Tekmira’s LNP Delivery Technology Enables Proof of RNAi in Man & Clinical Activity

Tekmira Pharmaceuticals Corporation recently provided comments on presented data from a Phase I human clinical trial with ALN-VSP conducted by Alnylam Pharmaceuticals, Inc. ALN-VSP, an RNAi therapeutic for the treatment of liver cancers that utilizes Tekmira’s LNP technology, the only RNAi delivery technology supporting multiple clinical candidates being advanced by Tekmira and its partners in several different disease indications.

The most recent ALN-VSP data was presented at the American Society of Clinical Oncology (ASCO) meeting in a poster titled Phase I Dose-Escalation Study of ALN-VSP02, a Novel RNAi Therapeutic for Solid Tumors With Liver Involvement. Alnylam disclosed that ALN-VSP was generally well tolerated, demonstrated evidence for anti-tumor activity, and was found to mediate RNAi activity in both hepatic and extra-hepatic tumors.

“Earlier this year, we were excited to see Alnylam’s interim clinical data with ALN-VSP, which demonstrated RNAi activity in human tumor biopsies and confirmed that our LNP technology enables bona fide RNAi activity in man. Now, another important advancement has been made in the RNAi field as Alnylam reports that its ALN-VSP data demonstrates anti-tumor activity,” said Dr. Mark J. Murray, Tekmira’s President and CEO.

“To date, this is the second completed human clinical trial that has reported Tekmira’s LNP technology is safe and well tolerated. We anticipate further clinical data being presented from a number of LNP-enabled products over the remainder of 2011. Building upon this momentum, Tekmira continues to innovate and protect our LNP technology with a focus on improvements to LNP potency and tolerability, as well as combining new RNAi payloads with LNP delivery,” he added.

Tekmira’s LNP technology is enabling the systemic RNAi product pipeline of Alnylam Pharmaceuticals, including the products ALN-VSP, ALN-TTR, and ALN-PCS. As Alnylam disclosed, ALN-VSP was administered to 41 patients at doses ranging from 0.1 to 1.5 mg/kg; a total of 182 doses have been administered, including to one patient who has received 24 doses at 0.7 mg/kg over the course of more than 1 full year, and continues to receive treatment in the study. The Phase I trial was designed as a multi-center, open label, dose escalation study in patients with advanced solid tumors with liver involvement who have failed to respond to or have progressed after standard treatment. The primary objective was to evaluate the safety, tolerability, and pharmacokinetics of intravenous ALN-VSP.

RNAi therapeutics have the potential to treat a broad number of human diseases by “silencing” disease-causing genes. The discoverers of RNAi, a gene-silencing mechanism used by all cells, were awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi therapeutics, such as siRNAs, require delivery technology to be effective systemically. LNP technology is one of the most widely used siRNA delivery approaches for systemic administration. Tekmira’s LNP technology (formerly referred to as stable nucleic acid-lipid particles or SNALP) encapsulates siRNAs with high efficiency in uniform lipid nanoparticles, which are effective in delivering RNAi therapeutics to disease sites in numerous preclinical models. Tekmira’s LNP formulations are manufactured by a proprietary method that is robust, scalable, and highly reproducible, and LNP-based products have been reviewed by multiple FDA divisions for use in clinical trials. LNP formulations comprise several lipid components that can be adjusted to suit the specific application.

Hovione & Particle Sciences Inc. Ink Deal to Speed Up Drug Solubilization Projects

Hovione and Particle Sciences Inc (PSI) recently announced a collaboration agreement under which they will pool their technologies together to significantly speed development projects targeting poorly water-soluble drugs. The companies expect to jointly be able to significantly reduce typical project times.

Hovione and PSI are joining their solid solution technologies based on spray-drying capabilities and aimed at targeting ways to maximize the bioavailability of BCS Class II APIs. Development will be fast-tracked at both companies, with PSI developing the solubilization process and resulting drug product for their clients and Hovione managing the scale-up and industrialization of the spray-drying process.

“It is truly incredible how versatile and useful spray-drying technology is,” said Dave Hoffman, President, Hovione US Operations. “We have used it from a gram scale to tons, with important time savings on the scale-up to manufacture products where other technologies failed. Teaming up with PSI will give their customers an integrated solution that will allow us to go from drug product and process design to feasibility and development to industrial application in record time.”

“We have a variety of drug delivery platforms, some of which are best scaled through spray-drying,” added Mark Mitchnick, Particle Sciences’ CEO. “Our unique contribution is to develop products that maximize clinical effect, and after that, Hovione takes over with their technological and industrial expertise and regulatory compliance. We will really be able to save our clients quite a lot of time.”

Hovione is an international company with over 50 years’ experience in API development and compliant manufacture. With four FDA-inspected sites in the US, China, Ireland, and Portugal, the company focuses on the most demanding customers, in the most regulated markets. Particle Sciences Inc is an integrated provider of drug development services, utilizing a broad suite of drug delivery technologies to address a diverse range of challenges. With special expertise in particulate-based formulations and drug/device combination products, it has become a leader in drug delivery development.

Evonik Degussa Provides Pharmaceutical Melt Extrusion Technology Services

Evonik Degussa Corporation recently announced the purchase of a Leistritz Nano 16-mm (TSE) Twin Screw Extruder to serve the growing number of customers using pharmaceutical melt extrusion technology. Installed at the Evonik Pharma Polymers Technical Lab in Piscataway, NJ, the new extruder is equipped with a micro-plunger feeding system and precision T-12 K-Tron top feeder. The TSE tackles solubility and bioavailability issues of poorly soluble drug substances, taste-masking, controlled/sustained release, and continuous manufacturing applications.

Twin screw extruders have become the industry standard in the manufacture of pharmaceutical products from feasibility to commercial scale.

“At early stages of melt extrusion formulation development of new molecular entities with limited drug availability, it is essential to use extrusion equipment for the smallest batch size,” said Dr. Firouz Asgarzadeh, Senior Technical Manager of Pharma Polymers business line. “The current set allows 30 g to several kg pharmaceutical in melt extrusion batch manufacturing.”

Evonik Pharma Polymers, a business line of Evonik Degussa Corporation, manufactures EUDRAGIT® acrylic functional polymers, used for immediate-release, enteric, sustained-release, taste-masking, and protective formulations.

Throughout the past 12 years, Evonik has built a network of global centers of excellence for pharmaceutical melt extrusion and spray-drying to help customers develop formulations for poorly soluble drugs via MemFis (Melt Extrusion Modeling & Formulation Information System), lab trials, and cGMP clinical supplies. Evonik Pharma Polymers provides full formulation development services for melt extrusion of drug substances with appropriate (EUDRAGIT or Non-EUDRAGIT) polymers.

“The market trend is to make molecular entity drugs more bioavailable,” said Yann d’Herve, Business Director North America of Pharma Polymers business line. “This latest addition to our state-of-the-art lab provides pharmaceutical formulators access to the latest new platform technology and a means to develop pharmaceutical melt extrusion formulations to bring drugs to the marketplace in a faster and more cost efficient way.”

Evonik is the creative industrial group from Germany. In its core business of specialty chemicals, it is a global leader. In addition, it has energy and residential real estate operations, and its performance is shaped by creativity, specialization, reliability, and continuous self-renewal. Evonik is active in over 100 countries around the world.

Pulmatrix Shows iSPERSE Effectively Delivers Doses of Multi-Drug Formulations

Pulmatrix recently announced that data relating to the preclinical efficacy and multi-drug formulation and delivery capabilities of the company’s novel iSPERSE inhaled dry powder drug delivery platform were presented at poster sessions on June 19 and 21, 2011, at The International Society for Aerosols in Medicine (ISAM) in Rotterdam, Netherlands. iSPERSE is a novel dry powder platform that uses certain proprietary cationic salts at tailored ratios to enable delivery of small or large molecule drugs via inhalation for local or systemic applications.

At ISAM, in a poster titled A Novel Inhaled Dry Powder Delivery Platform; Efficacy of Fluticasone and Salmeterol During Allergic Asthma, preclinical data on the iSPERSE platform highlighted the potential of this novel technology to support the effective delivery of a two drug iSPERSE formulation that underscores the uniqueness of the platform across a range of patient populations. The iSPERSE platform offers the potential to enable the aerosol delivery of small molecule drugs, drug combinations (including triple drug combinations or higher), and macromolecule drugs (ie, proteins, peptides, etc) at therapeutically relevant doses well in excess of those achievable by traditional dry powder lactose blend technologies.

“These data, as well as other studies we have conducted, clearly underscore the unique and compelling potential of our proprietary iSPERSE platform to create novel dry powder formulations for inhaled drug delivery for local and systemic therapeutic applications,” said Michael Lipp, PhD, Vice President of Development and Intellectual Property at Pulmatrix. “iSPERSE formulations have been shown to exhibit desirable properties, including high density and high dispersibility, that can lead to reliable inhaled drug dose delivery across a wide range of relevant flow rates. Additionally, the iSPERSE platform can support the inhaled delivery of single or combination drug formulations as well as a greater capacity to accommodate higher drug loadings and larger drug molecules than conventional inhaled technologies.”

In the data presented by Pulmatrix at ISAM, two mouse models of allergic asthma, the ovalbumin (OVA) model and house dust mite (HDM) model, were used to show the utility of Pulmatrix’s iSPERSE platform using a well-described inhaled combination, a long-acting bronchodilator, salmeterol xinafoate (SX), and a corticosteroid, fluticasone proprionate (FP). In these studies, animals inhaled FP/SX treatment or placebo by whole body exposure prior to allergen challenge (OVA or HDM). Specific airway resistance was determined by dual chamber plethysmography and was collected at baseline and during methacholine (MCh) challenge following the final iSPERSE-enabled dry powder treatment. Specific airway resistance values were decreased (33% on average) across the range of MCh challenge in both allergen models. To evaluate the effect of the corticosteroid, animals were treated with SX/FP (SX at 2.0% w/w / FP at 13.5% w/w), which resulted in decreased total inflammatory cells marked by reduced eosinophilia assessed by bronchoalveolar lavage. These data highlight the potential efficacy of iSPERSE as a novel dry powder delivery technology platform, as aerosol delivery of SX/FP demonstrated reduced inflammation and airway hyperreactivity.

With completion of comprehensive proof-of-concept validation of the iSPERSE platform along with extensive initial patent filings, Pulmatrix is now advancing a select number of proprietary iSPERSE drug candidates as well as actively pursuing iSPERSE partnerships with pharmaceutical companies to create novel therapeutics.

iSPERSE is a novel inhaled dry powder delivery platform developed by Pulmatrix for use in the delivery of drugs via inhalation for local or systemic applications. iSPERSE uses proprietary cationic salt formulations to create a robust and flexible platform that can accommodate low or high drug loads in highly dispersible particles, yielding drug delivery capabilities not feasible with conventional dry powder technologies that rely on the use of lactose blending or low-density particles. The properties of iSPERSE have meaningful therapeutic and patient benefits, including the potential for single formulations with multiple drugs, effective inhaled drug delivery to patients with normal or impaired lung function, and the use of simple and convenient inhaler devices. iSPERSE offers the potential of a strong safety profile, as, in addition to drug and drug molecules, iSPERSE dry powders comprise exclusively generally regarded as safe (GRAS) salts and small quantities of additional, safe excipients if needed. iSPERSE powders are made via a straightforward, proven one-step spray-drying process capable of high and consistent yields.

Pulmatrix is a clinical stage biotechnology company discovering and developing a new class of therapies for the prevention, treatment, and control of respiratory diseases. Pulmatrix’s lead proprietary therapies, called inhaled cationic airway lining modulators (iCALM), are a novel approach to prevent and treat acute exacerbations and improve lung function in patients with chronic respiratory diseases. iCALM therapies have broad potential to treat and prevent a wide range of respiratory diseases, including respiratory infections, such as influenza; ventilator associated pneumonia (VAP), and respiratory syncytial virus (RSV), as well as progressive or chronic respiratory diseases, such as COPD, asthma, and cystic fibrosis. For additional information about the company, visit www.pulmatrix.com.

Oxygen Biotherapeutics Approved to Expand Trials for Traumatic Brain Injury

Oxygen Biotherapeutics, Inc. recently announced it has received approval by the Drug Controller General of India to conduct its traumatic brain injury Phase IIb clinical trials known as STOP-TBI. Oxygen Biotherapeutics believes adding clinical investigators in India to its existing clinical sites in Switzerland and Israel will enable the company to conclude the study faster and more economically. The next cohort is expected to begin in the second half of fiscal year 2012.

Dr. Tim Bradshaw, Executive Vice President of Clinical Development at Oxygen Biotherapeutics, believes the addition of India to its existing clinical sites in Switzerland and Israel is an important step in the clinical development plan for Oxycyte(R) PFC. “Traumatic brain injury is a leading cause of mortality and morbidity in India with an estimated incidence of 150 per 100,000. In the city of Bangalore alone, nearly 10,000 individuals sustain brain injury and more than 1,000 die every year. Expanding our trial into countries such as India will help us to accelerate completion of the study.”

“We are pleased that we received this approval and look forward to working with our new clinical sites,” added Chris Stern, Chairman and Chief Executive Officer of Oxygen Biotherapeutics. “Currently, we are exploring whether to amend the protocol to include patients with milder forms of TBI, and we are developing the processes for manufacturing cGMP Oxycyte PFC for the study. In addition, we are seeking a partner to help us execute the remaining aspects of this trial because we believe that makes strategic sense and is in the best interest of our shareholders and patients.”

The STOP-TBI study is a double-blind, placebo controlled dose-escalation study designed to evaluate the safety, efficacy, and dosing parameters of Oxycyte PFC, a novel perfluorocarbon emulsion that is given intravenously to traumatic brain injury patients. The study’s first cohort has been completed and the database has been locked.

Headquartered in Morrisville, NC, Oxygen Biotherapeutics, Inc. is developing medical and cosmetic products that efficiently deliver oxygen to tissues in the body. The company has developed a proprietary perfluorocarbon (PFC) therapeutic oxygen carrier that is being formulated for both intravenous and topical delivery.

Alliqua Expands Patent Portfolio for Transdermal Drug Delivery Platform

Alliqua, Inc., an advanced biomedical products company focused on the development and manufacturing of proprietary drug delivery and liver health technologies, recently announced it has filed a provisional patent application with the US Patent and Trademark Office to enhance its transdermal delivery technology. The filing was based on positive test results with respect to specific chemical agents that improved the delivery of active ingredients when used in conjunction with the company’s hydrogel drug delivery platform. The patent application is directed to specific formulations that management believes will enhance the performance of its platform.

“This patent filing is the second in a series of filings that we hope to continue as we develop additional improvements and processes,” said David Stefansky, Chairman of Alliqua, Inc. “These filings are a meaningful step in building our intellectual property portfolio, strengthening our drug delivery platform position, and in increasing shareholder value.”

Alliqua, Inc., is an advanced biomedical products company focused on the development and manufacturing of proprietary technologies in the fields of drug delivery, advanced wound care, and liver health preservation. Through its wholly owned subsidiary, Alliqua BioMedical, Inc., Alliqua intends to develop active ingredient and transdermal drug delivery products, primarily utilizing the proprietary hydrogel technology platform of AquaMed Technologies, Inc., Alliqua’s subsidiary.

AquaMed manufactures custom hydrogels used for transdermal drug delivery, wound care, medical diagnostics, and cosmetics. These products use proprietary manufacturing technologies that enable AquaMed to produce what is known in the healthcare industry as high water content, electron beam cross-linked aqueous polymer sheet hydrogels. AquaMed believes that it is one of two manufacturers in the world for these gels. Alliqua’s third subsidiary, HepaLife Biosystems, Inc., focuses on the development of a cell-based bioartificial liver system, known as HepaMate.