On November 5, 2015 Medigene AG (MDG1, Frankfurt, Prime Standard) reported that early clinical data of its dendritic cell (DC) vaccines will be presented at the upcoming ASH (Free ASH Whitepaper) Annual Meeting taking place from December 5 – 8, 2015 in Orlando, Florida, USA, by its partner Oslo University Hospital, Norway (Press release, MediGene, NOV 5, 2015, View Source [SID:1234508023]). The clinical data were collected in an ongoing compassionate use[1] programme conducted by the Oslo University Hospital under the responsibility of Prof. Gunnar Kvalheim. The poster presentation shows data from patients with acute myeloid leukaemia (AML) and is entitled "AML Patients in Minimal Residual Disease Vaccinated with a Novel Generation of Fast Dendritic Cells Expressing WT-1 and PRAME Mount Specific Immune Responses That Relate to Clinical Outcome". The poster will be presented on December 7, 2015 at 6 PM – 8 PM (local time).

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The Oslo University Hospital has an agreement with Medigene for the use of Medigene`s new generation DC vaccines for their ongoing academic clinical studies. Medigene’s DC vaccines are produced according to GMP guidelines at the Department of Cellular Therapy at the Oslo University Hospital. Acute myeloid leukaemia is Medigene’s lead indication in its DC vaccine programme.

Link to the Abstract: View Source

About Medigene’s DC vaccines: The platform for the development of antigen-tailored DC vaccines is the most advanced platform of the three highly innovative and complementary immunotherapy platforms of Medigene Immunotherapies. Currently, Medigene evaluates its DC vaccines in a company-sponsored phase I/II clinical trial in acute myeloid leukaemia (AML). Further studies utilizing Medigene’s DC vaccine technology include two ongoing clinical investigator-initiated trials: a clinical phase I/II trial in AML at the Ludwig-Maximilian University Hospital Großhadern, Munich, and a clinical phase II trial in prostate cancer at Oslo University Hospital. Moreover, a compassionate use programme is being conducted at the Department of Cellular Therapy at Oslo University Hospital.

Dendritic cells (DCs) are the most potent antigen presenting cells of our immune system. Their task is to take up, process and present antigens on their cell surface, which enables them to activate antigen-specific T cells for maturation and proliferation. This way T cells can recognise and eliminate antigen-bearing tumour cells. Dendritic cells can also induce natural killer cells (NK cells) to attack tumour cells. The team of Medigene Immunotherapies GmbH’s scientists has developed new, fast and efficient methods for generating dendritic cells ex-vivo, which have relevant characteristics to activate both T cells and NK cells. The DC vaccines are developed from autologous (patient-specific) precursor cells, isolated from the patient’s blood, and can be loaded with tumor-specific antigens to treat different types of cancer. Medigene’s DC vaccines are in development for the treatment of minimal residual disease or use in combination therapies.

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.

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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.

(Filing, 10-Q, Infinity Pharmaceuticals, NOV 5, 2015, View Source [SID:1234508034])

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On November 5, 2015 Acceleron Pharma Inc. (NASDAQ:XLRN), a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of novel therapeutic candidates that regulate cellular growth and repair, reported that data in six abstracts on the investigational protein therapeutics sotatercept, luspatercept and ACE-1332 will be presented at the 57th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held in Orlando, Florida on December 5-8, 2015 (Press release, Acceleron Pharma, NOV 5, 2015, View Source [SID:1234507988]).

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Oral presentations

Title: Luspatercept Treatment Leads to Long Term Increases in Hemoglobin and Reductions in Transfusion Burden in Patients with Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS): Preliminary Results from the Phase 2 PACE-MDS Extension Study (Abstract #92)
Session: 637. Myelodysplastic Syndromes – Clinical Studies: New Therapeutic Approaches
Date: Saturday, December 5th
Time: 12:15 pm EST (Orange County Convention Center, W331)

Title: TGFβ1 Antagonist Inhibits Fibrosis in a Murine Model of Myelofibrosis (Abstract #605)
Session: 635. Myeloproliferative Syndromes: Basic Science II
Date: Monday, December 7th
Time: 11:30 am EST (Orange County Convention Center, W331)

Title: RAP-536 (Murine ACE-536/Luspatercept) Inhibits Smad2/3 Signaling and Promotes Erythroid Differentiation by Restoring GATA-1 Function in Murine β-Thalassemia (Abstract #751)
Session: 112. Thalassemia and Globin Gene Regulation: Therapeutic Approaches to Thalassemia and Their Mechanisms
Date: Monday, December 7th
Time: 4:35 pm EST (Orange County Convention Center, Valencia A (W415A))

Title: Luspatercept (ACE-536) Reduces Disease Burden, Including Anemia, Iron Overload, and Leg Ulcers, in Adults with Beta-Thalassemia: Results from a Phase 2 Study (Abstract #752)
Session: 112. Thalassemia and Globin Gene Regulation: Therapeutic Approaches to Thalassemia and Their Mechanisms
Date: Monday, December 7th
Time: 4:45 pm EST (Orange County Convention Center, Valencia A (W415A))

Poster presentations

Title: Biomarkers of Ineffective Erythropoiesis Predict Response to Luspatercept in Patients with Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS): Final Results from the Phase 2 PACE-MDS Study (Abstract #2862)
Session: 637. Myelodysplastic Syndromes – Clinical Studies: Poster II
Date: Sunday, December 6th
Time: 6:00 – 8:00 pm EST (Orange County Convention Center, Hall A)

Title: Phase 1 Dose-Escalation Study of Sotatercept (ACE-011) in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed and/or Refractory Multiple Myeloma (Abstract #4241)
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster III
Date: Monday, December 7th
Time: 6:00 – 8:00 pm (EST) (Orange County Convention Center, Hall A)

The posters and presentation slides will be available in the "Publications" section on Acceleron’s website (www.acceleronpharma.com).

About Luspatercept

Luspatercept is a modified activin receptor type IIB fusion protein that acts as a ligand trap for members in the Transforming Growth Factor-Beta (TGF-beta) superfamily involved in the late stages of erythropoiesis (red blood cell production). Luspatercept regulates late-stage erythrocyte (red blood cell) precursor cell differentiation and maturation. This mechanism of action is distinct from that of erythropoietin (EPO), which stimulates the proliferation of early-stage erythrocyte precursor cells. Acceleron and Celgene are jointly developing luspatercept as part of a global collaboration. Acceleron and Celgene are initiating phase 3 clinical trials that are designed to evaluate the safety and efficacy of luspatercept in patients with myelodysplastic syndromes (the "MEDALIST" study) and in patients with beta-thalassemia (the "BELIEVE" study). For more information, please visit www.clinicaltrials.gov.

About Sotatercept

Sotatercept is an activin receptor type IIA fusion protein that acts as a ligand trap for members in the Transforming Growth Factor-Beta (TGF-β) superfamily involved in the late stages of erythropoiesis (red blood cell production). Sotatercept regulates late-stage erythrocyte (red blood cell) precursor cell differentiation and maturation. This mechanism of action is distinct from that of erythropoietin (EPO), which stimulates the proliferation of early-stage erythrocyte precursor cells. Acceleron and Celgene are jointly developing sotatercept as part of a global collaboration. Sotatercept is currently in multiple phase 2 clinical trials. For more information, please visit www.clinicaltrials.gov.

On November 5, 2015 Celsion Corporation (NASDAQ: CLSN), an oncology drug development company, reported financial results for the quarter ended September 30, 2015 and provided an update on its development programs, including ThermoDox, its proprietary heat-activated liposomal encapsulation of doxorubicin, and GEN-1, an IL-12 DNA-based immunotherapy encased in a synthetic nanoparticle delivery system, which minimizes toxicity and maximizes the multiple antitumor effects of IL-12 and is currently under development for the localized treatment of ovarian and brain cancers (Press release, Celsion, NOV 5, 2015, View Source [SID:1234508004]).

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"During the past quarter, we reported positive data highlighting the multiple development opportunities for our chemotherapy and immunotherapy products, broadened our European Early Access Program to include primary liver cancer and realigned our current organization structure, which we expect to provide the most efficient path forward for our broad, diversified product pipeline with a focus on generating clinical data from our GEN-1 platform," said Michael H. Tardugno, Celsion’s chairman, president and CEO. "We plan to initiate multiple clinical studies over the next six to twelve months, including the Euro-DIGNITY study evaluating ThermoDox in breast cancer, a Phase 1b trial for GEN-1 in first-line ovarian cancer, and a second trial evaluating GEN-1 in combination with Avastin and Doxil in platinum-resistant ovarian cancer patients. Enrollment of patients in our global Phase III OPTIMA Study evaluating ThermoDox in primary liver cancer is continuing to build momentum. Lastly, we plan to leverage our TheraSilence RNAi lung-directed delivery platform through non-dilutive licensing and co-development collaborations."

Recent Developments

ThermoDox

Reported Positive Interim Data from the Phase II US DIGNITY Study in RCW Breast Cancer.

In July 2015, Celsion announced continuing positive interim data from its Phase II DIGNITY trial of ThermoDox in recurrent chest wall (RCW) breast cancer. Of the 17 patients enrolled and treated in the DIGNITY Study, 13 were eligible for evaluation of efficacy. Based on available data, every patient experienced a clinical benefit of their highly refractory disease with a local response rate of 69% observed in the 13 evaluable patients, including 5 complete responses, 4 partial responses and 4 patients with stable disease. Local tumor control in this population provides clinical benefit sufficient to warrant its designation as a primary endpoint for pivotal studies.

Announced Updated Overall Survival Data from Phase III HEAT Study, Providing Support for the Clinical Protocol for the Phase III OPTIMA Study.

In August 2015, Celsion announced the latest Overall Survival (OS) analysis (as of July 15, 2015) from the Phase III HEAT Study. The findings, which were demonstrated in a large, well bounded, well defined subgroup of patients (n=285, 41% of the study patients), showed that the combination of ThermoDox and optimized RFA provided a 58% improvement in OS compared to optimized RFA alone. The Hazard Ratio at this analysis is 0.63 (95% CI 0.43 – 0.93) with a p-value of 0.0198. Median overall survival for the ThermoDox group has been reached which translates into a 25.4 month (2.1 year) survival benefit over the optimized RFA only group (79 months for the ThermoDox plus optimized RFA group versus 53.6 months for the optimized RFA only group). An overall survival benefit greater than 60 months is widely recognized as curative.

In September 2015, the Company announced presentations by three leading experts in the treatment of primary liver cancer at the 2015 International Liver Cancer Association (ILCA) 9th Annual Conference during a symposium entitled "Intermediate HCC: Cure vs. Palliation." These experts noted that ThermoDox may represent a treatment with curative potential if the subgroup findings from the HEAT Study are confirmed.

Earlier this week, the Company announced several presentations by leading liver cancer experts in Asia highlighting the curative potential for ThermoDox plus optimized RFA at the 2nd Asian Conference on Tumor Ablation. The presentations at both of these meetings support the protocol for the Phase III OPTIMA Study which is expected to enroll up to 550 patients globally in up to 75 clinical sites in the United States, Europe, China and Asia Pacific. The Company noted that the presentations at ACTA now represent the fifth international medical conference and the seventh time that the Overall Survival data from the HEAT Study has been discussed by leading experts in HCC research.

Expanded the ThermoDox Early Access Program (EAP) in Europe.

In August, the Company and myTomorrows expanded the ThermoDox European Early Access Program to include patients with primary liver cancer and liver cancer metastases in all countries in the European Union territory, Switzerland, Turkey and Israel. The Company’s original EAP with myTomorrows, formed in January 2015, provides eligible patients with access to ThermoDox for the treatment of recurrent chest wall breast cancer. The EAP provides physicians with access to products in later stage development demonstrating evidence of clinical benefit, with an acceptable safety profile and a quality manufacturing process in place. Celsion will be allowed to price ThermoDox at commercial rates.

GEN-1 IL-12 DNA-Based Immunotherapy

Enrolled the First Patient in the OVATION Study

In October 2015, Celsion announced the enrollment of the first patient in its Phase Ib dose escalating clinical trial (the OVATION Study) combining GEN-1, the Company’s DNA-based immunotherapy, with standard of care for the treatment of newly diagnosed ovarian cancer patients who will undergo neoadjuvant chemotherapy. Interim results from this open label study will be available with patient evaluability and will continue through the first half of next year at higher doses of GEN-1.

Announced Confirmatory Preclinical Data for its GEN-1 IL-12 Immunotherapy in Combination with Avastin and Doxil for Ovarian Cancer

In October 2015, Celsion announced results from a large, comprehensive, preclinical program of the Company’s GEN-1 IL-12 immunotherapy in combination with Avastin and Doxil for the treatment of platinum resistant ovarian cancer. The preclinical studies provide evidence of a robust and synergistic anti-cancer advantage compared to untreated animals and suggest a statistically significant improvement over the combination of Avastin and Doxil. These studies support an IND filing for a Phase I/II trial evaluating the combination in ovarian cancer later this year.

Corporate Developments

Completed Integration of June 2014 EGEN Acquisition

During the third quarter of 2015, the Company completed the integration of its June 2014 acquisition of EGEN, Inc. with the consolidation of all early stage preclinical assets at its Huntsville, AL facility. All clinical development, commercialization, business development and administrative functions are now located in Lawrenceville, NJ. From this reorganization, the Company expects to realize a 15 to 20 percent reduction in personnel and related annual operational costs.

Financial Results

For the quarter ended September 30, 2015, Celsion reported a net loss of $4.3 million, or $(0.19) per share, compared to a net loss of $6.9 million, or $(0.40) per share, in the same period of 2014. Operating expenses were $4.4 million in the third quarter of 2015 compared to $6.8 million in the same period of 2014. For the nine month period ended September 30, 2015, the Company reported a net loss of $16.9 million, or $(0.79) per share, compared to $19.0 million, or $(1.12) per share, in the same period of 2014. Operating expenses were $16.3 million in the first nine months of 2015 compared to $18.7 million in the same period of 2014. Net loss and operating expenses for the three-month and nine-month periods ended September 30, 2014 included $0.1 million and $1.2 million, respectively of one-time costs associated with the June 2014 acquisition of EGEN, Inc. Net cash used in operations was $16.9 million in the first nine months of 2015 compared to $14.8 million in the same period last year. The Company ended the third quarter of 2015 with $24.4 million of total cash, investments and accrued interest on these investments.

Research and development (R&D) costs were $2.8 million in the third quarter of 2015 compared to $4.6 million the same period last year. Research and development costs were $11.0 million in the first nine months of 2015 compared to $10.7 million the same period last year. The increase in R&D costs in 2015 is primarily due to expenses associated with the operations of EGEN, Inc., the costs associated with the start-up and initiation of the Phase III OPTIMA Study in 2014 and the production of clinical supplies in 2015 for anticipated GEN-1 Phase I studies. General and administrative expenses were $1.5 million in the third quarter of 2015 compared to $2.0 million the same period of 2014. General and administrative expenses were $5.3 million in the first nine months of 2015 compared to $6.8 million the same period of 2014. These decreases were primarily the result of lower insurance premiums and lower personnel costs resulting from the reorganization and staff reductions announced during the third quarter of 2015.

Quarterly Conference Call

The Company is hosting a conference call to provide a business update and discuss the third quarter 2015 financial results at 11:00 a.m. EST on Thursday, November 5, 2015. To participate in the call, interested parties may dial 1-877-419-6594 (Toll-Free/North America) or 1-719-325-4755 (International/Toll) and ask for the Celsion Corporation Third Quarter 2015 Conference Call (Conference Code: 939465) to register ten minutes before the call is scheduled to begin. The call will also be broadcast live on the internet at View Source." target="_blank" title="View Source." rel="nofollow">View Source

The call will be archived for replay on Thursday, November 5, 2015 and will remain available until Thursday, November 19, 2015. The replay can be accessed at 1-888-203-1112 (Toll-Free/North America) or +1 719-457-0820 (International/Toll) using Conference ID: 939465. An audio replay of the call will also be available on the Company’s website, View Source, for 30 days after 2:00 p.m. EST Thursday November 5, 2015.