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I hope I’m wrong re: pancan. Good luck to you all.
Unfortunately, I have to agree with jam.
Since the SWOG results, I haven’t had much in HALO. Tomorrow I will sell the rest.
PFS seemed a slam dunk while OS seemed the more risky hurdle. (You can imagine the tumor staying small longer due to the de-bulking effect of PEG.) This change in trial protocol cannot be interpreted in any positive way.
I will reconsider the company in the future after trial results. I now expect them to be poor. That said, there is a lot going on in SD on Serrano Drive and I might like HALO better after they move on from pancan.
I take no joy in expressing these views here. I have lost huge sums overnight on more than one occasion when a trial result flubbed. I know the dagger in the heart feeling. But I keep researching and grinding and I build it back. But it takes continued honest re-evaluation of the investment premise. Good luck
fotd
He could have left for many reasons. He was not likely fired for cause as he landed quickly into a similar position at a much more successful company. Did he leave because he saw little future at ADXS? Did he leave because his good work opened up a door to a better career track? Did he leave because of an impending BO that would likely have seen his job downsized? My honest sense is more pessimistic, though that is probably colored by recent SP action.
https://www.linkedin.com/in/mayopujols
News happens when it happens and it is announced with a PR. This is just an investor conference. They happen according to the calendar. Do you believe all the companies presenting have somehow coordinated their news cycle so they can announce something this week?
You are off base.
"Well, Avastin has a FDA approved competitor now. Guess who? Amgen. Yup that's right. No need for them to buy our early stage product when they already have their own."
AXAL has better numbers than Avastin, and that includes any of its biosimilars. Now, the numbers are a little suspect since the two drugs did not go head to head, but even if Avastin were a little better, there would still be a tremendous market for AXAL. AXAL could be used for Avastin failures. Or, if I'm trying to choose between AXAL and Avastin and I know there is data that shows if my patient is one of the 80% with a certain bio marker that makes AXAL MUCH more efficacious, I'm going to test for the bio marker and let decide for me.
Hey Fritz, yes, nice to see. Doing well. Will have more to talk about when ph3 trial results come out. Good luck to you. fotd
Well, that helped cash flow!
I believe they looked at the costs and shelved it. There is no reason to believe they had anything npbut the best results in canine osteosarcoma. It will come to market and make pennies from dogs. But it would have cost an enormous amount to get anywhere in children's trials. Better to spend the money elsewhere.
I think it possible BMY gives ADXS $40-80 million upfront and agree to pay milestones as Dual advances thru trials in exchange for ex-NA rights to both AXAL and DUAL, paying ADXS low double digit royalties. BMY would market, sell and distribute outside North America, help pay for development, and allow ADVX to keep the US market while earing about 10% from overseas sales. This would be enough $$ to avoid another raise and should propel the SP into double digits immediately.
If this is an option, or something similar, I am for it.
"most obvious deal will involve AXAL EU rights, quite possibly with the U.S. rights included. The second guesses would be HOT, or DUAL with BMY."
I think their best shot is with DUAL. I'm hoping for some medium term revenues from AXAL but I expect it to be replaced by DUAL within a few years of approval. That short revenue life makes it a poor franchise to buy into, unless it is part of a deal that includes both.
So, what would 90% of all AXAL + DUAL, ex-US be worth - to BMY?
Of course, I hope you are right. But it takes two to tango.
What product or market do you have the most hope for regarding a deal?
While I don't like the HFT or how the SEC allows short selling abuses any more than you do, I think those factors are simply part of the landscape. IMO, what is happening now is a rational response to material news. What did we learn this week?
- the cash position is less robust than we hoped for.
- the early prostate results were just OK while many hoped for something unambiguously stellar.
- the early metastatic rectal cancer results were also just OK while many hoped for something stellar (esp in light of the locally advanced results)
- no news after a hyped "quiet period" led to anticipation that there was some kind of partnership or even buyout deal. "Hello darkness my old friend."
- no news on the only franchise that has a chance in the near term to save the company: AXAL. EU submission - same guidance without progress since last guidance. Ph3 AIM2SERVE without news but now kind of in the shadow of improvements that threaten to upstage it in a few years with DUAL and combinations and intelligent cohort selection.
Listen, I'm much more long this company than most here, so please don't shoot the messenger. It is bothersome that some respond to open discussion so defensively; as if what we discussed has any bearing on SP. It doesn't.
The platform is validated, in my opinion. The company could have put all its eggs in the AXAL basket sooner and had some properly controlled data in cervical cancer by now but they chose to explore other indications, likely with the hope the early results in one of the other cancers would be strong enough to land a partnership that would pay for the development of everything. It must have dawned on the BOD in June that rectal and prostate would not immediately deliver and that strategy was a mistake. This puts us at risk of dilution while awaiting an EU decision in 18mos (at best) and the results of AIM2 (expected about the same time).
I've been here for years, I will wait. The company is worth more than it is selling for today. But the traders have the upper hand and it could be rough for a while. Maybe the company will surprise us with a partnership. At any rate, I do best my best investing when looking out a few years and ignoring the day to day.
"What does your friend (at a non-live cancer vaccine company) have to do with ADXS's treatment, which you have confirmed has a stable safety profile?"
I believe my statement stands on its own, but let me try again to be clear.
Safety is NOT yet confirmed. That is why we do trials.
This trial in metastatic rectal cancer was done to show safety as well as efficacy. I was reminding people of that. Our vaccine did well.
My friend, who is well published and with many years in management at vaccine companies is now working on cancer vaccines. He is NOT an insider at Advaxis but he has worried in the past about the extra hurdle a live vector might have in proving safety. If you are not aware of this, be warned. His concerns predated the clinical hold and come from many years of working with the FDA for his companies. That said, I will repeat, every trial we do contributes to the safety profile.
Let me quibble about the word "very." While it is kind of amazing it worked in one PT who failed Opdivo, if there were many they would have likely mentioned that.
The ADXS platform clearly works. They have more info now with which to select the next cohort and even, perhaps, do a combination trial.
Every trial they do helps to confirm safety - which a friend at a non-live cancer vaccine company told me was his biggest worry with a listeria vector.
I think the future is in the data that further defines who benefits most, e.g. I love the idea of Dual excluding the 20% that have that factor.
The competition:
http://www.ascopost.com/News/41663
Kathy Eng should try them together.
The writer of that article is a bot.
The lesson with that company was you never know where your success ( or failure) may come from.
I was invested because I thought their subunit intranasal vaccine would be the market leader. (This was before FluMist was approved, though I had a good investment in that as well). Well, the Canadian gov wouldn't let a foreign pharma buy a flu antigen plant on Canadian soil and IDBE purchased it to supply their own vaccine. It never got that far since once they were owners of the plant, big pharma got the plant anyhow by buying the whole company, lock, stack and barrel for five times the past year's avg SP. As you noted, they then buried the technology and continued to make standard flu vaccines for sale.
"In metastatic CRPC, virtually all patients being treated will already have had a prostatectomy. So, there is no primary tumor on which to measure shrinkage in the usual manner"
While increasing numbers have been treated primarily with radiation, instead of surgery, you are correct that this is a tumor whose spread is not usually bulky and does not lend itself to evaluation by RECIST. Most useful has been following PSA, though that is not straightforward either. A decrease in the rate of rise (velocity) has been associated with increased survival.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3881217/
Man, Terry. You and I have been kicking around these messages boards a long time now. Remember ID Biomedical around the turn of the century? I was friendotd. I think you were yahooing with me back then. Maybe some other companies... I haven't run across you in awhile but your writing style hasn't changed a bit - always leaving the reader guessing a little. What ever happened to the Al Greenspan gang?
Whether you want to call it a vaccine or not, someone is paying for trialing this DNA vax. But it shouldn't hold a candle to a Lm vac. It makes sense that eventually all manner of immune regulators will find synergistic uses. Vaccines paired with checkpoint drugs are kind of a no-brainer if they can keep the side effects reasonable.
Today we read a pair of abstracts about Lm v prostate cancer. My initial reaction was disappointment in that there were no CRs or PRs. Then I looked at the history and found that stable disease is about as good as it gets with prostate cancer immunotherapy. We ought to get some good ph2 results with this combo in a couple of years. Perhaps that, along with everything else, will finally get the share price up!
Well, that's H&N. A different beast. Perhaps some prostate tumor regression could happen after a time.
My main point was that in prostate cancer, the tumor doesn't have to shrink before survival is positively affected. Keytruda is in ten trials for prostate cancer right now. Only one other trial pairs it with an antigen (vaccine): Biological: pTVG-HP Plasmid DNA Vaccine. The results of this weak vaccine by itself have not even shown stable disease - as far as I can see/find.
So, stable disease in the early stages of a Ph1/2 vaccine dosing trial ain't bad.
The treatment of CRPC is to use the next level of antiandrogen therapy, if it hasn't been used before, and then possibly some radiation. When Xtandi or Zytiga are finished, it will be time for immunotherapy. It is a long ways off but Ketruda + LmPSA has as good a shot as any.
Of course, it is too early to say if a Lm PSA vaccine will do much but while the results with this tiny cohort is not impressive, it seems to be in the ballpark and worth further study.
A 33% stable disease rate is strengthened by the associated rise in genes expressing T cell activation. That is the good news. The meh news is that there were no CRs or partial responses. That would have been the kind of news that you might go after a partnership with... Even still, there is reason to hope the combo with Keytruda might give better results than the current front runners in the prostate immunotherapy ring. Time (too much to be a factor in SP) will tell.
The state of the competition:
Provenge: FDA approval based upon improved OS of 4 mos. Never any change in tumor size so stable disease is really all they ever saw. Enough to get it to market. Lesson is the immune system can halt or slow growth without CRs.
Prostvac VF: The Bavarian Nordic PSA vaccine (plus immunostimulators) using a pox viral vector. Ph 2 results a few years ago improved OS 9 mos without any difference in 6 mo PFS between cohorts. Again, no real change in tumor size but a longer life! Now in Ph 3 with results expected very soon. Results likely good since they are running a handful of new label expansion studies with it, including one pairing it with BMS's Yervoy.
http://www.onclive.com/publications/urologists-in-cancer-care/2013/june-2013/survival-benefit-propels-prostate-cancer-vaccine-to-phase-iii-trial
Keytruda by itself: Ph 1 with 20 pts: 11 pts with stable disease including 4 pts with PSA reduction. Lot's of side effects though. Not too bad and similar to the ADVAXIS results seen today. Maybe together they do better. Certainly, as seen with the competition, CRs and PRs are not what you look for with immunotherapy in this disease.
http://www.oncotherapynetwork.com/genitourinary-cancer-targets/esmo-2016-early-results-pembrolizumab-against-metastatic-enzalutamide-refractory-prostate-cancer
Thanks. So maybe the cohort DOESN'T have to exclude the 20% with the biomarker. Though, I imagine the first trials will.
Good thoughts. Like Avastin with cervical CA, Xtandi and Zytiga have different MOAs (also antiandrogen, just intercellular) and should be complementary. Not worried about competition from them but looking at their OS results gives some perspective. If we want to know the competition, this study with Keytruda and Xtandi is as good as it gets:
http://www.oncotherapynetwork.com/genitourinary-cancer-targets/esmo-2016-early-results-pembrolizumab-against-metastatic-enzalutamide-refractory-prostate-cancer
We have a ways to go but there is no reason the Lm construct can't be the SOC. I imagine a good ph 3 will look at those who failed Xtandi or Zytiga.
Investor Day slides 109-111 and the talk around it regarding EU approval:
- discussed reasons why the EU would consider AXAL for approval despite lack of controlled studies (persuasive, if defensive - not a slam dunk)
- 210 days for CHMP approval and then another 3 mos average for commission ratification - avg 13 mos post submission (so early 2019 is a reasonable guess, though a denial by the CHMP would make the timeline shorter)
- "I can't handicap likelihood of EU approval."
And neither can we. I think Meishierwin has it mostly right in that this technology almost certainly works very well and will be approved some day. Though I'm not holding my breath on the EU.
I've been in this stock and accumulating steadily since the day AF said something good about DO and our company. Sold only above 30 and, unfortunately, very little then. I'm in this until we get FDA approval for AXAL, likely 2021. By then, with all of the corroborating data from all the other studies, SP could easily be close to 100. But until close to then, the road will be bumpy. The near term catalyst(s) I'd hope for are partnerships that bring enough cash to get us to 2021 so to avoid dilution. e.g.
All prostate entire world for $120 million + milestones to develop + high single digit percent of all revenues.
EU AXAL for $120 million upfront, they sell product + high single digit percent of EU revenues.
Those who would balk at giving these markets away should not forget the pipeline. HOT could be huge one day...
Of course, some cash flush company like AMGN might have an eye on ADXS and scoop it up before it can sign away future revenues. But I am just fine waiting for 2021, and enjoying the likely slow and very uneven rise that will accompany news on other products in the meantime.
I am most excited about that first biomarker. If they use that in the DUAL study prospectively (reducing those eligible by only 20%) I can see it being stopped early.
Biomarker(s). Have they suggested when they might be used prospectively? Simply followed?
It might be nice if the Dual trial cohort excluded biomarker 1. Any chance of that? Thanks
Agree. ADXS is not alone in this micro-biotech funk. If you look at the top ten holdings of the XBI, nine of ten are at 52 wk lows. Only Clovis is bucking that trend.
https://finance.yahoo.com/quotes/CLVS,EXEL,KITE,ALXN,CELG,GILD,ALNY,SRPT,EXAS,INCY/view/v1
My own micro-biotech portfolio looks similar. It won't last forever.
Unfortunately, he would be excluded from the Advaxis trial.
Exclusion criteria:
3: Has any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for invasive malignancy within 2 years. Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable.
From his blog:
I’m a big believer in the power of immunotherapy and believe that my recent treatment with the experimental M7824 (first-in-class, bispecific fusion protein of an avelumab-like antibody linked to two molecules of TGF-beta trap) had a positive effect on my disease.
short interest up across all biotech
http://247wallst.com/healthcare-business/2017/06/27/major-biotech-short-interest-surges/
Thank you. I'm trying to find time to read it still.
is anyone else seeing the banner above this site today advertising for Hyqvia? Pretty cool: "One Shot" These days, with the personalized ads, I always wonder what is directed straight at me and what is more generalized.
Not only did I miss that, I can't find it right now. Please help out my tired eyes. Where can I find it?
Thank you, Rod.
You're probably right. I had anticipated that and it didn't seem like "news" that should surprise. But Roche is way up and, as you and Rod and everyone else (except maybe jam knows, Halozyme is heavily involved in the development of versions of both drugs.
What news?
I think more than half the reason for today's increase is Fritz's observation that biotech in general is catching momentum.
Instead of looking for a reason to be up, I think it is just as useful to realize there is no reason to be so far down with all of the irons Halozyme has in the fire.
There are many catalysts that could surprise.
- HT said she had a goal of signing at least one more Enhanze contract this year. Knowing her, its already in the bag - or she wouldn't have said anything.
- You never know when sales of any current partnered project could jump. Hyqvia anyone?
- The PEG partnerships are real and add substance to my optimism about PEG being an active molecule that will eventually be approved. An early look into 301 is probably less than two years away.
- I don't any reason why the burn has to exceed the current 80-100 million per year. We have 200 million now. The hole isn't 450 million.
- Considering the wide uses of PEG, when it is approved for one indication, this is a ten billion company. I estimate that as being likely within four years. This market cap won't catch up with the future in one step overnight.
I don't agree about the SP. The likely need for funding was not a secret to you, or anyone else. They have a year to get it done and should find a way to get the SP up before then. The Enhanze biz is solid. Every year that goes by with more sales only confirms that the early adopters were right to take a chance on this technology. By itself, it justifies the market cap of Halozyme..
Yeah. We had to know they weren't going to finance the end of ph3 with what they had in the bank. Let's just hope they don't sell any shares until there is some bit of news that advances the SP first. eg: deal with Roche for ex-NA rights to PEG for $$$ + sale of 10 million shares for $18 per...
But, as you know, they may just sell a bunch for $9 per because they need the cash and have no options...
A thought, the size of the shelf may suggest something... could it simply be an avenue for a poison pill? Do they have one already?
Management given shares and options. Mr Market doesn't mind.
Thank you for the report. I didn't listen.
I wonder if aggressive HyQ marketing is waiting for availability of more IgG - next year they are able to produce more? I haven't thought about that for awhile.
It would be nice if Cinryse came back into the picture but I don't know of any reason to hope for that. The most interesting part of that story was the claims there was something to the "titre scare" that caused Viropharma to go it alone. Of course, subsequent development and sales of other products with Enhanze have shown its safety.
I think you ought give Humira no more tears. I see many patients who happily and easily give it to themselves at home every week or two. I believe any studies looking into its combination with Enhanze were never serious and I doubt anyone ever estimated any value for Halozyme from Humira.
As you suggest, I've long thought Halozyme might do well partnering with a generic company to develop a few of these large proteins separate from BP but, instead of contractual limitations holding them back, I suspect they don't because of a lack of resources. Besides, they probably want to be recognized as in the business of extending patents. I know docs don't like to hire lawyers to defend malpractice cases if they've dirtied themselves on the other side of the business.
They don't mention sc Herceptin containing the HALO enzyme either.
The whole set of trials wouldn't make sense if rHuPH20 was not included.
Thanks. Looking forward to February.
Define now
Hi Fritz,
Whenever I see something like this SEC doc, I wonder about timing. The "trigger date" is 12/31 and I'm aware some purchases by 5 or 10 percent owners have a trigger date that is "end of the year." The ph2 data came out afterward so this can't be taken as a sign of confidence in that.
All my biotechs are suffering these days. it seems Halozyme will drift with the market until 303 results. There may be a momentary bump if MabThera gains US approval or if there is a development with US Herceptin but 303 is the only thing, IMO, that is likely to move the needle permanently.
Regarding Trump's negative effect on biotech, it seems all wrong headed. Even if he could do the things he says, like put pressure on US drug prices and penalize ex-US aspects of the pharma business, the argument should be that would only spur pharma into more innovation and to buy US biotech companies. Whatever discount you want to try to calculate from eventual drug price to current biotech valuation can't amount to much compared to pharma's eventual need to repatriate, merge and acquire. Unless this is simply a sale of risk assets, it seems the ETF tail is wagging the dog and the ETF money is as dumb as can be.
If anyone has a link to a good article explaining the Trump effect on biotech, I'd love to read it. Thanks.