On May 01, 2016 Cempra, Inc. (Nasdaq:CEMP), a clinical-stage pharmaceutical company focused on developing antibiotics to meet critical medical needs in the treatment of bacterial infectious diseases, reported financial results for the quarter ended March 31, 2016 and provided an update on recent corporate developments (Press release, Cempra, MAY 1, 2016, View Source [SID:1234511732]). The company will host a webcast and conference call tomorrow at 8:00 a.m. ET.

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First Quarter 2016 and Recent Corporate Highlights

In April, Cempra completed its rolling submission of two New Drug Applications (NDA) to the U.S. Food and Drug Administration (FDA) for solithromycin (intravenous and capsules) in community-acquired bacterial pneumonia (CABP). Having been granted qualified infectious diseases product (QIDP) designation in 2013, solithromycin’s NDAs qualify for an eight month priority review. Subject to approval by the FDA, Cempra plans to launch solithromycin in the U.S. in the first quarter of 2017.

In March, Cempra received authorization under its existing contract with the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response within the U.S. Department of Health and Human Services, to receive funding of $25.5 million through mid-2018 for a Phase 2/3 pivotal clinical study of solithromycin in pediatric patients. Cempra is responsible for an additional designated portion of the cost of the planned Phase 2/3 study. Three dosage formulations of solithromycin, intravenous, capsule and oral suspension, will be tested in the trial and may provide pediatricians with greater dosing flexibility.

In January, Cempra completed a public offering of 4,166,667 shares at a price of $24.00 per share. Net proceeds after underwriting discounts and commissions and expenses of the offering were approximately $93.8 million. Cempra intends to use the funds for the commercial launch of solithromycin in CABP in the U.S., subject to the drug receiving FDA approval, and on research and development activities, working capital and general corporate and administrative expenses.

The Taksta (fusidic acid) acute bacterial skin and skin structure infection (ABSSSI) Phase 3 trial is enrolling patients, which is expected to be completed during the first half of 2017.
"I am truly delighted that Cempra is able to mark the tenth anniversary of its founding with our submission to the FDA of two NDAs for solithromycin in community-acquired bacterial pneumonia," said Prabhavathi Fernandes, Ph.D., president and chief executive officer of Cempra. "As a new chemical entity, we expect that solithromycin will be subject to an advisory committee review, however given the compelling data package that we have assembled, we look forward to working with the agency during the review process to bring this important new macrolide antibiotic to patients with CABP and the physicians who treat them. Our development programs for solithromycin for pediatric patients and urogenital gonorrhea, as well our development program for Taksta, are continuing to move forward."

Upcoming Clinical Development Milestones

Solithromycin

Solithromycin pediatric: patient enrollment for Phase 1b trial continues.
Enrollment in a Phase 2/3 pivotal trial with solithromycin for bacterial infections in pediatric patients is expected to initiate in Q2 2016.
Phase 3 trial for solithromycin in urogenital gonorrhea is ongoing.
Phase 2 trial in chronic obstructive pulmonary disease (COPD) is ongoing.
Phase 2 trial in nonalcoholic steatohepatitis (NASH) is ongoing.
Completion of the EMA submission for solithromycin in the treatment of CABP is expected by the end of the first half of 2016.
Taksta

Phase 3 trial in ABSSSI is ongoing.
An exploratory trial for Taksta in patients with refractory bone or joint infections is ongoing.
Financial Results for the Three Months Ended March 31, 2016

For the quarter ended March 31, 2016, Cempra reported a net loss of $29.4 million, or $0.61 per share, compared to a net loss of $17.4 million, or $0.41 per share for the first quarter in 2015. Research and development expense in the first quarter of 2016 was $23.5 million, a decrease of 10% compared to the same quarter in 2015. The lower R&D expense was primarily due to the timing of payments for the order of active pharmaceutical ingredient (API) necessary to support the launch of solithromycin as the company begins its commercial readiness activities and a decrease in clinical expenses as the Phase 3 Oral and Phase 3 IV-to-Oral studies are complete. General and administrative expense was $8.3 million, a 79% increase compared to the quarter ended March 31, 2015, driven primarily by commercial readiness activities and increased headcount as the company begins to plan for commercialization.

As of March 31, 2016, Cempra had cash and equivalents of $223.6 million and 48.2 million shares outstanding.

Financial Guidance

The company’s current cash and equivalents are expected to be sufficient to fund ongoing operations into the second quarter of 2017, assuming continued timely receipts under the BARDA contract and receipt of expected milestone payments from Toyama. This projection does not include any funds from new financings or partnerships.

On April 29, 2016 Shire plc ("Shire") (LSE: SHP, NASDAQ: SHPG) reported unaudited results for the three months ended March 31, 2016 (Press release, Shire, APR 29, 2016, View Source [SID:1234511736]).

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Financial Highlights Q1 2016 Growth(1) Non GAAP CER(1)(2)
Product sales $1,627 million +14% +16%
Total revenues $1,709 million +15% +17%

Non GAAP operating income $797 million +17% +16%
US GAAP operating income from continuing operations $544 million +15%

Non GAAP EBITDA margin (excluding royalties & other revenues)(3) 46% 0pps(4)
US GAAP net income margin(5) 25% -3pps

Non GAAP net income $632 million +13%
US GAAP net income $419 million +2%

Non GAAP diluted earnings per ADS $3.19 +12% +12%
US GAAP diluted earnings per ADS $2.12 +2%

Non GAAP cash generation $492 million -5%
Non GAAP free cash flow $338 million +38%
US GAAP net cash provided by operating activities $390 million -31%
(1) Percentages compare to equivalent 2015 period.
(2) On a Constant Exchange Rate ("CER") basis, which is a Non GAAP measure.
(3) Non GAAP earnings before interest, tax, depreciation and amortization ("EBITDA") as a percentage of product sales, excluding royalties and other revenues.
(4) Percentage point change ("pps").
(5) US GAAP net income as a percentage of total revenues.

The Non GAAP financial measures included within this release are explained on pages 25 – 26, and are reconciled to the most directly comparable financial measures prepared in accordance with US GAAP on pages 19 – 22.

First Quarter & Recent Highlights:

Product sales growth of 14% (16% on a Non GAAP CER basis) to $1.6 billion, driven by VYVANSE, LIALDA/MEZAVANT, CINRYZE, FIRAZYR, GATTEX/REVESTIVE and NATPARA.
Rare disease products acquired from NPS Pharmaceuticals, Inc. ("NPS") continued to perform well with GATTEX/REVESTIVE sales up 247% (up 97% on a pro-forma basis(1)) to $52 million, and NATPARA sales of $16 million.
Free cash flow remained strong, impacted primarily by net payments and receipts of taxes between Q1 2015 and Q1 2016.
Lifitegrast New Drug Application ("NDA") accepted by the US Food and Drug Administration ("FDA"), with Prescription Drug User Fee Act ("PDUFA") date set for July 22, 2016.
Pipeline progression with positive topline results from SHP465 safety and efficacy study in children and adolescents with Attention Deficit Hyperactivity Disorder ("ADHD").
Completed acquisition of Dyax Corp. ("Dyax") and enrollment on track for SHP643 (formerly DX2930) Phase 3 studies for the treatment of Hereditary Angioedema ("HAE").
Patent upheld for LIALDA (mesalamine) delayed release tablets by U.S. District Court for the Southern District of Florida; the case has been appealed.
Baxalta Incorporated ("Baxalta") acquisition on track with integration progressing well; shareholder votes set for May 27 and closing anticipated in early June.
(1) Sales prior to February 21, 2015 were recorded by NPS.
Flemming Ornskov, M.D. Chief Executive Officer, commented:

"Shire is off to a strong start in 2016, delivering double-digit product sales and Non GAAP earnings per ADS growth, and advancing our innovative pipeline. We were pleased to report positive Phase 3 topline results for SHP465 in children and adolescents with ADHD, a therapeutic area with significant need for additional treatment options. We are also looking forward to hearing from the FDA by late July regarding lifitegrast, a potential new treatment for dry eye disease.

While we maintain our sharp focus on Shire’s business, we closed the acquisition of Dyax during the quarter and we are making excellent progress with the Baxalta integration planning. Our shareholder vote is scheduled for May 27 and the closing is anticipated to follow in early June. We look forward to officially welcoming our Baxalta colleagues to Shire, and creating a global biotechnology leader focused on rare diseases and other highly specialized conditions."

On April 29, 2016 AbbVie (NYSE: ABBV), a global biopharmaceutical company, reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) issued a positive opinion in favor of the use of IMBRUVICA (ibrutinib) for the treatment of adult patients with previously-untreated chronic lymphocytic leukemia (CLL) in the European Union (EU) (Press release, AbbVie, APR 29, 2016, View Source [SID:1234511707]). The positive CHMP recommendation follows the March 4, 2016 U.S. Food and Drug Administration (FDA) approval of IMBRUVICA for the first-line treatment of patients with CLL.1 If approved by the European Commission (EC), this would be the fifth treatment indication for IMBRUVICA in the EU to date.

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CLL is a chronic disease, and the prevalence rate in Europe among men and women is approximately 5.87 and 4.01 cases per 100,000 persons per year, respectively.2 An expansion of the CLL indication in Europe would mean a larger number of CLL patients, in addition to those with the genetic mutations del 17p or TP53, could initiate their treatment with a safe and effective oral alternative option to chemotherapy, rather than having to wait until they have become relapsed or refractory on another treatment option.

IMBRUVICA is jointly developed and commercialized in the U.S. by Pharmacyclics LLC, an AbbVie company and Janssen Biotech, Inc. In Europe, Janssen-Cilag International NV (Janssen) holds the marketing authorization and its affiliates market IMBRUVICA in EMEA (Europe, Middle East, Africa), as well as the rest of the world. IMBRUVICA is already approved in Europe to treat adult patients with relapsed or refractory mantle cell lymphoma (MCL), adult patients with CLL who have received at least one prior therapy or who have del 17p or TP53 mutations, and adult patients with Waldenström’s macroglobulinemia (WM) who have received at least one prior therapy, or as a first-line treatment for WM patients unsuitable for chemo-immunotherapy.3 The EC will review the CHMP opinion and is expected to render a final decision on the use of IMBRUVICA for previously untreated patients with CLL later this year.

"If approved by the European Commission, IMBRUVICA will be available as a treatment option for all CLL patients, including those who are treatment-naïve. The ability to offer a safe and effective, oral, single-agent alternative to chemotherapy in the first-line setting is a landmark few therapies are able to reach," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "The fact that IMBRUVICA has been granted this initial recommendation in the first-line setting is a testament to the dedication of those working on the compound to improve the lives of patients around the world who are suffering from CLL."

The positive CHMP opinion was based on data from the Phase 3, randomized, open-label RESONATE-2 (PCYC-1115) trial, which were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2015 and simultaneously published in The New England Journal of Medicine (NEJM). After a median of 18 months of follow-up, IMBRUVICA was associated with a significant improvement in all efficacy endpoints versus chlorambucil in patients aged 65 or older with newly diagnosed CLL. Specifically, IMBRUVICA was associated with a 90% progression-free survival (PFS; the primary endpoint) rate versus 52% for chlorambucil. Moreover, IMBRUVICA significantly prolonged overall survival (OS; a key secondary endpoint), with a 24-month survival rate of 98% versus 85% for chlorambucil (HR: 0.16; 95% CI, 0.05, 0.56). The safety of IMBRUVICA in the treatment-naïve CLL patient population was consistent with previously reported studies.

About the RESONATE-2 Study
RESONATE-2 is a Pharmacyclics-sponsored study which enrolled 269 treatment-naïve patients with CLL or small lymphocytic lymphoma (SLL) aged 65 years or older in the U.S., EU and other regions. Patients were randomized to receive either IMBRUVICA 420 mg orally, once daily until progression or unacceptable toxicity, or chlorambucil on days 1 and 15 of each 28-day cycle for up to 12 cycles. The starting dose for chlorambucil in Cycle 1 was 0.5 mg/kg and was increased based on tolerability in Cycle 2 by increments of 0.1 mg/kg to a maximum of 0.8 mg/kg. The primary endpoint of the study was PFS as assessed by an Independent Review Committee (IRC) according to the International Workshop on Chronic Lymphocytic Leukemia (iWCLL) 2008 criteria, with modification for treatment-related lymphocytosis. Key secondary endpoints included overall response rate (ORR; based on the same iWCLL criteria), OS and safety.

About IMBRUVICA
IMBRUVICA is a first-in-class, oral, once-daily therapy that inhibits a protein called Bruton’s tyrosine kinase (BTK).1 BTK is a key signaling molecule in the B-cell receptor signaling complex that plays an important role in the survival and spread of malignant B cells.1,4 IMBRUVICA blocks signals that tell malignant B cells to multiply and spread uncontrollably.1

IMBRUVICA is approved in the U.S. to treat patients with chronic lymphocytic leukemia (CLL), patients with mantle cell lymphoma (MCL) who have received at least one prior therapy and patients with Waldenström’s macroglobulinemia (WM). Accelerated approval was granted for the MCL indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.1

IMBRUVICA is approved in the EU to treat adult patients with relapsed or refractory MCL, adult patients with CLL who have received at least one prior therapy or who have the genetic mutations del 17p or TP53, and adult patients with WM who have received at least one prior therapy, or as a first-line treatment for WM patients unsuitable for chemo?immunotherapy. 3

IMBRUVICA was one of the first medicines to receive U.S. FDA approval via the new Breakthrough Therapy Designation pathway.

IMBRUVICA is being studied alone and in combination with other treatments in several blood and solid tumor cancers. More than 6,000 patients have been treated with IMBRUVICA in clinical trials. Currently, 14 Phase 3 trials have been initiated with IMBRUVICA and more than 90 trials are registered on www.clinicaltrials.gov.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Hemorrhage – Fatal bleeding events have occurred in patients treated with IMBRUVICA. Grade 3 or higher bleeding events (intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and post-procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA.

The mechanism for the bleeding events is not well understood. IMBRUVICA may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and patients should be monitored for signs of bleeding. Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre- and postsurgery depending upon the type of surgery and the risk of bleeding.

Infections – Fatal and nonfatal infections have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 14% to 26% of patients. Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients treated with IMBRUVICA. Evaluate patients for fever and infections and treat appropriately.

Cytopenias – Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 19% to 29%), thrombocytopenia (range, 5% to 17%), and anemia (range, 0% to 9%) occurred in patients treated with IMBRUVICA. Monitor complete blood counts monthly.

Atrial Fibrillation – Atrial fibrillation and atrial flutter (range, 6% to 9%) have occurred in patients treated with IMBRUVICA, particularly in patients with cardiac risk factors, hypertension, acute infections, and a previous history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms (eg, palpitations, lightheadedness) or new-onset dyspnea should have an ECG performed. Atrial fibrillation should be managed appropriately and if it persists, consider the risks and benefits of IMBRUVICA treatment and dose modification.

Hypertension – Hypertension (range, 6% to 17%) has occurred in patients treated with IMBRUVICA with a median time to onset of 4.5 months (range, 0.03 to 18.40 months). Monitor patients for new-onset hypertension or hypertension that is not adequately controlled after starting IMBRUVICA. Adjust existing antihypertensive medications and/or initiate antihypertensive treatment as appropriate.

Second Primary Malignancies – Other malignancies (range, 5% to 16%) including non-skin carcinomas (range, 1% to 4%) have occurred in patients treated with IMBRUVICA. The most frequent second primary malignancy was non-melanoma skin cancer (range, 4% to 13%).

Tumor Lysis Syndrome – Tumor lysis syndrome has been infrequently reported with IMBRUVICA therapy. Assess the baseline risk (eg, high tumor burden) and take appropriate precautions. Monitor patients closely and treat as appropriate.

Embryo-Fetal Toxicity – Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Advise women to avoid becoming pregnant while taking IMBRUVICA and for 1 month after cessation of therapy. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

ADVERSE REACTIONS
The most common adverse reactions (?20%) in patients with B-cell malignancies (MCL, CLL, WM) were thrombocytopenia* (57%, 53%, 43%), diarrhea (51%, 48%, 37%), anemia* (41%, 37%, 13%), neutropenia* (47%, 46%, 44%), musculoskeletal pain (37%, 32%†, NA‡), fatigue (41%, 29%, 21%), bruising (30%, 25%†, 16%†), nausea (31%, 24%, 21%), rash (25%, 23%†, 22%†), and upper respiratory tract infection (34%, 19%, 19%).

*Based on adverse reactions and/or laboratory measurements (noted as platelets, neutrophils, or hemoglobin decreased).
†Includes multiple ADR terms.
‡Not applicable; no associated ADRs.

The most common Grade 3 or 4 non-hematologic adverse reactions (?5%) in MCL patients were pneumonia (7%), abdominal pain (5%), atrial fibrillation (5%), diarrhea (5%), fatigue (5%), and skin infections (5%).

Approximately 4% (CLL), 14% (MCL), and 11% (WM) of patients had a dose reduction due to adverse reactions.

Approximately 4%-10% (CLL), 9% (MCL), and 6% (WM) of patients discontinued due to adverse reactions. Most frequent adverse reactions leading to discontinuation were pneumonia, subdural hematomas, and atrial fibrillation (1% each) in CLL patients and subdural hematoma (1.8%) in MCL patients.

DRUG INTERACTIONS

CYP3A Inhibitors – Avoid coadministration with strong and moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA dose.

CYP3A Inducers – Avoid coadministration with strong CYP3A inducers.

SPECIFIC POPULATIONS

Hepatic Impairment – Avoid use in patients with moderate or severe baseline hepatic impairment. In patients with mild impairment, reduce IMBRUVICA dose.

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