It's part of the unwritten bargain. Mr. underwriter we sell you the shares cheap and pay big fees.You produce a new analyst report which is usually good. These days you just can't have an official quid pro quo.
Even though the market should not punish OGXI for the failure of gen1 AS drugs, it apparently does and might continue to do so. Thus OGXI might get affected by the success or failure of other AS oncology drugs even though it shouldnt.
The most advanced gen2 AS in oncology seems to be Lilly's Survivin (LY2181308). Does anyone following ISIS know what happened to LY2181308's trial in refractory acute myeloid leukemia? It seems to be completed but nothing published. I assume it was a failure but was it a complete failure?
Mr. ssss, agree regardless of the chemistry the target always has to prove itself clinically. It's the difference between biotechs blowing up or shooting up in price. I also see now from you and dr.kuvasz that OGXI people did everything for these targets and ISIS just licensed the 2nd gen chemistry and helped with the chemistry on the drug candidate.
If it works out it will obviously be a win-win as I think ISIS gets about 30% on what OGXI gets if it's like 011 and OGXI will hopefully be very successful with the 2nd gen ISIS backbone.
Actually a main reason I took another closer look at OGXI was my ISIS holding was too bloated so I sold a big bunch and looked around for where I might put the money and was frankly blown away by the cancer results and the market cap which was something like $130M which seemed ridiculously low.
I agree with almost everything you said. In particular, I agree that 2nd gen antisense has apparently overcome the delivery problem 1st gen antisense had and is able to achieve meaningful cellular target knockdown. As I mentioned, 011 has shown it can dramatically reduce clusterin levels in prostate tumor cells. And I don't dispute that ISIS' mipomersen has repeatedly demonstrated efficacy in reducing cholesterol levels (however valid or invalid the liver toxicity concerns may be).
My only caveat about 011 is that it remains to be proven that 011's reduction of clusterin levels in prostate tumor cells can extend survival. It appeared to do that in the 81-patient P2 trial and I think it's more likely than not that it will repeat that success in the 1,000-patient SYNERGY trial but it's not a slam-dunk.
I also tend to think Dr. Kuvasz is right in saying OGXI wasn't a satellite of ISIS. I believe Dr. Martin Gleave, one of the founders of OGXI, selected the DNA targets for 011 and 427 and OGXI then licensed ISIS' 2nd gen technology to go after those targets. It's possible I have that wrong since I wasn't following OGXI in its early days as a private company but I think Dr. K was.
I see from the 2001 PR that OGXI apparently had AS and the targets and then partnered to use ISIS' 2nd gen AS in developing the drugs. So while ISIS indicates OGXI as one of several satellite companies, I agree OGXI is far more than the other satellite companies that ISIS outsourced drugs to, but OGXI simply licensed the 2nd gen backbone technology from ISIS and worked with ISIS on the drugs but OGXI has much or most of the target specific IP and ISIS took an equity investment in OGXI.
http://www.evaluatepharma.com/Universal/View.aspx?type=Story&id=16194 That 2001 PR link follows:
OGXI developed a novel target and novel application of technology in 011 and 427; it has been called novel novel, or as the minimalists call it, novel squared. Patents have been filed and, as you note, the drugs will be protected against generic drugs for some time.
I am not sure if I agree that OGXI is a satellite of ISIS, I prefer to liken the relationship to how Steve Jobs did business with Oracle or other suppliers. Key relationships where both parties used respective technology for novel purposes to give the end user seamless and effective service which both parties, left to their own devices, could not provide.
re "Of course, that doesn't prove that 011 will extend survival as it appeared to do in the phase 2 trial, so Howard's concerns aren't groundless"
On this point I think he's poorly informed and the concerns are groundless. It gets back to the history. Antisense as a platform had a huge amount of excitement by both big pharma and biotech back around a decade ago. The first generation drugs, with the generation referring to the backbone structure of the oligonucleotide as opposed to to the mRNA target specific part, were noteworthy for many spectacular failures with most biotech companies and big pharma alike getting out of it. Also there were some issues of toxicity related to the backbone structure itself so the basic chemistry of AS got a bad name.
Stan Crooke of ISIS got through many spectacular late trial flops but survived and kept working on refining the chemistry. Every thing changed around 2005 when the first 2nd gen AS drug, mopipomersen,showed overwhelming unquestionable highly statistically significant efficacy.
The drug was also well tolerated with some liver issues that are related to the specific target and none of the 1st gen class specific toxicity. Virtually every AS drug tested since has shown dramatic efficacy in terms of protein knockdown which has been further greatly increased due to better screening for the "zip code" part of the oligonucleotide. They also now have gen 2.5 chemistry which has about a 10 fold increase in potency which are starting to move into the clinic.
Mipomersen has had 3 P3 trials and all had dramatic efficacy including in a very tough treatment resistant population like homozygous familial hypercholesterolemia. The stock is very cheap because there's no current second drug far enough along at the moment for the analysts to value and they give no credit for the early stage drugs which have many potential blockbusters.
So it may take mipomersen's approval which should happen late this year to get people like the one on the blog to realize things have dramatically changed once ISIS went to gen 2 chemistry. It' obviously a crucial point for OGXI since these are basically ISIS developed drugs they decided not to expend the resources on but to outsource instead to a satellite company which is what OGXI is to ISIS. While they still have a close partnership deal, ISIS sold out it's equity investment in OGXI for $20 a while back To the extent the OGXI drugs are showing good efficacy in cancer, it further validates ISIS AS but probably only a mipomersen approval will get skeptics of AS in general to be fully convinced. Finally I'll note as evidence of the acceptance of current gen ISIS AS they have a deal with GSK where GSK brings them targets they're interested in and ISIS then makes an AS drug for it and in a short time ISIS has developed two such drugs for GSK.
The other very relevant thing for OGXI is since these are not small molecules and ISIS manufacturers all the AS drugs itself, it's unlikely that an ISIS AS drug will face generic competition and if a patent does get late in life ISIS can simply make a more potent replacement with the latest backbone as a follow-on drug with a anew patent clock. So for 011 and 427 that can prove a big advantage down the road.
Marc, I am interested in seeing what the analysts have to say. However, my primary concern relates to what management is going to say about its plan to use the money to advance shareholders' interests. We've been diluted 50% over the last year, and some of us have been in this business for years.
It seems to me that there is no debate on one issue. Management is focused on 011's success in prostrate and lung. Did we need the recent financing to support this goal. The answer is a clear no.
But what about 427? Take it to the market or get it prettied up for a partnership? Either way, the recent financing makes sense only in the latter example.
If management wants a buy out if 011 is successful, then is a partnership on 427 productive? Definitely not.
If management wants to turn this company into a cancer drug powerhouse, then taking 427 into partnership is critical. Recent financing doesn't help that much. Unless it is to put pressure on Big Pharma to make the deal.
So we should analyze the recent financing in light of this framework.
If management wants a buy out, or big partnership on 427, then the financing is brilliant. If not, then ouch!
Dr. Kuvasz: Since the co just raised money and did not disclose its intentions except that it will be used "to advance our proprietary product OGX-427", it cant say much at this moment. "Sorry. While raising the money, we forgot to mention that we were planning to do ... with the proceeds" wont work.
I am sure they had something in mind while raising the money, but we need to wait until it's ok to pretend that the decision to do whatever they were planning to do occurred after they raised the money.
re "If management wants to turn this company into a cancer drug powerhouse, then taking 427 into partnership is critical. Recent financing doesn't help that much. Unless it is to put pressure on Big Pharma to make the deal."
I agree it's all about 427. They have early recent results in bladder that says they may have something really big here and of course the prostate results so far are promising. What the financing does is put them in the drivers seat to determine the fate of 427 or the company for that matter.
Now they're clearly in a position where don't need a partnership for 427 any time soon unless and until it's very favorable.The same goes for a takeover. The fact that 011 is partnered also give them the leverage with 427 they might not have had with 011 and they may have figured out whether you partner or not it's a lot better to be in a position where you don't feel forced to partner early for financial reasons.
As miserable as this financing was for current investors we'll probably still now have a market cap of under $200M with two extremely promising cancer drugs, one of which is not partnered, and a big wad of cash.
If trials continue to be positive the stock should take off and I expect a fairly rapid recovery now that the offering is out of the way.