Baxter International Makes $700-Million Acquisition

Inspiration Biopharmaceuticals and Ipsen recently announced the sale of its lead hemophilia program, OBI-1 (recombinant porcine factor VIII), to Baxter International. Baxter will acquire worldwide rights to OBI-1, a recombinant porcine factor VIII in development for congenital hemophilia A with inhibitors and acquired hemophilia A. OBI-1 is currently in a pivotal trial for the treatment of individuals with acquired hemophilia A.

Inspiration and Ipsen have signed an asset purchase agreement pursuant to which Baxter would acquire the worldwide rights to OBI-1, as well as Ipsen’s manufacturing facility for OBI-1 in Milford, MA. The total aggregate consideration for these rights may exceed $700 million, including the up-front payment of $50 million, development and sales milestones totaling $135 million, and annual net sales payments equivalent to a tiered double-digit percentage of global net sales.

“Inspiration was founded by families who are personally affected by hemophilia, so bringing innovative therapies to patients has always been at the core of our mission,” said John P. Butler, Chief Executive Officer of Inspiration. “Baxter has a long commitment to hemophilia, and we are excited they will be using their expertise to bring this innovative therapy to people who currently have limited treatment options.”

The asset purchase agreement was filed January 23, 2013, with the US Bankruptcy Court in Boston. The sale is a result of a joint sale process pursued by Inspiration and Ipsen shortly after Inspiration filed for protection under Chapter 11 of the US Bankruptcy Code on October 30, 2012. Ipsen has been providing Inspiration with Debtor-in-Possession (DIP) financing to fund Inspiration’s operations and the sale process.

The sale is subject to certain closing conditions, including Bankruptcy Court and regulatory approvals. Inspiration and Ipsen are in the final bidding stages of the sale process for IB1001, a recombinant factor IX that is currently under regulatory review in the US and Europe.

Biotrial Coming to US, Creating Hundreds of New Jobs

A French pharmaceutical research corporation that had been considering sites in New York and Boston to build its North American headquarters will soon break ground in an emerging mixed-use technology park in Newark, NJ, adjacent to the University of Medicine and Dentistry of New Jersey, the New Jersey Institute of Technology, and Rutgers University-Newark.

Biotrial S.A. recently purchased a 1.2-acre parcel of land in University Heights Science Park, where more than 90 incubator companies are located within the 351,000-sq-ft of office and research space that already has been developed. As Biotrial hopes to occupy the new building in early 2014, New York-based architecture firm Francis Cauffman has completed the master design plan for the facility and expects to commence its construction this spring.

Jean-Marc Gandon, President and Chief Executive Officer of Biotrial, said in a statement the company needed “proximity to superior research and medical facilities and to a major transportation center” to expand in the United States, and it “looked at many locations around the world before deciding that Newark and University Heights Science Park best meet the many key requirements and standards we have for conducting our research.”

In October 2011, the New Jersey Economic Development Authority board approved a $689,850 Business Employment Incentive Program grant for Biotrial S.A. to bring 60 jobs to Newark, though the board noted the incentive could increase to $1.2 million over 10 years if the company picked a site in the city over New York and Massachusetts.

EDA spokeswoman Rachel Hartman said the agency has not yet determined the exact award amount because it is awaiting confirmation on the site selection from Biotrial, and the company would then need to submit other conditions for the BEIP.

Joel Bloom, President of NJIT and Chairman of the science park’s 23-member board, said in a statement Biotrial’s planned 100-bed research unit and administrative space “continues the momentum for developing a world-class science and technology center in Newark. This means hundreds of construction jobs and permanent jobs to follow, and greatly enhanced purchasing power impacting the surrounding communities, which address the primary goals of the science park leadership team.”

Since the research organization desires to partner with nearby academic institutions to leverage their specialized intellectual and clinical services, Rutgers-Newark Interim Chancellor Phil Yeagle said in a statement Biotrial will “create an opportunity for the significant numbers of biologists and other life sciences researchers and educators that are members of our Newark faculties.”

Essex County College President Edith Abdullah said it “gives our region’s college students experiential education opportunities through internships, as well as creates research opportunities for the Newark-based universities’ PhD students.”

Noting that Biotrial currently manages more than 80 drug studies and trials each year, either in their own clinics or in cooperation with specialist hospitals and general practitioners, UMDNJ Interim President Denise V. Rodgers said in a statement “we anticipate Biotrial’s new headquarters here will spark a series of collaborations with the pharmaceutical and biotech industries to advance learning, discovery, and innovation.”

“This will focus more attention on Newark, the state, and the region as a research center, attracting the best in the biomedical and health sciences and advancing leading-edge interventions to improve health outcomes locally and around the world,” Rodgers added.

Since 2010, Biotrial has worked on every step of drug discovery companies’ development processes. The company’s Newark research unit will perform mostly early stage studies and serve European clients who need clinical trials to be performed in the United States. For more information on Biotrial, visit www.biotrial.com.

IBM Creating Superbug Busting Gel

Researchers from the Institute of Bioengineering and Nanotechnology (IBN) and IBM Research recently unveiled the first-ever antimicrobial hydrogel that can break apart biofilms and destroy multidrug-resistant superbugs upon contact. Tests have demonstrated the effectiveness of this novel synthetic material in eliminating various types of bacteria and fungi that are leading causes of microbial infections, and preventing them from developing antibiotic resistance. This discovery may be used in wound healing, medical device and contact lens coating, skin infection treatment, and dental fillings.

“As a multidisciplinary research institute, IBN believes that effective solutions for complex healthcare problems can only emerge when different fields of expertise come together,” said IBN Executive Director Professor Jackie Y. Ying. “Our long-standing partnership with IBM reflects the collaborative creativity across multiple platforms that we aim to foster with leading institutions and organizations. By combining IBN’s biomaterials expertise and IBM’s experience in polymer chemistry, we were able to pioneer the development of a new nanomaterial that can improve medical treatment and help to save lives.”

“The mutations of bacteria and fungi, and misuse of antibiotics have complicated the treatment of microbial infections in recent years,” added Dr. Yi-Yan Yang, Group Leader at IBN. “Our lab is focused on developing effective antimicrobial therapy using inexpensive, biodegradable, and biocompatible polymer material. With this new advance, we are able to target the most common and challenging bacterial and fungal diseases, and adapt our polymers for a broad range of applications to combat microbial infections.”

More than 80% of all human microbial infections are related to biofilm. This is particularly challenging for infections associated with the use of medical equipment and devices. Biofilms are microbial cells that can easily colonize on almost any tissue or surface. They contribute significantly to hospital-acquired infections, which are among the top five leading causes of death in the US and account for $11 billion in healthcare spending each year.

In Singapore, antimicrobial drug resistance is a major healthcare problem because of the extensive use of antibiotics and medical equipment, such as intravascular catheters and orthopedic implants in patients. Once in the body, these instruments become potential breeding grounds for bacterial growth. This provides a continuous source of contamination, which could result in prolonged hospitalization, higher medical costs, and greater risk of death. Research has shown that patients in Singapore with microbial infections were 10.2 times more likely to die during their hospitalization, had 4.6 times longer hospitalization, and incurred 4 times higher hospitalization cost compared to patients with no infections.

The emergence of new strains of superbugs and shortage of new drugs has exacerbated the need for an effective antimicrobial solution. Traditional household antiseptics and disinfectants are also proving to be ineffective in eliminating drug-resistant germs.

Under Dr Yang, IBN’s Nanomedicine group has been conducting research on polymer and peptide nanoparticles as antimicrobial agents since 2007. Her lab has published 15 papers in high-impact factor journals, such as Nature Nanotechnology, Nature Chemistry, Nano Today, Advanced Materials, ACS Nano, Biomaterials, and SMALL, as well as filed 10 patents on their antimicrobial technologies.

Recently, Dr Yang’s group and their collaborators from IBM Research co-developed a synthetic gel that is biodegradable, biocompatible, and cost-effective. With over 90% water content, the hydrogel is highly flexible and easy to adapt for different uses. This gel can target the bacteria and fungi behind seven of the most common hospital-acquired infections, such as MRSA (methicillin-resistant Staphylococcus aureus), VRE (vancomycin-resistant enterococcus), multidrug-resistant Acinetobacter baumannii and Klebsiella pneumoniae, E. coli, Candida albicans, and Cryptococcus neoformans fungi.

This new gel is composed of the novel polymer material jointly developed by IBN and IBM Research in 2010. When mixed with water and heated to body temperature, the polymers form spontaneously into a moldable gel, due to the self-associative interactions between the polymer molecules. This allows the hydrogel to target multidrug-resistant biofilms at various parts of the body and surfaces without being flushed away. Once the antimicrobial function is activated and performed, the biodegradable gel can be naturally eliminated by the body.

Using the new polymer material as a basic building block, IBN can now provide a comprehensive antimicrobial solution to combat drug-resistant bacteria and fungi for a range of medical and consumer products. “Bacterial biofilms are a serious health threat and the ability to disperse such films is critical. The soft consistency of our non-toxic materials makes them ideal for injectable and topical applications as well as coatings and lubricants for medical devices such as catheters,” said Dr James Hedrick, Advanced Organic Materials Scientist, IBM Research. “Whether it’s designing degradable materials to eliminate polymers occupying landfills or new antimicrobial hydrogels that don’t have drug resistance, our partnership with IBN has allowed us to take what the industry has deemed really important and create solutions that are applicable to many technologies in medicine.”

Bacteria primarily exist as free-floating cells or biofilms. When grouped together, the cells secrete a sticky polymeric substance, which weave and ‘glue’ the bacteria to surfaces. Compared to free-floating cells, biofilms are 100-1000 times less susceptible to antibiotics due to the acquired resistance from the tightly weaved microbial structure that blocks and prevents drug penetration. When applied to contaminated surfaces, the hydrogel will tear apart the membranes of the microbes in the biofilms and kill the harmful cells. This is made possible by the electrostatic interaction between the positively charged gel and the negatively charged bacterial or fungal cells. Unlike modern-day antibiotics, which only target the internal machinery of the micro-organisms, this new mode of action eliminates the superbugs completely and prevents any recurring infections. The antimicrobial gel can also be applied preventively to surfaces to avoid multidrug-resistant infections.

Idenix Announces Collaboration With Janssen

Idenix Pharmaceuticals, Inc. recently announced a non-exclusive collaboration with Janssen Pharmaceuticals, Inc. for the clinical development of all-oral direct-acting antiviral (DAA) HCV combination therapies. The collaboration will evaluate combinations, including IDX719, Idenix’s once-daily pan-genotypic NS5A inhibitor, simeprevir (TMC435), a once-daily protease inhibitor jointly developed by Janssen and Medivir AB, and TMC647055, a once-daily non-nucleoside polymerase inhibitor, boosted with low dose ritonavir, being developed by Janssen.

Clinical development plans include an initial drug-drug interaction study to begin in the first quarter of 2013, followed by Phase II studies as agreed between the companies, and pending approval from regulatory authorities. The Phase II program is expected to first evaluate the two-DAA combination of IDX719 and simeprevir plus ribavirin for 12 weeks in treatment-naïve HCV-infected patients.

Subsequently, the companies plan to evaluate a three-DAA combination of IDX719, simeprevir and TMC647055/r, with and without ribavirin. The clinical trials will be conducted by Idenix. Both companies retain all rights to their respective compounds under this agreement.

“We are very pleased to be working with Janssen and look forward to initiating a Phase II study in the first quarter of this year,” said Ron Renaud, Idenix’s President and Chief Executive Officer. “This will allow us to achieve a key goal of ours for 2013, which is to advance the development of IDX719 as part of all-oral HCV combinations in two- and three-drug regimens.”

IDX719 is an NS5A inhibitor with low picomolar, pan-genotypic antiviral activity in vitro. To date, IDX719 has been safe and well tolerated after single and multiple doses of up to 100 mg in healthy volunteers (n=36; up to 7 days duration) and HCV-infected patients (n=69; up to 3 days duration). There have been no treatment-emergent serious adverse events reported in the program. IDX719 has demonstrated potent pan-genotypic antiviral activity in HCV-infected patients with mean maximal viral load reductions up to approximately 4.0 log10 IU/mL across HCV genotypes 1-4 in a proof-of-concept, 3-day monotherapy study.

Simeprevir is a once-daily potent investigational hepatitis C protease inhibitor in late Phase III clinical development being jointly developed by Janssen R&D Ireland and Medivir AB to treat chronic hepatitis C virus infections. Simeprevir is being investigated in combination with PegIFN/RBV in Phase III trials and is also being evaluated with Direct-acting Antiviral (DAA) agents in three other Phase II interferon-free combinations both with and without ribavirin (RBV).

TMC647055 is a potent non-nucleoside hepatitis C polymerase inhibitor with broad genotypic coverage. TMC647055 is in Phase II clinical development and is developed by Janssen R&D Ireland to treat chronic hepatitis C virus infections. TMC647055 is being investigated in combination with other DAA agents in all oral interferon-free regimens.

There have been no treatment-emergent serious adverse events reported in the program.

Threshold Pharmaceuticals Earns $30-Million Milestone Payment

Threshold Pharmaceuticals, Inc. recently announced that its partner Merck KGaA, Darmstadt, Germany, through its division Merck Serono, initiated the global Phase III MAESTRO study assessing the efficacy and safety of investigational hypoxia-targeted drug TH-302 in combination with gemcitabine in patients with previously untreated, locally advanced unresectable or metastatic pancreatic adenocarcinoma. The initiation of the Phase III MAESTRO study resulted in Threshold earning a $30-million milestone payment from Merck KGaA pursuant to the terms of Threshold’s license and co-development agreement with Merck KGaA, which includes an option for Threshold to co-commercialize in the US MAESTRO stands for TH-302 in the treatment of MetastAtic or unrESectable pancreaTic adenocaRcinOma.

MAESTRO is a randomized, placebo-controlled, international, multi-center, double-blind Phase III trial of TH-302 plus gemcitabine compared with placebo plus gemcitabine and is expected to enroll 660 patients. The primary efficacy endpoint is overall survival; the secondary endpoints include efficacy measured by progression-free survival (PFS), overall response rate and disease control rate, as well as assessments of safety and tolerability, pharmacokinetics, and biomarkers. The study is being conducted under a Special Protocol Assessment (SPA) with the US FDA. An SPA is a review conducted by the FDA on a clinical trial that will form the primary basis of an efficacy claim in a marketing application.

The FDA provided written agreement that the design and planned analysis of this study could adequately address objectives in support of a regulatory submission. However, the determination for drug approval by the FDA is made after a complete review of a marketing application and is based on the entire data in the application. The study design was discussed with the FDA also at an End of Phase II meeting and with the European Medicines Agency (EMA) during a scientific advice procedure.

TH-302 is an investigational hypoxia-targeted drug that is designed to be activated under severe tumor hypoxic conditions, a hallmark of many cancers. Areas of low oxygen levels (hypoxia) in solid tumors are due to insufficient blood supply as a result of aberrant vasculature.

“Initiation of the Phase III MAESTRO study is an important advancement in the overall development of TH-302 for the treatment of patients living with cancer,” said Barry Selick, PhD, Chief Executive Officer of Threshold. “This marks the second Phase III study of TH-302 in addition to the ongoing Phase III pivotal trial in patients with soft tissue sarcoma. In addition, we continue to explore the potential breadth and activity of TH-302 against a variety of solid tumors and hematological malignancies in multiple ongoing earlier stage clinical trials.”

The Phase III MAESTRO study for TH-302 was initiated following results from a randomized, controlled Phase IIb trial of TH-302 in patients with pancreatic cancer. At the ESMO 2012 Congress (European Society for Medical Oncology) updated results were presented confirming a significant improvement (p=0.008) in PFS associated with 41% reduction of risk for disease progression or death for patients treated with TH-302