Industry Update: the Latest Developments in Therapeutic Delivery

Abstract

The present Industry Update covers the period 16 April–15 May 2012, which included the announcement of a major partnership between Merck & Co., and Endocyte for development of the latter‘s folate-conjugated vinca alkaloid chemotherapeutic in a variety of folate receptor-expressing cancers. The deal includes the rights to a companion diagnostic imaging agent. Alnylam announced positive results from two of its siRNA clinical programs using a lipid nanoparticle delivery system. A number of players in the delivery space announced completion of successful funding rounds, including Egalet, Eleven, miRagen and Sutro, with over US$70 million raised. In addition cancer stem cell player, OncoMed, announced plans for a $115 million initial public offering. Israel-based Prolor shared plans to raise $32.5 million to help fund continued development of its long-acting hGH product candidate, for which positive Phase II data were announced.

Business development

Acquisitions & mergers

Royal DSM Acquisition of Kensey Nash

Royal DSM (Heerlen, The Netherlands) announced that it would acquire Kensey Nash (PA, USA) for US$337 million. Kensey Nash, which manufactures medical device parts for cardiology and orthopedic uses, will add to DSM‘s new technology pipelines in regenerative medicine and tissue engineering, and strengthen its market position in polymers and drug-delivery materials [1].

Collaborations

Novo Nordisk & Caisson

Novo Nordisk (Bagsvaerd, Denmark) signed a $100 million deal with Caisson Biotech, LLC (OK, USA) for exclusive rights to its heparosan-based HEPtune™ technology. HEPtune is under development as a conjugation alternative to PEG [2]. The technology is based on the work of Paul DeAngelis at the University of Oklahoma Health Sciences Center (OK, USA), and was funded by Emergent Technologies, Inc. (TX, USA).

Merck & Endocyte

Merck & Co., Inc. (NJ, USA) signed a deal with Endocyte (IN, USA) for global rights to EC145 (vintafolid), a folate-conjugated vinca alkaloid chemotherapy. Upfront and milestone payments could total $1 billion. EC145 targets rapidly growing cancer cells expressing the folate receptor, including ovarian, non-small-cell lung, breast, colon and kidney cancers. The agreement includes a license to EC20, Endocyte‘s companion diagnostic imaging agent, which helps identify cells that are folate-receptor positive [3,4].

Silence, Quark & Pfizer

Silence Therapeutics (London, UK) and its partner Quark (CA, USA) both announced that their agreement with Pfizer (NY, USA) was amended to include a Phase IIa clinical study to assess PF-655, an siRNA therapeutic incorporating Silence‘s AtuRNAi technology, in patients with moderate and advanced open-angle glaucoma. PF-655 was sublicensed to Pfizer by Quark in 2006. PF-655 is also under evaluation for treatment of diabetic macular edema. Silence stands to receive up to $120 million through the licensing agreements, while Quark could net as much as $165 million [5].

Marina & Monsanto

Marina Biotech (WA, USA) announced an exclusive licensing agreement with Monsanto (MO, USA) providing the latter access to Marina‘s chemistry and delivery technologies. Terms of the agreement were not announced. Subsequently, Marina disclosed on 1 June 2012 that it would shut down the majority of its operations due to lack of funding [6].

IPO & other funding milestones

Egalet

Egalet Ltd (PA, USA) announced completion of a Series B financing, raising $14.3 million and adding CLS Capital to its original team of Atlas, Omega, Sunstone Capital and Index Ventures. Egalet is a specialty pharmaceutical company developing a proprietary abuse-resistant drug-delivery technology for opioids [7].

Eleven Biotherapeutics

Eleven Biotherapeutics (MA, USA) added $20 million to its Series A financing, bringing the total to $45 million, with the addition of JAFCO to an original syndicate of Third Rock and Flagship. The company is developing an IL-1 receptor antagonist, EBI-005, as a topical treatment for dry eye and other surface inflammatory disorders. EBI-005 is based on Eleven‘s AMP-Rx technology platform for protein optimization [8].

Mersana Therapeutics

Mersana Therapeutics (MA, USA) announced that it added $4 million to a previously disclosed debt financing round. The funds will be used to advance the application of Mersana‘s Fleximer^® technology to antibody–drug conjugates. Mersana had previously announced a collaboration with Endo Pharmaceuticals (PA, USA) to develop antibody–drug conjugates using Fleximer [9].

miRagen

miRagen Therapeutics (CO, USA) announced completion of a Series B financing for development of its miRNA-based therapeutics for treatment of cardiovascular and muscle diseases. The financing was led by Remeditex Ventures, LLC, which joined miRagen‘s existing syndicate of Atlas Ventures, Boulder Ventures, Amgen Ventures and Broadview Ventures [10].

OncoMed Pharmaceuticals

OncoMed (CA, USA) announced it is preparing for an initial public offering to raise $115 million to fund its continued work on cancer stem cell therapies. Since its 2004 founding, the company has raised $187 million in equity, in addition to $112 million through funded collaborations [11].

RXi spin out from Galena

RXi Pharmaceuticals Corp. (MA, USA) completed its spin out from Galena Biopharma Inc. (OR, USA). RXi was originally founded in Worcester (MA, USA) by Craig Mello of the University of Massachusetts Medical School (MA, USA) to focus on RNAi technology. The company changed its name to Galena, moved its headquarters and adopted a new focus on cancer. The newly spun out RXi will continue to work on RNAi [12].

Sutro

Sutro Biopharma (CA, USA) announced completion of its Series C financing, with the addition of $16.5 million in the form of a second tranche. The financing was led by Skyline, with participation of Lilly Ventures, Amgen Ventures, SV Life Sciences and Alta Partners. The company is focused on development of next generation antibody–drug conjugates and bispecific antibodies. The company previously announced an agreement with Pfizer (NY, USA) to work on peptide-based drugs. Sutro has raised approximately $60 million since its 2003 founding [13].

To-BBB

To-BBB (Leiden, The Netherlands) announced that it received funding from the Michael J Fox Foundation (NY, USA) to support preclinical development of 2B3–201, a brain-targeted liposomal formulation of methylprednisolone. The formulation is under investigation for treatment of neuroinflammation in Parkinson‘s disease [14].

Regulatory news & approvals

pSivida‘s Iluvien^® approved in the UK

pSivida (MA, USA) announced that its injectable sustained-release intravitreal insert, Iluvien^®, was approved in the UK for treatment of chronic diabetic macular edema. The insert, which incorporates fluocinolone acetonide for delivery up to 36 months, is licensed to Alimera Sciences, Inc. (GA, USA). Iluvien is expected to be available in the EU by the end of 2012 [15].

SkyePharma Flutiform^® receives favorable ruling

SkyePharma (London, UK) announced that the European Medicines Agency‘s Committee for Medicinal Products for Human Use issued a recommendation for the approval of Flutiform^®. Approval of the drug, a combination of corticosteroid fluticasone propionate and formoterol fumarate, a long-acting β2-agonist, is expected within months. The asthma treatment, which utilizes SkyePharma‘s SkyeDry™ technology with a single aerosol inhaler, has been under development since 2004 and is partnered with Mundipharma International (Cambridge, UK) for distribution throughout Europe and other territories [16].

Clinical trials

Alexza‘s Adasuve™ receives setback

Alexza Pharmaceuticals (CA, USA) announced that it received a complete response letter from the US FDA for Adasuve™, its rapidly-acting inhaled formulation of the antipsychotic loxapine. Approval of the product was denied due to manufacturing deficiencies pertaining to the device used to administer the product. The product application was refiled in 2011 with additional data addressing safety concerns previously raised by the FDA [17].

Alnylam Phase I results for ALN-PCS & ALN-TTR01

Alnylam Pharmaceuticals (MA, USA) announced results from a Phase I study of ALN-PCS, an RNAi therapy for treatment of severe hypercholesterolemia. The product candidate targets PCSK9 using the company‘s next-generation lipid nanoparticle delivery system. The study met primary endpoints of safety and tolerability. In addition, a single dose of ALN-PCS resulted in reductions of PCSK9 of up to 84% and reduced low-density lipoprotein cholesterol by up to 50% [18,19].

Separately, Alnylam presented final results from its Phase I evaluation of ALN-TTR01, an RNAi-based therapy targeting TTR for treatment of TTR-mediated amyloidosis. The therapy uses the company‘s first-generation lipid nanoparticle delivery system, in a partnership with Tekmira Pharmaceuticals (BC, Canada). ALN-TTR01 was found to be generally safe and well tolerated, and knockdown of TTR was found to be rapid and dose-dependent after a single dose. The company anticipates a potential for monthly or bimonthly dosing in future studies. Alnylam plans to initiate clinical studies of TTR02, which uses its second-generation delivery lipid nanoparticle technology with improved potency, in the third quarter of 2012 [20].

Genentech‘s Actemra^® meets endpoint

Genentech (CA, USA), a unit of the Roche Group (Basel, Switzerland), announced that a study of a subcutaneous (SC) formulation of Actemra^® (tocilizumab) met its primary endpoint. Actemra is a humanized IL-6 receptor-inhibiting monoclonal antibody approved for the treatment of rheumatoid arthritis. A 162 mg weekly SC dose of Actemra was compared with an 8 mg/kg intravenous dose every 4 weeks. The study is part of a broader effort by Roche to transition its biologics to more easily administered SC formulations [21,22].

Prolor Biotech Phase II results for long-acting hGH

Prolor Biotech (New-Ziona, Israel) announced results from a 4-month treatment extension of its Phase II clinical evaluation of hGH-CTP, a long-acting version of hGH. The study, which was conducted in GH-deficient adults, confirmed prior Phase II results with single weekly administration by injection. The protocol involved dosing adjustments based on a patient‘s IGF-1 levels, which were monitored regularly. The dosing regimen will be used in an upcoming Phase III study. The product candidate uses Prolor‘s carboxyl terminal peptide technology, discovered by Irving Boime of Washington University (MO, USA). Carboxyl terminal peptide is a small peptide naturally occurring in the body that provides longer circulating half-life when attached to other proteins. Long-acting versions of Factor VIIa, Factor IX and a GLP-1/glucagon dual receptor agonist peptide are all under development. Prolor separately announced plans to raise $32.5 million through sale of stock to fund its development programs [23,24].

Patents

BioDelivery Sciences

BioDelivery Sciences (NC, USA) announced that the US Patent and Trade Office granted its patent, US8147866, which covers its BioErodible MucoAdhesive (BEMA^®) products. The patent‘s issuance triggers a $15 million milestone payment from partner Endo Pharmaceuticals (PA, USA), associated with a license agreement for a transmucosal form of buprenorphine using the technology [25].

Novel lipids & targeting approaches for siRNA delivery & peptide conjugates

The coverage period saw publications of patent applications pertaining to lipid-mediated delivery of siRNA and other oligonucleotides, as well as peptide conjugates for oral delivery. Two applications covering novel lipids for siRNA delivery from Merck & Co., Inc. (NJ, USA) were published [101,102]. The claimed structures include lipids with at least one short lipid chain and those with cyclic amine-containing head groups, with benefits of enhanced delivery efficiency and tolerability in vivo. The Instituto Giannina Gaslini (Genova, Italy) applied for a patent covering lipid-based formulations containing siRNA with targeting agents directed against disialoganglioside GD₂, a tumor-associated membrane antigen. Delivery of siRNA against ALK was disclosed [103]. Aegis Therapeutics LLC (CA, USA) applied for a patent covering its alkyl-glycoside-conjugated peptides for increased oral bioavailability [104].

Financial & competing interests disclosure

P Burke is Principal of Burke Bioventures LLC, 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 share holder 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.