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Pierre Fabre and H-Immune announce research partnership to develop cancer immunotherapies

On March 21, 2017 Pierre Fabre, the second largest privately held pharmaceutical company in France, and H-Immune SAS, an emerging biotechnology company focused on developing first in class immunotherapies for treatment of various cancers, reported that they have entered into a strategic research partnership which will utilize H-Immune’s unique technology platform to generate lead candidates of fully human antibodies to serve as the initial step in a program to develop immuno-oncology therapeutics (Press release, Pierre Fabre, MAR 21, 2017, View Source [SID1234518248]).

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As a newly established bioscience company in the immuno-oncology field and spin out from the French Atomic Energy Commission, H-Immune has developed a proprietary In Vitro Immunization (IVI) technology leveraging a breakthrough approach to generate a series of fully human monoclonal antibodies (mAbs) against any therapeutic target, taking advantage of the affinity maturation processes performed in situ by B lymphocytes.

Pierre Fabre is an ideal partner for H-Immune to help us begin to realize the full potential of our science and IVI technology which we plan to exploit through multiple industry partnerships, said Luc Boblet, PhD, Co-Founder and CEO of H-Immune. This collaboration is designed to catalyze and create tremendous ongoing scientific and product development synergy by leveraging each company’s strengths and assets.

Under the terms of the agreement, Pierre Fabre will have access to H-Immune’s IVI technology for three different discovery programs in the field of immuno-oncology.

This transaction strengthens Pierre Fabre’s position in the areas of immuno-oncology and novel cutting-edge biotherapeutics,said Laurent Audoly, Head of R&D of Pierre Fabre Pharmaceuticals. H-Immune is developing an antibody technology platform that we are looking forward to accessing as part of our ongoing efforts to identify and develop world-class novel cancer therapeutics. We believe this collaboration enhances the potential of both partners to deliver transformational therapies to patients in areas of significant unmet medical needs.

Pierre Fabre has a longstanding commitment to development of pharmaceuticals through its Pierre Fabre Immunology Centre of excellence (CIPF) based in Saint-Julien-en-Genevois, France, which is dedicated to the identification, development and manufacturing of biologics.

The financial terms of the agreement, which include expertise contribution, R&D funding, and milestone payments to H-Immune, were not disclosed.

Onxeo to Present Data Supporting Three Key Orphan Oncology Assets at AACR Annual Meeting

On March 21, 2017 Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO), a biotechnology company specializing in the development of innovative drugs for the treatment of orphan diseases, in particular in oncology, reported the presentation of data from three studies supporting the company’s primary drug candidates in oncology, AsiDNATM, Livatag and Beleodaq in poster sessions at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, one of the most prestigious meetings on preclinical cancer research, being held April 1-5, 2017 in Washington, D.C.

Françoise Bono, PhD, Chief Scientific Officer, commented, “The various data we will be presenting at the prominent AACR (Free AACR Whitepaper) oncology meeting demonstrates our commitment to further explore and advance our three core pipeline assets. These data support delayed tumor growth with the combination of our signal-interfering molecule AsiDNATM and PARP inhibitors, the ability of Livatag to reverse chemo-resistance compared to free doxorubicin and increased anti-tumor response through the combination of our marketed drug Beleodaq with immune checkpoint inhibitors. The results provide a strong rationale for the continued development of each product candidate, and this validation is directly in-line with our mission of identifying and developing innovative approaches to fight some of the most aggressive cancer indications. We look forward to presenting these findings at the conference.”

Details of the sessions on April 3 and 4 include:

Abstract 1110 / Poster 3 – AsiDNA induce tumor sensitivity to PARP inhibitors in homologous recombination proficient breast cancer
Session: PO.ET03.01 – DNA Repair
Date: Monday, April 3
Time: 8:00 a.m. – 12:00 p.m. ET
Location: Section 3

The study highlights the therapeutic interest of combining Onxeo’s lead signal-interfering DNA product candidate AsiDNA and PARP (PolyADP-Ribose Polymerase) inhibitors. This combination significantly decreases tumor growth independent of genetic mutations, in contrast to the antitumoral efficacy of PARP inhibitors alone, which are only effective against tumors bearing mutations on genes coding for proteins involved in homologous recombination (HR) pathway. In a preclinical murine tumor model, while the PARP inhibitor olaparib failed to prevent tumor growth and AsiDNA partially delayed this growth, the combination of olaparib and AsiDNA demonstrated synergistic antitumor efficacy.
Most interestingly, no resistant clones to AsiDNA appeared, suggesting sustained clinical efficacy, unlike most targeted therapies.

Abstract 3076 / Poster 14 – A novel nanoparticle formulation of doxorubicin is clearly differentiated from free doxorubicin in overcoming resistance mechanisms in chemo-resistant tumors
Session: PO.ET02.04 – Determinants of Drug Sensitivity and Resistance
Date: Tuesday, April 4
Time: 8:00 a.m. – 12:00 p.m. ET
Location: Section 2

The study demonstrates the therapeutic potential of Livatag, doxorubicin loaded nanoparticles, to reverse chemo-resistance compared to free doxorubicin in hepatocellular carcinoma (HCC, primary liver cancer), pancreatic cancer and sarcoma models. Livatag showed a dose-dependent inhibition of cell proliferation in all tested resistant cancer cell lines with superior activity compared to free doxorubicin and other tested drugs. Moreover, in contrast to free doxorubicin, Livatag showed consistent anti-proliferative activity in the absence or presence of inhibitors of efflux pumps and autophagy. In a range of in vivo models, Livatag was preferentially taken up by the tumor tissue and significantly reduced tumor growth when compared with free doxorubicin, with at least equivalent reduction in tumor growth compared to currently approved treatments. Furthermore, Livatag administered in combination with current treatments significantly increased the inhibitory effect of each drug without additional toxicity.
In this study, Livatag is clearly differentiated from free doxorubicin in its ability to overcome resistance mechanisms linked to efflux and autophagy, and its superior bio-distribution profile, both of which result in significantly enhanced activity on chemotherapy-resistant tumors.
These new results collectively support the strong rationale behind the ongoing Phase III ReLive clinical trial comparing Livatag to the best standard of care in patients with advanced HCC. Recruitment in this trial is complete, and preliminary results are expected mid-year.

Abstract 1059 / Poster 12 – Enhanced anti-tumor efficacy of a checkpoint inhibitor in combination with the HDAC inhibitor belinostat in a murine hepatocellular carcinoma preclinical model
Session: PO.ET02.02 – Combination Strategies: Novel Agents and Standard Therapies
Date: Monday, April 3
Time: 8:00 a.m. – 12:00 p.m. ET
Location: Section 1

Results demonstrated that Beleodaq (belinostat) improved anti-tumor therapeutic response induced by the checkpoint inhibitor, anti-CTLA4, showing significantly superior tumor growth inhibition compared to control groups. Importantly, treatment with the combination resulted in complete cessation of tumor growth in all mice during the belinostat treatment period. Mechanistic studies showed that Beleodaq (belinostat) induces an increase in the production of interleukins (proteins involved in the signaling and regulation of immune response) by activated T-lymphocytes, and a concomitant decrease in the regulatory T cells (immunosuppressive cells) in the spleens of treated animals. These results provide strong rationale for using belinostat, which is approved in the U.S. for the treatment of second-line peripheral T cell lymphoma (PTCL), in combination with checkpoint inhibitors to reinforce therapeutic response. Currently, only 20 to 40% of patients respond to checkpoint inhibitors alone. In parallel, a new oral formulation of belinostat will allow potential use in multiple clinical situations.
Further studies are ongoing in order to fully characterize this finding and to facilitate translation into patients.

OncoSec Medical’s Intratumoral Plasmid IL-12 Demonstrates Effectiveness at Enhancing Tumor Immunogenicity in Preclinical Tumor Models

On March 21, 2017 OncoSec Medical Incorporated ("OncoSec") (NASDAQ: ONCS), a company developing DNA-based intratumoral cancer immunotherapies, reported a poster titled "Intratumoral Electroporation-mediated IL-12 Gene Therapy Can Enhance Tumor Immunogenicity" (Poster #2074), at the Keystone Symposia Conference, "Cancer Immunology and Immunotherapy: Taking a Place in Mainstream Oncology," in Whistler, British Columbia, Canada (Press release, OncoSec Medical, MAR 21, 2017, View Source [SID1234518230]). The poster included preclinical data demonstrating that in vivo electroporation of intratumoral plasmid IL-12 (ImmunoPulse IL-12) enhances immunogenicity in poorly immunogenic mouse cancer models. For more information about this meeting, please visit View Source

"These data support the hypothesis that intratumoral delivery of plasmid IL-12 with electroporation can alter the tumor’s immune environment in such a way that a ‘cold’ non-immunogenic tumor is converted to a ‘hot’ immunogenic tumor, thus further supporting recent clinical data that ImmunoPulse IL-12 is a rational combination therapy with anti-PD-1 checkpoint therapies," said Punit Dhillon, President and CEO. "Also, generation of an antigen-specific CD8 T-cell response provides evidence for a potential mechanism of action for the abscopal responses seen in both preclinical and clinical settings."

The full-text abstract is available on the Publications section of OncoSec’s website (www.oncosec.com).

Cellectar Biosciences Further Deepens Intellectual Property Portfolio with Patent Grant for PET Imaging PDC

On March 21, 2017 Cellectar Biosciences, Inc. (Nasdaq: CLRB) (the "company"), an oncology-focused, clinical stage biotechnology company, reported the United States Patent and Trademark Office has granted a method of use patent for CLR 124, the company’s cancer imaging agent, which utilizes Cellectar’s proprietary phospholipid drug conjugate (PDC) delivery platform (Press release, Cellectar Biosciences, MAR 21, 2017, View Source [SID1234518227]).

The recently issued patent, #9,579,406, titled "Phospholipid Ether Analogs as Agents for Detecting and Locating Cancer and Methods Thereof," outlines the use of CLR 124 in PET imaging to detect radiation-insensitive or chemotherapy-insensitive cancers and cancer metastases. Importantly, the patent also provides coverage for the use of CLR 124 in identifying the location of these cancers or cancer metastases specifically within an organ or tissue in a patient. This patent is a continuation-in-part of a previous patent application, #10,906,687, which has resulted in three previously issued patents. The current patent provides intellectual property protection through March 2, 2025.

"This patent further demonstrates the utility of our PDC delivery platform to effectively provide cancer targeting for both therapeutic and diagnostic oncologic payloads, potentially allowing for more effective treatment, regardless of the modality," said Jim Caruso, president and CEO of Cellectar. "We remain focused on developing our therapeutic assets, specifically CLR 131, for the treatment of multiple myeloma and other hematologic malignancies. However, the potential of the platform provides significant opportunity in a variety of clinical applications."

About Phospholipid Drug Conjugates (PDCs)
Cellectar’s product candidates are built upon its patented cancer cell-targeting delivery and retention platform of optimized phospholipid ether-drug conjugates (PDCs). The company deliberately designed its phospholipid ether (PLE) carrier platform to be coupled with a variety of payloads to facilitate both therapeutic and diagnostic applications. The basis for selective tumor targeting of our PDC compounds lies in the differences between the plasma membranes of cancer cells compared to those of normal cells. Cancer cell membranes are highly enriched in lipid rafts, which are glycolipoprotein microdomains of the plasma membrane of cells that contain high concentrations of cholesterol and sphingolipids, and serve to organize cell surface and intracellular signaling molecules. PDCs have been tested in more than 80 different xenograft models of cancer.

Actinium Announces Receipt of Positive Scientific Advice from the European Medicines Agency for Iomab-B

On March 21, 2017 Actinium Pharmaceuticals, Inc. (NYSE MKT:ATNM) ("Actinium" or "the Company"), a biopharmaceutical Company developing innovative targeted payload immunotherapeutics for the treatment of advanced cancers, announced today that the Company has received positive Scientific Advice from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) related to the EU approval pathway for Iomab-B (Press release, Actinium Pharmaceuticals, MAR 21, 2017, View Source [SID1234518226]). In its correspondence to Actinium, the EMA commented that the trial design, primary endpoint and planned statistical analysis of the U.S. pivotal Phase 3 SIERRA (Study of Iomab-B in Relapsed or Refractory AML) trial are acceptable and can serve as the basis for submission of a Marketing Authorization Application. In addition, the EMA commented that it does not anticipate the need for further standalone preclinical toxicology or safety studies. The EMA requested supporting data and information that is already being collected as part of the U.S. pivotal Phase 3 SIERRA trial. The SIERRA trial is a 150 patient, randomized controlled study of Iomab-B that is currently enrolling patients in the U.S. Upon approval, Iomab-B is intended to be an induction and conditioning agent prior to a bone marrow transplant (BMT), often referred to as a hematopoietic stem cell transplant (HSCT) with an initial indication in patients with relapsed or refractory acute myeloid leukemia (AML) who are age 55 and above.

"We thank the EMA for their assistance throughout the Scientific Advice process and for this helpful feedback." said Sandesh Seth, Executive Chairman of Actinium. "We are excited that the EMA finds the design, endpoints and statistical analysis of the Iomab-B SIERRA trial acceptable. Their opinion is an extremely favorable outcome as this will potentially reduce the time and cost to gain marketing authorization in the EU, which is a larger addressable market than the U.S. in terms of number of patients and transplant procedures. With orphan designation for Iomab-B in the EU and now with this positive Scientific Advice, a clear regulatory pathway, we are well positioned to maximize the value of Iomab-B by working strategically to make this potentially curative therapy available to patients in the EU in addition to our efforts in the U.S."

The EMA provides scientific advice to companies regarding the appropriate studies for the development of a medicine. The goal of scientific advice is to facilitate the development and availability of high-quality, effective and acceptably safe medicines, for the benefits of patients. Scientific Advice helps companies make sure they perform the appropriate tests and studies, so that no major objections regarding the design of tests are likely to be raised during the evaluation of a marketing authorization application. The EMA created this program to increase the probability of positive outcomes and to reduce the risk of objections during the evaluation of a market-authorization application. Following the EMA’s advice increases the probability of a positive outcome.

About Iomab-B

Iomab-B, Actinium’s lead product candidate, is currently being studied in the pivotal Phase 3 SIERRA (Study of Iomab-B in Relapsed or Refractory AML) trial, a 150-patient, randomized controlled clinical trial in patients with relapsed or refractory acute myeloid leukemia (AML) who are age 55 and above. The SIERRA trial is being conducted at preeminent transplant centers in the U.S. with the primary endpoint of durable Complete Remission (dCR) at six months and a secondary endpoint of overall survival at one year. Upon approval, Iomab-B is intended to prepare and condition patients for a bone marrow transplant, also referred to as a hematopoietic stem cell transplant in a potentially safer and more efficacious manner than intensive chemotherapy conditioning that is standard of care in bone marrow transplant conditioning currently. A bone marrow transplant is often considered the only potential cure for patients with certain blood-borne cancers and blood disorders. Iomab-B targets cells that express CD45, a pan-leukocytic antigen widely expressed on white blood cells with the monoclonal antibody, BC8, labeled with the radioisotope, iodine-131. By carrying iodine-131 directly to the bone marrow in a targeted manner, Actinium believes Iomab-B will avoid the side effects of radiation on most healthy tissues while effectively killing the patient’s cancer and marrow cells. In a Phase 2 clinical study in 68 patients with advanced AML or high-risk myelodysplastic syndrome (MDS) age 50 and older, Iomab-B produced complete remissions in 100% of patients and these patients experienced transplant engraftment at day 28. The overall survival rate of the 36 relapsed or refractory AML patients in the proof of concept study was 30% at one year and approximately 20% at two years. Iomab-B was developed at the Fred Hutchinson Cancer Research Center where it has been studied in several Phase 1 and Phase 2 trials in almost 300 patients in a number of blood cancer indications, including acute myeloid leukemia (AML), chronic myeloid leukemia (CML), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), Hodgkin’s disease (HD), Non-Hodgkin lymphomas (NHL) and multiple myeloma (MM) and is currently being studied in several ongoing physician trials. Iomab-B has been granted Orphan Drug Designation for relapsed or refractory AML in patients 55 and above by the U.S. Food and Drug Administration and the European Medicines Agency.