On March 28, 2016 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported a corporate update and reported financial results for the fourth quarter and year-ended December 31, 2015 (Press release, Onconova, MAR 28, 2016, View Source [SID:1234510063]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Onconova is focused on the execution of the global INSPIRE trial of IV rigosertib. This trial is now enrolling higher-risk MDS patients at multiple U.S. sites and in Europe, and we are initiating additional clinical centers in the U.S. and abroad. Patients have been enrolled in the U.S. and Europe, and we are pleased that our Japan/Korea partner SymBio Pharmaceuticals has announced plans to enroll patients in INSPIRE in Japan," said Ramesh Kumar, Ph.D., President and CEO of Onconova. "In addition, based on the encouraging Phase 2 results for oral rigosertib in combination with azacitidine presented in December 2015, we are planning to define a regulatory path forward with the FDA this year."

Recent Business Highlights:

Development of Rigosertib IV in Higher-Risk MDS (HR-MDS)

The global INSPIRE trial is now enrolling patients in the United States and Europe. INSPIRE will be conducted in the United States, Europe, Australia, Israel, and Japan. The first patient in Europe was enrolled this month and sites in Japan are expected to open shortly. The first patient in this trial was enrolled in December 2015 at the MD Anderson Cancer Center.

Results from Onconova’s ONTIME trial were published in the top-tier, peer-reviewed journal, Lancet Oncology. The article, titled, "Rigosertib versus best supportive care for patients with high-risk myelodysplastic syndromes after failure of hypomethylating drugs (ONTIME): a randomised, controlled, phase 3 trial," appeared in the March 8, 2016 online edition of the journal.
Development of Oral Rigosertib in Combination with Azacitidine for MDS and AML Patients

The Phase 2 portion of an open label Phase 1/2 clinical trial, designated 09-08, evaluating oral rigosertib in combination with the approved dose of injectable azacitidine for patients with HR-MDS and AML is fully enrolled. The Phase 2 study included both front-line patients (i.e. not previously treated with HMAs) and patients after failure of treatment with an HMA. Positive interim data from the 09-08 trial were presented at the 2015 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2015.

In the presentation at ASH (Free ASH Whitepaper), 30 MDS patients were evaluable for efficacy assessment per 2006 International Working Group, or IWG, criteria. Overall, 23 of 30 patients (77%) responded, including six patients who had complete remissions. Notably, 16 of 19 (84%) HMA-naïve patients had a response to the combination therapy and 7 of 11 (64%) patients whose disease had previously failed HMAs responded. Hematologic improvement was observed in 13 of 26 patients that were evaluable for this part of the analysis.

Patients received full dose (per label) of azacitidine and the recommended daily Phase 2 dose of oral rigosertib (560 mg in the morning and 280 mg in the afternoon). The combination of oral rigosertib and azacitidine was well tolerated, with a median duration of treatment of 4 months (range 1 to 27 months). Adverse events of Grade > 3 experienced across all cycles with the combination included thrombocytopenia (27%), neutropenia (22%), hypokalaemia (5%), hematuria (5%) and diarrhoea (3%).
Operational Update

On March 3, 2016, the Company received notice from Baxalta US Inc. of Baxalta’s election to terminate the September 2012 development and license agreement between Baxalta and the Company for convenience, effective August 30, 2016, following Baxalta’s reprioritization review. In accordance with the terms of the development and license agreement, upon termination, the rights that the Company had licensed to Baxalta will revert to the Company at no cost.

The Company recently cut its workforce by ~17% as an important step towards reducing its operating losses and cash expenditures. Additional cost-optimization measures are being considered for implementation over the next several months.
Upcoming Events

Enrollment of the first patient in the Phase 3 INSPIRE trial in Japan: 1H2016

Peer-reviewed publication of mechanism of action of rigosertib: 2Q2016

Presentation of updated Phase 2 data from oral rigosertib combination trial in MDS: 2Q2016

End of Phase 2 meeting with FDA to discuss data from oral rigosertib combination trial: 2H2016
2015 Financial Results

Cash, cash equivalents, and marketable securities as of December 31, 2015 totaled $19.8 million, compared to $43.6 million as of December 31, 2014. Onconova believes that its current cash and cash equivalents, together with anticipated contractual cost-sharing payments from Baxalta for a portion of the INSPIRE trial costs, and in consideration of the cost optimization measures previously noted, will be sufficient to fund its ongoing trials and operations into the first quarter of 2017.

Net loss was $24.0 million for the year ended December 31, 2015, compared to $63.8 million for the year ended December 31, 2014 due primarily to a 45% reduction in operating expenses and the recognition of deferred revenue in 2015.

Research and development expenses were $25.9 million for the year ended December 31, 2015, compared to $49.4 million for the year ended December 31, 2014,

General and administrative expenses were $9.5 million for the year ended December 31, 2015, compared to $15.1 million for the year ended December 31, 2014.

On March 28, 2016 OXiGENE, Inc. (Nasdaq:OXGN), a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of cancer, reported financial results for 2015 (Press release, OXiGENE, MAR 28, 2016, View Source [SID:1234510064]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

For the year ended December 31, 2015, OXiGENE reported a net loss of $13.7 million compared to a net loss of $12.6 million for the year ended December 31, 2014. R&D expenses increased to $9.1 million in 2015 compared to $7.4 million in 2014, while general and administrative expenses decreased to $4.6 million in 2015 compared to $5.2 million in 2014.

At December 31, 2015, OXiGENE had cash of $27.3 million.

"During the second half of 2015 the Company worked to define and optimize a clinical plan that would most efficiently advance the development of CA4P, our lead investigational drug. We built our plan on results from a phase 2 clinical trial completed in 2014 in which CA4P, a novel vascular disrupting agent, dramatically improved platinum-resistant ovarian cancer treatment outcomes when combined with the approved anti-angiogenic agent bevacizumab (Avastin)," stated William D. Schwieterman, M.D., OXiGENE’s President and Chief Executive Officer. "As we begin 2016 our progress continues. The FDA recently approved our protocol for FOCUS, a phase 2/3 clinical trial designed to provide us with data to support the registration of CA4P as a new drug for the treatment of platinum-resistant ovarian cancer, and we remain on track to enroll patients in this study before mid-year. I am pleased that our year-end cash balance is expected to provide us with a sufficient runway to collect and present important data from FOCUS and other programs we have on-going."

About OXiGENE

On March 28, 2016 CASI Pharmaceuticals, Inc. (Nasdaq: CASI), a biopharmaceutical company dedicated to innovative therapeutics addressing cancer and other unmet medical needs, reported financial results for the three and 12 months ended December 31, 2015 (Filing, Q4/Annual, EntreMed, 2015, MAR 28, 2016, View Source [SID:1234510065]).

The Company reported a net loss of ($1.7 million), or ($0.05) per share, for the three months ended December 31, 2015. This compares with a net loss of ($1.6 million), or ($0.05) per share for the fourth quarter of 2014. The increase in net loss can be attributed to costs associated with enrolling patients in our Phase 2 Trial for ENMD-2076 in fibrolamellar carcinoma (FLC) during the fourth quarter of 2015, as well as increasing costs associated with expanding our China operations.

The net loss for the year ended December 31, 2015 was ($7.2 million), or ($0.22) per share, compared with a net loss of ($26.2) million or ($0.92) per share for 2014. The reported net loss for 2014 included a non-cash expense of $19.7 million for acquired in-process research and development associated with the September 2014 successful in-license of the rights for greater China of MARQIBO, ZEVALIN and EVOMELA from Spectrum Pharmaceuticals. The Company secured these rights primarily with equity and no cash up front. Excluding this non-cash expense, the net loss for 2014 would have been ($6.5 million), or ($0.23) per share.

As of December 31, 2015, CASI had cash and cash equivalents of $5.1 million. In January 2016, the Company completed an initial closing of a strategic financing and received net proceeds of $10.2 million.

Sara B. Capitelli, CASI’s Vice President, Finance and Principal Accounting Officer, commented, "Our research and development expenses for the fourth quarter increased over the prior year due to clinical trial costs associated with the initiation of our FLC trial in November 2015 and higher costs associated with our growing China operations during 2015. The decrease in general and administrative expenses compared with the previous year primarily reflects higher costs incurred in 2014 associated with our in-license of Spectrum products in 2014. We are continuing to execute our clinical development plans in the U.S. and China, and expect operating expenses to increase in 2016."

Further information regarding the Company, including its Annual Report on Form 10-K for the year ended December 31, 2015, can be found at www.casipharmaceuticals.com.

Ken K. Ren, Ph.D., Chief Executive Officer, commented, "Our financial results for the fourth quarter and year ended December 31, 2015 were as anticipated. In January 2016, we received $10.2 million net proceeds in an initial closing of a strategic financing which included common stock priced at $1.19 per share, the proceeds of which will support our product pipeline and advance our clinical and regulatory activities. Our import drug registration activities for MARQIBO, ZEVALIN and EVOMELA in China are ongoing, including the filing of our import registration trial application with CFDA for MARQIBO in January 2016. Our partner, Spectrum Pharmaceuticals, recently received FDA approval for EVOMELA which now allows us to advance the CFDA registration process towards an import registration trial and market approval in China. We continue to advance the clinical development of our lead proprietary drug candidate, ENMD-2076. Our Phase 2 trial in FLC is progressing well with 60% of patients already recruited for stage one of our 2-stage trial, and our Phase 2 trials in ovarian clear cell carcinoma, triple negative breast cancer and soft tissue sarcoma continue to progress along with correlative biomarker analysis. We continue to carefully manage our expenses, while achieving interim milestones towards our mission to become a fully-integrated pharmaceutical company with a rich product pipeline."

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

DNA structural lesions are prevalent in sporadic colorectal cancer. Therefore, we proposed that gene variants that predispose to DNA double-strand breaks (DSBs) would be found in patients with familial colorectal carcinomas of an undefined genetic basis (UFCRC).
We collected primary T cells from 25 patients with UFCRC and matched patients without colorectal cancer (controls) and assayed for DSBs. We performed exome sequence analyses of germline DNA from 20 patients with UFCRC and 5 undiagnosed patients with polyposis. The prevalence of identified variants in genes linked to DNA integrity was compared with that of individuals without a family history of cancer. The effects of representative variants found to be associated with UFCRC was confirmed in functional assays with HCT116 cells.
Primary T cells from most patients with UFCRC had increased levels of the DSB marker γ(phosphorylated)histone2AX (γH2AX) after treatment with DNA damaging agents, compared with T cells from controls (P < .001). Exome sequence analysis identified a mean 1.4 rare variants per patient that were predicted to disrupt functions of genes relevant to DSBs. Controls (from public databases) had a much lower frequency of variants in the same genes (P < .001). Knockdown of representative variant genes in HCT116 CRC cells increased γH2AX. A detailed analysis of immortalized patient-derived B cells that contained variants in the Werner syndrome, RecQ helicase-like gene (WRN, encoding T705I), and excision repair cross-complementation group 6 (ERCC6, encoding N180Y) showed reduced levels of these proteins and increased DSBs, compared with B cells from controls. This phenotype was rescued by exogenous expression of WRN or ERCC6. Direct analysis of the recombinant variant proteins confirmed defective enzymatic activities.
These results provide evidence that defects in suppression of DSBs underlie some cases of UFCRC; these can be identified by assays of circulating lymphocytes. We specifically associated UFCRC with variants in WRN and ERCC6 that reduce the capacity for repair of DNA DSBs. These observations could lead to a simple screening strategy for UFCRC, and provide insight into the pathogenic mechanisms of colorectal carcinogenesis.
Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Controversy exists as to whether erectile response to phosphodiesterase type 5 inhibitors is compromised in men with low total testosterone (TT) levels. This is amplified by reports of improved response to phosphodiesterase type 5 inhibitor therapy after coadministration of testosterone replacement therapy in hypogonadal men unresponsive to phosphodiesterase type 5 inhibitors.
To determine whether TT and luteinizing hormone levels influence efficacy of tadalafil for erectile dysfunction in men with concomitant lower urinary tract symptoms and benign prostatic hyperplasia.
This integrated analysis included 1,075 men randomized to once-daily tadalafil 5 mg (n = 540) or placebo (n = 535) for 12 weeks in three prospective clinical trials who had not received concomitant testosterone replacement therapy. Subjects were categorized at baseline by low vs normal TT levels (n = 1,049; <300 vs ≥300 ng/dL) and normal vs high luteinizing hormone levels (n = 1,058; ≤9.4 vs >9.4 mIU/mL). Treatment-group differences in International Index of Erectile Function (IIEF) by hormone subgroups were assessed using analysis of covariance.
Changes in IIEF erectile function domain and other domain scores.
The overall study population was comprised primarily of white men (>86%) with a mean age range of 64 to 70 years. Median baseline TT level in the integrated population was 355 ng/dL; levels were lower than 300 ng/dL (cutoff for normal) in 32.4% of men. Men with low TT levels reported diabetes (21.8%), cardiovascular disease (54.1%), and hypertension (49.1%) numerically more often than men with normal TT levels (10.6%, 43.2%, and 36.7%, respectively). Low TT and high luteinizing hormone levels were associated with numerically, but not statistically significantly, lower 12-week IIEF domain scores compared with those with normal levels. Changes in most 12-week IIEF domain scores showed that tadalafil was significantly more effective than placebo (P < .02).
Low TT levels at baseline did not negatively influence response to tadalafil in men of advancing age with concomitant lower urinary tract symptoms and benign prostatic hyperplasia and erectile dysfunction.
Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!