VBL Therapeutics to Present at Upcoming Conferences in June

On May 24, 2018 VBL Therapeutics (Nasdaq:VBLT), a clinical-stage biotechnology company focused on the discovery, development and commercialization of first-in-class treatments for cancer, reported that the Company will present an update on the OVAL Phase 3 trial of VB-111 in platinum-resistant ovarian cancer at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2018 Annual Meeting, to be held June 1-5 in Chicago, Illinois (Press release, VBL Therapeutics, MAY 24, 2018, View Source [SID1234526889]). In addition the Company will present data on its novel MOSPD2 program at the 2018 BIO International Convention, to be held June 4-7, 2018 in Boston.

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2018 ASCO (Free ASCO Whitepaper) Annual Meeting – Presentation Details

Title: Clinical trial in progress: A study of VB-111 combined with paclitaxel vs. paclitaxel for treatment of recurrent platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018).
Abstract: TPS5609
Session Title: Gynecologic Cancer
Date: June 4, 2018
Time: 1:15 PM-4:45 PM CDT
Location: Hall A
Poster Board: #331b
Presenter: Dr. Richard T. Penson, M.D.,MRCP, associate professor of Medicine, Harvard Medical School, clinical director of Medical Gynecologic Oncology, Massachusetts General Hospital
2018 BIO International Convention – Presentation Details

Date: Tuesday, June 5, 2018
Time: 2:45 pm EDT
Presentation Room: Theater 1
Location: Boston Convention & Exhibition Center
Webcast: Bio International Webcast Link
About VB-111 (ofranergene obadenovec)
VB-111, a potential first-in-class anticancer therapeutic candidate, is the Company’s lead oncology product currently being studied in a Phase 3 trial for ovarian cancer. VB-111 has received an Orphan Designation for the treatment of ovarian cancer by the European Medicines Agency (EMA). At the 2016 ASCO (Free ASCO Whitepaper), the Company presented data in platinum-resistant ovarian cancer, demonstrating a meaningful and significant increase in overall survival with VB-111 given in combination with chemotherapy (810 days vs. 172 days, p=0.042), along with a 60% durable CA-125 response rate—approximately two times the historical response observed with bevacizumab (Avastin) plus chemotherapy in ovarian cancer. The OVAL study is conducted in collaboration with the Gynecologic Oncology Group (GOG) Foundation, Inc., a leading organization for research excellence in the field of gynecologic malignancies.

About MOSPD2
MOSPD2 is a novel tumor-related target identified by VBL that may be used as a marker for selective targeting of several types of tumors. Research conducted by VBL has shown that MOSPD2 is a novel membrane protein found on tumor cells that is present when they start invading tissues or creating metastatic lesions. The Company believes that targeting of MOSPD2 may have several therapeutic applications, including inhibition of tumor cell metastases and targeting of MOSPD2-positive tumor cells. There are also potential applications in the inhibition of monocyte migration in chronic inflammatory conditions. VBL is developing the VB-600 series of pipeline candidates towards these applications.

McKesson Reports Fiscal 2018 Fourth-Quarter and Full-Year Results

On May 24, 2018 McKesson Corporation (NYSE:MCK) reported that revenues for the fourth quarter ended March 31, 2018, were $51.6 billion, up 6% compared to $48.7 billion a year ago (Press release, McKesson, MAY 24, 2018, View Source [SID1234526887]). On a constant currency basis, revenues increased 4% over the prior year. For the fiscal year, McKesson had revenues of $208.4 billion, up 5% compared to $198.5 billion a year ago. On a constant currency basis, revenues increased 4% over the prior year.

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On the basis of U.S. generally accepted accounting principles ("GAAP"), fourth-quarter loss per diluted share from continuing operations was $(5.58), compared to earnings per diluted share of $16.79 a year ago. Full-year GAAP earnings per diluted share from continuing operations was $0.30, compared to $23.28 a year ago. Fourth-quarter GAAP loss per diluted share and full-year GAAP earnings per share included after-tax net charges totaling $1.9 billion and $2.6 billion, respectively, or $9.07 and $12.32 per diluted share, respectively, driven primarily by non-cash goodwill and long-lived asset impairment charges in the company’s European and Canadian retail businesses, partially offset by benefits related to the Tax Cuts and Jobs Act of 2017.

Prior year fourth-quarter and full-year GAAP earnings per diluted share included an after-tax net gain of $3.0 billion, or $14.10 per diluted share and $13.53 per diluted share, respectively, related to the creation of the Change Healthcare joint venture.

Fourth-quarter Adjusted Earnings per diluted share was $3.49, up 2% compared to $3.41 a year ago. Full-year Adjusted Earnings per diluted share was $12.62, up 1% compared to $12.54 for the prior year, which includes the $0.31 per diluted share contribution to create a non-profit foundation.

For the full year, McKesson generated cash from operations of $4.3 billion and ended the year with cash and cash equivalents of $2.7 billion. During the year, McKesson repaid approximately $765 million in net long-term debt, paid $2.9 billion for acquisitions, repurchased approximately $1.7 billion of its common stock, invested $580 million internally and paid $262 million in dividends."

"While we realized significant charges in the fourth quarter reflecting challenging market conditions in Europe and Canada, I’m pleased with the Fiscal 2018 performance across our other businesses. And the strength of our balance sheet and cash flow enabled us to make internal investments and acquisitions that will drive growth," said John H. Hammergren, chairman and chief executive officer. "This strong financial position, combined with actions we are taking in relation to our recently announced multi-year strategic growth initiative, ensures McKesson’s ongoing focus on delivering shareholder value.

"We also returned capital to shareholders through share repurchases and a quarterly dividend. And yesterday, our Board of Directors approved an additional share repurchase authorization of $4 billion, as we believe that the company’s shares are an attractive investment opportunity and repurchasing stock is an important part of our diversified capital allocation strategy," continued Hammergren.

Segment Results

Distribution Solutions revenues were $51.6 billion for the quarter, up 7% on a reported basis and 5% on a constant currency basis. For the full year, Distribution Solutions revenues were $208.1 billion, up 6% on a reported basis and 5% on a constant currency basis, compared to the prior year.

North America pharmaceutical distribution and services revenues of $42.7 billion for the quarter were up 5% on both a reported basis and constant currency basis. For the full year, North America pharmaceutical distribution and services revenues were $174.2 billion, up 6% on both a reported and constant currency basis, compared to the prior year. Revenue growth for the quarter and the full year was driven primarily by market growth and acquisitions, partially offset by branded to generic conversions.

International pharmaceutical distribution and services revenues were $7.2 billion for the quarter, up 19% on a reported basis and 4% on a constant currency basis, driven by acquisitions and market growth, which were the same factors that drove full year revenues of $27.3 billion, up 10% on a reported basis and up 5% on a constant currency basis, compared to the prior year.

Medical-Surgical distribution and services revenues were $1.7 billion for the quarter, up 9%, driven primarily by market growth, including the impact of a stronger flu season. For the full year, Medical-Surgical distribution and services revenues were $6.6 billion, up 6% compared to the prior year.

Fourth-quarter Distribution Solutions GAAP operating loss was $(689) million and GAAP operating margin was (1.33)%. On a constant currency basis, fourth-quarter adjusted operating profit was $1.1 billion, up 8% from the prior year on a reported basis and 7% on a constant currency basis. Adjusted operating margin for the Distribution Solutions segment was 2.26% on a constant currency basis. Adjusted operating margin excluding noncontrolling interests for the Distribution Solutions segment was 2.17% on a constant currency basis.

For the full year, Distribution Solutions GAAP operating profit was $1.2 billion and GAAP operating margin was 0.59%. On a constant currency basis, full-year adjusted operating profit was $4.1 billion, up 8% from the prior year on a reported basis and 7% on a constant currency basis. Adjusted operating margin for the Distribution Solutions segment was 1.96% on a constant currency basis. Adjusted operating margin excluding noncontrolling interests for the Distribution Solutions segment was 1.87% on a constant currency basis.

Fourth-quarter Technology Solutions GAAP operating profit was $23 million. Fourth-quarter adjusted operating profit was $72 million, driven by the company’s proportionate share of the income from McKesson’s equity investment in Change Healthcare.

Full-year Technology Solutions GAAP operating loss was $(23) million. Full-year adjusted operating profit was $304 million, primarily driven by the company’s proportionate share of the income from McKesson’s equity investment in Change Healthcare.

Fiscal Year 2018 Reconciliation of GAAP Results to Adjusted Earnings

Adjusted Earnings per diluted share of $12.62 for the fiscal year ending March 31, 2018, excludes the following GAAP items:

Amortization of acquisition-related intangibles of $2.60 per diluted share;
Acquisition-related expenses and adjustments of $1.20 per diluted share;
Last-In-First-Out ("LIFO") inventory-related credits of 31 cents per diluted share;
Restructuring charges of $2.82 per diluted share, including non-cash long-lived asset impairment charges; and
Other adjustment net charges of $6.01 per diluted share, primarily including non-cash goodwill asset impairment charges, partially offset by benefits related to the Tax Cuts and Jobs Act of 2017.
Revised Segment Financial Reporting Effective Fiscal Year 2019

Following the retirement of the president of Distribution Solutions in January 2018 and an evaluation of the company’s management and operating structure, McKesson has revised its reportable segments commencing in the first quarter of Fiscal 2019. McKesson’s new reportable segments are:

U.S. Pharmaceutical and Specialty Solutions, which includes the U.S. Pharmaceutical and McKesson Specialty Health businesses;
European Pharmaceutical Solutions; and
Medical-Surgical Solutions.
All remaining operating segments and business activities that are not significant enough to require reportable segment disclosure will be included in Other. Other primarily includes McKesson Canada, McKesson Prescription Technology Solutions (MRxTS) and the company’s equity method investment in Change Healthcare.

Please refer to a second 8-K filed today with the Securities and Exchange Commission for historical supplemental information for the fiscal years ending March 31, 2018; March 31, 2017; and March 31, 2016 reflecting historical results by revised reportable segment.

Fiscal Year 2019 Outlook

McKesson expects Adjusted Earnings per diluted share of $13.00 to $13.80 for the fiscal year ending March 31, 2019.

"Our Fiscal 2019 outlook represents mid- to high-single digit percentage growth year over year, reflecting a more stable market environment and effective capital allocation, while including the previously outlined headwinds in our European and Rexall businesses," Hammergren concluded.

McKesson has ceased providing forward-looking guidance on a GAAP basis as the company is unable to provide a quantitative reconciliation of this forward-looking non-GAAP measure to the most directly comparable forward-looking GAAP measure, without unreasonable effort, as items are inherently uncertain and depend on various factors, many of which are beyond the company’s control.

Key Assumptions for Fiscal 2019

The Fiscal 2019 outlook is based on the following key assumptions and is also subject to the Risk Factors outlined below:

McKesson to deliver mid-single digit percent revenue growth and down slightly to up mid-single digit percent adjusted income from operations growth in Fiscal 2019.
U.S. Pharmaceutical and Specialty Solutions to deliver low- to mid-single digit percent revenue growth and flat to down mid-single digit percent adjusted operating profit growth in Fiscal 2019.
European Pharmaceutical Solutions to deliver flat to mid-single digit percent revenue and adjusted operating profit growth in Fiscal 2019.
Medical-Surgical Solutions is expected to deliver low-double digit percent revenue growth and mid- to high-single digit percent adjusted operating profit growth in Fiscal 2019.
Other is expected to deliver low-single digit percent revenue growth and adjusted operating profit to be flat in Fiscal 2019, which includes a gross headwind of between $100 million and $120 million related to the generic pricing initiative the Canadian provincial governments enacted April 1, 2018, as well as the impact of an increase in minimum wage in multiple provinces.
Adjusted equity earnings from the company’s investment in Change Healthcare are expected to grow in the low- to mid-single digit percent in Fiscal 2019.
Expect low-double digit percent decline in corporate expenses compared to Fiscal 2018.
Interest expense is expected to decline year over year.
The guidance range assumes a full-year adjusted tax rate of approximately 21% to 23%, which may vary from quarter to quarter.
Income attributable to noncontrolling interests is expected to decline year over year.
The company’s ownership position in McKesson Europe is assumed to be approximately 77% for Fiscal 2019.
Foreign currency exchange rate movements are assumed to have a net favorable impact of up to 10 cents per diluted share year over year.
Commencing in Fiscal 2019, the company will provide free cash flow guidance. Free cash flow is expected to be approximately $3.0 billion, which is net of expected property acquisitions and capitalized software expenditures of between $600 million and $800 million.
Weighted average diluted shares used in the calculation of earnings per share are expected to be approximately 200 million for the year.
Adjusted Earnings

McKesson separately reports financial results on the basis of Adjusted Earnings. Adjusted Earnings is a non-GAAP financial measure defined as GAAP income from continuing operations, excluding amortization of acquisition-related intangible assets, acquisition-related expenses and adjustments, LIFO inventory-related adjustments, gains from antitrust legal settlements, restructuring charges, and other adjustments. A reconciliation of McKesson’s GAAP financial results to Adjusted Earnings is provided in Schedules 2, 3 and 4 of the financial statement tables included with this release.

The company will not provide forward-looking guidance on a GAAP basis prospectively as McKesson is unable to provide a quantitative reconciliation of this forward-looking non-GAAP measure to the most directly comparable forward-looking GAAP measure, without unreasonable effort, because McKesson cannot reliably forecast LIFO inventory-related adjustments, gains from antitrust legal settlements, restructuring charges, and other adjustments, which are difficult to predict and estimate. These items are inherently uncertain and depend on various factors, many of which are beyond the company’s control, and as such, any associated estimate and its impact on GAAP performance could vary materially.

Constant Currency

McKesson also presents its financial results on a constant currency basis. The company conducts business worldwide in local currencies, including the Euro, British pound and Canadian dollar. As a result, the comparability of the financial results reported in U.S. dollars can be affected by changes in foreign currency exchange rates. Constant currency information is presented to provide a framework for assessing how the company’s business performed excluding the effect of foreign currency exchange rate fluctuations. The supplemental constant currency information of the company’s GAAP financial results and Adjusted Earnings (Non-GAAP) is provided in Schedule 3 of the financial statement tables included with this release.

Non-GAAP Measures

McKesson also provides adjusted operating profit margin excluding noncontrolling interests. The company has arrangements involving third-party noncontrolling interests. As a result, pre-tax results are affected by the portion of pre-tax earnings attributable to noncontrolling interests. Adjusted operating profit margin excluding noncontrolling interests information is presented to provide a framework for assessing how the company’s business performed excluding the effect of pre-tax earnings that is not attributable to McKesson. The supplemental adjusted operating profit margin excluding noncontrolling interests information of the company’s GAAP financial results and Adjusted Earnings (Non-GAAP) is provided in Schedule 3 of the financial statement tables included with this release.

McKesson also provides a free cash flow estimate on a forward-looking basis. Free cash flow is defined as net cash provided by operating activities less property acquisitions and capitalized software expenditures, as outlined in the company’s condensed consolidated statements of cash flows.

Risk Factors

Except for historical information contained in this press release, matters discussed may constitute "forward-looking statements" within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, as amended, that involve risks and uncertainties that could cause actual results to differ materially from those projected, anticipated or implied. These statements may be identified by their use of forward-looking terminology such as "believes", "expects", "anticipates", "may", "will", "should", "seeks", "approximately", "intends", "plans", "estimates" or the negative of these words or other comparable terminology. The discussion of financial trends, strategy, plans or intentions may also include forward-looking statements. It is not possible to predict or identify all such risks and uncertainties; however, the most significant of these risks and uncertainties are described in the company’s Form 10-K, Form 10-Q and Form 8-K reports filed with the Securities and Exchange Commission and include, but are not limited to: changes in the U.S. healthcare industry and regulatory environment; managing foreign expansion, including the related operating, economic, political and regulatory risks; changes in the Canadian healthcare industry and regulatory environment; exposure to European economic conditions, including recent austerity measures taken by certain European governments; changes in the European regulatory environment with respect to privacy and data protection regulations; fluctuations in foreign currency exchange rates; the company’s ability to successfully identify, consummate, finance and integrate acquisitions; the performance of the company’s investment in Change Healthcare; the company’s ability to manage and complete divestitures; material adverse resolution of pending legal proceedings; competition and industry consolidation; substantial defaults in payment or a material reduction in purchases by, or the loss of, a large customer or group purchasing organization; the loss of government contracts as a result of compliance or funding challenges; public health issues in the U.S. or abroad; cyberattack, natural disaster, or malfunction of sophisticated internal computer systems to perform as designed; the adequacy of insurance to cover property loss or liability claims; the company’s proprietary products and services may not be adequately protected, and its products and solutions may be found to infringe on the rights of others; system errors or failure of our technology products or services to conform to specifications; disaster or other event causing interruption of customer access to data residing in our service centers; changes in circumstances that could impair our goodwill or intangible assets; new or revised tax legislation or challenges to our tax positions; general economic conditions, including changes in the financial markets that may affect the availability and cost of credit to the company, its customers or suppliers; changes in accounting principles generally accepted in the United States of America; withdrawal from participation in multiemployer pension plans or if such plans are reported to have underfunded liabilities; inability to realize the expected benefits from the company’s restructuring and business process initiatives; difficulties with outsourcing and similar third party relationships; risks associated with the company’s retail expansion; and the company’s inability to keep existing retail store locations or open new retail locations in desirable places. The reader should not place undue reliance on forward-looking statements, which speak only as of the date they are first made. Except to the extent required by law, the company undertakes no obligation to publicly release the result of any revisions to these forward-looking statements to reflect events or circumstances after the date hereof, or to reflect the occurrence of unanticipated events.

Conference Call Details

The company has scheduled a conference call for today, Thursday, May 24th, at 8:00 AM ET. The dial-in number for individuals wishing to participate on the call is 323-701-0225. Craig Mercer, senior vice president, Investor Relations, is the leader of the call, and the password to join the call is ‘McKesson’. A telephonic replay of this conference call will be available for five calendar days. The dial-in number for individuals wishing to listen to the replay is 719-457-0820 and the pass code is 3609926. An archive of the conference call will also be available on the company’s Investor Relations website at View Source

Shareholders are encouraged to review the company’s filings with the Securities and Exchange Commission.

Foundation Medicine Establishes Immuno-Oncology Companion Diagnostics Collaboration with Merck

On May 24, 2018 Foundation Medicine, Inc. (NASDAQ:FMI) reported a collaboration with Merck, known as MSD outside the United States and Canada, to develop companion diagnostic tests for use with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy and the first approved immunotherapy for microsatellite instability (MSI) high or mismatch repair deficient solid tumors (Press release, Foundation Medicine, MAY 24, 2018, View Source [SID1234526886]). The companion diagnostic tests will leverage FoundationOne CDx, Foundation Medicine’s FDA-approved comprehensive genomic profiling (CGP) assay for all solid tumors incorporating multiple companion diagnostics. The companies will collaborate on the development of a pan-cancer companion diagnostic to measure MSI. In addition, they plan to develop companion diagnostics for tumor mutational burden (TMB), as well as additional potential novel biomarkers of response.

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"By collaborating, Merck and Foundation Medicine can continue to push the frontier on innovation in immuno-oncology and personalized cancer care, making a positive difference in the lives of individuals with cancer," said Melanie Nallicheri, chief business officer and head, biopharma for Foundation Medicine. "The addition of MSI and TMB companion diagnostics to FoundationOne CDx re-affirms the validity and clinical utility of these critical immuno-oncology biomarkers, can simplify diagnostic testing through the use of one test that provides physicians with necessary information to both rule-in and rule-out potential treatment options based on each patient’s genomic and biomarker status, and can help accelerate patient access to personalized healthcare."

"Rapidly evolving knowledge of cancer biology and immuno-oncology continues to improve understanding of how to deploy our medicines to identify those patients most likely to respond effectively," said Dr. Eric Rubin senior vice president oncology clinical development, Merck Research Laboratories. "We look forward to working with Foundation Medicine on this companion diagnostics strategy."

FoundationOne CDx, an FDA-approved CGP assay for all solid tumors, assesses genomic alterations in 324 genes known to drive cancer growth, providing potentially actionable information to help guide treatment options. FoundationOne CDx is also FDA-approved as a broad companion diagnostic for patients with certain types of non-small cell lung cancer, melanoma, colorectal cancer, ovarian cancer or breast cancer to identify those patients who may benefit from treatment with one of 17 on-label targeted therapies, 12 of which are approved as first line therapy for their respective indications. FoundationOne CDx also reports genomic biomarkers, such as MSI and TMB, that can help inform the use of other targeted oncology therapies, including immunotherapies and relevant clinical trial information. In all of these ways, FoundationOne CDx is available to biopharma companies as an FDA-approved platform for clinical research and as a CGP platform for biopharma companies seeking to develop companion diagnostics for their precision therapeutics.

FoundationOne CDx is available to order online at www.foundationmedicine.com/genomic-testing/order, or visit View Source to sign up for an account.

Karyopharm and Antengene Sign Exclusive License Agreement to Develop and Commercialize Selinexor, Eltanexor, Verdinexor and KPT-9274 in China and Other Regions in Asia

On May 24, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI) (Karyopharm) and Antengene Corporation (Antengene), reported their entry into an exclusive license agreement for the development and commercialization of four of Karyopharm’s novel, oral drug candidates, including selinexor, Karyopharm’s lead SINE compound, eltanexor, Karyopharm’s second-generation SINE compound, verdinexor, Karyopharm’s lead compound in development for viral and other non-oncology indications, and KPT-9274, Karyopharm’s dual inhibitor of PAK4 and NAMPT (Press release, Karyopharm, MAY 24, 2018, View Source [SID1234526885]).The agreement includes the development and commercialization of selinexor and eltanexor for the diagnosis, treatment and/or prevention of all human oncology indications in China and Macau. The agreement also includes the development and commercialization of KPT-9274 in all human oncology indications and verdinexor in human non-oncology indications in mainland China, Macau, Taiwan, Hong Kong, South Korea, and the ASEAN countries.

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Under the terms of the agreement, Karyopharm will receive a one-time upfront payment of $12 million (USD) from Antengene. Karyopharm is eligible to receive up to an additional $150 million (USD) if certain future prespecified development, regulatory and commercial milestones are achieved by Antengene. Karyopharm is also eligible to receive tiered double-digit royalties based on future net sales of selinexor and eltanexor in China and Macau, and tiered single- to double-digit royalties based on future net sales of verdinexor and KPT-9274 in the relevant territories. In exchange, Antengene will receive exclusive rights to develop, manufacture and commercialize the compounds in the agreed to territories, at its own cost and expense. Antengene will also have the ability to participate in any global clinical study of selinexor, eltanexor, verdinexor or KPT-9274, and will bear the cost and expense for patients enrolled in clinical studies in the agreed to territories.

"This agreement with Karyopharm brings to our pipeline four promising, clinical-stage product candidates with broad applicability across multiple disease areas, with a particular focus in oncology, with the potential to help patients in a number of Asian territories. To complement the ongoing clinical development efforts by Karyopharm, Antengene may initiate additional clinical trials in diseases with high incidence in Greater China and other Asian regions," said Jay Mei, MD, PhD, Chairman and Chief Executive Officer of Antengene. "At Antengene, we are driven by a higher purpose and our goal is to become a market leader in developing innovative therapies that address unmet medical needs in the Asia Pacific region. We are delighted to partner with Karyopharm, a pioneering oncology company with a strong track record in the research and development of novel, targeted compounds, and we believe this transaction underscores our strong focus on and commitment to healthcare innovation."

"Antengene is dedicated to developing novel, cutting-edge therapies and has strong clinical and regulatory expertise and capabilities in China and the other licensed Asian regions," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. "This strategic alliance adds to the impressive consortium of global Karyopharm partners who are actively advancing our novel oral drug candidates in these important markets, while allowing us to focus our internal resources on executing our late-phase selinexor trials and pursue regulatory approval in the United States and the European Union. In particular, this collaboration for additional territories in Asia complements our existing partnership with Ono Pharmaceutical for selinexor and eltanexor in Japan, Taiwan, South Korea, Hong Kong and the ASEAN countries."

About Selinexor

Selinexor (KPT-330) is a first-in-class, oral Selective Inhibitor of Nuclear Export / SINE compound. Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells. To date, over 2,400 patients have been treated with selinexor. In April 2018, Karyopharm reported positive top-line data from the Phase 2b STORM study evaluating selinexor in combination with low-dose dexamethasone in patients with penta-refractory multiple myeloma. Selinexor has been granted Orphan Drug Designation in multiple myeloma and Fast Track designation for the patient population evaluated in the STORM study. Karyopharm plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) during the second half of 2018, with a request for accelerated approval for oral selinexor as a new treatment for patients with penta-refractory multiple myeloma. The Company also plans to submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in early 2019 with a request for conditional approval. Selinexor is also being evaluated in several other mid- and later-phase clinical trials across multiple cancer indications, including in multiple myeloma in a pivotal, randomized Phase 3 study in combination with Velcade (bortezomib) and low-dose dexamethasone (BOSTON) and as a potential backbone therapy in combination with approved therapies (STOMP), and in diffuse large B-cell lymphoma (SADAL), liposarcoma (SEAL), and an investigator-sponsored study in endometrial cancer (SIENDO), among others. Additional Phase 1, Phase 2 and Phase 3 studies are ongoing or currently planned, including multiple studies in combination with one or more approved therapies in a variety of tumor types to further inform Karyopharm’s clinical development priorities for selinexor. Additional clinical trial information for selinexor is available at www.clinicaltrials.gov.

About Eltanexor

Eltanexor is a second generation oral SINE compound. Eltanexor functions by binding to and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus. Eltanexor has demonstrated minimal brain penetration in animals, which has been associated with reduced toxicities in preclinical studies while maintaining potent anti-tumor effects. A Phase 1/2 clinical study is currently ongoing evaluating eltanexor in myelodysplastic syndrome, colorectal cancer and castrate-resistant prostate cancer.

About Verdinexor

Verdinexor (KPT-335) is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound being investigated across a variety of non-oncology indications in humans with an initial focus as a potential broad-spectrum treatment for viral diseases. Verdinexor functions by binding to and inhibiting the nuclear export protein XPO1 (also called CRM1), which is believed to be responsible for the movement of critical host cell and pathogen encoded cargoes across the nuclear membrane into the cytoplasm. Inhibition of this process with verdinexor results in accumulation of these cargoes in the nucleus, where they promote an anti-inflammatory state and prevent key steps in pathogen replication from occurring. Prior preclinical research showed efficacy of verdinexor in several viral models, including HIV and promising pre-clinical data has also been observed in multiple additional non-oncology indications. In a previously conducted randomized, double-blind, placebo-controlled, dose-escalating Phase 1 clinical trial in healthy human volunteers, verdinexor was found to be generally safe and well tolerated, with adverse events occurring in similar number and grade as placebo.

About KPT-9274

KPT-9274 is a first-in-class, orally bioavailable, small molecule immunometabolic modulator that works through non-competitive dual inhibition of p21-activated kinase 4 (PAK4) and nicotinamide phosphoribosyltransferase (NAMPT). NAMPT and NAPRT (Nicotinate Phosphoribosyltransferas) are the two main pathways for production of the NAD (nicotinamide dinucleotide). About 15-30% of all solid tumors are deficient in NAPRT, making them reliant on NAMPT for NAD production. Co-inhibition of PAK4 and NAMPT is believed to lead to synergistic anti-tumor effects through suppression of ß-catenin by blocking PAK4, leading to both immune cell activation and inhibition of tumor growth, blockade of DNA repair, cell cycle arrest, and energy depletion through NAMPT inhibition, and ultimately apoptosis. KPT-9274 may therefore have both immune-activating and direct antitumor effects. Tumors deficient in NAPRT may be particularly susceptible to KPT-9274’s actions. In contrast, normal cells are less sensitive to inhibition by KPT-9274 due in part to their relative genomic stability and lower metabolic demands. KPT-9274 is currently being evaluated in a Phase 1 clinical study in advanced solid tumors and non-Hodgkin’s lymphoma

Splash Pharmaceuticals Announces Dose Escalation in Phase I Clinical Trial in Platinum-resistant Ovarian Cancer Patients

On May 24, 2018 Splash Pharmaceuticals, Inc. ("Splash"), a closely held private biopharmaceutical company that develops novel cancer therapies, reported the successful completion of the first safety cohort of patients and initiation of dose escalation in its ongoing clinical trial in platinum-resistant ovarian cancer patients (Press release, Splash Pharmaceuticals, MAY 24, 2018, View Source [SID1234526884]). The Phase I trial is being conducted at Rutgers Cancer Institute of New Jersey, a National Cancer Institute-designated Comprehensive Cancer Center.

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SPL-108 has been examined in multiple Phase I and II clinical trials in over 100 human subjects with documented clinical activity and excellent safety and tolerability. SPL-108 has also demonstrated significant activity in animal models for a variety of cancers including ovarian, breast, endometrial, prostate, liver and brain. The current clinical trial is testing the safety and efficacy of SPL-108 in conjunction with paclitaxel in platinum-resistant ovarian cancer patients.

"The target, mechanism of action, and clinical data all support the idea of further testing SPL-108 and paclitaxel in ovarian cancer patients," said Dr. David Nelson, President and CEO of Splash. "We believe that SPL-108 will be synergistic with other anti-tumor drugs as well and could be applicable in many different tumor types including breast and endometrial cancers. We are pleased that the first patients have cleared this critical safety hurdle."

"Ovarian cancer is often first diagnosed in advanced stages and treated with platinum-based chemotherapy. For many patients, their disease will become resistant to this treatment. As a researcher, I am happy to have an opportunity to translate the discoveries in my laboratory and use SPL-108 in the clinic to further identify much needed therapy alternatives for this population," said Dr. Lorna Rodriguez, Principal Investigator and Chief of the Gynecologic Oncology Program at Rutgers Cancer Institute.