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 PIQUR Therapeutics AG, a Swiss clinical-stage pharmaceutical company, reported positive results from the Phase 1 first-in-human study with PQR309 in advanced solid tumors (Press release, PIQUR Therapeutics, MAY 27, 2015, View Source [SID1234527275]).

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PQR309 is a novel, balanced pan-class 1 PI3K/mTOR inhibitor formulated for oral administration. Preclinical studies demonstrated that PQR309 is a highly selective kinase inhibitor, penetrating blood-brain barrier with potent in vitro as well as in vivo antitumor activity.

The results from the first-in-man Phase 1 trial indicate that PQR309 is safe and well tolerated with expected pharmacokinetic profile, pharmacodynamic effect as well as clinical activity.

In total, 28 patients with advanced solid tumors were treated in cohorts of escalating PQR309 doses. The maximum tolerated dose (MTD) of PQR309 was determined to be 80 mg administered at continuous once-daily dosing schedule. Pharmacokinetic data indicate fast absorption of PQR309 as well as dose proportionality. Pharmacodynamic assessment in tumors shows downregulation of PI3K/mTOR pathway phosphoproteins.

One patient with a dysregulation of the mTOR-pathway demonstrated a confirmed partial response while another patient with a tumor containing a PI3K mutation, showed important tumor reduction and a minor response according to RECIST (Response Evaluation Criteria in Solid Tumors). "Data obtained from this first-in-human clinical study, including the evidence of clinical activity is very encouraging and highlights the clinical potential of PQR309", commented Dr. Sasa Dimitrijevic, Chief Development Officer of PIQUR.

The results of this study will be presented at ASCO (Free ASCO Whitepaper), May 29 to June 2, 2015:

"A phase 1 first-in-human (FIH) dose-escalation (DE) study of the oral dual PI3K/mTOR inhibitor PQR309 in patients (pts) with advanced solid tumors: Final DE results." [Poster Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics, Sub-category: Signal Transduction, Abstract Number 2592, Mon, May 30, 8:00 – 11:30 AM, Location: S Hall A, Poster Board #308]

PIQUR has also received approval from the health authorities for the initiation of a Phase 2 clinical trial with PQR309, which aims to obtain efficacy data at well-tolerated doses in patients with selected solid tumor and hematological indications with aberrant PI3K/mTOR signaling. "Following recent regulatory approval to start a Phase 2 study of PQR309, we are excited to advance our compound as a potential treatment option for selected cancer indications", commented Prof. Dr. Richard Herrmann, PIQUR’s Chief Medical Officer.

Helping patients to survive cancer
PIQUR aims to help patients to survive cancer. Two out of three people are now living at least five years after their cancer has been diagnosed. Despite of significant medical innovations in the treatment of cancer, there remains a high unmet medical need for therapies that prolong patients’ survival and improve their quality of life. PIQUR targets both PI3K (phosphoinositide 3-kinase) and mTOR (mammalian target of rapamycin), two key signaling molecules that are vital to several essential biological processes involved in malignant disease, such as cell proliferation, survival and metastasis, making them attractive targets in cancer therapy.

About PQR309
PIQUR’s lead compound, PQR309, is a novel, oral, balanced pan-class 1 PI3K/mTOR inhibitor with excellent prospects to become a powerful anti-cancer drug. PQR309 compares favorably to current and clinically most advanced pan-PI3K/mTOR inhibitors with respect to the drug-like properties. Unlike most of its competitors, PQR309 crosses the blood-brain barrier, expanding its use to oncologic as well as hematologic malignant diseases involving the brain. PQR309 showed activity in different aggressive cancer cell lines inhibiting the PI3K/mTOR pathway.