Navigate the Alnylam $ALNY Notes Pages
- Introduction (valuation, milestones, pipeline, general commentary)
- RNAi Background (science, delivery technologies, patents, litigation)
- ALN-TTR (lead 5x15 program for transthyretin amyloidosis)
- 5x15 Programs (details on 5x15 strategy and info on additional preclinical programs)
- Partnered Programs (partnered clinical and preclinical assets falling outside the 5x15 focus area)
- Alliances and Licensing (RNAi platform deals and other licensing agreements with pharma companies)
- "During 2009 and 2010, we presented data and advanced our efforts regarding the application of RNAi technologies to improve the manufacturing processes for biologics, including recombinant proteins and monoclonal antibodies. These applications of RNAi technology, which we are advancing in an internal effort referred to as Alnylam Biotherapeutics, have the potential to create new business opportunities. In particular, we are advancing RNAi technologies to improve the quantity and quality of biologics manufacturing processes using mammalian cell culture, such as Chinese hamster ovary, or CHO, cells. This RNAi technology potentially could be applied to the improvement of manufacturing processes for existing marketed drugs, new drugs in development and for the emerging biosimilars market. We have developed proprietary delivery lipids that enable the efficient delivery of siRNAs into CHO cells when grown in suspension culture, as well as other cell systems that are used for the manufacture of biologics. Studies have demonstrated that silencing certain target genes involved in certain CHO cell apoptotic and metabolic pathways resulted in improved cell viability as compared with untreated cells. Additional studies demonstrated the ability to target a viral infection of CHO cells and alter glycosylation pathways. During 2010, Alnylam Biotherapeutics formed two collaborations with leading biotechnology and pharmaceutical companies. As Alnylam Biotherapeutics advances the technology, it plans to seek additional collaborations with established biologic manufacturers, selling licenses, products and services."
- 10/2005 stock purchase agreement (5.27m shares at $11.11 for $58.5m- 19.9% w/ true up right. Later bought 0.34m for $7.6m, currently have 13.4% stake) alongside license/collaboration deal. Terms: 3 yr research term w/ two more 1 yr options (these were exercised and research period completed in 10/2010). $10m upfront, plus research funding and milestones.
- 9/2010 NVS exercised option to select 31 gene targets but declined to exercise broader technology integration option for $100m. This decision led to corporate restructuring that reduced workforce by 25% (25 FTE had been devoted to this work, much higher than Roche/Takeda which consumed about 10 FTE combined). NVS retains its subscription rights for futrue stock financings, but would lose this if they ever sell shares. The expiration of certain rights of first offer/negotiation may remove barriers to other future partnerships.
--The 31 targets represent a broad variety of indications, and are targets for which NVS believes there is unmet medical need and need for new treatment modality.
--NVS has an internal RNAi team in Boston now that will develop these programs. No comment from ALNY or guidance from NVS as to when these will reach the clinic. ALNY doesn't have complete readthru about the targets, there is an independent gatekeeper. ALNY made the RNAi constructs for many but not all of the targets, NVS will make the rest. Some programs have animal data and qualify as "preclinical status"
- As of 12/31/10: total of ~$65m in research funding and milestones received (but 9/2010 CC re restructuring said $125m received, looks like included stock purchases)
- 7/2007- nonexclusive IP license agreement in limited therapeutic areas with rights to expand to up to 18 additional areas at a cost of $50m each.
- Terms: $273.5 million upfront payment, plus up to $100m milestones for each target, plus royalties. Covered patents expire in US and ROW between 2016 and 2025. Agreement has not been terminated, can be on 180 days notice.
- 8/2007 Roche bought 1.975m shares at $21.50 for $42.5m total, with right to true-up in any future financing. Also Roche bought non IP assets of ALNY Europe subsidiary for $15m.
- 11/2010 Roche discontinued RNAi R&D efforts- they could assign rights to 3rd party in sale of entire RNAi business.
- $79.3m deferred revenue reamins at 3/31/2011, still being recognized under straight-line accounting. This could change if rights assigned by Roche to third party (via 1q2011 10q)
- 5/2008-nonexclusive worldwide license to IP, initially limited to oncology and metabolic diseases, can be expanded ($50m per field).
- Terms: exclusive platform partner in Asia thru May 2013. $100m upfront fee [$4.6m paid to ISIS] plus near term technology transfer payments ($20m 10/2008, $20m 3/2010, $10m 2q2011 for a total of $150m). Until start of p3, ALNY can opt-in for 50/50 development/comercialization split in US for up to four programs, plus 2x per additional optioned indication. Up to $171m development and commercial milestones for each selected candidate, plus royalties. Right of first negotiation for Asian rights for all pgms except RSV until 2013. Can terminate w/ 180 days notice.
- 5/2/11: have now recd full $150m in upfront and technology transfer payments and Takeda remains an important partner. Significant possible future milestones and royalties. ALNY also has opt-in rights for US market
- 5/2/11 question: When will Takeda take a program into p1? They have publicly said to expect IND in 2013-2014 timeframe [this seems really slow to me, but not sure of details of what they are trying to do]
- ALNY paid $5m total to licensors, primarily ISIS in 2008 related to this agreement.
- As of 3/31/2011, $91.3m deferred revenue remained (via 1q2011 10q)
- “To generate revenues from our intellectual property rights, we also grant licenses to biotechnology companies under our InterfeRx program for the development and commercialization of RNAi therapeutics for specified targets in which we have no direct strategic interest. We also license key aspects of our intellectual property to companies active in the research products and services market, which includes the manufacture and sale of reagents. Our InterfeRx and research product licenses aim to generate modest near-term revenues that we can re-invest in the development of our proprietary RNAi therapeutics pipeline.”
- "We expect to receive license fees, annual maintenance fees, milestone payments and royalties on sales of any resulting RNAi therapeutic products. Generally, we do not expect to collaborate with our InterfeRx licensees in the development of RNAi therapeutic products, but may do so in certain circumstances"
- Research reagent/services: ~15 licensed issued. Generally are "vendors that provide siRNAs and related products and services for use in biological research"
- Gene target licenses have been granted to: GeneCare, Quark Biotech, Calando Pharma, Tekmira. Benitec has an option for license. In sum, 22 targets licensed, 9 of which have been selected by partners (as of 1/31/11, 2010 10k)
Isis Discovery/Development Alliance
- 3/2004 and amended 4/2009. Cross-licensing for dsRNA products. Isis can develop dsRNA against certain targets. Isis has limitations on giving access to their IP to other companies. See additional info in Isis research page.
- Terms: Owe each other up to $3.4m milestones and royalties on products arising. Isis gets license related to ssRNA IP.
- Amendment created collaboration for ssRNA, ALNY paid $11m upfront and $3m per year for 3 yrs. 11/2010 terminated by ALNY, who loses access to ssRNAi IP, etc.
Biogen Discovery/Development Alliance
- 9/2006 alliance for treatments for PML.
- Terms: BIIB funds all research/development. $5m upfront and up to $51m milestones. Can terminate on 90 days notice
- 9/2006: awarded up to 4 yr, $23m contract from NIAID to develop broad-spectrum RNAi anti-viral therapeutic for hemorrhagic fever virus, including Ebola. Entire amount was awarded and contract was completed in 12/2010. Note that partner/competitor/legal opponent Tekmira $TKMR also has an ongoing government funded Ebola program entering phase 1 trials.
- 8/2007: awarded up to $10.9m contract from DTRA (Dept of Defense) for development of broad-spectrum RNAi anti-viral therapeutic for hemorrhagic fever virus. In early 2009, program was not continued (so potential additional $27.7m not received).