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Sunesis Pharmaceuticals Announces First Patient Treated in Vanderbilt University-Sponsored Phase 2 VITAL Study of Vosaroxin in Combination with Infusional Cytarabine in Patients with Previously Untreated AML

On March 24, 2016 Sunesis Pharmaceuticals, Inc. (Nasdaq:SNSS) reported that the first patients have been treated in the investigator-sponsored VITAL (Vosaroxin and Infusional Cytarabine for Frontline Treatment of Acute Myeloid Leukemia) Phase 2 study of vosaroxin in combination with cytarabine in patients with previously untreated acute myeloid leukemia (AML) (Press release, Sunesis, MAR 24, 2016, View Source [SID:1234509918]).

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The trial is being conducted at the Vanderbilt-Ingram Cancer Center at Vanderbilt University under the direction of Michael R. Savona, M.D., FACP, Associate Professor of Medicine and Director of Hematology Early Therapeutics Program, and Stephen A. Strickland, M.D., MSCI, Assistant Professor of Medicine.

"With an alarming rate of mortality in AML and no major change in induction therapy strategy for nearly four decades, there is an urgent need to find novel therapeutic strategies for this disease," said Dr. Strickland. "Given the established, acceptable safety profile of infusional cytarabine given concomitantly with vosaroxin, this combination offers a new approach for achieving remission in this population. It also provides the opportunity to expand upon the previously observed efficacy of vosaroxin in patients with relapsed/refractory AML and has the potential to serve as a foundation for a future randomized Phase 3 trial."

VITAL, a single-arm, open-label Phase 2 trial will enroll up to 61 previously untreated, newly diagnosed adult patients with AML. During stage 1 of the trial, 17 patients will be enrolled. The study design permits one interim look to examine evidence of futility after the first 17 patients are evaluable for response. If ≤ 7 patients achieve complete remission (CR), the VITAL DSMB will review the clinical data to determine the merits of continued enrollment. If > 7 CRs are observed, the second stage will open automatically and increase enrollment to 41 patients. During both stages, Vosaroxin will be administered intravenously at 90 mg/m2 on days 1 and 4. Cytarabine will be administered in standard fashion as a continuous infusion of 100 mg/m2 daily on days 1-7.

Patients with evidence of residual leukemia on "Day 14 biopsy" following initial induction will be offered re-induction with intravenous vosaroxin at 70 mg/m2 on days 1 and 4 in combination with continuous infusion cytarabine at 100 mg/m2 daily on days 1-7. The primary endpoint of the study is rate of CR. The secondary endpoints are to determine the safety and tolerability, presence of minimal residual disease, CR (including CR with incomplete blood count recovery), neutrophil and platelet recovery, disease free survival (DFS), overall survival (OS), and the correlation of HSCT comorbidity index and Wheatley index scores with disease response, DFS and OS.

"VITAL is the third investigator-sponsored combination trial of vosaroxin in frontline AML, and an important component of establishing our future development strategy in this setting," said Daniel Swisher, Chief Executive Officer of Sunesis. "We look forward to seeing results from these studies, which include two other leading institutions, MD Anderson and Indiana University, as we make progress on the review of our European Marketing Authorization Application for vosaroxin as a treatment for relapsed/refractory AML."

About QINPREZO (vosaroxin)

QINPREZO (vosaroxin) is an anti-cancer quinolone derivative (AQD), a class of compounds that has not been used previously for the treatment of cancer. Preclinical data demonstrate that vosaroxin both intercalates DNA and inhibits topoisomerase II, resulting in replication-dependent, site-selective DNA damage, G2 arrest and apoptosis. Both the U.S. Food and Drug Administration (FDA) and European Commission have granted orphan drug designation to vosaroxin for the treatment of AML. Additionally, vosaroxin has been granted fast track designation by the FDA for the potential treatment of relapsed or refractory AML in combination with cytarabine. Vosaroxin is an investigational drug that has not been approved for use in any jurisdiction.

The trademark name QINPREZO is conditionally accepted by the FDA and the EMA as the proprietary name for the vosaroxin drug product candidate.

Merrimack Announces Inclusion of ONIVYDE® (irinotecan liposome injection) as a Category 1 Treatment Option in the 2016 NCCN Guidelines for Pancreatic Adenocarcinoma

On March 24, 2016 Merrimack Pharmaceuticals, Inc. (Nasdaq: MACK) reported that the National Comprehensive Cancer Network (NCCN) has included ONIVYDE (irinotecan liposome injection) in combination with fluorouracil (5-FU) and leucovorin in its 2016 Clinical Practice Guidelines in Oncology for pancreatic adenocarcinoma (Press release, Merrimack, MAR 24, 2016, View Source [SID:1234509915]).

The new guidelines recognize the ONIVYDE regimen as a category 1 second-line therapy for patients with metastatic adenocarcinoma of the pancreas who have previously been treated with gemcitabine-based therapy. A category 1 classification represents the highest level of evidence and uniform NCCN consensus that the intervention is appropriate. The new guidelines are published on www.nccn.org .

"The addition of the ONIVYDE regimen to the 2016 NCCN guidelines further validates the importance of this treatment option for patients battling metastatic pancreatic cancer," said Edward J. Stewart, Head of Commercial at Merrimack. "ONIVYDE is the only FDA approved therapy available to patients whose disease has progressed after gemcitabine-based therapy and, more importantly, it addresses a critical unmet need in a patient population with very limited options. We believe these guidelines will further support the adoption of the ONIVYDE regimen as a standard-of-care in metastatic pancreatic cancer."

Pancreatic cancer is a rare and deadly disease. Each year approximately 53,000 patients are diagnosed with pancreatic cancer in the United States with only 7% surviving five years or longer1. The NCCN’s recommendation was based on a review by a multidisciplinary panel of experts from NCCN member institutions and supported by data from the NAPOLI-1 study, published in The Lancet in 2015, and the U.S. Food and Drug Administration (FDA) approval of the ONIVYDE regimen. NAPOLI-1 was a randomized, open label Phase 3 study in patients with metastatic adenocarcinoma of the pancreas who received prior gemcitabine-based therapy, and was the largest Phase 3 study in this setting to date. Patients were enrolled at 76 sites in North America, South America, Europe, Asia and Oceania.

NCCN is an alliance of 26 world-class cancer centers dedicated to the development of treatment guidelines for most cancers and to research that will ultimately improve the quality of patient care and outcomes. The NCCN guidelines are widely recognized as the standard of clinical practice in oncology and provide evidence-based treatment recommendations to assist key stakeholders, including physicians, patients and payers, in directing cancer patient care.

About ONIVYDE [pronounced \ ‘on – īh – vide \]

ONIVYDE (irinotecan liposome injection), also known as MM-398 or "nal-IRI," is a novel encapsulation of irinotecan in a liposomal formulation. The activated form of irinotecan is SN-38, which functions by inhibiting topoisomerase I (an essential enzyme involved in DNA transcription and replication) and promoting cell death. ONIVYDE was recently approved by the U.S. Food and Drug Administration in combination with fluorouracil and leucovorin for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy. For full prescribing information, including Boxed WARNING, please visit www.ONIVYDE.com.

20-F – Annual and transition report of foreign private issuers [Sections 13 or 15(d)]

(Filing, Annual, Rosetta Genomics, 2015, MAR 23, 2016, View Source [SID:1234509916])

Arbor Pharmaceuticals to Acquire XenoPort

On May 23, 2016 Arbor Pharmaceuticals, LLC (Arbor) and XenoPort, Inc. (XenoPort) (NASDAQ:XNPT) announced today that they have signed a definitive agreement under which Arbor will acquire XenoPort for $7.03 per share in cash, or a total equity value of approximately $467 million (Press release, Arbor Pharmaceuticals, MAR 23, 2016, View Source [SID1234523639]). The purchase price per share represents a 60 percent premium to the closing price of XenoPort shares on May 20, 2016.

"We are pleased to be adding HORIZANT and the XenoPort pipeline to the growing portfolio of Arbor products," said Ed Schutter, President and Chief Executive Officer of Arbor. "We believe that XenoPort’s lead product HORIZANT offers patients and physicians a valuable treatment option for moderate-to-severe primary restless legs syndrome and postherpetic neuralgia. The XenoPort sales team has done an excellent job of growing HORIZANT, and we look forward to supporting them to continue this significant momentum."

Vincent J. Angotti, Chief Executive Officer of XenoPort, stated, "This transaction provides immediate and substantial value to our stockholders, and we believe that Arbor is well positioned to provide the proper resources for a more expanded commercialization effort of HORIZANT. We evaluated many potential options to maximize the value for stockholders and believe this transaction represents a great outcome for XenoPort stockholders."

Under the terms of the agreement, Arbor will commence a tender offer to purchase all of the outstanding shares of XenoPort for $7.03 per share. Following the closing of the tender offer, the agreement provides for the parties to effect, as promptly as practicable, a merger that would result in all shares not tendered in the tender offer being converted into the right to receive $7.03 per share in cash. The transaction, which has been unanimously approved by both the Arbor Board of Directors and the XenoPort Board of Directors, is expected to close in the third quarter of 2016.

Closing of the tender offer and merger is subject to certain customary conditions, including the tender of more than 50 percent of all outstanding shares of XenoPort. The transaction is also subject to review by the U.S. Government under the Hart-Scott-Rodino (HSR) Antitrust Improvements Act, as amended, and other customary closing conditions.

Centerview Partners is serving as exclusive financial advisor to XenoPort, and Weil, Gotshal & Manges LLP is serving as legal advisor to XenoPort. Deutsche Bank has provided sole committed debt financing to Arbor in support of the transaction. Alston & Bird, LLP and Simpson, Thacher & Bartlett LLP acted as legal advisors to Arbor.

Foundation Medicine and Memorial Sloan Kettering Publish Validation Data for FoundationOne® Heme in the Journal Blood

On March 23, 2016 Foundation Medicine, Inc. (NASDAQ:FMI) and Memorial Sloan Kettering Cancer Center (MSK) reported the publication of new, seminal data validating FoundationOne Heme – the fully informative comprehensive genomic profiling assay for hematologic malignancies developed as part of their collaboration – further supporting its integration into oncology clinical practice (Press release, Foundation Medicine, MAR 23, 2016, View Source [SID:1234509929]). The data, available online as a first edition and soon to be published in an upcoming issue of the journal Blood, demonstrate that FoundationOne Heme has proven highly accurate in detecting the types of genomic alterations known to impact diagnosis, therapy selection and prognosis in hematologic cancers. Importantly, the publication demonstrates the molecular information gleaned from comprehensive genomic profiling can be utilized to accurately match patients with an appropriate therapeutic approach.

"Foundation Medicine has an established track record of developing genomic profiling assays with the highest standards of analytical and clinical validation," said Vincent Miller, M.D., chief medical officer, Foundation Medicine. "Publication of our validation data in this highly regarded, peer-reviewed journal supports the clinical significance of the FoundationOne Heme assay, in particular, for its ability to identify specific therapeutic targets, to help refine underlying diagnosis, and to improve prognostic and risk stratification of hematologic cancers."

"The development of FoundationOne Heme represents a state-of-the-art genomics assay which can be used to profile patients with hematologic malignancies worldwide, which is a critical step in improving outcomes for all patients," stated Ross Levine, M.D., a physician-scientist and the Laurence Joseph Dineen chair in leukemia research at MSK. "Our team’s expertise in hematologic malignancies and in translating genomics to the clinic has allowed us to partner with Foundation Medicine to bring this innovative genomic test to the patients we treat."

Conventional diagnostic assays, including FISH and real-time PCR, are designed to identify a sub-set of genomic alterations, and in some cases, there are no assays that can reliably identify specific rearrangements. FoundationOne Heme, an integrated DNA/RNA platform using targeted hybrid-capture next-generation sequencing, is a proven and effective comprehensive genomic profile developed to detect all types of genomic alterations with therapeutic relevance, including single-nucleotide substitutions, insertions and deletions, copy number alterations and rearrangements, which are not fully evaluated using conventional diagnostic assays.

MSK and Foundation Medicine collaborated to develop FoundationOne Heme, which was commercially launched in 2013. The assay is performed using archived FFPE, blood or bone marrow samples with high accuracy in a clinically relevant timeframe in Foundation Medicine’s laboratory, which is certified by New York State and CLIA and is CAP accredited. FoundationOne Heme simultaneously detects all classes of genomic alterations in the DNA of 405 cancer-related genes and employs RNA sequencing across 265 genes to capture a broad range of gene fusions, a type of alteration that is a common driver of hematologic cancers. It is designed to provide physicians with clinically actionable information to guide treatment options for patients based on the genomic profile of their cancer.

Key Study Findings

Established analytic accuracy of detecting substitutions, insertions and deletions (indels) and copy number alterations (CNAs) by comparing the performance of the new assay with Foundation Medicine’s DNA-only assay that has previously undergone comprehensive validation across a large number of clinical samples. Compared to FoundationOne, FoundationOne Heme contains an additional 90 genes relevant to hematologic malignancies.

Samples that were previously profiled with a validated test in which 169 alterations were identified in 55 genes common to both assays. The concordance between the two sets of results was 99.4%.

Blinded comparisons were performed with CLIA-certified diagnostic assays, including Sequenom, RT-PCR, FISH and PCR fragment analysis, for 76 clinical specimens previously tested for 214 clinical relevant alterations in 11 genes that are known and routinely tested in clinical practice in AML, ALL and MDS.

Overall concordance was 99% (211/214).

In addition to the concordance analysis, genomic profiling of the 76 test samples identified 126 additional somatic alterations which are not covered by available hot spot assays in the given disease type, including clinically relevant genomic alterations in KRAS, TET2, EZH2, and DNMT3A.

In independent low frequency variants ( < 10% mutant allele frequency), 20 of 21 variants were confirmed from AmpliSeq assay and another hotspot clinical assay.

Combined DNA and RNA sequencing approach accurately detects a wide variety of genomic rearrangements and gene fusions with immediate clinical value in hematologic malignancies.

Sensitivity for fusion detection at 20% or greater tumor fraction was 100% (161/161) and 98% (84/86) at 10% tumor fraction.
Clinical experiences from 3,696 hematologic malignancies are summarized, with a high fraction of clinically relevant genomic alteration detected.

At least one driver alteration was identified in 95% tumor specimens, and 77% cases harbored at least one alteration linked to a commercially available targeted therapy or one that is in clinical development. In addition, 61% of cases harbored at least one alteration with known prognostic relevance in that tumor type.

Genomic rearrangements were detected from 37% of clinical hematologic malignancies; known and novel fusions in kinase drug targets are highlighted.

In 16 cases of high-risk, BCR-ABL-negative B-ALL malignancies, known and novel clinical relevant genomic alterations were detected by FoundationOne Heme, and gene fusions involving JAK2, CRLF2 and EPOR were detected in 9 of 16 cases.