On March 14, 2019 Progenics Pharmaceuticals, Inc. (Nasdaq:PGNX) reported financial results for the fourth quarter and full-year 2018 and provided a business update (Press release, Progenics Pharmaceuticals, MAR 14, 2019, View Source [SID1234534366]).

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"2018 was an extremely productive year for the advancement of our portfolio of radiopharmaceuticals, highlighted by the FDA’s approval of AZEDRA for the treatment of advanced or metastatic pheochromocytoma and paraganglioma. As part of our ongoing U.S. commercial launch efforts, patient scheduling is ongoing at eight activated treatment centers across the country. We recently acquired the launch manufacturing facility for AZEDRA, allowing us to become a fully-integrated operation," said Mark Baker, Chief Executive Officer of Progenics.

Mr. Baker continued, "In parallel with our AZEDRA launch, we have made significant progress across our entire prostate cancer and AI portfolio, including the initiation of patient dosing in our Phase 3 CONDOR trial, which is evaluating the diagnostic potential and clinical impact of PyL in patients with suspected biochemical recurrence of prostate cancer. We have extended the reach of our PSMA-targeted portfolio with our collaboration with Curium for the development and commercialization of PyL in Europe, which validates the potential of our PET/CT imaging agent. We look forward to providing further updates on our PSMA-targeted programs during the year with the initiation of the Phase 2 trial of 1095 planned in the second quarter of 2019 and data presentations of deep convolutional neural network algorithms from our cutting-edge AI technology."

Fourth Quarter and Recent Key Business Highlights

AZEDRA (iobenguane I 131) 555 MBq/mL injection for intravenous use, Ultra-orphan Radiotherapeutic

U.S. Launch Progressing with 14 Patient Treatment Requests in Queue at Eight Activated Treatment Centers
AZEDRA is the first and only approved therapy in the U.S. for the treatment of adult and pediatric patients 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy. The AZEDRA salesforce is in active dialogue with over 30 multidisciplinary treatment centers across the U.S with eight activated for patient treatment. Fourteen patient treatment requests for patients to be treated at these eight centers have been received.
Acquisition of Radiopharmaceutical Manufacturing Facility to Support AZEDRA and 1095
In February 2019, the Company acquired the manufacturing facility for AZEDRA based in Somerset, New Jersey, for $8.0 million in cash. Progenics also secured the long-term supply of iodine necessary for the production of both AZEDRA and 1095. The acquisition positions the Company to have full internal control of the manufacturing facility, which has the potential to label multiple types of isotopes, including iodine-131, for AZEDRA and 1095.
Planned Meeting with FDA to Discuss Regulatory Path for Additional Indications
Following a productive advisory board meeting with leading physicians in February 2019, the Company plans to request a life cycle management meeting with the U.S. Food and Drug Administration (FDA) to discuss potential pathways for additional AZEDRA indications. Given the lack of available therapies, the advisory board was supportive of AZEDRA in multiple MIBG-avid tumor indications, including gastroenteropancreatic and other neuroendocrine tumors.
Upcoming Presentation at ENDO Highlighting AZEDRA Safety
A poster entitled, "Safety Analysis of High-Specific-Activity I-131 MIBG (AZEDRA) in Patients with Iobenguane Scan Positive Cancers," is expected to be presented on March 24, 2019 at the ENDO 2019 Meeting in New Orleans, Louisiana.
PSMA-Targeted Prostate Cancer Pipeline

Initiation of Patient Dosing in Phase 3 Trial of PyL (18F-DCFPyL)
In December 2018, the Company announced the first patient was dosed in the Phase 3 CONDOR trial evaluating the diagnostic performance and clinical impact of PyL, the Company’s PSMA-targeted small molecule PET/CT imaging agent designed to visualize prostate cancer. The Phase 3 CONDOR trial is a multi-center, open label trial that will enroll approximately 200 male patients with biochemical recurrence of prostate cancer in 14 sites in the United States and Canada. The Company expects to complete enrollment in the fourth quarter of 2019 and report data in early 2020.

European Collaboration with Curium for PyL
The Company entered into an exclusive license agreement in December 2018 with Curium, the largest global nuclear medicine company formed through the union of Mallinckrodt and IBA Molecular, to develop, manufacture and commercialize PyL in Europe. Under the terms of the collaboration, Curium will be responsible for the development, regulatory approvals and commercialization of PyL in Europe while Progenics is entitled to royalties on net sales. We understand from Curium that Curium plans to meet with European regulators in 2019 to agree upon the regulatory path forward for PyL in the territory.

Phase 2 Trial of 1095 Expected to Commence in the Second Quarter of 2019
Following discussions with the FDA in 2018, Progenics plans to initiate a Phase 2 trial of 1095 in combination with enzalutamide in chemo-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) who are refractory to novel anti-androgen drugs (NAAD) in the second quarter of 2019. 1095 is a small molecule radiotherapeutic designed to selectively bind to the extracellular domain of prostate specific membrane antigen (PSMA), a protein that is highly expressed on prostate cancer cells.

Enrollment of Phase 1 Trial of PSMA-TTC by Bayer Expected in 2019
Progenics’ partner, Bayer AG (Bayer), initiated a Phase 1 trial of PSMA-Targeted Thorium Conjugate (PSMA-TTC) in patients with mCRPC in 2018. Bayer was previously granted exclusive worldwide rights to develop and commercialize products using Progenics’ PSMA antibody technology in combination with Bayer’s alpha-emitting radionuclides.
Company Asserts Ownership of PSMA-617 Intellectual Property
Progenics has filed a lawsuit disputing the ownership of certain worldwide patent filings related to PSMA-617, a PSMA targeted radiopharmaceutical compound under development by Novartis AG for the treatment of prostate cancer. The Company claims that the discovery and development of PSMA-617 was related to work performed under research collaboration sponsored by Molecular Insight Pharmaceuticals (MIP), prior to its acquisition by Progenics in 2013, and that the Company accordingly has worldwide rights to intellectual property resulting from the collaboration.
Digital Technology

Statistically Significant Data from PSMA AI Program
Progenics recently completed a prospectively planned retrospective analysis using its deep convolutional neural network algorithms (PSMA AI) to automatically assess a set of PSMA images from prior trials. The reads with PSMA AI demonstrated a statistically significant improvement over manual assessment in terms of increased diagnostic accuracy, precision, speed, and reproducibility. The results from this analysis are expected to be presented at upcoming scientific conferences.
RELISTOR, Treatment for Opioid-Induced Constipation (partnered with Bausch Health Companies Inc.)

Fourth Quarter 2018 RELISTOR Net Sales of $21.0 Million
Full-year 2018 net worldwide sales totaled $99.4 million as reported to Progenics by its partner Bausch Health Companies, Inc. The fourth quarter 2018 net sales of $21.0 million translated to $3.2 million in royalty revenue for Progenics, while the full year net sales resulted in $14.9 million in royalty revenue.
Leronlimab (PRO 140), Monoclonal Antibody for HIV (owned and developed by CytoDyn)

CytoDyn Expected to File BLA for Leronlimab (PRO 140), an Anti-CCR5 Monoclonal Antibody for the Treatment of HIV Infection, in First Half of 2019; Progenics is Entitled to an Approval Milestone and Royalties

CytoDyn has announced its plan to submit a Biologics License Application (BLA) to the FDA for leronlimab for the treatment of HIV. Leronlimab is a fully-humanized, anti-CCR5 monoclonal antibody that Progenics sold to CytoDyn in 2012. Under the terms of the agreement, Progenics is eligible to receive an additional $5.0 million milestone payment upon U.S. or E.U. approval, as well as 5% royalty on net sales of the approved product.
Fourth Quarter and Full-Year 2018 Financial Results

Fourth quarter 2018 revenue totaled $3.2 million, down from $3.9 million in the fourth quarter of 2017. Revenue for the 2018 period reflects RELISTOR royalty income of $3.2 million compared to $3.7 million in the corresponding period of 2017. The full-year 2018 revenue totaled $15.6 million, up from $11.7 million for the full-year of 2017, resulting primarily from higher royalty income of $14.9 million in 2018 compared to $11.0 million in 2017.

Research and development expenses decreased by $1.3 million and $7.4 million in the fourth quarter and full-year 2018, respectively, compared to the corresponding periods in 2017, resulting primarily from lower external costs associated with the completion of the Phase 2 pivotal trial for AZEDRA and the Phase 3 trial for 1404. Fourth quarter and full-year selling, general and administrative expenses increased by $1.2 million and $4.5 million, respectively, compared to the corresponding periods in 2017, primarily attributable to higher costs associated with the commercial launch of AZEDRA. Progenics also recorded a net non-cash charge of $17.4 million in 2018, resulting from changes in the estimated fair values of intangible assets and contingent consideration liability, primarily related to 1404, following the decision not to invest in additional 1404 clinical trials.

For the three months and full-year ended December 31, 2018, Progenics recognized interest expense of $1.1 million and $4.7 million, respectively, related to the RELISTOR royalty-backed loan, compared to $1.2 million and $4.8 million recognized in the corresponding periods in 2017. For the three months and full-year ended December 31, 2018, Progenics recorded $0.1 million and $1.6 million, respectively, in income tax benefit. The primary driver of this tax benefit is related to the impairment and reclassification of the indefinite-lived intangibles for in process research and development assets. In the fourth quarter of 2017, Progenics recorded $11.7 million income tax benefit, primarily related to the reduction in the federal tax rate and the use of the Company’s deferred tax liability related to indefinite-lived intangible assets (naked tax credit) as a source of income to release a portion of its valuation allowance recorded against deferred tax assets.

Net loss attributable to Progenics for the fourth quarter was $14.7 million or $0.17 per diluted share, compared to a net loss of $2.7 million or $0.04 per diluted share in the corresponding 2017 period. Net loss for the full-year 2018 was $67.7 million or $0.87 per diluted share, compared to net loss of $51.0 million or $0.73 per diluted share for the full-year 2017.

Progenics ended the year with cash and cash equivalents of $137.7 million, reflecting a decrease of $11.2 million in the quarter and an increase of $47.0 million from 2017 year-end. During the year ended December 31, 2018, the Company raised net proceeds of $70.0 million in an underwritten public offering and an additional $27.5 million in at-the-market transactions.

Conference Call and Webcast

Progenics will review fourth quarter and year-end financial results in a conference call today at 8:30 a.m. EDT. To participate, please dial (877) 250-8889 (domestic) or (720) 545-0001 (international) and reference conference ID 7764968. A live webcast will be available in the Media Center of the Progenics website, www.progenics.com, and a replay will be available there for two weeks.

– Financial Tables follow –

PROGENICS PHARMACEUTICALS, INC.
CONSOLIDATED STATEMENTS OF OPERATIONS
(In thousands, except per share data)
For the Three Months Ended
December 31, For the Year Ended
December 31,
2018 2017 2018 2017
(Unaudited)
Revenues:
Royalty income $ 3,151 $ 3,683 $ 14,908 $ 10,965
Other revenues 87 206 714 733
Total revenues 3,238 3,889 15,622 11,698

Operating expenses:
Research and development 9,600 10,948 35,147 42,589
Selling, general and administrative 8,090 6,923 29,431 24,909
Intangible impairment charge - - 23,200 -
Change in contingent consideration liability 100 (700 ) (5,800 ) 2,600
Total operating expenses 17,790 17,171 81,978 70,098

Operating loss (14,552 ) (13,282 ) (66,356 ) (58,400 )

Other (expense) income:
Interest (expense) income and other income, net (235 ) (1,055 ) (2,933 ) (4,285 )
Total other (expense) income (235 ) (1,055 ) (2,933 ) (4,285 )

Loss before income tax benefit (14,787 ) (14,337 ) (69,289 ) (62,685 )

Income tax benefit 83 11,672 1,632 11,672

Net loss $ (14,704 ) $ (2,665 ) $ (67,657 ) $ (51,013 )

Net loss per share – basic and diluted $ (0.17 ) $ (0.04 ) $ (0.87 ) $ (0.73 )
Weighted average shares outstanding – basic and diluted 84,543 70,437 77,890 70,284

CONDENSED CONSOLIDATED BALANCE SHEETS
(In thousands)
December 31,
2018 December 31,
2017

Cash and cash equivalents $ 137,686 $ 90,642
Accounts receivable, net 3,803 3,972
Property and equipment, net 3,944 4,122
Intangible assets, net and goodwill 19,740 43,443
Other assets 4,324 3,778
Total assets $ 169,497 $ 145,957

Current liabilities $ 23,446 $ 15,359
Contingent consideration liability 3,950 16,800
Long-term debt, deferred tax and other liabilities 41,026 50,345
Total liabilities 68,422 82,504
Total stockholders’ equity 101,075 63,453
Total liabilities and stockholders’ equity $ 169,497 $ 145,957

Indication

AZEDRA (iobenguane I 131) is indicated for the treatment of adult and pediatric patients 12 years and older with iobenguane scan positive, unresectable, locally advanced or metastatic pheochromocytoma or paraganglioma who require systemic anticancer therapy.

Important Safety Information

Warnings and Precautions:

Risk from Radiation Exposure: AZEDRA contributes to a patient’s overall long-term radiation exposure. Long-term cumulative radiation exposure is associated with an increased risk for cancer. These risks of radiation associated with the use of AZEDRA are greater in pediatric patients than in adults. Minimize radiation exposure to patients, medical personnel, and household contacts during and after treatment with AZEDRA consistent with institutional good radiation safety practices and patient management procedures.
Myelosuppression: Among the 88 patients who received a therapeutic dose of AZEDRA, 33% experienced Grade 4 thrombocytopenia, 16% experienced Grade 4 neutropenia, and 7% experienced Grade 4 anemia. Five percent of patients experienced febrile neutropenia. Monitor blood cell counts weekly for up to 12 weeks or until levels return to baseline or the normal range. Withhold and dose reduce AZEDRA as recommended in the prescribing information based on severity of the cytopenia.
Secondary myelodysplastic syndrome, leukemia, and other malignancies: Myelodysplastic syndrome (MDS) and acute leukemias were reported in 6.8% of the 88 patients who received a therapeutic dose of AZEDRA. The time to development of MDS or acute leukemia ranged from 12 months to 7 years. Two of the 88 patients developed a non-hematological malignancy.
Hypothyroidism: Hypothyroidism was reported in 3.4% of the 88 patients who received a therapeutic dose of AZEDRA. Initiate thyroid-blocking medications starting at least 1 day before and continuing for 10 days after each AZEDRA dose to reduce the risk of hypothyroidism or thyroid neoplasia. Evaluate for clinical evidence of hypothyroidism and measure thyroid-stimulating hormone (TSH) levels prior to initiating AZEDRA and annually thereafter.
Elevations in blood pressure: Eleven percent of the 88 patients who received a therapeutic dose of AZEDRA experienced a worsening of pre-existing hypertension defined as an increase in systolic blood pressure to ≥160 mmHg with an increase of 20 mmHg or an increase in diastolic blood pressure to ≥ 100 mmHg with an increase of 10 mmHg. All changes in blood pressure occurred within the first 24 hours post infusion. Monitor blood pressure frequently during the first 24 hours after each therapeutic dose of AZEDRA.
Renal toxicity: Of the 88 patients who received a therapeutic dose of AZEDRA, 9% developed renal failure or acute kidney injury and 22% demonstrated a clinically significant decrease in glomerular filtration rate (GFR) measured at 6 or 12 months. Monitor renal function during and after treatment with AZEDRA. Patients with baseline renal impairment may be at greater risk of toxicity; perform more frequent assessments of renal function in patients with mild or moderate impairment. AZEDRA has not been studied in patients with severe renal impairment.
Pneumonitis: Fatal pneumonitis occurred 9 weeks after a single dose in one patient in the expanded access program. Monitor patients for signs and symptoms of pneumonitis and treat appropriately.
Embryo-fetal toxicity: Based on its mechanism of action, AZEDRA can cause fetal harm. Verify pregnancy status in females of reproductive potential prior to initiating AZEDRA. Advise females and males of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment with AZEDRA and for 7 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 4 months after the final dose.
Risk of infertility: Radiation exposure associated with AZEDRA may cause infertility in males and females. Radiation absorbed by testes and ovaries from the recommended cumulative dose of AZEDRA is within the range where temporary or permanent infertility can be expected following external beam radiotherapy.
Adverse Reactions:
The most common severe (Grade 3–4) adverse reactions observed in AZEDRA clinical trials (≥ 10%) were lymphopenia (78%), neutropenia (59%), thrombocytopenia (50%), fatigue (26%), anemia (24%), increased international normalized ratio (18%), nausea (16%), dizziness (13%), hypertension (11%), and vomiting (10%). Twelve percent of patients discontinued treatment due to adverse reactions (thrombocytopenia, anemia, lymphopenia, nausea and vomiting, multiple hematologic adverse reactions).

Drug Interactions:
Based on the mechanism of action of iobenguane, drugs that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells and therefore interfere with dosimetry calculations or the efficacy of AZEDRA. These drugs were not permitted in clinical trials that assessed the safety and efficacy of AZEDRA. Discontinue the drugs listed in the prescribing information for at least 5 half-lives before administration of either the dosimetry dose or a therapeutic dose of AZEDRA. Do not administer these drugs until at least 7 days after each AZEDRA dose.

For important risk and use information about AZEDRA, please see Full Prescribing Information.

To report suspected adverse reactions, contact Progenics Pharmaceuticals, Inc. at 844-668-3950 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Reference:
AZEDRA prescribing information. New York, NY: Progenics Pharmaceuticals, Inc.; 08 2018 and 07 2018.

About RELISTOR

Progenics has exclusively licensed development and commercialization rights for its first commercial product, RELISTOR, to Bausch Health Companies, Inc. RELISTOR Tablets (450 mg once daily) are approved in the United States for the treatment of opioid-induced constipation (OIC) in patients with chronic non-cancer pain. RELISTOR Subcutaneous Injection (12 mg and 8 mg) is a treatment for OIC approved in the United States and worldwide for patients with advanced illness and chronic non-cancer pain.

IMPORTANT SAFETY INFORMATION – RELISTOR (methylnaltrexone bromide) tablets, for oral use and RELISTOR (methylnaltrexone bromide) injection, for subcutaneous use

RELISTOR tablets and injection are contraindicated in patients with known or suspected gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation.

Cases of gastrointestinal perforation have been reported in adult patients with opioid-induced constipation and advanced illness with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, Ogilvie’s syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). Take into account the overall risk-benefit profile when using RELISTOR in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn’s disease). Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue RELISTOR in patients who develop this symptom.

If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR and consult their healthcare provider.

Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, and yawning have occurred in patients treated with RELISTOR. Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal and/or reduced analgesia and should be monitored for adequacy of analgesia and symptoms of opioid withdrawal.

Avoid concomitant use of RELISTOR with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.

The use of RELISTOR during pregnancy may precipitate opioid withdrawal in a fetus due to the immature fetal blood brain barrier and should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Because of the potential for serious adverse reactions, including opioid withdrawal, in breastfed infants, advise women that breastfeeding is not recommended during treatment with RELISTOR. In nursing mothers, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

A dosage reduction of RELISTOR tablets and RELISTOR injection is recommended in patients with moderate and severe renal impairment (creatinine clearance less than 60 mL/minute as estimated by Cockcroft-Gault). No dosage adjustment of RELISTOR tablets or RELISTOR injection is needed in patients with mild renal impairment.

A dosage reduction of RELISTOR tablets is recommended in patients with moderate (Child-Pugh Class B) or severe (Child-Pugh Class C) hepatic impairment. No dosage adjustment of RELISTOR tablets is needed in patients with mild hepatic impairment (Child-Pugh Class A). No dosage adjustment of RELISTOR injection is needed for patients with mild or moderate hepatic impairment. In patients with severe hepatic impairment, monitor for methylnaltrexone-related adverse reactions.

In the clinical studies, the most common adverse reactions were:

OIC in adult patients with chronic non-cancer pain

RELISTOR tablets (≥ 2% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (14%), diarrhea (5%), headache (4%), abdominal distention (4%), vomiting (3%), hyperhidrosis (3%), anxiety (2%), muscle spasms (2%), rhinorrhea (2%), and chills (2%).
RELISTOR injection (≥ 1% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (21%), nausea (9%), diarrhea (6%), hyperhidrosis (6%), hot flush (3%), tremor (1%), and chills (1%).
OIC in adult patients with advanced illness

RELISTOR injection (≥ 5% of RELISTOR patients and at a greater incidence than placebo): abdominal pain (29%) flatulence (13%), nausea (12%), dizziness (7%), and diarrhea (6%).

On March 14, 2019 BioTime, Inc. (NYSE American and TASE: BTX), a clinical-stage biotechnology company focused on degenerative diseases, reported financial and operating results for the fourth quarter and full year ended December 31, 2018. BioTime management will host a conference call and webcast today at 4:30 p.m. Eastern Time/1:30 p.m. Pacific Time to provide a business update (Press release, BioTime, MAR 14, 2019, View Source [SID1234534350]).

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"BioTime has been moving rapidly towards building a pioneering cell therapy company through strategic transactions on the corporate development, clinical, and operational fronts," stated Brian M. Culley, Chief Executive Officer of BioTime. "We have broadened our pipeline through the acquisition of Asterias, adding two innovative product candidates that we believe can substantially impact diseases in need of innovative therapeutic approaches. Moreover, we entered into an exclusive agreement with Orbit Biomedical Ltd. which will allow us access to its recently 510(k)-approved device for the sub-retinal delivery of OpRegen for the treatment of dry-AMD. We also completed the distribution of AgeX Therapeutics, Inc. shares to BioTime shareholders, following the sale of half of our ownership in AgeX to Juvenescence Ltd. for a total of $43.2 million. Importantly, we have continued to streamline BioTime’s corporate structure and priorities with a focus on creating value from our most compelling clinical opportunities. Executing on our stated milestones at each stage of corporate and clinical development and increasing our visibility within the investment, medical, and patient communities are vital activities which we believe will help drive the company’s success."

Recent Highlights

Completed acquisition of Asterias Therapeutics, Inc. BioTime acquired all of the remaining outstanding common stock of Asterias not previously owned by BioTime, and the operations of BioTime and Asterias were combined. BioTime is now advancing three clinical stage product candidates for the potential treatment of degenerative retinal diseases and neurological conditions associated with demyelination, and to potentially aid the body in detecting and combating cancer.
Announced exclusive agreement with Orbit Biomedical Ltd. (Orbit) under which BioTime and Orbit will collaborate on the use of Orbit’s proprietary injection technology to deliver OpRegen for the treatment of dry age-related macular degeneration (dry-AMD) in BioTime’s ongoing Phase I/IIa clinical study.
Completed the distribution of approximately 12.7 million shares of AgeX common stock owned by BioTime on a pro rata basis to eligible BioTime shareholders. BioTime retained an equity position in AgeX of 1.7 million shares, or approximately 5% of AgeX’s common stock. As of March 13, 2019, the value of BioTime’s AgeX share position was approximately $7.2 million.
Presented encouraging data on BioTime’s proprietary pluripotent stem cell technology as a platform to address the retinal degeneration disease continuum presented at the 14th Annual Scientific Meeting of the Association For Ocular Pharmacology and Therapeutics (AOPT 2019).
BioTime affiliate OncoCyte Corporation (NYSE American: OCX) recently reported positive results from an R&D validation study of DetermaVu, its non-invasive liquid biopsy test intended to facilitate clinical decision making in lung cancer diagnosis. Following a recently completed $40.25 million public offering by OncoCyte, BioTime owns approximately 28% of OncoCyte’s common stock, or 14.7 million shares. As of March 13, 2019, the value of BioTime’s OncoCyte share position was approximately $55.9 million.
Plans for 2019

Present updated results from the ongoing Phase I/IIa clinical study of OpRegen for the treatment of dry-AMD and the Vision Restoration Program at the 2019 Association for Research in Vision and Ophthalmology Annual Meeting on May 2, 2019 and April 30, 2019, respectively.
Pursuant to an exclusive collaboration with Orbit Biomedical Ltd. for the use of Orbit’s proprietary injection technology, initiate dosing of the first patient with the Orbit device and a new thaw and inject formulation in the ongoing Phase I/IIa clinical study of OpRegen for the treatment of dry-AMD, anticipated in Q2 2019.
Advance the OPC1 program and meet with the FDA to discuss plans for next steps in the clinical development of the program, anticipated in 2019.
Strengthen and expand existing partnerships with the California Institute for Regenerative Medicine and Cancer Research UK, for the ongoing support of the development of the OPC1 and VAC2 programs.
Complete patient enrollment in the ongoing Phase I/IIa clinical study of OpRegen for the treatment of dry-AMD, anticipated by year end 2019.
Evaluate the development of OPC1 as a candidate for the potential treatment of multiple sclerosis (MS) and ischemic stroke through ongoing research collaborations with major universities.
Announce decision on BioTime’s CE Mark application for Renevia, an investigational medical device being developed as an alternative for whole adipose tissue transfer procedures, expected in the second half of 2019.
Balance Sheet Highlights

Cash, cash equivalents and marketable securities totaled $30.7 million as of December 31, 2018.

BioTime’s investment in OncoCyte was valued at $20.3 million as of December 31, 2018 and at $55.9 million as of March 13, 2019, under the equity method of accounting.

BioTime’s promissory note from Juvenescence was valued at $22.1 million as of December 31, 2018. If Juvenescence completes an initial public offering (IPO) resulting in gross proceeds of not less than $50,000,000, the promissory note converts into Juvenescence ordinary shares based on the per-share price to the public in the IPO, subject to an upward adjustment in the number of shares that would be issued to BioTime upon such conversion if the 20-day volume-weighted average trading price of one share of AgeX’s common stock before the IPO is priced is above $3.00. If the promissory note is converted, the Juvenescence ordinary shares will be a marketable security that BioTime may use to supplement its liquidity, as needed. If the promissory note is not converted, it is payable in cash, plus accrued interest at 7% per year, at maturity in August 2020.

Fourth Quarter Operating Results

Revenues: BioTime’s revenue is generated primarily from research grants, licensing fees and royalties. Total revenues for the three months ended December 31, 2018 were $0.8 million, a decrease of $0.2 million, compared to $1.0 million for the same period in 2017. The decrease was primarily related to a reduction of $0.4 million attributable to the deconsolidation of AgeX operations from BioTime’s financial results in August 2018, offset by an increase of $0.2 million attributable to an increase in grant revenues.

Operating Expenses: Operating expenses are comprised of research and development ("R&D") expenses and general and administrative ("G&A) expenses. Total operating expenses for the three months ended December 31, 2018 were $10.8 million, as reported, and $8.1 million, as adjusted. AgeX was deconsolidated from BioTime on August 30, 2018, and beginning on that date, AgeX’s operating expenses are not included in BioTime’s operating expenses.

The reconciliation between GAAP and non-GAAP operating expenses, by entity, is provided in the financial tables included with this earnings release.

R&D Expenses: Beginning on August 30, 2018, BioTime ceased recognizing R&D expenses related to AgeX and its programs due to the AgeX deconsolidation on that date.

R&D expenses for the three months ended December 31, 2018 were $3.8 million, a decrease of $0.9 million, compared to $4.7 million for the same period in 2017. The decrease was primarily related to a $0.8 million decrease from the AgeX deconsolidation and the absence of AgeX research and development expenses incurred after August 30, 2018.

G&A Expenses: Beginning on August 30, 2018, BioTime ceased recognizing G&A expenses related to AgeX and its subsidiaries due to the AgeX deconsolidation on that date.

G&A expenses for the three months ended December 31, 2018 were $7.0 million, an increase of $1.2 million, compared to $5.8 million for the same period in 2017. The increase was primarily attributable to increases of $1.0 million in legal and related costs related to the Asterias merger announced in November 2018 and completed on March 8, 2019, and $0.8 million in noncash stock-based compensation expense due to additional equity award grants and vesting of certain restricted stock units for meeting performance milestones. These increases were partially offset by a decrease of $0.8 million from the AgeX deconsolidation and the absence of AgeX research and development expenses incurred after August 30, 2018.

Other Income/(Expenses), Net: Other expenses, net for the three months ended December 31, 2018 were $35.2 million, a decrease of $32.1 million, compared to $67.3 million for the same period in 2017. The decrease was primarily related to changes in the value of equity investments in OncoCyte, Asterias and AgeX for the applicable periods.

Net loss attributable to BioTime: The net loss attributable to BioTime for the three months ended December 31, 2018 was $45.0 million, or $0.35 per share (basic and diluted), compared to a net loss attributable to BioTime of $71.9 million, or $0.58 per share (basic and diluted), for the same period in 2017.

Year-to-Date Operating Results

Revenues: Total revenues for the year ended December 31, 2018 were $5.0 million, an increase of $1.5 million, compared to $3.5 million for 2017. The increase was primarily related to an increase in grant revenues of $1.9 million, offset by a reduction of $0.4 million in subscription and research related revenues attributable to the deconsolidation of AgeX operations from BioTime’s financial results in August 2018.

BioTime receives two types of grant revenues: one is for the development of OpRegen and is received through BioTime’s Israeli subsidiary, Cell Cure, from the Israeli Innovation Authority (IIA), and the second is for BioTime’s vision restoration program and is a Small Business Innovation Research grant from the National Institutes of Health (NIH). Revenues from the IIA grant and the NIH grant were $2.5 million and $1.1 million for the year ended December 31, 2018, respectively, compared to revenues from the IIA grant and the NIH grant of $1.5 million and $0.2 million, respectively, for 2017.

Operating Expenses: Total operating expenses for the year ended December 31, 2018 were $46.5 million, as reported, which is comprised of $38.8 million for BioTime and $7.7 million for AgeX. Total operating expenses for the year ended December 31, 2018 were $37.0 million, as adjusted, which is comprised of $31.0 million for BioTime and $6.0 million for AgeX.

R&D Expenses: R&D expenses for the year ended December 31, 2018 were $21.8 million, a decrease of $2.2 million, compared to $24.0 million for 2017. The decrease was mainly attributable to:

a decrease of $1.5 million in AgeX related programs, including LifeMap Sciences, due to the AgeX deconsolidation;
a decrease of $0.8 million from the absence of OncoCyte research and development expenses incurred in 2017 as a result of the OncoCyte deconsolidation in February 2017;
a decrease of $0.5 million in LifeMap Solutions expenses resulting from the cessation of its mobile health software development application business in July 2017; and
a decrease of $0.3 million in BioTime related program expenses, primarily related to completing the Renevia clinical trial in early 2018.
The decreases were partially offset by an $0.8 million write-off of certain acquired in-process R&D assets in March 2018 that have no alternative future use by AgeX.

G&A Expenses: G&A expenses for the year ended December 31, 2018 were $24.7 million, an increase of $4.8 million, compared to $19.9 million for 2017. The increase was primarily attributable:

an increase of $2.3 million related to management transition and other compensation related costs, including hiring costs for a new chief executive officer during September 2018;
an increase of $2.1 million for legal, audit and compliance costs related to distributing 12.7 million shares of AgeX common stock to BioTime shareholders in November 2018; and
an increase of $1.5 million in noncash stock-based compensation expense due to increases in equity award grants.
These increases were partially offset by decreases of $1.4 million in combined G&A expenses related to the OncoCyte deconsolidation in February 2017, and to LifeMap Solutions, which ceased conducting its mobile health software application business in July 2017, and $0.3 million in AgeX related costs, including LifeMap Sciences, due to the AgeX deconsolidation.

Other Income/(Expenses), Net: Other income/(expenses), net for the year ended December 31, 2018 were $5.3 million in expenses, as compared to $15.6 million in income for 2017. The variance was primarily driven by changes in market values of the Asterias and OncoCyte shares held by BioTime and gains from the AgeX deconsolidation in 2018 from the sale AgeX shares to Juvenescence, and from the OncoCyte deconsolidation in 2017.

Net loss attributable to BioTime: The net loss attributable to BioTime for the year ended December 31, 2018 was $46.0 million, or $0.36 per share (basic and diluted), compared to a net loss attributable to BioTime of $20.0 million, or $0.17 per share (basic and diluted), for 2017.

Conference Call and Webcast

BioTime will host a conference call and webcast today, at 1:30pm PT/4:30pm ET to discuss its fourth quarter and full year 2018 financial results and to provide a business update. Interested parties may access the conference call by dialing (866) 888-8633 from the U.S. and Canada and (636) 812-6629 from elsewhere outside the U.S. and should request the "BioTime Inc. Call". A live webcast of the conference call will be available online in the Investors section of BioTime’s website. A replay of the webcast will be available on BioTime’s website for 30 days and a telephone replay will be available through March 21st, 2019, by dialing (855) 859-2056 from the U.S. and Canada and (404) 537-3406 from elsewhere outside the U.S. and entering conference ID number 1091719.

On March 14, 2019 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology (I-O) company with a pipeline of immune checkpoint antibodies, cancer vaccines and adoptive cell therapies1, reported and update and reported financial results for the fourth quarter and full year of 2018 (Press release, Agenus, MAR 14, 2019, View Source [SID1234534331]).

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Agenus Logo

"We are rapidly advancing with the discovery and clinical development of our innovative I-O agents," said Garo H. Armen, Ph.D., Chairman and CEO of Agenus. "In the past year, we entered into an important partnership with Gilead, delivered 6 INDs, and confirmed benefit in the majority of patients treated with our lead CTLA-4 and PD-1 antibodies. Our next steps will target submission and commercial launch readiness for our first two antibodies."

Achievements
Strengthened balance sheet with the Gilead collaboration and payments from milestones achieved with Incyte and Merck
$150M payment from Gilead
$21.5M additional milestones for advancing LAG-3 (INCAGN02385), TIM-3 (INCAGN02390), ILT4 (MK-4830) and FDA acceptance of the IND for AGEN1423, licensed to Gilead
Advanced lead programs and reported clinical benefit in majority of patients across multiple solid tumors, including cervical cancer
Ongoing trials in cervical cancer are designed to support BLA via accelerated pathway
We plan to expand PD-1 development in additional indications
Advanced new discoveries, which will enter the clinic this year
Next-Gen CTLA-4, AGEN1181
First-in-class bispecific, AGEN1223 (a Gilead option program)
Revenues of GSK’s Shingrix, containing our QS-21 Stimulon, exceed $1Bn (USD)
Bill & Melinda Gates Foundation award Agenus ~$1M to develop novel technology for QS-21
AgenTus Cell Therapy Business:
2019 INDs are on track
Partnership and private financing discussions are underway
Fourth Quarter and Full Year 2018 Financial Results

We ended 2018 with a cash balance of $53 million followed by the $150 million received from Gilead in 2019.

For the fourth quarter ended December 31, 2018, we reported a net loss of $49 million or $0.40 per share compared to a net loss for same period in 2017 of $35 million, or $0.35 per share. In the fourth quarter, we recognized revenue of $6.5 million which includes non-cash royalties earned.

For the year ended December 31, 2018, we reported a net loss of $162 million or $1.44 per share compared to a net loss for the year ended 2017 of $121 million or $1.23 per share. The increased net loss reflects reduced revenue during 2018 due to an accelerated milestone received during 2017 from Incyte, the 2018 loss on early extinguishment of debt and increased non-cash interest on our liability related to the sale of future royalties.

Conference Call, Webcast and Prepared Statement Information

Date: Thursday, March 14, 2019

Time: 8:30 a.m. ET

Domestic Dial-in Number: 1-844-492-3727

International Dial-in Number: 1-412-317-5118

Conference ID: Agenus

Live Webcast: accessible from the Company’s website at View Source or with this link View Source

A replay will be available on the Company’s website approximately two hours after the call and will remain available for 90 days.

On March 14, 2019 argenx (Euronext & Nasdaq: ARGX), a clinical-stage biotechnology company developing a deep pipeline of differentiated antibody-based therapies for the treatment of severe autoimmune diseases and cancer, reported that ABBV-151, an antibody product candidate formerly named ARGX-115 and exclusively licensed to AbbVie, has now commenced clinical development with the initiation of a first-in-human clinical trial (Press release, argenx, MAR 14, 2019, View Source [SID1234534372]). The attainment of this development milestone triggers a $30 million payment by AbbVie.

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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

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"ABBV-151, previously called ARGX-115, was created as part of our Innovative Access Program translating the early work on novel immuno-oncology target glycoprotein A repetitions predominant (GARP) into an antibody with first-in-class therapeutic potential. We are pleased with the progress AbbVie has made since exercising its exclusive license option to this program last year and we look forward to following the ongoing clinical development closely in patients with locally advanced, or metastatic solid tumors," commented Tim Van Hauwermeiren, CEO at argenx.

argenx and AbbVie entered into a collaboration in April 2016 and argenx has received $90 million under the collaboration to date, including the first clinical development milestone achieved today. argenx is eligible to receive development, regulatory and commercial payments upon achievement of pre-determined milestones as well as tiered, up to double-digit royalties on net sales upon product commercialization.

About ABBV-151 (formerly ARGX-115)

ABBV-151 was discovered using argenx’s SIMPLE Antibody technology and is a fully human antibody binding specifically to the protein GARP, involved in the regulation of production and release of active transforming growth factor beta (TGF-β). ABBV-151 is believed to selectively limit the immunosuppressive activity of activated regulatory T-cells (Tregs), thereby stimulating the immune system to attack cancer cells. While the normal function of Tregs is to suppress certain compartments of the immune system to prevent self-directed immune responses through the release of active TGF-β, Tregs can also prevent the immune system from recognizing and suppressing pathogenic cells, including cancer cells. argenx believes the selective inhibition of TGF-β release by Tregs is potentially superior to systemic inhibition of TGF-β activity or depletion of Tregs and may give rise to therapeutic products with an improved safety profile.

ABBV-151 was discovered under argenx’s Innovative Access Program (IAP) with the de Duve Institute / Université Catholique de Louvain / WELBIO and exclusively licensed under a research and option agreement in 2013.

On March 14, 2019 the Vifor pharma group reported a strong sales and profit performance in 2018 with continued solid growth from its three strategic growth drivers (Press release, Vifor Pharma, MAR 14, 2019, View Source [SID1234534286]). Positive momentum is expected to continue during 2019 with the group on track to meet its milestone 2020 objectives. Sue Mahony and Kim Stratton nominated to the board of directors.

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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

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STRONG FINANCIAL PERFORMANCE FOR FULL-YEAR 2018

Net sales of CHF 1,584.6 million, up 22.7%; EBITDA of CHF 391.5 million, up 39.7%
Strong balance sheet with equity ratio of 74.8%
Core earnings per share of CHF 4.16, an increase of 95.9% versus prior year
Significant increase in cash flow from operations
Strong growth momentum continued in H2 for our three key strategic growth drivers, Ferinject, Vifor Fresenius Medical Care Renal Pharma (VFMCRP) and Veltassa
Net sales and EBITDA guidance, raised on 8 August 2018, were exceeded
FERINJECT/INJECTAFER IN-MARKET SALES POTENTIALLY A BLOCKBUSTER IN 2019

Reported net sales of CHF 485.1 million, up 23.8%
Increase in overall i.v. iron market share by value to 72.6% in 2018 compared to 70.3% in prior year
In-market sales of CHF 897.9 million, up 28.6%, potential to achieve blockbuster status already in 2019
VIFOR FRESENIUS MEDICAL CARE RENAL PHARMA GROWTH LED BY MIRCERA

Mircera net sales of CHF 451.3 million, up 32.8%
Agreement with Cara Therapeutics to develop and commercialise CR845 (difelikefalin) for chronic kidney disease-associated pruritus (CKD-aP) in haemodialysis patients worldwide outside US, Japan and South Korea
Venofer’s unique safety and efficacy profile confirmed by PIVOTAL trial results
VELTASSA CONTINUING TO TRANSFORM HYPERKALAEMIA TREATMENT

Net sales of CHF 90.5 million, up 75.1%
European launches in Germany, Sweden, Denmark, Norway; first successful ex-US reimbursement approvals in Sweden, Denmark, and Norway at prices demonstrating product value
Exclusive development and marketing licence signed with Zeria in Japan
SIGNIFICANT PROGRESS ON PARTNERING AND CLINICAL TRIALS

Increased stake in ChemoCentryx to 21.1% confirming rare diseases commitment
Two pivotal phase-III trials of CR485 ongoing, with completion and data read-out anticipated by end of 2019
Phase-II proof-of-concept trial for ferroportin inhibitor VIT-2763 to start in H2, following positive phase-I trial results
STRONG GROWTH EXPECTED TO CONTINUE IN 2019 AND BEYOND

Net sales expected to grow between 11% and 13% at constant exchange rates
Reported EBITDA expected to increase by 25%
Confirmation that 2020 net sales expected to exceed CHF 2 billion and EBITDA to be in the range of CHF 700 million
Implementation of Milestone 2020 according to plan
NOMINATIONS TO BOARD AND CHANGE IN MANAGEMENT

Sue Mahony and Kim Stratton will be proposed for election to the Board of Directors at the Annual Shareholder Meeting on 8 May 2019.
David Bevan, CEO of Vifor Fresenius Medical Care Renal Pharma (VFMCRP), has decided to leave the Vifor Pharma Group at the end of April 2019.
Etienne Jornod, Executive Chairman of the Vifor Pharma Group, commented on the 2018 results: "This was another outstanding performance by Vifor Pharma, our first full year as a pure play pharmaceutical company. The headline numbers highlight our strong growth story, with 2018 net sales up 22.7% to CHF 1,584.6 million, and EBITDA up 39.7% to CHF 391.5 million. Our three growth drivers – Ferinject/Injectafer, the joint company Vifor Fresenius Medical Care Renal Pharma, and Veltassa all continued to perform strongly. We are well on course to achieve the promises we made when we set out our plan to deliver sales of more than CHF 2 billion and EBITDA in the high triple-digit million range in 2020, and our focus is already moving ahead with an ambitious growth strategy to take us up to 2025 and beyond. We have set out guidance for continued strong growth in 2019 and look forward to making further progress towards achieving our vision of being a global leader in iron deficiency, nephrology and cardio-renal therapies."

1. FINANCIAL PERFORMANCE

In million CHF / in % 2018 2017 Change
Net sales 1,584.6 1,291.7 +22.7%
EBITDA 391.5 280.4 +39.7%
Net profit from continuing operations 244.4 124.0 +97.1%
Core earnings per share (in CHF) 4.16 2.12 +95.9%
Net debt -179.7 191.1 -370.8
KEY PROFIT AND LOSS FIGURES
Vifor Pharma Group net sales for 2018 grew to CHF 1,584.6 million, a strong increase of 22.7%, or 21.7% on a constant currency basis. Application of the new revenue recognition standard (IFRS 15) required a reclassification of certain elements between net sales and costs, with no impact on EBITDA. The new standard resulted in lower reported sales in 2018 of CHF 60.7 million and in 2017 of CHF 50.4 million.

Other operating income decreased to CHF 64.6 million in 2018 from CHF 91.6 million in 2017, primarily due to the expected sunset clause of royalty payments from CellCept.

EBITDA increased to CHF 391.5 million compared to CHF 280.4 million in the prior year, an increase of 39.7%, or 40.0% on a constant currency basis. This increase was due to strong sales growth combined with cost containment.

Cost of sales amounted to CHF 648.7 million in 2018 compared to CHF 517.9 million in the prior period, resulting in a gross profit margin of 60.7% compared to 62.6% in the prior year. The strong growth of higher margin products such as Ferinject/Injectafer was offset by decreasing CellCept royalties and the significant increase in net sales of Mircera.

Marketing and distribution expenses amounted to CHF 410.8 million, up 7.1%. The main driver was investments required in the European commercial organisations to further grow Ferinject and to support the continued rollout of Veltassa.

Investments in R&D amounted to CHF 206.4 million compared to CHF 185.1 million. The increase was driven by clinical studies on Ferinject, the phase-I study for the ferroportin inhibitor VIT-2763 and the initiation of the DIAMOND study for Veltassa.

General and administration expenses amounted to CHF 155.9 million compared to CHF 162.4 million in the prior year. The decrease is mainly attributable to lower personnel cost.

Core earnings per share grew to CHF 4.16 in 2018, an increase of 95.9% compared to CHF 2.12 in 2017, reflecting the strong growth of our operating business results. Core earnings are defined as reported earnings after minorities adjusted for proportionate amortisation of intangible assets of CHF 117.5 million in 2018 (2017: CHF 103.7 million).

CASH FLOWS AND FINANCIAL POSITION
Cash flow from operating activities for 2018 amounted to CHF +193.8 million compared to CHF +60.3 million in the prior year.

Cash flow from investing activities was CHF -376.1 million due to upfront and milestone payments for in-licensing agreements of CHF -213.3 million mainly in respect of the extension of commercialisation rights of Mircera of CHF -61.0 million, CR845 (Cara Therapeutics) of CHF -55.4 million, territory expansions for avacopan and CCX140 of CHF -10.0 million as well as additional milestone payments for Mircera of CHF -30.2 million and avacopan of CHF -49.1 million which were already capitalised in previous years. In addition, the Group performed strategic equity investments of CHF -106.2 million which mainly relate to ChemoCentryx of CHF -85.4 million and Cara Therapeutics of CHF -14.6 million.

Cash flow from financing activities of CHF +158.6 million was mainly impacted by the bond issuance in September 2018 with net proceeds of CHF +463.8 million. In addition, the private placement notes of CHF -114.5 million were repaid in Q1 2018. Dividend distributions in 2018 in respect of the financial year 2017 amounted to CHF -174.6 million, whereof CHF -45.0 million was paid to Fresenius Medical Care and CHF -129.6 million was distributed to shareholders in May 2018.

ROBUST BALANCE SHEET
Goodwill and intangible assets amounted to CHF 2,676.0 million at the end of 2018 compared to CHF 2,651.1 million in 2017, representing 59.5% of total assets (2017: 64.3%). The increase was related to the in-licensing agreements and extension of Mircera commercialisation rights described under cash flow from investing activities adjusted by amortisations.

Net debt was CHF -179.7 million resulting in a net-debt-to-EBITDA ratio of 0.46 at the end of 2018. With CHF 3,364.6 million of shareholders’ equity, the Vifor Pharma Group had a strong equity ratio of 74.8% at the end of 2018 compared to 80.8% in 2017. The slight decrease is due to the investments in intangibles assets.

2. THREE STRATEGIC DRIVERS MAINTAIN STRONG GROWTH

Ferinject/Injectafer
Reported net sales of Ferinject/Injectafer increased to CHF 485.1 million in 2018, up 23.8% from CHF 391.8 million the prior year, in line with Vifor Pharma’s commitment to full-year growth in excess of 20% at constant exchange rates. Given the significant remaining market opportunity around the world, Ferinject/Injectafer reported net sales are expected to continue to grow in the range of 20% in 2019.

The latest available data showed global in-market sales of Ferinject/Injectafer of approximately CHF 897.9 million for 2018, up 28.6% from the prior year period. In addition, there was a further increase in overall i.v. iron market share by value to 72.6% from 70.3% the prior year.

In the US, Injectafer continued to drive most of the i.v. iron market growth. Our US partner American Regent, a Daiichi Sankyo Group company, recorded net sales of USD 381.4 million in 2018, an increase of 39.4% compared to prior year. As a result, Vifor Pharma posted net sales of CHF 126.9 million. Growth was enhanced by an expanded promotion strategy and increased commercial resources, all despite greater competition. Injectafer is experiencing significant growth in the haematology/oncology and gastroenterology fields, where the majority of administrations occur across patient groups. American Regent’s initiatives have further raised awareness of the unmet medical need for optimal iron therapy in iron deficiency anaemia in gastroenterology, nephrology and women’s health.

In order to increase our geographical footprint in major pharmaceutical markets, ongoing clinical trials required for registration in Japan and China are on track. Ferinject is expected to be launched in Japan in the second half of 2019, focusing on women’s health and gastroenterology. Launch in China is expected in 2021 pending approvals, with a particular focus on patient blood management (PBM).

Vifor Fresenius Medical Care Renal Pharma (VFMCRP)
Net sales of Mircera increased by 32.8% to CHF 451.3 million in 2018 from CHF 339.9 million in 2017. Sales growth in 2018 was mainly due to mid-sized and independent dialysis organisations in the US and continued organic growth within Fresenius Kidney Care (FKC) clinics. Growth is expected to continue in 2019, primarily due to the annualised effect of sales to independent dialysis organisations and the expected increase in the number of patients receiving dialysis.

Venofer continued to be the leading intravenous iron brand by volume worldwide in 2018. Reported net sales were CHF 118.2 million in 2018, up 7.9% from CHF 109.6 million a year before. Overall monitored usage of Venofer now correlates to more than 25 million patient years of clinical experience.

The US continued to be the largest source of Venofer in-market sales in 2018, thanks to the strong collaboration between Vifor Pharma and its partner. Results of the pioneering PIVOTAL trial (which followed 2,141 patients for up to 4.4 years at 50 sites in the UK), published in October 2018 and January 2019 confirmed the unique safety and efficacy profile of Venofer, and will help to secure and consolidate its position in the highly competitive (i.v.) iron market.

Net sales of the phosphate binder Velphoro increased by 18.7% in 2018 to CHF 95.7 million, from CHF 80.6 million in 2017. Worldwide in-market sales generated by Vifor Pharma affiliates and partner companies in 2018 totalled around CHF 229 million. Sales in the US grew by 14.0% to CHF 69.6 million. Kidney Disease Improving Global Outcomes (KDIGO), which develops evidence-based clinical practice in kidney disease, recently updated their guidelines to recommend the use of non-calcium based phosphate binders. FKC US launched a communications program to physicians during 2018 to encourage them to follow this guidance.

In May 2018, the US FDA approved Retacrit injection for all indications of the reference drug, epoetin alfa, including treatment of anaemia associated with CKD and renal failure. It is the first biosimilar ESA approved for marketing in the US. Vifor Pharma recorded the first sales of Retacrit in Q4 2018, amounting to CHF 10.0 million.

Veltassa
In 2018, reported net sales of Veltassa were CHF 90.5 million compared to CHF 51.7 million in 2017, an increase of 75.1%. In 2018, net sales of Veltassa in the US were CHF 88.1 million (USD 89.9 million), a significant increase compared to CHF 51.6 million in 2017.

Since FDA approval in December 2015, Veltassa has experienced steady and sustained growth while also driving global expansion of the potassium binder market from CHF 173 million in 2016 to CHF 254 million in 2018.

In 2018, reimbursement approval was obtained in Sweden, Denmark and Norway, followed by Belgium in early 2019. Veltassa was launched in Germany, Sweden, Denmark and Norway. Reimbursement negotiations and further launches will continue in line with individual reimbursement process timelines across Europe throughout 2019 and 2020.

In March 2018, Vifor Pharma concluded a licensing agreement with Zeria Pharmaceutical Co., Ltd., granting Zeria exclusive rights to develop Veltassa for the Japanese market and, once marketing authorisation has been granted, to commercialise it in Japan. The collaboration with Zeria represents an important step in Vifor Pharma’s promise to make Veltassa available to patients worldwide.

In November 2018, Vifor Pharma reached a Special Protocol Assessment (SPA) agreement with the US FDA to study the benefits of Veltassa in patients with heart failure affected by or with history of hyperkalaemia. The DIAMOND study is designed to evaluate the potential of Veltassa in combination with renin-angiotensin-aldosterone inhibitor (RAASi) medications to improve patient outcomes, including reducing cardiovascular mortality and hospitalisations, by removing hyperkalaemia as a barrier to achieving the demonstrated benefits of RAASi treatment. Initiation of the study is expected in H1 2019, with anticipated results to provide strong guideline recommendations in cardiology/ heart-failure and improved treatment of patients through potassium control.

Results from the phase-II AMBER study will be published in 2019, evaluating the concomitant use of Veltassa and spironolactone in patients with CKD and resistant hypertension.

3. SIGNIFICANT PROGRESSION: IN-LICENSING DEALS, PARTNERING AND CLINICAL TRIALS

In May 2018, Vifor Fresenius Medical Care Renal Pharma announced a licensing agreement with US biopharmaceutical company Cara Therapeutics, Inc., to develop and commercialise CR845 (difelikefalin) injection for the treatment of CKD-associated pruritus (CKD-aP) in haemodialysis patients worldwide, excluding the US, Japan and South Korea. In the US, VFMCRP with Cara Therapeutics will promote CR845 to Fresenius Medical Care North America (FMCNA) dialysis clinics under a profit-sharing arrangement.

In September 2018, Vifor Pharma purchased an additional 7,343,492 shares of the common stock of ChemoCentryx Inc., increasing its stake from 6.6% to 21.1%.

Post balance sheet on 7 January 2019, Vifor Pharma reported positive phase-I trial results for VIT-2763, the first oral ferroportin inhibitor. Top-line results indicate that VIT-2763 has a favourable safety/tolerability profile. Following these positive results, Vifor Pharma will start a phase-II proof-of-concept trial in the second half of 2019. This trial will be conducted in patients with non-transfusion-dependent beta-thalassemia and documented iron overload.

4. OUTLOOK 2019

Market Access
Veltassa will continue to be launched in selected countries across Europe. Ferinject is expected to be launched in Japan in H2 2019. Vifor Pharma will continue to work towards finding a partner for the Japanese rights for CCX140.

Clinical Trials
Results from the AMBER study will be published in H1 2019, evaluating the impact of Veltassa in patients with chronic kidney disease (CKD) and resistant hypertension.

Initiation of the DIAMOND study looking at the benefits of Veltassa in patients with CKD and heart failure affected by hyperkalaemia is expected in H1 2019.

A phase-II study of the ferroportin inhibitor VIT-2763, designed to prevent excessive iron release into the blood, is expected to start in H2 2019.

Enrolment of the global phase-III ADVOCATE study of avacopan for anti-neutrophil cytoplasmic auto-antibody- associated vasculitis (ANCA-associated vasculitis) was completed in Q3 2018, with results expected in Q4 2019.

Cara Therapeutics is currently conducting two pivotal phase-III trials of CR845, with completion and data read-out anticipated by the end of 2019.

Business Development
We aim to complete at least one additional in-licensing, product acquisition or corporate transaction during the course of 2019.

Financial Guidance
In 2019 at constant exchange rates, Vifor Pharma net sales are expected to grow between 11% and 13%, and reported EBITDA is expected to increase by 25%.

In 2020 net sales are expected to exceed CHF 2 billion and EBITDA to be in the range of CHF 700 million.

Going forward the dividend is expected to remain at the current level of CHF 2 per share.

5. NOMINATIONS TO BOARD AND CHANGE IN MANAGEMENT

Vifor Pharma also announces that two highly experienced pharmaceutical leaders, Sue Mahony and Kim Stratton will be proposed for election to the Board of Directors at the Annual Shareholder Meeting on 8 May 2019. They will replace Sylvie Grégoire, Daniela Bosshardt-Hengartner and Fritz Hirsbrunner, who will not stand for re-election. The Executive Chairman and the Board takes the opportunity to thank them for their outstanding support and service to the Company over many years.

Sue Mahony was formerly Senior Vice President of Lilly and President of Lilly Oncology with more than a decade of sales and marketing experience with Schering-Plough, Amgen and Bristol-Myers Squibb. Sue is a British and US Citizen and holds a BSc and PhD in pharmacy from Aston University and an MBA from London Business School. She is a Member of the Board of Assembly Biosciences.

Kim Stratton was formerly Head of International Commercial at Shire Plc, responsible for all business outside the US across Specialty and Rare Diseases. Kim is an Australian citizen. She is a member of the Board of the European Federation of Pharmaceutical Industries and Associations (EFPIA) and a member of the Board of Novozymes.

The company also informs that David Bevan, CEO of Vifor Fresenius Medical Care Renal Pharma,

has decided to leave the group at the end of April 2019. The Executive Chairman, the President of the Executive Committee and COO, and the VFMCRP Board thank him for his excellent contribution and leadership and wish him every success in his future endeavours.

For further details, please see the Vifor Pharma Group 2018 Full-Year Report at viforpharma.com.

Live conference call and webcast

Vifor Pharma will host a live conference call (see phone numbers below) and webcast (View Source) on the 14 March 2019 at 13:00 (CET).

The pin code for the live conference call is 8175345.