Assembling my biofolio...
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Re Tykerb+Femara combo/implications for IMGN
>Note that only about 20% of the patients in the trial were HER2+.<
I realized that only a subset were HER2+ but was just hoping that I could roughly compare that subset to the patients in IMGN's Phase I. I'll forget about that exercise now.
Tykerb+Xeloda's historical PFS is about 6 months in second-line setting so IMGN hopes it can best that drug combo head-to-head in the Phase III, since T-DM1 has a PFS of 9.8 months in Phase I. The caveat of course is that you can't always rely on historical data to be borne out in a current trial.
RE: Book Recommendations
Thanks ghmm! Sounds like an interesting read. I added it to my wishlist.
Re Tykerb+Femara combo/implications for IMGN
Thanks for the info here Dew as this has potential implications for my largest holding, IMGN. The Tykerb+Femara combo attained a PFS of 8.2 months it appears in HER2-positive breast cancer patients. DNA will be testing T-DM1 (Herceptin plus IMGN's DM1 cell-killing agent) in a Phase III trial against Tykerb+Xeloda in second-line treatment of HER2 patients.
In a prior Phase I trial in the second-line setting, T-DM1 attained a PFS of 9.8 months. Do you know if the Tykerb+Femara trial was in a second-line setting? I just want to make sure I'm comparing apples to apples when I look at the 9.8 months PFS versus 8.2. I know the caveat is that these are two separate trials but I'm just curious if the patient type may at least be roughly similar in gauging the results.
Recommended Biotech Books
Does anyone have any must reads in this area? I'm currently reading Welcome to Biotech Nation. I've got Science Lessons (Binder/Amgen) and Science Business in the queue. And I've read The Billion-Dollar Molecule (VRTX). Any suggested reads are appreciated!
>>>You are leaving out one important reason to sell - even if a company is hitting all its targets, doing everything you hoped and more, racking up one success after another.
It may simply be overvalued.<<<
That is true that the stock may be overvalued. However, if the story is still intact, I'm more apt to hold on to my position, and possibly add to it, rather than sell. I just find it important to stick to fundamentals, let the story play out, and not get too concerned with price fluctuations as I don't believe biotech stocks are always priced efficiently. As long as you're diversified, you'll be fine even if you're wrong.
Separately, I just want to be clear on the etiquette here regarding posts/replies. If we're replying to someone, we don't need a formal heading but should just add arrows and italicize as I did in this post and you did in yours before. Is that correct?
RE Labels
LOL yes I apologize. I will try and do better on this going forward.
Support for efficacy of RIGL's R788
"I don’t remember what my reason was but it probably had to do with efficacy rather than safety. I haven’t followed this program closely."
Thanks Dew. I'll give the bull case for the efficacy here:
In the 100 mg twice/daily dose, which is the likely dose to be carried forward (RIGL will test 150mg once/daily), 65% of patients attained an ACR20 (meaning 65% of patients reported a 20% improvement in their RA symptoms), 49% of patients attained an ACR50, and 33% attained an ACR70. However, just 38%, 19%, and 4% of placebo patients, respectively, attained ACR20, ACR50, and ACR70. The results were statistically significant.
The aforementioned results are the pooled results from U.S. and Mexico patients. The numbers are admittedly a little skewed due to the significantly better results reported in Mexico. Specifically, those ACR20, ACR50, and ACR70 scores in Mexican patients at 100mg were 75%, 64%, and 46%, respectively. However, even if you just isolate the U.S. results, they are much better than placebo and statistically significant at ACR20, ACR50, and ACR70 scores of 52%, 29%, and 14%, respectively. Enbrel, by contrast, has demonstrated ACR20, ACR50, and ACR70 scores of 66%, 42%, and 15%, respectively.
So, the drug clearly showed activity in this Phase II trial. The robustness of that activity depends on how you view the results. If you just look at the U.S. patients, then the ACR scores appear to be a bit lower than Enbrel although the ACR70 score is almost a dead heat. If you take into account all patients, then R788 had an essentially equivalent ACR20 score but a much more robust ACR50 and ACR70 score than Enbrel. Of course R788 is an oral drug too which should offer a big advantage.
Dew RE RIGL Phase II RA trial results
>RIGL – I never really thought that the data justified the price rise but obviously someone did as the secondary pricing would indicate.<
"I didn’t think the data justified the price action either, FWIW."
Dew, I finally signed up for a premium trial and tracked down this post from you regarding the rise in RIGL's stock after the company released Phase II results for R788 in RA last December. Why didn't you think the data justified the price action? Was this due to efficacy or safety concerns, or both? The RA market is huge and an oral drug should have big potential. On the efficacy standpoint, the data appeared to be at least as good, if not better than, existing drugs like Enbrel. Pertaining to side effects, the hypertension appeared to be manageable and dose reduction helped manage most cases where there was evidence of neutropenia (10%) and mild elevation of liver enzymes.
"Wasn't that Dr. Steven Quay, M.D., Ph.D., CEO, President, Chairman of the BOD, at Nastech's mantra behind his entire investment pitch for people to spend money on Nastech before it became MDRNA MRNA ?
He learned his lesson well."
Having a diverse pipeline certainly doesn't guarantee you'll succeed in the end. But, all things being equal, I'd much rather invest in what I believe to be a reasonably priced biotech that has numerous drugs under developement than one that may also be reasonably priced but which has pinned its hopes on only one drug. Of course quality, and not just quantity, is just as important. For the quality, I'll look to those biotechs that have attracted a large partner on very favorable terms as I think that generally adds some validity to the quality and potential of a given drug.
"Most of the shots have been from outside the blue line."
I'm willing to bet that at least one of their 16 drugs under development (http://www.exelixis.com/pipeline.shtml ) will be an empty-net goal. ; )
"The company has accumulated about $1B of losses during its relatively short life. Only a very small number of biotechs (e.g. HGSI) can top that."
I think the short life is key here. Yes, they've accumulated large losses so far but I don't believe this is a biotech that has had numerous failures. (I'm fairly new on this one so correct me if I'm wrong on that.) So, we don't know yet the extent to which their approach will yield results, but the numerous "shots on goal" help to minimize risk while the partnerships that occur on very favorable terms add validity.
Dew, what don't you like about EXEL? Is it their approach to to try to hit several targets, as opposed to one, with each of their drug candidates (i.e. concerns about side effects)? I love the partnerships, the extensive pipeline, and now the additional big chunk of cash from BMY.
Edit: I just saw where you cited their cash-burning over the years as one reason. If there's anything else that concerns you about EXEL, I'd love to hear as I follow it pretty closely.
Thanks Dew. I think a subscription might serve me well. ; )
Fate of Panacos
http://biz.yahoo.com/bw/081210/20081210006102.html?.v=1
PANC doesn't strike me as the typical biotech on the brink of bankruptcy with absolutely nothing to offer a potential suitor. Anyone think someone out there takes a chance on them?
Thanks PGS, Dew, and ghmm. Good info.
RE Vrtx
"Only one thing: the relatively high valuation. The enterprise value (market cap less net cash) is about $3.5B fully-diluted.
On a probability-weighted basis, Telaprevir is probably the most valuable pre-approval drug today from any company. If VRTX’s enterprise value were, say, $2.5B instead of $3.5B, the decision to buy would be easy."
This is what I assumed and I feel the same. Also, even though the odds do look good for Telaprevir approval and commercial success at this point, the fact that so much of the valuation of VRTX is tied to Telaprevir coupled with the fact that crazy things can and do happen sometimes in Phase III, makes me cautious.
I hear you. I'm just saying from a general standpoint that if you've got a drug that shows clear activity in a disease indication for which there are no approved therapies, I would think the odds for an approval would be pretty high, regardless of whether you have an 8.7% CR (11/126) or 10% (11/109).
Dew,
What is keeping you from going long on VRTX? Is it that too much of the company's valuation is tied to telepravir? Do you feel that the safety and efficacy questions were sufficiently addressed in the Phase II trials?
Allos trial results (from Monday)
http://www.forbes.com/2008/12/08/allos-therapeutics-closer-markets-equity-cx_lal_1208markets38.html?partner=yahootix
"The study of pralatrexate showed that only 26.6% of 109 patients responded to the drug. Allos is developing a treatment for patients with peripheral T-cell lymphoma, an immune-system cancer that affects about 9,500 people in the United States each year, who have relapsed or did not respond to earlier treatments. If the treatment is approved, it would be the first of its kind."
I didn't get this one. Eleven patients had complete responses and there are currently no approved drugs for this type of lymphoma. The result: the stock dropped over 20%.
ARIA's backup plan
http://biz.yahoo.com/bw/081209/20081209005126.html?.v=1
"ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA - News) today announced results of studies on its investigational, multi-targeted kinase inhibitor – AP24534 – showing complete inhibition of all known mutant variants of the target protein, Bcr-Abl, including the T315I mutant that is resistant to currently marketed therapies for chronic myeloid leukemia (CML). Investigators from the Oregon Health & Science University Cancer Institute and the Howard Hughes Medical Institute, collaborating with ARIAD scientists, presented the data yesterday evening at the 50th American Society of Hematology (ASH) Annual Meeting."
As far as the Syk inhibitors go, they're behind RIGL as that is what RIGL's lead drug (R788) targets. It's in Phase II for both RA and various lymphomas. Again, the main questions with the drug seem to pertain to safety, not efficacy, and those questions still remain for me after listening to the conference call earlier today. They indicated they expect to have a partner for the drug by end of 1Q 09.
Hopefully it transpires without any "grossly inappropriate" behavior.
SNSS provides updated Voreloxin data in elderly AML patients
http://www.reuters.com/article/marketsNews/idINN0546592820081207?rpc=44
"Interim results from a Phase II trial showed that 11 of 29 evaluated patients, or 38 percent, with acute myeloid leukemia, or AML, achieved remission of their cancer after three weekly treatments."
Sunesis said infection, low white blood cell levels, fever and mucosal inflammation were the most frequent side effects from the Voreloxin treatment. The 30-day mortality rate was 17 percent, with infection the most common cause of early death, which Sunesis said compared favorably to chemotherapy treatment.
The company also is studying a different dose regimen and said early data suggested the alternative dose was better tolerated."
This is a single-agent trial.
RIGL conference call on Sunday
http://biz.yahoo.com/prnews/081203/aqw022.html?.v=82
"Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL - News) today announced that members of Rigel's senior management team will host a conference call with simultaneous webcast on Sunday, December 7, 2008, at 4:00 p.m. PST, to discuss the results of Rigel's Phase 2 clinical trial of R788, an oral Syk kinase inhibitor, in patients with B-cell non-Hodgkin's lymphomas."
This is the same drug that is being tested as an oral treatment for RA. I'm anxious to hear how side effects are in this trial as side effects may be the one thing that can derail the drug in RA. And now we'll see how well it works against B-cell non-Hodgkin's lymphomas.
Link to video of how drug treats RA:
http://www.rigel.com/rigel/rheumatoid_arthritis
Update on OGXI Web site
http://www.oncogenex.ca/products/ogx-011-03.html
"This clinical trial was designed as a non-comparative, randomized, Phase 2 study evaluating weekly administration of custirsen (OGX 011) in combination with docetaxel or docetaxel alone as first line chemotherapy treatment in patients with metastatic Hormone Refractory Prostate Cancer (HRPC). Any differences observed between treatment groups were not designed to be subject to statistical analyses but instead, were intended to guide future development of custirsen and to provide preliminary trends regarding activity and safety."
Perhaps they read our posts on here. lol
You can probably tell from the wording that I think this is a bogus question. In my experience, the investors who say these kinds of things on biotech message boards are the ones with an unduly emotional attachment to their stock picks. More often than not, you will find that these investors turn out to be the bagholders rather than the ones who actually make money from biotech investing.
Having an emotional attachment to a stock and refusing to sell regardless of circumstances is the quickest way to lose your money in the stock market, especially in biotech. You won't get any argument from me on that.
When I buy a biotech, it's normally for a very specific reason and I will hold until certain specific events pass, whether that's an FDA decision on a drug, Phase II or III trial results, etc. If those events don't transpire the way I expect, the stock tanks, and therefore the story/outlook has changed, I have no problem selling and moving on at a loss. I've had to do that a couple of times this past year.
So, the bottom line, at least for me, is to constantly re-evaluate your stocks. Would you still buy your current holdings today? That's something I try to constantly ask myself. If not, perhaps it's time to make a switch.
I didn't realize ACHN's CEO was one of those who resigned. That's one of my holdings and one I just added to. Yes, all this news coupled with my prior doubts will cause me to move on from this one.
This is correct. Pivotal data should be known by the end of 2009.
There are several “olimus” drugs on the market. Why do we need another?
Because I don't believe there are any approved for metastatic sarcoma (correct me if I'm wrong on that). Although this may not be a huge market, at a sub-$100 million market cap ARIA doesn't need a $1 billion blockbuster to experience significant share price appreciation. Also, a success in the initial Phase III may also generate further hype for the drug as it's being tested in several other cancer indications.
Notwithstanding, the fact that the Phase II did not include a control arm keeps me on the sidelines for now.
Buyout "risk"
I just want to see if anyone else shares this concern/frustration when investing in biotechs. Say you've found a little biotech that you feel has enormous long-term potential but the company gets bought out by a larger biotech/big pharma for a significant premium. So, the stock maybe doubles in one day but then you miss out on all that long-term upside. And if it is bought out by a larger company, you're not really going to experience that appreciation by investing in the acquiring company since it already has a large market cap.
E.g. Dew, I think you mentioned before that you didn't sell MNTA in the $20s because you felt the upside was much greater. How would you feel if NVS bought the company at $20/share? Sure, we'd get more than a double, which is nice, but then you miss out on all that long-term upside.
RE: ARIA
I saw this news and it troubles me as I'm watching, but don't yet own, ARIA. I'd like to know more about the "grossly inappropriate" behavior.
ARIA is under $100 million market cap and has Deforolimus (oral mTOR inhibitor, which is a proven target) in Phase III trials in partnership with Merck. So, there's a lot of upside in this one but a ton of risk as well since Deforolimus is their only late stage drug. Also, the Phase II trial for Deforolimus had no control arm and that always concerns me.
The more I hold off on buying this one, the more it goes up. lol
Thanks Dew (and pgs). Very helpful. I'm going to do more reading on my own just to become more familiar with the hazard ratio.
As far as the OGIX trial and OGIX itself, I think I have a little more confidence in both now but I'll have to do a little more research before I invest.
Based on the wording in the PR, it’s reasonable to infer that the median survival time in the control arm will indeed stay at 16.9 months. However, this in itself doesn’t mean much because it’s the hazard ratio—not the median value in the two arms—that will ultimately determine whether this trial is considered a success.
I think that's where I'm falling off the wagon just because I assumed that if we know that the minimum median survival for the OGX-011 arm is 22.7 months, as stated in the PR, and if we could infer that the median survival would be 16.9 months for the control, then you have at least a difference of almost 6 months in favor of the OGX-011 arm. I assumed that would be great news.
If you can expand any on why it's the hazard ratio, and not those median value differences, that really matters, I'd greatly appreciate it.
To be truly clear, they would have stated a p value and would have made it very clear whether or not all events had occurred in the control arm. I'm not sure if the fact that they seem to imply that is enough for me to pull the trigger on this one.
Nothing in the PR suggests that all deaths to date occurred in the control arm. This is an improper inference on your part.
Dew, I'm just not being clear on my point. I'm not inferring all deaths occurred in the control arm as I understand deaths have occurred in both arms. The question I'm seeking an answer for is whether or not all of the patients within the control arm have died. I know there are patients still alive in the OGX-011 arm because the PR clearly states that survival updates are needed before a mature median survival for the OGX-011 arm can be reported. Because the PR doesn't also state that survival updates are needed to determine median survival for the control arm, I'm curious if this implies that all patients in the control arm have died and we therefore have the median survival time at 16.9 months for the control arm.
…the Phase 2 randomized study in 82 patients with metastatic or locally recurring prostate cancer refractory to hormone therapy showed a median survival of 27.5 months for the patients in the OGX-011 arm and 16.9 months for patients in the control arm.
This is crystal clear: the median survival time for the deaths to date is 27.5 months in the treatment arm and 16.9 months in the control arm—a difference of 10.6 months mentioned earlier in the PR. The median survival time in each arm will change as the trial progresses because new deaths can occur with a survival time either above or below the tentative median.
Again, I know that 27.5 month number for the OGX-011 will change given that not all patients have died but I'm curious if that 16.9 month number for the control arm is static, which it would presumably be if all patients in that arm have died.
Biotech rule of thumb: If it's a piece of information that bodes well for the trial, then 90% of small biotechs will make sure it is stated clearly and advantageously in the PR.
Conversely, if there are ambiguities, they are there because the specifics themselves may add a negative hue to the results.
I can't argue with that. To be truly clear, they would have stated a p value and would have made it very clear whether or not all events had occurred in the control arm. I'm not sure if the fact that they seem to imply that is enough for me to pull the trigger on this one. I may just wait for more data.
It’s either a typo or sloppy English in omitting the second instance of the word median.
It's the language within the PR, moreso than the headline itself, that I think may be more revealing. The fact that they do not refer to the control arm along with the OGX-011 arm when noting the need for more survival updates to calculate median survival is what leads me to think maybe all events have in fact occurred in the control arm.
Overall survival per se cannot be stated as a unit of time—it must be stated as a ratio relative to the overall survival of a different trial arm.
I think they make the distinction in the PR between overall survival, where we know there is a 40% lower rate for the OGX-011 arm, and the current median survival time in months. Based on what I quoted before, assuming all events have occurred in the control arm, that median survival time in months in the control arm is 16.9 months.
One other point regarding the OGXI PR http://biz.yahoo.com/prnews/081203/to979.html?.v=4
"First-line trial currently shows median overall survival of 27.5 months
for OGX-011 in combination with docetaxel and prednisone and a 16.9
months overall survival for docetaxel and prednisone alone."
Does the fact that the headline makes a distinction between median overall survival of the OGX-011 arm and overall survial for the control arm imply perhaps that all events have occurred in the control arm?
There's also this language later in the PR: "Results currently indicate that patients in the OGX-011 arm have a death rate approximately 40% lower than patients in the control arm. The current results are based on study data with a median follow-up of approximately 30 months for both arms. Additional survival updates are needed before a mature median survival for the OGX-011 arm can be reported. Based on the current results, OncoGenex has calculated that the final median survival for patients in the OGX-011 arm can not be lower than 22.7 months." By not also referring to the contol arm in these last few sentences, this almost implies to me that the company is saying they have a final overall survival number for the control group and that is 16.9 months.
My point is that if we know 16.9 months is the final overall survival number for the control group and 22.7 months is the minimum overall survival number for the OGX-011 arm (again, assuming all events have occurred in the control arm but we must wait on the remainder of events in the OGX-011 arm), then this data should likely be viewed in very good light even if a p value wasn't quoted.
? Not sure what you are asking different than I already expressed. If HR=0.60 on a trial with 40 patients per arm then only a small percentage of patients could have died so far. As a greater percentage die the HR and the p value will change.
Ok thanks, I was just trying to ensure that I understood your point and I do.
The more interesting point is that they gave enough data to hint that the HR through, say, 20 months was a lot better than 0.60.
But again, that really doesn't mean much if you don't also get a p value <.05 does it? And it doesn't seem like we have any way of knowing the p value given the data we have so far. Are there instances where hazard ratios still matter even if p value >.05?
Iwfal: RE OGIX Phase II trial results
I assume by "events" you are referring to patient deaths. Wouldn't the company still be able to report a p-value even if there were few deaths/events? Just wondering if there's any chance that they didn't because the p-value may have been greater than .05 at this point (i.e. not stat sig).
Also, is it a valid concern to wonder if these results only pertain to a few deaths/events? If I understand what you're saying, the strong survival advantage so far may be due to just a few deaths/events so when more do occur the advantage of OGX-011 over the control arm may diminish.
Finally, do you have any thoughts on OGIX as an investment at this level ($25 million market cap)?