Today is the last official day for Chief Technology Officer Ian
MacLachlan at Tekmira. While scientifically
a great loss to Tekmira, the change
marks the end of Tekmira as a technology development company and the official beginning
as a commercially focused clinical product development company. From the clinical pipeline, it is TKM-HBV,
Tekmira’s gene silencing candidate for the finite treatment of HBV infection, which
stands out as the most important, if not existential asset to be watched in
2015.
After generation 1, 2, 3, and now even 4 SNALP LNP, and 10, 100,
1000x fold improvements in the potency and therapeutic window, the time has come to stop telling us that ‘next time will be better’ after yet another
immunostimulatory setback. In both cases (TKM-ApoB, TKM-EBOLAold),
I was willing to take the bait as the company and Dr MacLachlan explained the
basis for their continued confidence with scientific authority. For TKM-EBOLA, the plausible
explanation for the immunostimulation seen in the healthy volunteer study was particle heterogeneity following resuspension of the lyophilized
liposomes (note: a lyophilized formulation was used in that case because Ebola may have to be used in areas with unreliable cold chains; other SNALP LNP products are provided as 'wet' formulations).
However, with the recent initiation of phase I studies of generations 3 and 4 formulation of TKM-HBV and the departure of Dr MacLachlan, the company seems comfortable with taking their last two shots at proving that
SNALP LNPs can enable potent gene knockdown in the absence of transient immune suppression at comfortable safety margins and with
profiles that are competitive with the emerging conjugate platforms in RNAi and
RNaseH antisense.
Although a bit under the radar for the moment, the new
studies with non-lyophilized 3rd generation TKM-Ebola Guinea should
be informative as to whether the lyophilization hypothesis holds water. As these studies should likely be of shorter
duration than the TKM-HBV phase I studies, the safety results from those
studies should be a harbinger for the safety for at least TKM-HBVgen3, if not
TKM-HBVgen4.
The changes at the company will be welcome by some investors
which might have grown tired of holding shares in a lab experiment. On the other hand, they dampen my outlook for
other liposomal delivery opportunities not only in RNAi for oncology (see today's ho-hum update on TKM-PLK1), but also in the sizzling hot fields of mRNA and
CRISPR Therapeutics.
So good luck Ian and thanks for leaving the company in good order. Yours is also a great loss to the field of RNAi Therapeutics. Hope you will come back to Nucleic Acid Therapeutics with renewed motivation.
Hello 2015
Lastly, a Happy New Year to all my readers. 2015 should be a year that will be marked by clinical RNA Therapeutics data of ever higher quality which will make it crystal clear that RNA Therapeutics has become the 3rd major drug discovery engine of the pharmaceutical industry.
First up: Regulus end of January/February 4mg/kg RG-101 in HCV.
