...a leading developer of RNA interference (RNAi) therapeutics, today announced that the Company has received verbal notice from the U. S. Food and Drug Administration (FDA) that the TKM-Ebola Phase I healthy volunteer clinical study has been placed on clinical hold. This notice applies only to this study.
Joint Project Manager Medical Countermeasure Systems (JPM-MCS) U.S. Department of Defense (DoD)
In 2010, Tekmira signed a $140-million contract with the DoD to advance an RNAi therapeutic, which utilized our LNP technology, to treat Ebola virus infection. In 2013, the collaboration was expanded to include significant advances in LNP formulation technology, including a new LNP formulation that was more potent, the ability to be able to lyophilize (freeze-dry) LNP formulations and an LNP formulation that can be administered subcutaneously. In January 2014, Tekmira commenced TKM-Ebola Phase I clinical trial. JPM-MCS, a component of the Joint Program Executive Office for Chemical and Biological Defense, aims to provide U.S. military forces and the nation with safe, effective, and innovative medical solutions to counter chemical, biological, radiological, and nuclear threats. JPM-MCS facilitates the advanced development and acquisition of medical countermeasures and systems to enhance U.S. biodefense response capability. For more information, visit www.jpeocbd.osd.mil. Read more about TKM-Ebola here.
Patented iRNA Ebola is a version with changes/interfered with in the RNA to put into a vaccine and is not the original Ebola virus...as we assume is happening in Africa's outbreak... This is where the study above was conducted, and the outbreak occurred at the same hospital as the testing...
So you decide.
Monsanto Company
In 2014, Tekmira signed an Option Agreement with Monsanto, permitting Monsanto to obtain a license to use Tekmira's proprietary delivery technology. The companies' agreement and research collaboration will focus on the development of new innovative biological solutions for farmers, which have the potential to provide new options for sustainable pest, virus and weed control. The potential value of the transaction could reach up to $86.2 million following the successful completion of milestones.
Monsanto (MON) pays Tekmira Pharmaceuticals (TKMR) $1.5M for a milestone related to the research program under the Option Agreement the two companies signed in January covering Tekmira's proprietary delivery technology and IP for use in agricultural applications. The potential value of the agreement could be as high as $86.2M if all program milestones are met.
Bristol-Myers Squibb
In 2010, Tekmira entered into a multi-year, target validation agreement with Bristol-Myers Squibb. Tekmira will supply LNP formulations of siRNA provided by Bristol-Myers Squibb to silence target genes of interest. Bristol-Myers paid Tekmira $3-million concurrent with the signing of the agreement. Tekmira announced a further expansion of the collaboration to include broader applications of its LNP technology and additional target validation work.
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY)
Tekmira has granted a license to Alnylam to use Tekmira's LNP technology to enable RNAi therapeutic products. Tekmira will receive milestone and royalty payments as these LNP-enabled products are developed and commercialized. Alnylam currently has three LNP-enabled products in human clinical trials: ALN-TTR02, ALN-VSP, and ALN-PCS02. Read more about Tekmira’s Partnered Products here.
About Small interfering RNA
Small interfering RNA (siRNA) are synthetic RNA molecules designed to suppress the production of proteins through RNA interference (RNAi). Sequencing of the human genome has provided the information needed to design siRNA therapeutics to target a wide range of disease-causing proteins. In fact, a siRNA therapeutic can be designed in a shorter time frame than synthesizing and screening conventional small molecule drugs. Further, siRNA-based therapeutics can bind to a target protein mRNA with great specificity. When siRNA are introduced into the cell cytoplasm, they are rapidly incorporated into an RNA-induced silencing complex (RISC) and guided to the target mRNA. The RISC cuts and destroys the target mRNA, preventing the subsequent production of this specific protein. The RISC can remain stable inside the cell for weeks, destroying many more copies of the target mRNA and suppressing this specific protein for long periods of time.
Tekmira has a worldwide license for the discovery, development and commercialization of RNAi products using siRNA directed to 13 gene targets.
Joint Project Manager Medical Countermeasure Systems (JPM-MCS) U.S. Department of Defense (DoD)
In 2010, Tekmira signed a $140-million contract with the DoD to advance an RNAi therapeutic, which utilized our LNP technology, to treat Ebola virus infection. In 2013, the collaboration was expanded to include significant advances in LNP formulation technology, including a new LNP formulation that was more potent, the ability to be able to lyophilize (freeze-dry) LNP formulations and an LNP formulation that can be administered subcutaneously. In January 2014, Tekmira commenced TKM-Ebola Phase I clinical trial. JPM-MCS, a component of the Joint Program Executive Office for Chemical and Biological Defense, aims to provide U.S. military forces and the nation with safe, effective, and innovative medical solutions to counter chemical, biological, radiological, and nuclear threats. JPM-MCS facilitates the advanced development and acquisition of medical countermeasures and systems to enhance U.S. biodefense response capability. For more information, visit www.jpeocbd.osd.mil. Read more about TKM-Ebola here.
Patented iRNA Ebola is a version with changes/interfered with in the RNA to put into a vaccine and is not the original Ebola virus...as we assume is happening in Africa's outbreak... This is where the study above was conducted, and the outbreak occurred at the same hospital as the testing...
So you decide.
Monsanto Company
In 2014, Tekmira signed an Option Agreement with Monsanto, permitting Monsanto to obtain a license to use Tekmira's proprietary delivery technology. The companies' agreement and research collaboration will focus on the development of new innovative biological solutions for farmers, which have the potential to provide new options for sustainable pest, virus and weed control. The potential value of the transaction could reach up to $86.2 million following the successful completion of milestones.
Monsanto (MON) pays Tekmira Pharmaceuticals (TKMR) $1.5M for a milestone related to the research program under the Option Agreement the two companies signed in January covering Tekmira's proprietary delivery technology and IP for use in agricultural applications. The potential value of the agreement could be as high as $86.2M if all program milestones are met.
In 2010, Tekmira entered into a multi-year, target validation agreement with Bristol-Myers Squibb. Tekmira will supply LNP formulations of siRNA provided by Bristol-Myers Squibb to silence target genes of interest. Bristol-Myers paid Tekmira $3-million concurrent with the signing of the agreement. Tekmira announced a further expansion of the collaboration to include broader applications of its LNP technology and additional target validation work.
Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY)
Tekmira has granted a license to Alnylam to use Tekmira's LNP technology to enable RNAi therapeutic products. Tekmira will receive milestone and royalty payments as these LNP-enabled products are developed and commercialized. Alnylam currently has three LNP-enabled products in human clinical trials: ALN-TTR02, ALN-VSP, and ALN-PCS02. Read more about Tekmira’s Partnered Products here.
About Small interfering RNA
Small interfering RNA (siRNA) are synthetic RNA molecules designed to suppress the production of proteins through RNA interference (RNAi). Sequencing of the human genome has provided the information needed to design siRNA therapeutics to target a wide range of disease-causing proteins. In fact, a siRNA therapeutic can be designed in a shorter time frame than synthesizing and screening conventional small molecule drugs. Further, siRNA-based therapeutics can bind to a target protein mRNA with great specificity. When siRNA are introduced into the cell cytoplasm, they are rapidly incorporated into an RNA-induced silencing complex (RISC) and guided to the target mRNA. The RISC cuts and destroys the target mRNA, preventing the subsequent production of this specific protein. The RISC can remain stable inside the cell for weeks, destroying many more copies of the target mRNA and suppressing this specific protein for long periods of time.
Tekmira has a worldwide license for the discovery, development and commercialization of RNAi products using siRNA directed to 13 gene targets.
Implications of Ebola data for Tekmira HBV Program
Like it or not, it is the HBV program that is driving the interest in Tekmira, at least in the near-term. Therefore, the 15% sell-off in the stock yesterday following the Clinical Hold imposed by the FDA can be interpreted to be due to the uncertainty of what it means for the HBV program.
It is my working hypothesis that for the treatment of HBV via the immune reactivation pathway, the use of even transient immune suppression is to be avoided. On the other hand, the recent Ebola clinical results by Tekmira suggest that transient immune suppression may also be desirable for 3rd gen SNALP delivery. As TKM-HBV is expected to utilize '3rd gen' SNALP delivery, too, the Ebola results with immune activation seem like a bad omen.
While this cannot be ignored, there are a few reasons to believe that this might be too simplistic.
1. Difference in dose
Although there was an apparent tendency for immune stimulation throughout the dose escalation with TKM-EBOLA, it was only at the high dose of 0.5mg/kg where a dose-limiting toxicity was observed. And according the yesterday's press release on the Clinical Hold, it is in particular cytokine elevations that were observed at 'higher doses' that are the issue.
Since unlike Ebola, HBV only replicates in hepatocytes, and because SNALP potency is highest in hepatocytes, the efficacious dose for HBV may be well below 0.5mg/kg with 3rd gen formulations. Of note, even 2nd gen SNALPs are highly effective at 0.3mg/kg based on the Tekmira-enabled ALN-TTR02 candidate now in phase III.
2. Different sequence, different immune stimulation
It is known (e.g. Judge et al. 2005: Sequence-dependent immune stimulation of the mammalian innate immune response by synthetic siRNAs) that immune stimulation by RNAi, especially when liposomally formulated, is highly dependent on the actual sequence and modification pattern of the RNAi trigger. Since TKM-EBOLA and TKM-HBV are different in that regard, it is well possible that while one 3rd gen formulation is immunostimulatory, the other is not.
3. Immunostimulatory by design/by screen
Scientifically, I was most disappointed by the Ebola immune stimulations as Tekmira made a big deal in the wake of similar observation in 2010 with TKM-ApoB that with improved, more predictive immune stimulation assays, they would now be able to screen out the immunostimulatory formulations. In a black-and-white world you would conclude ‘obviously not!’.
In a world of shades of grey, I can imagine that TKM-EBOLA might have happened to slip through this part of the screening process. The reason is that since Ebola infects a number of cell types besides hepatocytes (endothelial cells, phagocytes etc), the impressive efficacy of TKM-EBOLA always stood out as something quite unusual. So while containing the spread of the virus by hitting it particularly hard in the liver might be part of the mechanism, I am quite receptive to the notion that the scientists did not mind all that much some immune stimulation when the RNAi formulation had so much efficacy.
With HBV, however, the company might be much more careful in screening out immunostimulatory potential.
I can now hear Sarepta investors yell ‘it’s an artefact’, but I would caution them that Sarepta and the morpholino field at large is proposing morpholinos with cationic appendices for infectious diseases while these are not really considered for genetic diseases. What I don’t understand is that why a modification that is supposed to be helpful in e.g. suppressing viral gene expression should not likewise be useful for suppressing human gene expression. So maybe the value of these modifications is in tickling the immune system?
http://rnaitherapeutics.blogspot.com/2014/07/implications-of-ebola-data-for-tekmira.html
USDA: RNA-interference Pesticides Will Need Special Safety Testing
http://www.gmoevidence.com/usda-rna-interference-pesticides-will-need-special-safety-testing/
USDA: RNA-interference Pesticides Will Need Special Safety Testing
http://www.gmoevidence.com/usda-rna-interference-pesticides-will-need-special-safety-testing/
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