Industry Update: the Latest Developments in Therapeutic Delivery

Abstract

The present industry update covers the period 16 February–15 March 2012, which included the announcement of two large deals in the drug conjugation space – Mersana partnered its Fleximer technology with Endo for application to antibody drug conjugates, and Angiochem partnered with GlaxoSmithKline for application of its LRP-1 receptor-targeting technology to lysosomal storage diseases. Two Boston, MA, USA-area start-ups reached early funding milestones: 4s3 Bioscience, developing an antibody-based system for enhanced intracellular delivery of proteins, closed a US$20 million Series A round, while Kala Pharmaceuticals, developing a mucus-penetrating particle technology, completed a US$11.2 million seed round. Organogenesis‘ cell-based mucogingival therapy and Discovery Labs‘ synthetic peptide-based pulmonary surfactant received product approvals. Endocyte announced plans to submit marketing applications for its folate-receptor targeting-based diagnostic and therapy for ovarian cancer.

Business development

Acquisitions & mergers

Flamel acquires Éclat

Drug-delivery concern, Flamel Technologies (Lyon, France), announced its purchase of Éclat Pharmaceuticals LLC (St. Louis, MO, USA), a speciality pharmaceutical company focused on the development, approval and commercialization of niche brands and generic products. Éclat Pharmaceuticals was previously an affiliate of Deerfield Capital L.P. – Flamel‘s largest shareholder. The deal includes Éclat‘s one marketed product, Hycet^® (hydrocodone acetaminophen oral solution), a prescription pain medication, in addition to products in various stages of development. Éclat‘s founder and CEO, Mike Anderson, has become CEO of Flamel, following the resignation of Steve Willar from this position [1].

Shire to buy FerroKin

Shire plc (Dublin, Ireland) announced its intention to buy startup FerroKin BioSciences, Inc. for an upfront payment of US$100 million plus milestones of up to US$225 million [2]. FerroKin‘s lead product candidate, FBS0701, is an orally bioavailable iron chelator for treatment of iron overload due to chronic blood transfusions, formulated as a once-daily capsule. The product, which has been designated an orphan product by the US FDA and the European Medicines Agency is currently in a Phase II clinical trial. The company, operating virtually with headquarters in the San Carlos (CA, USA)-based house of its founder and CEO, had raised a total of US$27 million to fund its activities [3].

Collaborations

Angiochem & GlaxoSmithKline

Angiochem (Montreal, Canada) announced a new collaboration with GlaxoSmithKline (GSK; Brentford, UK) to discover, develop and commercialize treatments of lysosomal storage diseases using the former‘s EPiC technology for enhancing blood–brain barrier penetration for the restoration of enzyme function in the CNS. Angiochem will receive up to US$31.5 million in upfront cash, research funding and other fees, with eligibility to receive over US$300 million during the collaboration [4].

Current therapies are administered intravenously and considered to act peripherally but not centrally, limiting their efficacy. Angiochem‘s technology is based on drug conjugation to a peptide binding to the LRP-1 receptor for transport across the blood–brain barrier, and claims to have shown proof-of-concept in mice. The GSK deal is Angiochem‘s first in the rare disease space [5].

Critical Pharmaceuticals & Nottingham

Critical Pharmaceuticals (Nottingham, UK) announced a GB£545,000 collaboration with the University of Nottingham for the development of a nanotechnology-enabled intranasal formulation of teriparatide for the treatment of osteoporosis. Teriparatide is currently administered as a daily injection. Funding for the project comes from the Technology Strategy Board (Swindon, UK) and the Engineering and Physical Sciences Research Council (Swindon, UK), as part of their investment in nanotechnology in healthcare [6].

Marina & ProNAi

Marina Biotech, Inc. (Bothel, WA, USA) announced an exclusive licensing agreement with privately-held ProNAi (Ann Arbor, MI, USA) for the development and commercialization of DNAi therapies using Marina‘s Smarticles^® liposomal-delivery technology. Under the agreement terms, Marina could receive up to US$14 million in milestone payments for each gene target, as well as royalties on sales [7]. The Smarticles technology, based on charge-reversible, amphoteric liposome carriers, was acquired by Marina from Novosom (Halle, Germany) in July 2010. ProNAi, which originally licensed the technology from Novosom in 2007, is evaluating drug candidate PNT2258 in a Phase I clinical trial in advanced solid-tumor patients, with results expected to be reported by the end of 2012. PNT2258 targets the bcl-2 oncogene using the Smarticles technology. The DNAi silencing approach targets genomic sequences in noncoding regions, disrupting transcription. The formulation is administered as a daily intravenous infusion [8,9].

Medicago & Mitsubishi Tanabe Pharma

Medicago Inc. (Quebec City, Canada) announced an alliance with Mitsubishi Tanabe Pharma Corp. (Osaka, Japan) for the development of vaccines based on the former‘s proprietary plant-based virus-like particle technology. Medicago will receive an initial upfront payment of C$3 million, with an initial focus on a rotavirus vaccine. The partnership is expected to include at least three new vaccines, with milestones potentially totaling up to C$33 million [10].

Mersana & Endo

Mersana Therapeutics (Cambridge, MA, USA) announced a collaboration with Endo Pharmaceuticals (Chadds Ford, PA, USA) to develop next-generation antibody–drug conjugates using Mersana‘s proprietary Fleximer^® polymer and customizable linker chemistry technologies. Mersana is responsible for creating antibody–drug conjugates with Endo‘s novel antibodies, with the potential for a total of three targets and over US$270 million in milestones plus royalties on sales of any resulting products [11].

Syneron & TransPharma

Syneron (Yokneum, Israel) announced that it acquired the assets of transdermal player TransPharma Medical Ltd. (Lod, Israel). TransPharma‘s RF-MicroChannel™ technology creates microscopic channels across the skin, for the delivery of drugs and to stimulate skin rejuvenation. The technology was previously evaluated for the delivery of Eli Lilly‘s (Indianopolis, IN, USA) osteoporosis drug, Forteo^®, as well as in a Phase Ia study of a GLP-1 agonist [12]. Syneron paid US$3.6 million for the assets and plans to use the technology for local administration of cosmetics and drugs [13].

Xenogenics & Rutgers

Xenogenics Corp., a subsidiary of MultiCell Technologies, Inc., (Canton, MA, USA) announced that it obtained exclusive rights to patented polyanhydride technology developed at Rutgers University (New Brunswick, NJ, USA). The technology involves conjugation of low-molecular-weight drugs to the polyanhydride. The company plans to apply the technology to its coated cardiac stent business [14].

IPO & other funding milestones

4s3 Bioscience

Privately-held 4s3 Bioscience, Inc. (Medford, MA, USA) announced closing of a US$20 million Series A financing with KLP Enterprises, whose subsidiary Alopexx Enterprises will work with 4s3 to build and manage the company. The 4s3 platform, based on technology licensed from the University of California (CA, USA), is an antibody-based system for enhanced intracellular delivery of proteins. According to the firm‘s website, intracellular delivery is dependent on membrane expression of a nucleoside transporter, ENT2, which is naturally enriched in skeletal muscle fibers and elevated in certain cancers. Myotubular myopathy and myotonic dystrophy are two areas of planned focus [15,16].

Kala

Kala Pharmaceuticals, Inc., (Waltham, MA, USA) focused on treatment of mucosal diseases, announced that it raised US$6.2 million to complete its seed financing, which totaled US$11.2 million. Kala‘s proprietary mucus-penetrating particle technology is reported to result in uniform distribution of drug-loaded particles in mucus, leading to enhanced local delivery with reduced systemic exposure. The technology was licensed from the Johns Hopkins University (Baltimore, MD, USA) laboratory of Justin Hanes, a Kala cofounder [17].

Nektar

Nektar Therapeutics (San Francisco, CA, USA) announced that it agreed to sell its royalties on future sales of PEGylated products, CIMZIA^® and MIRCERA^®, to Royalty Pharma (New York, NY, USA) for an aggregate cash payment of US$124 million. Proceeds were designated for the repayment of convertible debt. For the 12-month period that ended on 31 December 2011, aggregate royalties from net sales of the two products totaled US$8.3 million [18].

Tarsa

Tarsa Therapeutics (Philadelphia, PA, USA)raised US$28 million in a second-round financing, in support of its development of an oral tablet formulation of calcitonin for treatment of postmenopausal osteoporosis. The drug is licensed from Unigene Laboratories (Boonton, NJ, USA). Tarsa reported Phase III data for the formulation in 2011, and announced that it plans to file a new drug application for the drug (Ostora™), later in 2012 [19].

Regulatory news & approvals

Autoinjector approved for Biogen-Idec‘s Avonex

The FDA announced the approval of Biogen-Idec‘s (Weston, MA, USA) Avonex^® Pen™, the first intramuscular autoinjector for treating multiple sclerosis. The autoinjector incorporates a smaller needle than the currently available prefilled syringe. In a separate announcement, Biogen-Idec also announced that it filed a new drug application for BG-12, an oral multiple sclerosis treatment [20,21].

Discovery Labs wins approval for Surfaxin^®

The FDA-approved Discovery Laboratories Inc.‘s (Warrington, PA, USA) Surfaxin^® (lucinactant) for the prevention of respiratory distress syndrome in premature infants. The product, first filed for approval in 2004, had previously experienced setbacks including those related to shelf stability. Surfaxin is the first synthetic peptide-containing surfactant for neonatal use, providing an alternative to animal-derived surfactants. The product will compete with Abbott Pharmaceuticals‘ (Abbott Park, IL, USA) Survanta^®, among other respiratory distress syndrome drugs [22,23].

Endocyte

Endocyte, Inc. (West Lafayette, IN, USA), a developer of targeted small-molecule drug conjugates, announced the company will submit conditional marketing authorization applications for EC145 and EC20 for treatment of patients with folate-receptor-positive platinum-resistant ovarian cancer. EC145 is a conjugate of the vitamin folate and a highly potent vinca alkaloid. EC20 is a folate-targeted molecular imaging agent under development as a noninvasive method for identification of tumors overexpressing folate receptors. Both the EC145 therapeutic and the EC20 diagnostic imaging agent have been granted orphan drug status by the European Commission. The applications are planned for the third quarter of 2012 [24].

Organogenesis cell-based mucogingival product approved

Organogenesis (Canton, MA, USA) announced the FDA approval of Gintuit™, a cell-based product for generation of new gum tissue. Gintuit is a sheet containing human fibroblasts, keratinocytes, human extracellular matrix proteins and bovine collagen. The cells produce a wide array of cytokines, and growth factors are important for tissue healing and regeneration. Organogenesis expects that Gintuit will be commercially available beginning in the summer of 2012 [25].

Clinical trials

Anaeropharma & Eisai

Anaeropharma Science (Tokyo, Japan) reported that it will soon begin clinical testing in the USA of its bifidobacteria-based injectable cancer therapy. The anaerobic bacterium is reported to proliferate in the oxygen-depleted solid tumor environment; subsequent oral administration of anticancer agents resulted in fewer side effects in animal studies. The company, which was founded by professors at Shinshu University (Matsumoto, Nagano, Japan), received funding from the public–private partnership Innovation Network Corporation of Japan (Tokyo, Japan), which plans to invest up to JP¥2.2 billion (US$27 million) to fund clinical testing. The project is partnered with Eisai (Tokyo, Japan) [26,27].

EyeGate

EyeGate Pharmaceuticals (Waltham, MA, USA) reported results from a Phase III multicenter evaluation of their iontophoresis-based device for delivery of dexamethasone to the antechamber of the eye for treatment of dry eye. The device is attached to the forehead followed by a 3-min dosing period. Dexamethosone, which is already approved as a topical therapy for dry eye, is reportedly delivered with greater efficiency using the device. The treatment was reported to be both safe and efficacious in a presentation at the World Ophthalmology Congress 2012, held in Abu Dhabi, UAE [28].

MicroCHIPS

MicroCHIPS (Waltham, MA, USA) announced results from their first human clinical trial using their implantable, wirelessly controlled microchip-based drug-delivery device. The study involved administration of daily doses of the marketed osteoporosis drug teriparatide (Forteo) through microchip delivery, rather than by daily injection. The study occurred over a 1-month period and, according to the company, the results support device viability for 12 months or more of continuous therapy [29].

Viropharma & Halozyme

ViroPharma Inc. (Exton, PA, USA) and Halozyme Therapeutics (San Diego, CA, USA) announced positive data from the former‘s Phase II trial of Cinryze^®, a C1 esterase inhibitor, in combination with the latter‘s Enhanze™ technology in patients with hereditary angioedema. Enhanze uses Halozyme‘s recombinant human hyaluronidase for improved subcutaneous delivery of biologics. The study was concluded to show that subcutaneous coadministration of Cinryze with recombinant human hyaluronidase was easy to administer and well tolerated, providing sustained, physiologically relevant concentrations of the drug [30].

Financial & competing interests disclosure

P Burke is Principal of Burke Bioventures LLC (www.burkebioventures.com), providing consultancy and advisory services to pharmaceutical and biotechnology companies, including those working in the drug-delivery space. Current and ongoing clients cannot be named for confidentiality reasons but may be featured in industry news stories covered. The author is a shareholder in Pfizer Inc. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.