On October 29, 2018 QIAGEN N.V. (NYSE: QGEN; Frankfurt Prime Standard: QIA) reported results of operations for the third quarter and first nine months of 2018, making progress on goals set for 2018 while driving global expansion of its Sample to Insight portfolio of molecular testing solutions covering the continuum from basic research to clinical healthcare (Press release, Qiagen, OCT 29, 2018, View Source [SID1234530426]).

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"QIAGEN’s results for the third quarter of 2018 affirm the solid performance our teams are delivering in an exciting year of growth. We are making great progress on building a unique and differentiated portfolio of Sample to Insight molecular testing solutions across the continuum of customer needs from basic research to clinical healthcare. QIAGEN is well-positioned to achieve the goals set for 2018 and to continue our progress toward the mid-term targets set for 2020," said Peer M. Schatz, Chief Executive Officer of QIAGEN N.V. "

All customer classes and regions supported growth in the third quarter, including 9% growth at constant exchange rates in the Americas region and also 9% CER growth in Molecular Diagnostics. Our QuantiFERON latent TB test grew as planned at a 14% CER pace, and we are on track for our goal of about 20% CER growth for the full year. Growth in revenues from companion diagnostic co-development projects with pharmaceutical companies also supported gains in Molecular Diagnostics, along with high-single-digit CER growth in consumables for our QIAsymphony automation platform. We were also pleased with the Academia and Pharma customer classes maintaining good momentum, supported by the expansion of our offering for customers using next-generation sequencing (NGS) technologies. The distribution agreement with NeuMoDx, announced in September, adds two fully integrated testing platforms that offer the ease of clinical chemistry testing automation to molecular diagnostics laboratories. This agreement for outside the United States is highly synergistic with our portfolio and commercial channels. We are also excited about the footprint we are establishing for the QIAstat-Dx platform in Europe, and the potential of the syndromic testing market, and look forward to expanding the test menu and entering the U.S. in 2019. QIAGEN is emerging with the leading portfolio of new molecular diagnostic platform technologies addressing very large market opportunities: QuantiFERON, QIAstat-Dx, NeuMoDx and GeneReader. We continue to execute on QIAGEN’s strategy as a global leader in the emergence of molecular testing and diagnostics for a new era of breakthroughs driven by genomic insights."

(1) Adjusted figures exclude certain charges as detailed in accompanying reconciliation tables.
(2) Weighted number of diluted shares (Q3 2018: 235.2 m, Q3 2017: 232.7 m) (9M 2018: 233.8 m, 9M 2017: 233.4 m)
(3) Net cash provided by operating activities for 9M 2018 includes $30 million payment for pre-paid royalties for Natera partnership.
CER – Constant exchange rates (Q3 2018 CER sales: $387.7 m) (9M 2018 CER sales: $1,085.5 m) Tables may have rounding differences.
Net sales by product category and customer class

(1) Includes companion diagnostic co-development revenues (Q3 2018: $17 m, +49% CER and 9M 2018: $39 m, +54% CER) and U.S. HPV sales (Q3 2018: $6 m vs. Q3 2017: $8 m and 9M 2018: $15 m vs. 9M 2017: $19 m)
Growth rates at constant exchange rates (CER), sales and sales contributions at actual FX rates. Tables may have rounding differences.
Net sales by geographic region

Growth rates at constant exchange rates (CER), sales and sales contributions at actual FX rates. Tables may have rounding differences.
Third quarter 2018 results

Total net sales grew 3.8% at actual rates to $377.9 million in the third quarter of 2018 over the year-ago period, representing 6.5% growth at constant exchange rates that was reduced by 2.7 percentage points of adverse currency movements against the U.S. dollar. As expected, sales of the QIAstat-Dx system, acquired with STAT-Dx (in April 2018), provided less than one percentage point of incremental CER growth, while the rest of the portfolio provided a solid organic performance, also considering the adverse impact of sales associated with business changes announced in the fourth quarter of 2017 (China portfolio) and the first quarter of 2018 (veterinary assays).

Both consumables and related revenues (+6% CER / 88% of sales) and instruments (+11% CER / 12% of sales) advanced at robust rates. Molecular Diagnostics (+9% CER / 50% of sales) led the performance among the customer classes, supported by ongoing double-digit CER growth for the QuantiFERON-TB test, further expansion in Personalized Healthcare and companion diagnostic co-development agreements, and high-single-digit CER growth in consumables for use on QIAsymphony automation system. The Pharma (+5% CER / 19% of sales) and Academia (+5% CER / 22% of sales) customer classes maintained solid growth rates in light of improving trends in customer funding. Applied Testing (+1% CER / 9% of sales) grew at a mid-single-digit CER pace excluding the impact of the veterinary assays divestment.

Operating income rose to $77.0 million in the third quarter of 2018 from $63.9 million in the same period of 2017. Adjusted operating income – which excludes restructuring and other items such as business integration, acquisition-related costs, litigation costs and the amortization of intangible assets acquired in business combinations – rose 8% to $105.6 million from $97.9 million in the year-ago period. The adjusted operating income margin rose to 27.9% of sales in the quarter compared to 26.9% in the same period of 2017, with results in 2018 helped by an adjusted gross margin of 71.5% and the benefits of recent efficiency initiatives, which offset significant investments in the launch of the QIAstat-Dx system.

Net income was $60.3 million, or $0.26 per diluted share (based on 235.2 million diluted shares) compared to $48.5 million, or $0.21 per diluted share (based on 232.7 million diluted shares) in the third quarter of 2017. Adjusted net income was $81.5 million, or $0.35 per diluted share ($0.36 CER), compared to $75.5 million, or $0.32 per diluted share, in the year-ago period, with an adjusted tax rate of 19.1% in the third quarter of 2018 compared to 19.4% in the same period of 2017.

First nine months 2018 results

Total net sales grew 7.6% at actual rates to $1.1 billion in the first nine months of 2018 over the year-ago period, representing 6.4% growth at constant exchange rates, with 1.2 percentage points of positive currency movements against the U.S. dollar.

Operating income rose to $178.3 million in the first nine months of 2018 from $110.0 million in the same period of 2017. Adjusted operating income – which excludes restructuring and other items such as business integration, acquisition-related costs, litigation settlements and the amortization of intangible assets acquired in business combinations – grew 14% to $283.9 million from $249.7 million in the year-ago period. The adjusted operating income margin improved 1.4 percentage points to 25.8% of sales in the first nine months of 2018 compared to 24.4% in the same period of 2017, with an adjusted gross margin of 71.1% in the 2018 period compared to 70.7% in the year-earlier period.

Net income was $129.4 million, or $0.55 per diluted share (based on 233.8 million diluted shares) compared to $80.1 million, or $0.34 per diluted share (based on 233.4 million diluted shares) in the first nine months of 2017. Adjusted net income was $218.2 million, or $0.93 per diluted share ($0.94 CER), compared to $195.0 million, or $0.84 per diluted share, in the year-ago period, with an adjusted tax rate of 19.5% in the first nine months of 2018 compared to 18.1% in the year-ago period.

Balance sheet and cash flows

At September 30, 2018, cash and cash equivalents were $599.8 million, down from $657.7 million at December 31, 2017. Net cash provided by operating activities was $249.0 million in the first nine months of 2018 compared to $210.7 million in the same period of 2017, reflecting the improving business performance and including $30.0 million of prepaid royalties in 2018 for the Natera partnership to develop genetic assays for the GeneReader NGS System. Free cash flow was $176.7 million, up 21% from $146.1 million in the first nine months of 2017 and more than offset an increase in purchases of Property, Plant and Equipment to $72.3 million in the 2018 period compared to $64.6 million in the same period of 2017. Net cash used in investing activities was $232.6 million in the first nine months of 2018 compared to $371.9 million in the year-ago period. Net cash used in financing activities was $67.5 million compared to net cash provided by financing activities of $386.0 million in the same period of 2017, which included $726.3 million from debt issuances during 2017 that was partially offset by $304.9 million of payments in connection with the capital repayment to shareholders and share repurchase programs.

"Based on the strong sales and earnings growth to date this year, we have reaffirmed our target for about 6-7% CER sales growth and raised our guidance for adjusted EPS on a full-year basis to about $1.33-1.34 per share," said Roland Sackers, Chief Financial Officer of QIAGEN N.V. "The improving profitability comes from the solid business expansion coupled with benefits from efficiency initiatives launched in 2017, which have strengthened our competitive position, especially as we make significant investments in the launch of QIAstat-Dx and the European rollout of the fully integrated NeuMoDx platforms for molecular diagnostic testing. We continue to use our healthy financial position to strengthen our business through targeted operational investments, as well as improving returns to shareholders through our current $200 million repurchase commitment."

Highlights from our Sample to Insight portfolio

QIAGEN is focused on growth opportunities for its Sample to Insight portfolio across the continuum of molecular testing from basic research to clinical healthcare. Among recent developments:

NeuMoDx has granted QIAGEN rights to a novel, disruptive and scalable platform technology for molecular testing. This technology has been applied to next-generation automation systems for PCR (polymerase chain reaction) testing which open the important fully integrated segment of molecular diagnostics to QIAGEN. In September, QIAGEN began commercialization of the NeuMoDx 288 (high-throughput) and NeuMoDx 96 (mid-throughput) in Europe and other major markets outside the United States. QIAGEN is introducing these first two platforms, which are based on the same scalable core technology along with the first two CE-IVD marked diagnostic tests in a strategic partnership with NeuMoDx Molecular, Inc. The two companies have also entered into an agreement under which QIAGEN can acquire all remaining shares of NeuMoDx for $234 million between mid-2019 and mid-2020, subject to regulatory and operational milestones. An extensive menu of tests is in development to expand the diagnostic insights offered by the NeuMoDx systems.
QuantiFERON-TB, the gold-standard blood test for latent tuberculosis (TB) infection detection, continued to grow as authorities increasingly add screening with modern, accurate blood tests such as QuantiFERON-TB Gold Plus (QFT-Plus) to strategies for fighting TB. In September, at a United Nations meeting on tuberculosis, world leaders committed to invest $13 billion a year by 2022 for TB prevention and care. Also in September, QIAGEN and DiaSorin launched an automated, CE-marked workflow for processing QFT-Plus on DiaSorin’s widely used LIAISON immunodiagnostic instruments. Co-marketing has begun in Europe. Availability is planned for the United States in 2019 and China in 2020. Together with the previously announced Hamilton collaboration for pre-analytical sample processing, the enhanced level of workflow automation makes QFT-Plus even more unique, efficient and scalable for all settings from low-throughput laboratories to very large screening programs.
QIAstat-Dx, the powerful yet simple and highly flexible, one-step automation system for multiplex PCR analysis, is rapidly establishing a footprint in the growing market for syndromic testing. QIAGEN has launched the next-generation solution for diagnosis of complex syndromes in Europe and other markets, with the first two CE-IVD marked tests offering differential diagnosis of respiratory and gastrointestinal (GI) infections. A second GI panel was recently launched which includes comprehensive viral, bacterial and parasitic coverage. QIAstat-Dx benefits patients and saves money in healthcare with easy-to-use tests that can be analyzed rapidly, delivering results in about one hour to enable quick, accurate treatment decisions in hospitals, clinics or laboratories. QIAGEN plans to complete the FDA regulatory submission by the end of 2018 as part of plans for a U.S. launch in mid-2019.
Next-generation sequencing (NGS) continues to gain momentum from QIAGEN’s universal solutions for DNA and RNA sequencing on any platform, as well as from expanding market share of the GeneReader NGS System, the world’s first truly Sample to Insight benchtop NGS automation system. QIAGEN recently launched QIAseq FastSelect RNA Removal Kits, a breakthrough technology enabling much faster, simpler library preparation to address a bottleneck in RNA sequencing on any platform. The GeneReader NGS System is growing in placements and consumable sales, while the menu has been expanded with two new QIAact panels. One panel covers a broad range of cancer-causing variants and the other panel focuses on genes tied to breast and ovarian cancers.
In Personalized Healthcare, QIAGEN expanded its presence in developing molecular tests to support immuno-oncology (I-O), launching the NGS open-platform QIAseq TMB Panel to assess biomarkers for tumor mutation burden (TMB) that influence patient response to various immunotherapy drugs. QIAGEN Clinical Insight bioinformatics software has been expanded to interpret key I-O biomarkers. QIAGEN is the leader in co-development programs with pharmaceutical companies for personalized medicine approaches to I-O therapies. Separately, QIAGEN received FDA approval in September for the therascreen EGFR RGQ PCR Kit as a companion diagnostic to help guide the use of Pfizer’s VIZIMPRO (dacomitinib) as a first-line treatment of patients with non-small cell lung cancer (NSCLC). This is QIAGEN’s first approved companion diagnostic with Pfizer.
Update on share repurchase program

As part of a commitment to return $200 million to shareholders that was announced in January 2018, a total of 2.7 million shares have been repurchased through October 2018 on the Frankfurt Stock Exchange at a volume-weighted average price of EUR 31.43 per share for EUR 85.0 million (approximately $97 million at current exchange rates). Further information is available on the QIAGEN website (www.qiagen.com).

Outlook

QIAGEN has updated its outlook for full-year 2018, raising the target for adjusted EPS to $1.33-1.34 CER per share (previously $1.31-1.33 CER), while reaffirming expectations for sales growth of about 6-7% CER. This sales outlook includes anticipated sales of about $7 million during the second half of 2018 from the acquisition of STAT-Dx (on April 27, 2018), as well as about one percentage point of headwind from reduced U.S. HPV test sales compared to 2017. These expectations do not consider any further acquisitions that could be completed in 2018.

Based on exchange rates as of October 26, 2018, currency movements for full-year 2018 against the U.S. dollar are expected to have a negative impact of about one percentage point on 2018 net sales at actual rates, and a negative impact of about $0.02 per share on adjusted diluted EPS.

For the fourth quarter of 2018, total net sales are expected to rise about 6-7% CER, which includes about $5 million of sales from the QIAstat-Dx acquisition. Adjusted diluted EPS are expected to be about $0.39-0.40 CER.

Based on exchange rates as of October 26, 2018, currency movements against the U.S. dollar are expected to have a negative impact on net sales of about four percentage points, and a negative impact of about $0.01 per share on adjusted diluted EPS.

Quarterly results presentation, conference call and webcast details

A presentation with additional information can be downloaded at View Source A conference call will be held on Tuesday October 30, 2018, at 14:00 Central European Time (CET) / 13:00 GMT / 9:00 Eastern Standard Time (EST). (Note earlier European times due to the end of European Daylight Savings Time.) A live webcast will be made available at this website, and a replay will also be made available after the event.

Use of adjusted results

QIAGEN reports adjusted results, as well as results on a constant exchange rate (CER) basis, and other non-U.S. GAAP figures (generally accepted accounting principles), to provide additional insight into its performance. These results include adjusted gross margin, adjusted operating income, adjusted operating income margin, adjusted net income, adjusted diluted EPS, adjusted tax rates and free cash flow. Adjusted results are non-GAAP financial measures that QIAGEN believes should be considered in addition to reported results prepared in accordance with GAAP, but should not be considered as a substitute. Free cash flow is calculated by deducting capital expenditures for Property, Plant and Equipment from cash flow from operating activities. QIAGEN believes certain items should be excluded from adjusted results when they are outside of ongoing core operations, vary significantly from period to period, or affect the comparability of results with competitors and its own prior periods. Furthermore, QIAGEN uses non-GAAP and constant currency financial measures internally in planning, forecasting and reporting, as well as to measure and compensate employees. QIAGEN also uses adjusted results when comparing current performance to historical operating results, which have consistently been presented on an adjusted basis. Reconciliations are included in the tables accompanying this report.

On October 29, 2018 Takeda Pharmaceutical Company Limited (TSE: 4502) reported that it will present a total of six company-sponsored abstracts, including two oral presentations, at the 11th International Symposium on Hodgkin Lymphoma ) from 27 to 29 October 2018 in Cologne, Germany (Press release, Takeda, OCT 29, 2018, View Source [SID1234530423]). This year’s presentations will highlight Phase 3 and other clinical data from ADCETRIS (brentuximab vedotin) and will continue to build on our research on CD30 positive lymphoma.

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"Data to be presented at this year’s ISHL continue to reinforce Takeda’s dedication to advancing treatment for people affected by Hodgkin’s lymphoma," said Jesús Gómez-Navarro, MD, Vice President and Chief Clinical Research and Development of Oncology of Takeda. "The progress we have made in the development of ADCETRIS serves as a true testimony to the leadership role we have played in the treatment of CD30-positive malignancies. We are eager to share positive data, including the results of the Phase 3 ECHELON-1 and AETHERA trials, which confirm the long-term benefits of ADCETRIS through treatment lines and support its role as an important therapy targeting Hodgkin lymphoma . "

During the invited oral presentation, Takeda will share the results of the ECHELON-1 study, which showed that ADCETRIS, as part of a front-line combination chemotherapy regimen, improved the outcome compared to a current standard of care in patients not previously treated with advanced Hodgkin’s lymphoma. The safety profile of the ADCETRIS arm in the ECHELON-1 assay was generally consistent with that known for the single agent components of the regimen. In addition to the findings presented earlier during the Plenary Scientific Session at the 59th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in December 2017, the presentation of ISHL will highlight survival-free progression (PFS) results and data demonstrating the benefits of ADCETRIS in patients with stage IV disease. Additional data to be presented during the meeting include several sub-analyzes of the ECHELON-1 trial.

Takeda, in partnership with Seattle Genetics, will present five-year follow-up data from AETHERA’s Phase 3 trial, in which ADCETRIS demonstrated a sustained benefit in PFS as a consolidation treatment option for patients at high risk of relapse or progression after autologous stem cell transplantation (ASCT). The safety profile of ADCETRIS in the AETHERA trial was generally consistent with existing prescribing information.

Takeda will also disclose the results of a Phase 1/2 study evaluating ADCETRIS as part of a chemotherapy regimen in advanced pediatric Hodgkin’s lymphoma patients.

Also at the congress, ISHL invited Takeda to participate in PeD’s access to medical oncology program in Sub-Saharan Africa during the Developing Healthcare Environments workshop on Saturday, October 27, from 8:45 p.m. to 10:15 p.m. CET .

The six abstracts sponsored by Takeda Oncology accepted for submission during ISHL include:

Brentuximab vedotin frontline plus chemotherapy exhibits survival without modified upper progression compared to only chemotherapy in patients with stage III or IV Hodgkin’s lymphoma: ECHELON-1 Phase 3 study. Oral presentation: session "Advanced Placements". Monday, October 29, 7:30 a.m. – 9:00 p.m. CET. Poster: Abstract 0038. Sunday, October 28 – Monday, October 29.
Five-year progression-free survival results from a crucial Phase 3 study of the consolidation of brentuximab vedotin after autologous stem cell transplantation in patients with Hodgkin’s lymphoma at risk of recurrence or progression (AETHERA). Oral presentation. Session "Recidente / Refratário HL". Monday, October 29, 4:00 p.m. to 5:30 p.m. CET.
Phase 1/2 study of brentuximab vedotin + AVD in pediatric patients with recently diagnosed advanced stage classic Hodgkin’s lymphoma. Abstract 0149. Sunday, October 28 – Monday, October 29.
Serum CD30 and TARC do not correlate with evaluation of PET-based response in patients (Pcs) with stage III or IV classical Hodgkin’s lymphoma (cHL): ECHELON-1 Phase 3 study of brentuximab vedotin plus chemotherapy compared with only chemotherapy. Abstract 0159. Sunday, October 28 – Monday, October 29.
Brentuximab vedotin plus chemotherapy in patients with advanced high-risk classical Hodgkin’s lymphoma (cHL): results from pre-specified subgroup analyzes from the ECHELON-1 study. Abstract 0136. Sunday, October 28 – Monday, October 29.
Pharmacokinetic population modeling and assessment of response to exposure to efficacy and safety of brentuximab vedotin in patients with advanced classical Hodgkin lymphoma from the ECHELON-1 Phase 3 study. Abstract 0137. Sunday, October 28 – Monday, October 29.
* In partnership with Seattle Genetics

For more information, the ISHL program is available here: View Source .

About Hodgkin Lymphoma
Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two main categories of lymphoma: Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. Hodgkin’s lymphoma is distinguished from other types of lymphoma by the presence of a characteristic cell type, known as the Reed-Sternberg cell. The Reed-Sternberg cell expresses CD30.

According to the Lymphoma Coalition, approximately 67,000 people worldwide are diagnosed with Hodgkin’s lymphoma every year, and more than 25,000 people die from this cancer.

About 30 percent of patients newly diagnosed with Hodgkin’s lymphoma progress after first-line therapy, depending on the stage of the disease. Only 50 percent of patients with relapsed or refractory Hodgkin’s lymphoma gain long-term remission with high dose chemotherapy and an autologous stem cell transplantation (ASCT), a treatment used historically, highlighting the importance of first- successful.

About ADCETRIS
ADCETRIS is an ADC comprising an anti-CD30 monoclonal antibody linked by a protease cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), using proprietary technology from Seattle Genetics. The ADC employs a binding system that is designed to be stable in the bloodstream, but to release MMAE after internalization into CD30-expressing tumor cells.

Intravenous infusion ADCETRIS injection received FDA approval for five indications in adult patients with: (1) untreated classic Hodgkin’s lymphoma (HLC), stage III or IV, in combination with chemotherapy, (2) high-risk cHL relapse or progression such as consolidation of post-autologous hematopoietic stem cell transplantation (auto-HSCT), (3) LCH after self-HSCT failure or failure of at least two multi-agent chemotherapy regimens in patients who are not candidates for self- TCTH, (4) sALCL after failure of at least one previous multiagent chemotherapy regimen, and (5) primary cutaneous anaplastic cutaneous lymphoma (pcALCL) or mycosis fungoides (MF) expressing CD30 that received prior systemic treatment.

Health Canada granted approval of ADCETRIS with conditions for relapsed or refractory Hodgkin’s lymphoma and sALCL in 2013, and unconditional approval for post-autologous stem cell transplantation (ASCT) consolidation treatment of patients with Hodgkin’s lymphoma at risk increased relapse or progression.

ADCETRIS received a conditional marketing authorization from the European Commission in October 2012. The indications approved in Europe are: (1) for the treatment of adult patients with relapsed or refractory Hodgkin’s lymphoma after ASCT or after at least two therapies when treating ASCT or multi-agent chemotherapy is not a treatment option, (2) treating adult patients with recurrent or refractory slam, (3) for the treatment of adult patients with CD30 positive Hodgkin’s lymphoma at increased risk of relapse or progression after ASCT, and (4) for the treatment of adult patients with cutaneous CD30-positive T-cell lymphoma (CTCL) after at least one prior systemic therapy.

ADCETRIS has been approved by regulatory authorities in 70 countries for relapsed or refractory Hodgkin’s lymphoma and sALCL See important safety information below.

ADCETRIS is being extensively evaluated in more than 70 clinical trials, including a Phase 3 study in first-line Hodgkin’s lymphoma (ECHELON-1) and another Phase 3 study in first-line CD30-positive peripheral T cell lymphomas ( ECHELON-2) as well as assays in many additional types of CD30-positive malignancies.

Seattle Genetics and Takeda are developing ADCETRIS together. Under the terms of the collaboration agreement, Seattle Genetics has marketing rights in the US and Canada, and Takeda has the right to market ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding the joint development costs for ADCETRIS on a half-way basis, except in Japan, where Takeda is solely responsible for development costs.

ADCETRIS (brentuximab vedotin) Important safety information (European Union)

Consult the Summary of Product Characteristics (RCM) before prescribing.

CONTRAINDICATIONS

ADCETRIS is contraindicated in patients with hypersensitivity to brentuximab vedotin and its excipients. In addition, the combined use of ADCETRIS with bleomycin causes pulmonary toxicity.

SPECIAL WARNINGS AND PRECAUTIONS

Progressive multifocal leukoencephalopathy (PML): reactivation of John Cunningham virus (JCV) resulting in progressive multifocal leukoencephalopathy (PML) and death may occur in ADCETRIS-treated patients. PML has been reported in patients receiving ADCETRIS after receiving multiple prior chemotherapy regimens. PML is a rare demyelinating disease of the central nervous system that results from the reactivation of latent JCV and is often fatal.

Carefully monitor patients for new or worsening neurological, cognitive or behavioral signs or symptoms, which may be suggestive of PML. Suggested evaluation of PML includes neurological consultation, magnetic resonance imaging of the brain with gadolinium, and analysis of cerebrospinal fluid for JCV DNA by polymerase chain reaction (PCR) or brain biopsy with evidence of JCV. A negative JCV PCR does not exclude PML. Additional monitoring and evaluation may be necessary if no alternative diagnosis can be established. Maintain dosage for any suspected case of PML and permanently discontinue ADCETRIS if a PML diagnosis is confirmed.

Be aware of PML symptoms that the patient may not notice (for example, cognitive, neurological, or psychiatric symptoms).

Pancreatitis: Acute pancreatitis was observed in patients treated with ADCETRIS. Fatal outcomes were reported. Monitor patients closely for new or aggravating abdominal pains, which may be suggestive of acute pancreatitis. Patient assessment may include physical examination, laboratory evaluation of serum amylase and serum lipase, and abdominal imaging such as ultrasound and other appropriate diagnostic measures. Discontinue ADCETRIS in any suspected case of acute pancreatitis. ADCETRIS should be discontinued if a diagnosis of acute pancreatitis is confirmed.

Pulmonary toxicity: Cases of pulmonary toxicity, some with fatal outcomes including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome (ARDS) have been reported in patients receiving ADCETRIS. Although no causal association has been established with ADCETRIS, the risk of pulmonary toxicity can not be ruled out. Evaluate promptly and treat new or worsened lung symptoms adequately. Consider dosing during evaluation and even symptomatic improvement.

Severe infections and opportunistic infections: severe infections such as pneumonia, staphylococcal bacteremia, sepsis / septic shock (including fatal outcomes) and herpes zoster, and opportunistic infections such as Pneumocystis jiroveci pneumonia and oral candidiasis have been reported in ADCETRIS-treated patients. Carefully monitor patients during treatment for possible serious and opportunistic infections.

Infusion-related reactions (IRR): immediate and late IRR, as well as anaphylaxis, occurred with ADCETRIS. Monitor patients closely during and after an infusion. If anaphylaxis occurs, immediately and permanently discontinue administration of ADCETRIS. Appropriate medical treatment should be given. If an IRR occurs, stop the infusion and institute appropriate medical treatment. The infusion can be restarted at a slower rate after resolution of symptoms. Patients who had a previous IRR should be pre-medicated for subsequent infusions. IRRs are more frequent and more severe in patients with antibodies to ADCETRIS.

Tumor lysis syndrome (TLS): TLS has been reported with ADCETRIS. Patients with rapidly proliferating tumor and high tumor burden are at risk of TLS. Monitor these patients closely and administer them according to best medical practice.

Peripheral neuropathy (PN): treatment with ADCETRIS may cause PN, both sensory and motor. PN induced by ADCETRIS is typically cumulative and reversible in most cases. Monitor patients for NP symptoms such as hypoaesthesia, hyperesthesia, paresthesia, discomfort, burning sensation, neuropathic pain, or weakness. Patients who present with new or worsening PN may require a delay and a reduction in the dose or discontinuation of ADCETRIS.

Hematologic toxicities: grade 3 or grade 4 anemia, thrombocytopenia and prolonged grade 3 neutropenia (equal to or greater than 1 week) may occur with ADCETRIS. Monitor complete blood counts before each dose is given.

Febrile neutropenia: Febrile neutropenia was reported. Carefully monitor patients for fever and manage according to best medical practice in case of developing febrile neutropenia.

Stevens-Johnson Syndrome (SJS): SJS and toxic epidermal necrolysis (TEN) have been reported with ADCETRIS. Fatal outcomes were reported. Discontinue treatment with ADCETRIS if SJS or TEN occurs and administer appropriate medical therapy.

Gastrointestinal (GI) complications : gastrointestinal complications, some with fatal outcomes including intestinal obstruction, ileus, enterocolitis, neutropenic colitis, erosion, ulceration, perforation and hemorrhage have been reported. Promptly evaluate and treat patients if new or aggravating gastrointestinal symptoms occur.

Hepatotoxicity: elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) have been reported. Severe cases of hepatotoxicity, including fatal outcomes, also occurred. Test liver function before starting treatment and routinely monitor patients receiving ADCETRIS for hepatic elevations. Patients with hepatotoxicity may require a delay, dose modification or discontinuation of ADCETRIS.

Hyperglycemia: Hyperglycemia has been reported during studies in patients with a high body mass index (BMI), with or without a history of diabetes mellitus. Monitor serum glucose closely in patients experiencing an event of hyperglycemia. Administer antidiabetic treatment as appropriate.

Renal and hepatic impairment: There is limited experience in patients with renal and hepatic impairment. Available data indicate that clearance of MMAE may be affected by severe renal insufficiency, hepatic insufficiency, and low serum albumin concentrations.

CD30 + CTCL: The size of the treatment effect on CD30 + CTCL subtypes other than mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL) is unclear due to lack of high level evidence. In two ADCETRIS single-arm phase II studies, disease activity was demonstrated in the Sézary syndrome (SS), lymphomatoid papulosis (LyP) and mixed histology of LCTC subtypes. These data suggest that efficacy and safety can be extrapolated to other subtypes of CD30 + CTCL. Carefully consider the risk benefit per patient and be careful in other types of patients with CTCL + CDCL.

Sodium content in the excipients: ADCETRIS contains a maximum of 2.1 mmol (or 47 mg) sodium per dose. Take this into consideration for patients on a controlled sodium diet.

Interactions
Patients receiving a strong CYP3A4 or P-gp inhibitor concomitantly with ADCETRIS may be at increased risk of neutropenia and should be monitored closely. Concomitant administration of ADCETRIS with a CYP3A4 inducer did not alter the plasma exposure of ADCETRIS but appeared to reduce the plasma concentrations of the metabolites of MMAE that could be tested. ADCETRIS is not expected to alter exposure to drugs metabolised by CYP3A4 enzymes.

PREGNANCY: Inform women of childbearing potential to use two effective contraceptive methods during ADCETRIS treatment and up to six months after treatment. There are no data on the use of ADCETRIS in pregnant women, although animal studies have shown reproductive toxicity. Do not use ADCETRIS during pregnancy unless the benefit to the mother outweighs the potential risks to the fetus.

LACTATION (breast-feeding): There are no data on whether ADCETRIS or its metabolites are excreted in human milk, so it is not possible to rule out a risk to the newborn / infant. At the potential risk, a decision should be made on discontinuation of breastfeeding or discontinuation / abstention from treatment with ADCETRIS.

FERTILITY: In non-clinical studies, treatment with ADCETRIS resulted in testicular toxicity and may alter male fertility. Inform men on ADCETRIS treatment not to be parents during treatment and up to six months after the last dose.

Effects on the ability to drive and use machines: ADCETRIS may have a minor influence on the ability to drive and use machines.

SIDE EFFECTS
The most common adverse reactions (≥10%) were infections, peripheral sensory neuropathy, nausea, fatigue, diarrhea, pyrexia, upper respiratory tract infection, neutropenia, rash, cough, vomiting, arthralgia, peripheral motor neuropathy, related reactions with perfusion, pruritus, constipation, dyspnea, weight loss, myalgia and abdominal pain.

Serious adverse drug reactions were pneumonia, acute respiratory distress syndrome, headache, neutropenia, thrombocytopenia, constipation, diarrhea, vomiting, nausea, pyrexia, peripheral motor neuropathy, peripheral sensory neuropathy, hyperglycemia, demyelinating polyneuropathy, tumor lysis syndrome and syndrome of Stevens-Johnson. Serious adverse drug reactions occurred in 12% of patients. The frequency of serious adverse drug reactions was ≤1%.

ADCETRIS (brentuximab vedotin) Important safety information in the USA

WARNING IN THE BOX: PROGRESSIVE MULTIFOCAL LEUCOENCEPHALOPATHY (PML)

JC virus infection resulting in PML and death may occur in patients treated with ADCETRIS.

Contraindication
ADCETRIS concomitant with bleomycin due to pulmonary toxicity (eg, infiltration and / or interstitial inflammation).

Warnings and Precautions

Peripheral neuropathy (PN): ADCETRIS causes PN to be predominantly sensory. Cases of motor PN were also reported. The PN induced by ADCETRIS is cumulative. Monitor symptoms such as hypoaesthesia, hyperesthesia, paresthesia, discomfort, burning sensation, neuropathic pain or weakness. Establish dose modifications accordingly.

Anaphylaxis and infusion reactions : Infusion- related reactions (IRR), including anaphylaxis, have occurred with ADCETRIS. Monitor the patients during infusion. If an IRR occurs, stop the infusion and institute appropriate medical treatment. If anaphylaxis occurs, immediately and continuously discontinue the infusion and administer appropriate medical treatment. Pre-med the patients with IRR before the subsequent infusions. Pre-medication may include acetaminophen, an antihistamine, and a corticosteroid.

Hematologic toxicities: severe prolonged neutropenia (≥1 week) and thrombocytopenia or Grade 3 or 4 anemia may occur with ADCETRIS. Severe and fatal cases of febrile neutropenia have been reported with ADCETRIS. Monitor complete blood counts before each dose of ADCETRIS. Consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. Monitor fever in patients. If Grade 3 or 4 neutropenia occurs, consider delays, reductions, discontinuation, or prophylaxis with G-CSF at subsequent doses.

Severe infections and opportunistic infections: infections such as pneumonia, bacteremia and sepsis or septic shock (including fatal outcomes) have been reported in patients treated with ADCETRIS. Monitor closely the patients during treatment of bacterial, fungal, or viral infections.

Tumor lysis syndrome: follow closely the patients with tumor of rapid proliferation and high tumor burden.

Increased toxicity in the presence of severe renal impairment: the frequency of adverse reactions and ≥ Grade 3 deaths was greater in patients with severe renal impairment compared with patients with normal renal function. Avoid use in patients with severe renal impairment.

Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of adverse reactions and deaths in Grade 3 was greater in patients with moderate or severe hepatic impairment compared to patients with normal hepatic function. Avoid use in patients with moderate or severe hepatic impairment .

Hepatotoxicity : Severe and fatal cases occurred in patients treated with ADCETRIS. Cases were consistent with hepatocellular damage, including elevations of transaminases and / or bilirubin, and occurred after the first dose or recount of ADCETRIS. Pre-existing liver disease, elevated basal liver enzymes and concomitant medications may increase risk. Monitor liver enzymes and bilirubin. Patients with recent, aggravated or recurrent hepatotoxicity may require a delay, dose change or discontinuation of ADCETRIS.

PML: fatal cases of JC virus infection resulting in PML and death were reported in patients treated with ADCETRIS. The first onset of symptoms occurred at various times from the start of ADCETRIS therapy, with some cases occurring within three months of the initial exposure. Other possible contributory factors other than ADCETRIS include previous treatments and underlying disease that may cause immunosuppression. Consider the diagnosis of PML in patients with signs and symptoms of recent onset of central nervous system abnormalities. Stop ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.

Pulmonary toxicity: Severe and fatal non-infectious pulmonary toxicity events including pneumonitis, interstitial lung disease and acute respiratory distress syndrome have been reported. Monitor patients for signs and symptoms, including cough and dyspnea. In case of new or aggravated pulmonary symptoms, administer the ADCETRIS dose during evaluation and until symptomatic improvement.

Severe dermatological reactions: severe and fatal cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (NET) have been reported with ADCETRIS. If SJS or TEN occurs, discontinue ADCETRIS and administer appropriate medical treatment.

Gastrointestinal (GI) complications: Severe and fatal cases of acute pancreatitis have been reported in patients treated with ADCETRIS. Other serious and fatal gastrointestinal complications include perforation, bleeding, erosion, ulceration, intestinal obstruction, enterocolitis, neutropenic colitis and ileus have been reported in ADCETRIS-treated patients. Lymphoma with preexisting gastrointestinal involvement may increase the risk of perforation. In case of new or aggravated gastrointestinal symptoms, perform an immediate diagnostic evaluation and treat appropriately.

Fetal embryonal toxicity: Based on the mechanism of action and animal studies, ADCETRIS may cause fetal damage. Inform women about the potential reproductive potential of the potential risk to the fetus and to avoid pregnancy during treatment with ADCETRIS and for at least six months after the last dose of ADCETRIS.

Common adverse reactions (≥20%): neutropenia, anemia, peripheral sensory neuropathy, nausea, fatigue, constipation, diarrhea, vomiting and pyrexia.

Drug interactions
Concomitant use of strong inhibitors or inducers of CYP3A4, or inhibitors of P-gp, has the potential to affect exposure to monomethyl auristatin E (MMAE).

Use in specific populations
Moderate or severe hepatic impairment or severe renal impairment: MMAE exposure and adverse reactions are increased. Avoid use.

Inform men with female sexual partners with reproductive potential to use effective contraceptive methods during ADCETRIS treatment and for at least six months after the last dose of ADCETRIS.

Inform patients to report pregnancy immediately and avoid breastfeeding while receiving ADCETRIS.

On October 29, 2018 Apexian Pharmaceuticals reported that researchers will continue to explore the impact of Apexian’s target molecule, APX3330, on cancer cachexia with additional grant funding from the National Institutes of Health (NIH) National Cancer Institute(NCI) (Press release, Apexian Pharmaceuticals, OCT 29, 2018, View Source [SID1234530421]). Cancer cachexia is weight loss with chronic inflammation and defective metabolism, which causes roughly one third of all cancer deaths. It is particularly prevalent in pancreatic ductal adenocarcinoma (PDAC), which has a dismal five-year survival rate.

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Dr. Mark R. Kelley, Apexian Chief Scientific Officer and the Betty and Earl Herr Professor of Pediatric Oncology Research at the Indiana University Simon Cancer Center; Dr. Melissa Fishel, Research Associate Professor, Wells Center for Pediatric Research; and Dr. Teresa Zimmers, Associate Professor of Surgery at the Indiana University School of Medicine, have been working to define mechanisms of cachexia stemming from treatment in PDAC, as well as for identifying mechanism-driven, targeted anti-cachexia therapies.

"The goal of this research is to determine the anti-cachexia potential of Ref-1 inhibition, HIF-1a inhibition, or the combination in mouse models of PDAC," said Dr. Kelley. "APX3330 has proven effective at inhibiting Ref-1, and has been safe and well tolerated when taken by patients with advanced cancers in our Phase 1 clinical study."

Previous studies support Ref-1 as a target in PDAC, on-target effects of APX3330, and the use of APX3330 as a clinical agent in cancer. This study will focus on demonstrating improvement in fat/muscle mass and PDAC cachexia symptoms using APX3330. Positive results from this study would lead to immediate clinical trials using APX3330 to prevent or reverse PDAC cachexia.

"Dr. Kelley’s research on APX3330 as a Ref-1 inhibitor continues to offer promise as a treatment for cancer and cancer-related issues like cachexia and cancer chemotherapy-induced neuropathy," said Steve Carchedi, CEO of Apexian Pharmaceuticals. "As we complete our Phase I trial, we continue to aggressively pursue additional therapeutic uses for APX3330 and build on our pipeline of novel, first in class molecules."

The NIH grant of $227,554 pushes Kelley’s grant budget for research on Ref-1 inhibitors to nearly $700,000 just in 2018.

On October 29, 2018 Veracyte, Inc. (Nasdaq: VCYT) reported financial results for the third quarter ended September 30, 2018 and provided an update on recent business progress (Press release, Veracyte, OCT 29, 2018, View Source [SID1234530385]). For the third quarter of 2018, revenue was $23.5 million, an increase of 34 percent, compared with $17.5 million for the third quarter of 2017. Genomic test volume was 8,006, an increase of 23 percent compared with the same period in 2017.

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"We delivered another quarter of strong revenue and genomic volume growth for our Afirma and Percepta classifiers, which are changing practice in the diagnosis of thyroid and lung cancer," said Bonnie Anderson, Veracyte’s chairman and chief executive officer. "In addition, we are thrilled that we recently received draft Medicare coverage for our third product, the Envisia Genomic Classifier."

Anderson continued, "As a result of our strong third quarter performance and our outlook for the remainder of this year, we are raising our annual revenue guidance and lowering our cash burn guidance for 2018. And, as we look to 2019 and beyond, we believe we are well-positioned to continue making a difference in the lives of patients, providing solutions to physicians to help better inform clinical decisions, and delivering cost savings to the healthcare system."

Third Quarter 2018 Financial Results

For the three-month period ended September 30, 2018 as compared with the third quarter of 2017:

Revenue was $23.5 million, an increase of 34 percent;
Genomic test volume was 8,006, an increase of 23 percent;
Gross margin was 65 percent, an increase of 6 percent;
Operating expenses, excluding cost of revenue, were $19.5 million, an increase of 17 percent;
Net loss and comprehensive loss was ($4.5) million, an improvement of 37 percent;
Basic and diluted net loss per common share was ($0.12), an improvement of 43 percent;
Cash burn1 was $2.4 million, an improvement of 58 percent; and
Cash and cash equivalents was $77.8 million at September 30, 2018.
For the nine-month period ended September 30, 2018, as compared to the prior year period of 2017:

Revenue was $66.3 million, an increase of 27 percent;
Genomic test volume was 22,556, an increase of 20 percent;
Gross margin was 63 percent, an increase of 2 percent;
Operating expenses, excluding cost of revenue were $61.1 million, an increase of 16 percent
Net loss and comprehensive loss was ($19.9) million, an improvement of 12 percent;
Basic and diluted net loss per common share was ($0.56), an improvement of 16 percent; and
Cash burn1 was $13.7 million, an improvement of 28 percent.
1 Refer to the "Non-GAAP Financial Measures" for an explanation of cash burn and the "Reconciliation of Net Cash Used in Operating Activities to Cash Burn" table included in the financial statements in this press release.

Third Quarter 2018 and Recent Business Highlights

Commercial Growth:

Completed national transition from the Afirma Gene Expression Classifier (GEC) to the Genomic Sequencing Classifier (GSC), retiring all GEC testing and accelerating the adoption of the Afirma Xpression Atlas for surgical and treatment decisions in the third quarter of 2018.
Increased the number of physicians ordering Percepta to nearly 200, across 140 institutions, primarily through a continued focus on sales and marketing initiatives, as of September 30, 2018.
Expanded Envisia Early Access Program sites that have submitted samples for genomic testing to 15 – exceeding the company’s expectations.
Reimbursement Expansion:

Received draft Medicare coverage for the Envisia Genomic Classifier through the MolDX program; upon anticipated finalization in early 2019, Veracyte will be positioned to ramp commercial adoption of Envisia and begin to grow associated revenue next year.
Evidence Development:

Positive performance and clinical utility data for the Afirma GSC and Xpression Atlas were presented at the American Thyroid Association annual meeting. Results show that the Afirma GSC is identifying even more benign thyroid nodules in real-world practice than was demonstrated in the company’s clinical validation study, previously published in JAMA Surgery.
Early results of the ongoing Percepta registry clinical utility study were presented at CHEST 2018 and show that the genomic test changed clinical decision-making and reduced invasive procedures at every evaluation time point up to 12 months post-testing.
Clinical validation data for the Envisia classifier were also presented at CHEST 2018 and confirm the test’s ability to improve diagnosis of idiopathic pulmonary fibrosis – without the need for surgery.
Financing:

In July 2018, Veracyte issued and sold 5,750,000 shares of common stock in a registered public offering, including the underwriters’ exercise in full of their option to purchase an additional 750,000 shares, at a price to the public of $10.25 per share. Net proceeds from the offering were approximately $55.0 million.
Updated 2018 Financial Outlook

Veracyte is increasing its 2018 annual revenue guidance to a range of $90.0 million to $91.0 million from its previous guidance range of $87 million and $89 million. In addition, the company is reducing its annual cash burn guidance to a range of $17.0 million to $18.0 million from its previous guidance range of $18 million to $21 million.

Conference Call and Webcast Details

The company will host a conference call and simultaneous webcast today at 4:30 p.m. EDT to discuss its financial results and provide a general business update. The call and webcast may be accessed as follows:

Webcast:
View Source

Dial-in number (U.S.): (855) 541-0980
International Number: (970) 315-0440
Conference ID: 1658434

The webcast should be accessed 10 minutes prior to the conference call start time. A replay of the webcast will be available for one year following the conclusion of the live broadcast and will be accessible on the company’s website at View Source.

On October 29, 2018 Neuralstem, Inc. (Nasdaq:CUR), a biopharmaceutical company focused on developing novel treatments for nervous system diseases, reported that it has entered into definitive agreements with institutional investors for the purchase of 3,000,000 shares of its common stock, at a purchase price per share of $0.70, in a registered direct offering (Press release, Neuralstem, OCT 29, 2018, View Source [SID1234530381]). Additionally, Neuralstem has also agreed to issue to the investors unregistered warrants to purchase up to 3,000,000 shares of its common stock. The closing of the offering is expected to take place on or about October 29, 2018, subject to the satisfaction of customary closing conditions.

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H.C. Wainwright & Co. is acting as the exclusive placement agent for the offering.

The warrants have an exercise price of $0.75 per share of common stock, will be exercisable commencing six months following the issuance date and will expire five and one-half years from the issuance date.

The gross proceeds to Neuralstem, before deducting placement agent fees and other offering expenses, are expected to be $2.1 million. Neuralstem intends to use the net proceeds from this offering to further its clinical and preclinical programs, and for general working capital.

The shares of common stock (but not the warrants or the shares of common stock underlying the warrants) are being offered by Neuralstem pursuant to a "shelf" registration statement on Form S-3 that was filed and declared effective by the Securities and Exchange Commission ("SEC") on June 23, 2017 and the base prospectus contained therein (File No. 333-218608). The offering of the shares of common stock will be made only by means of a prospectus supplement and accompanying base prospectus that form a part of the registration statement.

A final prospectus supplement and accompanying base prospectus relating to the shares of common stock being offered will be filed with the SEC. Copies of the final prospectus supplement and accompanying base prospectus may be obtained, when available, on the SEC’s website at View Source or by contacting H.C. Wainwright & Co., LLC at 430 Park Avenue, 3rd Floor, New York, New York 10022, by phone at 646-975-6996 or e-mail at [email protected].

The warrants described above were offered in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Act"), and Regulation D promulgated thereunder and, along with the shares of common stock underlying the warrants, have not been registered under the Act, or applicable state securities laws. Accordingly, the warrants and underlying shares of common stock may not be offered or sold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Act and such applicable state securities laws.

This press release shall not constitute an offer to sell, or the solicitation of an offer to buy any of the securities described herein, nor shall there be any sale of these securities in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction