On May 1, 2018 Incyte Corporation (Nasdaq:INCY) reported 2018 first-quarter financial results, highlighting strong growth in total product-related revenue and providing a status update on the Company’s development portfolio (Press release, Incyte, MAY 1, 2018, View Source;p=RssLanding&cat=news&id=2345828 [SID1234525889]).

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"Jakafi continues to grow with significant momentum as we bring the benefits of this first-in-class treatment to an increasing number of patients," stated Hervé Hoppenot, Incyte’s Chief Executive Officer. "We expect to be able to provide important updates from our development portfolio over the coming months—including the results of the first pivotal trial of Jakafi in graft-versus-host disease and initial data from our FGFR program in cholangiocarcinoma—as we continue to work on developing innovative therapies for patients in need."

Portfolio Update

Oncology – key highlights

Results from the REACH1 trial evaluating ruxolitinib in patients with steroid-refractory acute graft-versus-host disease (GVHD) are expected in the first half of 2018. Data emerging from this open-label, pivotal trial continue to support Incyte’s intention to submit an sNDA in the second half of 2018, seeking approval of ruxolitinib in this indication.

Initial data from the trial evaluating INCB54828 in patients with cholangiocarcinoma are expected in second half of 2018.

As previously announced, the external Data Monitoring Committee (eDMC) review of the pivotal Phase 3 ECHO-301 study evaluating epacadostat in combination pembrolizumab in patients with unresectable or metastatic melanoma determined that the study did not meet the primary endpoint of improving progression-free survival in the overall population compared to pembrolizumab monotherapy. The study’s second primary endpoint of overall survival also was not expected to reach statistical significance. Based on these results, and at the recommendation of the eDMC, the study has been stopped to enable patients and their physicians to consider alternative therapeutic options, and Incyte is also significantly downsizing the epacadostat development program.

In consultation with Incyte’s collaboration partners, and after the results of ECHO-301, the two pivotal trials of epacadostat in combination with pembrolizumab in lung cancer (ECHO-305 and ECHO-306) will be converted into randomized phase 2 trials. Enrollment will be discontinued in the four additional pivotal trials of epacadostat in combination with pembrolizumab, and in the two pivotal trials of epacadostat in combination with nivolumab; each of these studies will be amended to enable patients and their physicians to consider alternative therapeutic options. The pivotal trial in combination with durvalumab in Stage 3 lung cancer will not be initiated.

Incyte intends to continue to investigate epacadostat’s potential as a component of combination immunotherapy in proof-of-concept trials, which will include hypotheses distinct from combinations with PD-1 and PD-L1 antagonists.

Status updates for Incyte’s most advanced clinical programs are provided below.

Indication

Status Update

Ruxolitinib
(JAK1/JAK2)

Steroid-refractory acute GVHD Pivotal Phase 2 (REACH1); Phase 3 (REACH2)
Ruxolitinib
(JAK1/JAK2)

Steroid-refractory chronic GVHD Phase 3 (REACH3)
Ruxolitinib
(JAK1/JAK2)

Essential thrombocythemia Phase 2 (RESET)
Itacitinib
(JAK1)

Treatment-naïve acute GVHD Phase 3 (GRAVITAS-301)
Itacitinib
(JAK1)

NSCLC Phase 1/2 in combination with osimertinib (EGFR)
Epacadostat
(IDO1)

Lung cancer Phase 2 (ECHO-305; ECHO-306) in combination with pembrolizumab (PD-1)
INCMGA0012
(PD-1)1

Solid tumors Phase 1 dose-escalation completed, monotherapy expansion cohorts ongoing
INCB50465
(PI3Kδ)

DLBCL Phase 2 (CITADEL-202)
INCB50465
(PI3Kδ)

Follicular lymphoma Phase 2 (CITADEL-203)
INCB50465
(PI3Kδ)

Marginal zone lymphoma Phase 2 (CITADEL-204)
INCB50465
(PI3Kδ)

Mantle cell lymphoma Phase 2 (CITADEL-205)
INCB54828
(FGFR1/2/3)

Bladder cancer Phase 2 (FIGHT-201)
INCB54828
(FGFR1/2/3)

Cholangiocarcinoma Phase 2 (FIGHT-202)
Notes:
1) INCMGA0012 licensed from MacroGenics

A brief status update for Incyte’s earlier-stage clinical candidates is provided below.

Status Update

INCB57643
(BRD)

First-in-man data presented at ASH (Free ASH Whitepaper) 2017, showing optimized PK profile for combination therapy
INCB53914
(PIM)

First-in-man data at ASH (Free ASH Whitepaper) 2017; development expected to focus on combination therapy, including with JAK and PI3Kδ inhibition in hematological malignancies
INCB52793
(JAK1)

Development in AML to be discontinued due to lack of efficacy
INCB59872
(LSD1)

Epigenetic mechanism targeting cell differentiation; evaluating both oncology indications and sickle-cell disease
INCB62079
(FGFR4)

250x greater selectivity for FGFR4 over FGFR1/2/3; initial development expected to focus on hepatocellular carcinoma
INCB81776
(AXL/MER)

Expected to enter clinical trials in 2018
INCB01158
(ARG)1

Novel mechanism targeting myeloid cells; development expected to focus on combination therapy
INCAGN1876
(GITR)2

Dose escalation completed; development expected to focus on combination therapy
INCAGN1949
(OX40)2

Dose escalation completed; development expected to focus on combination therapy
INCAGN2390
(TIM-3)2

Expected to enter clinical trials in 2018
INCAGN2385
(LAG-3)2

Expected to enter clinical trials in 2018
Notes:
1) INCB01158 co-developed with Calithera
2) INCAGN1876, INCAGN1949, INCAGN2390 and INCAGN2385 from discovery alliance with Agenus

Non-oncology

Data from the randomized Phase 2 trial of topical ruxolitinib versus vehicle and triamcinolone creams in adult patients with atopic dermatitis are expected in the second half of 2018.

Indication

Status Update

Topical ruxolitinib
(JAK1/JAK2)

Atopic dermatitis Phase 2
Topical ruxolitinib
(JAK1/JAK2)

Vitiligo Phase 2

Partnered – key highlights

In April 2018, the US. Food and Drug Administration (FDA) convened its Arthritis Advisory Committee to discuss the resubmission of the baricitinib NDA, which recommended approval of the 2mg dose of baricitinib as a once-daily oral medication for the treatment of moderately-to-severely active rheumatoid arthritis for adult patients who have had an inadequate response or intolerance to methotrexate. While the Advisory Committee unanimously supported the efficacy of the 4mg dose of baricitinib, it did not recommend approval of the 4mg dose of baricitinib for the proposed indication based on the adequacy of the safety and benefit-risk profiles. The FDA action date for baricitinib is in June 2018.

Indication

Status Update

Baricitinib (JAK1/JAK2)1

Rheumatoid arthritis Approved in Europe and Japan at 2mg and 4mg doses; NDA resubmitted to FDA
Baricitinib (JAK1/JAK2)1

Atopic dermatitis Phase 3
Baricitinib (JAK1/JAK2)1

Psoriatic arthritis Lilly expects the Phase 3 program to begin in 2018
Baricitinib (JAK1/JAK2)1

Systemic lupus erythematosus Phase 2
Capmatinib (MET)2

Non-small cell lung cancer, liver cancer Phase 2 in EGFR wild-type, ALK negative NSCLC patients with MET amplification and mutation
Notes:
1) Baricitinib licensed to Lilly
2) Capmatinib licensed to Novartis

Corporate Update

In April 2018, Maria E. Pasquale joined the Incyte Executive Management team as Executive Vice President and General Counsel. Maria joined Incyte from Celgene Corporation, where for 17 years she held positions of increasing responsibility including Chief Counsel and Senior Vice President, Legal & Deputy General Counsel, where she led the legal department through Celgene’s global expansion. Most recently, Maria served as Celgene’s Executive Vice President and Global Chief Compliance Officer, responsible for GxP and healthcare compliance globally.

2018 First-Quarter Financial Results

The financial measures presented in this press release for the three months ended March 31, 2018 and 2017 have been prepared by the Company in accordance with U.S. Generally Accepted Accounting Principles ("GAAP"), unless otherwise identified as a Non-GAAP financial measure. Management believes that Non-GAAP information is useful for investors, when considered in conjunction with Incyte’s GAAP disclosures. Management uses such information internally and externally for establishing budgets, operating goals and financial planning purposes. These metrics are also used to manage the Company’s business and monitor performance. The Company adjusts, where appropriate, for both revenues and expenses in order to reflect the Company’s core operations. The Company believes these adjustments are useful to investors by providing an enhanced understanding of the financial performance of the Company’s core operations. The metrics have been adopted to align the Company with disclosures provided by industry peers. Reconciliations of GAAP net loss to Non-GAAP net income (loss) for the three months ended March 31, 2018 and 2017 have been included at the end of this press release.

Guidance related to research and development and selling, general and administrative expenses does not include estimates associated with any potential future strategic transactions.

Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used in conjunction with and to supplement Incyte’s operating results as reported under GAAP. Non-GAAP measures may be defined and calculated differently by other companies in our industry.

Revenues For the quarter ended March 31, 2018, GAAP net product revenues of Jakafi were $314 million as compared to $251 million for the same period in 2017, representing 25 percent growth. For the three months ended March 31, 2018, GAAP net product revenues of Iclusig were $21 million as compared to $14 million for the same period in 2017.

For the quarter ended March 31, 2018, GAAP product royalties from sales of Jakavi, which has been out-licensed to Novartis outside of the United States, was $41 million, as compared to $29 million for the same period in 2017. For the quarter ended March 31, 2018, GAAP product royalties from sales of Olumiant outside of the United States from Lilly were $6 million, as compared to less than $1 million for the same period in 2017.

For the quarter ended March 31, 2018, GAAP milestone revenues were $0 million, as compared to $90 million for the same period in 2017. GAAP milestone revenues in 2017 related to milestones earned from our collaborative partners.

For the quarter ended March 31, 2018, total GAAP revenues were $382 million as compared to $384 million for the same period in 2017. Total Non-GAAP revenues for the quarter ended March 31, 2018 were $382 million as compared to $294 million for the same period in 2017.

Year Over Year Revenue Growth
(in thousands, unaudited)

Three Months Ended
March 31, %
2018 2017 Change
Revenues:
Jakafi net product revenue $ 313,720 $ 251,077 25%
Iclusig net product revenue 20,785 13,730 51%
Product royalty revenues 47,716 29,221 63%
Product-related revenues 382,221 294,028 30%
Milestone revenues - 90,000
Other revenues 61 54
Total GAAP revenues $ 382,282 $ 384,082
Milestone revenues - (90,000)
Total Non-GAAP revenues $ 382,282 $ 294,082

Cost of product revenues GAAP cost of product revenues for the quarter ended March 31, 2018 was $18 million, as compared to $15 million for the same period in 2017. Non-GAAP cost of product revenues for the quarter ended March 31, 2018 were $13 million, as compared to $9 million for the same period in 2017. Non-GAAP cost of product revenues exclude the amortization of licensed intellectual property for Iclusig relating to the acquisition of the European business of ARIAD Pharmaceuticals, Inc.

Research and development expenses GAAP research and development expenses for the quarter ended March 31, 2018 were $303 million as compared to $408 million for the same period in 2017. Decreased GAAP research and development expenses were driven primarily by upfront and milestone expenses of $209 million related to our collaborative agreements recorded in the quarter ended March 31, 2017 partially offset by an overall increase in development costs to advance our clinical pipeline. For the quarter ended March 31, 2018, GAAP research and development expenses included $12 million related to our collaboration agreement with Syros Pharmaceuticals, Inc. and $291 million of ongoing expenses.

Non-GAAP research and development expenses for the quarter ended March 31, 2018 were $266 million, as compared to $177 million for the same period in 2017. Non-GAAP research and development expenses exclude the cost of stock-based compensation of $24 million and $21 million for the quarters ended March 31, 2018 and 2017, respectively, and upfront consideration and milestones paid to our collaborative partners of $12 million and $209 million for the quarters ended March 31, 2018 and 2017, respectively.

Selling, general and administrative expenses GAAP selling, general and administrative expenses for the quarter ended March 31, 2018 was $121 million, as compared to $87 million for the same period in 2017. Increased GAAP selling, general and administrative expenses were driven by additional costs related to the commercialization of Jakafi.

Non-GAAP selling, general and administrative expenses for the quarter ended March 31, 2018 was $109 million, as compared to $78 million for the same period in 2017. Non-GAAP selling, general and administrative expenses exclude the cost of stock-based compensation.

Change in fair value of acquisition-related contingent consideration GAAP change in fair value of acquisition-related contingent consideration for the quarters ended March 31, 2018 and 2017 was $7 million.

Unrealized gain (loss) on long term investments GAAP unrealized gain on long term investments for the quarter ended March 31, 2018 was $23 million as compared to an unrealized loss of $6 million for the same period in 2017. The unrealized gain on long term investments for the quarter ended March 31, 2018 represents the fair market value adjustments of the Company’s investments in Agenus, Calithera, Merus, and Syros.

Expense related to senior note conversions GAAP expense related to senior note conversions for the quarter ended March 31, 2017 was $54 million related to the conversions of certain of our 2018 and 2020 convertible senior notes.

Net income (loss) GAAP net loss for the quarter ended March 31, 2018 was $41 million, or $0.19 per basic and diluted share, as compared to a net loss of $187 million, or $0.96 per basic and diluted share for the same period in 2017. Non-GAAP net loss for the quarter ended March 31, 2018 was $3 million, as compared to net income of $29 million for the same period in 2017. Non-GAAP net loss per share for the quarter ended March 31, 2018 was $0.01 per basic and diluted share, as compared to Non-GAAP net income per share of $0.15 per basic and $0.14 per diluted share for the same period in 2017.

Cash, cash equivalents and marketable securities position As of March 31, 2018 and December 31, 2017, cash, cash equivalents and marketable securities totaled $1.2 billion.

2018 Financial Guidance

The Company has updated its full year 2018 financial guidance, as detailed below.

Current Previous
GAAP and Non-GAAP Jakafi net product revenues $1,350 – $1,400 million Unchanged
GAAP and Non-GAAP Iclusig net product revenues $80 – $85 million Unchanged

GAAP Cost of product revenues $85 – $95 million Unchanged
Non-GAAP Cost of product revenues(1) $64 – $74 million Unchanged

GAAP Research and development expenses $1,150 – $1,250 million $1,200 – $1,300 million
Non-GAAP Research and development expenses(2) $1,013 – $1,108 million $1,077 – $1,172 million

GAAP Selling, general and administrative expenses $390 – $410 million $515 – $535 million
Non-GAAP Selling, general and administrative expenses(3) $340 – $355 million $465 – $480 million

GAAP Change in fair value of acquisition-related contingent consideration $30 million Unchanged
Non-GAAP Change in fair value of acquisition-related contingent consideration(4) $0 million Unchanged

(1)

Adjusted to exclude the amortization of licensed intellectual property for Iclusig relating to the acquisition of the European business of ARIAD Pharmaceuticals, Inc.
(2)

Adjusted to exclude the estimated cost of stock-based compensation, upfront consideration of approximately $12 million relating to the Syros collaboration and upfront consideration of $15 million related to a license agreement.
(3)

Adjusted to exclude the estimated cost of stock-based compensation.
(4)

Adjusted to exclude the change in fair value of estimated future royalties relating to sales of Iclusig in the licensed territory relating to the acquisition of the European business of ARIAD Pharmaceuticals, Inc.

Future Non-GAAP financial measures may also exclude upfront and ongoing milestones relating to third-party collaboration partners, impairment of goodwill or other assets, changes in the fair value of equity investments in our collaboration partners, non-cash interest expense related to the amortization of the initial discount on our 2018 and 2020 Senior Notes and the impact on our tax provision of discrete changes in our valuation allowance position on deferred tax assets.

On May 1, 2018 Vaxart, Inc., a clinical-stage biotechnology company developing oral recombinant vaccines that are administered by tablet rather than by injection, reported the appointment of David Taylor, M.D., as Chief Medical Officer. Dr. Taylor brings over 35 years of extensive experience in medical research, drug and vaccine development and clinical trial management for government organizations, non-profits, academia and both private and public healthcare companies (Press release, Vaxart, MAY 1, 2018, View Source [SID1234525899]).

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"Strengthening our leadership team with the appointment of David is an important milestone for Vaxart as we continue to advance our oral vaccine platform. Dr. Taylor is a drug discovery and development veteran with deep industry knowledge developing recombinant and enteric vaccines, with expertise in the design, execution and analysis of norovirus and influenza vaccine clinical trials," said Wouter Latour, chief executive officer of Vaxart. "We are pleased to welcome David and are confident his guidance will prove invaluable as we move our vaccine programs further in the clinic."

Prior to joining Vaxart, Dr. Taylor served as a senior medical officer of the drug and vaccine development global programs at PATH, where he developed clinical trial designs and executed studies for seasonal and universal flu vaccines and enteric vaccines. Earlier, he was senior medical director of vaccines at Takeda Vaccines, developing clinical trial plans for norovirus and dengue vaccines. Previously, Dr. Taylor served as chief medical officer at VaxInnate Corporation, where he focused on the development of recombinant vaccines for influenza and other infectious diseases, and chief medical officer and vice president of medical and safety at Salix Pharmaceuticals, where he developed Rifaximin (Xifaxan) for the treatment of traveller’s diarrhea and headed medical affairs and pharmacovigilance.

Before Salix, he was a research professor for the Department of International Health at Johns Hopkins Bloomberg School of Public Health. Dr. Taylor began his career as an epidemic intelligence service officer in the Enteric Disease Branch at the Centers for Disease Control and Prevention (CDC) and served 22 years in various capacities at research institutes in the United States Army including founder and chief of the Department of Clinical Trials and acting director for the Division of Communicable Diseases and Immunology at the Walter Reed Army Institute of Research.

Dr. Taylor earned his MSc. in Medical Parasitology from the London School of Hygiene and Tropical Medicine, M.D. from Harvard Medical School, D.M.S. from Dartmouth Medical School and B.S. in Biology from Kenyon College.

About Vaxart

On May 1, 2018 Novartis reported the US Food and Drug Administration (FDA) has approved Kymriah (tisagenlecleucel) suspension for intravenous infusion for its second indication – the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy including diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma and DLBCL arising from follicular lymphoma (Press release, Novartis, MAY 1, 2018, View Source [SID1234525917]). Kymriah is not indicated for the treatment of patients with primary central nervous system lymphoma. Kymriah, developed in collaboration with the University of Pennsylvania, became the first chimeric antigen receptor T cell (CAR-T) therapy to receive regulatory approval in August 2017 for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse. Kymriah is now the only CAR-T cell therapy to receive FDA approval for two distinct indications in non-Hodgkin lymphoma (NHL) and B-cell ALL.

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"Today’s FDA approval of Kymriah provides another opportunity for Novartis to build on its leadership in CAR-T development, delivering a potentially transformative therapy with durable and sustained response rates and a well-characterized safety profile to help patients in dire need of new treatment options," said Liz Barrett, CEO, Novartis Oncology. "We look forward to leveraging all of our learnings and new capabilities from the initial launch of Kymriah in pediatric and young adult B-cell ALL for this larger group of patients."

DLBCL is the most common form of NHL[2],[3]. For patients who relapse or don’t respond to initial therapy, there are limited treatment options that provide durable responses, and median life expectancy is approximately six months[4],[5].

"The goal of Kymriah is to provide physicians with a therapy that has demonstrated durable response rates in relapsed or refractory DLBCL patients, a patient population that has endured multiple rounds of chemotherapy with many having experienced unsuccessful stem cell transplants," said Stephen J. Schuster, MD, the Robert and Margarita Louis-Dreyfus Professor in Chronic Lymphocytic Leukemia and Lymphoma Clinical Care and Research in Penn’s Perelman School of Medicine and director of the Lymphoma Program at the Abramson Cancer Center. "With this approval, physicians now have a meaningful therapeutic option that can achieve and maintain a sustained response without stem cell transplant along with a consistent safety profile."

Kymriah is an innovative immunocellular therapy that is a one-time treatment manufactured individually for each patient using the patient’s own T cells. Kymriah uses the 4-1BB costimulatory domain in its chimeric antigen receptor to enhance cellular expansion and persistence. In 2012, Novartis and Penn entered into a global collaboration to further research, develop and commercialize CAR-T cell therapies, including Kymriah, for the investigational treatment of cancers.

As part of the Novartis commitment to ensure eligible patients have access to Kymriah, the company continues to collaborate with the Centers for Medicare and Medicaid Services (CMS) on the creation of an appropriate value-based pricing approach. Novartis continues to be an innovator and leader in value and innovative-based pricing options, and is proud to work with CMS and other stakeholders across the healthcare spectrum on creating a sustainable and modern healthcare payment system.

To ensure all hospitals and their associated clinics are aware of how to manage the risks of cytokine release syndrome (CRS) and neurological toxicities, Kymriah is available through a Risk Evaluation and Mitigation Strategy (REMS) program. The REMS program serves to inform and educate healthcare professionals about the risks that may be associated with Kymriah treatment. To support safe patient access, Novartis has established a network of certified treatment centers throughout the country, which are fully trained on the use of Kymriah and appropriate patient care, and there are currently treatment centers which are certified and fully operational to begin treatment of eligible patients with DLBCL.

To address the unique aspects of this therapy, Novartis offers various patient programs and resources to support safe and timely access for patients and address a range of needs.

Novartis is also committed to bringing Kymriah to patients outside the US. In January 2018, Novartis announced that the European Medicines Agency (EMA) granted accelerated assessment to the Marketing Authorization Application (MAA) for Kymriah for the treatment of children and young adults with r/r B-cell ALL and for adult patients with r/r DLBCL who are ineligible for ASCT. Accelerated assessment is granted to therapies which may provide a significant improvement in the safety and effectiveness of the treatment of a serious disease, and the designation is intended to expedite the standard review time. Novartis plans additional regulatory submissions for Kymriah in pediatric and young adult patients with r/r B-cell ALL and adult patients with r/r DLBCL beyond the US and EU in 2018.

About Kymriah JULIET Pivotal Study
The FDA approval of Kymriah in adult patients with r/r DLBCL is based on the pivotal phase II JULIET clinical trial, the first multi-center global registration study for Kymriah in adult patients with r/r DLBCL. JULIET was conducted in collaboration with Penn, and is the largest study examining a CAR-T therapy in DLBCL, enrolling patients from 27 sites in 10 countries across the US, Canada, Australia, Japan and Europe, including: Austria, France, Germany, Italy, Norway and the Netherlands. In the JULIET trial, patients were infused in the inpatient and outpatient setting.

In this Novartis-sponsored study, Kymriah showed an overall response rate (ORR) of 50% (95% confidence interval [CI], 38% – 62%), with 32% of patients achieving a complete response (CR) and 18% achieving a partial response (PR) in 68 patients evaluated for efficacy. The median duration of response was not reached among these patients, indicating sustainability of response[1].

In all patients infused with Kymriah (n=106), severe or life-threatening (grade 3/4) CRS, defined by the Penn Grading Scale -a rigorous scale for grading this reaction-, occurred in 23% of patients. CRS is a known complication of CAR-T therapy that may occur when the engineered cells become activated in the patient’s body. CRS was managed globally using prior site education on implementation of the CRS treatment algorithm. Eighteen percent of all infused patients experienced grade 3/4 neurologic events, which were managed with supportive care. Encephalopathy, a distinctive neurotoxicity associated with CAR-T therapies, was seen as severe or life-threatening in 11% of patients. There were no deaths attributed to neurological events, and no fatal cases of cerebral edema have occurred. Grade 3/4 cytopenias lasting more than 28 days included thrombocytopenia (40%) and neutropenia (25%), and grade 3/4 infections occurred in 25%. The most common (>20%) adverse events (AEs) in the JULIET study are CRS, infections, pyrexia, diarrhea, nausea, fatigue, hypotension, edema and headache[1].

About Kymriah Manufacturing
Kymriah is manufactured for each individual patient using their own cells at the Novartis Morris Plains, New Jersey facility. In the US, the target turnaround time for manufacturing Kymriah is 22 days. The reliable and integrated manufacturing and supply chain platform for Kymriah allows for an individualized treatment approach on a global scale. The process includes cryopreservation of a patient’s harvested (or leukapheresed) cells, giving treating physicians and centers the flexibility to initiate therapy with Kymriah based on the individual patient’s condition. Novartis has significant CAR-T manufacturing experience and has demonstrated a reproducible product. Novartis has manufactured CAR-T cells for more than 300 patients from 11 countries. Novartis continues to advance its CAR-T manufacturing expertise in Morris Plains where we have been supplying CAR-T cells for global clinical trials and where we continue to invest in support of the anticipated demand to meet the needs of patients.

Novartis has also successfully established the Kymriah manufacturing process at the Fraunhofer-Institut for cell therapy and immunology (Fraunhofer-Institut für Zelltherapie and Immunologie) facility in Leipzig, Germany, which currently supports the manufacturing of Kymriah for global clinical trials.

Novartis Leadership in Immuno-Oncology
Novartis is at the forefront of investigational immunocellular therapy as the first pharmaceutical company to initiate global CAR-T trials, and has significantly invested in CAR-T research and worked with pioneers in the field. Kymriah, the first approved CAR-T cell therapy, is the cornerstone of this strategy. Active research programs are underway targeting other hematologic malignancies and solid tumors, and include efforts focused on next generation CAR-Ts that involve simplified manufacturing schemes and gene edited cells.

Kymriah (tisagenlecleucel) US Important Safety information
Kymriah may cause side effects that are severe or life-threatening, such as Cytokine Release Syndrome (CRS) or Neurological Toxicities. Patients with CRS may experience symptoms including difficulty breathing, fever (100.4°F/38°C or higher), chills/shaking chills, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure, or dizziness/lightheadedness. Patients may be admitted to the hospital for CRS and treated with other medications.

Patients with neurological toxicities may experience symptoms such as altered or decreased consciousness, headaches, delirium, confusion, agitation, anxiety, seizures, difficulty speaking and understanding, or loss of balance. Patients should be advised to call their healthcare provider or get emergency help right away if they experience any of these signs and symptoms of CRS or neurological toxicities.

Because of the risk of CRS and neurological toxicities, Kymriah is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called Kymriah REMS.

Serious allergic reactions, including anaphylaxis, may occur after Kymriah infusion.
Kymriah can increase the risk of life-threatening infections that may lead to death. Patients should be advised to tell their healthcare provider right away if they develop fever, chills, or any signs or symptoms of an infection.

Patients may experience prolonged low blood cell counts (cytopenia), where one or more types of blood cells (red blood cells, white blood cells, or platelets) are decreased. The patient’s healthcare provider will do blood tests to check all of their blood cell counts after treatment with Kymriah. Patients should be advised to tell their healthcare provider right away if they get a fever, are feeling tired, or have bruising or bleeding.

Patients may experience hypogammaglobulinemia, a condition in which the level of immunoglobulins (antibodies) in the blood is low and the risk of infection is increased. It is expected that patients may develop hypogammaglobulinemia with Kymriah, and may need to receive immunoglobulin replacement for an indefinite amount of time following treatment with Kymriah. Patients should tell their healthcare provider about their treatment with Kymriah before receiving a live virus vaccine.

After treatment with Kymriah, patients will be monitored lifelong by their healthcare provider, as they may develop secondary cancers or recurrence of their cancer.

Patients should not drive, operate heavy machinery, or do other dangerous activities for eight weeks after receiving Kymriah because the treatment can cause temporary memory and coordination problems, including sleepiness, confusion, weakness, dizziness, and seizures.

Some of the most common side effects of Kymriah are difficulty breathing, fever (100.4°F/38°C or higher), chills/shaking chills, confusion, severe nausea, vomiting and diarrhea, severe muscle or joint pain, very low blood pressure, dizziness/lightheadedness, and headache. However, these are not all of the possible side effects of Kymriah. Patients should talk to their healthcare provider for medical advice about side effects.

Prior to a female patient starting treatment with Kymriah, their healthcare provider may do a pregnancy test. There is no information available for Kymriah use in pregnant or breast-feeding women. Therefore, Kymriah is not recommended for women who are pregnant or breast feeding. Patients should talk to their healthcare provider about birth control and pregnancy.

Patients should tell their healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

After receiving Kymriah, patients should be advised that some commercial HIV tests may cause a false-positive test result. Patients should also be advised not to donate blood, organs, or tissues and cells for transplantation after receiving Kymriah.

Please see the full Prescribing Information for Kymriah, including Boxed WARNING, and Medication Guide at www.Kymriah.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 Kymriah or the other investigational products described in this press release, regarding our ability to scale and sustain commercial manufacturing for Kymriah or such other products, or regarding potential future revenues from Kymriah and such other 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 Kymriah or the other investigational 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. Neither can there be any guarantee that Novartis will successfully scale and sustain commercial manufacturing for Kymriah or the other products described in this press release, or successfully sustain a network of treatment centers to offer Kymriah. Nor can there be any guarantee that Novartis will successfully establish and implement indication-based pricing for Kymriah or the other investigational products described in this press release, or that such indication-based pricing will achieve the intended goals of such pricing. Neither can there be any guarantee that Kymriah and such other products will be commercially successful in the future. In particular, our expectations regarding Kymriah and such other products could be affected by, among other things, our ability to successfully scale and sustain commercial manufacturing and sustain a network of treatment centers; our ability to successfully establish and implement indication-based pricing; 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 May 1, 2018 Savara Inc. (NASDAQ: SVRA), an orphan lung disease company, reported it will release its first quarter 2018 financial results on Wednesday, May 9, 2018 (Press release, Savara, MAY 1, 2018, View Source [SID1234525935]). Savara management will also host a conference call for investors beginning at 5:30 p.m. ET on Wednesday, May 9, 2018 to discuss its first quarter 2018 financial results and to provide a business update.

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Shareholders and other interested parties may access the conference call by dialing (855) 239-3120 from the U.S., (855) 669-9657 from Canada, and (412) 542-4127 from elsewhere outside the U.S. and requesting the Savara Inc. call. A live webcast of the conference call will be available online in the Investors section of Savara’s website at View Source Replays of the webcast will be available on Savara’s website for 30 days and a telephone replay will be available through May 16th, 2018 by dialing (877) 344-7529 from the U.S., (855) 669-9658 from Canada, and (412) 317-0088 from elsewhere outside the U.S. and entering replay access code 10119917.

Michelle Mitchell OBE has been appointed as CEO of Cancer Research UK, replacing Sir Harpal Kumar who is due to stand down in the summer (Press release, Cancer Research UK, MAY 1, 2018, View Source [SID1234525907]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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"I am delighted to be able to announce Michelle’s appointment as Cancer Research UK’s new CEO. She is an outstanding and seasoned charity leader, with the skill and ambition to lead the charity in the next phase of achieving our vision of 3 in 4 people surviving cancer by 2034." – Sir Leszek Borysiewicz, chairman of Cancer Research UK
Michelle Mitchell said: "It’s a privilege to be appointed as CEO of the world’s leading charity dedicated to beating cancer through research. Like many people, I have family who have been affected by cancer and I’m passionate about Cancer Research UK’s goal to speed up impact on survival. I have admired the work of the charity for many years, and I look forward to leading it as we embark on the next chapter of our critically important mission."

Michelle has been CEO of the MS Society since 2013. Under her leadership, there has been a 40% increase in access to effective MS treatments and she has developed a £100m research fundraising appeal.

Before joining the MS Society, Michelle’s previous leadership roles were as Director General of Age UK and Chair of the Fawcett Society.

Michelle is a non-executive director of NHS England, and has been a trustee of The King’s Fund and the Power to Change Trust.

Michelle has a BA in Economics, an MA in Politics and Administration and an International Executive Diploma from INSEAD. Michelle is an alumna of the Innovations in Government Programme at Harvard University JFK School and of the Strategic Perspectives in Non-profit Management programme at Harvard Business School.