On January 23, 2017 Sunesis Pharmaceuticals, Inc. (Nasdaq:SNSS) reported clinical and regulatory updates to its two lead programs, SNS-062, a second-generation reversible and non-covalent BTK inhibitor, and vosaroxin, an anti-cancer quinolone derivative currently under review for marketing authorization as a treatment for relapsed/refractory acute myeloid leukemia (AML) in Europe (Press release, Sunesis, JAN 23, 2017, View Source;p=RssLanding&cat=news&id=2238918 [SID1234517515]).

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For SNS-062, the company announced that its Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) is now active, supporting the initiation of a Phase 1B/2 study to assess the candidate’s safety and efficacy in patients with advanced B-cell malignancies after prior ibrutinib exposure, including in patients with C481S mutations.

"With a now active IND for SNS-062, another important milestone in the rapid development of this next generation product candidate, we will work toward site activation at our U.S. clinical centers and dosing of the first patients within the first half of 2017," said Daniel Swisher, President and Chief Executive Officer of Sunesis. "The data presented at ASH (Free ASH Whitepaper) from our Phase 1A Healthy Volunteer study were encouraging, and we look forward to understanding the potential for SNS-062 to address the growing unmet needs of patients with B-cell malignancies."

The company also announced today continued progress with its Marketing Authorization Application (MAA) for vosaroxin. Sunesis recently received the Day 180 List of Outstanding Issues, issued by the Committee for Medicinal Products for Human Use (CHMP) as part of the centralized review process.

Mr. Swisher continued, "We are working diligently to complete a comprehensive and detailed response to the Day 180 List of Outstanding Issues, which we expect to submit by the end of the first quarter. As we enter the final phase of the European approval process for vosaroxin, we are preparing to go before the Scientific Advisory Group’s Oncology Division (SAG-O) in April, which will assist the CHMP in its evaluation of our application. We anticipate a decision from the CHMP by mid-year and continue to advance active dialogues with potential pharma collaborators toward the goal of supporting a market launch of vosaroxin in 2017."

About SNS-062

SNS-062 is a novel, second-generation BTK inhibitor, a class of kinase inhibitors that selectively inhibits the enzyme Bruton’s tyrosine kinase (BTK). This target mediates signaling through the B-cell receptor, which is critical for adhesion, migration, proliferation and survival of normal and malignant B-lineage lymphoid cells. Unlike other drugs in its class, SNS-062 binds non-covalently and reversibly to the BTK enzyme. Its binding profile along with improved PK/PD properties potentially provide SNS-062 an opportunity to address the leading acquired resistance to ibrutinib, a mutation in the enzyme’s binding site required for covalent binding. In preclinical studies, SNS-062 demonstrated potent activity against C481S mutated B-cell malignancies, and has been studied in healthy subjects in a completed Phase 1A, randomized, double-blind, placebo-controlled dose-ranging study to investigate the drug’s safety, pharmacokinetics, and pharmacodynamics. With the reported successful study outcome, SNS-062 is proceeding to a Phase 1B/2 study in patients with B-cell malignancies.

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. Vosaroxin is an investigational drug that has not been approved for use in any jurisdiction.

Vosaroxin’s Marketing Authorization Application for relapsed refractory AML is currently under review by the European Medicines Agency, and a regulatory decision regarding approval is expected in 2017.

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

CureMeta is a Therapeutic Biotech Company Developing Novel Antibody-Drug-Conjugates to Unique Embryonic Cancer Stem Cell Targets (Company Pipeline, CureMeta, JAN 22, 2017, View Source [SID1234517499]).

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On January 23, 2017 Sumitomo Dainippon Pharma Co., Ltd. (Head Office: Osaka, Japan; President: Masayo Tada; "Sumitomo Dainippon Pharma") reported that two poster presentations of napabucasin (BBI608) were delivered on January 21, 2017 (U.S. time) at the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, January 19 to 21, 2017, in San Francisco (Press release, Dainippon Sumitomo Pharma, JAN 22, 2017, View Source [SID1234517525]).

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Overview of poster presentations at the ASCO (Free ASCO Whitepaper)-GI

1. Results of Phase 1b/2 study of napabucasin with FOLFIRI, or FOLFIRI and bevacizumab administered to colorectal cancer patients. (BBI608-246:NCT02024607)

Abstract Number 593

Title Cancer stemness inhibition and chemosensitization: Phase Ib/II study of cancer stemness inhibitor napabucasin (BBI608) with FOLFIRI +/- bevacizumab (Bev) administered to colorectal cancer (CRC) patients (pts)

Lead presenter Johanna Bendell, Sarah Cannon Cancer Research Institute/Tennessee Oncology, Nashville, TN

Overview of the study result 63 CRC pts with an average of >2 prior therapy lines were enrolled. This phase Ib/II study suggests napabucasin may sensitize chemorefractory CRC to FOLFIRI +/- Bev and encouraging signs of synergistic activity was observed in CRC pts regardless of p-STAT3 status.

Safety No pharmacokinetic interactions or dose-limiting toxicity was observed. Most common adverse events (AEs) included grade 1/2 diarrhea, nausea, vomiting and fatigue. 1 pt had grade 4 diarrhea and 27 pts had grade 3 AEs, including diarrhea (14), fatigue (4), dehydration (2), electrolyte imbalance (4), nausea (1), vomiting (1), abdominal pain (1) and weight loss (1), all of which resolved with dose reduction and supportive care. Efficacy Among 56 pts enrolled who received RECIST evaluation, disease control rate(DCR:CR+PR+SD) was observed in 88%(49 pts) with an overall response rate(ORR:CR+PR) of 29%(16 pts) with 1 pt achieving CR. 2 (Reference: DCR and ORR) Subset DCR ORR Evaluable ITT Evaluable ITT FOLFIRI naïve 93% (28/30) 82% (28/34) 33% (10/30) 29% (10/34) FOLFIRI exposed 81% (21/26) 72% (21/29) 23% (6/26) 21% (6/29) p-STAT3high 84% (26/31) 79% (26/33) 26% (8/31) 24% (8/33) p-STAT3low 92% (23/25) 77% (23/30) 32% (8/25) 27% (8/30)

2. Results of Phase 1b/2 study of napabucasin with panitumumab administered to K-ras wild-type patients with metastatic colorectal cancer (BBI608-224: NCT01776307)

Abstract Number 677

Title BBI608-224: A phase Ib/II study of cancer stemness inhibitor napabucasin (BBI608) administered with panitumumab in K-ras wild-type patients with metastatic colorectal cancer.

Lead presenter Tim Larson, Minnesota Oncology, Minneapolis, MN

Overview of the study result 72 pts were enrolled, 48 pts were evaluable by RECIST of which 7 (15%) and 41 (85%) had 2 or ≥3 prior treatment lines, respectively. Of the 48 evaluable pts, 37 (77%) were previously treated with an anti-EGFR agent. Napabucasin was safely combined with panitumumab at full dose with no unexpected adverse events and no evidence of pharmacological interaction. Encouraging anti-tumor activity in pts with K-ras, wt mCRC was observed. Napabucasin may sensitize pts to repeat anti-EGFR therapy.

Safety The safety profile was consistent with that of each agent as monotherapy and most common AEs included grade 1/2 diarrhea, nausea, abdominal cramps, and vomiting.

Efficacy Among 48 pts enrolled who received RECIST evaluation, Disease Control Rate (DCR) was observed in 54.2%(26 pts) of which 2 pts achieved PR (4%) and 24 pts achieved SD (50%). Among 37 pts previously treated with anti-EGFR therapy, DCR was observed in 54%(20 pts) compared with DCR of 54.5% observed in 6 out of 11 anti-EGFR naïve pts receiving a scan.

(Reference: mPFS and mOS)

Population Subgroup mPFS (months) mOS (months) ITT Anti-EGFRNaïve n=18 3 13.3 Anti-EGFRExposed n=54 2.1 9.1 Total n=72 2.1 9.1 3 Evaluable Anti-EGFRNaïve n=11 3.9 17.9 Anti-EGFRExposed n=37 2.6 9.9 Total n=48 3 12.2 (Reference)

About napabucasin (BBI608)
Napabucasin is an investigational first-in-class anti-cancer agent created and currently under development by Boston Biomedical, Inc. Napabucasin is an orally-administered small molecule agent designed to inhibit cancer stemness pathways by targeting STAT3

On January 20, 2017 The Cancer Research Technology Pioneer Fund LP (CPF) reported that it will further develop a promising class of cancer drugs called RET inhibitors, through a collaboration with the Cancer Research UK Manchester Institute Drug Discovery Unit*, at The University of Manchester (Press release, Cancer Research Technology, 20 20, 2017, View Source [SID1234523171]).

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A potential drug candidate identified through the collaboration has entered preclinical studies, the stage necessary to enable an investigational new drug (IND) application. These studies ensure the drug is safe to be given to patients. If the studies are successful the experimental drug will be funded through early clinical trials.

Ian Miscampbell, managing partner of Sixth Element Capital which manages the CPF, said: "We’re delighted to announce this significant project milestone. And the further investment we’ve made will pave the way for a potential new cancer drug to be taken into phase I clinical trials. If the first studies are successful we’ll seek industry partners to further develop and commercialise these drugs."

The RET inhibitor programme was led by scientists at Cancer Research UK’s Manchester Institute. Investment by the CPF in 2014 built on the research of the group and enabled the acceleration of the programme.

The RET gene plays a critical role in the development of medullary thyroid cancer. Up to two percent of non-small cell lung adenocarcinomas – originating in the mucus-secreting cells lining the airways – have RET mutations. The project aims to discover novel compounds targeting the RET gene in a specific population of patients.

Dr Donald Ogilvie, head of drug discovery at the Cancer Research UK Manchester Institute at The University of Manchester, said: "We’re pleased to work with the CRT Pioneer Fund to accelerate progress on the exciting RET inhibitors discovered by Cancer Research UK scientists at our Institute.

"Lung cancer can be difficult to treat successfully. As part of the Cancer Research UK Lung Cancer Centre of Excellence, we’re determined to get new lung cancer treatments to patients. Identifying this candidate drug molecule offers the potential to help boost survival from this disease."

Dr Phil L’Huillier, Cancer Research Technology’s director of business development, said: "It’s fantastic news that CRT’s Pioneer Fund has helped speed up this important research from the lab to potentially benefit patients. It’s essential that we bridge the innovation gap in UK drug discovery, so that patients can quickly get the promising new drugs being developed in Cancer Research UK labs and elsewhere around the world."

On January. 20, 2017 Mateon Therapeutics, Inc. (OTCQX:MATN), a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of orphan oncology indications, reported the presentation of final data from Study OX4218 in patients with neuroendocrine tumors (NETs) at a poster session at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium being held today in San Francisco.

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Study OX4218 was a multi-center, open label, phase 2 clinical trial to investigate the safety and activity of combretastatin A4-phosphate (CA4P) in the treatment of well-differentiated, low-to-intermediate-grade unresectable, recurrent or metastatic pancreatic or gastrointestinal neuroendocrine tumors/carcinoid (PNETs or GI-NETs) with elevated biomarkers. Following patients’ completion of Study OX4218, patients were eligible to enroll in Study OX4219, a long term extension study, if they achieved a biomarker or symptom response. In OX4218 patients were treated with CA4P 60 mg/m2 on Days 1, 8, and 15 of a 21-day cycle for 3 cycles, and in OX4219 patients received CA4P maintenance on Day 1 of a 21-day cycle until disease progression or up to one year.

A total of 18 patients were enrolled in OX4218. One patient (6%) experienced significant symptomatic improvement as measured by ECOG Status and had a partial response per investigator-assessed RECIST and an additional 7 patients (39%) had stable disease. In addition, a majority of patients (53%) experienced an improvement in patient-reported quality of life. A statistically significant mean change in biomarkers from baseline, the primary endpoint of the study, was not achieved in OX4218 due to the small sample size along with a high intra- and inter-patient variability observed in the biomarkers. A total of 7 patients were enrolled in OX4219, of which 5 patients (71%) had stable disease, including one that continued for 14 months. The partial response and stable disease analyses, as well as other measures from the trial, suggest that CA4P monotherapy has activity in this indication.

"The results of OX4218 and OX4219 confirm that CA4P monotherapy has efficacy in the indications studied, as we have seen with the investigational drug in a number of other monotherapy trials," said William D. Schwieterman, M.D., President and Chief Executive Officer of Mateon. "However, we believe that the efficacy of CA4P only becomes compelling when it is used in combination with an anti-angiogenic agent, due to the complementary mechanisms of action for the two agents. Based on the evidence of efficacy observed in this trial, plus an understanding of the benefits of combination therapy, a lead investigator in this trial is sponsoring a 20 patient study in NETs using CA4P in combination with everolimus (AFINITOR, marketed by Novartis), an anti-angiogenic agent which is already approved and commonly used in this indication."

Overall CA4P monotherapy was well tolerated. Treatment related adverse events were reported in 77% of subjects. The most common Grade 3-5 AEs ( > 10%) included: anemia, abdominal pain, fatigue, hypertension, and ALT and AST increases. One Grade 5 adverse event, carcinoid syndrome, was reported and attributed to the underlying disease.