502 for diabetes in the U.S. is highly unlikely based on preclinical and clinical trials now required by FDA for any drug in the GRA class intended for long-term use. Metavant may choose to explore certain other indications and/or geographies for RVT-1502 and expects to make a decision later this year.
Sermonix Pharmaceuticals announced that lasofoxifene has been granted Fast Track designation by the FDA and presented a poster on the preclinical performance of its lead investigational drug, lasofoxifene, at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting.
Daiichi Sankyo announced the launch in Japan of MINNEBRO (esaxerenone) tablets.
Melinta Therapeutics announced the FDA has accepted a supplemental New Drug Application (sNDA) for BAXDELA (delafloxacin) for priority review. The sNDA filing seeks to expand the current indication for BAXDELA to include adult patients with community-acquired bacterial pneumonia.
Verona Pharma announced the initiation of a Phase 2b dose-ranging study evaluating nebulized ensifentrine (RPL554) added on to a long-acting bronchodilator in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD) and also presented clinically relevant findings from its COPD clinical trial program with ensifentrine at the American Thoracic Society International Conference.
Nucorion Pharmaceuticals announced the closing of a $5 million Series B Preferred Stock financing to support the Phase 1 clinical development in the US for its lead program, NCO-1010 for the potential treatment of hepatitis B, which utilizes Ligand’s LTP Platform technology. Guangdong Ji-Bao Pharmaceutical Company of Guangzhou, China invested $4 million and Ligand invested $1 million in the round.
Internal R&D

Ligand announced positive top-line results from a Phase 1 clinical trial of its internal Captisol-enabled (CE) Iohexol program. The trial achieved the primary endpoint by demonstrating pharmacokinetic bioequivalence of CE-Iohexol injection and a reference Iohexol injection (OMNIPAQUE) after intravenous (IV) administration in healthy adults. CE-Iohexol injection was safe and well tolerated, and adverse events were in line with the known safety profile of OMNIPAQUE.
Adjusted Financial Measures

The Company reports adjusted net income and adjusted net income per diluted share in addition to, and not as a substitute for, or superior to, financial measures calculated in accordance with GAAP. The Company’s financial measures under GAAP include stock-based compensation expense, amortization of debt-related costs, amortization related to acquisitions and intangible assets, changes in contingent liabilities, mark-to-market adjustments for amounts relating to its equity investments in public companies, unissued shares relating to its Senior Convertible Notes, gain on the sale of Promacta and others that are listed in the itemized reconciliations between GAAP and adjusted financial measures included at the end of this press release. However, other than with respect to total revenues, the Company only provides financial guidance on an adjusted basis and does not provide reconciliations of such forward-looking adjusted measures to GAAP due to the inherent difficulty in forecasting and quantifying certain amounts that are necessary for such reconciliation, including adjustments that could be made for changes in contingent liabilities, changes in the market value of its investments in public companies, stock-based compensation expense and effects of any discrete income tax items. Management has excluded the effects of these items in its adjusted measures to assist investors in analyzing and assessing the Company’s past and future core operating performance. Additionally, adjusted earnings per diluted share is a key component of the financial metrics utilized by the Company’s board of directors to measure, in part, management’s performance and determine significant elements of management’s compensation.

Conference Call

Ligand management will host a conference call today beginning at 9:00 a.m. Eastern time (6:00 a.m. Pacific time) to discuss this announcement and answer questions. To participate via telephone, please dial (833) 591-4752 from the U.S. or (720) 405-1612 from outside the U.S., using the conference ID 1997313. To participate via live or replay webcast, a link is available at www.ligand.com.

On July 30, 2019 The U.S. Food and Drug Administration (FDA) reported that it approved Nubeqa (darolutamide), an androgen receptor inhibitor (ARi), for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) (Press release, Bayer, JUL 30, 2019, View Source [SID1234537914]).1 The FDA approval is based on the Phase III ARAMIS trial evaluating Nubeqa plus androgen deprivation therapy (ADT), which demonstrated a highly significant improvement in the primary efficacy endpoint of metastasis-free survival (MFS), with a median of 40.4 months versus 18.4 months for placebo plus ADT (p<0.0001).1 MFS is defined as the time from randomization to the time of first evidence of blinded independent central review (BICR)-confirmed distant metastasis or death from any cause within 33 weeks after the last evaluable scan, whichever occurred first. Nubeqa was approved under the FDA’s Priority Review designation, which is reserved for medicines that may provide significant improvements in the safety or effectiveness of the treatment for serious conditions.

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!

"Patients at this stage of prostate cancer typically don’t have symptoms of the disease. The overarching goals of treatment in this setting are to delay the spread of prostate cancer and limit the burdensome side effects of therapy," said Matthew Smith, M.D., Ph.D., Director of the Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center. "This approval marks an important new option for the prostate cancer community."

In the U.S., over 73,000 men are estimated to be diagnosed with castration-resistant prostate cancer (CRPC) in 2019.2 About 40 percent of these patients have prostate cancer that has not spread to other parts of the body and is also associated with a rising prostate-specific antigen (PSA) level, despite a castrate testosterone level, which is known as nmCRPC.2,3 This is important because about one-third of men with nmCRPC go on to develop metastases within two years.4 PSA monitoring is important to identify patients and help offset undertreatment in men before the disease spreads.5,6

"We know that men with nmCRPC are still in the prime of their lives and are at a critical point in their disease when action needs to be taken," said Howard R. Soule, Ph.D., Executive Vice President and Chief Science Officer, Prostate Cancer Foundation (PCF). "For 26 years, PCF has been focused on research aimed at improving patient outcomes and we welcome the addition of new treatment options that provide men with more choices when working with their doctor to select what’s right for them."

"With the approval of Nubeqa, we now have a new therapy that extends MFS and allows physicians greater flexibility to treat men living with nmCRPC," said Robert LaCaze, Member of the Executive Committee of Bayer’s Pharmaceuticals Division and Head of the Oncology Strategic Business Unit at Bayer. "Bayer is proud to take this latest step forward in the nmCRPC treatment landscape. Nubeqa is the newest addition to our prostate cancer portfolio and reflects Bayer’s commitment to finding treatments for men at different stages along the prostate cancer continuum."

In the ARAMIS trial, both arms showed a 9 percent discontinuation rate due to adverse reactions.1 The most frequent adverse reactions requiring discontinuation in patients who received Nubeqa included cardiac failure (0.4 percent), and death (0.4 percent).1 Adverse reactions occurring more frequently in the Nubeqa arm (≥2 percent over placebo) were fatigue (16 percent versus 11 percent), pain in extremity (6 percent versus 3 percent) and rash (3 percent versus 1 percent).1 Nubeqa was not studied in women and there is a warning and precaution for embryo-fetal toxicity.1

Overall survival (OS) and time to pain progression were additional secondary efficacy endpoints.1 OS data were not yet mature at the time of final MFS analysis.1 The MFS result was supported by a delay in time to pain progression, defined as at least a 2-point worsening from baseline of the pain score on Brief Pain Inventory-Short Form or initiation of opioids, in patients treated with Nubeqa as compared to placebo.1 Pain progression was reported in 28 percent of all patients on study.1

Bayer has filed for approval of Nubeqa in the European Union (EU), Japan, and with other health authorities. Nubeqa is developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company.

Nubeqa will be available in oral tablets for adults.1 For more information, visit www.NUBEQA.com.

Value Program for Nubeqa Patients
Bayer is committed to ensuring that patients in the U.S. who are prescribed Nubeqa can access the medication and receive the support they may need. As part of this commitment, Bayer is launching an innovative patient support program, DUDE (Darolutamide User Drug Experience) Access Services, which offers a two-month Free Trial Program to eligible patients along with a $0 co-pay for commercially insured patients who qualify. To learn more about these and other services, please visit the website or call 1-833-337-DUDE (1-833-337-3833) available Monday-Friday, 9:00am-7:00pm EST.

Clinical Trial Results
The FDA approval of Nubeqa (darolutamide) is based on the ARAMIS trial, a randomized, double-blind, placebo-controlled, multi-center Phase III study, which evaluated the safety and efficacy of oral Nubeqa in patients with nmCRPC who were receiving a concomitant gonadotropin-releasing hormone (GnRH) analog or had a bilateral orchiectomy. In the clinical study, 1,509 patients were randomized in a 2:1 ratio to receive 600 mg of Nubeqa orally twice daily or placebo plus ADT. Patients with a history of seizure were allowed in the study.1

The primary efficacy endpoint of the trial was MFS, defined as the time from randomization to the time of first evidence of BICR-confirmed distant metastasis or death due to any cause within 33 weeks after the last evaluable scan, whichever occurred first.1 Nubeqa plus ADT demonstrated a statistically significant improvement in MFS, with a median MFS of 40.4 months versus 18.4 months with placebo plus ADT [HR=0.41, 95% CI (0.34, 0.50), p<0.0001].1 OS and time to pain progression were additional secondary efficacy endpoints.1 OS data were not yet mature at the time of final MFS analysis.1 The MFS result was supported by a delay in time to pain progression, defined as at least a 2-point worsening from baseline of the pain score on Brief Pain Inventory-Short Form or initiation of opioids, in patients treated with Nubeqa as compared to placebo.1 Pain progression was reported in 28 percent of all patients on study.1

Adverse reactions occurring more frequently in the Nubeqa arm (≥2 percent over placebo) were fatigue (16 percent versus 11 percent), pain in extremity (6 percent versus 3 percent) and rash (3 percent versus 1 percent).1 The only observed adverse reaction in ≥10 percent of patients receiving Nubeqa was fatigue.1 Additionally, clinically significant adverse reactions occurring in 2 percent or more of patients treated with Nubeqa included ischemic heart disease (4.0 percent versus 3.4 percent on placebo) and heart failure (2.1 percent versus 0.9 percent on placebo).1 Discontinuation due to adverse reactions occurred in 9 percent of patients in both arms of the study.1 The most frequent adverse reactions requiring discontinuation in patients who received Nubeqa included cardiac failure (0.4 percent), and death (0.4 percent).1 Dose interruptions due to an adverse reaction occurred in 13 percent of patients treated with Nubeqa.1 The most frequent adverse reactions requiring dosage interruption in patients who received Nubeqa included hypertension (0.6 percent), diarrhea (0.5 percent), and pneumonia (0.5 percent).1 Dose reductions due to an adverse reaction occurred in 6 percent of patients treated with Nubeqa.1 The most frequent adverse reactions requiring dosage reduction in patients treated with Nubeqa included fatigue (0.7 percent), hypertension (0.3 percent), and nausea (0.3 percent).1

About Nubeqa (darolutamide)
Nubeqa (darolutamide) is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription.1 Nubeqa is approved for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC).1 A Phase III study in metastatic hormone-sensitive prostate cancer (ARASENS) is ongoing. Information about this trial can be found at www.clinicaltrials.gov.

Bayer has submitted filings for darolutamide in the European Union (EU), Japan, and additional countries.

About Prostate Cancer
Prostate cancer is the second most commonly diagnosed malignancy and fifth leading cause of cancer in men worldwide.7 In 2018, an estimated 1.2 million men were diagnosed with prostate cancer, and about 358,000 died from the disease worldwide.7 Prostate cancer results from the abnormal proliferation of cells within the prostate gland, which is part of a man’s reproductive system.8 It mainly affects men over the age of 50, and the risk increases with age.9 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.10 However, in nearly all cases, the cancer eventually becomes resistant to conventional hormone therapy.11

Castration-resistant prostate cancer (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 two years ago, there have been no FDA-approved treatment options for CRPC patients who have prostate cancer that has not spread to other parts of the body with rising prostate-specific antigen (PSA) levels despite a castrate testosterone level, which is called non-metastatic castration-resistant prostate cancer, or nmCRPC.6,12 About one-third of men with nmCRPC go on to develop metastases within two years.4 In men with progressive nmCRPC, a short PSA doubling time is correlated with shortened time to first metastasis and death.12

IMPORTANT SAFETY INFORMATION

Embryo-Fetal Toxicity: Safety and efficacy of NUBEQA have not been established in females. NUBEQA can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with NUBEQA and for 1 week after the last dose.

Adverse Reactions

Serious adverse reactions occurred in 25% of patients receiving NUBEQA and in 20% of patients receiving placebo. Serious adverse reactions in ≥ 1 % of patients who received NUBEQA were urinary retention, pneumonia, and hematuria. Overall, 3.9% of patients receiving NUBEQA and 3.2% of patients receiving placebo died from adverse reactions, which included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%) for NUBEQA.

Adverse reactions occurring more frequently in the NUBEQA arm (≥ 2% over placebo) were fatigue (16% vs. 11%), pain in extremity (6% vs. 3%) and rash (3% vs. 1%).

Clinically significant adverse reactions occurring in ≥ 2% of patients treated with NUBEQA included ischemic heart disease (4.0% vs. 3.4% on placebo) and heart failure (2.1% vs. 0.9% on placebo).

Drug Interactions

Effect of Other Drugs on NUBEQA – Concomitant use of NUBEQA with a combined P-gp and strong or moderate CYP3A4 inducer decreases darolutamide exposure, which may decrease NUBEQA activity. Avoid concomitant use of NUBEQA with combined P-gp and strong or moderate CYP3A4 inducers.

Concomitant use of NUBEQA with a combined P-gp and strong CYP3A4 inhibitor increases darolutamide exposure, which may increase the risk of NUBEQA adverse reactions. Monitor patients more frequently for NUBEQA adverse reactions and modify NUBEQA dosage as needed.

Effects of NUBEQA on Other Drugs – NUBEQA is an inhibitor of breast cancer resistance protein (BCRP) transporter. Concomitant use of NUBEQA increases the exposure (AUC) and maximal concentration of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use with drugs that are BCRP substrates where possible. If used together, monitor patients more frequently for adverse reactions, and consider dose reduction of the BCRP substrate drug. Consult the approved product labeling of the BCRP substrate when used concomitantly with NUBEQA.

For important risk and use information about Nubeqa, please see the full Prescribing Information.

About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer now expands to six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.

On July 30, 2019 NewLink Genetics Corporation (NASDAQ:NLNK) ("NewLink Genetics" or the "Company") reported financial results for the second quarter ended June 30, 2019 and provided an update on clinical and corporate developments, including a transition of management (Press release, NewLink Genetics, JUL 30, 2019, View Source [SID1234537880]). Charles J. Link, Jr, M.D. has chosen to retire from his posts as Chairman, Chief Executive Officer and Chief Scientific Officer, and has also resigned from the Board, effective August 3, 2019. Dr. Link cofounded NewLink Genetics in 1999 and served as the Company’s Chief Scientific Officer until his additional appointment to CEO and Chairman in 2003.

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!

NewLink Genetics’ Board of Directors has established an Office of the CEO. Effective August 3rd, members of the Office of the CEO will lead the company to advance its strategic goals. The Board of Directors has elected Carl Langren, Chief Financial Officer; Eugene Kennedy, M.D., Chief Medical Officer; Brad Powers, General Counsel; and Lori Lawley, Vice President, Finance and Controller to the Office of the CEO. Reporting to the Board of Directors, the members of the Office of the CEO have been given full executive authority and will oversee the execution of the Company’s operations and strategic initiatives.

"I am grateful and deeply honored to have had the opportunity to lead NewLink Genetics and work alongside some incredibly talented people on projects dedicated to patients with great unmet medical need," said Charles J. Link Jr, M.D. "I have confidence that the company and its leadership have the resources to move forward and succeed and I look forward to watching the company’s progress. I plan to enjoy spending more time with my family as well."

"NewLink Genetics is grateful to our co-founder, Charles Link, for his 20 years of service in building the Company," said Thomas A. Raffin, M.D., Lead Independent Director of NewLink Genetics. "The Board of Directors and Company are thankful to Chuck for his many contributions and for fostering our mission of improving the lives of patients and their families. Moving forward, we are fully confident that the leadership team in the Office of the CEO is positioned to advance the Company’s goals following Chuck’s retirement."

NewLink Genetics ended the second quarter with $105.4 million in cash. The Company continues to evaluate potential acquisition, in-licensing, or other opportunities to broaden its pipeline, assist patients, and create value for shareholders.

Clinical Update

The Company presented updated data from a Phase 1 dose-escalation study of NLG802, a prodrug of indoximod, at the Immuno-Oncology 2019 2nd World Congress in Barcelona, Spain, May 23-24, 2019.

Updated results from the cohort of patients with DIPG in the efficacy portion of a Phase 1b study of indoximod for the treatment of pediatric patients with recurrent malignant brain tumors are anticipated later in 2019.

In reference to NewLink Genetics’ partnered Ebola vaccine candidate, Merck recently announced that the licensing application for this vaccine, V920 (rVSV∆G-ZEBOV-GP), is under review at the FDA, the European Medicines Agency (EMA), the World Health Organization (WHO), and African countries. Should this vaccine be approved by the FDA, a Priority Review Voucher (PRV) would be issued, in which NewLink Genetics owns a substantial financial interest.

Financial Results for the Three-Month Period Ended June 30, 2019

Cash Position: NewLink Genetics ended the quarter on June 30, 2019, with cash and cash equivalents totaling $105.4 million compared to $120.7 million on December 31, 2018. The Company projects its cash position is sufficient to fund planned operations through the end of 2021.

R&D Expenses: Research and development expenses for the second quarter of 2019 were $5.2 million, a decrease of $6.9 million from $12.1 million for the same period in 2018. The decrease was primarily due to reductions of $2.4 million in contract research and manufacturing spend, $2.0 million in clinical trial expense, $1.8 million in personnel-related and stock compensation expense, $400,000 in supplies and licensing, and $300,000 in legal and consulting expense.

G&A Expenses: General and administrative expenses in the second quarter of 2019 were $5.6 million, a decrease of $2.3 million from $7.9 million for the same period in 2018. The decrease was due primarily to reductions of $1.9 million in personnel-related and stock compensation expense and $400,000 in supplies.

Net Loss: NewLink Genetics reported a net loss of $(10.1) million or $(0.27) per diluted share for the second quarter of 2019 compared to a net loss of $(17.3) million or $(0.47) per diluted share for the second quarter of 2018.

NewLink Genetics ended the second quarter of 2019 with 37,300,960 shares outstanding.

On July 30, 2019 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported financial results for the second quarter of 2019 (Press release, Merck & Co, JUL 30, 2019, View Source [SID1234537898]).

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!

"Our science-led strategy and execution across our key growth pillars have driven another quarter of accelerating revenue growth with strength across our global portfolio," said Kenneth C. Frazier, chairman and chief executive officer, Merck. "We remain confident that our innovative products and significant pipeline opportunities will continue to deliver strong results and provide sustainable value to patients and shareholders."

Worldwide sales were $11.8 billion for the second quarter of 2019, an increase of 12% compared with the second quarter of 2018; excluding the negative impact from foreign exchange, worldwide sales grew 15%.

GAAP (generally accepted accounting principles) earnings per share assuming dilution (EPS) were $1.03 for the second quarter of 2019. Non-GAAP EPS of $1.30 for the second quarter of 2019 excludes acquisition- and divestiture-related costs, restructuring costs and certain other items. Year-to-date results can be found in the attached tables.

Pipeline Highlights

Oncology

Merck continued to advance the development programs for KEYTRUDA (pembrolizumab), the company’s anti-PD-1 therapy; Lynparza (olaparib), a PARP inhibitor being co-developed and co-commercialized with AstraZeneca; and Lenvima (lenvatinib mesylate), an orally available tyrosine kinase inhibitor being co-developed and co-commercialized with Eisai Co., Ltd. (Eisai).

KEYTRUDA

Merck announced that the U.S. Food and Drug Administration (FDA) approved KEYTRUDA for the following indications:
First-line treatment of patients with metastatic or with unresectable, recurrent head and neck squamous cell carcinoma (HNSCC) as monotherapy for patients whose tumors express PD-L1 (Combined Positive Score [CPS] >1) or in combination with platinum and fluorouracil (FU), a commonly used chemotherapy regimen, based on overall survival results from the KEYNOTE-048 trial; and
Treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy based on the results from the KEYNOTE-158 and KEYNOTE-028 trials.
Merck announced that the European Medicines Agency (EMA) adopted a positive opinion for KEYTRUDA in combination with axitinib as a first-line treatment for advanced renal cell carcinoma (RCC) based on the findings from the pivotal KEYNOTE-426 trial.
Merck announced that the FDA has accepted for review six supplemental Biologics License Applications (sBLAs) to update the dosing frequency for KEYTRUDA to include an every-six-weeks (Q6W) dosing schedule option for certain monotherapy indications. The FDA has set a PDUFA date of Feb. 18, 2020.
Merck presented five-year survival data for KEYTRUDA in advanced non-small cell lung cancer (NSCLC) from the first KEYNOTE trial (Phase 1b KEYNOTE-001) and updated overall survival analysis and new data for disease progression after next-line treatment (progression-free survival2) from the KEYNOTE-189 trial in metastatic nonsquamous NSCLC at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting.
Merck announced that the Phase 3 KEYNOTE-522 trial investigating KEYTRUDA in combination with chemotherapy met the primary endpoint of pathological complete response (pCR) following the neoadjuvant part of the neoadjuvant/adjuvant study regimen in patients with triple-negative breast cancer (TNBC). The trial will continue to evaluate the other dual-primary endpoint of event-free survival (EFS). Results will be presented at an upcoming medical congress.
Lynparza

Merck and AstraZeneca announced approval of Lynparza in Japan and separately in the European Union for use as first-line maintenance therapy in patients with BRCA-mutated advanced ovarian cancer based on the results of the Phase 3 SOLO-1 trial. Lynparza is the only PARP inhibitor approved for this indication and the only PARP inhibitor approved in Japan.
Merck and AstraZeneca presented results from the Phase 3 POLO trial in patients with germline BRCA-mutated metastatic pancreatic cancer whose disease had not progressed following platinum-based chemotherapy. In the trial, Lynparza reduced the risk of disease progression or death by nearly half (47%). These results were presented at the 2019 ASCO (Free ASCO Whitepaper) annual meeting and simultaneously published in the New England Journal of Medicine.
Merck and AstraZeneca also presented results from the Phase 3 SOLO3 trial at the 2019 ASCO (Free ASCO Whitepaper) annual meeting. This study evaluated the objective response rate of Lynparza compared to chemotherapy in patients with platinum-sensitive relapsed germline BRCA1/2-mutated advanced ovarian cancer, who have received two or more prior lines of chemotherapy.
Lenvima

Merck and Eisai announced receipt of a Breakthrough Therapy Designation from the FDA for the KEYTRUDA plus Lenvima combination regimen for potential first-line treatment of patients with advanced unresectable hepatocellular carcinoma not amenable to loco-regional treatment, representing the third such designation.
Vaccines

Merck announced the U.S. Centers for Disease Control and Prevention’s (CDC’s) Advisory Committee on Immunization Practices (ACIP) voted to recommend Human Papillomavirus (HPV) vaccination with GARDASIL 9 (Human Papillomavirus 9-valent Vaccine, Recombinant) based on shared clinical decision making for individuals ages 27 through 45 who are not adequately vaccinated. The ACIP also voted to expand routine and catch-up recommendations for males through age 26 who are not adequately vaccinated.
Merck presented Phase 2 trial results of V114, the company’s investigational 15-valent pneumococcal conjugate vaccine, which demonstrated noninferiority to PCV 13 for all shared serotypes and an immune response for two additional disease-causing serotypes, 22F and 33F in healthy infants. Results were presented at the European Society for Paediatric Infectious Diseases (ESPID). V114 is currently in Phase 3 development.
HIV and Hospital Acute Care

Merck presented late-breaking data with islatravir (formerly MK-8591), the company’s investigational nucleoside reverse transcriptase translocation inhibitor (NRTTI) in development for the prevention and treatment of HIV-1 infection, at the recent 10th International AIDS Society Conference on HIV Science (IAS 2019), which included:
Phase 2b results demonstrating the combination of islatravir with doravirine maintained antiviral activity in treatment-naïve adults through 48 weeks. Based on these results, the company plans to initiate a Phase 3 program evaluating islatravir in combination with doravirine across diverse patient populations; and
Phase 1 results evaluating the pharmacokinetics and safety of a prototype subdermal drug-eluting implant for extended administration of islatravir in healthy volunteers for HIV pre-exposure prophylaxis (PrEP).
Merck announced FDA approval of an expanded use for ZERBAXA (ceftolozane and tazobactam) for the treatment of adults with hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) and separately announced the EMA adopted a positive opinion recommending ZERBAXA for HABP and VABP, which is now under consideration by the European Commission.
Merck announced FDA approval of RECARBRIO (imipenem, cilastatin, and relebactam) for the treatment of adults with complicated urinary tract and complicated intra-abdominal bacterial infections where limited or no alternative treatment options are available.
Business Development Highlights

Merck acquired Peloton Therapeutics (Peloton), a biopharmaceutical company focused on the development of novel small molecule therapeutic candidates targeting hypoxia-inducible factor-2A (HIF-2a) for the treatment of patients with cancer and other non-oncology diseases, including a novel oral HIF-2a inhibitor in late-stage development for RCC. The acquisition closed in July.
Merck acquired Tilos Therapeutics, gaining a portfolio of investigational antibodies targeting TGFβ for the potential application in the treatment of cancer, fibrosis and autoimmune diseases. The acquisition closed in June.
Merck acquired Immune Design, providing potential next-generation in vivo approaches to enable the body’s immune system to fight disease. The acquisition closed in April.
Second-Quarter Revenue Performance

The following table reflects sales of the company’s top pharmaceutical products, as well as sales of animal health products.

Pharmaceutical Revenue

Second-quarter pharmaceutical sales were $10.5 billion, an increase of 13% compared with the second quarter of 2018; excluding the unfavorable effect of foreign exchange, sales grew 17% in the second quarter. The increase was driven primarily by growth in oncology and vaccines, partially offset by the ongoing impacts of the loss of market exclusivity for several products. International pharmaceutical sales represented 55% of total sales in the quarter. Performance in international markets was led by China, which had pharmaceutical sales of $745 million representing growth of 41% compared with the second quarter of 2018, driven by oncology and vaccines. Excluding the unfavorable effect of foreign exchange, pharmaceutical sales in China grew by 51%.

Growth in oncology was largely driven by a nearly $1 billion increase in sales for KEYTRUDA to $2.6 billion, reflecting strong momentum from the NSCLC indications as well as continued uptake in other indications, including the recently launched RCC and adjuvant melanoma indications, along with growth from Lynparza and Lenvima.

Growth in vaccines reflects higher sales of GARDASIL [Human Papillomavirus Quadrivalent (Types 6, 11, 16 and 18) Vaccine, Recombinant] and GARDASIL 9, vaccines to prevent certain cancers and other diseases caused by HPV, primarily due to public sector buying patterns, demand and pricing in the United States, and the ongoing commercial launch in China. Higher demand in Europe, driven primarily by increased vaccination rates for both boys and girls, also contributed to sales growth.

Growth in pediatric vaccines was driven by M-M-R II (Measles, Mumps and Rubella Virus Vaccine Live), a vaccine to help prevent measles, mumps and rubella; VARIVAX (Varicella Virus Vaccine Live), a vaccine to help prevent chickenpox; and PROQUAD (Measles, Mumps, Rubella and Varicella Virus Vaccine Live), a combination vaccine to help protect against measles, mumps, rubella and varicella; reflecting higher demand, including private-sector buy-in, and pricing in the United States; government tenders in Latin America and higher demand in Europe.

Performance in hospital acute care reflects strong demand in the United States for BRIDION (sugammadex) Injection 100 mg/mL, a medicine for the reversal of neuromuscular blockade induced by rocuronium bromide or vecuronium bromide in adults undergoing surgery; and the ongoing launch of PREVYMIS (letermovir), a medicine for the prevention of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant.

Pharmaceutical sales growth for the quarter was partially offset by the ongoing impacts from the loss of market exclusivity for ZETIA (ezetimibe) and VYTORIN (ezetimibe/simvastatin), INVANZ (ertapenem sodium) and REMICADE (infliximab). In addition, the decline in sales of JANUVIA (sitagliptin) and JANUMET (sitagliptin and metformin HCI) reflects continued pricing pressure in the United States, which more than offset higher demand globally.

Animal Health Revenue

Animal Health sales totaled $1.1 billion for the second quarter of 2019, an increase of 3% compared with the second quarter of 2018. Excluding the unfavorable effect from foreign exchange, Animal Health sales grew 9%. Growth in the second quarter was primarily driven by livestock, predominantly due to products acquired in the Antelliq acquisition. Companion animal sales performance reflects volume growth in vaccine and insulin products, partially offset by the timing of customer purchases in the prior year for the BRAVECTO (fluralaner) line of products for parasitic control.

Animal Health segment profits were $405 million in the second quarter of 2019, a decrease of 10% compared with $450 million in the second quarter of 2018, primarily reflecting the unfavorable impact of foreign exchange.3

Second-Quarter Expense, EPS and Related Information

GAAP Expense, EPS and Related Information

Gross margin was 71.1% for the second quarter of 2019 compared to 67.3% for the second quarter of 2018. The increase in gross margin for the second quarter of 2019 was primarily driven by lower acquisition- and divestiture-related costs, favorable product mix and lower amortization of intangible assets related to collaborations, partially offset by higher restructuring costs.

Selling, general and administrative expenses were $2.7 billion in the second quarter of 2019, an 8% increase compared to the second quarter of 2018. The increase primarily reflects higher administrative, acquisition- and divestiture-related, restructuring and promotion costs, partially offset by the favorable effects of foreign exchange.

Research and development (R&D) expenses were $2.2 billion in the second quarter of 2019, a decline of 4% compared with the second quarter of 2018. The decline was driven primarily by lower expenses related to business development transactions, largely reflecting a $344 million charge recorded in the second quarter of 2018 related to the Viralytics Limited acquisition. The decline was partially offset by higher expenses related to clinical development and increased investment in discovery research and early drug development.

Other (income) expense, net, was $140 million of expense in the second quarter of 2019 compared to $48 million of income in the second quarter of 2018. Other (income) expense, net, in the second quarter of 2019 reflects impairment charges and lower income from investments in equity securities.

GAAP EPS was $1.03 for the second quarter of 2019 compared with $0.63 for the second quarter of 2018.

Non-GAAP Expense, EPS and Related Information

The non-GAAP gross margin was 75.4% for the second quarter of 2019, compared to 74.4% for the second quarter of 2018. The increase in non-GAAP gross margin reflects favorable product mix and lower amortization of intangible assets related to collaborations.

Non-GAAP selling, general and administrative expenses were $2.6 billion in the second quarter of 2019, a 5% increase compared to the second quarter of 2018. The increase reflects higher administrative and promotion costs, partially offset by the favorable effects of foreign exchange.

Non-GAAP R&D expenses were $2.2 billion in the second quarter of 2019, a 13% increase compared to the second quarter of 2018. The increase reflects higher expenses related to clinical development, investment in discovery research and early drug development, as well as business development transactions.

Non-GAAP other (income) expense, net, was $56 million of income in the second quarter of 2019 compared to $121 million of income in the second quarter of 2018, driven primarily by lower income from investments in equity securities.

Non-GAAP EPS was $1.30 for the second quarter of 2019 compared with $1.06 for the second quarter of 2018.

A reconciliation of GAAP to non-GAAP net income and EPS is provided in the table that follows.

Financial Outlook

Merck narrowed and raised its full-year 2019 revenue range to be between $45.2 billion and $46.2 billion, including a negative impact from foreign exchange of slightly more than 1% at mid-July exchange rates.

Merck narrowed and reduced its full-year 2019 GAAP EPS range to be between $3.78 and $3.88. The reduction in the GAAP EPS range primarily reflects the inclusion of an approximately $1.1 billion charge related to the acquisition of Peloton. Merck narrowed and raised its full-year 2019 non-GAAP EPS range to be between $4.84 and $4.94, including a slightly negative impact from foreign exchange at mid-July exchange rates. The non-GAAP range excludes acquisition- and divestiture-related costs, costs related to restructuring programs, a net benefit from the settlement of certain federal income tax matters, the charge for the acquisition of Peloton and certain other items.

The following table summarizes the company’s full year 2019 financial guidance.

*The company does not have any non-GAAP adjustments to revenue.

**EPS guidance for 2019 assumes a share count (assuming dilution) of approximately 2.6 billion shares.

A reconciliation of anticipated 2019 GAAP EPS to non-GAAP EPS and the items excluded from non-GAAP EPS are provided in the table below.

The expected full-year GAAP effective tax rate of 16.0% to 17.0% reflects a net favorable impact of approximately 2.5 percentage points from the above items.

Earnings Conference Call

Investors, journalists and the general public may access a live audio webcast of the call today at 8:00 a.m. EDT on Merck’s website at View Source Institutional investors and analysts can participate in the call by dialing (706) 758-9927 or (877) 381-5782 and using ID code number 4263838. Members of the media are invited to monitor the call by dialing (706) 758-9928 or (800) 399-7917 and using ID code number 4263838. Journalists who wish to ask questions are requested to contact a member of Merck’s Media Relations team at the conclusion of the call.

On July 30, 2019 Nektar Therapeutics (Nasdaq: NKTR) reported that it will announce its financial results for the second quarter on Thursday, August 8, 2019, after the close of U.S.-based financial markets (Press release, Nektar Therapeutics, JUL 30, 2019, View Source [SID1234537915]). Howard Robin, President and Chief Executive Officer, will host a conference call to review the results beginning at 5:00 p.m. Eastern Daylight Time/2:00 p.m. Pacific Daylight Time.

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 press release and a live Webcast of the conference call can be accessed through a link that is posted on the home page and Investors section of the Nektar website: View Source The web broadcast of the conference call will be available for replay through Monday, September 9, 2019.

To access the conference call, follow these instructions:

Dial: (877) 881-2183 (U.S.); (970) 315-0453 (international)
Conference ID: 2879328 (Nektar Therapeutics is the host)