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Provectus Biopharmaceuticals Reports Immune Mechanism of Action Data for PV-10 Presented at Society for Immunotherapy of Cancer Annual Meeting Authored by Researchers at Moffitt Cancer Center

On November 5, 2015 Provectus Biopharmaceuticals, Inc. (NYSE MKT: PVCT, www.pvct.com), a clinical-stage oncology and dermatology biopharmaceutical company ("Provectus"), reported that researchers from Moffitt Cancer Center in Tampa, Florida, presented a poster titled, "Intralesional Rose Bengal in Melanoma Elicits Tumor Immunity via High Mobility Group Box 1," at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 30th Anniversary Annual Meeting in National Harbor, Maryland (Press release, Provectus Pharmaceuticals, NOV 5, 2015, http://www.pvct.com/pressrelease.html?article=20151105.2 [SID:1234508057]).

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Authors Hao Liu, Pasquale Patrick Innamarato, Krithika Kodumudi, Amy Weber, John L Robinson, Satoshi Nemoto, Georgina Crago, Timothy McCardle, Erica Royster, Amod A Sarnaik and Shari Pilon-Thomas state that their "results reveal a clinically relevant immunoadjuvant pathway triggered by tumor cell death secondary to ablation with RB." The data presented were from nonclinical models of melanoma in mice and clinical data from the team’s recent clinical mechanism of action study (Clinical Trials ID NCT01760499). To view the poster, visit http://www.pvct.com/publications/SITC-Poster-2015.pdf.

In the reported work, the authors showed that tumor-specific T cells were increased in the blood of both mouse and man after tumor ablation with PV-10. This was initiated by tumor cell necrosis, leading to release of High Mobility Box Group 1 (HMBG1), one of a class Damage-Associated Molecular Pattern molecules (DAMPs) released by dying cancer cells that can lead to activation of dendritic cells. HMBG1 release was observed in vitro and after ablation of melanoma tumors in mice and clinical trial participants. This was also correlated with dendritic cell activation and infiltration into lymph nodes draining ablated tumors.

Eric Wachter, Ph.D., Chief Technology Officer of Provectus, observed, "The data reported by our collaborators at Moffitt further clarify the mechanism by which tumor ablation with PV-10 can initiate a finely tuned immune response against injected tumor cells. This has important potential implications for overall response and durability of response when PV-10 is used as a single agent therapy, while the central role played by T cells in this response is notable for combination of PV-10 with other agents that function on T cells."

Provectus is currently enrolling patients in a phase 3 study of PV-10 as a single agent therapy for patients with locally advanced cutaneous melanoma (Clinical Trials ID NCT02288897) and in a phase 1b study of PV-10 in combination with the immune checkpoint inhibitor pembrolizumab in patients with metastatic melanoma (Clinical Trials ID NCT02557321).

OXiGENE Announces Positive Initial Data From Phase 1b Study of CA4P in Combination With Pazopanib in Patients With Advanced Recurrent Ovarian Cancer

On November 5, 2015 OXiGENE, Inc. (Nasdaq:OXGN), a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of cancer, reported initial data from a Phase 1b/2 study of the company’s lead investigational drug, CA4P, in combination with the anti-angiogenic agent Votrient (pazopanib) in patients with advanced recurrent ovarian cancer (Press release, OXiGENE, NOV 5, 2015, View Source [SID:1234508054]). The data are from the ongoing "PAZOFOS" study and were presented at the 19th International Meeting of the European Society of Gynaecological Oncology (ESGO) in Nice, France.

"The initial results we’ve seen to date from the Phase 1b portion of PAZOFOS are encouraging and we expect to move into the phase 2 portion of the study in early 2016," said Professor Gordon Rustin, Director of Medical Oncology, Mount Vernon Cancer Centre and a chief investigator for the trial. "We are excited about continuing our clinical evaluation of this complementary combination—a combination that utilizes the potential synergistic effects of CA4P and pazopanib and could offer a new treatment approach for patients with relapsed ovarian cancer."

Dr. Rustin reported that 12 patients have been enrolled in the phase 1b portion of the study. Nine of the patients were evaluated for objective response using RECIST criteria, showing two partial responses, five stable diseases and two progressive diseases. Eight of the ten patients with evaluable data demonstrated decreases in the tumor marker CA125, with three achieving a response according to CGIC criteria. Dr. Rustin also noted that four patients were still on treatment, and that the efficacy data are currently preliminary and unverified. Safety data showed that the combination of CA4P and pazopanib was generally well tolerated with no Grade 4-5 adverse events (AEs). The most commonly reported AEs were hypertension, fatigue, and pain. The Development Safety Update Report #1 submitted to the regulatory body stated that no definitive conclusions can be made regarding the benefit of treatment in the small subset of patients treated so far.

"The results seen thus far with CA4P combined with pazopanib broaden and strengthen the body of evidence indicating that CA4P can be effectively used as a component of combination therapy for patients with solid tumors," said William D. Schwieterman, MD, OXiGENE’s President and CEO. "We look forward to the continued results from this trial, and to advancing CA4P in combination with Avastin in phase 2/3 studies in platinum-resistant ovarian cancer and glioblastoma multiforme in 2016."

PAZOFOS is a randomized, controlled clinical study consisting of a phase 1b dose escalation portion (CA4P plus pazopanib) and a phase 2 portion comparing CA4P plus pazopanib versus pazopanib alone. The study is designed to enroll up to 128 patients at up to ten sites in the United Kingdom. The primary endpoint for the phase 2 portion is progression-free survival; secondary endpoints include safety, overall survival, objective response rate and relevant biomarkers.

PAZOFOS is sponsored by The Christie NHS Foundation Trust and coordinated by the Manchester Academic Health Science Centre, Trials Coordination Unit (MAHSC-CTU) with additional support from The University of Manchester, the Royal Marsden NHS Foundation Trust and Mount Vernon Cancer Centre (part of the East and North Hertfordshire NHS Trust). CA4P and pazopanib are being provided by OXiGENE and GlaxoSmithKline/Novartis, respectively.

About CA4P

CA4P (also known as fosbretabulin) is a vascular disrupting agent and is OXiGENE’s lead investigational drug. CA4P exerts its anti-tumor effects by targeting an established tumor’s immature endothelial cells within the tumor’s blood vessels, compromising the tumor vasculature and leading to widespread ischemia and necrosis of the cells within the central core of the tumor. OXiGENE plans to advance CA4P in clinical development in combination with approved anti-angiogenic agents which prevent the growth of new tumor blood vessels. Following an extensive clinical review, OXiGENE recently announced its plans to focus on initiation of two late-stage clinical programs for CA4P in 2016. These planned programs combine CA4P with standard-of-care in platinum-resistant ovarian cancer and in glioblastoma multiforme. In addition to PAZOFOS, CA4P is also being evaluated in an ongoing study in neuroendocrine tumors.

8-K – Current report

On November 5, 2015 Geron Corporation (Nasdaq: GERN) reported financial results for the third quarter ended September 30, 2015 (Filing, 8-K, Geron, NOV 5, 2015, View Source [SID:1234508051]).

For the third quarter of 2015, the company reported net income of $27.2 million, or $0.17 per share, compared to a net loss of $9.5 million, or $(0.06) per share, for the comparable 2014 period. Net income for the first nine months of 2015 was $8.5 million, or $0.05 per share, compared to a net loss of $26.7 million, or $(0.18) per share, for the comparable 2014 period. The company ended the third quarter of 2015 with $151.8 million in cash and investments.

Revenues for the third quarter of 2015 were $35.4 million compared to $160,000 for the comparable 2014 period. Revenues for the first nine months of 2015 were $36.2 million compared to $975,000 for the comparable 2014 period. Revenues for the three and nine month periods ending September 30, 2015 included the full recognition of the $35.0 million upfront payment from Janssen Biotech, Inc. (Janssen) as collaboration revenue upon the company’s transfer of the imetelstat license rights and completion of technology transfer-related activities outlined under the imetelstat collaboration agreement with Janssen. The upfront cash payment was received in December 2014 and recorded as deferred revenue at that time.

Total operating expenses for the third quarter of 2015 were $8.3 million compared to $10.1 million for the comparable 2014 period. Research and development expenses for the third quarter of 2015 were $4.1 million compared to $6.0 million for the comparable 2014 period. General and administrative expenses for the third quarter of 2015 were $4.3 million compared to $4.1 million for the comparable 2014 period.

Total operating expenses for the first nine months of 2015 were $28.1 million compared to $28.3 million for the comparable 2014 period. Research and development expenses for the first nine months of 2015 were $13.8 million compared to $16.4 million for the comparable 2014 period. General and administrative expenses for the first nine months of 2015 were $12.9 million compared to $11.9 million for the comparable 2014 period. Year-to-date operating expenses for 2015 also included restructuring charges of $1.3 million in connection with the company’s organizational resizing announced in March 2015.

The decrease in research and development expenses for the three and nine month periods ending September 30, 2015, compared to the same periods in 2014, was primarily the net result of lower costs for the manufacturing of imetelstat and reduced personnel-related costs resulting from the organizational resizing, partially offset by increased costs for the development of imetelstat for hematologic myeloid malignancies in collaboration with Janssen. The company expects research and development expenses to increase during the remainder of the year as the development of imetelstat continues in collaboration with Janssen. The increase in general and administrative expenses for the three and nine month periods ending September 30, 2015, compared to the same periods in 2014, was primarily the result of higher non-cash stock-based compensation expense and increased legal costs associated with the company’s patent portfolio.

Interest and other income for the third quarter of 2015 amounted to $187,000 compared to $91,000 for the comparable 2014 period. Interest and other income for the first nine months of 2015 was $481,000 compared to $273,000 for the comparable 2014 period. The increase in interest and other income for the three and nine month periods ending September 30, 2015, compared to the same periods in 2014, primarily reflects higher yields on the company’s investment portfolio. The company has not incurred any impairment charges on its investment portfolio.

Recent Company Events

● Two papers were published in the September 3, 2015 issue of The New England Journal of Medicine (NEJM) with results from two clinical studies in which imetelstat was shown to have disease-modifying activity thought to be associated with the selective inhibition of the malignant progenitor cell clones responsible for the underlying disease in two hematologic myeloid malignancies, essential thrombocythemia (ET) and myelofibrosis (MF). The papers are available online at www.NEJM.org.

● In September 2015, the first patient was dosed in the IMbark study, a Phase 2 clinical trial to evaluate the activity of two dose levels of imetelstat in patients with DIPSS intermediate-2 or high-risk myelofibrosis who have relapsed after or are refractory to a JAK inhibitor. Multiple medical centers across North America, Europe and Asia are planned to participate in this clinical trial. For more information about the IMbark study being conducted by Janssen, please visit View Source

● Three abstracts describing clinical and non-clinical data on imetelstat were accepted for presentation at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition to be held in Orlando, Florida from December 5-8, 2015. The abstracts were published on November 5, 2015 on the ASH (Free ASH Whitepaper) website at www.hematology.org.

Five Prime Therapeutics Immuno-Oncology Research Activities Featured in Poster Presentations at SITC 2015

On November 5, 2015 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing novel protein therapeutics for cancer and inflammatory diseases, reported that three posters featuring the company’s research activities are being presented during the Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), taking place November 4-8, 2015, in National Harbor, Maryland (Press release, Five Prime Therapeutics, NOV 5, 2015, View Source [SID:1234508048]). The posters will be made available at View Source following the presentations.

cmFPA008, an Anti-Mouse CSF-1R Antibody, Combines with Multiple Immunotherapies to Reduce Tumor Growth in Nonclinical Models
Bellovin D, Wondyfraw N, Levin A, et al
Thursday, November 5, 2015

The authors sought to determine whether inhibition of CSF1R when combined with other immuno-oncology therapeutics enhanced the anti-tumor impact. The results show that treatment with cmFPA008, a surrogate antibody targeting mouse CSF1R, resulted in a marked reduction in tumor-associated macrophages (TAMs) and an increase in the relative abundance and activation of cytotoxic CD8+ T cells in preclinical models. In multiple murine tumor models, treatment with cmFPA008 also induced an increase in PD-L1 and significantly enhanced anti-tumor efficacy when combined with an anti-PD1 antibody. In addition, co-administration of cmFPA008 with an agonistic anti-CD40 antibody significantly enhanced tumor suppression compared to either therapy alone. The results provide support for ongoing clinical efforts to evaluate FPA008 as an anti-cancer immunotherapy, particularly in combination with other immuno-oncology therapeutics, including agonists of CD40. Five Prime has initiated a Phase 1a/1b clinical trial with Bristol-Myers Squibb to investigate the efficacy of FPA008 in combination with the anti-PD1 therapeutic OPDIVO (nivolumab) in six tumor types. Five Prime is also developing an agonist antibody to glucocorticoid-induced tumor necrosis factor receptor (GITR) that is expected to enter the clinic in 2017.

Identification of Novel Immune Regulators of Tumor Growth Using RIPPSSM Screening in vivo
Brennan T, Bellovin D, De La Torre J, et al
Friday, November 6, 2015

Five Prime is using its proprietary Rapid In Vivo Protein Production System (RIPPS) screening platform to discover novel protein therapeutics, targets, and drug combinations that can be used in alone or in combinations with other immuno-oncology agents. The authors screened 350 immune cell targets by RIPPS in the CT-26 tumor model and identified proteins that either enhance (potential drug target) or inhibit (potential therapeutic) tumor growth and display favorable changes in TIL (tumor-infiltrating lymphocyte) profiles. Five Prime identified several proteins with novel tumor-inhibiting or tumor-promoting activities. One of these proteins has been evaluated further and displays both strong CD3 infiltrate activity into the tumor and synergistic activity with PD1 blockade. Five Prime is conducting additional studies on each protein in other tumor models and in combination with known immune-modulating drugs.

Identification of a Novel T Cell Co-Inhibitory Receptor and Potential Therapeutic Antibody Target in Oncology
Sallee N, Karasyov A, Bellovin D, et al
Friday, November 6, 2015

In order to identify novel immune regulatory proteins and evaluate their potential as immuno-oncology therapeutic targets, Five Prime screened a subset of its library of human extracellular proteins in vitro for the ability to modulate immune responses. The authors discovered a number of novel T cell co-inhibitors, including one referred to as Novel Co-Inhibitor 1 (or NCI1), which was identified through its inhibitory activity on anti-CD3-stimulated human T cells in an in vitro assay. To confirm its activity, the authors demonstrated that the native protein expressed on an antigen-presenting cell line could inhibit antigen-stimulated CD8+ T cell activation and that blocking antibodies against this protein relieved the inhibition in vitro. This inhibitory activity translated to a murine system and overexpression of the protein in tumor-bearing mice resulted in increased tumor growth. However, blocking NCI1 with an antibody did not have a significant effect on tumor growth as a single agent in in vivo models, and the company is prioritizing other potential targets. The authors will report the further characterization of NCI1.

CTI BioPharma Announces Data Presentations at the 57th American Society of Hematology Annual Meeting

On November 6, 2015 CTI BioPharma Corp. (CTI) (NASDAQ and MTA: CTIC) reported that data highlighting two compounds (pacritinib and tosedostat) from the company’s investigational pipeline will be presented at the upcoming 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, being held December 5-8 in Orlando, FL – including three oral presentations (Press release, CTI BioPharma, NOV 5, 2015, View Source;p=RssLanding&cat=news&id=2107857 [SID:1234508044]).

The presentations will include data analyses from the Phase 3 PERSIST-1 trial of pacritinib, an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R that is currently under investigation for the treatment of patients with myelofibrosis and acute myeloid leukemia (AML) as well as findings from a Phase 2 study of tosedostat, an investigational oral selective inhibitor of aminopeptidases that has demonstrated anti-tumor responses in blood-related cancers and solid tumors in Phase 1-2 clinical trials.

"We look forward to the presentation of data for both pacritinib and tosedostat at this year’s ASH (Free ASH Whitepaper) annual meeting," said James A. Bianco, M.D., President and CEO of CTI BioPharma. "With six abstracts accepted, the data involving two of our investigational compounds is a further example of our focused commitment on advancing the development of our pipeline candidates."

A summary of the oral and poster presentations are below, and full abstracts can be accessed on the ASH (Free ASH Whitepaper) website at www.hematology.org.

Oral Presentations

Analysis of Outcomes by Patient Subgroups in Patients with Myelofibrosis Treated with Pacritinib vs Best Available Therapy (BAT) in the Phase III PERSIST-1 Trial
First Author: Alessandro M Vannucchi, M.D., Associate Professor of Hematology, University of Florence, Italy
Date/Time: Saturday, December 5 at 10:15 a.m. ET
Location: W224, Level 2
Oral Session: 634. Myeloproliferative Syndromes: Clinical: Early and Late Stage Trials in MPN
Abstract #58

Pacritinib, a Dual FLT3/JAK2 Inhibitor, Reduces IRAK-1 Signaling in Acute Myeloid Leukemia
First Author: Megan M Cleary, B.S., B.A, Knight Cancer Institute, Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, OR
Date/Time: Monday, December 7 at 11:45 a.m. ET
Location: Room W109
Oral Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Novel Targeting Approaches
Abstract #570

Tosedostat Plus Low Dose Cytarabine Induces a High Rate of Responses That Can be Predicted By Genetic Profiling in Elderly AML
First Author: Giuseppe Visani, M.D., Director of Hematology and Stem Cell Transplant Center at AORMN, Pesaro, Italy
Date/Time: Sunday, December 6 at 5:30 p.m. ET
Location: Room W109
Oral Session: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: New Drugs
Abstract #329

Poster Presentations

Relationship Between Patient-Reported Outcomes (PROs) and Health-Related Quality of Life (HRQoL) and Efficacy in Patients with Myelofibrosis in the Phase III PERSIST-1 Trial of Pacritinib Vs. Best Available Therapy (BAT)
First Author: Ruben Mesa, M.D., Chair, Hematology and Medical Oncology Division Mayo Clinic, Scottsdale, AZ
Date/Time: Saturday, December 5 at 5:30-7:30 p.m. ET
Location: Hall A, Level 2
Poster Session: 634. Myeloproliferative Syndromes: Clinical: Poster I
Abstract #1609

Targeting JAK2 by Gene Knockout or Pacritinib Treatment Reduces GVHD and Xenograft Rejection by Promoting Induced Treg Differentiation
First Author: Brian C. Betts, M.D., Medical Oncologist and Assistant Member of the Department of Blood and Marrow Transplant, Moffitt Cancer Center, Tampa, FL
Date/Time: Saturday, December 5 at 5:30-7:30 p.m. ET
Location: Hall A, Level 2
Poster Session: 702. Experimental Transplantation: Immune Function, GVHD and Graft-versus-Tumor Effects
Abstract #1874

Pacritinib (PAC) Synergistically Potentiates Azacitidine (5AZA) Cytotoxicity in Chronic Myelomonocytic Leukemia (CMML)
First Author: Yan Ma, M.D., H. Lee Moffitt Cancer Center, Tampa, FL
Date/Time: Saturday, December 5 at 5:30-7:30 p.m. ET
Location: Hall A, Level 2
Poster Session: 636. Myelodysplastic Syndromes – Basic and Translational Studies: Poster I
Abstract #1658

About Pacritinib

Pacritinib is an investigational oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1 and CSF1R. In August 2014, pacritinib was granted Fast Track designation by the FDA for the treatment of intermediate and high risk myelofibrosis, including but not limited to patients with disease-related thrombocytopenia, patients experiencing treatment-emergent thrombocytopenia on other JAK2 inhibitor therapy, or patients who are intolerant of, or whose symptoms are sub-optimally managed on other JAK2 inhibitor therapy. The FDA’s Fast Track process is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need. Pacritinib does not have regulatory approval and is not commercially available.

CTI BioPharma and Baxalta (NYSE:BXLT) are parties to a worldwide license agreement to develop and commercialize pacritinib. CTI BioPharma and Baxalta will jointly commercialize pacritinib in the U.S. while Baxalta has exclusive commercialization rights for all indications outside the U.S.

About Tosedostat

Tosedostat is an investigational oral aminopeptidase inhibitor that has demonstrated anti-tumor responses in blood-related cancers and solid tumors in Phase 1-2 clinical trials. Tosedostat is currently being evaluated in multiple Phase 2 clinical trials for the treatment of patients with AML or high-risk MDS. Tosedostat is not approved or commercially available.