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A researcher into gene silencing as a technology for improving the lives of those suffering from incurable diseases. Benitec Biopharma is my primary investment in this technology as ddRNAi offers one-time treatments for a broad range of these diseases.
  • Alnylam And Benitec 4 comments
    Jun 16, 2014 6:51 AM | about stocks: BNIKF, BTEBY, ALNY

    I don't know if I have had a reprieve from SA or not but, as it looks like I can still post for the time being, I thought that I would post the following.

    Alnylam and Benitec

    Alnylam (NASDAQ:ALNY) is a $5.1B company and Benitec Biopharma (BTEBY, BNIKF) is a $120M company. Both are biothech companies working in the field of RNAi (RiboNucleic Acid Interference). Both have access to a wide patent estate: Alnylam's estate covering Small Interfering RNA (siRNA) and Benitec's estate covering DNA Directed RNAi (ddRNAi and shRNA).

    In theory they are competitors, each looking to silence genes which produce harmful levels of proteins. However, in reality this competition has not been manifest. Alnylam has concentrated its pipeline efforts primarily on rare diseases of the liver (TTR Amyloidosis, Complement Mediated Disease, Porphyria and Hypercholesterolemia) whereas Benitec has focused on a broader range of more mainstream diseases (Hepatitis C, Hepatitis B, Cancer Related Pain, Non-Small Cell Lung Cancer and Age Related Macular Degeneration).

    Both companies have partnered with others to develop treatments for disease outside of their own pipelines. It is noteworthy that, to date, Alnylam's partnership deals have been of significantly greater value than those of Benitec and this is one reason for the disparity in market capitalisation.

    But is this degree of separation about to change?

    Alnylam has already included Hepatitis B (HBV) in its pipeline, which is in direct competition with Benitec's program, and it has now applied for a patent to cover Hepatitis C (HCV).

    Alnylam's HBV treatment will involve subcutaneous injections (number to be determined). Benitec's treatment will involve a single, intravenous injection. Neither party has firmed up on the genetic sequences that they expect to target.

    Benitec hopes to piggyback on the experience it gains in the trial of its TT-034 treatment for HCV in order to fast-track its HBV candidate. However, in order to do this and remain in the HBV race, it has to finalise its target sequences first as the TT-034 experience will help mostly in the area of delivery; the HBV ddRNAi molecule design has already been modified because of improvements in the design of TT-033, leading to TT-034. Benitec's recent capital raising should provide them with the funds to complete this discovery work.

    Alnylam says that its pre-clinical, HBV work is progressing well and it intends to be in clinical trial in twelve months or so.

    Alnylam is not the only siRNA developer of a treatment for HBV, Arrowhead Research (NASDAQ:ARWR) is already in clinical trials for its treatment (ARC-520). With Alnylam's acquisition of Merck's (NYSE:MRK) RNAi business it obtained new patents (the MacSwiggen patents) which have direct implications for the development of siRNA therapies for HBV. Some commentators believe that this has new and significant impact on Arrowhead going forward but the company itself believes it has access to all the IP it needs.

    Alnylam, while applying for a patent to cover a target for HCV, is yet to announce a program to develop a treatment for the disease. It does have an interest in Regulus Therapeutics (NASDAQ:RGLS) which is developing a microRNA drug to treat HCV. This may mean that Alnylam won't develop a candidate itself but will seek to obtain royalties if it considers that others are using its IP.

    Do these latest developments mean that Alnylam and Benitec are about to go head-to-head, target sequence to target sequence, patent to patent? Well maybe but maybe not.

    As the fields of RNAi and gene therapy evolve, new technologies beyond siRNA and ddRNAi are being developed. One such development may threaten Alnylam's Hypercholesterolemia program. This new treatment would be a once only injection as opposed to Alynlam's monthly (or at best quarterly) injection.

    And this is where it gets interesting.

    Alnylam and Benitec have crossing licensing agreements where each company has the right to develop up to five, mutually agreed programs using the other's technology. In the case of Hypercholesterolemia, Alnylam's acquisition of Merck's RNAi assets came with an advanced pre-clinical treatment for Hypercholesterolemia. So, in theory, if Alnylam wanted to thwart the threat of this new treatment it could make arrangements with Benitec to replace its own monthly injection program with a one shot ddRNAi treatment. As this ex-Merck program is well in advance of the new comer, this may well be a good strategy for Alnylam.

    In terms of market capitalisation, Benitec certainly has some catching up to do but in terms of IP and technology it is certainly on par, and arguably, in advance of Alnylam. As their paths are now set to cross and the need to secure IP becomes more important as the commercialisation of RNAi products draws closer to a reality, it remains to be seen whether or not this relationship will turn into an adversarial one or one of mutual co-operation.

    I for one would hate to see potentially life changing medicines being held up because of legal disputes over whose IP takes priority. Hopefully these two doyens of the RNAi field can establish their place in the market without the need make lawyers rich and patients wait. If they cannot settle any differences outside of court, then maybe, just maybe, one of the newer developments in RNAi and gene therapy will swamp them both and that would not be good for either set of shareholders.

    Stocks: BNIKF, BTEBY, ALNY
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Comments (4)
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  • pga2003
    , contributor
    Comments (70) | Send Message
    Once again, Panno proves he is THE source for Benitec market knowledge. Thanks, and hopefully the hits will keep coming.
    16 Jun 2014, 08:35 AM Reply Like
  • SmokeyNYY
    , contributor
    Comments (95) | Send Message
    Thanks. Great article. I never even knew about that agreement between ALNY and Benitec. It is crazy that its been 9 years since then and nothing accomplished yet in regards to approved medicines.
    17 Jun 2014, 06:54 PM Reply Like
  • Pannobhaso
    , contributor
    Comments (245) | Send Message
    Author’s reply » Yes, it is a real pity that it has taken nine years and still no products on the market. The delays have been caused not by the actual RNAi cellular technology itself but by the fact that, once RNAi was discovered, no one could get RNAi molecules safely and efficiently to the appropriate cells.


    This technology can really be looked at as two technologies in one, the actual gene silencing component and the delivery component. Even though RNAi/ddRNAi was discovered all those years ago, it is only now that the delivery technology has become mature enough to prove that the RNAi technology actually works in humans.


    It's a bit like someone discovering the internal combustion engine before the wheel.
    17 Jun 2014, 09:12 PM Reply Like
  • Pannobhaso
    , contributor
    Comments (245) | Send Message
    Author’s reply » I should of added that, when Alnylam is ready to commercialise one of its therapies, the cross licenses which Benitec holds should really be seen as a asset on Benitec's balance sheet. Any company wanting to takeover Benitec would gain immediate access to these licenses. This should make them worth hundreds of millions of dollars. The current share price of Benitec does not reflect the value of these licenses, let alone the true value of its own technology.
    18 Jun 2014, 12:45 AM Reply Like
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