Targeting BCR/ABL with tyrosine kinase inhibitors (TKIs) is a proven concept for the treatment of Philadelphia chromosome-positive (Ph+) leukemias. Resistance attributable to either kinase mutations in BCR/ABL or nonmutational mechanisms remains the major clinical challenge. With the exception of ponatinib, all approved TKIs are unable to inhibit the ‘gatekeeper’ mutation T315I. However, a broad spectrum of kinase inhibition increases the off-target effects of TKIs and may be responsible for cardiovascular issues of ponatinib. Thus, there is a need for more selective options for the treatment of resistant Ph+ leukemias. PF-114 is a novel TKI developed with the specifications of (i) targeting T315I and other resistance mutations in BCR/ABL; (ii) achieving a high selectivity to improve safety; and (iii) overcoming nonmutational resistance in Ph+ leukemias. PF-114 inhibited BCR/ABL and clinically important mutants including T315I at nanomolar concentrations. It suppressed primary Ph+ acute lymphatic leukemia-derived long-term cultures that either displayed nonmutational resistance or harbor the T315I. In BCR/ABL- or BCR/ABL-T315I-driven murine leukemia as well as in xenograft models of primary Ph+ leukemia harboring the T315I, PF-114 significantly prolonged survival to a similar extent as ponatinib. Our work supports clinical evaluation of PF-114 for the treatment of resistant Ph+ leukemia.

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On May 28, 2015 Medigene AG (MDG1, Frankfurt, Prime Standard) reported that the US Patent Office has prolonged the term of patent no. 8,679,840 titled "Composition for the preparation of mature dendritic cells" to the year 2031 (Press release, MediGene, MAY 28, 2015, View Source [SID:1234506561]). The previous term would have ended in 2028. The patent protects the process of generating mature polarised dendritic cells developed by the scientists of Medigene Immunotherapies GmbH. Dendritic cells generated with this process are being used in the ongoing clinical trials using Medigene’s DC vaccines. Additionally, Medigene announced the European issue of the respective patent in March 2015. Medigene holds an exclusive licence on these patents which are central for the DC programme.

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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.

The DC vaccines are currently being evaluated in a company-sponsored clinical trial in acute myeloid leukaemia (AML) as well as in 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 the Oslo University Hospital. Moreover, a compassionate use program is being conducted at the Department of Cellular Therapy at the Oslo University Hospital.

Medigene’s dendritic cell product platform allows the design of new generation dendritic cell vaccines. Dendritic cells can take up antigens efficiently, process them and present them on their surface in a form that can induce antigen-specific T cells to proliferate and mature. This way T cells can recognize and eliminate antigen-bearing tumour cells. Dendritic cells can also induce natural killer cells (NK cells) to become active and attack tumour cells. Scientists of Medigene Immunotherapies have developed new, fast and efficient methods for preparing autologous (patient-specific) mature dendritic cells which have relevant characteristics to activate both T cells and NK cells. The dendritic cells can be loaded with various tumour antigens to treat different types of cancer and are designed for treatment of minimal residual disease or use in combination therapies.

Further audio-visual education about Medigene’s DCs at: View Source

Aduro Biotech has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission (Filing, 10-Q, Aduro BioTech, MAY 28, 2015, View Source [SID1234504871]).

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On May 28, 2015 Fibrocell Science, Inc., (Nasdaq:FCSC), an autologous cell and gene therapy company focused on developing first-in-class treatments for rare and serious skin and connective tissue diseases with high unmet medical needs, and Intrexon Corporation (NYSE:XON), a leader in synthetic biology, together reported that a poster will be presented highlighting in vitro pre-clinical data for FCX-007, a gene-therapy drug candidate for the treatment of recessive dystrophic epidermolysis bullosa (RDEB), at the 2015 European Society of Human Genetics (ESHG) Annual Meeting in Glasgow, Scotland, United Kingdom from June 6-9, 2015 (Press release, Intrexon, MAY 28, 2015, View Source;p=irol-newsArticle&ID=2054246 [SID:1234506593]).

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John Maslowski, Vice President of Scientific Affairs at Fibrocell, will present the poster highlighting FCX-007, which is in development for RDEB, a congenital, orphan skin disease caused by the deficiency of the protein collagen VII (COL7). FCX-007 is a gene-modified autologous fibroblast that encodes for COL7, and is being developed in collaboration with Intrexon.

The details of the poster presentation session are as follows:

Session: PM04. Skeletal, connective tissue, ectodermal and skin disorders
Title: Development of a Genetically-Modified Human Dermal Fibroblast for the Treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB)
Poster Board #: PM04.60
Date: Monday, June 8, 2015
Time: 10:30 – 11:30 a.m. GMT
Location: Exhibition Hall at Scottish Exhibition & Conference Center

About FCX-007

FCX-007 is Fibrocell’s novel gene-therapy drug candidate for the treatment of recessive dystrophic epidermolysis bullosa (RDEB), a congenital and progressive orphan skin disease caused by the deficiency of the protein type VII collagen (COL7). FCX-007 is a gene-modified autologous fibroblast that encodes for COL7 and is being developed in collaboration with Intrexon. By genetically modifying autologous fibroblasts ex vivo to produce COL7, culturing them and then treating blisters and wounds locally via injection, FCX-007 offers the potential to address the underlying cause of the disease by providing high levels of COL7 directly to the affected areas, avoiding systemic treatment. The drug is currently in late stage pre-clinical development with an IND filing targeted for mid-2015.

About Recessive Dystrophic Epidermolysis Bullosa (RDEB)

Recessive dystrophic epidermolysis bullosa (RDEB) is the most severe form of dystrophic epidermolysis bullosa (DEB), a congenital, progressive, devastatingly painful and debilitating genetic disorder that leads to death. RDEB is caused by a mutation of the COL7A1 gene, the gene which encodes for type VII collagen (COL7), a protein that forms anchoring fibrils. Anchoring fibrils hold together the layers of skin, and without them, skin layers separate causing severe blistering, open wounds and scarring in response to any kind of friction, including normal daily activities like rubbing or scratching. Children who inherit the condition are often called "butterfly children" because their skin is as fragile as a butterfly’s wings. There are approximately 1,100 – 2,500 RDEB patients in the U.S. Currently, there is no cure for RDEB and treatments address only the sequelae, including daily bandaging, hydrogel dressings, antibiotics, feeding tubes and surgeries.

About Fibrocell Science, Inc.

Fibrocell Science, Inc. (Nasdaq:FCSC) is an autologous cell and gene therapy company focused on developing first-in-class treatments for rare and serious skin and connective tissue diseases with high unmet medical needs. Fibrocell’s most advanced drug candidate, azficel-T, uses its FDA-approved proprietary autologous fibroblast technology and is in a Phase II clinical trial for the treatment of chronic dysphonia resulting from vocal cord scarring or atrophy. In collaboration with Intrexon Corporation (NYSE:XON), a leader in synthetic biology, Fibrocell is also developing gene therapies for orphan skin diseases using gene-modified autologous fibroblasts. The Company’s lead orphan gene-therapy drug candidate, FCX-007, is in late stage pre-clinical development for the treatment of recessive dystrophic epidermolysis bullosa (RDEB). Fibrocell is also in pre-clinical development of FCX-013, its second gene-therapy drug candidate, for the treatment of linear scleroderma. For more information, visit www.fibrocellscience.com.

On May 27, 2015 MacroGenics reported the publication of a nonclinical research paper on MGD006 in Science Translational Medicine (Press release, MacroGenics, MAY 27, 2015, View Source [SID:1234504851]). MGD006 is a humanized, Dual-Affinity Re-Targeting (DART) molecule that recognizes both CD123 and CD3. CD123, the Interleukin-3 receptor alpha chain, is expressed on malignant cells, including leukemic stem cells (LSC), in acute myeloid leukemia (AML) and other hematological diseases. The primary mechanism of action of MGD006 is its ability to redirect T lymphocytes to kill CD123-expressing cells. To achieve this, the DART combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123 on the target cells. The recently published research shows anticancer activity in vitro and in mouse models together with favorable pharmacodynamic and safety profile in nonhuman primates.

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The prognosis of patients with AML remains poor overall despite existing therapy, and substantial unmet need exists for these individuals. AML patients may benefit from targeted immunotherapy approaches. The paper titled "A CD3xCD123 bispecific DART for redirecting host T cells to myelogenous leukemia: Preclinical activity and safety in nonhuman primates," describes how MacroGenics’ scientists engineered the MGD006 DART and demonstrated in vitro that the molecule can arm T cells from AML patients to reduce blast counts and is effective in eliminating AML cells implanted in mice. Furthermore, MGD006 administered to cynomolgus monkeys demonstrated potent pharmacodynamic activity in the form of near complete elimination of circulating CD123-positive cells at doses that were safe and well tolerated.

"This research paved the way for our initiation of a Phase 1 clinical study of MGD006 in 2014," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "This was a significant milestone for our DART platform and I am pleased to say that the study is progressing well. MGD006 has demonstrated great promise as a T-cell re-directed cancer immunotherapy in pre-clinical studies. We are hopeful that these studies will translate into clinical trial results indicative of clinical improvement for patients with AML, myelodysplastic syndrome and several other forms of leukemia and lymphoma."

About the Phase 1 Study of MGD006

MacroGenics continues to enroll patients in the dose escalation portion of a Phase 1 study of MGD006 for the treatment of AML. The Phase 1 dose-escalation study is designed to assess the safety and tolerability of MGD006 in patients with relapsed or refractory AML. In addition to the primary safety endpoint, secondary endpoints of pharmacokinetics and pharmacodynamic activity will be evaluated, as will a number of biomarkers examining the immunobiology of MGD006. The Phase 1 study was initiated at Washington University School of Medicine in St. Louis. In addition, Emory University and Providence Portland Medical Center are now recruiting patients and a fourth site is expected to commence patient recruitment in June.

About MGD006

MGD006 is a humanized DART molecule that can simultaneously bind CD123 and CD3. CD123 has been reported to be overexpressed on malignant cells in a wide range of hematological malignancies including AML and myelodysplastic syndrome (MDS). AML and MDS are thought to arise in, and be perpetuated by, a small population of LSCs that generally resist conventional chemotherapeutic agents. LSCs are characterized by comparably high levels of CD123 expression in contrast to the limited or absent CD123 expression in the corresponding hematopoietic stem cell population in normal human bone marrow.

MacroGenics has retained development and commercialization rights to MGD006 in the U.S., Canada, Mexico, Japan, South Korea and India. MacroGenics’ partner, Servier, has rights to MGD006 in all other countries.

About the DART Platform

MacroGenics’ DART platform enables the targeting of multiple antigens or cells by using a single molecule with dual antibody-like binding regions. The Company has created over 100 DART molecules, which have been designed for evaluation in the potential treatment of cancer, autoimmune disorders and infectious disease. These DART molecules can be tailored for either short or prolonged pharmacokinetics and have demonstrated good stability and manufacturability. MacroGenics and its partners expect to have a total of five DART molecules in clinical development by the end of 2015.