Tekmira Pharmaceuticals (TKMR) and European drug developer Bavarian Nordic (BAVA.CO) are receiving significant attention in early trading on Wednesday morning with announcements that their two distinct approaches to Ebola, a therapeutic and vaccine respectively, are advancing.
On October 21 after the bell, Tekmira announced that it has commenced the limited GMP manufacturing of a new TKM-Ebola therapeutic (TKM-EbolaGuinea) specifically targeting the Ebola-Guinea variant, the strain responsible for the ongoing Ebola outbreak in West Africa. Tekmira has stated supply of this therapeutic will be available in early December 2014 for use by various collaborators and will provide updates as definitive agreements for supply/use of this therapeutic are established. In addition, Tekmira stated it plans to continue to provide TKM-EbolaZaire, the company’s existing RNAi therapeutic, to infected patients under the proper regulatory framework and expects the partial clinical hold on this program will be resolved by the end of the current quarter.
Meanwhile, Bavarian Nordic A/S (BAVA.CO) (BVNRY) announced overnight on the 21st a license and supply agreement for its MVA-BN Filovirus vaccine candidate with Crucell Holland, a segment of Johnson & Johnson (JNJ). A combination of Bavarian’s Filovirus vaccine and J&J’s AdVac technology demonstrated complete protection against Ebola recently in preclinical studies. J&J plans to move into the clinic early next year, and expects to have 250,000 doses ready to be released for broad application in clinical trials by May of 2015.
Bavarian Nordic has granted J&J an exclusive license for the vaccine, which is expected to protect against Ebola Zaire, Ebola Sudan, and Marburg, in exchange for an upfront payment of $25 million, up to $20 million in development and regulatory milestones. In addition, Bavarian Nordic will scale up production with a target of more than 1 million doses of the vaccine worth $99.3 million, for which J&J will make an upfront payment of $70.8 million. J&J also made a $43 million investment in Bavarian Nordic stock.
TKM-EbolaGuinea
This new candidate is an important development in the TKM-Ebola program, and RNAi therapeutics in general, for a number of reasons. First, the ability for Tekmira to rapidly develop, manufacture, and deploy a sequence-specific RNAi therapeutic matching the outbreak’s demonstrates the power of an RNAi platform. A small molecule drug such as Avigan, Chimerix’s (CMRX) Brincidofovir, or a monoclonal antibody cocktail such as zMAPP (Mapp Bio) cannot be rapidly modified in the same way. Additionally, the development demonstrates Tekmira’s ongoing commitment to an efficacious Ebola therapeutic for use in the ongoing outbreak, positioning themselves to potentially realize monetary benefits from this program.
Tekmira’s reasoning behind developing TKM-EbolaGuinea: a modified, sequence-specific Ebola-Guinea variant RNAi therapeutic most likely stems from 2 of 3 RNAi triggers in the currently deployed TKM-Ebola therapeutic, TKM-EbolaZaire, being mismatched against the Ebola-Guinea variant. This mismatch in the 2 individual RNAi triggers targeting the VP35 protein (2 mismatches) and L-polymerase complex (1 mismatch) can be seen when comparing the RNAi triggers to a sequenced sample of the Ebola-Guinea variant (bold and underline represent mismatches):
TKM-EbolaZaire VP35-855 RNAi trigger:
Sense 5’-GCAACUCAUUGGACAUCAUUC-3’
Guinea-Ebola variant sample VP35 protein: 3841 agcaattcat tggacattat tcatgctgag ttccaggcca
TKM-EbolaZaire EK-1 (L polymerase) RNAi trigger:
Sense 5’-GmUACGAAGCUmGUAUAmUAAAUU-3’
Guinea-Ebola variant sample L-Polymerase: 17341 cagatcgaaa ttgtacgaag ctgtacataa attgatctta
Even though TKM-EbolaZaire has been administered to several infected patients and has 2 mismatched RNAi triggers, this does not mean the candidate does not ‘work’. This simply means the RNAi therapeutic currently deployed, TKM-EbolaZaire, will not have maximum efficacy in patients infected with the Ebola-Guinea variant. In our view, it’s smart and strategic development by Tekmira to hold-off on deploying TKM-Ebola in West Africa until its most efficacious therapeutic can be used. I suspect TKM-EbolaGuinea is also to a degree already derisked in humans given that TKM-EbolaGuinea employs the same SNALP delivery vehicle and similar RNAi triggers (swapping mismatched nucleotides) as those in TKM-EbolaZaire, which has been well tolerated in infected patients.
As Tekmira stated previously, the TKM-Ebola program was nominated as a potential therapeutic for use in an international consortium conducting clinical trials of Ebola therapeutics in West Africa. Although Tekmira’s TKM-Ebola program has not been confirmed for use in this consortium, it appears Tekmira has proactively developed and started manufacturing TKM-EbolaGuinea prior to being selected. Tekmira has “taken the bull by the horns” in order to have this therapeutic available and manufactured for potential use by various collaborators.
I suspect Tekmira’s TKM-Ebola program will emerge as the “dark-horse” of Ebola therapeutics to be deployed in infected individuals and eventually in West Africa. This is due to the robust validation of TKM-EbolaZaire outlined above, as well as the rapid development and manufacture of TKM-EbolaGuinea: an RNAi therapeutic with the potential to provide maximum efficacy for patients infected with the Guinea-Ebola variant. Tekmira’s robust data package and ability to modify the RNAi therapeutic to match the Guinea-Ebola variant, and any potential mutations, is unparalleled compared to other Ebola therapeutics being deployed. I suspect this will pave the way for Tekmira to eventually realize some monetary benefits from this program and position TKM-EbolaGuinea as an ideal therapeutic for use in the current West African outbreak.
One or more of PropThink’s contributors are long JNJ or TKMR.
