On June 15, 2018 Kitov Pharma Ltd. (NASDAQ: KTOV) (TASE: KTOV), an innovative biopharmaceutical company, reported positive results in a pre-clinical study testing NT219, a first-in-class small molecule targeting IRS1/2 and STAT3, two signal proteins that are part of an anti-cancer drug resistance mechanism (Press release, Kitov Pharmaceuticals , JUN 15, 2018, View Source [SID1234527349]). The study, conducted by Kitov’s majority-owned subsidiary, TyrNovo Ltd., evaluated NT219 in combination with gemcitabine in a patient-derived xenograft (PDX) model of pancreatic cancer and was conducted in accordance with guidance from the U.S. Food and Drug Administration (FDA). The results support the planned submission of the Investigational New Drug (IND) Application for NT219.

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NT219 was tested at three dose levels in combination with gemcitabine vs. gemcitabine alone. A clear dose response effect was observed among treatment arms with statistically significant differences among groups (p-value <= 0.0166). In addition, the study confirmed previous findings that demonstrated the beneficial effect of the combination of NT219 with gemcitabine vs. gemcitabine alone (p-value <0.0001).

Kitov also announced that it has agreed to acquire all of the shares of TyrNovo held by the last remaining unaffiliated shareholder, representing approximately 3.1% of TyrNovo’s issued and outstanding shares, based on an agreed upon TyrNovo company valuation of $10 million. In exchange for the TyrNovo shares and termination of all shareholder and investment agreements with this shareholder, Kitov will issue 2,816,900 new ordinary shares (equivalent to 140,845 American Depositary Shares (ADS)) of Kitov. Following the closing of this transaction, Kitov will hold approximately 97.1% of TyrNovo’s issued and outstanding ordinary shares. The remaining 2.9% of TyrNovo’s shares are held by Dr. Hadas Reuveni, TyrNovo’s founder and chief technology officer.

"These compelling NT219 pre-clinical results represent an important milestone towards the submission of an IND and the initiation of a clinical trial, which we expect will occur in 2019," said Isaac Israel, Kitov’s CEO. "Based on the results generated to date and its profile, we believe NT219 has the potential to be a new treatment option for pancreatic cancer patients. This compelling product candidate previously demonstrated impressive efficacy results in converting non-responding tumors to responders, as well as blocking tumor progression in combination with various oncology drugs, and in a wide range of tumor types. These positive data also further our confidence in the potential of TyrNovo to create significant value for Kitov’s shareholders. As such, we are pleased to have completed the acquisition of substantially all of the remaining minority shares of TyrNovo, and look forward to the continued development of NT219 in oncology."

About TyrNovo

TyrNovo Ltd., a Kitov Pharma (NASDAQ/TASE: KTOV) company, is a developer of novel small molecules in the oncology therapeutic field. TyrNovo is developing NT219, an oncology product designed to be used in combination with other oncology drugs. NT219 is a small molecule dual inhibitor of Insulin Receptor Substrate (IRS1/2) and of Signal Transducer and Activator of Transcription (STAT3), two signal pathways that are involved in the development of cancer drug resistance. In combination with various approved oncology drugs, NT219 has demonstrated potent anti-tumor effects and increased survival in various cancer models, including sarcoma, melanoma, pancreatic, lung, ovarian, head & neck, prostate and colon cancers. Its mechanism of action is through the prevention of acquired resistance in tumors and by regression of resistant tumors. For more information on TyrNovo please visit View Source

On June 15, 2018 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported that three posters highlighting clinical data from the ongoing Phase 1b/2 STOMP study in patients with multiple myeloma (MM) will be presented at the European Hematology Association (EHA) (Free EHA Whitepaper) 2018 Annual Meeting taking place June 14-17, 2018 in Stockholm, Sweden (Press release, Karyopharm, JUN 15, 2018, View Source [SID1234527336]). These three poster presentations will feature updated data from the STOMP arms evaluating selinexor, the Company’s lead, novel, oral SINE compound, and dexamethasone in combination with standard approved therapies, Velcade (bortezomib), Pomalyst (pomalidomide) or Darzalex (daratumumab), in patients with previously treated MM.

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"The Phase 1b/2 STOMP study continues to generate important efficacy and safety data from the multiple ongoing arms evaluating selinexor and dexamethasone (dex) in combination with the standard approved therapies Velcade, Pomalyst and Darzalex in patients with multiple myeloma following at least one prior therapy," said Sharon Shacham, PhD, MBA, President and Chief Scientific Officer of Karyopharm. "Based on the positive STOMP results reported to date, we have initiated a new all-oral STOMP arm to investigate selinexor plus Revlimid and dex in the front-line setting. Given the observed synergistic activity of selinexor with standard approved myeloma therapies, we believe oral selinexor has the potential to be a future backbone therapy in myeloma, and we look forward to elucidating its activity as part of a front-line treatment regimen."

Selinexor in Combination with Velcade and Low-dose Dexamethasone (SVd)

In the poster presentation titled, "Selinexor combined with low dose bortezomib and dexamethasone (SVd) induces a high response rate in patients with relapsed or refractory multiple myeloma (MM)," (Abstract code PS1322) Nizar Bahlis, MD, Southern Alberta Cancer Research Institute, will present updated clinical data from the SVd arm of the STOMP study. This study includes patients whose disease was proteasome inhibitor (PI) naïve, exposed or refractory, provided their disease was not refractory to Velcade as a last therapy. In this study arm, oral selinexor was dose-escalated in once-weekly (80 or 100mg) or twice-weekly (60 or 80mg) regimens. Velcade (1.3mg/m2 subcutaneously) was administered once-weekly or twice-weekly. Dex was administered orally either 40mg once-weekly or 20mg twice-weekly. The following table is a summary of the efficacy results:

Key: ORR=Overall Response Rate (sCR+CR+VGPR+PR), sCR=Stringent Complete Response, CR=Complete Response, VGPR=Very Good Partial Response, PR=Partial Response
1Responses were adjudicated according to the International Myeloma Working Group criteria
2Based on interim unaudited data
3Two patients not evaluable for response: one death unrelated to myeloma and one withdrawal of consent before disease follow up
4One unconfirmed PR
5Patient population eligible for the ongoing Phase 3, randomized BOSTON study evaluating SVd versus Vd. This a subset of the PI Relapsed/Naïve, ≤3 Prior Treatments

In the PI Relapsed/Naïve population (N=19), the ORR was 84% and the median PFS was 17.8 months with similar results in the "BOSTON" population (N=18). Nearly all patients (38 of 40) had reductions in M-protein, including 33% with a ≥90% reduction. This indication of efficacy in the SVd combination, with weekly Velcade and selinexor, warranted the further evaluation of SVd versus Vd in the BOSTON study given the previously reported ORR of 60-65% and PFS of 7-9 months in the Vd regimen among similar patient populations.

Among the 42 patients evaluable for safety, adverse events were consistent with those reported previously from the SVd arm of the STOMP study, with nausea (60%), anorexia (57%), fatigue (45%), diarrhea (40%), vomiting (29% and weight loss (24%) the most commonly reported Grade 1/2 events. Importantly, the reported peripheral neuropathy across all patients was Grade 1/2 and limited to six patients (14%), of which five had prior Velcade exposure. Grade 3/4 adverse events were also consistent with those reported previously with thrombocytopenia (45%), neutropenia (26%), fatigue (14%) and anemia (12%) being the most common. Based on the activity and tolerability observed in this study arm, the recommended Phase 2 dose (RP2D) regimen for SVd is oral selinexor (100mg once weekly), Velcade (1.3mg/m2 once-weekly subcutaneously) and oral dex (40mg weekly), which represents 40% less Velcade and 25% less dex compared to the approved standard Velcade + dex (Vd) regimen. This once weekly regimen is being evaluated in BOSTON.

Dr. Bahlis commented, "These updated data from the SVd arm of the STOMP study continue to show rapid time to response, high response rates, including an 83% ORR and the emergence of complete responses, along with a 17.8-month median PFS, in patients with relapsed or refractory myeloma. The combination also continues to be well tolerated with low rates of peripheral neuropathy. Importantly, these results are being achieved with 40% less Velcade and 25% less dex than the standard approved regimen, with no overt major organ toxicities."

Selinexor in Combination with Darzalex and Low-dose Dexamethasone (SDd)

In the poster presentation titled, "A Phase 1b study using the combination of selinexor, daratumumab, and dexamethasone in multiple myeloma patients previously exposed to proteasome inhibitors and immunomodulatory drugs," (Abstract code PS1329) Cristina Gasparetto, MD, Duke University Cancer Center, will present new clinical data from the SDd arm of the STOMP study evaluating myeloma patients who received at least three prior lines of therapy, including a PI and an immunomodulatory drug (IMiD), or patients with myeloma refractory to both a PI and an IMiD. In this study arm, oral selinexor was dose escalated using either 100mg once weekly or 60mg twice weekly, with Darzalex (16mg/kg intravenously once weekly) and dex (orally, 40mg once weekly or 20mg twice weekly).

Key: ORR=Overall Response Rate (VGPR+PR)
1Responses were adjudicated according to the International Myeloma Working Group criteria
2Based on interim unaudited data
3One patient not evaluable for response withdrew consent prior to disease follow up, one patient pending response
4 Three unconfirmed PR

Despite the heavily pretreated nature of the patients in the study, with 100% of the patients having dual- (PI and IMID-) refractory disease, responses occurred rapidly, with a median of one month to onset; 12 of the 19 patients remain on treatment. Based on published data the expected ORR for Darzalex therapy without selinexor in the Darzalex-naïve population is ~30%. Thus, the ORR of 82% provides a basis for further evaluation of the weekly SDd combination.

Among the 21 patients evaluable for safety, the most common Grade 1/2 adverse events were nausea (48%), fatigue (38%), diarrhea (24%), constipation (24%), and anorexia (24%). The most common Grade 3/4 adverse events were thrombocytopenia (48%), leukopenia (43%), anemia (33%), neutropenia (33%) and decreased lymphocyte count (24%). Gastrointestinal adverse events were generally manageable with supportive care. The maximum tolerated dose was not reached. Two DLTs (Grade 3 thrombocytopenia and Grade 2 fatigue) were observed in patients receiving selinexor 60mg twice weekly; both patients showed responses. Based on the preliminary tolerability and efficacy data, the RP2D of SDd is selinexor (100mg orally, once weekly), Darzalex (16mg/kg, once weekly) and dex (40mg orally, weekly).

Dr. Gasparetto commented, "These preliminary results from the SDd arm of the STOMP study show high response rates, including an 82% ORR in Darzalex-naïve patients with refractory myeloma. This combination regimen appears to be well tolerated with responses observed rapidly occurring within a median one cycle of treatment. We look forward to continuing enrollment in this treatment arm."

Selinexor in Combination with Pomalyst and Low-dose Dexamethasone (SPd)

In the poster presentation titled, "Selinexor combined with pomalidomide and low dose dexamethasone (SPd) in a relapsed/refractory multiple myeloma patient population," (Abstract code PF586) Christine Chen, MD, FRCP, University of Toronto, Princess Margaret Cancer Center, will present updated clinical data from the SPd arm of the STOMP study which includes patients with multiple myeloma who previously received Revlimid and a PI. In this study arm, selinexor was dosed orally either once weekly (80 or 100mg) or twice weekly (60 or 80mg) with Pomalyst (3 or 4mg orally, once daily) and dexamethasone (dex; orally, 40mg once weekly or 20mg twice weekly). The following table is a summary of the efficacy results:

Key: ORR=Overall Response Rate (VGPR+PR)
1Responses were adjudicated according to the International Myeloma Working Group criteria
2Based on interim unaudited data
3Four patients not evaluable for response: one death unrelated to myeloma, one non-compliance with study procedures, two withdrawal of consent before disease follow up
4One unconfirmed PR

Responses tended to occur rapidly with a median of one month to onset. Median PFS among all evaluable patients was 10.3 months, with a follow up of 9.4 months. The efficacy of the SPd combination warrants further clinical evaluation.

Among the 34 patients evaluable for safety, the most common Grade 1/2 adverse events were anorexia (56%), nausea (47%), fatigue (41%), weight loss (38%), diarrhea (26%) and thrombocytopenia (26%). The most common Grade ≥3 adverse events were neutropenia (56%), thrombocytopenia (32%) and anemia (29%). Gastrointestinal adverse events were generally manageable with supportive care. There were two Grade 5 treatment-related events (febrile neutropenia and intracranial hemorrhage). Six DLTs (Grade 3 fatigue, febrile neutropenia, hyponatremia, neutropenia and thrombocytopenia) were observed in patients receiving selinexor 60mg twice weekly, 80mg twice weekly and 80mg once weekly. Based on the activity and tolerability observed in this study arm, doses of oral selinexor 60-80mg once weekly are being evaluated in combination with Pomalyst (3mg orally, once daily) and low dose dex to determine the RP2D for this combination regimen.

Dr. Chen stated, "This novel, all oral regimen continues to demonstrate strong response rates, including a 55% ORR, along with an 11.6-month median PFS, in Pomalyst-naïve and Revlimid-relapsed or -refractory patients. In this STOMP arm, once-weekly selinexor has been generally well tolerated and rapidly induced durable responses in patients with PI- and Revlimid-exposed myeloma."

Details for the EHA (Free EHA Whitepaper) 2018 presentations are as follows:

Company-sponsored Trials

Title: Selinexor combined with low dose bortezomib and dexamethasone (SVd) induces a high response rate in patients with relapsed or refractory multiple myeloma (MM)
Lead author: Nizar Bahlis, Southern Alberta Cancer Research Institute
Final Abstract Code: PS1322
Topic/Session Title: Myeloma and other monoclonal gammopathies – Clinical
Date and Time: Saturday, June 16, 2018; 17:30 – 19:00 CEST
Location: Poster area

Title: A Phase 1b study using the combination of selinexor, daratumumab, and dexamethasone in multiple myeloma patients previously exposed to proteasome inhibitors and immunomodulatory drugs
Lead author:Cristina Gasparetto, Duke University
Final Abstract Code: PS1329
Topic/Session Title: Myeloma and other monoclonal gammopathies – Clinical
Date and Time: Saturday, June 16, 2018; 17:30 – 19:00 CEST
Location: Poster area

Title: Selinexor combined with pomalidomide and low dose dexamethasone (SPd) in a relapsed/refractory multiple myeloma patient population
Presenter:Christine Chen, University of Toronto, Princess Margaret Cancer Center
Final Abstract Code: PF586
Topic/Session Title: Myeloma and other monoclonal gammopathies – Clinical
Date and Time:Friday, June 15, 2018; 17:30 – 19:00 CEST
Location: Poster area

Investigator-sponsored Trials

Title: A Phase II study of selinexor (KPT-330) combined with bortezomib and dexamethasone (SVD) for induction and consolidation for patients with progressive or refractory multiple myeloma; the selvedex trial
Lead author: Annemiek Broijl, Erasmus MC Cancer Institute
Final Abstract Code: PS1338
Topic/Session Title: Myeloma and other monoclonal gammopathies – Clinical
Date and Time: Saturday, June 16, 2018; 17:30 – 19:00 CEST
Location: Poster area

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 by the U.S Food and Drug Administration (FDA) for the patient population evaluated in the STORM study. Karyopharm plans to submit a New Drug Application (NDA) to the 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.

On June 15, 2018 Novartis reported results from a new comparison study showing that Jakavi(ruxolitinib)-treated patients with polycythemia vera (PV), who were resistant or intolerant to hydroxyurea (HU), had a significantly reduced risk of thrombosis (blood clots) and death compared to PV patients who received best available therapy[1] (Press release, Novartis, JUN 15, 2018, View Source [SID1234527352]). The study findings are based on a comparison of patients in the Phase III RESPONSE Jakavi clinical trial and the real-world Spanish GEMFIN patient registry. PV is a rare and incurable blood cancer associated with an overproduction of blood cells that can cause serious cardiovascular complications, such as blood clots, stroke and heart attack[4].

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The new findings were presented at the 23rd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Stockholm, Sweden.

"When you can complement clinical trial data with real-world experiences, it can provide valuable insight into how treatments affect patients in their day-to-day lives," said lead study investigator, Alberto Alvarez-Larran, MD, Hematology Department, Hospital Clinic, Barcelona, Spain. "This latest research supports the use of Jakavi to help people with polycythemia vera gain better control of their disease when hydroxyurea is not an option."

Additional Jakavi data presented at the EHA (Free EHA Whitepaper) Annual Congress includes efficacy and safety analyses of the largest expanded access trial of myelofibrosis (MF) patients treated with Jakavi to date (JUMP). An efficacy analysis showed that patients with lower-risk MF achieved spleen size reductions when treated with Jakavi, with most patients (82.1%) achieving a >=50% reduction at any time[2],[3]. A separate analysis identified factors that may lead to a greater spleen response in patients with MF treated with Jakavi, including treating earlier in the course of the disease and at a higher dose (>=10 mg BID)[5].

"With limited treatment options, patients with myeloproliferative neoplasms (MPNs) often struggle to keep their disease under control," said Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development. "The research conducted by Novartis teams and our physician partners in both PV and MF is helping to clarify how Jakavi can help relieve disease burden for patients."

Additionally, 48-week data from the EXPAND study support Jakavi 10 mg BID as a starting dose in patients with MF with low platelet counts, providing important information in a patient population at an increased risk of bleeding and serious complications[5]. Nearly one-third of patients in the study treated with Jakavi achieved a >=50% reduction in spleen size at week 48 (31.8% of patients [7/22] with a platelet count of 75 to 99 x 109/L and 35.7% [5/14] of patients with a platelet count of 50 to 74 x 109/L)[5].

About the PV Real-World Comparison Study
The new data presented at EHA (Free EHA Whitepaper) compares overall survival and thrombosis (blood clots) rates using data from patients treated in the Jakavi arm of the RESPONSE trial and patients treated in a real-world setting with best available therapy (BAT) from the Grupo Español de Enfermedades Mieloproliferativas Crónicas Filadelfia Negativas (GEMFIN) registry[1].

In the previously reported Phase III RESPONSE trial, the high rate of crossover from BAT to Jakavi precluded the comparison of overall survival and thrombosis rates. RESPONSE was a global, open-label study that included patients with PV resistant to or intolerant of hydroxyurea, who were randomized 1:1 to receive either Jakavi (starting dose of 10 mg twice daily) or BAT, which was defined as investigator-selected monotherapy or observation only. The GEMFIN registry patients in the real-world BAT group had resistance or intolerance to hydroxyurea according to the modified European Leukemia Net criteria and received hydroxyurea (44%), busulfan (10%), radioactive phosphorus (2%), interferon (6%), anagrelide (12%), other therapy (11%) or no cytoreductive therapy (26%). Some patients were also treated with multiple therapies[1].

In the GEMFIN study, patients treated with Jakavi had a significantly prolonged overall survival (HR=0.28 [0.11-0.72]) and a lower risk of blood clots (HR=0.21 [0.06-0.76]) when compared to real-world patients treated with BAT[1].

About the JUMP Study
JUMP is an expanded access Phase IIIb study designed to further evaluate the safety and efficacy of Jakavi in MF. It includes the largest cohort of patients with MF treated with Jakavi, 2,233, to date. The study provided access to Jakavi for patients who had no access to the treatment outside of a clinical trial and included 60 patients who were determined to have DIPSS low-risk disease[2],[3].

About the EXPAND Study
EXPAND is an open-label, Phase Ib, dose-finding study in patients with MF with baseline platelet counts of 50 to 99 x 109/L. Results presented at EHA (Free EHA Whitepaper) are from the 48-week follow- period[5].

The study evaluated 10 mg BID as a safe starting dose of Jakavi. The key secondary endpoints are safety and efficacy, including proportion of patients achieving >=50% of reduction in spleen size. Safety findings were also consistent with previous studies of Jakavi[5].

About Myelofibrosis and Polycythemia Vera
Myelofibrosis (MF) and polycythemia vera (PV) are part of a group of related and rare blood cancers called myeloproliferative neoplasms (MPNs) in which bone marrow cells responsible for the body’s blood cells develop and function abnormally[4],[6].

In patients with MF, the bone marrow can no longer produce enough normal blood cells, causing the spleen to enlarge. MF affects approximately one in every 100,000 people[6].

PV is associated with an overproduction of blood cells that can cause serious cardiovascular complications if left inadequately controlled, such as blood clots, stroke and heart attack. PV affects up to three per 100,000 people globally each year[4].

About Jakavi
Jakavi (ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases. Jakavi is approved by the European Commission for the treatment of adult patients with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea and for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (MF) (also known as chronic idiopathic MF), post-polycythemia vera MF or post-essential thrombocythemia MF. Jakavi is approved in 101 countries for patients with MF, including EU countries, Switzerland, Canada, Japan and in more than 75 countries for patients with PV, including EU countries, Switzerland, Japan and Canada. The exact indication for Jakavi varies by country. Additional worldwide regulatory filings are underway in MF and PV.

Novartis licensed ruxolitinib from Incyte Corporation for development and commercialization outside the United States. Jakavi is marketed in the United States by Incyte Corporation as Jakafi for the treatment of patients with PV who have had an inadequate response to or are intolerant of hydroxyurea and for the treatment of patients with intermediate or high-risk MF.

The recommended starting dose of Jakavi in PV is 10 mg given orally twice daily. The recommended starting dose of Jakavi in MF is 15 mg given orally twice daily for patients with a platelet count between 100,000 cubic millimeters (mm[3]) and 200,000 mm[3], and 20 mg twice daily for patients with a platelet count of >200,000 mm[3]. Doses may be titrated based on safety and efficacy. There is limited information to recommend a starting dose for MF and PV patients with platelet counts between 50,000/mm[3] and <100,000/mm[3]. The maximum recommended starting dose in these patients is 5 mg twice daily, and patients should be titrated cautiously[7].

Jakavi is a registered trademark of Novartis AG in countries outside the United States. Jakafi is a registered trademark of Incyte Corporation. The safety and efficacy profile of Jakavi has not yet been established outside the approved indications.

Jakavi Important Safety Information for Treatment of Myelofibrosis (MF) and Polycythemia Vera (PV)
Jakavi can cause serious side effects, including a decrease in blood cell count and infections. Complete blood count monitoring is recommended. Dose reduction or interruption may be required in patients with any hepatic impairment or severe renal impairment or in patients developing hematologic adverse reactions such as thrombocytopenia, anemia and neutropenia. Dose reductions are also recommended when Jakavi is co-administered with strong CYP3A4 inhibitors or fluconazole. Use of Jakavi during pregnancy is not recommended, and women should avoid becoming pregnant during Jakavi therapy. Women taking Jakavi should not breast feed. Progressive multifocal leukoencephalopathy (PML) has been reported. Physicians should be alert for neuropsychiatric symptoms suggestive of PML. Hepatitis B viral load (HBV-DNA titer) increases have been reported in patients with chronic HBV infections. Patients with chronic HBV infection should be treated and monitored according to clinical guidelines. Non-melanoma skin cancer (NMSC) has been reported in Jakavi treated patients. Periodic skin examination is recommended. Very common adverse reactions in MF (>10%) include urinary tract infections, anemia, thrombocytopenia, neutropenia, hypercholesterolemia, dizziness, headache, alanine aminotransferase increased, aspartate aminotransferase increased, bruising and weight gain. Common adverse reactions in MF (1 to 10%) include herpes zoster and flatulence. Uncommon adverse reactions in MF include tuberculosis. Very common adverse reactions in PV (>10%) include anemia, thrombocytopenia, hypercholesterolemia, hypertriglyceridemia, dizziness, alanine aminotransferase increased and aspartate aminotransferase increased. Common adverse reactions in PV (1 to 10%) include urinary tract infections, herpes zoster, weight gain, constipation and hypertension.

Please see full Prescribing Information available at www.jakavi.com.

Disclaimer
This press release contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995. Forward-looking statements can generally be identified by words such as "potential," "can," "will," "plan," "expect," "anticipate," "look forward," "believe," "committed," "investigational," "pipeline," "launch," or similar terms, or by express or implied discussions regarding potential marketing approvals, new indications or labeling for the investigational or approved products described in this press release, or regarding potential future revenues from such products. You should not place undue reliance on these statements. Such forward-looking statements are based on our current beliefs and expectations regarding future events, and are subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. There can be no guarantee that the investigational or approved products described in this press release will be submitted or approved for sale or for any additional indications or labeling in any market, or at any particular time. Nor can there be any guarantee that such products will be commercially successful in the future. In particular, our expectations regarding such products could be affected by, among other things, the uncertainties inherent in research and development, including clinical trial results and additional analysis of existing clinical data; regulatory actions or delays or government regulation generally; global trends toward health care cost containment, including government, payor and general public pricing and reimbursement pressures; our ability to obtain or maintain proprietary intellectual property protection; the particular prescribing preferences of physicians and patients; general political and economic conditions; safety, quality or manufacturing issues; potential or actual data security and data privacy breaches, or disruptions of our information technology systems, and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US Securities and Exchange Commission. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

On June 14, 2018 ArQule, Inc. (Nasdaq: ARQL) reported that Paolo Pucci, Chief Executive Officer, and Dr. Brian Schwartz, Chief Medical Officer and Head of Research and Development, will present at The JMP Securities Life Sciences Conferenceon June 21, 2018, at 10:30am EDT at the St. Regis in New York (Press release, ArQule, JUN 14, 2018, View Source [SID1234527307]).

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The live webcast of the presentation will be available via the "Investors & Media" section of ArQule’s website, www.arqule.com, under "Events & Presentations." A replay of the webcast will be available shortly after the conclusion of the presentation.

On June 14, 2018 Avelas Biosciences, Inc., a clinical stage oncology-focused platform technology company that is developing products to advance a new standard-of-care for cancer surgery and therapeutic intervention, reported that Carmine N. Stengone, President and Chief Executive Officer, will present at the JMP Securities Life Sciences Conference on Thursday, June 21, 2018, at 1:30 p.m. EDT (10:30 a.m. PDT) in New York City (Press release, Avelas Biosciences, JUN 14, 2018, View Source [SID1234527308]).

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