On August 15, 2017 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3 stage biopharmaceutical company focused on discovering and developing novel small molecule drug candidates to treat cancer, with a primary focus on Myelodysplastic Syndromes (MDS), reported a corporate update and reported financial results for the second quarter ended June 30, 2017 (Press release, Onconova, AUG 15, 2017, View Source [SID1234520247]).

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"We are advancing IV rigosertib in a late stage clinical trial for patients with unmet medical needs in MDS. Our Phase 3 INSPIRE trial with IV rigosertib is enrolling globally and the next milestone of interim analysis is anticipated in the fourth quarter," said Dr. Ramesh Kumar, President and Chief Executive Officer.

"After consulting with regulators in the US and Europe following Phase 1/2 data with oral rigosertib in combination with azacitidine, we are designing a Phase 3 trial in first-line higher risk MDS patients for submission under a Special Protocol Assessment," continued Dr. Kumar. "We also believe there is interest for our pediatric RASopathies rare disease collaborative program from the National Cancer Institute, academia, and patient advocacy which we find extremely gratifying."

INSPIRE Trial of IV Rigosertib in 2nd Line Higher-risk (HR) MDS

Interim Analysis

The INSPIRE protocol allows for a pre-planned interim analysis. This analysis will be triggered after reaching 88 events (deaths). Although it is difficult to accurately forecast the timing of this milestone, based on when we expect to finalize our statistical analysis plan, enrollment statistics, and our expectations for survival of the trial population, we anticipate this to occur in Q4-2017.
The Statistical Analysis Plan (SAP) for interim and top-line analysis is under review by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA).
Trial Progress

As of July 31, 72 sites in 16 countries across four continents have enrolled patients for this study. Countries and trial sites were carefully chosen to ensure availability of appropriate patients meeting stringent eligibility criteria. Since these criteria were purposely designed to be narrow and selective, extensive eligibility verification and trial site education are integral to our plan.
Enrollment for the trial has slowed recently, which could be related to seasonality. The Company is taking proactive measures to increase enrollment including the addition of trial sites in three new countries and changes within its CRO group. Should enrollment not return to desired levels, full enrollment may be delayed by several months.
Oral Rigosertib in Combination with Azacitidine for 1st-line HR-MDS

Pivotal Phase 3 Trial Protocol

Following receipt of the final minutes from our End-of-Phase 2 discussion with the FDA in 3Q-2016, a Scientific Advice process was initiated with the EMA and was completed in July. Based on this feedback, we are designing a Phase 3 protocol for a 1:1 randomized controlled trial of oral rigosertib + azacitidine compared with azacitidine + placebo in first-line patients with HR-MDS. We plan to initiate the FDA Special Protocol Assessment (SPA) process following completion of the ongoing Expansion Phase 1/2 trial.
Initiation of the trial, which is planned to be conducted globally, requires additional financing.
Expansion of Phase 1/2 Trial of Oral Rigosertib in Combination with Azacitidine

This expansion phase is designed to enroll up to approximately 40 patients. The key objectives are to optimize dosing and schedule of administration of oral rigosertib in combination with azacitidine.
After appropriate amendments were filed with the regulatory agencies, we started the expansion phase of this trial. Four sites are now open in the U.S. and we plan to activate additional sites in US, Europe and Australia. The first patient was enrolled in April.
Other Programs for Future Development or Partnership and Presentations

New Collaborative Program in "RASopathies": Rare Disease in Children

Based on new mechanism of action data published last year (Cell, 2016), we initiated a collaborative development program focusing on a group of rare diseases, RASopathies, which share a well-defined molecular basis in expression or defects involving Ras Effector Pathways. Pediatric "RASopathies" is a subset of these rare diseases, and we are embarking on a multifaceted collaborative program involving patient advocacy, government, and academic organizations. In addition to drug supply and expertise, we believe we can contribute organizational oversight to this project.

We expect to execute a formal Collaborative Research and Development Agreement (CRADA) with the National Cancer Institute (NCI) of the National Institutes of Health.

Investigators in the NCI have designed a protocol for a trial in pediatric patients with certain RASopathies complicated by cancer.

Since our focus area of MDS is related to a pediatric rare disease, Juvenile Myelomonocytic Leukemia (JMML), we are exploring collaboration with an academic group focused on development of novel therapeutics for these children. Initial non-clinical studies in Stem Cells and animal models may influence the design of an appropriate clinical study in this patient population.

In July 2017, we presented a summary of our targeted approach to a symposium organized by Rasopathiesnet.org, a patient advocacy organization. We are also sponsoring an educational event (a "Key Opinion Leader" breakfast) in the fourth quarter to bring together disease area experts, patient advocacy groups and our knowledge, to draw attention to this unmet medical need and the potential for rigosertib in this quest.
Recent Presentations

The Company presented a poster at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on Monday, June 5th focusing on "Further Rationale for Rigosertib in a Second-line HR-MDS Setting." Bone marrow response was evaluated as a surrogate for survival in this trial of 64 patients who had failed hypomethylating agents. 22% of these patients achieved marrow complete response (mCR) and 47% of patients achieved disease stabilization.

The Company contributed multiple presentations at the 22nd Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) on June 24th. The presentations incorporated clinical and non-clinical data evaluating oral rigosertib plus azacitidine. The data presented demonstrated that the combination may overcome hypomethylating agent resistance, and also indicates that further study in acute myeloid leukemia is warranted. SymBio, Onconova’s partner in Japan and Korea, presented Phase 1 safety data for intravenous rigosertib in Japanese patients with recurrent/relapsed or refractory Myelodysplastic Syndromes.

Dr. Steven Fruchtman, Onconova’s Chief Medical Officer, highlighted approaches for studying rigosertib in RAS-associated cancers on Sunday, July 30th at the 5th International RASopathies Symposium organized by RASopathies Network. The primary focus of this presentation was JMML, which is incurable without an allogenic hematopoietic stem cell transplant.
Proprietary Preclinical Next Generation CDK4/6 + ARK5 Inhibitor

New CDK inhibitors are making an impact for patients with breast and lung cancers. These orally available agents have potential utilities in a broad range of solid tumors and we believe will become an integral part of cancer therapy in the future.

Our CDK inhibitor is differentiated from other agents on the market (such as Palbociclib, Ribociclib and Abemaciclib) or in development (such as the compounds being developed by G1 Therapeutics) by its dual inhibition of CDK4/6 + ARK5. We continue to carry out preclinical research to enhance the data package for this compound in an attempt to seek partners for co-development of this novel new chemical entity.
Second-Quarter Business Highlight:

On April 26, 2017, Onconova closed a public offering resulting in gross proceeds of approximately $5.2 million, before underwriting discounts, commissions and estimated offering costs. New institutional investors, existing investors, as well as Directors and Management of the Company participated in the round. On May 17, 2017, the underwriters exercised their option to purchase an additional 363,580 shares, which resulted in additional gross proceeds of $0.8 million.
Second-Quarter Financial Results:

Cash, cash equivalents, and marketable securities as of June 30, 2017 totaled $15.0 million, compared to $21.4 million as of December 31, 2016.

Total net revenue was $0.3 million for the second quarter of 2017 and $0.5 million for the six months ended June 30, 2017, compared to $2.2 million and $3.7 million, respectively, for the comparable periods in 2016.

Research and development expenses were $4.6 million for the second quarter of 2017 and $9.5 million for the six months ended June 30, 2017, compared to $5.6 million and $11.4 million, respectively, for the comparable periods in 2016.

General and administrative expenses were $1.8 million for the second quarter of 2017 and $3.9 million for the six months ended June 30, 2017, compared to $2.1 million and $5.3 million, respectively, for the comparable periods in 2016.

About IV Rigosertib

The intravenous form of rigosertib has been employed in Phase 1, 2, and 3 clinical trials involving more than 800 patients, and is currently being evaluated in the randomized Phase 3 international INSPIRE trial for patients with higher-risk (HR) MDS, after failure of hypomethylating agent, or HMA, therapy. This formulation is intended for patients with advanced disease, to provide long duration of exposure, and to ensure dosing under a controlled setting.

About INSPIRE

The INternational Study of Phase III IV RigosErtib, or INSPIRE, is based on guidance received from the U.S. Food and Drug Administration and European Medicines Agency and derives from the analysis of the ONTIME Phase 3 trial. INSPIRE is a multi-center, randomized controlled study to assess the efficacy and safety of IV rigosertib in HR-MDS patients who had progressed on, failed to respond to, or relapsed after previous treatment with an HMA within the first 9 months or nine cycles over the course of one year after initiation of HMA treatment. This time frame optimizes the opportunity to respond to treatment with an HMA prior to declaring treatment failure, as per the National Comprehensive Cancer Network (NCCN) Guidelines. The trial will enroll approximately 225 patients randomized at a 2:1 ratio into two treatment arms: IV rigosertib plus Best Supportive Care versus Physician’s Choice plus Best Supportive Care. The primary endpoint of INSPIRE is overall survival and an interim analysis is anticipated. Full details of the INSPIRE trial, such as inclusion and exclusion criteria, as well as secondary endpoints, can be found on clinicaltrials.gov (NCT02562443).

About Oral Rigosertib

The oral form of rigosertib was developed to provide more convenient dosing for use where the duration of treatment may extend to multiple years. This dosage form also supports many combination therapy modalities. To date, 368 patients have been treated with the oral formulation of rigosertib. Initial studies with single-agent oral rigosertib were conducted in hematological malignancies, lower-risk MDS, and solid tumors. Combination therapy of oral rigosertib with azacitidine and chemoradiotherapy has also been explored. Currently, oral rigosertib is being developed as a combination therapy together with azacitidine for patients with higher-risk MDS who require HMA therapy. A Phase 1/2 trial of the combination therapy has been fully enrolled and the preliminary results were presented in 2016. This novel combination is the subject of an issued US patent with earliest expiration in 2028.

On August 15, 2017 Celsion Corporation (NASDAQ:CLSN), an oncology drug development company, reported financial results for the quarter and six month period ended June 30, 2017 and provided an update on its development programs for ThermoDox, its proprietary heat-activated liposomal encapsulation of doxorubicin and GEN-1, an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein (Press release, Celsion, AUG 15, 2017, View Source [SID1234520240]). The Company’s lead program is ThermoDox which is currently in Phase III development for the treatment of primary liver cancer. The Company’s immunotherapy program consists of GEN-1 and is currently in Phase I development for the localized treatment of ovarian cancer.

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"We are extremely pleased with the momentum that we have built and the meaningful developments in our two lead programs," said Michael H. Tardugno, Celsion’s chairman, president and CEO. "The data from our immunotherapy program, both the clinical data as well as the recently announced translational data from our OVATION Study in first line ovarian cancer, continue to provide important insights into GEN-1’s favorable clinical and safety profile and reinforce our confidence in its potential to serve as an effective therapy in a broad range of cancers."

Mr. Tardugno continued, "We have also made great strides to advance our global Phase III OPTIMA Study evaluating ThermoDox in primary liver cancer, with clinical sites currently enrolling patients in 14 countries worldwide. In addition, we are pleased to report that the independent Data Monitoring Committee recently recommended continuation of the OPTIMA Study after their review of the safety and efficacy data for 275 patients enrolled in the study. Enrollment momentum continues to improve with the addition of new clinical sites in China and Vietnam."

Recent Developments

ThermoDox
OPTIMA Study Update. On August 7, 2017, the Company announced that the independent Data Monitoring Committee (DMC) for the Company’s OPTIMA Study completed a regularly scheduled review of the first 50% of patients enrolled in the trial as of April 2017 and has unanimously recommended that the OPTIMA Study continue according to protocol to its final data readout. The DMC reviewed study data at regular intervals, with the primary responsibilities of ensuring the safety of all patients enrolled in the study, the quality of the data collected, and the continued scientific validity of the study design. As part of its review, the DMC monitored a quality matrix relating to the total clinical data set, confirming the timely collection of data, that all data are current as well as other data collection and quality criteria.

The Company hosted an Investigators Meeting with physicians in SE Asia and key opinion leaders on July 22-23, 2017 in Bangkok, Thailand. A second Investigators Meeting is being planned for October with physicians in China. The Company has initiated approximately 70 clinical sites in 14 countries with plans to activate up to 8 additional clinical trial sites in China or Vietnam by the end of 2017. China and Vietnam represent significant markets for ThermoDox where HCC incidence rates are among the highest in the world.

In addition, the Company announced that patient enrollment in the 550 patient Phase III global study has reached over 60%. Based on current enrollment rates, the Company expects to complete enrollment of the OPTIMA Study by mid – 2018.

GEN-1 Immunotherapy
Announced Latest Translational Data from the OVATION Study Showing That Patients in All Cohorts Showed Convincing Evidence of IL-12 Gene Transfer and Immune System Activity. On August 2, 2017, the Company reported that translational research data from its Phase Ib dose escalating clinical trial was reviewed with leading immuno-oncology experts from the Roswell Park Cancer Institute. The data showed evidence of IL-12 gene transfer by dose dependent increases in IL-12 levels and immune system activity and significant increases in interferon-gamma (IFN- γ) and decreases in VEGF levels. The treatment-related changes in immune activating cytokines and pro-tumor VEGF levels followed a dose-dependent trend and were predominantly in the peritoneal fluid compartment with little to no changes observed in the patients’ systemic blood stream.

Key translational research findings from the first 12 of 15 patients enrolled in four patient cohorts are summarized below:
The treatment-related changes in immune activating cytokines and pro-tumor VEGF and IFN- γ levels followed a dose-dependent trend and were predominantly in the peritoneal fluid compartment with little to no changes observed in the patients’ systemic circulation. The observed immunological changes are consistent with an IL-12 based mechanism.

Effects observed in the immunohistochemistry (IHC) analysis were pronounced decreases in the density of immunosuppressive T-cell signals (FoxP3, PD-1, PDL-1, IDO-1) and increases in CD8+ cells in the tumor microenvironment.

The ratio of CD8+ cells to immunosuppressive cells was increased in approximately 75% of patients suggesting an overall shift in the tumor microenvironment from immunosuppressive to pro-immune stimulatory following treatment with GEN-1. An increase in CD8+ to immunosuppressive T-cell populations is a leading indicator and believed to be a good predictor of improved overall survival.

Presented OVATION Study Findings in Newly Diagnosed Advanced Ovarian Cancer Patients at the ASCO (Free ASCO Whitepaper) 2017 Annual Meeting. In June 2017, the Company reported clinical data from the first fourteen patients who have completed treatment in the OVATION Study. GEN-1 plus standard chemotherapy produced positive results, with no dose limiting toxicities and promising dose dependent efficacy signals which appear to correlate well with successful surgical outcomes as summarized below:

Of the fourteen patients treated to date in the entire study, two (2) patients demonstrated a complete response, ten (10) patients demonstrated a partial response and two (2) patients demonstrated stable disease, as measured by RECIST criteria. This translates to a 100% disease control rate ("DCR") and an 86% objective response rate ("ORR"). Of the five patients treated in the highest dose cohort, there was a 100% objective response rate with one (1) complete response and four (4) partial responses.

Fourteen patients had successful resections of their tumors, with nine (9) patients (64%) having an R0 resection, which indicates a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed. Of the five patients treated at the highest dose cohort, all five patients (100%) experienced a R0 surgical resection. Seven out of eight (87%) patients in the highest two dose cohorts experienced a R0 surgical resection.

All patients experienced a clinically significant decrease in their CA-125 protein levels as of their most recent study visit. CA-125 is used to monitor certain cancers during and after treatment. CA-125 is present in greater concentrations in ovarian cancer cells than in other cells.

Of the seven patients who have received GEN-1 treatment over one year ago and are being followed, only one patient’s cancer has progressed after 11.7 months. This compares favorably to the historical median progression free survival (PFS) of 12 months for newly-diagnosed patients with Stage III and IV ovarian cancer that undergo neoadjuvant chemotherapy followed by interval debulking surgery. Of the remaining six patients who have been on the study for over one year, their average PFS is 16.4 months with the longest progression-free patient at over 22 months.

Corporate Development
Raised $10.1 Million through Warrant Exercises and Registered Direct Offering. During the second quarter of 2017, the Company raised $5.1 million through the exercise of outstanding common stock warrants. In July 2017, the Company completed a $5 million registered direct equity offering of shares of common stock, or pre-funded warrants in lieu thereof, and a concurrent private placement of warrants to purchase common stock with several institutional healthcare investors.

Financial Results
For the quarter ended June 30, 2017, Celsion reported a net loss of $4.9 million, or $(0.79) per share, compared to a net loss of $4.5 million, or $(2.63) per share, in the same period of 2016. Operating expenses were $4.7 million in the second quarter of 2017 compared to $4.9 million in the same period of 2016. This decrease was primarily due to a tighter clinical development focus coupled with lower general and administrative and interest expenses. For the six month period ended June 30, 2017, the Company reported a net loss of $10.1 million, or $(1.75) per share, compared to $10.2 million, or $(6.04) per share, in the same six month period of 2016. Operating expenses were $9.6 million in the first half of 2017 compared to $10.2 million in the same period of 2016. Net cash used in operations was $7.3 million in the first half of 2017 compared to $9.0 million in the same period last year. The Company ended the second quarter of 2017 with $3.6 million of total cash and investments, which was subsequently increased with proceeds from a $5 million registered direct offering completed in early July 2017.

Research and development costs were $3.0 million in the second quarter of 2017 compared to $3.3 million in the same period last year. Research and development costs were $6.5 million in the first half of 2017 compared to $6.8 million in the same period last year. Clinical development costs for the Phase III OPTIMA Study remained relatively unchanged at $1.5 million in each of the second quarter of 2017 and 2016. R&D costs for other development programs were lower as a result of the Company’s tighter clinical development focus around the pivotal Phase III OPTIMA Study for the treatment of primary liver cancer and the clinical development program for GEN-1 IL-12 immunotherapy for the localized treatment of ovarian cancer coupled with lower costs in the first half of 2017 associated with the production of ThermoDox clinical supplies to support the OPTIMA Study.

General and administrative expenses were $1.6 million in the second quarter of 2017 compared to $1.5 million in the same period of 2016. The increase during the second quarter of 2017 was due to higher non-cash stock compensation expense partially offset by reduced professional fees. General and administrative expenses were $3.1 million in the first half of 2017 compared to $3.4 million in the same period of 2016. The decrease during the first six months of 2017 was primarily the result of lower personnel costs and professional fees.

During the three and six months ended June 30, 2017, the Company recognized deemed dividends totaling $0.4 million collectively in regard to multiple agreements with certain warrant holders, pursuant to which these warrant holders agreed to exercise, and the Company agreed to reprice, certain warrants. Warrants to purchase 790,410 shares of common stock were repriced at $2.70 and warrants to purchase 506,627 shares of common stock were repriced at $1.65. The Company received $3.0 million in gross proceeds from the sale of these repriced warrants.

On August 14, 2017 Cellectar Biosciences, Inc. (Nasdaq:CLRB), an oncology-focused, clinical stage biotechnology company (the "company"), reported financial results for the second quarter of 2017 (Press release, Cellectar Biosciences, AUG 15, 2017, View Source [SID1234520238]). Management will host a teleconference and live webcast to review these results, including a review of corporate performance, at 5:00 PM ET today.

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Summary of Q2 and Q3 2017 Accomplishments to Date

Announced median overall survival for Cohort 1 patients in Phase 1 study of CLR 131 in relapsed/refractory multiple myeloma exceeds 22 months
Signed new collaboration with Avicenna Oncology to develop new chemotherapies, which includes a preclinical side-by-side investigation of the company’s PDC platform against an antibody-drug conjugate (ADC)
Positive safety, tolerability and activity data observed through Cohort 3 of Phase 1 study of CLR 131 in multiple myeloma
Initiated fourth cohort of Phase 1 study of CLR 131 in multiple myeloma
Initiated NCI-supported Phase 2 clinical study of CLR 131 in multiple myeloma and other hematologic malignancies
"We have realigned our investments into programs with the greatest potential to accelerate Cellectar’s growth and development, and are encouraged by the pace of this repositioning and execution on our strategic plan," said Jim Caruso, president and CEO of Cellectar Biosciences. "The CLR 131 clinical data observed to date have been promising and we look forward to announcing additional results from our Phase 1 and Phase 2 trials. We are also driving value creation through strategic collaborations such as the Avicenna deal to enrich the company’s small molecule pipeline with proprietary assets."

Summary of Q2 2017 Financial Results
Research and development expenses were $2.2 million, an increase of $1.2 million from the prior year. The increase was due primarily to the initiation of our Phase 2 clinical trial in hematologic malignancies and the establishment of a secondary CLR 131 manufacturing capability, while investing to support the company’s ongoing Phase 1 relapsed/refractory multiple myeloma trial remained relatively consistent.

General and administrative expenses totaled $1.0 million, which was a $0.3 million reduction from the second quarter of 2016. The improvement was due to lower spending on professional services, particularly consulting, legal and accounting fees.

The company generated a loss from operations of $3.2 million for the three months ended June 30, 2017, while in the second quarter of 2016 the operating loss was $2.3 million; the larger loss resulted from the increase in research and development investment referenced above.

Net loss for second quarter 2017 was $3.1 million, or $0.23 per share. As of June 30, 2017, the company had $8.3 million in cash and cash equivalents on hand, as compared to December 31, 2016, when the company had $11.4 million in cash and cash equivalents. In line with previous guidance, the company estimates that available cash and cash equivalents will fund its planned operations into the second quarter of 2018. Additional capital will be required for operations beyond the second quarter of 2018.