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PIQUR announces positive Phase 1 study results and the start of Phase 2 of PQR309

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.

Halozyme, Ventana Enter Into Global Agreement To Collaboratively Develop Companion Diagnostic For Cancer Treatment

On May 27, 2015 Halozyme and Ventana Medical Systems reported a global agreement to collaborate on the development of, and for Ventana to ultimately commercialize, a companion diagnostic assay for use with Halozyme’s investigational new drug, PEGPH20 (Press release, Halozyme, MAY 27, 2015, View Source [SID:1234504843]).

The Ventana assay will be used to identify high levels of hyaluronan (HA). HA is a glycosaminoglycan – a chain of natural sugars distributed throughout human tissue – that can accumulate around cancer cells. Halozyme has announced plans for rollout of a global phase 3 clinical study in 2016 targeting metastatic pancreatic cancer patients with high HA levels using its PEGPH20 in combination with ABRAXANE (nab-paclitaxel) and gemcitabine.

Under the agreement, Ventana will develop an in vitro diagnostic (IVD), under design control, using Halozyme’s proprietary HA binding protein, with the intent of submitting it for regulatory approval in the United States, Europe and other countries.

"Ventana brings a high level of development, regulatory and commercial expertise to our companion diagnostic strategy, which will help ensure we are well prepared for the initiation of our phase 3 study in pancreatic cancer," said Dr. Helen Torley, president and CEO of Halozyme. "The agreement is an important milestone in our PEGPH20 program as we study the potential of PEGPH20 across multiple tumor types."

"We are pleased to enter into this master collaboration agreement with Halozyme, which may produce the first diagnostic to target tumor-associated HA and possibly the first companion diagnostic assay in pancreatic cancer," said Doug Ward, Vice President, Ventana Companion Diagnostics. "The PEGPH20 program, coupled with our global reach, has the potential to improve the standard of care in pancreatic cancer for patients around the world."

The financial terms of the agreement were not disclosed.

This pharma collaboration is one of many at Ventana, where the Companion Diagnostics team is developing patient stratifying diagnostic tools that can help identify those individuals who are most likely to benefit from specific treatments.

Companion diagnostics (CDx) are tests designed to confirm the presence of a specific biomarker to assist physicians in selecting effective therapies for their patients, based on the individual characteristics of each person. Incorporating a companion diagnostic strategy into a drug development program may expedite the drug approval process and help generate more effective treatments with improved safety profiles for patients.

About Ventana Medical Systems, Inc.

Ventana Medical Systems, Inc. ("VMSI") (SIX: RO, ROG; OTCQX: RHHBY), a member of the Roche Group, innovates and manufactures instruments and reagents that automate tissue processing and slide staining for cancer diagnostics. VENTANA products are used in clinical histology and drug development research laboratories worldwide. The company’s intuitive, integrated staining, workflow management platforms, and digital pathology solutions optimize laboratory efficiencies to help reduce errors, support diagnosis and enable informed treatment decisions by anatomic pathology professionals. Together with Roche, VMSI is driving Personalized Healthcare through accelerated drug discovery and the development of companion diagnostics to identify the patients most likely to respond favorably to specific therapies.

Visit www.ventana.com to learn more.

About PEGPH20

PEGPH20 is an investigational PEGylated form of Halozyme’s proprietary recombinant human hyaluronidase under clinical development for the systemic treatment of tumors that accumulate hyaluronan.

The FDA granted orphan drug designation to PEGPH20 for treatment of pancreatic cancer and fast track for PEGPH20 in combination with gemcitabine and nab-paclitaxel for the treatment of metastatic pancreatic cancer. Additionally, the European Commission, acting on the recommendation from the Committee for Orphan Medicinal Products of the European Medicines Agency, designated investigational drug PEGPH20 an orphan medicinal product for the treatment of pancreatic cancer.

Clinical trials are currently ongoing for development of PEGPH20 in pancreatic ductal adenocarcinoma and in non-small cell lung cancer. More information may be found at: View Source

Juno Therapeutics and Editas Medicine Announce Exclusive Collaboration to Create Next-Generation CAR T and TCR Cell Therapies

On May 27, 2015 Juno and Editas Medicine reported an exclusive collaboration focused on creating chimeric antigen receptor (CAR T) and high-affinity T cell receptor (TCR) therapies to treat cancer (Press release, Juno, MAY 27, 2015, View Source [SID:1234504840]). The companies will pursue three research programs together utilizing Editas’ genome editing technologies, including CRISPR/Cas9, with Juno’s CAR and TCR technologies.

"We are impressed and inspired by the scope and sophistication of Juno’s scientific vision and the exceptional product development experience of the Juno team"

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"Encouraged by the clinical results we have seen to date with our product candidates, we are committed to accessing and investing in leading science to create next generation therapeutics that maximize benefits and increase the breadth of cancers we address," said Hans Bishop, CEO, Juno Therapeutics. "Editas’ disruptive genome editing technology may unlock the ability of CAR T and TCR technologies to address a much wider range of cancers, giving hope to countless patients and families waiting for treatments."

"We are impressed and inspired by the scope and sophistication of Juno’s scientific vision and the exceptional product development experience of the Juno team," said Katrine Bosley, CEO, Editas Medicine. "They are intensely focused on advancing T cell based therapies for cancer patients, and we share their ambition to significantly expand the types of cancers that can be treated with this approach."

Under the terms of the agreement, Juno will pay Editas an upfront payment of $25 million and up to $22 million in research support over the next five years across the three programs in the alliance. Editas is also eligible to receive future research, regulatory, and commercial sales milestones in excess of $230 million for each program. Following the approval of any products resulting from the alliance, Editas is also eligible to receive tiered royalties.

bluebird bio and Five Prime Therapeutics Enter into License Agreement for Novel Antibodies to Develop Chimeric Antigen Receptor T Cell Therapy

On May 26, 2015 bluebird bio and Five Prime Therapeutics reported that they have entered into an exclusive license agreement to research, develop and commercialize chimeric antigen receptor (CAR) T cell therapies using Five Prime’s proprietary human antibodies to an undisclosed cancer target for hematologic malignancies and solid tumors (Press release, Five Prime Therapeutics, MAY 26, 2015, View Source [SID:1234504833]).

Under the terms of the agreement, Five Prime will provide bluebird bio exclusive rights to its novel human antibodies to the target, and bluebird bio will leverage its proprietary lentiviral gene therapy platform and CAR T capabilities to develop CAR T therapies against the target.

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Financial terms of the agreement include a $1.5 million upfront payment and subsequent milestone payments to Five Prime, which together could total over $130 million per licensed product if certain development, regulatory, and commercial milestones are achieved. Five Prime is also eligible to receive tiered royalties on product sales. bluebird bio will conduct and fund clinical development as well as regulatory and commercial activities.

"CAR T cell therapies have emerged as a very promising approach for treating a number of cancers," said Lewis "Rusty" T. Williams, M.D., Ph.D., chief executive officer & president of Five Prime. "bluebird bio brings a wealth of knowledge in the area of gene therapy, a key component of building CAR T therapeutics. We are also impressed by bluebird bio’s development and manufacturing infrastructure. We feel that bluebird bio is well positioned to succeed with converting Five Prime’s human antibodies to CAR T cell products that can benefit patients, and we are pleased that our proprietary platform continues to demonstrate its versatility in the field of immuno-oncology."

"We are very pleased to enter into this agreement with Five Prime, a company with a track record of success in the characterization and development of therapeutic antibodies to extracellular proteins," said Jeffrey T. Walsh, chief operating officer of bluebird bio. "Five Prime’s program offers a strategic fit to our research and will augment bluebird bio’s growing pipeline of immuno-oncology research and preclinical programs."

Pivotal Study Results Published in Journal of Clinical Oncology Showed Talimogene Laherparepvec Improved Durable Response Rates in Patients With Metastatic Melanoma

On May 26, 2015 Amgen reported the publication of primary results from the Phase 3 OPTiM study in the Journal of Clinical Oncology (JCO) (Press release, Amgen, MAY 26, 2015, View Source [SID:1234504832]).

The data published in JCO, which were previously presented at the Annual Meetings of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) in 2013 and 2014, demonstrated a significantly higher durable response rate (DRR) in patients with unresected stage IIIB, IIIC or IV metastatic melanoma receiving the investigational oncolytic immunotherapy talimogene laherparepvec compared to those who received granulocyte-macrophage colony-stimulating factor (GM-CSF). Results showed that the primary endpoint of DRR was met, however the secondary endpoint of overall survival (OS) was not met, although there was a strong trend in favor of talimogene laherparepvec.

"Oncolytic virus immunotherapy may become a new approach to melanoma treatment, and the OPTiM study demonstrated durable responses in talimogene laherparepvec treated patients with metastatic melanoma," said lead investigator Howard L. Kaufman, M.D., associate director for Clinical Science at the Rutgers Cancer Institute of New Jersey and president of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). "Talimogene laherparepvec may offer a potential new treatment option for patients with this aggressive form of skin cancer."

A DRR measures the number of patients who had a complete response or partial response within the first 12 months of treatment and maintained the response continuously for at least 6 months.

The most frequent adverse events (AEs) observed in this study were chills, pyrexia, injection-site pain, nausea, flu-like symptoms and fatigue. The most common serious AEs included disease progression, cellulitis and pyrexia. No treatment-related deaths were observed.

"While there have been some important new treatment options in recent years, the incidence of melanoma has risen dramatically, and we need additional approaches for treating advanced disease," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "The OPTiM trial data provide strong evidence supporting the local and distant effects of talimogene laherparepvec and its potential to stimulate a systemic anti-tumor immune response."

The OPTiM data serve as the basis of a Biologics License Application which has been accepted for review by the U.S. Food and Drug Administration (FDA), and a Marketing Authorization Application in the European Union for talimogene laherparepvec for the treatment of adults with regionally or distantly metastatic melanoma. The FDA has set a review goal date under the Prescription Drug User Fee Act of Oct. 27, 2015.

Trial Design
The OPTiM study was a global, randomized, open-label, Phase 3 trial designed to evaluate the safety and efficacy of talimogene laherparepvec compared to a control therapy with GM-CSF in over 400 patients with unresected stage IIIB, IIIC or IV melanoma.

Patients were randomized 2:1 to receive either talimogene laherparepvec intralesionally every two weeks or GM-CSF subcutaneously for the first 14 days of each 28 day cycle. Treatment could last for up to 18 months. Where appropriate, stable or responding patients could receive additional treatment on an extension protocol.

About Talimogene Laherparepvec
Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumors (but not normal tissue) and to initiate an immune response to target cancer cells that have metastasized. Talimogene laherparepvec was designed to work in two important and complementary ways. First, it is injected directly into tumors where it replicates inside the tumor’s cells causing the cell to rupture and die in a process called lysis. Then, the rupture of the cancer cells can release tumor-derived antigens, along with GM-CSF, that can stimulate a system-wide immune response where white blood cells are able to seek out and target cancer that has spread throughout the body.

Amgen has initiated a comprehensive clinical development program for talimogene laherparepvec in metastatic melanoma, which includes combination studies with checkpoint inhibitors in patients with late-stage disease and monotherapy prior to surgery (neoadjuvant) in patients with resectable disease. Additionally, based on its clinical profile, talimogene laherparepvec has the potential to be studied in a variety of solid tumor types.

About Melanoma
Melanoma is a type of skin cancer that is characterized by the uncontrolled growth of melanocytes, which are the cells responsible for providing the pigment to skin.1 Melanoma is the most aggressive and serious form of skin cancer. Currently, 132,000 melanoma cases occur globally each year.2 In the U.S., while melanoma accounts for less than five percent of skin cancer cases, it causes the most skin cancer deaths.3 The number of new cases of melanoma in the U.S. has been increasing for the last 30 years.3

Melanoma is considered to be advanced when it has spread, or metastasized, from the origin site to deeper parts of the skin or other organs such as the lymph nodes, lungs or other parts of the body distant from the primary tumor site.4