who is here in HALO now because they think there will be breakthrough status this year will be very disappointed. This drop has nothing to do with that. The large shareholders who might have influenced trading today have other things on their minds, I assure you. This has NOTHING to do with breakthrough status.
Don't sweat it. Today march options expire and someone big sold 2000 March 15 calls a couple of weeks ago. That represents 200,000 shares that need to go for under 15 today. Since HFT represents many times the volume of real trading, those 200,000 shares probably represents most of the real trading today.
Take heart; the same entity bought 2000 April 16 calls at the same time so you know we are likely to be well over 16 in a month. You might consider trading around this knowledge.
In order of probability, IMO:
I am hoping they stay independent until PEG approval. Should be able to fetch 10billion by then.
When is enough enough? :-)
I've got plenty. Thanks for the tip.
I've listened to that presentation three times. I LOVE it. I am very confident in this company. I also have a very good feel for FDA decisions and, IMO, they require more than this to approve. I don't at all believe there is data manipulation. I am only pointing out room for that and the FDA has zero tolerance for this kind of ambiguity.
I suppose we'll have to agree to disagree. If you are correct that HALO gets BTS in 2015, I will toast your health and our mutual wealth.
"This data, along with the gestalt of all preclinical and clinical results, is good enough for me to invest a boatload in Halozyme, but it won't be good enough for the FDA. "
So, not only isn't it clear that the new test will replicate the old method, it appears the HA determination had been done after results had started to be known. How can you cite data from a study that threw out more subjects than was kept in without once mentioning that flaw? Since the very good results on ORR completely depend upon high HA rating, one has to ask themselves how independent these evaluations are in an open label study. I know the FDA will. Review the results you cite- on slides 66 and 67. From a post a few weeks ago on i-HUB:
To continue to play the devil's advocate (the genesis of my NdP) it wouldn't take too many non-responders on that ORR slide #66 to be classified as "HA rating not available" to make excellent results out of poor results. (The data on the next slide on PFS has similar, if lesser, problems.)
Notice that of the 74 subjects in the PAG arm, there were only 35 who had HA classification. This, despite the fact that HA classification of biopsied material is supposedly a criteria for enrollment. Also note that 12/17 High HA responded while only 9/18 Low HA responded to PAG. This might be above reproach if there weren't only 25/74 responders in the whole PAG treatment group.
Think about it; you randomize 74 subjects to PAG and 25 respond. Twenty one of those responders are in the group they have HA id on. Only four responders are in the group that, for some reason, they have no HA id on. It doesn't take much to see how data could be manipulated here. If it were truly randomized, the percentage of responders in the PAG arm without HA status id should be consistent with the cohort with HA identification. It should be about 60% (9+12 /35), not 10% (4/39).
This is why I believe the FDA will demand efficacy data in Ph3 on a cohort PROSPECTIVELY identified as High HA by a reproducible test. . They've got the test. Should be able to start the study early, we hope.
The interim look was unplanned because the interruption in the trial was unplanned. It made sense to look at the pre-interruption data on its own. It is probably strong enough, along with accumulated post-halt data, to get permission from the FDA to start a Ph3 trial before the Ph2 is finished. There even might be an agreement to use some of the Ph2 subjects toward Ph3 results, thus setting us up for possible an early Ph3 stop.
Good numbers like those your cite are not enough for breakthrough status (BTS). The study behind the numbers must have good methodology. The main problem with this Ph 2 data is that the determination of the HA status by an older method and it is retrospective. This data, along with the gestalt of all preclinical and clinical results, is good enough for me to invest a boatload in Halozyme, but it won't be good enough for the FDA.
let me explain further
I, for one, would rather nobody anticipated breakthrough status. For reasons I've gone over, it is highly unlikely in 2015. And I'd rather not worry about any downward pressure this year from the frustration of not getting it. I'd rather focus on the abundant probable milestones that will take us to the promised land in due time. OTOH, I doubt message board psychology has too much effect on share price so I probably shouldn't care.
That's better than anything I could come up with.
Certainly Enhanze reduces infusion times dramatically. Does anyone know any evidence it reduces infusion reactions too? I'm wondering if the analyst at Danskebank misspoke.
Tissue is relatively easy to obtain thru needle biopsy; either endoscopic/ultrasound guided or CT guided. Less frequently a met is obtained (eg, liver) and, yes, studies show the mets reflect the primary HA content.
The prelim results of 201 and 202 strongly suggest PEG has no effect on low HA tumors but has a very strong effect on high HA tumors. The ph3 will very likely require HA content to be determined to be high as a criterion for enrollment. The biopsy shouldn't be too hard to obtain. And the stage will preclude any thought of resection so biopsy will be the likely source of tissue.
The cost and the side effects of PEG will make its use in all pancreas tumors regardless of HA status very unlikely.
I appreciate you pointing me here. ADXS is already my third largest biotech position. Despite the run-up, it is still a great value.
More from the same article. This deal shines a light on the value of cancer vaccines in the new era of checkpoint inhibition. Cancer vaccines are back in and ADXS has the goods:
Bristol-Myers' deal today could go a long way toward reviving expectations for cancer vaccines, which have experienced a multitude of setbacks in the clinic at Merck KGaA and elsewhere. The pioneering cancer vaccines just haven't had the efficacy punch needed to prove their value. But with checkpoint inhibitors like Bristol-Myers' leading program for Opdivo stealing the limelight in cancer R&D, leaders in the field are demonstrating a renewed interest in matching a therapy that can jump-start an immune attack on specific cancer cells with new therapies that are taking the brakes off an immune system assault.
Obviously, we've been looking for a partner for some time," Bavarian Nordic CEO Paul Chaplin tells FierceBiotech. In the early days the field's risky profile had an effect. But with the arrival of checkpoint inhibitors and the booming market for collaborations, the pendulum swung in Bavarian Nordic's favor, particularly as new data rolled in on Prostvac's efficacy.
"The world has changed," adds Chaplin, pointing to the large percentage of cancer patients who don't respond to the checkpoint drugs and could well benefit substantially by adding a cancer vaccine. "I think we became quite popular in the last 18 months."
Bristol-Myers already has a mid-stage combination study underway with Prostvac and Yervoy to test that theory. More combo studies are being planned, according to today's announcement. And just days ago Bristol-Myers and Aduro noted that they had begun a midstage study of a combination therapy that includes Opdivo and GVAX, one of the failed cancer vaccines that has now come back into the spotlight.
March 4, 2015 |
Determined to stay ahead of the growing pack of rivals in immuno-oncology, Bristol-Myers Squibb ($BMY) has swooped in with $60 million upfront to gain an option on Bavarian Nordic's Phase III therapeutic prostate cancer vaccine Prostvac, ready to shell out an additional $915 million-plus in milestones if it takes the next step to license and ultimately commercialize the therapy. In the meantime, Bristol-Myers--which has now committed up to $2.6 billion in three new cancer R&D deals over the past two weeks--and its new partner are hatching plans for a slate of combination studies.
If Bristol-Myers does take the next step, it will be on the hook for another $80 million payment, more than $230 million in development milestones if the therapy tops its Phase II efficacy results, $110 million in regulatorymilestones and $495 in sales milestones. The Danish biotech will manufacture Prostvac and also stands to earn a double-digit royalty.
(Reuters) - An experimental therapeutic vaccine from Danish drugmaker Bavarian Nordic helped significantly extend survival in patients with advanced prostate cancer, according to results of a small early-stage trial conducted by the U.S. National Cancer Institute.
Patients were treated with the company's Prostvac vaccine, in addition to escalating doses of Bristol-Myers Squibb Co's Yervoy, an approved injectable treatment for advanced melanoma that works by taking the brakes off the body's immune system.
On average, patients taking both drugs survived 31.3 months, compared with a predicted survival period of 18.5 months that had been based on historical survival data for older chemotherapy treatments.
Among the 15 patients who received the highest 10 milligram dose of Yervoy in combination with Prostvac, 20 percent remained alive at 80 months.
Data from the combination trial were especially impressive, considering that Yervoy had previously failed in Bristol-Myers' own trials to prolong survival in patients with advanced prostate cancer.
Yervoy and an emerging group of immuno-oncology drugs called PD-1 inhibitors from Bristol-Myers, Merck & Co and other drugmakers are expected to have greatest effectiveness when used in combination. The PD1-inhibitors make cancer cells more visible to the immune system, removing their natural camouflage.
Prostvac is a prostate cancer vaccine regimen consisting of a recombinant vaccinia vector as a primary vaccination, followed by multiple booster vaccinations employing a recombinant fowlpox vector. Both vectors contain the transgenes for prostate-specific antigen (PSA) and multiple T-cell co-stimulatory molecules (TRICOM). The PSA-TRICOM vaccines infect antigen-presenting cells (APCs) and generate proteins that are expressed on the surface ..
Breakthrough status is rare, but becoming more frequent in the past year. It is a MUCH better status than fast track because it will allow for FDA approval on less than completed Ph3 data. That could save years in development. Fast Track status only gets you priority reviews and the ability to work more closely with the FDA on trial design.
I believe that fezz is correct that PEG could qualify for Breakthrough status. I am just qualifying his comments to opine that the FDA will require HALO to first show efficacy in a cohort prospectively chosen with the new HA test - and that will take at least another 18 mos, probably longer.
I picked up some last week. My MO is to average into new stocks over a few months, so I will likely be buying more. My two largest holding are HALO and NVAX. Another half dozen round out the fotd biotech fund. ADXS is rising but, heck, I haven't even got thru that 2.5 hour analyst day presentation yet... My day job, and my kids, are keeping me too busy right now.
Did it cut me off? :-)
inside a larger ph 3 study that has official measured outcomes of PFS and OS. That way we might hope for breakthrough approval by late 2016. That would be a wild success.
Many other milestones along the way will continue to propel HALO upward.
Interesting. Thanks, Sudn. But I do not hold much hope for breakthrough status in 2015. Perhaps 2016.
As you know, I am very bullish on HALO. It is my largest holding. But sometimes I feel it is my duty to put the brakes on what I consider unrealistic expectations. I think the upcoming meeting between Torley and the FDA is about what a Ph 3 will need to show. My hopes are there might be two stages with some early stage able to be combined with Ph 2 safety data to possibly qualify for breakthrough status.
At present, we have been shown some very early 202 data. The results are outstanding and the fact that this cohort had an interrupted course suggests those in the second half of the study with full uninterrupted pEG dosing will do even better. That said, we are missing consistent prospective high HA tumor identification.
The post-halt cohort of 202 didn't start enrolling until July. They are probably still enrolling the last of the 100 subjects now. It will likely be a year from now before the data is mature enough for the FDA to consider it. Remember that the subjects from the first cohort, that we were treated to some early analysis at Analyst's Day, started the trial in 2013, and even that wasn't mature.
In addition, all of these subjects had their HA status determined by a method that will not be used commercially when PEG is approved. In fact, IIRC, more than half never had their HA status determined at all for the ORR analysis. And when there is NO therapeutic effect shown for addition of PEG to chemo on those with low HA, and, likewise, NO therapeutic effect for PEG on the cohort that did not have PEG status determined, then you can conclude that new HA test will become key to final approval.
What I hope for is that the FDA tells Torley that the safety data from the Ph2 202 study will be sufficient, but that there needs only to be shown efficacy with ORR in a cohort identified prospectively with their new HA test in a small cohort inside a l