Roche acquires Trophos to expand portfolio in neuromuscular disease with high medical need

On January 16, 2015 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that it has agreed to acquire Trophos, a privately held biotechnology company based in Marseille, France (Press release, Hoffmann-La Roche , JAN 16, 2015, View Source [SID:1234513489]). Trophos’s proprietary screening platform generated olesoxime (TRO19622), which is being developed for SMA – a rare and debilitating genetic neuromuscular disease that is most commonly diagnosed in children. Results from a pivotal phase II clinical trial with olesoxime in SMA showed a beneficial effect on the maintenance of neuromuscular function in individuals with Type II and non-ambulatory Type III SMA, as well as a reduction in medical complications associated with the disease. These data were first presented in April 2014 at the annual meeting of the American Academy of Neurology (AAN).

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"This acquisition highlights Roche’s commitment to developing medicines for spinal muscular atrophy, a serious disease with no effective treatment," said Sandra Horning, M.D., Chief Medical Officer and Head of Global Product Development at Roche. "We will build on the work done by Trophos and the French Muscular Dystrophy Association to advance the development of olesoxime and to bring it to people who live with this devastating condition as quickly as possible."
Under the terms of the agreement, Trophos’s shareholders will receive an upfront cash payment of EUR 120 million, plus additional contingent payments of up to EUR 350 million based on achievement of certain predetermined milestones.
"SMA is a grievous disease with a huge impact on the daily life of patients and their families, who are currently left only with supportive care. We are proud to see the development of this medicine evolving, with the ultimate goal of a potential first medicine for SMA," said Christine Placet, Chief Executive Officer of Trophos. "This is a tremendous recognition of the work done by Trophos’s teams and supporters over the past 16 years."

About Spinal Muscular Atrophy (SMA)
SMA is a life-limiting and highly disabling genetic disease characterised by progressive muscle weakness and loss of motor function. SMA affects the motor neurons of the voluntary muscles used for activities such as crawling, walking, head and neck control and swallowing. Typically, SMA presents in early childhood and is the most common genetic cause of infant mortalityi. It is one of the most common rare diseases, with one in 6,000 to one in 10,000 children affected. SMA is an autosomal recessive genetic disease caused by a loss of function of the Survival Motor Neuron (SMN) 1 gene, which leads to insufficient levels of SMN protein, progressive deterioration of nerve cells in the spinal cord and loss of motor neurons. The mutated SMN1 gene responsible for SMA is carried by up to 20 million potential parents in the United States and European Union, most of them unaware that they are carriers.

Patients with SMA are usually categorised by having one of the four types of the disease, based on severity, the highest level of motor functioning achieved and time of onset:
Type I : The most severe form of SMA. Symptoms usually emerge within the first six months of life. Affected infants have low muscle tone, profound muscle weakness and impaired ability to move. Babies with type I SMA never sit. Simple tasks, such as holding up their heads, feeding and swallowing, can be very difficult. Progressive weakness of chest muscles increases the risk of respiratory infections and poor lung growth. Babies with type I SMA are at very high risk of irreversible decline in respiratory capacity. Type I SMA carries a high mortality rate, with more than half of all affected children not surviving beyond two years of age.

Type II : Intermediate form of SMA. Symptoms usually emerge between six and 18 months of age. Individuals with Type II SMA typically are able to sit, but cannot walk, have severe and progressive motor disability and often require care 24 hours a day for their whole life. Individuals with Type II often develop severe curvature of the spine (scoliosis) and weakness of the chest muscles leading to high risk of severe respiratory infections. The severity and progression of the disease varies from person to person, life expectancy ranges from early childhood to adulthood.

Type III : Symptoms can emerge anywhere between 18 months and early adulthood and include difficulty walking, muscle weakness and an increased risk of respiratory infections. A significant number of people with Type III SMA lose the ability to walk and can also develop severe scoliosis and other orthopaedic problems. Many patients become non-ambulatory and are wheelchair bound at the age of 40.

Type IV : Adult form of SMA. A less common form of SMA, this type affects adults and is characterised by a slower progression of symptoms that mainly affect the ability to walk. Symptoms typically emerg after the age of 35 and patients have a normal life expectancy.

About Olesoxime
Olesoxime (TRO19622) is an investigational medicine designed to protect the health of motor nerve cells. Results of a pivotal phase II study of olesoxime in Type II and non-ambulatory Type III SMA patients from the ages of three to 25 years were first presented in April 2014 at the 66th American Academy of Neurology (AAN), Philadelphia, PA, USA. Trophos’s development program was supported by the French Muscular Dystrophy Association. Olesoxime has been granted ‘Orphan Medicinal Product’ designation for the treatment of SMA by the European Medicines Agency and orphan drug designation by the US Food and Drug Administration.

Amgen Presents New Data Supporting First-Line Use Of Vectibix® (Panitumumab) In Combination With FOLFOX In Patients With Wild-Type RAS Metastatic Colorectal Cancer

On January 15, 2015 Amgen reported on new data from the Phase 2 PEAK and Phase 3 PRIME studies that support the first-line use of Vectibix (panitumumab) in combination with FOLFOX, an oxaliplatin-based chemotherapy regimen, in patients with wild-type RAS (absence of exons 2, 3, or 4 KRAS or NRAS mutations) metastatic colorectal cancer (mCRC) (Press release Amgen, JAN 15, 2015, View Source;p=RssLanding&cat=news&id=2008116 [SID:1234501347]). The data will be presented during a poster session at the 2015 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium taking place in San Francisco from January 15 to 17.

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In an exploratory analysis from the PEAK study (abstract #660), treatment with Vectibix compared to bevacizumab (Avastin) resulted in a significantly higher proportion of patients with earlier tumor shrinkage at week eight (64 percent vs. 45 percent, respectively; 95 percent CI, p=0.0232), and among responding patients, a significantly longer duration of response (11.4 vs. 8.5 months, respectively; 95 percent CI, p=0.0142) and greater depth of response (65 percent vs. 46 percent, respectively; p=0.0007). Overall response rates (ORR) appeared to be similar between Vectibix and bevacizumab. This is consistent with observed overall survival (OS) and progression-free survival (PFS) rates, and with data previously reported. The safety profile of Vectibix was consistent with previously reported studies.

"These analyses help deepen our understanding of how Vectibix works when added to a standard first-line chemotherapy for the treatment of wild-type RAS metastatic colorectal cancer," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Our Vectibix clinical trial program continues to yield new insights regarding biomarkers and drug sequencing."

While the primary analysis from PEAK showed similar ORR between the Vectibix- and bevacizumab-based regimens, this exploratory analysis demonstrates that Vectibix produces early, sustained anti-tumor activity, which may in part explain the OS and PFS benefits seen with Vectibix versus bevacizumab in this trial.

A separate analysis from the Phase 3 PRIME study (abstract #537), demonstrated that there were no significant differences in quality of life among patients treated with Vectibix plus FOLFOX versus FOLFOX alone despite the incidence of adverse events associated with each treatment regimen. The quality of life analysis included a scale that assessed mobility, self-care, usual activities, pain/discomfort and anxiety/depression.

Colorectal cancer is the third most common cancer found in both men and women in the U.S. and is the second leading cause of cancer deaths. Approximately 1.2 million cases of colorectal cancer are expected to occur globally each year.

8-K – Current report

On January 12, 2015 Tokai Pharmaceuticals reported that it has entered into an agreement with the Johns Hopkins University related to the development of a companion diagnostic to determine the AR-V7 status of patients with castration-resistant prostate cancer (CRPC) for use with the Company’s lead product, galeterone, which is in development for the treatment of AR-V7 positive metastatic CRPC (Filing 8-K , Tokai Pharmaceuticals, JAN 15, 2015, View Source [SID:1234501348]).

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Under the agreement, the Company has obtained an exclusive, worldwide license from the Johns Hopkins University to patent applications and know-how covering an assay that has been used to determine the AR-V7 status of prostate cancer patients.

AR-V7 positive prostate tumors express a truncated form of the androgen receptor (AR). These truncated ARs are missing the C-terminal end of the receptor that contains the ligand binding domain, which is known as C-terminal loss. The AR splice variant AR-V7 is the most prevalent of the splice variants that cause C-terminal loss.

Clinical data from a prospective trial at the Johns Hopkins University as well as retrospective analyses of studies at MD Anderson Cancer Center and Memorial Sloan Kettering Cancer Center have shown that AR-V7 specifically and C-terminal loss generally is associated with poor responsiveness to Zytiga (abiraterone acetate) and Xtandi (enzalutamide), two commonly used oral therapies for metastatic CRPC. The Company believes that galeterone has the potential to treat patients with AR-V7 based on data from preclinical studies and retrospective data in patients with C-terminal loss from the Company’s Phase 2 ARMOR2 trial of galeterone.

"We are pleased to have formalized the agreement with the Johns Hopkins University to support our ongoing AR-V7 companion diagnostic program. This license adds to the intellectual property around galeterone and is a critical milestone in the development of the companion diagnostic that will be used in our 148 patient Phase 3 ARMOR3-SV trial scheduled to begin in the first half of this year," stated Jodie Morrison, president and chief executive officer of Tokai Pharmaceuticals. "It is our hope that future availability of a companion diagnostic will allow prostate cancer patients and their physicians to make more informed decisions regarding their care."

In addition, the Company announced that it has entered into an agreement with Qiagen N.V. under which Qiagen will develop a non-invasive companion diagnostic utilizing an array of novel technologies for use with galeterone. The agreement formalizes an existing collaboration under which work has been ongoing.

Roche licenses additional EGFR pathway-related intellectual property to QIAGEN

On January 14, 2015 Roche licenses additional EGFR pathway-related intellectual property to QIAGEN(Press release Hoffmann-La Roche, JAN 14, 2015, View Source [SID:1234501342]).

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Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the company has entered into an agreement with QIAGEN that includes a provision of non-exclusive licenses to recently granted Roche patents pertaining to the detection of mutations in the EGFR pathway (including in the KRAS gene). Financial details were not disclosed.

The licenses apply to testing products which detect these mutations using molecular techniques including PCR, next generation sequencing (NGS) and other applications to aid in identification of cancer patients eligible for treatment with certain tyrosine kinase inhibitors. The licenses can be applied to existing and future products.

"As a leader in molecular assay development, we are pleased to provide licenses to the applicable patents so that existing and new tests can support patient treatment decisions," said Paul Brown, Head of Roche Molecular Diagnostics. "Ensuring that assays that utilize Roche proprietary information are fully licensed is a key business strategy for us."

"We are pleased with the agreement, which expands our existing intellectual property portfolio covering more than 35 biomarkers and our deep intellectual property estate in EGFR-related testing, including KRAS- testing", said Dr. Achim Ribbe, Vice President Corporate Business Development Licensing. "As a global leader in personalized healthcare, QIAGEN is working with numerous pharmaceutical companies to develop and market molecular companion diagnostics that can help improve patient outcomes and better utilize healthcare resources."

NANTWORKS ANNOUNCES LAUNCH OF AN IMMUNO-ONCOLOGY COMPANY, NANTCELL, AND LICENSING AGREEMENT WITH AMGEN FOR AN ONCOLOGY ANTIBODY

On January 14, 2015 NantCell, LLC, a subsidiary of NantWorks, LLC, focusing on the discovery and development of immunology based innovative treatments for diseases through cell-based treatments at the molecular level, reported that it has entered into a licensing agreement with Amgen Inc. for AMG 479 (ganitumab), previously in Phase 3 development (Press release, NantWorks, JAN 14, 2015, View Source [SID:1234511990]). Under the agreement, NantCell acquired the exclusive rights to develop and commercialize worldwide, excluding Japan, AMG 479, a fully human monoclonal antibody that targets Type 1 insulin-like growth factor receptor (IGF-1R), a promising target for cancer therapy. Financial terms were not disclosed.

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"We are pleased to enter into this agreement with Amgen," said Dr. Patrick Soon-Shiong, founder and chief executive officer of NantCell. "We acquired an immuno-oncology compound in late-stage development, with the potential to address a number of cancers affecting significant patient populations. This month marks the 10 year anniversary of the FDA approval of Abraxane, the first protein-based chemotherapy delivery vehicle now approved in multiple countries worldwide for breast, lung and pancreatic cancer. It is our belief that the future of cancer care will involve combination therapy with low dose, metronomic use of multiple chemotherapeutic agents, but combined also with immuno-oncology molecules, or with engineered killer cells targeted at the proteomic profile of the specific tumor, regardless of the anatomical type. The development of antibody molecules such as IGF-1R will require next generation sequencing at the proteomic level with a deep level of molecular interrogation to establish the appropriate combination with other drugs."

Patients entering clinical trials conducted by NantCell would be identified after a comprehensive "omic" analysis from DNA, RNA and protein, and treated on the resulting molecular profile to maximize clinical outcome and minimize side effects.

"We are pleased to collaborate with NantCell and NantWorks in their mission to establish a new level of quantitative predictability of patient selection," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "Their integrated suite of technologies may help to improve patient selection and further clinical development of AMG 479."

Scientific and medical research suggest that IGF-1R plays a role in the development and progression of many cancers, possibly due to its anti-apoptotic properties, which allow cancerous cells to resist the cytotoxic properties of chemotherapeutic drugs or radiation therapy. The novel IGF-1R antibody inhibits cancer cell proliferation through disruption of the P13K/Akt and MAPK pathways. Signaling through IGF-1R plays an important role in the regulation of cell growth and survival, and has been shown to be a critical promoter of anchorage independent growth, a well-recognized mechanism for malignancy.

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About NantCell

NantCell, a wholly-owned subsidiary of NantWorks, LLC, is an immuno-oncology company focused on the discovery of innovative antibody, T cell and NK cell based treatments by developing molecularly targeted therapeutics, based on the proteomic profile of the patient’s tumor, independent of the cancer’s anatomical type. Dr. Patrick Soon-Shiong, the creator of Abraxane and the founder of the nab technology platform established NantCell to develop a pipeline of human antibodies and inhibitors of proteins which drive tumor growth and pursue Chimeric Receptor Antigen platforms in both T and NK cells. NantCell’s mission is to make obsolete the standard method of clinical trial design of "trial and error" and replace it with a level of quantitative predictability based on both the genomic and proteomic profile performed a priori. The Company will tap into comprehensive "omic" analytic tools and "big data" generated from supercomputing to develop molecularly designed drugs in this era of genomics and proteomics and identify patients and their tumor signature at the most granular cellular, DNA and protein levels. Patients entering clinical trials would be identified after a comprehensive "omic" analysis from tissue to cell to DNA to RNA to protein to peptide to drug, and tested based on this molecular profile to maximize clinical outcome and minimize side effects. For more information please visit www.nanthealth.com and follow Dr. Soon-Shiong on Twitter@solvehealthcare.

About NantWorks

NantWorks, LLC, founded by renowned physician scientist and inventor of the first human nanoparticle chemotherapeutic agent Abraxane, Dr. Patrick Soon-Shiong, is the umbrella organization for the following entities: NantHealth, NantMobile, NantMedia, NantOmics, NantBioScience, NantCell, NantPharma, NantCapital and NantCloud. Fact-based and solution-driven, each of NantWorks’ division entities operates at the nexus of innovation and infrastructure.

The core mission of NantWorks is convergence: to develop and deliver a diverse range of
technologies that accelerates innovation, broaden the scope of scientific discovery, enhance
groundbreaking research, and improve healthcare treatment for those in need. NantWorks is building an integrated fact-based, genomically-informed, personalized approach to the delivery of care and the development of next generation diagnostics and therapeutics.