Monday, March 31, 2008
Tekmira and Protiva Reunification Forms Leading RNAi Therapeutics Delivery Company
Over the past weekend, as the RNAi world was congregating in nearby Whistler, something very unusual happened in Vancouver, BC. For the sake of RNAi Therapeutics, personal ambition has been set aside and an equitable and very cleverly crafted outcome was found. The outcome relates to a fight for one of the leading systemic RNAi delivery platforms that has cost the Tekmira and Protiva literally almost as much in legal and other related expenses and management time as was spent on technology development. It has also put their many partners, currently Alnylam, Regulus, Merck, Roche, and others, with at least four more pharmaceutical parties evaluating the technology, in a difficult situation and created many inefficiencies.
With more than $35M in cash (Tekmira: ~$20M; Protiva: ~$15M; Roche and Alnylam equity investments: $10M; minus fees, minus severance pay), leading liposomal siRNA delivery IP and science, numerous and lucrative partnership activities, lawsuits out of the way, plus 7 InterfeRx licenses from Alnylam, the new Tekmira will emerge as the first strong public RNAi Therapeutics delivery-focused company. The $10M equity investments for $2.4 a share, $5M each by the Roche Venture Fund and Alnylam, values the combined company at over $100M, almost 3x the current price, with 48% owned by former Tekmira, 44% by formerly privately held Protiva, and 4% by Alnylam and Roche each. It is moreover more than likely that this sets the stage for further partnership arrangements, some of them potentially similar to the one involved in the exercise of the first target pick under the InterfeRx license.
Through this reunion, Tekmira has now also selected its long-awaited first target under InterfeRx. The target is polo-like kinase 1 which Protiva had been developing for the treatment of liver cancer and metastatic colorectal cancer. Perhaps related to the fact that one of Alnylam’s lead development programs is also aimed at liver cancer, Alnylam has retained the right to obtain this program prior to the start of phase II trials. The other development program in Protiva’s portfolio is/was ApoB 100, for which no InterfeRx pick was exercised. This is consistent with the observation from probably half a dozen RNAi studies on ApoB knockdown that I have heard from which have reported sequence-specific fatty liver phenotypes in pre-clinical models.
This very positive business development goes hand in hand with the recent presentations of much improved SNALP and SNALP-like formulations pushing the IC50s down to the 0.1mg/kg range, particularly important since the therapeutic index is by far the most pressing issue with liposomal RNAi delivery. Methods enabling the delivery of liposomes into the endosomes of target cells, with subsequent safe, yet efficient escape of the siRNA cargo into the cytoplasm, will be critical. I am sure the scientific group led by Ian MacLachlan will be best qualified to find such solutions.
This is also the time to congratulate the managements of the parties to a deal that until now almost seemed impossible given the complicated entanglements and heated exchanges in the past. One can only hope that this sets an example for RNAi Therapeutics to hold off on the legal battles until real products come close to reality.
Disclosure: The author currently owns Tekmira stock.
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