As part of its long term growth and development strategy, Tekmira has a range of agreements with industry leaders and partners and will continue to support the ongoing activities of its research and development collaborators and licensees by providing new lipid-based nanoparticle formulations for different RNAi therapeutics.
Alnylam Pharmaceuticals Inc.
Alnylam has a license to use Tekmira’s LNP technology to advance RNAi therapeutic products, and Tekmira is eligible to receive milestones and royalties as Alnylam’s LNP enabled products are developed and commercialized.
Alnylam’s ALN-TTR01 and ALN-TTR02 are RNAi therapeutics targeting transthyretin (TTR) for the treatment of TTR-mediated amyloidosis (ATTR), a systemic disease caused by mutations in the TTR gene. ALN-TTR01 and ALN-TTR02 utilize our LNP technology. In July 2010, Alnylam announced the initiation of a Phase 1 human clinical trial for ALN-TTR01, which triggered a US$0.5 million milestone payment to us. Alnylam has initiated a Phase 1 trial with ALN-TTR02 aimed at evaluating safety, tolerability, and clinical activity of ALN-TTR02 in healthy volunteers. New data were presented on July 16, 2012 at Boston University School of Medicine. Alnylam reported results that showed that administration of ALN-TTR02 resulted in statistically significant reductions in serum TTR protein levels of up to 94%. Suppression of TTR, the disease-causing protein in ATTR, was found to be rapid, dose dependent, durable, and specific after just a single dose. Alnylam has initiated a Phase 2 study of ALN-TTR02 in patients with ATTR and has guided that its goal is to start a pivotal trial in 2013. The initiation of the Phase 2 study of ALN-TTR02 triggered a US$1.0 million milestone payment to Tekmira. Tekmira is entitled to receive a US$5 million milestone payment when ALN-TTR02 enters a pivotal or Phase 3 clinical trial, which is expected to occur in 2013. Tekmira is also eligible to receive royalty payments based on commercial sales of ALN-TTR.
In April 2009, Alnylam announced that they had initiated a Phase 1 human clinical trial for a product candidate that utilizes our LNP technology. The Alnylam product candidate, ALN-VSP, is being developed as a treatment for advanced solid tumors with liver involvement. ALN-VSP comprises siRNA molecules delivered systemically using our LNP technology. The initiation of the ALN-VSP Phase 1 clinical trial triggered a milestone payment of $0.6 million (US$0.5 million) which we received in May 2009. In June 2011, Alnylam presented Phase 1 human clinical trial data at American Society of Clinical Oncology (ASCO) meeting and 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. The most recent ALN-VSP data were presented at the American Society of Clinical Oncology (ASCO) meeting in June 2012. Alnylam disclosed that, overall, the results demonstrated disease control lasting more than six months in the majority of patients treated on the extension study, including a complete response (CR) in an endometrial cancer patient who had multiple liver metastases. In this study, chronic dosing of up to 23 months with ALN-VSP was found to be generally safe and well tolerated. In July 2012, Alnylam disclosed that it has formed a strategic alliance with Ascletis Pharmaceuticals (Hangzhou) Co., Ltd., a privately held US-China joint venture pharmaceutical company, to develop and commercialize ALN-VSP in China, including Hong Kong, Macau, and Taiwan. On June 21, 2013, Tekmira's manufacturing process technology was transferred to Ascletis to enable them to produce ALN-VSP. Tekmira believes that this fulfills the obligations in order to earn a US$5.0 million milestone from Alnylam. However, Alnylam has demanded a declaration that Tekmira has not yet met the obligations related to the milestone, and wishes to exercise arbitration proceedings as provided for under the agreement. Tekmira disputes Alnylam's position..
Alnylam is also developing ALN-PCS, an RNAi therapeutic, which is enabled by our LNP delivery technology, to treat hypercholesterolemia, or high levels of cholesterol in the blood. On September 26, 2011, Alnylam announced the initiation of a Phase 1 human clinical trial for ALN-PCS which triggered a US$0.5 million milestone payment to us. On April 20, 2012, Alnylam presented ALN-PCS data at the American Heart Association's Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB) 2012 Scientific Sessions held in Chicago, IL, updating interim data released earlier this year. Alnylam reported results that showed that administration of a single dose of ALN-PCS, in the absence of concomitant lipid-lowering agents such as statins, resulted in statistically significant and durable reductions of PCSK9 plasma levels of up to 84% and lowering of low-density lipoprotein cholesterol (LDL-C), or "bad cholesterol," of up to 50%. ALN-PCS was shown to be safe and well tolerated in this study. Alnylam expects to partner its ALN-PCS program prior to initiating a Phase 2 clinical study. Tekmira is eligible to receive royalty payments based on commercial sales of ALN-PCS.
In addition, we have rights under the RNAi intellectual property of Alnylam to develop thirteen RNAi therapeutic products. You can read more about Tekmira's internal pipeline of products here.
Merck has access to certain Tekmira delivery technology for the delivery of small interfering RNAs (siRNAs). Currently, there is no active research program underway with Merck; however, Tekmira is eligible to receive up to US$17 million in milestones and royalties on each and every RNAi product that Merck advances using Tekmira’s technology.
In the second quarter of 2010, Tekmira entered into a multi-year, target validation agreement with Bristol-Myers Squibb. Tekmira will provide LNP formulations of siRNA provided by Bristol-Myers Squibb to silence target genes of interest. Bristol-Myers paid Tekmira US$3.0 million concurrent with the signing of the agreement. Importantly, Bristol-Myers Squibb will share of the target validation data it generates and Tekmira can use this data to develop its own RNAi therapeutic products. In May 2011, we announced a further expansion of the collaboration to include broader applications of Tekmira's LNP technology and additional target validation work.
Transformational Medical Technologies Program
In July 2010, Tekmira was awarded up to a US$140 million contract with the United States Government's Transformational Medical Technologies (TMT) Program, to advance an RNAi therapeutic, TKM-Ebola, to treat Ebola virus infection. In the initial phase of the contract Tekmira is eligible to receive up to US $34.7 million over the next three years. This initial funding is for the development of TKM-Ebola through pre-clinical development, filing of an Investigational New Drug (IND) application with the United States Food and Drug Administration (FDA), and completion of a Phase 1 human safety clinical trial. In February 2012, Tekmira initiated its TKM-Ebola Phase 1 clinical trial.
Spectrum Pharmaceuticals, Inc.
In 2006, Tekmira licensed three liposomal chemotherapy products to Talon Therapeutics: Marqibo® (a liposomal formulation of the chemotherapy drug vincristine); Alocrest (a liposomal formulation of the chemotherapy drug vinorelbine); and, Brakiva (a liposomal formulation of the chemotherapy drug topotecan). In July 2013, Talon announced that it was acquired by Spectrum Pharmaceuticals, Inc. (Nasdaq:SPPI), who has guided that it expects Marqibo to be launched in late 2013 through Spectrum's existing hematology sales force. Tekmira will receive royalty payments based on Marqibo's commercial sales.