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Onconova Presents Clinical Data from Oral Rigosertib and Azacitidine Combination Study in Higher-Risk Myelodysplastic Syndromes at EHA Annual Meeting

On June 13, 2016 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3 clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported the presentation of data by Onconova collaborators from the U.S. and Europe from the ongoing Phase 2 clinical trial of oral rigosertib in combination with azacitidine in patients with either first- or second-line higher-risk myelodysplastic syndromes (HR-MDS) at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Copenhagen, Denmark, which took place June 9 — 11, 2016 (Press release, Onconova, JUN 13, 2016, View Source [SID:1234513246]).

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The results of this study are being finalized to initiate end of Phase 2 discussions with U.S. and European regulatory agencies to define the next steps in the development plan for this combination therapy. These interim results were initially presented at the Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in December 2015.

"We are encouraged by the interim overall response rate results of this Phase 2 trial, which demonstrated that 23 of 30 patients, or 77%, responded to treatment, and anticipate further updates to the data set," stated Steve Fruchtman, M.D., Chief Medical Officer of Onconova. "Of note, 84% of HMA-naïve patients responded to this novel combination. We look forward to discussing these results, and the longer-term follow-up from this study, with U.S. and European regulatory agencies in order to define the next step of development for this combination therapy."

A full copy of the EHA (Free EHA Whitepaper) poster entitled, "Results from Phase I/II Study of the Combination of Oral Rigosertib and Azacitidine in Patients with Myelodysplastic Syndromes (MDS)," may be accessed by visiting "Posters" in the Investors and Media section of Onconova’s website at www.onconova.com.

Sunesis Pharmaceuticals Announces Presentation of Positive Results from MD Anderson Sponsored Trial in Frontline Elderly AML and MDS at the EHA Annual Meeting

On June 13, 2016 Sunesis Pharmaceuticals (NASDAQ:SNSS) reported the presentation of updated results from an ongoing Phase 1b/2 University of Texas MD Anderson Cancer Center-sponsored trial of vosaroxin in combination with decitabine in older patients with previously untreated acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS) (Press release, Sunesis, JUN 13, 2016, View Source;p=RssLanding&cat=news&id=2177015 [SID:1234513244]). The results were presented Saturday in an oral session titled "New Compounds in AML Treatment" at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Copenhagen, Denmark. The presentation (abstract S505, Bella Center, Hall A3), titled "Phase I/ll study of vosaroxin and decitabine in newly diagnosed older patients with acute myeloid leukemia and high-risk myelodysplastic syndrome," is available at www.sunesis.com.

"Older patients diagnosed with AML and MDS have limited treatment options and exceedingly poor outcomes," said Naval Daver, M.D., Assistant Professor, Department of Leukemia, University of Texas MD Anderson Cancer Center, and a study investigator. "At the optimized induction dose of 70 mg/m2 of vosaroxin, the combination of vosaroxin and decitabine demonstrates a compelling CR/CRp/CRi rate of 76% and a median overall survival of 16.1 months. This response rate and survival are significantly better than seen with single-agent decitabine among similar patients at our institution. This outcome was achieved with <5% induction mortality and good tolerability. In this vosaroxin-decitabine cohort, 23 of 41 patients remain alive."

Daniel Swisher, CEO of Sunesis, added: "We believe these results warrant further exploration in a larger outcome study, with plans currently under review to conduct a multicenter clinical trial comparing vosaroxin plus decitabine and vosaroxin plus cytarabine to the 7+3 regimen in patients with AML."

To date, 63 patients (56 AML, 7 high-risk MDS) with a median age of 69 years (range 60-78) have been enrolled in the trial. All 63 patients have completed at least 2 treatment rounds, rendering them evaluable for response; with a 75% overall response rate, 49% (31 patients) achieved complete remission (CR), 17% (11 patients) achieved CR with incomplete platelet recovery (CRp), and 8% (5 patients) achieved CR with incomplete peripheral blood count recovery (CRi). The therapy was well-tolerated, with the main therapy related grade 3 or higher toxicities being mucositis in 11 (17%) patients.

Initially for the first 22 patients in the study, the selected induction dose of vosaroxin was 90 mg/m2. Thereafter to reduce the incidence of mucositis, the induction dose was reduced to 70 mg/m2 for the next 41 patients. The lower dose of vosaroxin in combination with decitabine was associated with reduced early mortality and an improved overall response rate and OS, as follows:

Induction
Dose
(vosaroxin) N Median
OS 8-week
Mortality Overall
Response Need >1 Cycle to
Response
90 mg/m2 22 5.5 27 % 73 % 19 %
70 mg/m2 41 16.1 5 % 76 % 42 %

Sunesis also announced that follow-up data from the company’s VALOR trial was presented as an e-poster during the EHA (Free EHA Whitepaper) meeting. The poster (abstract E930, Bella Center, E-Poster Screens), titled "Characterization of patients with relapsed or refractory AML in continued follow-up after treatment with vosaroxin/cytarabine vs placebo/cytarabine in the VALOR trial," shows that, as of January 22, 2016, 83 of 711 patients enrolled in VALOR remain alive (46/356 in the vosaroxin/cytarabine arm, 37/355 in the placebo/cytarabine arm) and in follow up, which has reached a median of 40 months. In patients ≥60 years, more than twice as many patients were alive in the vosaroxin/cytarabine arm (23 vs. 10 patients).

All but seven patients in this follow up underwent allogeneic hematopoietic stem cell transplant (HCT). Of note, the non-HCT survivors were all in the vosaroxin/cytarabine treatment arm (68-71 years old, 2 primary refractory and 5 early relapsed).

Mr. Swisher added: "We are encouraged by the long-term benefit seen in the VALOR follow-up and also the potential for vosaroxin and cytarabine to provide long-term benefit in older patients who need more options."

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.

Progenics Pharmaceuticals Announces Presentations on its Prostate Cancer Imaging Programs at SNMMI 2016

On June 13, 2016 Progenics Pharmaceuticals, Inc. (Nasdaq:PGNX) reported that data from its 1404 and PyLTM prostate cancer imaging programs will be presented at the upcoming Society of Nuclear Medicine and Molecular Imaging 2016 Annual Meeting, taking place from June 11 — 15, 2016 in San Diego, California (Press release, Progenics Pharmaceuticals, JUN 13, 2016, View Source [SID:1234513241]).

The details of the presentations are included below.

1404 Tc-99m Diagnostic Imaging Agent

Title: SPECT/CT Imaging of Prostatic PSMA Expression with Tc99m trofolastat chloride in Healthy Volunteers
Date and Time: June 13th from 3:00 — 4:30 p.m. PT
Poster Number: 1546
Session: Meet the Author Poster Session I: Prostate/GU Posters

PyL F-18 Diagnostic Imaging Agent

Title: Normal Organ Uptake Variability on PSMA-Targeted 18F-DCFPyL PET/CT
Date and Time: June 14th at 4:54 p.m. PT
Poster Number: 519
Session: SS76: Prostate/GU: Prostate and Other Malignancies

Title: Application of 18F-labeled PSMA-imaging using [18F]DCFPyL at very low PSA-values may allow curative treatment in recurrent prostate cancer
Date and Time: June 15th at 8:24 a.m. PT
Poster Number: 561
Session: SS82: Prostate/GU: PSMA Imaging in Advanced Disease

About 1404, an Imaging Compound Targeting Prostate Specific Membrane Antigen

Progenics’ molecular imaging radiopharmaceutical product candidate 1404 targets the extracellular domain of prostate specific membrane antigen (PSMA), a protein amplified on the surface of >95% of prostate cancer cells and a validated target for the detection of primary and metastatic prostate cancer. 1404 is labeled with technetium-99m, a gamma-emitting isotope that is widely available, is easy to prepare, and is attractive for nuclear medicine imaging applications. The image created provides the opportunity to visualize cancer, potentially allowing for improved detection and staging, more precise biopsies, and a targeted treatment plan including active surveillance as a disease management tool.

About PyL for PET Imaging of Prostate Cancer

PyL (also known as [18F]DCFPyL) is a clinical-stage, fluorinated PSMA-targeted PET imaging agent for prostate cancer that was discovered and developed at the Center for Translational Molecular Imaging at the Johns Hopkins University School of Medicine. A proof-of-concept study published in the April 2015 issue of the Journal of Molecular Imaging and Biology demonstrated that PET imaging with PyL showed high levels of PyL uptake in sites of putative metastatic disease and primary tumors, suggesting the potential for high sensitivity and specificity in detecting prostate cancer.

About Prostate Cancer

Prostate cancer is the second most common form of cancer affecting men in the United States: an estimated one in seven men will be diagnosed with prostate cancer in his lifetime. The American Cancer Society estimates that approximately 180,890 new cases of prostate cancer will be diagnosed and about 26,120 men will die of the disease and that approximately 2.9 million men in the U.S. currently count themselves among prostate cancer survivors.

Acetylon Presents Data on the Use of HDAC6 Inhibitors Ricolinostat (ACY-1215) and ACY-241 in Combination with Pomalidomide and Dexamethasone for the Treatment of Multiple Myeloma

On June 13, 2016 Acetylon Pharmaceuticals, Inc., the leader in the development of selective histone deacetylase (HDAC) inhibitors for enhanced therapeutic outcomes, reported that it presented data from multiple clinical trials evaluating the safety and efficacy of two selective HDAC6 inhibitors in combination with pomalidomide (Pom) (Pomalyst, Celgene) and dexamethasone (Dex) for the treatment of relapsed or relapsed-and-refractory multiple myeloma (RRMM) at the 21st Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) in Copenhagen, Denmark (Press release, Acetylon, JUN 13, 2016, View Source [SID:1234513281]).

“The data from these studies demonstrate that selective HDAC6 inhibition combines favorably with Pom and Dex, and support the continued clinical development of our selective HDAC6 inhibitors for the treatment of relapsed or relapsed-and-refractory multiple myeloma,” said Catherine Wheeler, SVP Clinical Development & CMO of Acetylon. “The results of the Phase 2 ACE-MM-102 trial have established proof of concept for selective HDAC6 inhibition and demonstrated that the addition of ricolinostat to Pom/Dex treatment increases response rate and progression-free survival compared to Pom/Dex alone in relapsed-and-refractory MM. We believe that this approach has the potential to become a powerful treatment option for patients with multiple myeloma without the severe side effects commonly seen with pan-HDAC inhibition. We are further encouraged by early results with ACY-241 in a similar patient population that it will deliver the same efficacy and safety as ricolinostat, however in a tablet form.”

Phase 2 ACE-MM-102 Data

The ACE-MM-102 clinical trial is a multicenter, single arm, open-label Phase 2 study designed to evaluate the safety and efficacy of ricolinostat administered at an optimal dose and schedule in combination with Pom and Dex in patients with RRMM. Results of this study indicated that treatment with ricolinostat in combination with Pom and Dex was very well tolerated, and toxicities were predominantly low grade. Pharmacokinetic and pharmacodynamic analysis demonstrated selective inhibition of HDAC6 at therapeutic doses. Analysis of 67 efficacy-evaluable patients enrolled at least 6 months prior to the data cut confirmed an overall response rate (ORR) of 46%, a clinical benefit rate (CBR) of 58%, a disease control rate (DCR) of 82%, 9 months duration of response (DOR), and 7 months progression free survival (PFS). These data compare favorably to mature historical data for the MM-002 and MM-003 trials of Pom and Dex alone which demonstrated 31-33% ORR, 7-8 months DOR, and 4 months median PFS. More mature data on the entire 96 patient study population will be available by the end of the year.

Phase 1b ACE-MM-104 Data

The Phase 1b ACE-MM-104 clinical trial is a dose-escalation study of an alternative liquid formulation (ALF) of ricolinostat in combination with Pom and Dex in patients with RRMM. Daily dosing (QD) was better tolerated than twice-daily dosing. One dose-limiting toxicity (DLT), neutropenia, was observed at 180 mg QD, and cohort expansion to 6 patients showed no further DLTs. Pharmacokinetic and pharmacodynamic analysis demonstrated selective inhibition of HDAC6 at therapeutic doses, with no evidence of ricolinostat accumulation or drug-drug interaction with Pom. Early efficacy data indicates a confirmed ORR of 53% and a DCR of 87% after 6 months median follow-up. These results demonstrate that the alternative liquid formulation of ricolinostat is well tolerated in combination with Pom and Dex at doses up to 180 mg QD without major toxicities. This formulation of ricolinostat is also being used in ongoing investigator-sponsored studies in combination with paclitaxel and abraxane to treat solid tumors.

Preliminary Phase 1a/1b ACE-MM-200 Data

The Phase 1a/1b ACE-MM-200 clinical trial utilizes a sequential monotherapy/combination trial design to establish the safety, pharmacokinetics, and pharmacodynamics of ACY-241 as both a monotherapy and in combination with Pom and Dex in patients with relapsed or relapsed-and-refractory MM. ACY-241 is an orally available selective HDAC6 inhibitor that is structurally similar to ricolinostat and administered in tablet form. Results of the study demonstrated that ACY-241 is well tolerated as a monotherapy and in combination with Pom and Dex, and toxicities did not differ substantially in frequency or severity from those reported with Pom and Dex alone. Pharmacokinetic and pharmacodynamic analysis indicated dose-linear increases in exposure and dose-dependent, selective increases in acetylated tubulin and histones. ACY-241 achieved exposures several fold higher than ricolinostat without severe toxicity, both alone and in combination with Pom and Dex. Early efficacy data for combination treatment indicates a confirmed ORR of 50% and a DCR of 95% after 3.5 months median follow-up. These results indicate that ACY-241 is well tolerated in combination with Pom and Dex, and early response data for combination treatment even with short follow-up are similar to those of ricolinostat in combination with Pom and Dex. Cohort expansion at biologically relevant combination doses is ongoing.

About HDAC6 Inhibition

Ricolinostat (ACY-1215) and ACY-241 selectively inhibit the intracellular enzyme HDAC6, which leads to an accumulation of excess protein and in addition may disrupt critical proliferative signals in malignant cells. Disruption of these molecular processes in cancer cells triggers programmed cell death, called “apoptosis,” with little or no effect on normal cells. Currently available HDAC drugs also affect the expression of numerous other genes in normal cells as well as cancer cells, which can result in side effects such as gastrointestinal dysfunction, lowered blood platelet levels and risk of hemorrhage and profound fatigue as well as potential for significant cardiac toxicity. Selective inhibition of HDAC6 is expected to reduce or eliminate these often-severe side effects associated with non-selective HDAC inhibition and to enable the development of optimized treatment regimens, including maximally effective combination drug therapies.

Acetylon Presents Data on the Use of HDAC6 Inhibitors Ricolinostat (ACY-1215) and ACY-241 in Combination with Pomalidomide and Dexamethasone for the Treatment of Multiple Myeloma

Positive results from a Phase 2 clinical trial of ricolinostat were presented in an oral presentation by Noopur Raje, M.D. of Massachusetts General Hospital in Boston, Massachusetts. In addition, results of a Phase 1b clinical trial of an alternative liquid formulation of ricolinostat were presented in a poster presentation by Sumit Madan, M.D. of University of Texas Southwestern Medical Center. Early favorable results from a Phase 1a/1b clinical trial of ACY-241, a selective HDAC6 inhibitor administered in tablet form, were also presented as an e-poster.

"The data from these studies demonstrate that selective HDAC6 inhibition combines favorably with Pom and Dex, and support the continued clinical development of our selective HDAC6 inhibitors for the treatment of relapsed or relapsed-and-refractory multiple myeloma," said Catherine Wheeler, SVP Clinical Development & CMO of Acetylon. "The results of the Phase 2 ACE-MM-102 trial have established proof of concept for selective HDAC6 inhibition and demonstrated that the addition of ricolinostat to Pom/Dex treatment increases response rate and progression-free survival compared to Pom/Dex alone in relapsed-and-refractory MM. We believe that this approach has the potential to become a powerful treatment option for patients with multiple myeloma without the severe side effects commonly seen with pan-HDAC inhibition. We are further encouraged by early results with ACY-241 in a similar patient population that it will deliver the same efficacy and safety as ricolinostat, however in a tablet form."

Phase 2 ACE-MM-102 Data

The ACE-MM-102 clinical trial is a multicenter, single arm, open-label Phase 2 study designed to evaluate the safety and efficacy of ricolinostat administered at an optimal dose and schedule in combination with Pom and Dex in patients with RRMM. Results of this study indicated that treatment with ricolinostat in combination with Pom and Dex was very well tolerated, and toxicities were predominantly low grade. Pharmacokinetic and pharmacodynamic analysis demonstrated selective inhibition of HDAC6 at therapeutic doses. Analysis of 67 efficacy-evaluable patients enrolled at least 6 months prior to the data cut confirmed an overall response rate (ORR) of 46%, a clinical benefit rate (CBR) of 58%, a disease control rate (DCR) of 82%, 9 months duration of response (DOR), and 7 months progression free survival (PFS). These data compare favorably to mature historical data for the MM-002 and MM-003 trials of Pom and Dex alone which demonstrated 31-33% ORR, 7-8 months DOR, and 4 months median PFS. More mature data on the entire 96 patient study population will be available by the end of the year.

Phase 1b ACE-MM-104 Data

The Phase 1b ACE-MM-104 clinical trial is a dose-escalation study of an alternative liquid formulation (ALF) of ricolinostat in combination with Pom and Dex in patients with RRMM. Daily dosing (QD) was better tolerated than twice-daily dosing. One dose-limiting toxicity (DLT), neutropenia, was observed at 180 mg QD, and cohort expansion to 6 patients showed no further DLTs. Pharmacokinetic and pharmacodynamic analysis demonstrated selective inhibition of HDAC6 at therapeutic doses, with no evidence of ricolinostat accumulation or drug-drug interaction with Pom. Early efficacy data indicates a confirmed ORR of 53% and a DCR of 87% after 6 months median follow-up. These results demonstrate that the alternative liquid formulation of ricolinostat is well tolerated in combination with Pom and Dex at doses up to 180 mg QD without major toxicities. This formulation of ricolinostat is also being used in ongoing investigator-sponsored studies in combination with paclitaxel and abraxane to treat solid tumors.

Preliminary Phase 1a/1b ACE-MM-200 Data

The Phase 1a/1b ACE-MM-200 clinical trial utilizes a sequential monotherapy/combination trial design to establish the safety, pharmacokinetics, and pharmacodynamics of ACY-241 as both a monotherapy and in combination with Pom and Dex in patients with relapsed or relapsed-and-refractory MM. ACY-241 is an orally available selective HDAC6 inhibitor that is structurally similar to ricolinostat and administered in tablet form. Results of the study demonstrated that ACY-241 is well tolerated as a monotherapy and in combination with Pom and Dex, and toxicities did not differ substantially in frequency or severity from those reported with Pom and Dex alone. Pharmacokinetic and pharmacodynamic analysis indicated dose-linear increases in exposure and dose-dependent, selective increases in acetylated tubulin and histones. ACY-241 achieved exposures several fold higher than ricolinostat without severe toxicity, both alone and in combination with Pom and Dex. Early efficacy data for combination treatment indicates a confirmed ORR of 50% and a DCR of 95% after 3.5 months median follow-up. These results indicate that ACY-241 is well tolerated in combination with Pom and Dex, and early response data for combination treatment even with short follow-up are similar to those of ricolinostat in combination with Pom and Dex. Cohort expansion at biologically relevant combination doses is ongoing.

About HDAC6 Inhibition

Ricolinostat (ACY-1215) and ACY-241 selectively inhibit the intracellular enzyme HDAC6, which leads to an accumulation of excess protein and in addition may disrupt critical proliferative signals in malignant cells. Disruption of these molecular processes in cancer cells triggers programmed cell death, called "apoptosis," with little or no effect on normal cells. Currently available HDAC drugs also affect the expression of numerous other genes in normal cells as well as cancer cells, which can result in side effects such as gastrointestinal dysfunction, lowered blood platelet levels and risk of hemorrhage and profound fatigue as well as potential for significant cardiac toxicity. Selective inhibition of HDAC6 is expected to reduce or eliminate these often-severe side effects associated with non-selective HDAC inhibition and to enable the development of optimized treatment regimens, including maximally effective combination drug therapies.