Your search found 4 records.

Company focus: Drug Development

Company focus: Diagnostics

Company focus: Enabling Technology

Doug Fambrough, PhD, CEO Martin D. Williams, SVP and CBO Roberto Guerciolini, MD, SVP-Pharmaceutical Development Bob D. Brown, PhD, SVP-Research
480 Arsenal Street, Building 1, Suite 120
Watertown, MA 02472 USA
Tel: 614-621-8097
Website: http://www.dicerna.com/

Profile
(Private) Drug development • Enabling technology
Dicerna Pharmaceuticals is a venture-backed biopharmaceutical company developing novel therapeutic agents in multiple therapeutic areas based on its proprietary Dicer Substrate Technology, which triggers RNA interference (RNAi) in a potent and specific manner. Dicerna was founded by Jim Jenson, Doug Fambrough and Roberto Guerciolini based on technology developed by Dicerna’s two scientific co-founders, John Rossi, PhD, and Mark Behlke, MD, PhD. Dicerna’s pipeline of RNAi-targeted drugs and delivery systems is focused primarily in the therapeutic areas of oncology and metabolic diseases. In addition to these internal focus areas, Dicerna expects to broadly use its Dicer Substrate Technology in several other therapeutic areas, such as inflammation, immunology, cardiovascular diseases, and others, through collaborations with pharmaceutical and biotechnology companies.

In August 2010, Dicerna Pharmaceuticals closed a $25 million Series B round of financing. New investor Domain Associates led the round, with all existing investors Oxford Bioscience Partners, Skyline Ventures and Abingworth participating in the round.

In July 2008, Dicerna Pharmaceuticals raised $8.4 million to cap off a first round venture funancing totaling $21.4 million.

In November 2007, Dicerna closed a $13 million Series A financing, led by Oxford Bioscience Partners and Skyline Ventures.

Technology
Dicerna's Dicer Substrate Technology was invented by Dicerna co-founders John Rossi, PhD, a Professor in the Division of Molecular Biology and Dean, Graduate School of Biological Sciences at City of Hope's Beckman Research Institute (Duarte, CA), and Mark Behlke, MD, PhD, at Integrated DNA Technologies (Coralville, IA). In the oncology sector, Dicerna is focusing on solid tumor targets that have been elusive in the past decade that are not druggable by conventional methods but are exquisitely amenable to RNAi.

In March 2010, Dicerna Pharmaceuticals and Ipsen entered into an exclusive research collaboration agreement to leverage their expertise in Dicer Substrate siRNA (DsiRNA) research and peptide engineering to develop novel conjugates of Dicerna’s DsiRNA molecules and Ipsen’s peptide targeting vectors in oncology and endocrinology. The aim is to develop new DsiRNA-based therapies with targeted delivery, superior potency and extended duration of action. Both companies will contribute their breakthrough technologies to the joint research collaboration. Dicerna and Ipsen may also collaborate to move the programs discovered under this partnership into development and eventual commercialization.

In January 2010, Dicerna Pharmaceutical and Kyowa Hakko Kirin Co. entered into a collaboration and license agreement for the research, development and commercialization of drug delivery systems and siRNA pharmaceuticals based on Dicerna’s proprietary Dicer Substrate Technology platform for therapeutic targets in oncology. Under the terms of the collaboration, Dicerna will receive $4 million in upfront cash payments including research funding, and up to $120 million in additional research funding, development and commercial milestones for exclusive rights to one target in the field of oncology. According to the progress of the research collaboration, Kyowa Hakko Kirin and Dicerna may expand the scope of the collaboration by adding approximately up to 10 targets under similar terms and may broaden the therapeutic focus of the partnership. Dicerna is entitled to royalty payments on sales from products for these targets. Dicerna also has an option to equally co-promote and profit-share (50:50) in the USA for the initial target.

In July 2009, Archemix and Dicerna Pharmaceuticals entered into an agreement to collaborate on aptamer-DsiRNA therapeutics (see Archemix record).

In March 2009, Dicerna Pharmaceuticals secured the exclusive, worldwide right to grant sublicenses to the Dicer Substrate RNAi (DsiRNA) intellectual property estate in-licensed by Dicerna.

In November 2007, Dicerna Pharmaceuticals licensed broadly enabling intellectual property from City of Hope.

Current as of August 11, 2010

Company focus: Drug Delivery

Marina Biotech (Formerly Nastech Pharmaceutical; formerly MDRNA; acquired Cequent Pharmaceuticals in July 2010)

J. Michael French, CEO Barry Polisky, PhD, CSO
3830 Monte Villa Parkway
Bothell, WA 98021 USA
Tel: 425-908-3600 Fax: 425-908-3650
Website: http://www.marinabio.com/

Profile
(Public NASDAQ:MRNA (FY 12/31)) Drug development • Drug delivery
MDRNA (formerly Nastech Pharmaceutical) is a biotechnology company developing RNAi-based therapeutics. The company's primary focus is on the safe and effective delivery of MDRNAi and siRNA drug candidates for the treatment of a wide range of human diseases, including inflammation, viral infections, cancer and metabolic disorders.

In August 2010, Marina Biotech entered into an Asset Purchase Agreement with Cypress Bioscience under which Cypress will acquire Marina Biotech's patent rights and technology related to to a novel, intranasal formulation of carbetocin, a potential treatment for the core symptoms of autism. Marina Biotech will receive an upfront payment of $750,000 and potential milestone payments up to $27 million in exchange for the asset. Cypress will be responsible for all future development and IP related expenses. In addition, Cypress will pay Marina Biotech royalties on commercial sales.

In July 2010, Marina Biotech acquired Cequent Pharmaceuticals. In March 2010, MDRNA and Cequent Pharmaceuticals signed a definitive agreement pursuant to which MDRNA will acquire Cequent in an all stock transaction valued at approximately $46 million. The transaction will include certain loan provisions that will fund MDRNA operations through the anticipated closing of the merger in July 2010. The merged company is to be named Marina Biotech.

In January 2010, MDRNA entered into a definitive agreement with investors to raise gross proceeds of $5.5 million through a registered direct offering. Under the terms of the agreement, the company will sell 5,385,557 shares of its common stock at $1.02125 per share. As part of the transaction, the investors also will receive warrants, with a 5-year term, to purchase 3,500,612 shares of common stock at an exercise price of $1.00 per share.

In December 2009, MDRNA closed a bridge loan pursuant to a Note and Warrant Purchase Agreement. Under the terms of the loan, the company sold promissory notes in the aggregate principal amount of $1.0 million and issued warrants to purchase an aggregate of approximately 1.1 million shares of the company's common stock at $1.02 per share to certain accredited investors. The loan will become due and payable on February 1, 2010 with interest calculated at 12% per annum and payable on the due date. The loan is to be secured against the assets of MDRNA and its subsidiaries. The warrants are being offered by the company pursuant to an effective shelf registration statement.

In June 2009, MDRNA repaid all of its remaining debt to General Electric Capital under the January 2009 Loan and Security Agreement by retiring a $5.5 million loan created to consolidate its GE Capital leases. The repayment of this loan removes all liens MDRNA's IP, equipment and other assets.

In June 2009, MDRNA entered into definitive agreements with existing investors to raise gross proceeds of $10.5 million though a registered direct offering. Under terms of the agreements, the company will sell 5.25 million shares of its common stock at $2.00 per share. As part of the transaction, the investors also will receive warrants, with a 5 1/2 year term, to purchase 5.25 million shares of common stock at an exercise price of $2.38 per share. The warrants will be exercisable after a 6-month period.

In August 2008, corporate restructuring resulted in a workforce of about 55 from a high of 235 in late 2007.

In June 2008, Nastech Pharmaceutical changed the company's name to MDRNA. MDRNA will leverage its scientific and intellectual property (IP) position surrounding the research, development and delivery of Dicer substrates and 'Meroduplex' (mdRNA) RNA interference (RNAi) drug candidates to build a position in the development and commercialization of RNAi-based therapeutics. Nastech Pharmaceutical was formerly engaged in the research, development, manufacturing and commercialization of nasally administered forms of pharmaceuticals that are currently delivered in oral, injectable or other dosage forms. Nastech began work on RNAi in 2002 and assigned its intellectual property, as it relates to the development of RNA-based therapeutics, to MDRNA, a wholly owned subsidiary of Nastech, in order to bring greater focus on the development of RNA-based technologies and enhance shareholder value arising from this field.

In May 2008, Nastech confirmed it ceased development of its non-RNAi programs, mainly intrabasal delivery projects, after ongoing clinical trials are completed, to concentrate on its RNAi assets.

In April 2008, Nastech Pharmaceutical entered into definitive agreements with new and existing investors to raise gross proceeds of $7,932,500 though a registered direct offering. Under terms of the agreement, the company will sell 4,585,260 shares of its common stock at $1.73 per share. As part of the transaction, the investors also will receive warrants, with a 7-year term, to purchase 4,585,260 shares of common stock at an exercise price of $2.38 per share. The warrants are exercisable beginning October 25, 2008. In addition, the investors have the right to purchase up to 1,375,578 shares of common stock at a price of $2.17 per share during the 90-day period beginning October 25, 2008. If fully exercised, total gross proceeds would be $2,985,005.

In February 2008, Nastech Pharmaceutical's Board of Directors approved a plan to further reduce operating expenses and align the company's workforce with its strategic, business and clinical development requirements.

In December 2007, Nastech Pharmaceutical assigned certain Nastech licenses to third-party IP and Nastech's own intellectual property, as such intellectual property relates to the development of RNA-based therapeutics, to its subsidiary, MDRNA.

In November 2007, Nastech Pharmaceutical decided to move forward with the process of establishing Nastech's wholly owned subsidiary, MDRNA, as an independent company. Nastech is transferring its intellectual property and agreements related to RNA interference (RNAi) into MDRNA. The planned change in corporate structure will enable Nastech to continue its focus on the development of peptide and protein drug delivery technologies while better positioning MDRNA for strategic alliances and direct investment as it develops RNAi therapeutics targeting a broad range of diseases. The establishment of MDRNA as an independent company will also allow it to be better compared and valued relative to other companies in the field of RNAi therapeutics.

In January 2007, Nastech Pharmaceutical completed an underwritten public offering of 3.25 million shares of its common stock which raised net proceeds of approximately $41.0 million. All of the shares were sold by Nastech. UBS Investment Bank acted as sole bookrunner for the offering.

In February 2006, acquired Galenea's RNAi-related intellectual property and technologies, which are largely focused on the development of drugs against influenza. The acquisition includes IP both generated by Galenea and in-licensed from the Massachusetts Institute of Technology (MIT) for the development of RNAi therapeutics against viral respiratory infections including influenza, rhinovirus, and other respiratory diseases, as well as IP related to pulmonary drug delivery.

In August 2005, Nastech announced the pricing of an underwritten public offering of 1.725 million shares of common stock at $13.50 per share. The gross proceeds of the offering are expected to be approximately $23.3 million before underwriting discounts and commission and offering expenses. The offering is being made from a shelf registration statement that became effective on October 8, 2004. All shares are being sold by Nastech. The offering is expected to close on August 30, 2005. Needham & Company, is acting as sole book-running manager in this offering. SunTrust Robinson Humphrey and Delafield Hambrecht are acting as co-managers.

In December 2004, Nastech Pharmaceutical company completed its public offering of 4.25 million shares of common stock at a price of $13.50 per share, with gross proceeds of approximately $57.4 million.

In June 2004, Nastech Pharmaceutical raised $12.5 million through the sale of approximately 1.14 million shares of common stock at a price of $11.00 per share to an institutional investor. The purchase price represents a premium of 15% to the closing price of Nastech's common stock on June 24, 2004, the day prior to the sale. The transaction also includes warrants to purchase initially 511,364 shares of Nastech common stock, subject to adjustment pursuant to the terms of the warrants, at an exercise price of $14.40 per share.

In September 2003, Nastech completed a private placement of equity securities to institutional investors totaling $11.0 million in gross proceeds. The net proceeds will be used for general corporate purposes, including working capital. Lehman Brothers acted as exclusive placement agent for the financing. In the private placement, the company issued 1.513 million shares of common stock and warrants to purchase up to 0.53 million shares of common stock at an exercise price of $11.09 per share. The warrants are exercisable up to and including September 4, 2008.

In October 2001, Nastech completed a private placement of $5.8 million from institutional investors.

In the first quarter of 2001, Nastech raised approximately $4.2 million in gross proceeds through a private sale of 860,000 newly issued shares of its common stock to a select group of investors including Safeco Growth Opportunities Fund and an asset management division of a leading money center bank.

In August 2000, Nastech acquired Atossa Healthcare to strengthen its nasal therapeutics area and also further develop Atossa's breast cancer diagnostic product.

Technology
MDRNA has a broad intellectual property estate that encompasses four key RNAi technology platforms, siRNA constructs, chemistry, nucleic acid delivery, and gene targets. The MDRNA-owned siRNA constructs and chemistry include its proprietary UsiRNA construct, which is a duplex siRNA chemically modified with non-nucleotide acyclic monomers (UNA), and is distinct from the standard siRNA construct used by others in the industry. UsiRNA are fully recognized by the RNAi machinery and provide for potent RNAi activity while specific placement of UNA in a duplex siRNA minimizes potential off-target effects by the guide strand and reduces undesired passenger strand activity. Furthermore, UsiRNA escape the surveillance mechanisms associated with cytokine induction, and provide protection from nuclease degradation.

MDRNA's drug candidates are based on various siRNA constructs such as Dicer substrates and meroduplexes within novel liposome and peptide-based delivery systems to ensure optimal siRNA delivery, activation of the RNAi process, and downregulation of protein expression. Nastech entered the RNAi therapeutics field in early 2004 by obtaining a license to the fundamental Fire-Mello patent. The RNAi program stemmed from the work of Galenea co-founder and MIT researcher Jianzhu Chen who was developing antivirals based on RNAi.

Dicer substrates are synthetic RNA ligonucleotides duplexes comprising 25-27 nucleic acid base pairs that are processed intracellularly by the Dicer enzyme into shorter siRNA strands, i.e. RNA-induced silencing complex (RISC) substrates typically spanning 19-23 base pairs, which then activate the RNAi pathway. Dicer-Substrate technology may enable the development of short interfering RNA (siRNA) with improved pharmacologic properties important for drug development and delivery when compared to conventional, first generation RNAi technology. First generation RNAi technology used siRNA that bypassed the natural process controlled by the Dicer enzyme. These conventional siRNA were typically 21 base pair duplexes. The synthetic Dicer substrates may be 100 times more effective at silencing genes, at lower concentrations than the corresponding conventional 21- base pair duplexes that bypass Dicer and without inducing an interferon response. Dicer substrates are believed to have unique RNAi characteristics including increased efficiency of RNAi activation because Dicer facilitates a 'hand-off' of the substrate directly to the RISC protein complex. RISC substrates are not processed by Dicer and, therefore, would not see this advantage during RNAi activation. Dicer substrates are also amenable to direct conjugation of delivery moieties for targeting to specific cells and tissues. Nastech Pharmaceutical entered into a license agreement with City of Hope for rights to Dicer-substrate RNA interference (RNAi) IP and technology. Nastech obtained exclusive rights to five undisclosed targets selected by Nastech, as well as broad non-exclusive rights to siRNA directed against all mammalian targets subject to certain City of Hope limitations that will have no impact on Nastech's programs.

One of the intermediate steps in RNAi involves the loading of small, siRNA into the RNA RISC. Either strand of the siRNA duplex may assemble into the active RISC complex, and only one strand of the siRNA duplex is incorporated into the RISC while the other strand is degraded and removed. It has been generally accepted that a continuous siRNA duplex is required for efficient RISC assembly. However, MDRNA has shown that siRNA containing a nick or gap in the sense strand, referred to meroduplexes, can also be extremely active in RNAi. The use of these types of siRNA constructs may help eliminate the off-target potential of the sense strand by preventing its loading into RISC.

In the drug delivery area, MDRNA's proprietary DiLA2 Platform creates novel lipids from amino acids, allowing for modifying key aspects the delivery system such as charge, linker and acyl chains to optimize the properties of the liposome for delivery to the target tissue, and is effective and efficient at silencing gene targets in the liver and jejunum. The DiLA2 Platform enables tailoring the charge, linker and acyl chains of amino acids in order to optimize the liposome for delivery to the target tissue of interest. The DiLA2 Platform is also designed to permit attachment of various peptides and other targeting molecules to improve a variety of delivery characteristics. In addition, MDRNA is using peptides for nanoparticle formulations to increase cellular uptake and endosomal release.. Furthermore, the in vivo tolerability of the DiLA2 technology is excellent with no delivery related adverse effects observed in the liver as measured by typical serum chemistries or any significant increases in cytokine levels, indicating cell damage. Also in the drug delivery area, in August 2008, MDRNA signed an exclusive license agreement to intellectual property from the University of Michigan covering cationic peptides for enhanced delivery of nucleic acids. Terms of the agreement were not disclosed. The small cationic peptides covered by the University of Michigan intellectual property are capable of forming stable siRNA nanoparticle complexes, thereby protecting the siRNA while increasing the efficiency and efficacy of the formulations. In addition, they can also enhance endosomal release, an important step in delivering siRNA to their site of action inside cells. Results to date have demonstrated both enhanced knockdown of target proteins in vivo as well as improvement in delivery efficiency.

In January 2010), the State Intellectual Property Office of the People's Republic of China (PRC) granting patent # PRC 200480018784 which includes the use of nucleic acids, e.g., an siRNA, for the treatment of cancer. The patent describes modulation of claudins, which are proteins implicated in tumor progression and metastasis.

In September 2009, the USPTO issued MDRNA a notice of allowance for patent application 11/624,630 covering a siRNA directed against a junctional adhesion molecule-1 (JAM-1) gene. The siRNA of the allowed claim has a broad array of potential applications, most notably as a therapeutic for the treatment of certain malignancies, thrombosis, atherosclerosis, strokes, and hypertension; and enhances the delivery of drugs across the skin and the blood-brain barrier. JAM-1 is a tight junction protein that plays a key role in maintaining epithelial and endothelial barrier functions, leukocyte transmigration and platelet adhesion and also functions as a pro-inflammatory molecule.

In March 2009, MDRNA entered into a licensing agreement with Novartis for MDRNA's liposomal technology platform for siRNA delivery. MDRNA will receive $7.25 million in upfront fees for the nonexclusive license. Additionally, the companies have entered into a separate agreement, which provides Novartis with an exclusive period to negotiate an R&D collaboration and broader licensing rights related to MDRNA's RNAi drug delivery platform. Terms of this separate agreement were not disclosed.

In February 2009, Roche obtained a non-exclusive license to a portion of MDRNA's technology platform for the development of RNAi-based therapeutics. Terms of the agreement were not disclosed.

In October 2008, MDRNA acquired IP related to non-nucleotide chemistry (Unlocked Nucleic Acid) technology from RiboTask, a privately held Danish company specializing in the development and synthesis of novel RNA chemistries. Jesper Wengel, PhD, the Co-founder of RiboTask, and the Director of the Nucleic Acid Center, University of Southern Denmark, is the inventor of the UNA technology. UNA is an acyclic ribonucleoside analog in which the bond between C2' and C3' atoms is broken. This change in sugar structure renders this nucleoside analog very flexible, in sharp contrast to the widely used locked nucleosides (LNA) that locks the sugar conformation by a bridged bond between C2' and C4' atoms. The flexible nature of UNA reduces the binding affinity between two strands of a siRNA molecule endowing its gene-silencing abilities with unique characteristics. UNA may improve siRNA therapeutics by increasing stability and reducing sense- and antisense-mediated off-target effects while retaining potency. The addition of UNA increases siRNA stability, reduces off-target activity and improves gene silencing. MDRNA plans to employ this technology to improve siRNA safety and efficacy and create proprietary RISC and Dicer length siRNA with drug-like properties. Terms of the agreement were not disclosed.

In January 2008, the USPTO issued a notice of allowance for patent application # 10/976,942, entitled "Phage Displayed Trp Cage Ligands" with claims that relate to a novel, high throughput method for identifying peptides which can bind to specific cell types. These targeting peptides can then be combined with therapeutics to enhance overall delivery and overcome this key challenge in drug development.

Current as of August 26, 2010