On January 19th, 2015 Karcinolys SAS, a privately-held biotechnology company developing the Myb34.5 oncolytic virus, reported that data from preclinical studies in pancreatic cancer models were featured in the peer-reviewed journal Human Gene Therapy (Press release, Karcinolys, JAN 19, 2015, View Source [SID1234525529]).

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The paper titled "Targeted oncolytic HSV-1 eradicates experimental pancreatic tumours" was authored by Marion Gayral and Pierre Cordelier, Ph.D., Senior Scientist, INSERM U1037, Cancer Research Center of Toulouse and Université Paul Sabatier Toulouse III, and can be accessed at: View Source

The paper featured preclinical studies of the Myb34.5 oncolytic virus. The authors found that cellular transcription factor B-myb was present in experimental pancreatic ductal adenocarcinoma (PDAC) and tumours, and was over expressed in patients’ tumours, as compared to normal adjacent pancreas. Myb34.5 replicated to high level in human PDAC cell lines and not in adjacent normal tissues, and was associated with cell death by apoptosis. In experimental models of PDAC, mice receiving intratumoral Myb34.5 injections appeared healthy and tumour progression was inhibited, with evidences of tumour necrosis, haemorrhage, viral replication and cancer cell death by apoptosis. Combining standard-of-care chemotherapy with Myb34.5 successfully led to a very impressive antitumoral effect that is rarely achieved in this experimental model, and resulted in a greater reduction in tumour growth than chemotherapy alone.

"The publication of data from our lead compound, Myb34.5, in this respected peer-reviewed journal emphasizes the potential importance of Karcinolys’ oncolytic virus may have in oncology," said Jean-Luc Béjot, MD, MBA, Chief Executive Officer of Karcinolys. "As we plan to move Myb34.5 through the clinic in 2017, we will continue to share our findings with the medical community through peer-reviewed publications, increasing the exposure of our drug candidate and expanding partnering opportunities."

About Myb34.5

Myb34.5 is a replication-conditional oncolytic virus derived from herpes simplex virus type 1 (HSV-1) through targeted genetic engineering. The key mutation is the insertion of cellular transcription factor b-myb gene as a promoter gene sequence controlling and retargeting the expression of HSV-1 virulence gene gamma34.5 (?34.5). Replication of Myb34.5 in infected cells is conditioned by the expression of b-myb, which has been found to be over-expressed in pancreatic ductal adenocarcinoma cells. Myb34.5 selectively replicates in cancer cells, resulting in infected cancer cell death, while sparing normal surrounding tissue cells. Karcinolys in-licensed Myb34.5 from Massachusetts General Hospital (MGH, Harvard University, Boston, Ma., USA) in 2007. Myb34.5 was granted orphan drug designation by the FDA on December 23, 2014.

On January 16, 2016 Xenetic Biosciences, Inc. (OTCBB: XBIO), a biopharmaceutical company focused on developing next-generation biologic drugs and novel oncology therapeutics, reported that it will hold a conference call on Tuesday, January 20, at 12:00 UK time, 7:00 a.m. ET. M. Scott Maguire, chief executive officer, and Colin Hill, chief financial officer and board member, will provide a business update and answer questions (Press release, Xenetic Biosciences, JAN 16, 2015, View Source [SID1234537815]).

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To access the conference call, U.K.-based participants should call 0800 368 0649, and participants in all other locations should call +44 20 3059 8125. The participant password will be: Sciences. A telephone replay will be available for seven days following the call’s conclusion. Replay dial-in numbers are as follows: United Kingdom 0121 260 4861; United States 866-268-1947; and all other locations + 44 121 260 4861. Please provide conference ID 3245500# when accessing the replay. In addition, the call will be webcast and available at the Investor Relations section of www.xeneticbio.com in the "Events and Presentations" tab.

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.

On January 16, 2015 Peregrine Pharmaceuticals reported on the presentation of clinical data related to the company’s immuno-oncology development program and its lead investigational immunotherapy drug candidate bavituximab at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium (Press release Peregrine Pharmaceuticals, JAN 16, 2015, View Source [SID:1234501385]). This conference is being held January 15-17, 2015 at the Moscone West Convention Center in San Francisco, California.

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The clinical presentation titled: "A Phase II Study of Bavituximab and Sorafenib in Advanced Hepatocellular Carcinoma (HCC)" will be presented this afternoon by Adam Yopp, M.D., assistant professor of surgery at the University of Texas Southwestern Medical Center Dallas, Texas.

In this single-center, single-arm, open-label investigator-sponsored trial (IST), 38 patients with advanced HCC received bavituximab (3mg/kg) weekly and sorafenib (400 mg) twice daily until disease progression or toxicity. Data show that the combination of bavituximab and sorafenib is associated with an improved time to progression (TTP) of 6.7 months, a disease specific survival (DSS) of 8.7 months, a disease control rate (DCR) of 58% (22 out of 38 patients) and a 4-month progression-free survival (PFS) of 62%. Two patients (5%) achieved a partial response according to Response Evaluation Criteria In Solid Tumors (RECIST). The secondary endpoint of median overall survival (OS) was 6.2 months. The combination of bavituximab and sorafenib was well-tolerated in patients with advanced HCC with no indications of autoimmune adverse events that have been seen with other checkpoint immunotherapies.

"These clinical outcomes of time to progression, disease control rate and 4-month progression-free survival are quite encouraging, especially in this heavily pretreated patient cohort with very poor prognosis due to their unfavorable disease biology including a high rate of macrovascular invasion," said Dr. Yopp. "I was also pleased to see an extended tail in the survival curve that is typical of emerging immunotherapies for cancer. The positive data from this study should be considered as rationale for future randomized trials to further evaluate the potential of bavituximab in liver cancer."

"These data, along with recently reported translational data from this study, continue to build the knowledge base for the bavituximab clinical program and, in particular, highlight the potential immunotherapeutic synergies of bavituximab and sorafenib. We agree with Dr. Yopp that these data warrant further clinical evaluation of this combination in later stage clinical trials," said Joseph Shan, vice president of clinical and regulatory for Peregrine. "We continue to build value in the bavituximab program across multiple programs including the execution of the SUNRISE Phase III trial in second-line, non-small cell lung cancer and from data generated from this and other investigator-sponsored trials as well as other ongoing clinical trials. We look forward to new clinical collaborations with the goal of further exploring the utility of bavituximab in combination with other immuno-oncology drugs."

Liver IST Clinical Translation Data

Recently presented translational data of six patients from this trial show that half of the patients evaluated had an increase in tumor fighting immune cells following one cycle of bavituximab treatment, similar to what has been shown for PS-targeting antibodies in multiple preclinical cancer models. In addition, the increase in immune response was associated with patients that remained on study treatment for longer time periods, suggesting the possibility of a clinically meaningful anti-tumor immune response. Three of the six patients evaluated had increased infiltration of activated tumor-fighting T-cells (CD8) into the tumor microenvironment which correlated with a prolonged time to disease progression. In addition, these responding patients initially expressed lower levels of PD-1 positive cells, an established marker of T-cell activation and disease outcome, prior to the initiation of therapy that was followed by a measurable rise post bavituximab treatment.

On January 16, 2015 OncoMed Pharmaceuticals reported final safety, efficacy and biomarker data from the company’s Phase 1b "ALPINE" clinical trial of tarextumab (anti-Notch2/3, OMP-59R5) in 40 patients with frontline metastatic pancreatic cancer (Press release OncoMed, JAN 16, 2015, View Source [SID:1234501384]).

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Tarextumab was generally well tolerated when administered with gemcitabine and Abraxane (paclitaxel protein-bound particles for injectable suspension) (albumin bound), with manageable, on-target drug-related toxicities. The Phase 2 dose of tarextumab was determined to be 15 mg/kg every two weeks in combination with the standard-of-care. Among patients evaluable for response using RECIST criteria, 38 percent (11 of 29) achieved partial responses, with an additional 35 percent achieving stable disease (10 of 29) for an overall clinical benefit rate of 73 percent (21 of 29 patients). Median progression-free survival and overall survival values for the three drug combination of tarextumab-gemcitabine-Abraxane were 5.6 months and 11.6 months, respectively, for all patients treated with the three-drug combination.

The data presented included biomarker analyses that showed that among patients whose tumor samples had elevated levels of Notch3 gene expression, trends toward higher response rates and longer survival were noted, as compared to patients with low Notch3 expression. Median PFS and OS for patients with high Notch 3 expression (using a 50% cut-off) were 6.6 months and 14.6 months, respectively. Given the small sample size and potential imbalances in patient characteristics, these encouraging preliminary efficacy and predictive biomarker observations are being assessed in the ongoing randomized, placebo-controlled, Phase 2 ALPINE trial

"The positive data from the Phase 1b study of tarextumab in first line pancreatic cancer patients provide us with clear support for the advancement of this drug into Phase 2," said Paul J. Hastings, OncoMed’s Chairman and Chief Executive Officer. "The randomized Phase 2 ALPINE study, which began enrolling patients in July of 2014, is enrolling rapidly and we believe the ALPINE study will be the first of our randomized Phase 2 trials to read out, with data expected in the first half 2016."

"Tumor Notch3 gene expression is estimated to be elevated in approximately 70 percent of pancreatic cancer patients and it is thought to be an indicator of poor prognosis and chemotherapy resistance. The data suggesting that the biomarker-positive patients may have improved response rates and survival with tarextumab treatment are supportive of the Phase 2 design of the ALPINE study where tarextumab’s impact on efficacy of all patients enrolled as well as the biomarker positive patients will be assessed. The Notch3 predictive biomarker may enable us to identify those patients that would gain the greatest benefit from tarextumab treatment," added Jakob Dupont, M.D., OncoMed’s Chief Medical Officer.

"Pancreatic cancer remains among the most challenging cancers in spite of recent treatment advances. The Phase 1b tarextumab data confirm safety and early signals of efficacy observed in earlier stage studies," said Eileen O’Reilly, M.D., Associate Director, Clinical Research with Memorial Sloan Kettering Cancer Center and a Principal Investigator of ALPINE. "Further exploration of tarextumab’s potential as a new treatment option for pancreatic cancer patients is warranted and ongoing in the randomized Phase 2 portion of the study. The trial will evaluate the addition of tarextumab in a frontline untreated pancreas cancer population and in specific biomarker-selected subsets."

In the Phase 1b study, tarextumab was administered to standard-of-care chemotherapy to 40 patients with previously untreated, metastatic pancreatic cancer. Thirty-one of the patients received the combination of gemcitabine, Abraxane and tarextumab. Escalating doses of tarextumab were administered every two weeks, ranging from 2.5 mg/kg to 15 mg/kg. Diarrhea, fatigue and anemia were the most common treatment-related toxicities, and the events were mostly Grade 1 or 2, and managed with supportive care. The randomized, double blinded Phase 2 portion of the ALPINE study is currently enrolling patients with first-line advanced pancreatic cancer at 36 clinical sites in the United States. Data are anticipated in the first half of 2016 for both the intent to treat population as well as the tumor Notch3 biomarker positive patients.