On February 26, 2019 Clovis Oncology, Inc. (NASDAQ:CLVS) reported financial results for the quarter and year ended December 31, 2018, and provided an update on the Company’s clinical development programs and regulatory and commercial outlook for 2019 (Press release, Clovis Oncology, FEB 26, 2019, View Source [SID1234533683]).

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"We are pleased to have renewed U.S. revenue growth in the fourth quarter, and with our maintenance treatment indication approved in the EU, we look forward to our initial European launch in Germany on March 1," said Patrick J. Mahaffy, President and CEO of Clovis Oncology. "In addition, we are targeting an sNDA filing for BRCA1/2-mutant metastatic castration-resistant prostate cancer (mCRPC) in late 2019, and we expect to present data from both the TRITON2 mCRPC study and the ATLAS study in advanced bladder cancer at a Fall 2019 medical meeting. We are also very pleased to further our clinical collaboration with Bristol-Myers Squibb to not only include a combination study of Opdivo and lucitanib, but also to discuss tumor types for potential additional combination studies with Rubraca."

Fourth Quarter and Year-End 2018 Financial Results

Clovis reported product revenue for Rubraca of $30.4 million for the fourth quarter of 2018 and $95.4 million for the year ended December 31, 2018. For both the fourth quarter and year, the supply of free drug distributed to eligible patients through the Rubraca patient assistance program was approximately 26 percent of overall commercial supply. This represented $10.4 million in commercial value for the fourth quarter and $33.4 million in commercial value for the full year. Net product revenue for the quarter and fiscal year ended December 31, 2017 was $17.0 million and $55.5 million. Rubraca was initially approved and launched in the ovarian cancer treatment setting in the U.S. in December 2016 and in April 2018 the Rubraca label was expanded to include the broader and earlier-line maintenance treatment indication.

Clovis had $520.1 million in cash, cash equivalents and available-for-sale securities as of December 31, 2018. Cash used in operating activities was $82.7 million for the fourth quarter of 2018 and $366.0 million for the year ended December 31, 2018, compared with $65.6 million and $260.9 million for the comparable periods of 2017. This includes product supply costs of $22.7 million in the fourth quarter of 2018 and $98.8 million for the year ended December 31, 2018, compared to $12.0 million and $53.5 million for the comparable periods in 2017. Clovis had approximately 52.8 million shares of common stock outstanding as of December 31, 2018. In April 2018, Clovis raised net proceeds of $93.9 million through an offering of 1.8 million shares of common stock and $290.9 million in proceeds on $300 million aggregate principal amount of 1.25% convertible senior notes due 2025. The net proceeds from these offerings were $384.8 million, after deducting underwriting discounts and commissions, and offering expenses.

Clovis reported a net loss for the fourth quarter of 2018 of $99.3 million, or ($1.88) per share, and $368.0 million or ($7.07) per share for the year ended December 31, 2018. The net loss for the fourth quarter of 2017 was $51.9 million, or ($1.04) per share and $346.4 million, or ($7.36) per share for the year ended December 31, 2017. Net loss for the fourth quarter of 2018 included share-based compensation expense of $11.4 million and $49.1 million for the full year 2018, respectively, compared to $12.5 million and $44.7 million for the comparable periods of 2017.

The net loss for the year ended December 31, 2018 includes a one-time charge of $20 million related to a final settlement reached with the Securities and Exchange Commission which resolves their investigation related to rociletinib, and a charge of $8.0 million related to a legal settlement. The net loss for the year ended December 31, 2017 included a charge of $105.5 million related to the portion of a legal settlement that was paid in Clovis common stock. The adjusted net loss excluding these items was $99.3 million or ($1.88) per share for the fourth quarter and $340.0 million or ($6.53) per share for the fiscal year ended 2018 and $63.4 million or ($1.27) per share for the fourth quarter and $240.9 million or ($5.12) per share for the fiscal year ended 2017.

Research and development expenses totaled $71.2 million for the fourth quarter of 2018, and $231.3 million for the full year 2018, compared to $38.0 million and $142.5 million, respectively, for the comparable periods in 2017. The increase year over year is primarily due to higher research and development costs for rucaparib clinical trials, including increased enrollment in ongoing ovarian and prostate studies, increased costs related to initiating new ovarian and bladder studies during 2018, as well as additional headcount to support these increased rucaparib clinical trial activities.

Selling, general and administrative expenses totaled $49.1 million for the fourth quarter of 2018, and $175.8 million for the full year 2018, compared to $38.5 million and $138.9 million for the comparable periods in 2017. The increase year over year is primarily due to higher selling, general and administrative expenses related to the commercialization of Rubraca in the U.S. and the EU, including facility expenses and personnel expenses associated with establishing the EU infrastructure.

Key Milestones and Objectives for Rubraca

Recurrent Ovarian Cancer Maintenance Treatment Indication Approved in both U.S. and the EU

In April 2018, Rubraca was granted its second indication by the U.S. FDA as maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. This approval, in a broader and earlier-line indication, was based on positive data from the phase 3 ARIEL3 clinical trial. Biomarker testing is not required for patients to be prescribed Rubraca in this maintenance treatment indication.

In January 2019, the European Commission (EC) also approved the use of Rubraca for its second indication, as monotherapy for the maintenance treatment of adults with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. This approval expands rucaparib’s indication beyond its initial marketing authorization in the EU granted in May 2018, and in this indication Rubraca is available to eligible patients regardless of their BRCA mutation status. Rucaparib was the first PARP inhibitor licensed for an ovarian cancer treatment indication in Europe and is the first to be available for both treatment and maintenance treatment among eligible patients. Clovis has established its EU organization to support its initial launch in Germany this Friday, March 1 and anticipates launching in other EU countries later in 2019 and 2020.

Regulatory Path for Supplemental NDA in BRCA-mutant Advanced Prostate Cancer Based on TRITON2 Dataset and Breakthrough Therapy Designation

Initial data from the Company’s ongoing TRITON studies of Rubraca in advanced prostate cancer were presented at the ESMO (Free ESMO Whitepaper) 2018 Congress (European Society for Medical Oncology) in October 2018. The initial TRITON2 data showed a 44% confirmed objective response rate (ORR) by investigator assessment in 25 RECIST1/PCWG3** response-evaluable patients with a BRCA1/2 alteration, and results by independent assessment were consistent. The median duration of response in these patients had not yet been reached. In addition, a 51% confirmed prostate specific antigen (PSA) response rate was observed in 45 PSA response-evaluable patients with a BRCA1/2 alteration. Preliminary safety data for Rubraca in men with mCRPC were consistent with those observed in patients with ovarian cancer and other solid tumors.

The TRITON2 results were the basis for Breakthrough Therapy designation for Rubraca as a monotherapy treatment of adult patients with BRCA1/2 mutated mCRPC who have received at least one prior androgen receptor (AR)-directed therapy and taxane-based chemotherapy, which was granted on October 1, 2018 by the U.S. Food and Drug Administration (FDA). Both studies in the TRITON program, TRITON2 and TRITON3, continue to enroll patients.

Pending data maturity, Clovis is targeting the filing of a supplemental NDA (sNDA) for Rubraca in BRCA-mutant advanced prostate cancer in late 2019.

____________________

1
Response Evaluation Criteria in Solid Tumors (RECIST) is a standardized methodology for determining therapeutic response to anticancer therapy using changes in lesion appearance on imaging studies.

**
Prostate Cancer Working Group (PCWG3) is an international expert committee of prostate cancer clinical investigators who have recommended modifications to RECIST for use in the conduct of trials in metastatic castration-resistant prostate cancer (mCRPC) which were adopted in the TRITON2 protocol.

Rubraca Clinical Development

Clovis has a robust clinical development program underway in multiple tumor types, including Clovis-sponsored, partner-sponsored and investigator-initiated trials. The following clinical studies are open for enrollment or are anticipated to open during the next several months:

The Clovis-sponsored ARIEL4 confirmatory study in the treatment setting is a Phase 3 multicenter, randomized study of Rubraca versus chemotherapy in relapsed ovarian cancer patients with BRCA mutations who have failed two prior lines of therapy. This study is currently enrolling patients.
The Clovis-sponsored Phase 3 ATHENA study in advanced ovarian cancer in the first-line maintenance treatment setting evaluating Rubraca plus Opdivo (PD-1 inhibitor), Rubraca, Opdivo and placebo in newly-diagnosed patients who have completed platinum-based chemotherapy. This study, as part of a broad clinical collaboration with Bristol-Myers Squibb, is currently enrolling patients.
The Clovis-sponsored TRITON3 study, a Phase 3 comparative study in mCRPC enrolling BRCA-mutant and ATM-mutant (both inclusive of germline and somatic) patients who have progressed on androgen-receptor (AR)-targeted therapy and who have not yet received chemotherapy in the castration-resistant setting. TRITON3 compares Rubraca to physician’s choice of AR-targeted therapy or chemotherapy in these patients. This study is currently enrolling patients.
The Clovis-sponsored TRITON2 study in mCRPC, a Phase 2 single-arm study in patients with BRCA mutations (inclusive of germline and somatic) and is also enrolling patients with deleterious mutations of other homologous recombination (HR) repair genes. All patients will have progressed after receiving one line of taxane-based chemotherapy and one or two lines of AR-targeted therapy. This study is currently enrolling patients. Updated data from the ongoing TRITON2 study are anticipated at a Fall 2019 medical meeting.
The Clovis-sponsored ATLAS study is a single-arm Phase 2 open-label monotherapy study of Rubraca in recurrent, metastatic bladder cancer. This study is currently enrolling patients, and initial data from the ongoing ATLAS study are anticipated at a Fall 2019 medical meeting.
The Phase 1 RUCA-J study, sponsored by Clovis, has identified the 600mg BID dose of rucaparib as the recommended dose in Japanese patients; this will enable development of a bridging strategy and potential inclusion of Japanese sites in planned or ongoing global studies. This study is currently enrolling patients.
The Phase 2, open-label, multi-cohort ARIES study evaluating the combination of Rubraca and Opdivo in patients with relapsed ovarian cancer and patients with locally advanced or metastatic bladder carcinoma. This study is sponsored by Clovis and is expected to begin enrolling patients in the first half of 2019.
The Phase 1/2 combination study of sacituzumab govitecan and Rubraca for the treatment of advanced metastatic triple-negative breast cancer, relapsed platinum-resistant ovarian cancer and metastatic urothelial cancers is sponsored by Clovis and is expected to begin enrolling patients in 2019.
The Phase 2 combination study of Opdivo with Rubraca for the treatment of mCRPC. This study, sponsored by Bristol-Myers Squibb, is being conducted as an arm in the CHECKMATE 9KD prostate cancer study, and is currently enrolling patients.
Exploratory studies in other tumor types are also underway, as well as active discussions with Bristol-Myers Squibb regarding additional potential combination studies.

Lucitanib Clinical Development

Lucitanib is an investigational, oral, potent inhibitor of the tyrosine kinase activity of vascular endothelial growth factor receptors 1 through 3 (VEGFR1-3), platelet-derived growth factor receptors alpha and beta (PDGFRα/β) and fibroblast growth factor receptors 1 through 3 (FGFR1-3), which was previously evaluated in breast and lung cancers in partnership with Servier. Clovis has global rights (excluding China) for lucitanib.

Recent data for a drug that inhibits these same three pathways – when combined with a PD-1 inhibitor – are extremely encouraging and represent a scientific rationale for the development of lucitanib in combination with a PD-1 inhibitor, and a Clovis-sponsored study of lucitanib in combination with Opdivo is planned in gynecologic cancers. Clovis also intends to initiate a study of lucitanib in combination with rucaparib in ovarian cancer, based on encouraging data of VEGF and PARP inhibitors in combination. Each of these Phase 1b/2 studies is expected to initiate during the first half of 2019.

Conference Call Details

Clovis will hold a conference call to discuss Q4/FY 2018 results this morning, February 26, at 8:30am ET. The conference call will be simultaneously webcast on the Company’s web site at www.clovisoncology.com, and archived for future review. Dial-in numbers for the conference call are as follows: US participants 866.393.4306, International participants 734.385.2616, conference ID: 6675335.

About Rubraca (rucaparib)

Rubraca is an oral, small molecule inhibitor of PARP1, PARP2 and PARP3 being developed in ovarian cancer as well as several additional solid tumor indications. Studies open for enrollment or under consideration include ovarian, prostate, breast, gastroesophageal, pancreatic, lung and bladder cancers. Clovis holds worldwide rights for Rubraca.

In the United States, Rubraca is approved for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy. Rubraca is also approved in the United States for the treatment of adult patients with deleterious BRCA mutation (germline and/or somatic) associated epithelial ovarian, fallopian tube, or primary peritoneal cancer who have been treated with two or more chemotherapies and selected for therapy based on an FDA-approved companion diagnostic for Rubraca.

In the EU, Rubraca is approved for the maintenance treatment of adults with platinum-sensitive relapsed high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to platinum-based chemotherapy. This expands rucaparib’s indication beyond its initial marketing authorization in the EU granted in May 2018 and with this label expansion, rucaparib is now available to patients regardless of their BRCA mutation status. Rubraca is also approved in the EU for the treatment of adult patients with platinum sensitive, relapsed or progressive, BRCA mutated (germline and/or somatic), high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have been treated with two or more prior lines of platinum-based chemotherapy, and who are unable to tolerate further platinum-based chemotherapy.

Rubraca is an unlicensed medical product outside of the U.S. and the EU.

On February 26, 2019 Selexis SA and Turgut Pharmaceuticals (Turgut Ilaclari AS) reported that they have signed two trademark license agreements (CLMs) through which Turgut will operate the SURE Technology Platform and SURE CHO-M Cell Line by Selexis for the development of two high-end biosimilar antibodies: a control point inhibitor for the treatment of certain cancers and a monoclonal antibody for the treatment of HER2-positive metastatic breast cancer (Press release, Selexis FEB 26, 2019, View Source [SID1234533699]). With the addition of these CLMs, companies are now collaborating on the development of multiple biosimilars for cancer and inflammatory diseases. The companies announced the signing of the most recent CLMs in December 2017 .

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"In just under three years, we have signed five brand license agreements, in collaboration with the Turgut team, to advance its high-end biosimilar pipeline. Our technology and our cell line have proven their impact on biosimilar development, which is very important given the huge demand to offer patients expanded access to life-changing organic products, "said Marco Bocci., PhD at DPharm, Vice President of Licensing and Business Development at Selexis. "Turgut shares our passion for bringing advanced medicines to patients faster and at a lower cost. The success we have had with Turgut so far has been fueled by our collaboration and we are very pleased to continue supporting their efforts to bring biosimilars to the market under these new licenses. "

Selexis’ proprietary SURE technology platform facilitates the rapid, stable and cost-effective production of virtually all recombinant proteins, including biosimilars, and provides a seamless integration of the organic product development continuum, from discovery to commercialization. Using the SURE technology platform, Selexis has managed to generate many biosimilars, including marketed products, whose glycan profiles correspond to the originator drugs.

"These two products are innovative treatments that can improve accessibility for a much larger patient population," said Serdar Alpan, MD, PhD, head of the Biotechnology Group at Turgut Pharmaceuticals. "As a cell line development specialist and Turgut’s strong partner, Selexis’ tools and technologies provide us with the competitiveness we need to move forward on our biosimilar programs. We look forward to moving these programs forward. "

The SURE CHO-M cell line from Selexis is a high performance mammalian cell line derived from CHO-K1 cells and used for the production of recombinant therapeutic proteins and monoclonal antibodies. The growth and production properties of the Selexis SURE CHO-M cell line are well defined and the feeding strategy has been optimized to allow for faster and more efficient scaling of the bioreactors. Therapies generated with Selexis SURE CHO-M cells undergo clinical trials and are transformed into marketed products.

On February 26, 2019 Coherus BioSciences, Inc. (Nasdaq: CHRS), reported that senior management will present at two upcoming investor healthcare conferences (Press release, Coherus Biosciences, FEB 26, 2019, View Source [SID1234533743]).

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Management will deliver a company presentation at the 38thCowen & Company Healthcare Conference on Tuesday, March 12th at 10 a.m. ET taking place in Boston, Massachusetts.
Management will deliver a company presentation at Barclays Global Healthcare Conference on Wednesday, March 13th at 8:00 a.m. ET taking place in Miami, Florida.
The audio portion of the presentations will be available on the investors page of the Coherus BioSciences website at View Source

On February 26, 2019 Medigene AG (FSE: MDG1, Prime Standard, SDAX), a clinical stage immuno-oncology company focusing on the development of T cell immunotherapies, reported that it has dosed the first patient in its first-in-human clinical trial with its TCR therapy candidate MDG1011 (Press release, MediGene, FEB 26, 2019, View Source [SID1234533684]). The Phase I/II trial investigates the safety and feasibility of MDG1011 for the treatment of various types of blood cancer, including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and multiple myeloma (MM). MDG1011 is a novel immunotherapy candidate using patient-derived, T cell receptor (TCR)-modified T cells targeting the tumor antigen PRAME (PReferentially expressed Antigen in MElanoma) and was administered for the first time to a multiple myeloma patient in the Department of Medicine 5 (Director Prof. Dr. Andreas Mackensen) at the Universitätsklinikum Erlangen, Germany. MDG1011 is designed as a one-time treatment.

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Dr. Kai Pinkernell, CMO/CDO of Medigene, comments: "Hematologic cancers such as AML, MDS and MM in advanced stages are difficult to treat and usually associated with a very poor prognosis for patients. With our TCR therapy, we hope to open new treatment options for seriously ill patients and the first-time use on patients is a very important step in the development of this new therapeutic candidate."

In the Phase I portion of the trial, approximately 12 patients who are suffering from advanced stage AML, MDS and MM and have previously undergone several cycles of standard therapies will be treated with MDG1011. PRAME expression on the tumor cells as well as the blood serotype HLA-A * 02:01 are further inclusion criteria for patients who can participate in this multicenter, open-label, dose escalation study using a 3 + 3 design. Three dose cohorts and an optional fourth dose cohort will test dose ranges from 100,000 to 10,000,000 transduced T cells per kg of body weight. Each dose cohort consists of 3 patients. At least one MM patient and at least one AML or MDS patient need to be included in each cohort. Patients will undergo preconditioning treatment with cyclophosphamide and fludarabine. After completing treatment of all patients in a dose cohort and a four-week safety follow-up period, dose escalation will be determined by an independent Data and Safety Monitoring Board (DSMB). The primary endpoint for the Phase I portion of this clinical trial will be safety and feasibility at three months with a total follow-up period of up to 12 months. Several secondary endpoints (i.e. overall response rate (ORR)) will be assessed as well.

In the Phase II portion of the trial, presumably two of the three indications will be carried forward after a positive DSMB assessment regarding the safety of MDG1011 and review by the competent authority and central ethics committee. In the Phase II portion, 40 HLA-A*02:01 and PRAME positive patients will be treated with MDG1011; another 40 patients, who are positive for PRAME but negative for HLA-A*02:01, will be included in the control groups (20 treated and 20 control patients per indication) and treated with investigator choice therapy. Co-primary endpoints of the Phase II portion are safety and preliminary efficacy, where efficacy is measured as ORR at 3 months. Several secondary endpoints will be assessed here as well.

The clinical trial is being conducted by the Department of Internal Medicine III of the University Hospital Regensburg (Director: Prof. Dr. Wolfgang Herr) under the leadership of the coordinating investigator PD Dr. Simone Thomas, as well as by the University Hospitals of Erlangen and Würzburg, Germany. Up to five additional clinical centers in Germany are currently being opened and are anticipated to open recruitment within the next three to five months and screen additional patients for their suitability to participate in the study.

About Medigene’s TCR therapy: The TCR-T cell technology aims at arming the patient’s own T cells with tumor-specific T cell receptors. The receptor-modified T cells are then able to detect and efficiently kill tumor cells. This immunotherapy approach attempts to overcome the patient’s tolerance towards cancer cells and tumor-induced immunosuppression by activating and modifying the patient’s T cells outside the body (ex vivo). TCR-T therapy is developed to utilize a higher number of potential tumor antigens than other T cell-based immunotherapies, such as chimeric antigen receptor T cell (CAR-T) therapy. Medigene is establishing a pipeline of recombinant T cell receptors and has a collaboration with bluebird bio, Inc. for the development of six TCR-Ts.

About acute myeloid leukemia (AML): AML is a malignant disease of the hematopoietic system. The cause of the disease is the uncontrolled growth of nonfunctioning hematopoietic progenitor cells in the bone marrow. Typical symptoms of AML are anemia, fever, increased susceptibility to infection and bleeding. The disease develops rapidly and, if left untreated, can lead to death within a few weeks or months. AML therapy is usually started with intensive chemotherapy, often followed by consolidation therapy, with or without allogeneic hematopoietic stem cell transplantation. In a significant number of patients, relapse of the disease is expected.

About multiple myeloma (MM): Multiple myeloma (MM) is a malignant disease characterized by monoclonal plasma cell proliferation in the bone marrow, with increased production of complete or incomplete monoclonal immunoglobulins. These proteins are detectable in serum and / or urine. Every year around 3,000 men and about 2,700 women in Germany develop multiple myeloma. MM is thus the third most frequent hematological neoplasia after leukemia and non-Hodgkin’s lymphoma and responsible for about 1% of all cancers in Germany.

About myelodysplastic syndrome (MDS): The term myelodysplastic syndrome is a group of diseases of the bone marrow, in which blood formation does not originate from healthy, but from mutated cells of origin (stem cells). The bone marrow of patients suffering from myelodysplastic syndromes is no longer able to produce fully mature and functional blood cells from these stem cells. In advanced stages of these diseases, more and more immature blood cells are produced. The blood formation process is therefore permanently disturbed and may also lead to acute myeloid leukemia (AML) in some patients at a later date.

Medigene AG (FSE: MDG1, ISIN DE000A1X3W00, Prime Standard, SDAX) is a publicly listed biotechnology company headquartered in Martinsried near Munich, Germany. The company is developing highly innovative immunotherapies to target various forms and stages of cancer. Medigene concentrates on the development of personalized T cell-based therapies with the focus on T cell-receptor modified T cells (TCR-Ts) and has associated projects currently in pre-clinical and clinical development. For more information, please visit View Source

This press release contains forward-looking statements representing the opinion of Medigene as of the date of this release. The actual results achieved by Medigene may differ significantly from the forward-looking statements made herein. Medigene is not bound to update any of these forward-looking statements. Medigene is a registered trademark of Medigene AG. This trademark may be owned or licensed in select locations only.

On February 26, 2019 Theravance Biopharma, Inc. ("Theravance Biopharma" or the "Company") (NASDAQ: TBPH) reported financial results for the fourth quarter and full year ended December 31, 2018 (Press release, Theravance, FEB 26, 2019, View Source [SID1234533700]). Revenue for the fourth quarter and full year 2018 was $15.7 million and $60.4 million, respectively. Full year operating loss was $238.8 million or $187.4 million excluding share-based compensation expense, in line with the Company’s previously stated financial guidance. Cash, cash equivalents, and marketable securities totaled $517.1 million as of December 31, 2018.

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Rick E Winningham, chairman and chief executive officer, commented: "Following a highly productive 2018, we begin the year with great momentum and continue to make meaningful progress towards our goal of designing more effective and safer medicines to address unmet patient needs. Early in 2018, we entered into a global collaboration with Janssen for TD-1473, our gut-selective pan-JAK inhibitor for inflammatory intestinal diseases, for which we are beginning late-stage clinical trials. In the middle of the year, we showed positive four-week results for ampreloxetine in neurogenic orthostatic hypotension, providing us with the confidence to advance into a registrational Phase 3 program which is now underway. In the latter part of 2018, we and our partner Mylan achieved product approval for YUPELRI in COPD, and formal launch efforts are now underway. We closed out the year with R&D Day where we described our innovative research and development strategy of organ-selective medicines designed to expand the therapeutic index beyond that of conventional therapy and introduced several new research programs. Underpinning the progress of our own business, GSK’s TRELEGY ELLIPTA for COPD continues its impressive sales trajectory, and we await the results of the Phase 3 CAPTAIN study in asthma in the first half of 2019.

"We anticipate multiple clinical readouts and milestones over the next several months, including supplemental data presentations at upcoming scientific meetings for TD-1473 in ulcerative colitis and ampreloxetine in nOH, as well as Phase 1 data for TD-8236, and initial commercial metrics for YUPELRI. Following our recently completed note financing tied to our economic interest in TRELEGY ELLIPTA, we enter 2019 with a strong cash balance and are well-positioned to execute against our milestones and continue to deliver value to stakeholders."

Program and Corporate Updates

YUPELRITM (revefenacin) inhalation solution (lung-selective nebulized long-acting muscarinic antagonist (LAMA)):

First and only once-daily, nebulized bronchodilator approved in the US for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD)
Formal launch activities underway with partner Mylan; combined sales infrastructures covering the hospital, hospital discharge, and home health settings
TD-1473 (gut-selective pan-Janus kinase (JAK) inhibitor):

First patients dosed in Phase 2 DIONE induction study in Crohn’s disease
Sites initiated in registrational Phase 2b/3 RHEA induction and maintenance study in ulcerative colitis
Results from the Phase 1b study of TD-1473 in patients with ulcerative colitis accepted as an oral presentation at Digestive Disease Week (DDW) in May 2019
Ampreloxetine (TD-9855, norepinephrine reuptake inhibitor (NRI)):

Recently announced initiation of dosing in registrational Phase 3 program in symptomatic neurogenic orthostatic hypotension (nOH)
Phase 2 study in patients with nOH complete; 5-month data further support previously-announced clinical observations after four weeks of treatment. Detailed study data to be submitted for presentation at mid-year scientific meeting
TD-8236 (novel, lung-selective inhaled pan-JAK inhibitor for serious respiratory diseases):

Discovery leverages organizational expertise in respiratory diseases and JAK inhibition
Phase 1 clinical study underway; designed to evaluate safety and provide biomarker data of TD-8236 in healthy volunteers and asthma patients; completion expected in mid-2019
Multiple JAK-dependent pathways clinically validated in asthma and COPD
Potentially broad activity with JAK inhibition across a range of respiratory indications and phenotypes
TD-8236 shown to potently inhibit targeted mediators of Th2-high and Th2-low asthma in human cells in preclinical studies
R&D Day in December 2018:

Highlighted our innovative research and development strategy of organ-selective medicines and introduced several new research programs that we plan to advance towards clinical development, each specifically tailored to the organ of interest
TRELEGY ELLIPTA (first once-daily single inhaler triple therapy for COPD)1:

GSK reported fourth quarter 2018 net sales of $100 million and $207 million for the full year 2018; Theravance Biopharma entitled to approximately 5.5% to 8.5% (tiered) of worldwide net sales of the product
Currently available in 26 countries, with additional countries expected over the course of 2019; recent regulatory filings include Japan and China
Expanded COPD indication in Europe for patients not adequately treated with dual bronchodilation, making it the first single inhaler triple therapy indicated for patients with moderate to severe COPD
Completion of Phase 3 CAPTAIN study in asthma patients expected in 1H 2019; if positive, submission of supplemental New Drug Application (sNDA) for TRELEGY ELLIPTA in asthma anticipated in 2H 2019
Completed a non-dilutive private placement of $250.0 million in aggregate principal amount of non-recourse notes secured by a portion of the future payments the Company expects to receive related to royalties due on net sales1 of TRELEGY ELLIPTA
75% share of the payments will be used to satisfy the debt obligations until notes repaid
Remaining 25% of the payments will be directed to benefit the Company on an ongoing basis
Proceeds were approximately $229.0 million net of debt issuance costs and a 5% retention of the notes by the Company
Strategic infusion of cash in late 2018 with retained economics over TRELEGY ELLIPTA’s commercial lifespan; proceeds to support key strategic priorities
VIBATIV (telavancin): Sale of VIBATIV to Cumberland Pharmaceuticals Inc. completed in November 2018

Notes:
1 As reported by Glaxo Group Limited or one of its affiliates (GSK); reported sales converted to USD; economic interest related to TRELEGY ELLIPTA (the combination of fluticasone furoate, umeclidinium, and vilanterol, (FF/UMEC/VI), jointly developed by GSK and Innoviva, Inc.) entitles Company to upward tiering payments equal to approximately 5.5% to 8.5% on worldwide net sales of the product (net of TRC LLC expenses paid and the amount of cash, if any, expected to be used by TRC pursuant to the TRC LLC Agreement over the next four fiscal quarters)

Fourth Quarter and Full Year Financial Results

Revenue

Revenue for the fourth quarter of 2018 was $15.7 million, comprised of collaboration revenue primarily related to our global collaboration with Janssen for TD-1473 of $10.0 million, profit sharing revenue related to YUPELRI of $3.3 million, and product sales of VIBATIV (telavancin) of $2.4 million. Revenue in the fourth quarter represents an increase of approximately $11.2 million over the same period in 2017. The increase was primarily related to revenue recognized from the upfront payment associated with the global collaboration agreement with Janssen for TD-1473. The increase was partially offset as a full quarter of Product Sales was not recognized due to the sale of VIBATIV to Cumberland Pharmaceuticals in November 2018. Full year 2018 revenue was $60.4 million, comprised of collaboration revenue of $41.8 million primarily associated with the upfront payment from Janssen for TD-1473, product sales of VIBATIV of $15.3 million and profit sharing revenue related to YUPELRI of $3.3 million.

Research and Development (R&D) Expenses

R&D expenses for the fourth quarter of 2018 were $52.3 million, compared to $51.1 million in the same period in 2017. The increase was primarily due to higher external expenses to support our key programs and was partially offset by lower employee-related and share-based compensation expenses. Full year 2018 R&D expenses were $201.3 million, or $175.8 million excluding non-cash share-based compensation.

Selling, General and Administrative (SG&A) Expenses

SG&A expenses for the fourth quarter of 2018 were $25.5 million, compared to $29.5 million in the same period in 2017. The decrease was primarily due to lower expenses related to share-based compensation. Full year 2018 SG&A expenses were $97.1 million, or $71.3 million excluding non-cash share-based compensation.

Cash, Cash Equivalents and Marketable Securities

Cash, cash equivalents and marketable securities totaled $517.1 million as of December 31, 2018, which includes net proceeds of $229.4 million resulting from the private placement of notes secured by a portion of the future payments related to royalties due on net sales of TRELEGY ELLIPTA.

2019 Financial Guidance

The Company expects full-year 2019 operating loss, excluding share-based compensation, of $210 million to $230 million. Operating loss guidance does not include royalty income for TRELEGY ELLIPTA which we recognize in our statement of operations as "income from investment in TRC, LLC." Our share of US profits and losses related to the commercialization of YUPELRI, potential future business development collaborations as well as the timing and cost of clinical studies associated with our key programs, among other factors, could impact our financial guidance.

Conference Call and Live Webcast Today at 5:00 pm ET

Theravance Biopharma will hold a conference call and live webcast accompanied by slides today at 5:00 pm ET. To participate in the live call by telephone, please dial (855) 296-9648 from the US, or (920) 663-6266 for international callers, and use the confirmation code 8086288. Those interested in listening to the conference call live via the internet may do so by visiting Theravance Biopharma’s website at www.theravance.com, under the Investor Relations section, Presentations and Events. Please go to the website 15 minutes prior to the start of the call to register, download, and install any necessary audio software.

A replay of the conference call will be available on Theravance Biopharma’s website for 30 days through March 28, 2019. An audio replay will also be available through 8:00 pm ET on March 5, 2019 by dialing (855) 859-2056 from the U.S., or (404) 537-3406 for international callers, and then entering confirmation code 8086288.