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Sunesis Pharmaceuticals Announces Clinical and Regulatory Updates to SNS-062 and Vosaroxin Programs

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.

Aptose Prioritizes Development of CG’806 First-in Class FLT3/BTK Inhibitor

On January 23, 2017 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS), a clinical-stage company developing new therapeutics and molecular diagnostics that target the underlying mechanisms of cancer, reported it will prioritize its resources toward the development of CG’806, an oral preclinical compound being developed for patients with FLT3-driven acute myeloid leukemia (AML) and certain BTK-driven B-cell malignancies (Press release, Aptose Biosciences, JAN 23, 2017, View Source [SID1234517513]). Aptose will temporarily delay clinical activities with APTO-253, a phase 1 stage compound for AML, in order to elucidate the cause of recent manufacturing setbacks related to the intravenous formulation of APTO-253, with the intention of restoring the molecule to a state supporting clinical development and partnering.

Although Aptose has two compelling cancer drugs, current resources can support the full development activities of only one at this time. Recent advances with CG’806 have elevated this agent as having the best risk-reward profile to pursue with those resources. Such data established CG’806 as a well-differentiated pan-FLT3 inhibitor that demonstrates tumor eradication in the absence of toxicity in AML xenograft models, and it is on track for development as a therapy for certain AML patients. In addition, CG’806 is a potent non-covalent inhibitor of proliferation among certain BTK-driven B-cell derived cancer cells. The encouraging properties of CG’806, including its potency against well-established targets in diseases of severe medical need, warrant expeditious advancement and prioritization of resources toward this molecule.

"Concurrent evidence of a unique activity profile with CG’806 along with manufacturing delays for APTO-253 have led us to reprioritize our corporate strategy," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "While we remain confident in the viability of APTO-253 as a potential treatment for AML, we believe the greater value proposition to shareholders and patients is to focus our available resources on CG’806."
In November 2015, Aptose’s phase 1b trial of APTO-253 in patients with AML was placed on clinical hold. Since that time, the company has actively evaluated multiple formulation and production methodologies with the goal of developing a superior IV formulation. After successfully manufacturing multiple non-cGMP batches of a new drug product formulation for APTO-253, including a batch that has been stable and soluble for over six months, the company recently encountered an additional manufacturing setback which further delayed the return of APTO-253 to the clinic. While Aptose has made significant advances in understanding the novel c-Myc inhibitory mechanism of APTO-253, additional time will be required to define the cause of the cGMP manufacturing delay and to potentially restore APTO-253 to a state it can be developed clinically and partnered.

Based on information currently available, Aptose expects to report total cash and cash equivalents to be at a similar level as at September 30, 2016. As a result of activities to reprioritize its resources towards the development of CG’806, the cash on hand, which includes additional cash raised through its At-The-Market facility, is expected to provide sufficient resources to fund research and development and operations into Q4, 2017. Information reported above with respect to the financial year ended December 31, 2016 are preliminary and are subject to change and adjustment as the company’s 2016 financial results are finalized. Accordingly, investors are cautioned not to place undue reliance on the foregoing guidance. The company does not intend to continue to provide preliminary results in the future. Aptose expects to report its financial results for the financial year ended December 31, 2016 on or around March 14, 2016.

About CG’806
CG ‘806 is a once daily, oral, first-in-class FLT3/BTK inhibitor. This small molecule demonstrates potent inhibition of mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain), eliminates AML tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with FLT3-driven AML. Likewise, CG’806 demonstrates potent, non-covalent inhibition of the Cys481Ser mutant of the BTK enzyme, suggesting the agent may be developed for CLL and MCL patients that are resistant/refractory/intolerant to covalent BTK inhibitors.

Sumitomo Dainippon Pharma Announces Clinical Data of Investigational Cancer Stemness Inhibitor Napabucasin were presented at 2017 ASCO GI Symposium

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]).

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

Pipeline Review Check

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]).

PAMREVLUMAB PANCREATIC CANCER CLINICAL DATA PRESENTED AT ASCO 2017 GASTROINTESTINAL CANCERS SYMPOSIUM

On January 20, 2017 FibroGen, Inc. (Nasdaq:FGEN) reported that updated results from an ongoing clinical study of pamrevlumab (FG-3019) in combination with standard-of-care chemotherapy in patients with locally advanced pancreatic ductal adenocarcinoma (PDAC) were presented in a poster session during the ASCO (Free ASCO Whitepaper) 2017 Gastrointestinal Cancers Symposium in San Francisco (Press release, FibroGen, JAN 20, 2017, View Source;p=IROL-news&nyo=0 [SID1234517531]). Pamrevlumab is a fully human monoclonal therapeutic antibody that inhibits connective tissue growth factor (CTGF), a common factor in chronic fibrotic and proliferative disorders.

"I am very encouraged by these additional results from this clinical trial of pamrevlumab evaluated in combination with standard-of-care chemotherapy in patients with locally advanced pancreatic ductal adenocarcinoma," said Vincent J. Picozzi, Jr., M.D., Director of the Pancreas Center, Virginia Mason Hospital & Seattle Medical Center, and principal investigator. "Based on our participation in this trial, and a previous clinical study (FGCL- MC3019-028), I believe pamrevlumab has the potential to provide meaningful benefit for pancreatic cancer patients with locally advanced and/or metastatic disease."

Of the 33 subjects enrolled to date:

Twenty-two have been randomized to pamrevlumab plus chemotherapy, 10 remain on treatment
– Three discontinued treatment due to complications not related to pamrevlumab, and nine completed treatment
– Seven subjects who completed treatment met protocol defined criteria eligible for tumor resection and were considered operable following treatment. Three subjects had complete tumor removal (R0), and one subject had microscopic tumor remaining after surgery (R1)
Of the 11 subjects randomized to chemotherapy alone, five subjects discontinued treatment due to various reasons, and six subjects completed treatment
– Of the six subjects who received chemotherapy alone, one subject met protocol defined criteria eligible for tumor resection and had a complete tumor removal (R0)
Differences in overall survival (OS) between subjects treated with and without pamrevlumab look encouraging
There were no complications from laparoscopy or biopsies that were clinically significant or delayed dosing, and, to date, there have been no safety imbalances between treatment arms.
In this open-label, randomized study, pamrevlumab in combination with gemcitabine and nab-paclitaxel is compared to chemotherapy alone for the treatment of patients with locally advanced pancreatic ductal adenocarcinoma who have failed resection scoring and were characterized as inoperable assessed by histology, CT scans, and laparoscopy. Subjects are randomized to six cycles of chemotherapy with gemcitabine and nab-paclitaxel, with or without pamrevlumab. The study has enrolled 33 patients, and is targeted to enroll up to 42 subjects.

About Pancreatic Ductal Adenocarcinoma and Connective Tissue Growth Factor

Pancreatic ductal adenocarcinoma (PDAC), or pancreatic cancer, is the fourth leading cause of cancer deaths in the United States. According to the National Cancer Institute, in 2016, there were approximately 53,000 new cases of pancreatic cancer projected in the United States alone. Pancreatic cancer is aggressive and typically not diagnosed until it is largely incurable. Most patients are diagnosed after the age of 45, and overall five-year survival is about 7%, due to many factors, including advanced stage at diagnosis and limited response to currently available therapies (View Source). PDAC tumors often exhibit a high degree of desmoplasia, characterized by extensive connective tissue stroma and elevated levels of Connective Tissue Growth Factor (CTGF). Cancer-stroma interactions affect tumorigenesis, angiogenesis, resistance to therapy and metastatic spread of tumor cells. CTGF is overexpressed in PDAC and facilitates local desmoplasia, tumor progression and metastasis in animal models.

About Pamrevlumab

Pamrevlumab (FG-3019) is an investigational therapeutic antibody developed by FibroGen to inhibit the activity of CTGF, a common factor in chronic fibrotic and proliferative disorders characterized by persistent and excessive scarring that can lead to organ dysfunction and failure. FibroGen is currently conducting clinical studies of pamrevlumab in idiopathic pulmonary fibrosis, pancreatic cancer, and Duchenne muscular dystrophy.

In desmoplastic, or fibrotic, cancers such as pancreatic cancer, CTGF in the extensive fibrous stroma associated with the tumor promotes abnormal proliferation of stromal cells and tumor cells. Studies in a transgenic mouse model of pancreatic cancer indicate that treatment with pamrevlumab in combination with chemotherapy may enhance the efficacy of chemotherapy and improve survival.