On September 6, 2016 Karyopharm Therapeutics Inc. (Nasdaq:KPTI), a clinical-stage pharmaceutical company, reported positive top-line results from its Phase 2b STORM study evaluating the activity of selinexor (KPT-330) in multiple myeloma (MM) (Press release, Karyopharm, SEP 6, 2016, View Source [SID:1234514955]). Selinexor, the Company’s lead, novel, oral Selective Inhibitor of Nuclear Export / SINE compound, is being developed for the treatment of a variety of malignancies, including MM. Karyopharm also provided an overview of the planned development path for selinexor in MM.

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The Phase 2b STORM study is a single-arm clinical trial evaluating selinexor in combination with low-dose dexamethasone in heavily pretreated MM patients, meaning patients with quad-refractory disease or penta-refractory disease. Patients with quad-refractory disease have previously received two proteasome inhibitors (PIs) (bortezomib (Velcade) and carfilzomib (Kyprolis)) and two immunomodulatory agents (IMiDs) (lenalidomide (Revlimid) and pomalidomide (Pomalyst)), and their disease is refractory to at least one PI, at least one IMiD, and has progressed following their most recent therapy. Patients with penta-refractory myeloma have quad-refractory disease that is also refractory to an anti-CD38 monoclonal antibody, such as daratumumab (Darzalex) or isatuximab.

Among the 78 evaluable patients (median seven prior treatment regimens), the overall response rate (ORR) was 20.5% based on Independent Review Committee adjudication, including very good partial responses (VGPR) and partial responses (PR). Among the 48 patients in the quad-refractory group, the ORR was 20.8%. For comparison, in a similar quad-refractory patient population, Darzalex had an ORR of 21% and isatuximab had an ORR of 20%. Among the 30 patients in the penta-refractory group, the ORR was 20.0%. Several patients remain on study, including those with VGPRs, PRs and minor responses. To the Company’s knowledge, no agent has previously shown activity in this penta-refractory population. The side effect profile for selinexor was consistent with previous trials, and no new safety signals were identified. Additional data will be presented later this year.

Keith Stewart, MB. ChB., Anna Maria and Vasek Polack Professor of Cancer Research at the Mayo Clinic and lead investigator of the STORM study, said, "Although treatment of multiple myeloma has improved dramatically, eventually many patients will develop refractory disease, no longer responding to any of the immunomodulatory agents and proteasome inhibitors commonly used (quad-refractory). These patients will also eventually progress on anti-CD38 monoclonal antibodies, which we refer to as penta-refractory disease. These are clearly the patients with the highest unmet need, as they have no remaining viable treatment options. The STORM data are compelling because they demonstrate that oral selinexor achieves a 20.8% response rate in the quad-refractory group, similar to recently reported intravenous anti-CD38 therapy results in the same patient population. Selinexor also achieves an equally notable 20.0% response rate in the penta-refractory group, with the significant advantage of oral administration. We are currently unaware of any other therapy, oral or intravenous, reporting such activity in these difficult-to-treat patients who have exhausted all available therapies."

In addition to the STORM study, Karyopharm initiated the Phase 1b/2 STOMP (Selinexor and Backbone Treatments of Multiple Myeloma Patients) study to evaluate selinexor in combination with existing therapies across the broader population in MM. In the arm evaluating the combination of selinexor, bortezomib and dexamethasone, dose escalation has been completed and the recommended dose has been determined, providing a basis for the randomized Phase 3 "BOSTON" study described below.

Sagar Lonial, MD, Professor and Chair, Department of Hematology and Medical Oncology, Emory University School of Medicine and Chief Medical Officer, Winship Cancer Institute of Emory University, commented, "Myeloma continues to be an incurable blood cancer in most patients and our main goal in treating refractory disease is to induce responses and maintain them as long as possible. In addition to these new data with oral selinexor and low-dose dexamethasone, the emerging clinical data from selinexor in combination with bortezomib, including in proteasome-inhibitor refractory disease, suggests a synergistic effect and favorable safety profile. These data are quite exciting and will form the basis for future studies."

Selinexor: Multiple Myeloma Clinical Development Plans and Timelines

Based on these positive top-line STORM data and existing unmet medical need, Karyopharm plans to implement the following clinical development initiatives focusing on obtaining regulatory approval of selinexor in MM:

Karyopharm is expanding the STORM study to include approximately 120 additional patients with penta-refractory MM. To the Company’s knowledge, this will be the largest study ever undertaken in this patient population. Assuming a positive outcome and remaining unmet medical need, Karyopharm intends to use the data from the expanded STORM study to support a request that the FDA consider granting accelerated approval for selinexor in MM. The Company anticipates reporting top-line data from the expanded cohort in early 2018.

The FDA instituted its Accelerated Approval Program to allow for expedited approval of drugs that treat serious conditions and that fill an unmet medical need based on a surrogate endpoint or an intermediate clinical endpoint thought to predict clinical benefit, like ORR. Accelerated approval is available only for drugs that provide a meaningful therapeutic benefit over existing treatments at the time of consideration of the application for accelerated approval, which the FDA has reiterated in its feedback to the Company. Particularly in disease areas with multiple available and potential new therapies, such as MM, accelerated approval carries a high regulatory threshold. Drugs approved under the Accelerated Approval Program are also typically required to be studied in randomized confirmatory trials on a post-approval basis to confirm clinical benefit. Given the number of approved and experimental therapies in development to treat MM, and consistent with its standard guidance, the FDA has recommended that the Company conduct a randomized study geared towards full approval, which the Company is planning with the BOSTON study discussed below. In addition, to the Company’s knowledge, no other studies are currently being conducted in the penta-refractory patient population and no agents have shown activity in these patients. In light of this unmet medical need, the Company believes that positive data in this patient population could support accelerated approval. The FDA has stated to the Company that other therapies in MM may receive full approval prior to the potential action date on any accelerated approval request for selinexor that the Company may submit, which may prevent accelerated approval for selinexor if the FDA deems that such therapies constitute earlier lines of therapy in MM that were not administered to patients in the STORM study. Also, while the FDA has previously indicated its preference for studies that isolate the effects of individual drugs, steroids like dexamethasone are part of nearly every myeloma treatment regimen, and low-dose dexamethasone is not a single-agent treatment for MM. Other available therapies for MM, such as pomalidomide (Pomalyst), have received accelerated approval based on studies that were conducted in combination with dexamethasone or a similar steroid. Based on these factors, the Company believes that the STORM study design and the planned expansion in the penta-refractory patient group present an opportunity for the Company to request that the FDA grant accelerated approval if data from the expansion confirm the data presented today.

The Company also plans to initiate a pivotal randomized Phase 3 study, known as the BOSTON (Bortezomib, Selinexor and dexamethasone) study, which will evaluate selinexor in combination with bortezomib (Velcade) and low-dose dexamethasone (SVd) compared to bortezomib and low-dose dexamethasone (Vd) in patients with MM who have had one to three prior lines of therapy. Based on data from the Phase 1b portion of the STOMP study, which was most recently presented at the 2016 European Hematology Association (EHA) (Free EHA Whitepaper) Annual Meeting, the Company has identified the combination dose to be used in the BOSTON study. Karyopharm expects that the study will enroll approximately 360 patients. The Company intends to seek additional FDA input on the protocol for the BOSTON study prior to commencing the trial in early 2017.

Based in part on its plans to conduct the pivotal randomized BOSTON study to support full regulatory approval of selinexor for patients with previously-treated MM and the Company’s planned expansion of STORM to support potential accelerated approval, Karyopharm will not pursue the SCORE study at this time. The SCORE study was designed to assess the combination of selinexor with carfilzomib (Kyprolis) and low-dose dexamethasone. The ongoing Phase 1/2 investigator sponsored study evaluating selinexor in combination with carfilzomib and dexamethasone in refractory MM, including carfilzomib-refractory MM, continues to enroll patients, and updated data from this study is expected to be presented later this year.
"Our updated clinical development plan for selinexor in myeloma reflects the strong foundation of clinical data from both the STORM and STOMP studies," said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. Dr. Kauffman was instrumental in the clinical development and regulatory approvals of Velcade and Kyprolis in MM. "We believe this development plan provides a path to potential FDA and EMA filings for oral selinexor in MM, with the potential to support accelerated or conditional approval if the FDA or EMA, respectively, agree. We look forward to sharing the additional data from both STORM and STOMP later this year. We believe selinexor has the potential to be a much-needed oral treatment option for patients suffering with this incurable disease."

More About the Phase 2b STORM Study

The Phase 2b STORM (Selinexor Treatment of Refractory Myeloma) (NCT02336815) study is a multi-center, single-arm clinical trial evaluating selinexor in combination with low-dose dexamethasone in patients with heavily-pretreated multiple myeloma (MM), which the Company refers to as having at least quad-refractory MM. These are patients who have received bortezomib (Velcade) and carfilzomib (Kyprolis), each of which is a proteasome inhibitor (PI), and lenalidomide (Revlimid) and pomalidomide (Pomalyst), each of which is an immunomodulatory agent (IMiD), and whose disease is refractory to at least one PI, at least one IMiD, and is refractory to their most recent therapy. Prior treatment regimens must have also included an alkylating agent and a glucocorticoid. In the original version of the protocol, at least 25% of patients in this study must have had MM that is also refractory to an anti-CD38 monoclonal antibody, such as daratumumab (DarzalexTM), which the Company refers to as having penta-refractory MM. Of the 79 patients enrolled in the first cohort, 78 had measurable disease at baseline, with 48 (62%) patients classified as having quad-refractory and 30 (38%) patients classified as having penta-refractory MM.

The primary endpoint of the STORM study is overall response rate (ORR). The original trial had several secondary endpoints, including ORR in patients whose disease is relapsed/refractory to an anti-CD38 monoclonal antibody, duration of response (DOR) and clinical benefit rate (CBR). Karyopharm is now expanding the STORM study to include additional sites in the United States and Europe to enroll approximately 120 additional patients with penta-refractory MM to further evaluate the safety and efficacy of selinexor as a basis for potential regulatory submission requesting accelerated (FDA) or conditional (EMA) approval, based on ORR.

More About the Phase 1b/2 STOMP Study

The Phase 1b/2 STOMP (NCT02343042) study is a multi-arm clinical trial evaluating selinexor and low-dose dexamethasone in combination with backbone therapies bortezomib (Velcade), pomalidomide (Pomalyst) or lenalidomide (Revlimid) in patients with heavily pretreated relapsed/refractory MM. Each combination is evaluated on a separate arm of the STOMP study and, within each combination, each of two treatment cohorts will receive either once weekly or twice weekly dosing of selinexor.

Data from the STOMP study was initially reported at the European Hematology Association (EHA) (Free EHA Whitepaper) 2016 annual meeting. As of June 8, 2016, of the 16 patients treated in the SVd combination arm, all of whom are evaluable, 11 responded (1 patient with a complete response (CR), 3 with VGPRs and 7 with PRs for an ORR of 69%). An additional three patients achieved a minor response (MR), for a CBR of 88%. Several of the patients on this selinexor, Velcade and low-dose dexamethasone (SVd) combination arm had high-risk haplotypes, including deletion of chromosome 17p, and 10 of the 16 evaluable patients had MM previously refractory to a proteasome inhibitor. Seven of these 10 patients responded (1 CR, 1 VGPR, and 5 PRs) for an ORR of 70%. An additional patient achieved an MR for a CBR of 80% in this subgroup. Overall, side effects reported in the SVd arm were similar to, or less severe than, those observed with single-agent selinexor. Karyopharm plans to submit updated data from the STOMP study for presentation at a medical conference later this year. The Company is also planning to add two additional arms to the STOMP study — one to evaluate selinexor in combination with daratumumab (Darzalex) and the other to evaluate selinexor in combination with Pomalyst, Velcade and low-dose dexamethasone.

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. Over 1,600 patients have been treated with selinexor in company- and investigator-sponsored Phase 1 and Phase 2 clinical trials in advanced hematologic malignancies and solid tumors. Selinexor is currently being evaluated in several mid- and later-stage clinical trials, including a Phase 2b single-arm trial of selinexor and low-dose dexamethasone in multiple myeloma (STORM), a Phase 1b/2 trial in combination with backbone therapies in multiple myeloma (STOMP), a Phase 2 trial in older patients with acute myeloid leukemia (SOPRA), a Phase 2b trial in diffuse large B-cell lymphoma (SADAL), and a Phase 2/3 trial in liposarcoma (SEAL), 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 the Company’s clinical development priorities for selinexor. The latest clinical trial information for selinexor is available at www.clinicaltrials.gov.

About Multiple Myeloma

Multiple myeloma (MM) is form of blood cancer that develops in the bone marrow. In multiple myeloma, normal plasma cells transform into malignant myeloma cells and produce large quantities of an abnormal immunoglobulin called monoclonal protein or M protein. The monoclonal protein produced by myeloma cells interferes with normal blood cell production. In addition, the levels of functional immunoglobulins are depressed in individuals with multiple myeloma. Although the process is not completely understood, it appears that the functional immunoglobulins made by existing, healthy plasma cells breaks down more quickly in patients with multiple myeloma than in healthy individuals. MM is the second most commonly diagnosed blood cancer after Non-Hodgkin’s Lymphoma (NHL). According to SEER data from the National Cancer Institute, in the United States in 2016 approximately 30,000 new cases of MM will be diagnosed, and approximately 12,500 patients will die from the disease. Approximately 100,000 people in the United States were living with MM in 2013. According to GlobalData, the 2015 MM market was valued at approximately $11 billion and the size of the myeloma market is projected to increase to over $22 billion by 2023.

On September 6, 2016 (GLOBE NEWSWIRE) Cyclacel Pharmaceuticals, Inc. (Nasdaq:CYCC) (Nasdaq:CYCCP) ("Cyclacel" or the "Company"), a biopharmaceutical company developing oral therapies that target various phases of cell cycle control for the treatment of cancer and other serious disorders, reported the presentation of preclinical data demonstrating that both Cyclacel’s CYC065, a clinical stage, second generation, cyclin-dependent kinase CDK2/9 inhibitor, and CCT68127, a preclinical stage CDK2/9 inhibitor, prolong survival in MYCN-addicted neuroblastoma models (Press release, Cyclacel, SEP 6, 2016, View Source [SID:1234514936]). The data were presented at the Childhood Cancer Meeting, September 5 — 7th in London, UK.

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"This study adds to the growing evidence of the value of CDK inhibition as an approach to treating cancer. MYCN is an important therapeutic target in oncology and a major oncogenic driver of neuroblastoma, a childhood cancer. There are no approved drugs that act against MYCN or MYC proteins," said Spiro Rombotis, President and Chief Executive Officer of Cyclacel. "We are encouraged by the preclinical data, which extend and support earlier findings, showing that CYC065 and CCT68127 reduce MYCN transcription and protein levels and have antitumor activity in neuroblastoma models. Additionally, we have demonstrated in other preclinical studies, that our transcriptional CDK2/9 inhibitors target key molecular features of cancers with poor prognosis, such as MLL-r leukemias or MYC-driven lymphomas. Furthermore, evidence from early clinical trials show that CDK2/9 inhibitors can have a synergistic effect with other anticancer agents. We look forward to reporting data from our ongoing Phase 1 study of CYC065 in patients with solid tumors."

In this preclinical study, an international group of researchers led by Prof. Louis Chesler from The Institute of Cancer Research, London, explored in vitro and in vivo the sensitivity of neuroblastoma cells to CYC065 and CCT68127. Neuroblastoma cells with MYCN amplification and overexpression were found to be particularly sensitive to both CDK2/9 inhibitors. The mechanism of action of CYC065 and CCT68127 included inhibition of MYCN transcription, downregulation of N-MYC protein, blocking neuroblastoma cell proliferation and induction of apoptosis. Treatment with either CYC065 or CCT68127 significantly reduced tumor burden and prolonged survival in several neuroblastoma models in vivo.

Citation

Poon E, Jamin Y, Walz S, Hakkert S, Kwok C, Hallsworth A, Thway K, Barker K, Sbirkov Y, Pickard L, Urban Z, Tardif N, Webber H, Box G, Valenti M, De Haven Brandon A, Petrie K, Ebus M, Molenaar J, Eccles S, Robinson SP, Zheleva D, Eilers M, Workman P, Chesler L. The small molecule CDK2 and CDK9 inhibitors CYC065 and CCT68127 are potent inhibitors of MYCN via transcriptional repression. Childhood Cancer Meeting 2016, September 5 — 7th, London, UK, Abs. 1-19.

About MYCN

The MYCN gene encodes a transcription factor that is expressed in fetal brain and neural crest and is critical for normal development of the brain and nerves. The MYCN oncogene is over-expressed in a number of different types of cancer, most notably neuroblastoma, and also rhabdomyosarcoma, medulloblastoma, astrocytoma, Wilms’ tumor and small cell lung cancer. Amplification of the MYCN oncogene is the most common genomic alteration in aggressive neuroblastomas and is associated with poor clinical outcome. There are no approved drugs that directly target MYCN prompting the investigation of indirect approaches such as exploitation of a synthetic lethal relationship between MYCN amplification/overexpression and inhibition of CDK2.

About Neuroblastoma

According to the American Cancer Society, neuroblastoma is the most common cancer in infants less than one year old and it accounts for about six percent of all pediatric cancers or about 700 cases per year. The disease has a fatal outcome in one out of every seven children diagnosed with it. Preclinical data from an international investigator group demonstrated that Cyclacel’s CYC065 and CCT68127 target MYCN gene expression and have potent in vitro and in vivo anti-tumor activities, suggesting therapeutic potential in neuroblastoma, including high-risk patients with MYCN amplification.

About CYC065

CYC065 is a highly-selective, orally- and intravenously-available, second generation inhibitor of CDK2 and CDK9 and causes apoptotic death of cancer cells at sub-micromolar concentrations. Antitumor efficacy has been achieved in vivo with once a day oral dosing at well tolerated doses. Evidence from published nonclinical studies show that CYC065 may benefit patients with adult and pediatric hematological malignancies, including certain Acute Myeloid Leukemias (AML), Acute Lymphocytic Leukemias (ALL), Chronic Lymphocytic Leukemias (CLL), B-cell lymphomas, multiple myelomas, and certain solid tumors, including breast and uterine cancers. Independent investigators published nonclinical evidence that CYC065 induced regression or tumor growth inhibition in a model of HER2-positive breast cancer addicted to cyclin E that is resistant to trastuzumab, reduced tumor growth in models of CCNE1-amplified uterine serous carcinoma and reduced tumor burden and prolonged survival in several neuroblastoma models in vivo.

CYC065 is mechanistically similar but has much higher dose potency, in vitro and in vivo, improved metabolic stability and longer patent protection than seliciclib, Cyclacel’s first generation CDK inhibitor. Translational biology data support development of CYC065 as a stratified medicine for solid and liquid cancers. CYC065 has been shown to reverse drug resistance associated with the addiction of cancer cells to cyclin E and may inhibit CDK9-dependent oncogenic and leukemogenic pathways, including malignancies driven by certain oncogenes and mixed lineage leukemia rearrangements (MLL-r). CYC065 causes prolonged down regulation of the Mcl-1-mediated pro-survival pathway in cancer cells.

On September 6, 2016 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) reported that new preclinical data as well as early clinical data from an ongoing Phase 1 study will be presented for IPI-549, an immuno-oncology development candidate that selectively inhibits PI3K-gamma, during the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper): Translating Science into Survival taking place September 25-28, 2016, in New York City (Press release, Infinity Pharmaceuticals, SEP 6, 2016, View Source;p=RssLanding&cat=news&id=2199662 [SID:1234514950]).

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The following two presentations will take place during the poster session being held on Monday, September 26, from 5:15 p.m. – 7:45 p.m. ET:

Title: IPI-549-01: A Phase 1/1b first-in-human study of IPI-549, a PI3K-gamma inhibitor, as monotherapy and in combination with an anti-PD1 antibody in subjects with advanced solid tumors
Poster Board: B070
Presentation Time: Monday, September 26, 6:15 p.m. – 7:15 p.m. ET

Title: The PI3K-gamma inhibitor, IPI-549, increases antitumor immunity by targeting tumor-associated myeloid cells and remodeling the immune-suppressive tumor microenvironment
Poster Board: B032
Presentation Time: Monday, September 26, 6:15 p.m. – 7:15 p.m. ET

About IPI-549
IPI-549 is an orally administered immuno-oncology development candidate that selectively inhibits PI3K-gamma. In preclinical studies, IPI-549 inhibits immune-suppressive macrophages within the tumor microenvironment, whereas other immunotherapies such as checkpoint modulators more directly target immune effector cell function. As such, IPI-549 may have the potential to treat a broad range of solid tumors and represents a potentially complementary approach to restoring anti-tumor immunity in combination with other immunotherapies such as checkpoint inhibitors.

IPI-549 is an investigational compound and its safety and efficacy has not been evaluated by the U.S. Food and Drug Administration or any other health authority.

On September 6, 2016 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported that data from six abstracts will be presented at the 2016 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) annual meeting, October 7 to October 11, 2016, in Copenhagen (Press release, TESARO, SEP 6, 2016, View Source [SID:1234514953]). In addition, TESARO will webcast an investor and analyst briefing from Copenhagen on Saturday, October 8 at 7:00 PM local time in conjunction with the ESMO (Free ESMO Whitepaper) annual meeting.

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Please plan to visit TESARO at Booth #415 for information about our pipeline.

Presentation Details (all times local):

Niraparib

Saturday, October 8, 2016, 4:30 PM to 6:00 PM — Presidential Symposium 1
A randomized, double-blind phase 3 trial of maintenance therapy with niraparib vs placebo in patients with platinum-sensitive recurrent ovarian cancer (ENGOT-OV16/NOVA trial)
Presentation: LBA3_PR, Presidential Symposium 1, Location: Copenhagen Room, Time: 5:30 PM
Results selected for inclusion in the ESMO (Free ESMO Whitepaper) Press Programme

Sunday, October 9, 2016, 1:00 PM to 2:00 PM
Modeling maintenance therapy in ovarian cancer
Poster: 1043P, Location: Hall E

Niraparib is an investigational product candidate that has not been approved by any regulatory agencies.

Rolapitant

Sunday, October 9, 2016, 1:00 PM to 2:00 PM
Efficacy and safety of rolapitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) in elderly patients
Poster: 1441P, Location: Hall E

Sunday, October 9, 2016, 1:00 PM to 2:00 PM
Efficacy of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with gastrointestinal and colorectal cancers
Poster: 1440P, Location: Hall E

Sunday, October 9, 2016, 1:00 PM to 2:00 PM
Safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving Breast Cancer Resistant Protein (BCRP) substrate chemotherapy agents
Poster: 1442P, Location: Hall E

Sunday, October 9, 2016, 1:00 PM to 2:00 PM
Systematic review of the efficacy and safety of neurokinin-1 receptor antagonists for chemotherapy-induced nausea and vomiting: identification of the relevant clinical trials
Poster: 1443P, Location: Hall E

Rolapitant is marketed in the United States under trade name VARUBI. Rolapitant has not been approved by any regulatory agencies outside of the United States.

Investor Briefing and Webcast
TESARO will webcast an investor and analyst briefing in Copenhagen on Saturday, October 8 at 7:00 PM local time in conjunction with the ESMO (Free ESMO Whitepaper) annual meeting. At this briefing, TESARO management will review the niraparib development program and data presented at ESMO (Free ESMO Whitepaper) and answer questions from investors and analysts. This event will be webcast live and archived for 30 days, and may be accessed from the TESARO Investor Events and Presentations webpage at www.tesarobio.com.

About Niraparib
Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in four ongoing pivotal trials. TESARO is building a robust niraparib franchise by assessing activity across multiple tumor types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development program for niraparib includes the Phase 3 trial in patients with recurrent ovarian cancer (the NOVA trial); a registrational Phase 2 treatment trial in patients with ovarian cancer (the QUADRA trial); a Phase 3 trial for the treatment of patients with BRCA-positive breast cancer (the BRAVO trial); and a Phase 3 trial in patients with first-line ovarian cancer (the PRIMA trial). Several collaborator-sponsored studies are also underway, including combination trials of niraparib plus pembrolizumab and bevacizumab. Janssen Biotech has licensed rights to develop and commercialize niraparib specifically for patients with prostate cancer worldwide, except in Japan.

About VARUBI (Rolapitant)
Rolapitant is marketed in the United States under trade name VARUBI. VARUBI is a substance P/neurokinin-1 (NK-1) receptor antagonist indicated in the U.S. in combination with other antiemetic agents in adults for the prevention of delayed nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy. VARUBI is contraindicated in patients receiving thioridazine, a CYP2D6 substrate. The inhibitory effect of a single dose of VARUBI on CYP2D6 lasts at least seven days and may last longer. Avoid use of pimozide; monitor for adverse events if concomitant use with other CYP2D6 substrates with a narrow therapeutic index cannot be avoided. Please see full prescribing information, including additional important safety information, available at www.varubirx.com.

An intravenous formulation of rolapitant is also being developed. TESARO licensed exclusive rights for the development, manufacture, commercialization, and distribution of VARUBI (rolapitant) from OPKO Health, Inc.

On September 6, 2016 Valeant Pharmaceuticals International, Inc. (NYSE: VRX and TSX: VRX) ("Valeant") and Progenics Pharmaceuticals, Inc. (Nasdaq: PGNX) ("Progenics") reported the U.S. commercial launch of RELISTOR (methylnaltrexone bromide) Tablets, which is now available for prescribing. RELISTOR Tablets (450 mg once daily) were approved by the U.S. Food and Drug Administration (FDA) for the treatment of opioid-induced constipation (OIC) in adults with chronic non-cancer pain on July 19, 2016.

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"We are very pleased to launch RELISTOR Tablets in the U.S. and provide an exceptional new treatment option for the millions of patients who suffer from extreme discomfort due to OIC," said Joseph C. Papa, Chief Executive Officer of Valeant. "This new method of delivery for RELISTOR offers healthcare professionals a novel alternative to address the treatment of OIC – a growing need in pain management – and demonstrates Valeant’s continued commitment to delivering innovative products that improve people’s lives."

In addition, RELISTOR Tablets will be highlighted during poster presentations at PAINWeek, the largest U.S. pain conference for frontline clinicians, in Las Vegas, Nevada, from September 6-10. The posters will include the following:
Webster LR, Harper JR, Israel RJ. "Oral methylnaltrexone is efficacious and well tolerated for the treatment of opioid-induced constipation in patients with chronic noncancer pain taking concomitant methadone." PAINWeek Poster, public viewing begins on
Thursday, September 8 at 12:30 p.m. PT.

Webster LR, Harper JR, Israel RJ. "Oral methylnaltrexone does not negatively impact analgesia in patients with opioid-induced constipation and chronic noncancer pain." PAINWeek Poster, public viewing begins on Thursday, September 8 at 12:30 p.m. PT.
The RELISTOR Tablets data will also be presented by Steven Simon, M.D., Professor of Pathology, University of Miami Health System, during a product theatre, "Opioid-Induced Constipation When Reliable and Rapid Relief Matters," on Friday, September 9 at 8 a.m. PT.

Important Safety Information about RELISTOR
RELISTOR (methylnaltrexone bromide) Tablets are contraindicated in patients with known or suspected gastrointestinal obstruction and patients at increased risk of recurrent obstruction, due to the potential for gastrointestinal perforation.
Cases of gastrointestinal perforation have been reported in adult patients with OIC and advanced illness with conditions that may be associated with localized or diffuse reduction of structural integrity in the wall of the gastrointestinal tract (e.g., peptic ulcer disease, Ogilvie’s syndrome, diverticular disease, infiltrative gastrointestinal tract malignancies or peritoneal metastases). Take into account the overall risk-benefit profile when using RELISTOR in patients with these conditions or other conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn’s disease). Monitor for the development of severe, persistent, or worsening abdominal pain; discontinue RELISTOR in patients who develop this symptom.

If severe or persistent diarrhea occurs during treatment, advise patients to discontinue therapy with RELISTOR and consult their healthcare provider.

Symptoms consistent with opioid withdrawal, including hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, and yawning have occurred in patients treated with RELISTOR.

Patients having disruptions to the blood-brain barrier may be at increased risk for opioid withdrawal and/or reduced analgesia. Take into account the overall risk-benefit profile when using RELISTOR in such patients. Monitor for adequacy of analgesia and symptoms of opioid withdrawal in such patients.

Avoid concomitant use of RELISTOR with other opioid antagonists because of the potential for additive effects of opioid receptor antagonism and increased risk of opioid withdrawal.

The most common adverse reactions (≥ 12%) in adult patients with opioid-induced constipation and chronic non-cancer pain receiving RELISTOR tablets were abdominal pain, diarrhea, headaches, abdominal distention, hyperhidrosis, anxiety, muscle spasms, rhinorrhea, and chills. Adverse reactions of abdominal pain, diarrhea, hyperhidrosis, anxiety, rhinorrhea, and chills may reflect symptoms of opioid withdrawal.

Please see complete Prescribing Information for RELISTOR at www.valeant.com. For more information about RELISTOR, please visit www.relistor.com.

About RELISTOR
Progenics has exclusively licensed development and commercialization rights for its first commercial product, RELISTOR, to Valeant. RELISTOR Tablets (450 mg once daily) is approved in the United States for the treatment of OIC in patients with chronic non-cancer pain. RELISTOR Subcutaneous Injection (12 mg and 8 mg) is a treatment for opioid-induced constipation approved in the United States and worldwide for patients with advanced illness and chronic non-cancer pain.