On May 7, 2019 Genomic Health, Inc. (NASDAQ: GHDX) reported financial results and business progress for the quarter ended March 31, 2019 (Press release, Genomic Health, MAY 7, 2019, View Source [SID1234535864]).

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"In the first quarter of 2019, we delivered more than 17 percent overall revenue growth and $13.0 million in profit driven by significant growth across all key product areas," said Kim Popovits, chairman of the board, chief executive officer and president of Genomic Health. "Our first quarter performance was very strong, based in part on the impact of the landmark TAILORx trial results, which are continuing to drive increased Oncotype DX Breast Recurrence Score test usage both in the United States and globally. We expect to achieve double-digit revenue growth for the year with continued growth across key products and look forward to the national reimbursement decision in Germany for the Oncotype DX breast cancer test."

First Quarter Financial Results

Total revenue for the first quarter of 2019 was $108.8 million, compared with $92.6 million for the first quarter of 2018, an increase of 17.4 percent, and an increase of 18.0 percent on a non-GAAP constant currency basis. U.S. product revenue was $91.0 million for the first quarter of 2019, compared with $78.9 million for the first quarter of 2018, an increase of 15.4 percent.

Revenue delivered across key product areas was as follows:

U.S. invasive breast revenue from Oncotype DX Breast Recurrence Score tests was $79.8 million for the first quarter of 2019, compared with $71.0 million for the first quarter of 2018, an increase of 12.5 percent.
U.S. prostate test revenue from Oncotype DX Genomic Prostate Score (GPS) tests was $8.5 million for the first quarter of 2019, compared with $5.8 million for the first quarter of 2018, an increase of 46.6 percent.
International product revenue for the first quarter of 2019 was $17.8 million, compared with $13.8 million for the first quarter of 2018, an increase of 29.0 percent, and an increase of 32.9 percent on a non-GAAP constant currency basis.
Net income was $13.0 million, or $0.35 and $0.34 per share on a basic and diluted basis, respectively, for the first quarter of 2019, an improvement of $16.8 million, compared with a net loss of $3.8 million, or $0.11 per share on a basic and diluted basis, for the first quarter of 2018. Operating income was $11.5 million for the first quarter of 2019, an improvement of $15.9 million, compared with an operating loss of $4.4 million for the first quarter of 2018.

More than 37,580 Oncotype test results were delivered in the first quarter of 2019, an increase of 15.9 percent, compared with more than 32,440 test results delivered in the same period in 2018. Tests delivered across key product areas was as follows:

Oncotype DX Breast Recurrence Score tests delivered in the U.S. grew 9.4 percent in the first quarter of 2019, compared with the same period in 2018.
Oncotype DX Genomic Prostate Score tests delivered in the U.S. grew 24.5 percent in the first quarter of 2019, compared with the same period in 2018.
Oncotype DX international tests delivered grew 28.1 percent in the first quarter of 2019, compared with the same period in 2018 and represented approximately 25 percent of total test volume in the first quarter of 2019.
Recent Business Highlights

Presented results from five studies at the 16th St. Gallen International Breast Cancer Conference, including real-world evidence that reinforces the treatment paradigm established by the TAILORx trial. Additionally, two decision impact studies from the UK and the Czech Republic highlighted the value of Oncotype DX in personalizing and improving the quality of clinical decisions in patients with early-stage breast cancer, including those with node positive disease .
Multiple private insurers established new coverage for the Oncotype DX Genomic Prostate Score test, bringing the total number of U.S. covered lives to more than 114 million, including Medicare.
First private insurer established reimbursement for the Oncotype DX AR-V7 Nucleus Detect test, bringing the total number of U.S. covered lives to more than 61 million, including Medicare.
The National Comprehensive Cancer Network (NCCN) strengthened its prostate cancer guidelines, recommending the consideration of AR-V7 testing in metastatic castrate resistant prostate cancer (mCRPC) patients following abiraterone/enzalutamide to help guide the selection of further therapy.
Conference Call Details
To access the live conference call today, May 7, 2019, at 4:30 p.m. Eastern Time via phone, please dial (877) 303-7208 from the United States and Canada, or +1 (224) 357-2389 internationally. The conference call ID is 6535029. Please dial in approximately 10 minutes prior to the start of the call. To access the live and subsequently archived webcast of the conference call, go to the Investor Relations section of the company’s website at View Source Please connect to the website at least 15 minutes prior to the presentation to allow for any software download that may be necessary.

On May 7, 2019 Aptose Biosciences Inc. ("Aptose" or the "Company") (NASDAQ: APTO, TSX: APS), a clinical-stage company developing highly differentiated therapeutics that target the underlying mechanisms of cancer, reported financial results for the three months ended March 31, 2019 and reported on corporate developments (Press release, Aptose Biosciences, MAY 7, 2019, View Source [SID1234535816]).

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The net loss for the quarter ended March 31, 2019 was $5.5 million ($0.14 per share) compared with $6.8 million ($0.23 per share) for the quarter ended March 31, 2018. Total cash and cash equivalents and investments as of March 31, 2019 were $17.0 million. Based on current operations, cash on hand and available sources of capital provide the Company with sufficient resources to fund research and development and operations into 1H 2020.

"With the FDA allowance of our IND for CG-806, our oral, first-in-class pan-FLT3/pan-BTK inhibitor, we entered the second quarter advancing two separate clinical programs with two well-differentiated, small molecule targeted agents for the treatment of patients with hematologic malignancies," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "I’m most pleased to announce that we have eleven clinical sites committed to our Phase 1 clinical trial with CG-806 and that we expect to dose our first patient soon. In preclinical studies, CG-806 demonstrated the ability to potently inhibit all wild type and mutant forms of BTK and FLT3 driver kinases and to suppress additional oncogenic signaling pathways upon which cancer cells rely for survival, yet with a precision that avoids targets typically associated with toxicity. In those studies, CG-806 has repeatedly shown superiority to other approved and development stage BTK inhbitors and FLT3 inhibitors. In addition,CG-806 demonstrated safety and tumor elimination in animal models of cancer. Our second compound, APTO-253, is the only clinical-stage molecule shown to directly inhibit expression of the MYC oncogene in a patient with acute myeloid leukemia (AML), without the myelosuppression common to many MYC targeting approaches. Both CG-806 and APTO-253 are investigational products that address unmet needs and substantial market opportunities in hematology."

Key Corporate Highlights

Phase 1 a/b CG-806 Clinical Trial – In March 2019, Aptose announced regulatory allowance from the U.S. Food and Drug Administration (FDA) to initiate a Phase 1 a/b clinical trial program with CG-806, an oral, first-in-class small molecule inhibitor of all known forms of FLT3 and BTK kinases. CG-806 is being developed for the treatment of patients with select hematologic malignancies, including CLL/SLL and non-Hodgkin’s lymphomas (NHL), as well as for patients with relapsed/refractory AML and MDS. The IND allows for immediate testing of CG-806 in patients with certain relapsed or refractory B-cell malignancies, including CLL/SLL and NHL having wild type or C481S mutated forms of the BTK kinase. The first patient will receive 150 mg of oral CG-806 every 12 hours for 28 days. The second patient is planned to receive 300 mg every 12 hours for 28 days, and we anticipate six dose levels during the dose escalation phase of the study. Following identification of the recommended phase 2 dose, we plan to perform four separate expansion trials with up to 25 patients each from four different groups of B-cell malignancy patients. All of these patients will be assessed for safety, tolerance, PK, and a host of biomarkers and scans. Such analyses will characterize the safety and efficacy of CG-806 in this population of patients with B-cell malignancies. In addition, these analyses will inform the dose related plasma exposure levels of CG-806. Once a dose level achieves plasma concentrations that we believe will be therapeutic for AML patients, we plan to present the findings to the FDA and seek to initiate a separate Phase 1 trial for patients with AML and MDS. This strategy avoids treating the acutely ill AML patients to potentially non-efficacious doses and increases the likelihood that responses could be achieved rapidly in the AML/MDS patient population.

Phase 1b Clinical Study of APTO-253 | Favorable Tolerability and Inhibition of MYC Gene Expression in First Patient at Lowest Dose Level | Dosing Begins in Second Patient – Aptose previously announced that dosing had begun in the APTO-253 clinical trial in patients with relapsed or refractory hematologic malignancies. APTO-253 is the only known clinical-stage molecule that can directly inhibit expression of the MYC oncogene, shown to reprogram survival signaling pathways and contribute to drug resistance in many malignancies, including acute AML. The first patient in the trial tolerated the lowest dose of 20 mg/m2 of APTO-253 favorably. In addition, a reduction in MYC gene expression was observed, as well as the induction of p21, an indication of cell cycle arrest and apoptosis, and consistent with target engagement. Dosing of an MDS patient at the second dose level (40 mg/m2 APTO-253) has been initiated, and only one patient will be required at this dose level if no safety issues are observed. APTO-253 is being administered once weekly, over a 28-day cycle, and the study is expected to enroll up to 20 patients with relapsed or refractory AML and high-risk MDS patients. The study is designed to then transition to single-agent expansion cohorts in AML and MDS, followed by combination studies.

New Preclinical Data at AACR (Free AACR Whitepaper) – New preclinical data on CG-806 and APTO-253 were presented in separate poster presentations at the 2019 AACR (Free AACR Whitepaper) Annual Meeting in April. In studies that were conducted in collaboration with the Beat AML Initiative, CG-806 demonstrated significant potency across sub-groups of AML cells, and superior potency when compared to other FLT3 inhibitors, including midostaurin, sorafenib, sunitinib, dovitinib, quizartinib, crenolanib and gilteritinib. Sensitivity of patient cells with IDH1 R132 mutations was an unexpected finding. Additionally, in 28-day GLP toxicity and toxicokinetic studies, CG-806 continued to demonstrate a favorable safety profile. The poster highlights results of combination studies with CG-806 and venetoclax, which demonstrated enhanced killing of primary cancer cells from patients with AML and B-cell cancers. Researchers also presented in vitro studies of APTO-253 focused on its mechanism of action that involves targeting the MYC oncogene. Both AACR (Free AACR Whitepaper) posters are available on the Aptose website.

New $20MM Common Share Purchase Agreement with Aspire Capital Fund, LLC Replaces Prior Agreement – Aptose entered into a new Common Share Purchase Agreement (the "Agreement") with Aspire Capital Fund, LLC ("Aspire Capital") where Aspire Capital has committed to purchase up to $20MM of common shares of Aptose, at Aptose’s request from time to time, for up to 30 months. This Agreement replaces the agreement that Aptose entered into with Aspire Capital on May 30, 2018, which has been terminated by the parties. The Agreement is subject to approval by the Toronto Stock Exchange ("TSX") and NASDAQ, limits the amount of Aptose’s common shares that Aspire can own at one time to 9.99% of the issued and outstanding common shares of the Company, and limits the maximum number of common shares that can be issued under the Agreement to 19.99% of the Company’s outstanding common shares on the date of the Agreement unless shareholder approval is obtained or the shares issued to date once the 19.99% threshold is reached have an average purchase price equal to or exceeding $2.10.

Under the Agreement, no common shares will be sold on the TSX or on other trading markets in Canada. For the purpose of TSX approval, the Company intends to rely on the exemption set forth in Section 602.1 of the TSX Company Manual, which provides that the TSX will not apply its standards to certain transactions involving eligible interlisted issuers on a recognized exchange, such as NASDAQ, provided that the transaction is being completed in compliance with the requirements of such other recognized exchange.

Upon receipt of the TSX and NASDAQ approval, as consideration for Aspire Capital’s obligation under the Agreement, Aptose will issue 171,428 common shares to Aspire Capital as a commitment fee.

Under the terms of the Agreement:
Aptose will control the timing and amount of the sale of common shares to Aspire Capital.
On any business day, Aptose shall have the right to direct Aspire Capital to purchase up to 200,000 common shares with a value not exceeding $500,000. However, upon mutual agreement, Aptose can direct Aspire Capital to purchase up to an additional 2,000,000 common shares.
The purchase price shall be equal to the lesser of: (i) the lowest sale price of the common shares on NASDAQ on the purchase date, or (ii) the average of the three lowest closing sale prices of the common shares on NASDAQ during the 10 business days prior to the purchase date.
In addition to the regular purchases, Aptose shall also have the right to require Aspire Capital to purchase up to an additional 30% of the trading volume of the common shares for the next business day at a purchase price (the "VWAP Purchase Price") equal to the lesser of: (i) the closing price of the common shares on NASDAQ on the VWAP purchase date, or (ii) ninety-seven percent (97%) of the VWAP purchase date’s volume weighted average price on NASDAQ (each such purchase, a "VWAP Purchase").
Aptose shall have the right, in its sole discretion, to determine a maximum number of common shares and set a minimum market price threshold for each VWAP Purchase and there are no limits on the number of VWAP purchases that Aptose may require.
For any business day that the closing sale price of the common shares on NASDAQ is below $0.25, the obligation of Aspire Capital to purchase common shares shall be automatically suspended for that business day only.

Research and development expenses of $3.3 million for the three-month period ended March 31, 2019 were comparable with $3.1 million for the comparative period. Changes to the components of our research and development expenses presented in the table above are primarily as a result of the following events:

In the three-month period ended March 31, 2019, program costs for our CG-806 consisted mostly of costs to complete the preclinical studies and prepare regulatory filings in support of an IND filing, and the manufacturing of drug product for the Phase 1clinical trial. In the comparative period, expenses reflected the completion of two dose range finding studies and the manufacturing of a batch of the drug substance to be used in toxicity studies.
In the three-month period ended March 31, 2019, program costs for our APTO-253 program consisted mostly of costs related to the Phase 1b clinical trial, and manufacturing costs for a second GMP batch of APTO-253. In the comparative period, the Company completed production of a GMP batch of drug product, and initiated necessary studies to present to the FDA in support of removing the clinical hold.
An increase in personnel expenses mostly related to additional clinical research staff to support two Phase 1 clinical trials.
A decrease in stock option compensation related mostly to stock options granted in the three-month period ended March 31, 2018, of which 100,000 with a grant date fair value of $2.03 vested immediately, contributing to higher expenses in that period.

General and administrative expenses of $2.3 million for the three-month period ended March 31, 2019 decreased by approximately $1.4 million compared with $3.7 million for the comparative period, primarily as a result of the following:

General and administrative expenses, excluding non-cash items, decreased by approximately $138.0 thousand, primarily as a result of higher professional and regulatory fees in support of financing activities in the three months ended March 31, 2018, and offset by higher travel, rent and salaries expense in the current period, in support of increased activities in the business.
Stock-based compensation decreased by approximately $1.3 million in the three months ended March 31, 2019, compared with the three months ended March 31, 2018 mostly related to approximately 1,059,000 stock options granted to directors, executive officers and general and administrative employees in the three-month period ended March 31, 2018, of which 750,000 with a grant date fair value of $2.03 vested immediately. In the current period, 1,024,000 stock options were granted to directors, executive officers and general and administrative employees with a grant date fair value of $1.29. Stock options granted by the Company during the three months ended March 31, 2019, vest over four years, except for 335,000 options which vest after one year.
Conference Call and Webcast

Aptose will host a conference call to discuss results for the year and three months ended March 31, 2019 today, Tuesday, May 7, 2019 at 5:00 PM ET. Participants can access the conference call by dialing 1-844- 882-7834 (North American toll free number) and 1-574-990-9707 (International) and using conference ID # 4879249. The conference call can be accessed here and will also be available through a link on the Investor Relations section of Aptose’s website at View Source An archived version of the webcast along with a transcript will be available on the Company’s website for 30 days. An audio replay of the webcast will be available approximately two hours after the conclusion of the call for seven days by dialing 1-855-859-2056, using the conference ID # 4879249.

The press release, the financial statements and the management’s discussion and analysis for the quarter ended March 31, 2019 will be available on SEDAR at www.sedar.com and EDGAR at www.sec.gov/edgar.shtml.

On May 7, 2019 Pfizer Inc. (NYSE: PFE) reported that the European Commission (EC) granted conditional marketing authorization for LORVIQUA (lorlatinib, available in the U.S., Canada and Japan under the brand name LORBRENA), as a monotherapy for the treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer (NSCLC) whose disease has progressed after alectinib or ceritinib as the first ALK tyrosine kinase inhibitor (TKI) therapy, or crizotinib and at least one other ALK TKI (Press release, Pfizer, MAY 7, 2019, View Source [SID1234535832]). LORVIQUA is a third-generation ALK TKI that was specifically developed to penetrate the blood brain barrier, in the presence or absence of resistance mutations.

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"Pfizer has worked to pioneer biomarker-driven medicine for patients with ALK-positive non-small cell lung cancer and we continue to advance patient care with the approval of LORVIQUA," said Andreas Penk, M.D., regional president, Oncology International Developed Markets at Pfizer. "We are proud that LORVIQUA is our second lung cancer medication approved in Europe within two months and our third biomarker-driven medicine for lung cancer. We look forward to making LORVIQUA available for European patients with ALK-positive non-small cell lung cancer who have progressed on prior therapy with a second generation ALK medicine."

The conditional marketing authorization was based on results from a non-randomized, dose-ranging and activity-estimating, multi-cohort, multi-center Phase 1/2 study, B7461001, evaluating LORVIQUA for the treatment of patients with ALK-positive advanced NSCLC, who were previously treated with one or more ALK TKIs. A total of 139 patients with ALK-positive metastatic NSCLC after treatment with at least one second-generation ALK TKI, such as alectinib, brigatinib or ceritinib, were enrolled in the Phase 2 portion of the study. Among these patients, the overall response rate (ORR) for those who have been treated with one prior ALK TKI (N=28) was 42.9% (95% CI: 24.5, 62.8) and 39.6% (95% CI: 30.5, 49.4) for those with two or more prior ALK TKI treatments (N=111). In the trial, 67% of patients had a history of brain metastases.

"Over the last decade, our understanding of ALK-positive non-small cell lung cancer has advanced dramatically, leading to multiple medications for patients. However, the common challenges associated with treating the disease, including resistance and brain metastases have created an urgent need for additional treatment options," said Enriqueta Felip, M.D., Ph.D., Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology in Spain. "The LORVIQUA approval marks an exciting time in lung cancer innovation and I look forward to using this next-generation ALK inhibitor to treat my patients."

Among 295 ALK-positive or ROS1-positive metastatic NSCLC patients who received LORVIQUA 100 mg once daily in study B7461001, the most common (≥ 20%) adverse reactions were hypercholesterolemia (84.4%), hypertriglyceridemia (67.1%), edema (54.6%), peripheral neuropathy (47.8%), cognitive effects (28.8%), fatigue (28.1%), weight increased (26.4%), arthralgia (24.7%), mood effects (22.7%) and diarrhea (22.7%).

Conditional approval is granted to a medicinal product that fulfils an unmet medical need, where the benefit-risk balance is positive and the benefit of the product’s immediate availability outweighs the risk of less comprehensive data than normally required.1 Under the provisions of the conditional approval, Pfizer will provide additional data from the post-marketing studies, including the Phase 3 CROWN study of LORVIQUA versus crizotinib in the first-line treatment of patients with ALK-positive NSCLC, which is currently ongoing.

About LORVIQUA (lorlatinib)

LORVIQUA is a TKI that has been shown to be highly active in preclinical lung cancer models harboring chromosomal rearrangements of ALK. LORVIQUA was specifically developed to inhibit tumor mutations that drive resistance to other ALK inhibitors and to penetrate the blood brain barrier. LORVIQUA is approved in the EU as monotherapy for the treatment of adult patients with ALK-positive advanced NSCLC whose disease has progressed after:

alectinib or ceritinib as the first ALK TKI therapy; or
crizotinib and at least one other ALK TKI.
LORVIQUA is also approved:

Under the brand name LORBRENA in Japan for the treatment of ALK fusion gene-positive unresectable advanced and/or recurrent NSCLC with resistance or intolerance to ALK tyrosine kinase inhibitor(s).
Under the brand name LORBRENA in Canada, where it is conditionally approved as monotherapy for the treatment of adult patients with ALK-positive metastatic NSCLC who have progressed on: crizotinib and at least one other ALK inhibitor, or patients who have progressed on ceritinib or alectinib.
Under the brand name LORBRENA in the U.S. for the treatment of patients with ALK-positive metastatic NSCLC whose disease has progressed on:
crizotinib and at least one other ALK inhibitor for metastatic disease; or
alectinib as the first ALK inhibitor therapy for metastatic disease; or
ceritinib as the first ALK inhibitor therapy for metastatic disease.
The U.S. indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

LORBRENA (lorlatinib) IMPORTANT SAFETY INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

Contraindications: LORBRENA is contraindicated in patients taking strong CYP3A inducers, due to the potential for serious hepatotoxicity.

Risk of Serious Hepatotoxicity with Concomitant Use of Strong CYP3A Inducers: Severe hepatotoxicity occurred in 10 of 12 healthy subjects receiving a single dose of LORBRENA with multiple daily doses of rifampin, a strong CYP3A inducer. Grade 4 ALT or AST elevations occurred in 50% of subjects, Grade 3 in 33% of subjects, and Grade 2 in 8% of subjects. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to initiating LORBRENA. Avoid concomitant use of LORBRENA with moderate CYP3A inducers. If concomitant use of moderate CYP3A inducers cannot be avoided, monitor AST, ALT, and bilirubin 48 hours after initiating LORBRENA and at least 3 times during the first week after initiating LORBRENA. Depending upon the relative importance of each drug, discontinue LORBRENA or the CYP3A inducer for persistent Grade 2 or higher hepatotoxicity.

Central Nervous System (CNS) Effects: A broad spectrum of CNS effects can occur. These include seizures, hallucinations, and changes in cognitive function, mood (including suicidal ideation), speech, mental status, and sleep. Withhold and resume at the same or reduced dose or permanently discontinue based on severity.

Hyperlipidemia: Increases in serum cholesterol and triglycerides can occur. Grade 3 or 4 elevations in total cholesterol occurred in 17% and Grade 3 or 4 elevations in triglycerides occurred in 17% of the 332 patients who received LORBRENA. Eighty percent of patients required initiation of lipid-lowering medications, with a median time to onset of start of such medications of 21 days. Initiate or increase the dose of lipid-lowering agents in patients with hyperlipidemia. Monitor serum cholesterol and triglycerides before initiating LORBRENA, 1 and 2 months after initiating LORBRENA, and periodically thereafter. Withhold and resume at same dose for the first occurrence; resume at same or reduced dose of LORBRENA for recurrence based on severity.

Atrioventricular (AV) Block: PR interval prolongation and AV block can occur. In 295 patients who received LORBRENA at a dose of 100 mg orally once daily and who had a baseline electrocardiography (ECG), 1% experienced AV block and 0.3% experienced Grade 3 AV block and underwent pacemaker placement. Monitor ECG prior to initiating LORBRENA and periodically thereafter. Withhold and resume at reduced or same dose in patients who undergo pacemaker placement. Permanently discontinue for recurrence in patients without a pacemaker.

Interstitial Lung Disease (ILD)/Pneumonitis: Severe or life-threatening pulmonary adverse reactions consistent with ILD/pneumonitis can occur. ILD/pneumonitis occurred in 1.5% of patients, including Grade 3 or 4 ILD/pneumonitis in 1.2% of patients. Promptly investigate for ILD/pneumonitis in any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis. Immediately withhold LORBRENA in patients with suspected ILD/pneumonitis. Permanently discontinue LORBRENA for treatment-related ILD/pneumonitis of any severity.

Embryo-fetal Toxicity: LORBRENA can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use an effective non-hormonal method of contraception, since LORBRENA can render hormonal contraceptives ineffective, during treatment with LORBRENA and for at least 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with LORBRENA and for 3 months after the final dose.

Adverse Reactions: Serious adverse reactions occurred in 32% of the 295 patients; the most frequently reported serious adverse reactions were pneumonia (3.4%), dyspnea (2.7%), pyrexia (2%), mental status changes (1.4%), and respiratory failure (1.4%). Fatal adverse reactions occurred in 2.7% of patients and included pneumonia (0.7%), myocardial infarction (0.7%), acute pulmonary edema (0.3%), embolism (0.3%), peripheral artery occlusion (0.3%), and respiratory distress (0.3%). The most common (≥20%) adverse reactions were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea; the most common (≥20%) laboratory abnormalities were hypercholesterolemia, hypertriglyceridemia, anemia, hyperglycemia, increased AST, hypoalbuminemia, increased ALT, increased lipase, and increased alkaline phosphatase.

Drug Interactions: LORBRENA is contraindicated in patients taking strong CYP3A inducers. Avoid concomitant use with moderate CYP3A inducers and strong CYP3A inhibitors. If concomitant use of moderate CYP3A inducers cannot be avoided, monitor ALT, AST, and bilirubin as recommended. If concomitant use with a strong CYP3A inhibitor cannot be avoided, reduce the LORBRENA dose as recommended. Concomitant use of LORBRENA decreases the concentration of CYP3A substrates.

Lactation: Because of the potential for serious adverse reactions in breastfed infants, instruct women not to breastfeed during treatment with LORBRENA and for 7 days after the final dose.

Hepatic Impairment: No dose adjustment is recommended for patients with mild hepatic impairment. The recommended dose of LORBRENA has not been established for patients with moderate or severe hepatic impairment.

Renal Impairment: No dose adjustment is recommended for patients with mild or moderate renal impairment. The recommended dose of LORBRENA has not been established for patients with severe renal impairment.

Please see full prescribing information for LORBRENA in the U.S. here.

About Non-Small Cell Lung Cancer

Lung cancer is the most common cancer worldwide, with more than two million new cases diagnosed globally in 2018.2 About 85 percent of all lung cancers are identified as non-small cell, and approximately 75 percent of these are metastatic, or advanced, at diagnosis.3

ALK gene rearrangement is a genetic alteration that drives the development of lung cancer in some patients.4,5 Epidemiology studies suggest that approximately three to five percent of NSCLC tumors are ALK-positive.6

About Pfizer in Lung Cancer

Pfizer Oncology is committed to addressing the unmet needs of patients with lung cancer, the leading cause of cancer-related deaths worldwide and a particularly difficult-to-treat disease. Pfizer strives to address the diverse and evolving needs of patients with non-small cell lung cancer (NSCLC) by developing efficacious and tolerable therapies, including biomarker-driven therapies and immuno-oncology (IO) agents and combinations. By combining leading scientific insights with a patient-centric approach, Pfizer is continually advancing its work to match the right patient with the right medicine at the right time. Through our growing research pipeline and collaboration efforts, we are committed to delivering renewed hope to patients living with NSCLC.

On May 7, 2019 Premier Inc. (NASDAQ: PINC) reported financial results for the fiscal 2019 third quarter ended March 31, 2019 (Press release, Premier, MAY 7, 2019, View Source [SID1234535849]).

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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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The company adopted new revenue recognition standard ASC 606 on July 1, 2018, in conjunction with the beginning of fiscal 2019, using the modified retrospective approach and did not restate prior periods. Therefore, fiscal 2019 results of operations under the new revenue standard ASC 606 are compared with fiscal 2018 results under the previous revenue standard ASC 605 in the body of this press release, and the comparisons are not necessarily meaningful. However, solely for informational purposes, current period results under the previous standard are included in the tables at the back of this press release.

Q3 2019 Highlights:

GAAP net revenue was $422.9 million, compared with $425.3 million a year ago; Supply Chain Services segment revenue was $330.2 million, compared with $330.7 million a year ago; and Performance Services segment revenue was $92.6 million, compared with $94.6 million a year ago.
GAAP net income was $73.8 million, compared with $76.5 million a year ago, and diluted net income was $0.48 per share, compared with a loss of $1.93 per share a year ago.
Non-GAAP adjusted EBITDA* was $137.6 million, compared with $142.2 million a year ago.
Non-GAAP adjusted fully distributed net income* was $84.7 million, or $0.66 per diluted share, compared with $90.6 million, or $0.67 per diluted share a year ago.
Nine-month results demonstrate financial performance remains on track with existing guidance ranges for the full fiscal year, with net administrative fees up 4% from a year ago, supply chain services and performance services revenue up 1% and 3%, respectively, non-GAAP adjusted EBITDA up 6% and non-GAAP adjusted fully distributed earnings per share up 22%.
For full fiscal-year, Supply Chain Services revenue projected to perform near midpoint of existing range, Performance Services segment revenue near higher end of the range, non-GAAP adjusted EBITDA near lower end of the range, and non-GAAP adjusted fully distributed earnings per share near midpoint of the range.
Outlook raised for full fiscal-year non-GAAP free cash flow, which is now expected to exceed 55% of non-GAAP adjusted EBITDA for the full fiscal year.
On April 26, 2019, Premier’s board of directors authorized an additional $300.0 million for the potential repurchase of Class A stock, following the completion of the previous $250.0 million repurchase program during the fiscal third quarter.
* Descriptions of non-GAAP financial measures are provided in "Use and Definition of Non-GAAP Financial Measures," and reconciliations are provided in the tables at the end of this release.

"Our fiscal third-quarter results reflect the timing-related impact of revenue recognition under the new ASC 606 revenue standard, continuing headwinds in our products business, and, to a lesser extent, incremental investments in future growth opportunities that we believe will enhance our core capabilities across the supply chain, enterprise analytics and performance improvement businesses," said Susan DeVore, chief executive officer. "While our results are consistent with our expectation that the second half of our fiscal year would be less profitable than the first half, we remain on track to deliver full fiscal-year 2019 results within our previously disclosed guidance ranges.

"We are actively managing Premier’s portfolio, as underscored by our decision to exit the specialty pharmacy business, and focusing on our core capabilities to deliver best-in-class solutions for our member health systems and sustainable, long-term value creation for stockholders," DeVore continued. "The company’s flexible balance sheet and strong cash flow provide a solid foundation and support our balanced approach to pursuing both organic and external growth opportunities while returning capital to stockholders. The board’s decision to authorize a new $300.0 million stock repurchase program underscores its continued confidence in our strategy."

On May 7, 2019 Rigel Pharmaceuticals, Inc. (Nasdaq:RIGL), reported financial results for the first quarter ended March 31, 2019, including sales of TAVALISSE (fostamatinib disodium hexahydrate), for the treatment of thrombocytopenia in adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment (Press release, Rigel, MAY 7, 2019, View Source [SID1234535865]).

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"Since the U.S. launch of TAVALISSE one year ago, a growing number of physicians are utilizing our product in earlier lines of therapy and with an increasing number of their chronic ITP patients," stated Raul Rodriguez, president and CEO. "Internationally, the recent collaboration with Grifols in Europe enhances our potential access to a majority of the ex-U.S. ITP market. Meanwhile, our pipeline is expanding with the initiation of our Phase 3 trial in warm autoimmune hemolytic anemia and additional ongoing clinical and research projects."

Financial Update

For the first quarter of 2019, Rigel reported a net loss of $17.6 million, or $0.11 per share, compared to a net loss of $24.4 million, or $0.17 per share, in the same period of 2018.

For the first quarter of 2019, Rigel reported total revenues of $12.6 million, consisting of $8.1 million in net product sales of TAVALISSE and $4.6 million in contract revenues from collaborations. The increase in net product sales of TAVALISSE reflects the continuing growth of its business since commercial launch in May 2018. There were no net product sales nor contract revenues from collaborations in the first quarter of 2018.

Contract revenues from collaborations of $4.6 million during the three months ended March 31, 2019 primarily related to a portion of the $30.0 million upfront fee recognized as revenue upon delivery of license rights to Grifols, S.A. and Rigel’s performance of certain research and development services. There were no contract revenues from collaborations during the three months ended March 31, 2018.

Rigel reported total costs and expenses of $31.0 million in the first quarter of 2019, compared to $24.7 million for the same period in 2018. The increase in costs and expense was primarily due to the increases in personnel costs, including its customer-facing and medical affairs teams, and third-party costs to support Rigel’s commercialization of TAVALISSE.

As of March 31, 2019, Rigel had cash, cash equivalents and short-term investments of $127.9 million, compared to $128.5 million as of December 31, 2018.

Business Update

Rigel’s launch of TAVALISSE in the U.S. continued to build upon its early success with growth driven by expansion of the prescriber base, steady use of the product as an early treatment option in steroid refractory patients, physicians prescribing to an increased number of patients, and strong reimbursement from the payer community.
Rigel advanced the regulatory review of fostamatinib in chronic ITP by responding to day-120 questions from the European Medicines Agency (EMA) and remains on track for potential approval in the EU by the end of 2019.
In January, Rigel entered into a collaboration with Grifols, S.A. for the rights to fostamatinib in all indications in Europe and Turkey enabling a commercial launch preparation well ahead of the anticipated approval date.
Kissei Pharmaceuticals, Rigel’s collaborator in Japan, has initiated discussions with the Pharmaceuticals and Medical Devices Agency (PMDA) to define a path towards fostamatinib approval in Japan.
In warm AIHA, Rigel opened clinical trial sites for its pivotal Phase 3 clinical study of fostamatinib. The clinical trial protocol calls for approximately 80 patients in a 24-week study with enrollment of the first patient expected this month. Topline trial results are projected in early 2021, positioning fostamatinib to potentially be the first FDA-approved treatment for this indication.
The company’s research and development team continues to investigate potential molecules that modulate the immune system, including R835, Rigel’s IRAK 1/4 inhibitor currently in Phase 1 development. In addition, Rigel has four partnered programs that are in Phase 1 and 2 of their clinical development and continue to advance.
About ITP
In patients with ITP, the immune system attacks and destroys the body’s own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP are excessive bruising and bleeding. People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. Current therapies for ITP include steroids, blood platelet production boosters (TPOs) and splenectomy. However, not all patients are adequately treated with existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP.

About AIHA
AIHA is a rare, serious blood disorder in which the immune system produces antibodies that result in the destruction of the body’s own red blood cells. AIHA affects approximately 40,000 adult patients in the U.S. and can be a severe, debilitating disease. To date, there are no disease-targeted therapies approved for AIHA, despite the unmet medical need that exists for these patients.

About R8351
The investigational candidate, R835, is an orally available, potent and selective inhibitor of IRAK1 and IRAK4 that has been shown preclinically to block inflammatory cytokine production in response to toll-like receptor (TLR) and the interleukin-1 (IL-1R) family receptor signaling. TLRs and IL-1Rs play a critical role in the innate immune response and dysregulation of these pathways can lead to a variety of inflammatory conditions. R835 is active in multiple rodent models of inflammatory disease including psoriasis, arthritis, lupus, multiple sclerosis and gout. The safety and efficacy of R835 has not been established by the FDA or any healthcare authority.

Conference Call and Webcast with Slides Today at 4:30PM Eastern Time
Rigel will hold a live conference call and webcast today at 4:30pm Eastern Time (1:30pm Pacific Time).

Participants can access the live conference call by dialing 855-892-1489 (domestic) or 720-634-2939 (international) and using the Conference ID number 3999559. The webcast, with slide presentation, can be accessed from Rigel’s website at www.rigel.com. The webcast will be archived and available for replay after the call via the Rigel website.

About TAVALISSE
Indication
TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Important Safety Information
Warnings and Precautions

Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required.
Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to >3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation.
Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE.
Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation.
TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose.
Drug Interactions

Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose.
It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406.
Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug.
Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (e.g., rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (e.g., digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug.
Adverse Reactions

Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%).
Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.
Please see www.TAVALISSE.com for full Prescribing Information.

To report side effects of prescription drugs to the FDA, visit www.fda.gov/medwatch or call 1-800-FDA-1088 (800-332-1088).