On February 5, 2020 QIAGEN N.V. (NYSE: QGEN; Frankfurt Prime Standard: QIA) reported results of operations for the fourth quarter and full-year 2019 (Press release, Qiagen, FEB 4, 2020, View Source [SID1234553871]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"QIAGEN’s performance for the fourth quarter and full-year 2019 delivered on the updated outlook we had set for sales growth, and exceeded the targets set for adjusted earnings," said Thierry Bernard, Interim CEO and Senior Vice President, Head of Molecular Diagnostics Business Area of QIAGEN.

"We continue to focus on attractive growth opportunities from the Life Sciences to Molecular Diagnostics and are determined to make QIAGEN a stronger and more differentiated leader. We have set balanced targets for 2020 that capitalize on growth opportunities in our Sample to Insight portfolio while acknowledging challenges, in particular the weakness in our China business that began in mid-2019 and expectations for a continued reduction in revenues from companion diagnostic co-development projects due to the 2019 changes in our next-generation sequencing strategy. While we are currently seeing an increase in global demand for instruments and consumables that can be used for infectious disease testing for the coronavirus, we remain cautious and have not included it in our outlook for 2020 given the uncertainties and disruptions to macro business trends in China at this time," Bernard said.
"We have reallocated resources to support business expansion, while also enabling us to set an outlook for adjusted earnings per share to grow at a significantly faster rate than sales growth. This is supported in particular by the decision to discontinue development of our own NGS instruments but also by the efficiency measures and resulting gains that were announced in 2019," said Roland Sackers, Chief Financial Officer of QIAGEN. "We are reaffirming our commitment to improving operating efficiencies and to maintaining disciplined capital allocation to support growth and increase returns."

Please refer to accompanying tables for reconciliation of reported to adjusted figures.
CER – Constant exchange rates. Tables may have rounding differences. CER sales results (Q4 2019: $417.9 million, FY 2019: $1.566 billion)
(1) Weighted number of diluted shares (Q4 2019: 231.3 million, Q4 2018: 232.4 million); (FY 2019: 232.4 million, FY 2018: 233.5 million).
Reported diluted EPS for FY 2019 based on basic shares of 226.8 million. Percentage changes are to prior-year periods.

(1) Includes companion diagnostic co-development sales (Q4 2019: $9 million, -55%, -54% CER, FY 2019: $42 million, -28%, -27% CER)
Tables may have rounding differences
(1) Asia-Pacific / Japan sales excluding China (Q4 2019: 0%, 0% CER and FY 2019: +2%, +4% CER)
Tables may have rounding differences. Percentage changes are to prior-year periods. Rest of world represented less than 1% of sales.

Fourth quarter 2019 results
Total net sales rose 3% to $413.5 million in the fourth quarter of 2019 from $403.2 million in the same period of 2018. Growth was 4% at constant exchange rates (CER) as currency movements against the U.S. dollar had a negative impact of one percentage point. The acquisition of N-of-One (acquired in January 2019) provided revenues of about $1 million in the fourth quarter of 2019.

Gains in consumables and related sales (+7% CER / 88% of sales) more than outweighed weaker instrument revenues (-16% CER / 12% of sales). Amid solid placements of the QIAsymphony and QIAstat-Dx systems, lower instrument revenues reflected a sharp decline in instrument sales of the GeneReader NGS System as well as a shift to reagent-rental agreements for which revenues are generated through consumables over the rental contract period. The Americas and Europe / Middle East / Africa regions grew at solid single-digit CER rates, while the Asia-Pacific / Japan region fell 4% CER due to an ongoing decline in China, mainly due to a slowdown in orders from distributors and the end of the China NGS joint venture, and weaker sales trends in Japan. Among the customer classes, Molecular Diagnostics (+3% CER / 48% of sales) was fueled by double-digit CER gains in consumables for use in universal NGS applications, along with solid gains in consumables used for Precision Medicine and companion diagnostics. Sales of the QuantiFERON-TB test rose 1% CER on a combined high-single-digit CER growth rate in the Americas and EMEA regions but lower sales in Asia, particularly due to China and Japan. Revenues from companion diagnostic co-development projects (-54% CER / $9 million) declined sharply as expected due to the decision to end companion diagnostic projects based on the GeneReader system in light of the new clinical NGS agreement with Illumina announced in October 2019. Sales in Life Sciences (+4% CER / 52% of sales) benefited from good CER gains in consumables and related revenues, in particular from the universal NGS portfolio, the QIAcube Connect instrument and QIAGEN Digital Insights as well as the Americas region, which more than offset lower instrument sales. Pharma (+5% CER / 19% of sales) was led by high-single-digit CER growth in the Americas and Asia-Pacific / Japan regions, while Academia / Applied Testing (+3% CER / 33% of sales) also showed solid growth trends in the Americas, in particular the U.S., against a softer performance in the EMEA region.

Operating income declined to $80.0 million in the fourth quarter of 2019 from $88.3 million in the same period of 2018. Results for the fourth quarter included pre-tax charges of $24.9 million related to the decision announced in October 2019 to discontinue NGS instrument development programs and prioritize resource allocation. Adjusted operating income – which excludes purchased intangibles amortization, long-lived asset impairments and other items such as business integration, acquisition-related costs, litigation costs and restructuring – rose 16% to $138.6 million (33.5% of sales) in the fourth quarter of 2019 from $119.4 million (29.6% of sales) in the 2018 period.

Net income was $44.9 million in the fourth quarter of 2019, or $0.19 per diluted share (based on 231.3 million diluted shares), compared to $60.9 million, or $0.26 per diluted share (based on 232.4 million diluted shares) in the same period of 2018. Adjusted net income rose to $110.1 million, or $0.48 per diluted share ($0.48 CER), from $93.7 million, or $0.40 per diluted share, in the prior-year quarter. Results for the fourth quarter of 2019 included an after-tax charge of $0.12 per share (based on 231.3 million diluted shares) for restructuring measures.
Full-year 2019 results
Total net sales grew 2% at actual rates to $1.526 billion in 2019 compared to $1.502 billion in 2018, and rose 4% CER as currency movements against the U.S. dollar had a negative impact of two percentage points. The acquisition of N-of-One provided revenues of about $5 million for full-year 2019.
Operating loss was $26.1 million in 2019 compared to operating income of $266.6 million in 2018. Results in 2019 included $301.8 million of pre-tax charges related to the decision to discontinue NGS instrument development programs and prioritize resources. Adjusted operating income – which excludes purchased intangibles amortization, long-lived asset impairments and other items such as business integration, acquisition-related costs, litigation costs and restructuring – rose 5% to $421.8 million (27.6% of sales) from $403.3 million (26.9% of sales) in 2018.
The net loss for 2019 was $41.5 million, or a net loss of $0.18 per share (based on 226.8 million basic shares) compared to net income for 2018 of $190.4 million, or $0.82 per diluted share (based on 233.5 million diluted shares). Adjusted net income for 2019 was $332.8 million, or $1.43 per diluted share ($1.46 CER), compared to $311.9 million, or $1.34 per diluted share, in 2018. Results for the 2019 period included an after-tax charge of $1.01 per share (based on 232.4 million diluted shares) for the restructuring measures.
Balance sheet and cash flows

At December 31, 2019, cash, cash equivalents and restricted cash were $629.4 million compared to $1.16 billion at December 31, 2018. Net cash provided by operating activities in 2019 was $330.8 million compared to $359.5 million in the year-ago period. Free cash flow was $212.9 million compared to $249.7 million, as purchases of Property, Plant and Equipment rose to $117.9 million (7.7% of sales) from $109.8 million (7.3% of sales) in 2018. Net cash used in investing activities was $222.3 million in 2019, including $125.0 million for the acquisition of digital PCR assets, compared to $211.4 million in 2018. Net cash used in financing activities was $639.1 million for 2019, which included $430.0 million for redemption of the 2019 convertible notes, $73.0 million in repayments during the fourth quarter for a tranche of the U.S. private placement and $74.4 million for share repurchases. This compares to net cash provided by financing activities of $360.4 million in 2018, which included $494.9 million from debt issuances during the year, partially offset by $104.7 million for share repurchase programs.
Sample to Insight portfolio update
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:

The QIAsymphony automation system surpassed 2,500 cumulative placements at the end of 2019, supporting solid single-digit CER growth in related consumables. QIAGEN is adding applications to this modular system, including a newly launched kit to automate microbiome sample preparation, further confirming QIAGEN’s leadership in sample technologies.

Automation of QuantiFERON-TB Gold Plus (QFT-Plus) on DiaSorin’s widely used LIAISON platforms gained U.S. regulatory approval in November 2019, and the two companies launched U.S. commercial activities for this new processing option.

QIAGEN’s next-generation sequencing (NGS) solutions continued to expand in 2019, with sales totaling over $180 million.

The QIAstat-Dx system is approaching 1,000 cumulative placements and reached $15 million of sales in 2019. The U.S. submission for regulatory approval of a new gastrointestinal panel was completed in late 2019, while a new meningitis panel remains on track for launch in Europe in the first half of 2020.

More than 660 placements of the QIAcube Connect low-throughput sample processing instrument were completed in 2019, primarily targeting Life Sciences customers. The new automation solution builds on over 8,000 placements of the first-generation QIAcube system. The QIAcube connect and QIAsymphony automation systems together provide a full range of options for sample processing.

The launch of QIAcuity, the new nanoplate-based digital PCR system, is on track for mid-2020. QIAGEN is developing this series of differentiated new platforms to make cost-efficient, highly versatile digital PCR technology available to Life Sciences laboratories worldwide.

In Precision Medicine, a new collaboration with Amgen was announced in January 2020 with the aim to develop tissue-based companion diagnostics for Amgen’s investigational new therapy in non-small cell lung cancer targeting KRAS G12C, a genetic mutation and common cause of cancer.

Late in the fourth quarter, QIAGEN completed the divestment of its NeXtal Biotechnologies line of structural biology products, which had sales of less than $5 million in 2019.
Measures to prioritize resource allocation implemented
QIAGEN implemented a set of initiatives announced in October 2019 as part of a new orientation for the NGS portfolio and measures to prioritize resource allocation. These steps include a new 15-year partnership with Illumina to broaden the global availability and use of NGS-based in vitro diagnostic (IVD) kits to deliver insights for clinical decision-making, including companion diagnostics for precision medicine. QIAGEN also announced in October that it was discontinuing development of new NGS instruments and implementing other measures, resulting in a pre-tax charge of $276.8 million in operating results (net loss of $0.89 per share) for the third quarter of 2019, and a pre-tax charge of $24.9 million in operating results (net loss of $0.12 per share) for the fourth quarter of 2019. QIAGEN currently anticipates additional pre-tax charges of about $20 million in the first half of 2020 from these measures.
Outlook
QIAGEN announced its outlook for full-year 2020, with net sales expected to grow about 3-4% CER and adjusted diluted EPS to be about $1.52-1.54 CER per share. The sales outlook takes into consideration overall growth in QIAGEN’s Sample to Insight portfolio, offset by significant headwinds from an anticipated double-digit CER decline in companion diagnostic co-development revenues due to the new orientation for QIAGEN’s NGS strategy announced in October 2019. The outlook also takes into consideration expectations for lower sales in China in the first half of 2020 mainly due to the slowdown in orders from distributors that began in mid-2019 and the end of the China NGS joint venture announced in 2019. It does not take into account any exceptional sales of products that can be used for testing related to efforts to contain the coronavirus outbreak. This outlook also does not take into consideration any future acquisitions, including the potential acquisition of the remaining stake in NeuMoDx Molecular, Inc., for approximately $234 million through an option that expires in mid-2020.
Based on exchange rates as of January 31, 2020, currency movements against the U.S. dollar are expected to create an adverse impact of about one percentage point on net sales growth at actual rates for full-year 2020, and an adverse impact of $0.01 per share on adjusted EPS.

For the first quarter of 2020, net sales are expected to grow about 2-3% CER. Adjusted diluted EPS is expected to be $0.28-0.29 CER. Based on exchange rates as of January 31, 2020, currency movements against the U.S. dollar are expected to create an adverse impact of about 1-2 percentage points on net sales growth at actual rates, and an adverse impact of up to $0.01 per share on adjusted EPS.
Quarterly results presentation, conference call and webcast details
A presentation with additional information can be downloaded at View Source A conference call is planned for Wednesday February 5, 2020, at 15:00 Central European Time (CET) / 9:00 Eastern Standard Time (EST). 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 & 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 February 3, 2020 OncoSec Medical Incorporated ("OncoSec") (Nasdaq: ONCS), a company developing late-stage intratumoral cancer immunotherapies, reported data from a feasibility study of its visceral lesion applicator (VLA) electroporation device that were presented at the Annual Meeting of the Society of Interventional Oncology (SIO) in New Orleans (Press release, OncoSec Medical, FEB 3, 2020, View Source [SID1234553763]). The study, which was awarded "Best Technology Scientific Abstract" at SIO, showed investigators were able to successfully and safely reach target organs located deep inside the body and deploy the device’s applicator tip in a large animal model.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

In the study, titled, "Novel Electroporation Device Platform Supports Controlled Delivery of Potent Immunotherapy Directly to Target Organs," healthy animal subjects were placed under general anesthesia while investigators safely and successfully accessed and deployed the VLA in the lungs with a flexible, catheter-based applicator using a bronchoscope and a steerable catheter, and liver using ultrasound-guided laparoscopy with a rigid-trocar-based applicator. Electroporation was performed in the liver using the APOLLO generator with no adverse effects recorded during or after electroporation. Additionally, initial data from the APOLLO generator’s built-in feedback system embedded within the platform detected and recorded trends in impedance values between different tissue types, as well as between the presence and absence of DNA. The APOLLO generator was also able to indicate when the applicator tip was not effectively placed within the tissue. These data highlight the safety mechanisms as well as the future possibility of differentiating between healthy tissue and a local tumor.

"These early feasibility trials are an important confirmation of our VLA platform and help to pave the way toward, initially, safety data to include in an investigational device exemption (IDE) application and eventually a Phase 1 safety trial in human subjects," said Daniel J. O’Connor, President and CEO of OncoSec. "It is an important step toward the development of our platform as a complete and dynamic treatment system that will allow us to continue to treat cancer in internal organs utilizing the electroporation of TAVO (plasmid-based interleukin-12) to eliminate cancer cells."

On February 3, 2020 United Therapeutics Corporation (Nasdaq: UTHR) reported topline results from the phase 2/3 DISTINCT clinical study evaluating Unituxin (dinutuximab) Injection added to irinotecan compared to irinotecan or topotecan alone in patients with relapsed or refractory small cell lung cancer (SCLC) (Press release, United Therapeutics, FEB 3, 2020, View Source [SID1234553764]). The DISTINCT trial did not meet its primary efficacy objective of extending the overall survival with Unituxin and irinotecan versus using irinotecan alone. The safety profile of dinutuximab in DISTINCT was consistent with prior studies and the current Unituxin product label.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

Full data from the DISTINCT study will be made available through scientific disclosure at upcoming conferences and in peer-reviewed publications.

"We thank the principal investigators, patients and their families for participating in the DISTINCT study" said Gil Golden, M.D., Ph.D., Chief Medical Officer of United Therapeutics. "We’re clearly disappointed with the DISTINCT results but we’ll continue to seek out underappreciated avenues in our core therapeutic areas addressing rare diseases in oncology and pulmonary hypertension. In addition, we look forward to announcing the results of our INCREASE study by the end of the first quarter or shortly thereafter."

United Therapeutics is also pursuing a label expansion for Unituxin in combination with irinotecan and temozolomide for the treatment of pediatric patients with relapsed or refractory neuroblastoma, based on results from the ANBL1221 study conducted by the Children’s Oncology Group. United Therapeutics plans to meet with the FDA to discuss the proposed label expansion in the first half of 2020 and file a supplemental BLA shortly thereafter.

About DISTINCT

DISTINCT was a phase 2/3, two-part, open-label, randomized, international, multi-center study of dinutuximab and irinotecan versus irinotecan for second line treatment of patients with relapsed or refractory small cell lung cancer. The phase 2 portion of the study of 12 patients was completed in October 2017. Global enrollment in the phase 3 portion of the study was completed in October 2018 with a total of 471 patients. Patients were randomized 2:2:1 into three arms: irinotecan (190 patients); irinotecan and dinutuximab (187 patients); or topotecan (94 patients). This event-driven study was conducted in 198 centers from 22 countries in North America, Europe, and Asia-Pacific, with 312 observed deaths in the dinutuximab plus irinotecan and irinotecan alone groups as of the data extract used for analysis. The primary objective of this study was to compare overall survival (OS) in patients treated with dinutuximab and irinotecan versus patients treated with irinotecan alone as a second-line treatment for relapsed or refractory small cell lung cancer (SCLCThe secondary objectives of the study were:

·To compare progression-free survival (PFS), objective response rate (ORR) (complete response [CR] + partial response [PR]), and clinical benefit rate (CR + PR + stable disease [SD]) in patients treated with dinutuximab and irinotecan to patients treated with irinotecan alone.
·To compare the safety of patients treated with dinutuximab and irinotecan to patients treated with irinotecan alone.
·To evaluate the pharmacokinetics (PK) of patients treated with dinutuximab.
·To compare OS, PFS, ORR, and clinical benefit rate (CBR) in patients treated with dinutuximab and irinotecan to patients treated with topotecan alone.

The exploratory objective of the study was to assess the relationship between selected biomarkers and survival of patients treated with dinutuximab.

About Unituxin

Indication

Unituxin is a GD2-binding monoclonal antibody indicated, in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and 13-cis-retinoic acid (RA), for the treatment of pediatric patients with high-risk neuroblastoma who achieve at least a partial response to prior first-line multiagent, multimodality therapy.

Important Safety Information for Unituxin

CONTRAINDICATIONS

Unituxin is contraindicated in patients with a history of anaphylaxis to dinutuximab.

WARNINGS AND PRECAUTIONS

BOXED WARNING

Serious Infusion Reactions

·Serious and potentially life-threatening infusion reactions (facial and upper airway edema, dyspnea, bronchospasm, stridor, urticaria, and hypotension) occurred in 26% of patients treated with Unituxin.

·Administer required prehydration and premedication including antihistamines prior to each Unituxin infusion.

·Monitor patients closely for signs and symptoms of an infusion reaction during and for at least four hours following completion of each Unituxin infusion.

·Immediately interrupt Unituxin for severe infusion reactions and permanently discontinue Unituxin for anaphylaxis.

Neurotoxicity

·Unituxin causes serious neurologic adverse reactions including severe neuropathic pain and peripheral neuropathy.

·Severe neuropathic pain occurs in the majority of patients.

·Administer intravenous opioid prior to, during, and for 2 hours following completion of the Unituxin infusion.

·In clinical studies of patients with high-risk neuroblastoma, severe (Grade 3) peripheral sensory neuropathy ranged from 2% to 9%.

·In clinical studies of Unituxin and related GD2-binding antibodies, severe motor neuropathy has occurred. Resolution of motor neuropathy did not occur in all cases.

·Discontinue Unituxin for severe unresponsive pain, severe sensory neuropathy, and moderate to severe peripheral motor neuropathy.

Serious Infusion Reactions

·Serious infusion reactions requiring urgent intervention including blood pressure support, bronchodilator therapy, corticosteroids, infusion rate reduction, infusion interruption, or permanent discontinuation of Unituxin included facial and upper airway edema, dyspnea, bronchospasm, stridor, urticaria, and hypotension. Infusion reactions generally occurred during or within 24 hours of completing the Unituxin infusion. Due to overlapping signs and symptoms, it was not possible to distinguish between infusion reactions and hypersensitivity reactions in some cases.

·Severe (Grade 3 or 4) infusion reactions occurred in 35 (26%) patients in the Unituxin/13-cis-retinoic acid (RA) group compared to 1 (1%) patient receiving RA alone. Severe urticaria occurred in 17 (13%) patients in the Unituxin/RA group but did not occur in the RA group. Serious adverse reactions consistent with anaphylaxis and resulting in permanent discontinuation of Unituxin occurred in 2 (1%) patients in the Unituxin/RA group. Additionally, 1 (0.1%) patient had multiple cardiac arrests and died within 24 hours after having received Unituxin in Study 2.

Neurotoxicity

·Pain: 114 (85%) patients treated in the Unituxin/RA group experienced pain despite pretreatment with analgesics including morphine sulfate infusion. Severe (Grade 3) pain occurred in 68 (51%) patients in the Unituxin/RA group compared to 5 (5%) patients in the RA group. For severe pain, decrease the Unituxin infusion rate to 0.875 mg/m2/hour. Discontinue Unituxin if pain is not adequately controlled despite infusion rate reduction and institution of maximum supportive measures.

·Peripheral Neuropathy: Severe (Grade 3) peripheral sensory neuropathy occurred in 2 (1%) patients and severe peripheral motor neuropathy occurred in 2 (1%) patients in the Unituxin/RA group. Permanently discontinue Unituxin in patients with peripheral motor neuropathy of Grade 2 or greater severity, Grade 3 sensory neuropathy that interferes with daily activities for more than 2 weeks, or Grade 4 sensory neuropathy.

·Neurological Disorders of the Eye:

·Neurological disorders of the eye experienced by two or more patients treated with Unituxin included blurred vision, photophobia, mydriasis, fixed or unequal pupils, optic nerve disorder, eyelid ptosis, and papilledema. In Study 1, 3 (2%) patients in the Unituxin/RA group experienced blurred vision, compared to no patients in the RA group. Diplopia, mydriasis, and unequal pupillary size occurred in 1 patient each in the Unituxin/RA group, compared to no patients in the RA group. The duration of eye disorders occurring in Study 1 was not documented. In Study 3, eye disorders occurred in 16 (15%) patients, and in 3 (3%) patients resolution of the eye disorder was not documented. Among the cases with documented resolution, the median duration of eye disorders was 4 days (range: 0, 221 days).

·Interrupt Unituxin in patients experiencing dilated pupil with sluggish light reflex or other visual disturbances that do not cause visual loss.

·Upon resolution and if continued treatment with Unituxin is warranted, decrease the Unituxin dose by 50%.

·Permanently discontinue Unituxin in patients who experience loss of vision and in patients with recurrent eye disorder following dose reduction.

·Prolonged Urinary Retention: Urinary retention that persists for weeks to months following discontinuation of opioids has occurred in patients treated with Unituxin. Permanently discontinue Unituxin in patients with prolonged urinary retention that does not resolve with discontinuation of opioids.

·Transverse Myelitis: Transverse myelitis has occurred in patients treated with Unituxin. Promptly evaluate any patient with signs or symptoms such as weakness, paresthesia, sensory loss, or incontinence. Permanently discontinue Unituxin in patients who develop transverse myelitis.

·Reversible Posterior Leukoencephalopathy Syndrome (RPLS): RPLS has occurred in patients treated with Unituxin. Institute appropriate medical treatment and permanently discontinue Unituxin in patients with signs and symptoms of RPLS (e.g., severe headache, hypertension, visual changes, lethargy, or seizures).

Capillary Leak Syndrome

·Severe (Grade 3 to 5) capillary leak syndrome occurred in 31 (23%) patients in the Unituxin/RA group and in no patients treated with RA alone.

·Depending on severity, manage by immediate interruption, infusion rate reduction or permanent discontinuation of Unituxin and institute supportive management in patients with symptomatic or severe capillary leak syndrome.

Hypotension

·Severe (Grade 3 or 4) hypotension occurred in 22 (16%) patients in the Unituxin/RA group compared to no patients in the RA group.

·Prior to each Unituxin infusion, administer required intravenous hydration.

·Closely monitor blood pressure during Unituxin treatment.

·Depending on severity, manage by immediate interruption, infusion rate reduction or permanent discontinuation of Unituxin and institute supportive management in patients with symptomatic hypotension.

Infection

·Severe (Grade 3 or 4) bacteremia requiring intravenous antibiotics or other urgent intervention occurred in 17 (13%) patients in the Unituxin/RA group compared to 5 (5%) patients treated with RA alone. Sepsis occurred in 24 (18%) of patients in the Unituxin/RA group and in 10 (9%) patients in the RA group.

·Monitor patients closely for signs and symptoms of systemic infection and temporarily discontinue Unituxin in patients who develop systemic infection until resolution of the infection.

Bone Marrow Suppression

·Severe (Grade 3 or 4) thrombocytopenia (39% vs. 25%), anemia (34% vs. 16%), neutropenia (34% vs. 13%), and febrile neutropenia (4% vs. 0 patients) occurred more commonly in patients in the Unituxin/RA group compared to patients treated with RA alone.

·Monitor peripheral blood counts closely during Unituxin therapy.

Electrolyte Abnormalities

·Electrolyte abnormalities occurring in at least 25% of patients who received Unituxin/RA in Study 1 included hyponatremia, hypokalemia, and hypocalcemia. Severe (Grade 3 or 4) hypokalemia and hyponatremia occurred in 37% and 23% of patients in the Unituxin/RA group, respectively, compared to 2% and 4% of patients in the RA group.

·Monitor serum electrolytes daily during therapy with Unituxin.

Atypical Hemolytic Uremic Syndrome

·Hemolytic uremic syndrome in the absence of documented infection and resulting in renal insufficiency, electrolyte abnormalities, anemia, and hypertension occurred in two patients following receipt of the first cycle of Unituxin.

·Permanently discontinue Unituxin and institute supportive management.

Embryo-Fetal Toxicity

·Unituxin may cause fetal harm.

·Advise pregnant women of the potential risk to a fetus.

·Advise females of reproductive potential to use effective contraception during treatment, and for two months after the last dose of Unituxin.

ADVERSE REACTIONS

The most common serious adverse reactions (≥ 5%) are infections, infusion reactions, hypokalemia, hypotension, pain, fever, and capillary leak syndrome.

The most common adverse drug reactions (≥ 25%) in Unituxin/RA compared with RA alone are pain (85% vs. 16%), pyrexia (72% vs. 27%), thrombocytopenia (66% vs. 43%), lymphopenia (62% vs. 36%), infusion reactions (60% vs. 9%), hypotension (60% vs. 3%), hyponatremia (58% vs. 12%), increased alanine aminotransferase (56% vs. 31%), anemia (51% vs. 22%), vomiting (46% vs. 19%), diarrhea (43% vs. 15%), hypokalemia (43% vs. 4%), capillary leak syndrome (40% vs. 1%), neutropenia (39% vs. 16%), urticaria (37% vs. 3%), hypoalbuminemia (33% vs. 3%), increased aspartate aminotransferase (28% vs. 7%), and hypocalcemia (27% vs. 0%). In post-approval use of Unituxin, the adverse reactions of prolonged urinary retention, transverse myelitis, and reversible posterior leukoencephalopathy syndrome were observed. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency.

On February 3, 2020 Kitov Pharma Ltd. ("Kitov") (NASDAQ/TASE: KTOV), a clinical-stage company advancing first-in-class therapies to overcome tumor immune evasion and drug resistance, reported receipt from the U.S. Patent and Trademark Office (USPTO) of a Notification of Issuance for a patent application entitled, "Humanized antibodies against CEACAM1 (Press release, Kitov Pharmaceuticals , FEB 3, 2020, View Source [SID1234553782])." The patent, which expires in 2035, covers protein and DNA sequences pertaining to humanized antibodies capable of specific binding to human CEACAM1 molecules, including Kitov’s first-in-class monoclonal antibody, CM-24, pharmaceutical compositions comprising these antibodies, as well as methods for their use in treating and diagnosing cancer and other conditions.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"This recognition from the USPTO validates the unique profile of Kitov’s CM-24. The mechanism of action of CM-24 results in an enhanced cytotoxic activity of the immune system cells, inducing a tumor’s death," commented Isaac Israel, Chief Executive Officer of Kitov. "CEACAM1 expression was found to correlate with poor prognosis in patients with non-small cell lung cancer (NSCLC). We strongly believe that the combination of CM-24 with nivolumab has the potential to result in a significant synergistic benefit in patients with NSCLC tumors expressing CEACAM1. We look forward to the initiation of our phase 1/2 clinical trial with CM-24 in the second half of 2020."

About CM-24

CM-24 is a clinical-stage monoclonal antibody blocking CEACAM1, a well-validated target which is highly expressed in many solid tumors as well as on immune cells and plays a pivotal role in the immune system by blocking immune cells’ access to tumors by CEACAM1-CEACAM1 and CEACAM1-CEACAM5 interaction. CEACAM1 was also shown to regulate TIM3 which induce immune fatigue. This unique mechanism of action positions CM-24 with a differentiated inhibitor of a multi-role immune checkpoint. In a monotherapy phase 1 study, CM-24 demonstrated safety and efficacy with standard dose in about 30% of patients. Kitov will advance CM-24 as a combination therapy with anti-PD1 checkpoint inhibitors for the treatment of non-small cell lung cancer (NSCLC). Kitov has entered into a clinical collaboration agreement with Bristol Myers Squibb Company (NYSE:BMY) for the planned Phase 1/2 clinical trials to evaluate the combination of CM-24 with the PD-1 inhibitor nivolumab (Opdivo).

On February 3, 2020 Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company pioneering immuno-neurology, reported the closing of its previously announced underwritten public offering of 9,602,500 shares of its common stock at the public offering price of $25.00 per share (Press release, Alector, FEB 3, 2020, View Source [SID1234553766]). This includes 1,252,500 shares sold pursuant to the underwriters’ full exercise of their option to purchase additional shares. Alector received total gross proceeds of approximately $240.0 million, before deducting the underwriting discounts and commissions and other offering expenses.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

Morgan Stanley, Goldman Sachs & Co. LLC, BofA Securities, and Cowen acted as joint book-running managers for the offering.

Registration statements relating to the securities were filed with, and declared effective by, the Securities and Exchange Commission (the "SEC"). Copies of the registration statements can be accessed through the SEC’s website at www.sec.gov. This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

The offering was made only by means of a prospectus. Copies of the final prospectus relating to the offering may be obtained from:

Morgan Stanley & Co. LLC, Attention: Prospectus Department, 180 Varick Street, 2nd Floor, New York, New York 10014 or by email at [email protected];
Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, New York 10282, or by email at [email protected];
BofA Securities, NC1-004-03-43, 200 North College Street, 3rd Floor, Charlotte, NC 28255-0001, Attn: Prospectus Department, or by email [email protected]; or
Cowen and Company, LLC c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY, 11717, Attn: Prospectus Department, by email at [email protected] or by telephone at (833) 297-2926.