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Well if the Jak's are multi-billion dollar drugs, then imetelstat has a lot of room in this space (if indeed they are complimentary).
I believe I have heard GERN CEO in the past say that no other drugs can alleviate symptoms (AND) hit the underlying cause of the disease --- which I believe he was hinting at -- imetelstat hitting both of those.
Guaranteed more color coming on this on the poster at ASH - however, this is clearly an active drug and potentially disruptive.
GERN - is it logical to conclude that if BM and peripheral blood has received a CR, then the other "symptoms" will be alleviated via the underlying aspect of the blood which is driving those symptoms?
I would find it hard to believe that it wouldn't, which is why I am asking.
Chalk up yet another clinical development screwup courtesy Curis. They're much smarter than both Roche and Novartis, right?
CRIS are a bunch of nincompoops and just did what their LI suggested (see comments from R&D Day, below). Further, there were other patients in this current trial on higher dosing that did not experience any such issue or a DLT. Clearly, IMO, the LI wasnt bright to enroll a patient with liver impairment when in the previous Ph1, there were 2 incidence of liver enzyme issues at 450-600 mg. I am not even sure they need to dose this differently, it may be more stringent enrollment requirements.
So in summary, GDC-0917 had a favorable safety profile. We didn't actually determine the maximum tolerated dose, had, what we consider, a reliable PK profile. We stopped at a dose of 600 milligrams once daily for 14 days, every 21 days, based on the dose that portended the effective concentration for 90% inhibition. We saw, as Ali showed, that you can actually down-regulate cIAP in tumor biopsies, and we saw encouraging antitumor activity. Now this agent then subsequently was in-licensed by Curis. And so, we had an opportunity, like, say -- to say, okay, what needs to be done to explore this and try to find and determine what is the optimal dose, what is the optimal schedule, what are the optimal patient populations? So the first point. In the studies that we did in-house in start, we tried to determine, with the help of Curis, whether indeed there's dose-dependent antitumor activity in preclinical model.
Since the elimination of half-life range between 4 and 8 hours on averaging about 6 hours, the question arose: Can you deliver the drug twice daily and hence, improve the antitumor effectiveness? Is it possible to give the drug continuously? The 2 weeks on, 1 week off, dose would base somewhat empirically, and so one wanted to see, can you give the drug safely on a continuous daily dosing? And finally, if you saw antitumor activity in ovarian cancer patients, can we actually try to determine what might separate those patients who respond versus those that don't?
So let me address first and foremost, the dose-dependent nature of CUDC-427. And this is the same cell line that's a triple negative breast cancer model. And this is actually performed independently in our lab, not in Genentech or at Curis. And as you can see, we examined the dose schedule. This is a dose that was actually recommended by -- for preclinical studies, by Genentech, 10 milligrams per kilogram every day for 28 days. And we examined both increase of dose 20 30 and also a BID schedule. And I'll bring your attention to the fact that the recommended dose from Genentech was actually 10 milligrams, which is the blue line. But we found that as you increase the dose, you were then more able to improve upon the antitumor activity.
If you compare BID to once-daily dosing in the animal model, it's not quite so apparent because, of course, the overlapping error bars that are present. But what this really suggests, first and foremost is, that we can't be content with just a dose at the ED 90. We really need to explore how high we can go to try to get maximum antitumor activity out of this molecule.
So to address this, we've launched a Phase I study right now where we give the agent twice daily to patients with advanced malignancies, and the cycles are every 21 days. And so schematically, this is how this new schedule appears.
Now I've addressed dose, and I've addressed schedule. The most important question in targeted therapies is how do you identify the right patient? Because if you can get the right dose and right schedule, but you don't have the right patient, the whole system falls down.
Maybe Berger is in denial (or was in denial at that point) but an anti-platelet really would seem to make sense.
That's a good NEJM article to read.
$ARIA
What evidence do you have that there was no demand for the shares? (other than speculation on Twitter). It could also very well have been that the stock is down substantially from where they issued the S-1. If their bankers were floating them the idea that they already had a "bought deal" lined up for them, and then the stock drops 30-35% from original price, I don't blame management for yanking this deal.
You could be right about the demand issue, but it could also be a banking issue as well.
IMO, its the least talked about game-changer drug in CLL, and quite possibly, right up there with ibrutinib.
What do you think of ABT-199?
Would really think that if I was a very large pharma that was "kicking tires" on Ariad at $3.5 billion marketcap, it's looking a lot better at $800 million marketcap (*assuming they don't think Ponatinib is worth nothing w this recent debacle).
If I were the CEO of a big pharma that was interested in Ariad, I would be sitting on the bid, all day long, buying everything in sight up to 20% of the entire company.
Is there a poison pill in Ariad anymore (I haven't paid much attention to the story in months)('113 was of more interest to me than Ponatinib).
Sorry...I can't answer any questions about what happened recently ---- so please don't ask--- you guys would know more than I would. And I have no comments on future price as well...
All good catalysts.
IMO, 1135 is a much more compelling reason to own the stock at these levels, than 1127 is.
Its not surprising to hear they were/are having trouble enrolling 1135 because of Soliris. They actually got FDA approval to begin dosing in August of 2012....and almost a year later still didnt have a single patient dosed (they used the excuse they needed summer school vacation to start ).
No credible company is going to release data at an investor show (unless you're thinking that "news" = we have a "X" number of patients on the drug)
I happen to agree with Patrick here...1127 is probably nothing more than "stable disease" (at best). Nothing from the scientific community on the target, nothing from the patient community in terms of evidence it has worked in anyone (and it is a large trial with several centers), and not a single word from any of the medical conferences about the target or the compound. I suspect even if the results stink("meh"), the bankers will say, "it was never meant to be a single agent, but it would be a perfect 'bolt on' for PD-1 and see it as an acquisition target" and run it another 50 points.
Having said that, doesn't really matter if the compound is crap or not --- sellside thinks its a good story, and good stories drive stocks....I bought in very low single digits in 2011, and bought more, and more, and sold as high as 21 and change. Do I wish I still held it? I sure do---- but I still got 600%. So, rather make money than be right about 1127 being a dud. Having said that, no way I am going to chase this up here.
I completely agree. Stock was my biggest winner this year. Bought in the low single digits in 2011 and started selling at 15 through 21.00.
I just don't think the current hype around '1127 is warranted - but it is great for those who still own the stock, so, congrats. Rather make money than be right!
Why do you say CDX-1127 is a "dud?" Do you have supporting evidence?
IMO, CDX-1127 is a dud and sellside firms are pushing this compound to drum up a good story (immunotherapy) and drum up trading revenues. Sellside firms are now claiming CDX-1127 will be a great combo drug for PD1 (meanwhile, no one has seen any data on it, and I have heard zero buzz on the CD27 target from any science folks).
I would like to know who his source is.
A "source" can be anyone. A complete schmuck, or a legitimate investor.
I think Deerfield has been doing this for a long long time (they just have never been caught, so, probably figured... let's just keep doing it).
Hopefully, this is a wake up call for firms that do this - although, the penalties should be much higher as they clearly knew a financing was coming (especially in the ARRY financing where they shorted 1.4 million ahead of the offering in the quiet period). Probably did the same thing with the Exelixis financing in 2012 as well.
See Deerfield financings - http://www.sec.gov/litigation/admin/2013/34-70398.pdf
Aquillo Capital issues letter to Board of Directors of Astex (ASTX)
http://www.marketwire.com/press-release/-1828265.htm
SOURCE: Aquilo Capital Management
September 09, 2013 05:00 ET
Aquilo Capital Management Submits Open Letter to the Board of Directors and Fellow Shareholders of Astex Pharmaceuticals
SAN FRANCISCO, CA--(Marketwired - Sep 9, 2013) -
Dear members of the Board and fellow shareholders of Astex Pharmaceuticals,
We are the Managing General Partner and Portfolio Manager of Aquilo Capital Management, a life science investment fund based in San Francisco. Our fund invests exclusively in small-cap biotech companies globally. We are long term, value-oriented investors with extensive experience in assessing the economic potential, operations and management teams of companies in the health care sector. We have been shareholders of Astex Pharmaceuticals (the "Company") for three years. At present, Astex is one of our top five holdings.
We are writing to express our extreme disappointment in the Company's recent announcement that it agreed to be acquired by Otsuka Pharmaceuticals Co., Ltd for approximately $866 million or $8.50/share (the "Otsuka Offer"). Based on our analysis of the Company, we believe the Otsuka Offer does not reflect the Company's current value, or its ability to generate value in the coming years, and we urge the Company to reconsider its options.
We believe the Company should: (1) remain independent and execute on important near-term milestones, and unlock the intrinsic value within the full development pipeline, or (2) seek to significantly increase the Otsuka Offer to account for the combined value of the current cash, the Dacogen royalties, two wholly-owned Phase 2 assets, a productive discovery platform, and five fully-funded partner programs, each with significant milestones and royalties, or 3) spin out a special purpose entity that allows the Company's shareholders to share in the future potential royalty streams from the partnered programs. The Company can easily be valued at $13 to $14 per share today, and potentially two to three times that amount within 18 months.
We base our opinion on the following:
With ample cash resources, recurring revenues, and considerable financial flexibility, the Company can remain sustainably independent
The Company had $134 million in cash on June 30, 2013, enough capital to sustain operations for several years even under aggressive spending scenarios. In addition, the Company has guided to $65 million in royalty revenue in 2013 for its hematology drug Dacogen and acknowledged that generic competition is less severe than originally contemplated. With the recent approval and launch of Dacogen in Europe by the Company's partner, Johnson & Johnson, and the recent filing for regulatory approval in China, the Company stands to receive an unusually high royalty rate on net sales of Dacogen, up to 30%, for years to come. Owning a royalty stream of this magnitude is extremely rare in biotech and even a modesty successful product will yield meaningful recurring revenues. Our conservative estimates yield an NPV of $4 to $5 per share of value for the Dacogen royalty alone, since the Company spends nothing on Dacogen and the revenues drop straight to the bottom line. Considering the Company has nearly $1.50 per share in cash today, and a royalty stream that could earn up to $1 per share per annum on a single product, the $8.50 per share is paltry and insufficient. This is especially true considering that the Company could almost certainly monetize the Dacogen royalty stream today for a substantial payment, if it desired.
There is a significant market opportunity for SGI-110 in multiple therapeutic indications with a major value inflection point in the coming months
The Company's lead development program is SGI-110, a wholly owned drug that is a more potent and more convenient formulation of Dacogen. Our view is that SGI-110's mechanism of action, validated by the clinical and commercial success of Dacogen, suggests a high likelihood of successfully reaching the market. To date, SGI-110 has shown compelling early clinical data in hematological settings beyond that for which Dacogen is used, was selected as a highly-promising investigational agent by the Stand Up to Cancer Foundation, and could be entering into pivotal studies as earlier as next year. Importantly, the Otsuka Offer clearly does not account for the fact that SGI-110 may have utility in numerous solid tumor indications, such as ovarian and liver cancers, which would dramatically increase the drug's peak value to well above $1 billion annually. Important data from several clinical trials with SGI-110 will read out in the next several quarters, including essential data to be presented at the annual meeting of the American Society of Hematology in December. If these data are positive, the value of the drug and the Company as a whole would increase dramatically and there would be several potential avenues to monetize the asset should the Company choose to do so. Selling the company on the eve of this important data release significantly undermines the value creation shareholders have worked hard to support.
The Company's other development programs, both partnered and wholly-owned, have considerable value.
The Otsuka Offer does not reflect the value of the Company's pipeline of 11 additional drug candidates, including the five programs that are fully-funded by Pharmaceutical partners. For each of the partnered programs, the Company spends nothing, yet is eligible for nearly $2 billion in potential milestone payments and high-single to mid-teen percentage royalties on each product that reaches the market. Critically, these programs are just now, or will soon, reveal their potential clinical value and shareholders will have received zero value. The Company's second cancer drug, AT13387, is in well-designed Phase 2 trials in prostate and lung cancer, with data expected next year. A partnered program with Novartis, a CDK4/6 inhibitor called LEE011, is currently in eight clinical trials in multiple cancers. We note that a competing drug with the same mechanism of action recently received FDA's Breakthrough Therapy Designation, is expected to be a multi-billion dollar drug, and added hundreds of millions to the market cap of the originator company based on an 8% royalty. Two additional novel cancer drugs are progressing with partners. AstraZeneca is now running five clinical trials with an Akt inhibitor AZD5363 after presenting encouraging data earlier this year, and Janssen/J&J have recently initiated a clinical trial with an FGFR inhibitor, JNJ42756493. As these and other programs progress, their value could ultimately exceed the Company's currently market cap. The Otsuka Offer is particularly frustrating because the proposed acquirer has minimal operations in oncology and adding a ready-made pipeline of assets should be a center point in the deal. As it stands, the offer price clearly ascribes no value whatsoever to the Company's pipeline.
The Company's proprietary fragment-based drug discovery platform has been highly productive and has favorable future prospects.
The Company's core chemistry technology, called Pyramid, has been highly productive in discovering small molecule drug candidates against a wide variety of disease targets. It has yielded at least seven drug candidates that reached the clinic in the last ten years. This output exceeds that of discovery efforts at far larger competitors. The value of the Pyramid platform is apparent in the unusually high number of industry and academic partnerships. Major pharmaceutical companies, such as Novartis, AstraZeneca, Janssen and GSK all collaborate with the Company on drug discovery, as do highly-regarded academic institutions such as Cancer Research UK, Canada's NCIC Clinical Trials Group, and the Stand Up to Cancer Foundation. Each organization has elected to spend their limited resources on testing the Company's drug candidates in clinical trials. The Pyramid platform has generated tens of millions in non-dilutive research funding and there is no reason to doubt that it will continue to be productive. As we noted for the clinical pipeline, the Otsuka Offer is upsetting because the Company's Pyramid platform will provide the acquiring company with a valuable discovery operation that they do not have, nor have ever had.
Management's rationale for the merger of Supergen -- Astex has yet to be realized
Lastly, the timing and acceptance of the Otsuka Offer interrupts a new chapter in the Company's growth. Over just the next 18 months, the Company and its partners will complete numerous clinical trials, starting with the presentation of vital clinical data for SGI-110 in December. In addition, we anticipate important data for SGI-110 and AT13387 in various solid tumors in 2014. Partners will report progress with other programs, notably Novartis's LEE011 and AstraZeneca's AZD5363. After five years of indifference, the market began to recognize the Company's intrinsic value, bolstering the stock price more 100% in the months leading up to the Otsuka Offer. We are perplexed as to why the Otsuka Offer would be accepted now at this pivotal point in the Company's history. Major inflection points are within sight, material clinical data for the SGI-110 program just two months away, yet we, as shareholders, are being asked to tender our shares at the grossly inadequate Otsuka Offer price. Quite frankly, management's promise to shareholders at the time of the merger of Supergen and Astex Therapeutics in 2011 -- that of a robust combined entity with ample cash resources and a deep product pipeline -- is being inexplicably undermined by an ill-timed acceptance of exceedingly low bid for the Company.
The Board and Management's fiduciary duty to shareholders was not fulfilled
The peculiar timing of the Otsuka Offer leads us to believe that the Board and current management did not fulfill their fiduciary duty to shareholders. We were disappointed that the conference call following the announcement of the deal was exceedingly brief, lacking in details, and did not allow for questions. We are left without answers to several important questions: Why would a 5 year business review, at this juncture, result in a decision to sell the company? Are executives from the former Astex Therapeutics in agreement with this decision? What other options did the Company consider? Without clarity on these and other issues, we are left to wonder if the lucrative change of control provisions and severance packages in management compensation packages resulted in a gross misalignment with shareholders and a distorted view of the Company's current situation.
In closing, we believe that the Company is currently on the path to success, making great strides in becoming an important player in the oncology market. In a robust capital market environment in which biotech companies with fewer resources, lower commercial potential, and minimal clinical pipelines are being valued for far more, the board has decided to short-change shareholders of the value that they have supported and helped to create.
Thank you in advance for your careful consideration. We would welcome the opportunity to speak with you in person to discuss our concerns.
Sincerely,
Marc R. Schneidman
Managing General Partner
Adam S. Bristol, PhD
Portfolio Manager
IMO, ASTX is now "in play"
"(Otsuka) will make an announcement once a decision is made."---- ergo, Otsuka agreed on a price and presented that price to ASTX who HASNT agreed to anything at this point.
Otsuka Denies Report It Has Decided to Purchase Astex
By Alex Nussbaum & Marco Lui - 2013-09-05T00:27:06Z
Otsuka Holdings Co. (4578), the maker of the mood-stabilizing drug Abilify, denied a Nikkei report that it has decided to buy Astex Pharmaceuticals Inc. (ASTX) for 90 billion yen ($900 million).
Otsuka isn’t the source of yesterday’s newspaper report, the company said today in a statement to the Tokyo Stock Exchange. It will make an announcement once a decision is made. Astex surged 24 percent to a nine-year high of $8.27 at the close in New York yesterday, valuing the Dublin, California-based biotechnology company at $785 million.
Otsuka, which also makes Pocari Sweat drinks and Soyjoy nutrition bars, wants to buy Astex to increase its stable of cancer drugs, the Nikkei report said. With one leukemia drug on the market and other treatments under development, Astex may command a higher price or attract other bidders, said Gene Mack, a Brean Capital LLC analyst based in New York.
“If it’s for real, I think the offer is too low,” Mack said in a telephone interview. “Any oncology company would look at it as a target.”
Otsuka gained as much as 0.6 percent to 3,000 yen in Tokyo trading, and rose 0.2 percent at 2,987 yen as of 9:09 a.m. The shares have advanced 23 percent this year, lagging behind the 35 percent increase of the benchmark Topix index.
Astex’s SGI-110, an experimental treatment for acute myeloid leukemia, had positive results in a mid-stage clinical trial, the company said in an Aug. 28 statement. It has one marketed product, Dacogen, a leukemia drug licensed for sale by Eisai Co. and a unit of Johnson & Johnson.
Timothy Enns, a spokesman for Astex, didn’t respond to an e-mail and telephone call seeking comment on the report.
Abilify is one of the world’s best-selling schizophrenia treatments. Otsuka has been searching for new products before 2015, when its patent on Abilify expires.
Yes, pretty obvious now what happened with that vague PR, in hindsight. They released full data-set to acquiring company, put out minimal info to the public to satisfy RegFD...
I hear you re: giving up shares. Seems about $8.50 is where its going to be valued - my biggest regret was trying to figure out what the full value and conversion was/is in the absence of any PR from ASTX (still nothing as of now!), and not selling entire position above 9.00 when I could have.
Still no clue if this is even real or not. As of 4:23 PM, no PR from any of the companies - and no lawsuits filed by law firms saying the value is too low ! :)
The entire tivantinib program is a screw up.
Complete mismanagement at every single step
[My guess is that HCC AEs @120 mg will be mild. Cannot even guess about efficacy
ASTX BRIEF-Otsuka to acquire Astex Pharmaceuticals Inc for JPY 90 billion - Nikkei
1:25 PM Eastern Daylight Time Sep 04, 2013
Sept 5 (Reuters) - Nikkei:
* Otsuka Holdings Co Ltd <4578.T> has decided to acquire Astex Pharmaceuticals Inc <ASTX.O> for an estimated JPY 90 billion - Nikkei
* Source text - http://link
Lots of evidence out there that this PARP has good stuff in BRCA1+ ovarian
AZN
If I'm not mistaken, there are zero prior data for efficacy at the 120 dose for HCC
Does anyone know if the PD-1 class of drugs has an effect on this sub-population?
If so, tivantinib, here, is a non-starter, IMO.
ARQL
IMO, if another shoe drops in the tivantinib program ARQL will likely trade for less than cash.
I have very little faith in this entire program now.
That's because Pucci is not a competent CEO
IMHO, MET-high pts are much more sick and more sensitive to AEs.
The problem I have is the fact that they are reducing the daily dose 50% from 240 to 120. Or, put another way, they thought they needed at least 100% (double) increase from 120 to 240 to get a good therapeutic dose in HCC for it to benefit the most for the Phase 3 trial. Why did they make this assumption....? Can 120 mg BID actually hit MET hard enough to knock out the pathway? If they thought so, why bother going to 240 mg BID to begin with. This is just another checkmark next to incompetency for Pucci and Daiichi when it comes to this ENTIRE tivantinib clinical program (this is very Exelexis'esque in that they are now essentially doing a dose DE-escalation exploratory study, in an actual Phase 3 pivotal study). Just how bad could the neutropenia have been in the tivantinib arm, this early in the trial, for the DMC to recommend they DECREASE the dose...not 25%, not 33%.. but 50% ! IMO, this is stretching it, but it wreaks of Arqule and Daiichi begging the DMC to 'please dont halt the entire study, we'll drop this 50% and see where the shoe drops next' type of scenario.
Simple fact of the matter is, these things generally don't happen with very good drugs....
I sold some today, and will continue to sell on any additional strength - Phase 3 HCC is a total crapshoot now, and ESMO, while it might give a 20-30% pop, it's not enough for me to get all hot and bothered over----I'd rather find a drug that can give me 500% over the long term --- and, after this latest fiasco from Pucci & Co., I just don't see ARQL as that company.
ARQL
Do you have any evidence to suggest that they can even get a good response in HCC at 120 mg BID ?
ARQL
read my previous post
ARQL
Can they even get a good tx dose at 120 MG BID ???
Item 8.01 Other Events.
ArQule, Inc. (“ArQule” or the “Company”) and its partner, Daiichi Sankyo, Inc. (“Daiichi Sankyo”) are currently sponsoring a Phase 3 trial of tivantinib in the treatment of hepatocellular cancer (“HCC”). This trial is known as the METIV-HCC study. Recently the Company and Daiichi Sankyo received a letter from the trial Data Monitoring Committee (“DMC”) recommending that the study dosage be reduced from 240 mg twice daily (“BID”) to 120 mg BID and that certain enhanced patient monitoring procedures be instituted to confirm the safety profile of the lower dose. This recommendation resulted from the observation of a higher incidence of neutropenia in the METIV-HCC trial than was observed in the Company’s and Daiichi Sankyo’s Phase 2 trial in the same patient population.
The Company and Daiichi Sankyo have accepted the recommendation of the DMC to implement the lower dose and will be filing a protocol amendment with regulatory authorities and related parties. After a prescribed number of patients have been dosed at 120 mg BID, the DMC will review data from that patient cohort to determine the safety profile of the lower dose and whether to recommend any further action. Because the trial is still in the early stages of recruitment, the Company and Daiichi Sankyo are not able to comment at this time on whether the timeline for recruitment of the trial may be delayed compared with original estimates as a result of the proposed amendment and subsequent data review.
The Company and Daiichi Sankyo expect that the dose reduction will reduce the incidence of neutropenia observed to date in the METIV-HCC trial, resulting in greater patient safety and fewer early patient terminations. The Companies also believe they have now selected a dose that will offer the best possibility for a favorable benefit-risk ratio.
The Company and Daiichi Sankyo will continue to review available data from this and other studies to better understand the increased incidence of neutropenia observed in the METIV-HCC trial compared with the Phase 2 HCC trial, including any possible impact from a change in dosage form. The incidence of neutropenia seen in the METIV-HCC trial to date has not been observed in other trials with tivantinib, which continue to employ a dose of 360 mg BID.
The METIV-HCC trial is a randomized, double-blinded study of tivantinib as single agent therapy in previously treated patients with MET diagnostic-high inoperable HCC. It is being conducted under a Special Protocol Assessment with the FDA. The primary endpoint of the study is overall survival in the intent-to-treat population, and the secondary endpoint is progression free survival in the same population.
$CLDX has done this many times in the past. Management has told me they do conference calls when there is something material other than simple quarterly updates and numbers.
Thats gonna be a bummer when some 90 year old woman goes looking for her 3% dividend in $XON after the fact.
Didn't Acetylon's drug have favorable stable disease, but other than that, nosomuch? Essentially, this drug will be most beneficial with a proteasome inhibitor, and not very effective as single agent?
Yeah, they must have done a 1-for-20 reverse split to take care of Morrisey's awesome mega dilution from a year ago. :)
HDACs have been around for a while now -- vorinostat, panobinostat. Either one of these aren't knocking the cover off the ball. Any comments regarding the HDAC class and if these what people would consider epigenetics when they refer to epigenetics?
Thanks
Do you guys really think their final results in NSCLC are going to be meaningful to the stock?
And good for other money managers who will pick up the assets of SAC...