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Onconova Therapeutics, Inc. Reports Recent Business Highlights and Third Quarter 2016 Financial Results

On November 14, 2016 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3 clinical-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, reported a corporate update and reported financial results for the third quarter ended September 30, 2016 (Press release, Onconova, NOV 14, 2016, View Source [SID1234516681]).

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"Onconova continues to reach important milestones in the development of rigosertib for patients with myelodysplastic syndromes (MDS). In July, our partner SymBio Pharmaceuticals announced the enrollment of the first patient in Japan for our INSPIRE pivotal trial for rigosertib in 2nd-line higher-risk MDS (HR-MDS). In September, we announced the results of a successful End-of-Phase 2 meeting with the FDA for oral rigosertib in combination with azacitidine for 1st-line HR-MDS patients," said Ramesh Kumar, Ph.D., President and CEO of Onconova. "We are pleased with the progress of our oral rigosertib development program, as well as the INSPIRE trial that is now running on four continents with more than 150 trial-sites in 15 countries."

Recent Business Highlights:

Progress in Oral Rigosertib Combination with Azacitidine for 1st-line HR-MDS

Following evaluation of 54 enrolled patients in the Phase 2 Trial 09-08 of oral rigosertib plus azacitidine, Onconova conducted an End-of-Phase 2 meeting during which updated results from this trial were discussed with the FDA. Based on these discussions, and guidance from the Agency, Onconova will design a randomized, controlled Phase 3 clinical trial comparing the combination of oral rigosertib plus azacitidine to azacitidine plus placebo in hypomethylating agent (HMA) naïve HR-MDS patients. This sizable population of MDS patients not previously treated with HMAs is a poorly met medical need where the front-line treatments (HMAs) are effective for only a fraction of the indicated patients. Notably, in contrast to the INSPIRE trial, where the primary efficacy endpoint was Overall Survival (OS), the new pivotal trial will employ Response Rate (RR) as the approval endpoint, permitting more rapid completion and evaluation of the study. The RR will be a composite of complete remission (CR) and partial remission (PR).
Progress in INSPIRE Pivotal Trial of IV Rigosertib in 2nd-line HR-MDS

The global Phase 3 INSPIRE trial of IV rigosertib in patients who have failed to respond to or progressed with an HMA therapy is now enrolling in the United States, Europe, Australia, and Japan. As of October 3, 2016, 157 sites were open for the INSPIRE trial to recruit patients.
The INSPIRE trial was recently reviewed in a pre-planned first meeting of the Drug Safety Monitoring Board. Following a review of the safety data of enrolled patients, the Board recommended continuation of the trial without any modifications.
Key Opinion Leader Meeting on Novel Approaches to Targeting RAS

Onconova hosted an investor event featuring two pioneers in the area of RAS biology, Dr. Channing J. Der of the University of North Carolina, and Dr. E. Premkumar Reddy of Mount Sinai School of Medicine. The meeting focused on novel approaches for targeting the RAS pathway and highlighted the therapeutic potential for rigosertib as a novel RAS-directed therapy. A replay of the webcast for this event can be found by clicking the following link: View Source
Recent Rigosertib Publications

Two peer-reviewed articles describing clinical and non-clinical studies with rigosertib in MDS were published in Expert Review of Anticancer Therapy (link to article) and Expert Opinion on Orphan Drugs (link to article).
Upcoming Events

Presentation of updated data from 09-08 combination therapy trial at ASH (Free ASH Whitepaper) Annual Meeting: December 2016
Presentations highlighting safety and tolerability in more than 500 patients, and analysis of previously completed randomized clinical trial of rigosertib at ASH (Free ASH Whitepaper) Annual Meeting: December 2016
Completion of site activation for INSPIRE trial: 1Q2017
Third Quarter 2016 Financial Results

Cash, cash equivalents and marketable securities as of September 30, 2016, totaled $25.8 million, compared to $19.8 million as of December 31, 2015.
Total net revenue was $1.7 million for the third quarter of 2016 and $5.4 million for the nine months ended September 30, 2016, compared to $1.6 million and $1.9 million, respectively, for the comparable periods in 2015.
Research and development expenses were $4.0 million for the third quarter of 2016 and $15.4 million for the nine months ended September 30, 2016, compared to $5.3 million and $21.3 million, respectively, for the comparable periods in 2015.
General and administrative expenses were $2.0 million for the third quarter of 2016 and $7.2 million for the nine months ended September 30, 2016, compared to $2.2 million and $7.8 million, respectively, for the comparable periods in 2015.

Compugen Immune Checkpoint Program Demonstrates Potential
for Development of New Cancer Immunotherapy Treatments

On November 11, 2016 Compugen Ltd. (NASDAQ: CGEN), a leading predictive drug discovery company, reported new data for its preclinical CGEN-15029 program demonstrating the potential for the development of new cancer immunotherapy treatments for solid tumors, including the potential for drug combination with current immune checkpoint blockers (Filing, 6-K, Compugen, NOV 14, 2016, View Source [SID1234516652]). CGEN-15029 is the internal designation for PVRIG, a novel immune checkpoint identified by Compugen utilizing its in silico predictive discovery infrastructure. The Company plans to file an IND in 2017 for COM701, its lead antibody targeting PVRIG.

Today’s presentation, titled "Computational identification, functional characterization and antibody blockade of a new immune checkpoint in the TIGIT family of interacting molecules" was made by John Hunter, Ph.D., Site Head and Vice President, Antibody R&D, Compugen USA, Inc. The presentation included the discovery by Compugen of PVRIG and its expression pattern in the context of cancer, demonstrating that PVRIG is expressed in infiltrating immune cells in solid tumors, specifically on cells with potent anti-tumor activity, such as effector T-cells and natural killer cells. Also disclosed was the identification of PVRL2 as PVRIG’s ligand, and the functional characterization and anti-tumor in vitro and in vivo efficacy of blocking antibodies developed by Compugen targeting the interaction of PVRIG with PVRL2. Binding of PVRIG to PVRL2 is of particular therapeutic interest, as it links PVRIG to the axis of a second immune checkpoint, TIGIT, which is recently gaining traction in the field of immuno-oncology.

In his presentation, Dr. Hunter presented additional data demonstrating that antibodies developed by Compugen, which block the interaction between PVRIG and PVRL2, enhance activation of the immune system by activating both primary CD4+ T-cells and tumor-derived CD8+ T-cells.

Consistent with the placement of PVRIG in the TIGIT axis, antibody blockade of both TIGIT and PVRIG had an additive effect on human T-cell stimulation, indicating the potential of the two to generate enhanced immune response against the cancer. Moreover, antibodies targeting the mouse PVRIG developed by the Company were assessed in vivo for effects on tumor growth inhibition in mouse models, commonly used to study immune checkpoint inhibitors. In these studies, antibodies that block the mouse PVRIG/PVRL2 interaction, similar to those generated against the human target, were shown to inhibit tumor growth when used in combination with PD1 pathway blockade. These results were further reinforced when tumor growth was tested in knock-out (KO) mice. Tumor growth was significantly reduced in KO mice, where the PVRIG gene was removed. Consistent with the antibody combination data, this effect was even further enhanced in the KO mice when they were treated with anti-PDL1 blocking antibodies.

Collectively, the experimental data strongly suggest that PVRIG, which was initially predicted computationally by the Company to serve as a novel immune checkpoint target, presents a new opportunity for the development of cancer immunotherapy treatments, including the potential for drug combination with current immune checkpoint blockers.

In June 2016, the Company selected COM701, a high affinity antagonist antibody against PVRIG, as the lead therapeutic candidate for the program. COM701, which is currently in preclinical development by the Company, demonstrates potent and reproducible enhancement of T-cell activation, consistent with the desired mechanism-of-action required to generate anti-tumor immune responses.

Anat Cohen-Dayag, Ph.D., CEO and President of Compugen, explained, "While antibody blockade of the CTLA4 and PD1 pathways has emerged as an effective treatment modality for certain types of cancer, the majority of patients do not derive long-term benefits, suggesting a need for additional approaches such as new immune checkpoints targeting new pathways and providing new mechanisms to activate the immune response against the tumor. Employing our unique predictive infrastructure to define new immune checkpoint targets, we identified PVRIG, among other novel immune checkpoint target candidates in our target pipeline."

Dr. Cohen-Dayag continued, "We are very pleased to see the rapidly increasing amount of preclinical data demonstrating the potential utility of COM701, an antibody targeting PVRIG, as a new cancer immunotherapy treatment. These results highlight, once more, the power and uniqueness of our computational predictive approach – from computer prediction of novel drug targets to preclinical validation. This capability, along with our significantly enhanced development infrastructure, allows us now to pursue and advance a number of novel immuno-oncology programs with potentially different mechanisms-of-action, thus providing us with a diversified early-stage internal target pipeline, in addition to the two programs that are the subject of an ongoing pharma collaboration."

About PVRIG
PVRIG (designated internally as CGEN-15029) is one of the novel B7/CD28-like immune checkpoint target candidates discovered by Compugen utilizing its predictive discovery infrastructure. The CGEN-15029 target was predicted in silico and experimentally confirmed to be a receptor-like immune checkpoint protein expressed on immune cells. In June 2016, COM701, a high affinity antagonist antibody against CGEN-15029, was selected as the lead therapeutic candidate for the program.

Puma Biotechnology Announces Presentations of Investigational Data at the San Antonio Breast Cancer Symposium (SABCS)

On November 14, 2016 Puma Biotechnology, Inc. (NYSE: PBYI), a biopharmaceutical company, reported that its lead drug candidate PB272 (neratinib) will be featured in 11 poster presentations at the 2016 San Antonio Breast Cancer Symposium (SABCS), December 6 – 10, 2016, in San Antonio, Texas (Press release, Puma Biotechnology, NOV 14, 2016, View Source [SID1234516643]). Abstracts are available to the public online on the SABCS website: www.sabcs.org.

Details of the poster and poster discussion presentations are as follows:

OT1-02-05: Phase II clinical trial of neratinib in patients 60 and older with HER2 over-expressed or mutated breast cancer: Trial design considerations for older adults.
Wednesday, Dec. 7; 5:00 – 7:00 p.m. CST

P1-07-12: An exploratory correlative biomarker analysis of NSABP FB-7, a phase II randomized trial evaluating neoadjuvant therapy with weekly paclitaxel (P) plus neratinib (N) or trastuzumab (T) or neratinib and trastuzumab (N+T) followed by doxorubicin and cyclophosphamide (AC) with postoperative T in women with locally advanced HER2-positive breast cancer.
Wednesday, Dec. 7; 5:00 – 7:00 p.m. CST

PD2-05: Inhibition of mutant HER2 results in synthetic lethality when combined with ER antagonists in ER+/HER2 mutant human breast cancer cells.
Poster Discussion, Wednesday, Dec. 7; 5:00 – 7:00 p.m. CST

PD2-08: Neratinib + fulvestrant in ERBB2-mutant, HER2-non-amplified, estrogen receptor (ER)-positive, metastatic breast cancer (MBC): Preliminary analysis from the phase II SUMMIT trial.
Poster Discussion, Wednesday, Dec. 7; 5:00 – 7:00 p.m. CST

P2-03-05: Identification, clinical characteristics and treatment outcomes of somatic human epidermal growth factor receptor 2 (ERBB2) mutations in metastatic breast cancer patients.
Thursday, Dec. 8; 7:30 – 9:00 a.m. CST

P2-03-10: A fit-for-purpose NGS system that reports ERBB2 (HER2) mutations and copy number variants for clinical trials research and drug development.
Thursday, Dec. 8; 7:30 – 9:00 a.m. CST

P2-11-03: Incidence and severity of diarrhea with neratinib + intensive loperamide prophylaxis in patients (pts) with HER2+ early-stage breast cancer (EBC): Interim analysis from the multicenter, open-label, phase II CONTROL trial.
Thursday, Dec. 8; 7:30 – 9:00 a.m. CST

P3-03-03: An acquired HER2 T798I gatekeeper mutation induces resistance to neratinib in a patient with HER2 mutant-driven breast cancer.
Thursday, Dec. 8; 5:00 – 7:00 p.m. CST

P3-05-02: Quantitative ERα measurements in TNBC from the I-SPY 2 TRIAL correlate with HER2-EGFR co-activation and heterodimerization.
Thursday, Dec. 8; 5:00 – 7:00 p.m. CST

P4-12-06: Quantification of HER2-driven signaling (HER2 S ) inhibition of four different anti-HER2 drugs tested ex vivo in live primary HER2-negative breast cancer cell samples with abnormal HER2 signaling activity.
Friday, Dec. 9; 7:30 – 9:00 a.m. CST

P4-21-10: Characterization of neratinib-induced diarrhea in patients with early-stage HER2+ breast cancer: Analyses from the phase III ExteNET trial.
Friday, Dec. 9; 7:30 – 9:00 a.m. CST

Heat Biologics Presents ComPACT Preclinical Data at the Society for Immunotherapy of Cancer Annual Meeting

On November 14, 2016 Heat Biologics, Inc. (Nasdaq:HTBX), a leader in the development of gp96-based immunotherapies that are designed to activate a patient’s immune system to fight cancer, reported that preclinical data from its c platform, a single product that combines Heat’s ImPACT therapeutic vaccine with an immune co-stimulatory molecule, was presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting (Press release, Heat Biologics, NOV 14, 2016, View Source [SID1234516630]). In the poster, "Gp96-Ig/Costimulator (OX40L, ICOSL, or 4-IBBL) Combination Vaccine Improves T-cell Priming and Enhances Immunity, Memory and Tumor Elimination," researchers assessed ComPACT/OX40L in a third preclinical mouse tumor model: colorectal cancer (MC38). ComPACT/OX40L amplified antigen-specific CD8+ T cells and memory precursor effector cells (MPECs). It also blocked tumor growth, and increased both tumor rejection and animal survival, generating better results than an OX40 antibody, and without the broad systemic inflammation typically seen with OX40 antibody therapy. Furthermore, ComPACT/OX40L, combined with either PD1 or PD-L1 blocking antibodies, produced even greater antitumor immunity than either compound alone.

The researchers concluded that ComPACT synergizes well with checkpoint inhibitors, which could provide an effective cancer treatment approach in humans.

These studies expand on previous ComPACT studies, which demonstrated anti-tumor efficacy of ComPACT/OX40L in two mouse models: colon cancer and melanoma, where it was attributed to amplified antigen-specific CD8+ T cell expansion (Fromm et. al. Cancer Immunology Research. 2016).

"These data provide a compelling mechanistic rationale for combinations between ComPACT vaccines and PD-1/L1 blockade," said Taylor Schreiber, M.D., Ph.D., Heat’s Chief Scientific Officer, and a study author. "The combination significantly increased the frequency of tumor-antigen specific CD8+ T cells, and increased the fraction of those cells that are most likely to become long-lived memory cells capable of providing durable tumor immunity."

The poster is available in the Publications section of Heat’s corporate website.

CLEVELAND BIOLABS REPORTS THIRD QUARTER 2016 FINANCIAL RESULTS AND DEVELOPMENT PROGRESS

On November 14, 2016 Cleveland BioLabs, Inc. (NASDAQ:CBLI) reported financial results and development progress for the third quarter ended September 30, 2016 (Filing, Q3, Cleveland BioLabs, 2016, NOV 14, 2016, View Source [SID1234516629]).

Cleveland BioLabs reported net income of $1.1 million, excluding minority interests, for the third quarter of 2016, or $0.10 per share, compared to a net loss, excluding minority interests, of $(3.1) million, or $(0.31) per share, for the same period in 2015. Net loss, excluding minority interests, for the first nine months of 2016 was $(1.4) million, or $(0.13) per share, compared to a net loss, excluding minority interests, of $(11.2) million, or $(1.93) per share, for the same period in 2015. The reduction in net loss for both periods due to operating results was attributable to increased revenues and lower costs with the most significant being a reduction in the non-cash adjustment to our warrant liabilities and reduced operating costs aligned with our streamlined focus primarily on pursuing a pre Emergency Use Authorization ("pre-EUA") for entolimod with the U.S. Food and Drug Administration ("FDA"). Additionally, the weighted average outstanding shares for the nine month period significantly increased, which thereby lowers the per share results, due to the issuance of approximately 6.5 million shares in July 2015.

As of September 30, 2016, the Company had $14.9 million in cash, cash equivalents and short-term investments, which, based on the Company’s current operational plan, is expected to fund the Company’s operating requirements beyond one year.

Yakov Kogan, Ph.D., MBA, Chief Executive Officer, stated, "The side-by-side analytical comparability analysis of two formulations of entolimod is on schedule to be completed in the fourth quarter of 2016. Once we have this data and once the FDA has finalized the biocomparability study design, the biocomparability study in non-human primates ("NHP") may commence. We expect the NHP study will require approximately 6 months to complete, and we will update guidance on this point after the FDA has completed its reviews and our vendors have confirmed timing."

"In addition, we are in ongoing discussions with the European Medicines Agency ("EMA") for a pediatric investigational plan ("PIP") for entolimod as a medical radiation countermeasure. A proposed PIP was filed with the EMA. The EMA requires an agreement on a PIP with the sponsor as a prerequisite to filing a Marketing Authorization Application ("MAA"). We cannot currently estimate when an agreement on the PIP will be reached or if any additional studies will be required for an MAA submission."

"Clinical oncology studies with entolimod, CBLB612 and Mobilan are progressing in the Russian Federation," added Dr. Kogan. "Recruitment was completed in a Phase 2 study of entolimod as a neo-adjuvant therapy in treatment-naïve patients with primary colorectal cancer and a Phase 2 study of CBLB612 as myelosuppressive prophylaxis in patients with breast cancer receiving doxorubicin-cyclophosphamide chemotherapy. The data from these studies are being analyzed. Panacela Labs is now dosing Mobilan in two dose-escalation Phase 1 studies evaluating single and double injection regimens administered directly into the prostate of patients with prostate cancer. All of these studies are supported by development contracts with the Russian Federation Ministry of Industry and Trade."

Further Financial Results

Revenue for the third quarter of 2016 increased to $1.1 million compared to $0.5 million for the third quarter of 2015. Revenue for the first nine months of 2016 increased to $2.5 million compared to $1.4 million for the first nine months of 2015. These increases were primarily attributable to work performed under contracts from the Department of Defense for the continued development of the entolimod as a medical radiation countermeasure.

Research and development costs for the third quarter of 2016 decreased to $1.1 million compared to $2.1 million for the third quarter of 2015. Research and development costs for the first nine months of 2016 decreased to $4.3 million compared to $5.2 million for the first nine months of 2015. The reduction in research and development costs for both periods is due to our streamlined focus primarily on pursuing a pre-EUA with the FDA.

General and administrative costs for the third quarter of 2016 decreased to $0.8 million compared to $1.3 million for the third quarter of 2015. General and administrative costs for the first nine months of 2016 decreased to $2.7 million compared to $5.2 million for the first nine months of 2015. This decrease was primarily attributable to reductions in personnel and outside professional costs.

As of October 31, 2016 the Company had approximately 11 million shares of common stock outstanding. In addition, the Company has approximately 0.2 million shares of common stock reserved for issuance pursuant to outstanding stock options with a weighted average exercise price of $42.50 and approximately 2.1 million shares of common stock reserved for issuance pursuant to outstanding warrants exercisable at a weighted average price of $11.04.