Isis should make good on its pledges to finish certain tasks by the end of the year. First, during the call discussing the cancer franchise, Stan stated data from ISIS-eIF4E should be reported by the end of the year. They completed enrollment over a year ago. Failing to report this data - good or bad - would be a big disappointment and harken back to times when Isis would bury data like they did for the ALS drug. Second, during the Morgan Stanley call on Sept. 10 Lynne stated Isis would have a plan for pursuing a FAC indication for ISIS-TTR by the end of the year. If they think it will work in FAP, then why not agressively pursue an FAC indication? Also, anyone know what is going on with the Factor XI drug? They used to highlight this drug but have gone quiet on it. According to clinicaltrials the 2 Canadian sites are recruiting but the multiple Eastern European sites haven't started. At the JP Morgan conference in January Stan stated the Factor XI study would "unblind by the end of the year."
Management has been talking "potential deal" for months now. Failing to close some sort of deal by the end of the year would be a disappointment. Stifel has yet to initiate - maybe they are helping TKMR evaluate a potential deal? Potential deal partners include Moderna (tons of cash, may need delivery mRNA technology), Shire (big presenter at recent mRNA conference TKMR unveiled its mRNA data at) and ag companies. I'd prefer a higher royalty at the end versus cash upfront. Something along the lines of $25 m in cash up front (another year of COE) plus high-single digit to high-teens royalties.
On slides, ISRs reported in less than 10% of injections. That's excellent. In comparison, ISRs reported in 90% of patients treated with mipomersen in its phase III (and placebo in that study reported 32% ISRs)
Why no disclosure of non-HDL changes like in the prior reports? Would have also liked to have seen a quantification of the ISRs.
Somewhat disappointing to me that Isis only initiated one Phase I (that I know of) this year: the Phase I for APO(a), which they will report data from on Sunday at AHA (so it should be pretty good). However, looks like 2014 could see Isis initiate the following Phase I's:
1. ISIS-DMPK (for myotonic dystrophy)
2. ISIS-PKK (for HAE)
3. ISIS-AR (AZN prostate cancer target)
4. ISIS- GSK3 (speculation is Hep B)
5. ISIS-GSK4 (just announced GSK ocular target)
6. ISIS-DGAT2 (NASH)
7. ISIS-ANGPTL3 (Hyperlipidemia)
Would also be good to see compound selected and Phase I initiated for Huntington's. I'd like to see at least 3 of these put into Phase I by mid-2014 and 5 by the end of 2014.
They should net $32 million out of the raise (assuming its oversubscribed). At the end of the second quarter they guided that they'd end the year with 30-35 million cash on hand that will provide a runway to mid-2015. Thus, although expenses may ramp up after mid-2015 if PLK1 enters a Phase III trial, the raise extends TKMR's cash runway until at least mid-2016 and possibly all the way to mid-2017. This will get them past potential approval for the ebola drug, initiation of Phase III for PLK1 (may even get them to Phase III results for this drug), and possibly Phase II data on the alcohol and HBV drugs and initiation of Phase I on the other two preclinical candidates discussed during the conference call. I think the raise was worth the dilution. Also, maybe they will use some of the cash to license or acquire additional trigger technology to give them some more options.
Now would be a great time to raise funds. Every other biotech has raised funds this year. If TKMR doesn't raise funds in the next week or two, then one would think that they are not doing so because a deal with a cash infusion is imminent. Maybe a deal with an ag company with at least $10 million up front? ALNY got $29.2 million up front from Monsanto. An additional $10 m would extend TKMR cash runway well into 2016.
Unfortunately I can't make the PropThink call. If I could I'd ask the following:
1. How are you progressing on developing non-ALNY payload technology?
2. Is the payload for Marburg ALNY's? Will it be one of your "non-exclusive targets" under the ALNY agreement?
3. Have you given the Marburg drug to non-human primates 96 hours after exposure? If so, what were the results? If not, any plans to do so? (would be good to have this to compare to the SRPT product)
4. What are the next steps for the Marburg drug? Would you take any additional steps without defense or NIH funding?
5. Is your ApoB program dead, or could you revive it in a SubQ format using your new LNPs?
6. Given appreciation in shares of TKMR, is a secondary in the near future? If so, how will you utilize the proceeds? Would it give you the resources to put 2 new products into Phase I in 2014 instead of just 1?
7. How close is the WEE1/CSN5 from entering the clinic?
If TKMR can hit ebola and marburg, then why not HepB? As they stated today, their experience with ebola and marburg form a strong foundation for future anti-viral therapeutics. A subQ HepB would be differentiated from ARWR's IV HepB.
Run a google search on hammersmith sma reliability and pull up a 2006 article by Mercuri et al and 2012 article by Kaufmann et al. Shows how remarkable the 5.75 mean Hammersmith improvement in the 9 mg cohort is.
The WEE1/CSN5 drug will be the next to enter clinical development, and we should all be happy about it. Merck just got $50 m upfront from AZN for their WEE1 and its only in Phase IIa. TKMR can get WEE1/CSN5 through a Phase I and then outlicensed by the end of 2015. NCI or other nonprofits may even provide support for a Phase II which would allow TKMR to keep it longer. While I would like to see an orphan target, the orphan drug will need to be subQ, and its premature to do a subQ now - wait until the Ebola Phase I proves subQ is safe.