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You guys sell at positive phase 3 results and get a 6-bagger
I, instead will hold, and wait for buyout news like CPXX or just better valuations. At the end you guys will have a 6-bagger and I will have a 30-bagger.
Institutional ownership update:
1. Increased postions: 5,4 million shares
2. Decreased positions: 4 million shares
3. New positions: 4,5 million shares
4. Sold out positions: 1,47 million shares
http://www.nasdaq.com/symbol/mstx/institutional-holdings
Thanks!Why Phase 3 on sickle cell will meet the primary and secondary endpoint.
"Does the EPIC Ph 3 have a 99.9999% chance of failure?
"The treatment difference between vepoloxamer and placebo only starts to become apparent after 80-120 hours. My investor source views this delayed response as an insurmountable problem because vepoloxamer is administered only for the first 48 hours of the study. The drug's half life is 4-6 hours. Mast's study also doses vepoloxamer for 48 hours."
"There's simply no way vepoloxamer could be responsible for the separation of the treatment curves at 80-120 hours given the exposure profile of the drug, my investor source believes."
I am glad someone, anyone, has finally given a bearish view on the science, but to me this seems like a fairly simplistic view. This is a complex story and one needs to dig into all the publicly available information on the development of Vepoloxmer to properly review the current phase 3 trial known as EPIC.
Firstly, the "investor source" is looking at the VERY poorly designed phase 3 of Poloxamer-188, published in JAMA 2001. Despite all of its shortcomings and vs EPIC: 1) The trial was underpowered as it was designed to enroll 350 patients and only enrolled 255 due to capital constraints. 2) The primary endpoint was limited to 168 hours. 3) Only 29% of those enrolled were under 15 yrs old 4) Only 21% were on concurrent Hydroxyurea + P-188 and 5) Muddy endpoint of "time to discharge, the trial barely missed hitting its primary endpoint , N=249 p=.072, however among the 255 randomized patients, the results were deemed statistically significant, N=255, p=.04. Incidentally, the curves actually start to separate at around 70 hrs for the peds and those on concurrent Hydroxyurea and a subgroup analysis for these 2 groups showed statistically significant results that were "very encouraging" (according to JAMA)
"VERY ENCOURAGING"
"Nevertheless, the decrease in the duration of vaso-occlusive crisis and increase in the proportion of patients able to achieve crisis resolution, particularly in children, are very encouraging. It is possible that children exhibit a better response to PP188 because they have less overall tissue and organ damage due to previous crises and experience less chronic pain, thereby making more evident the rheologic and anti-inflammatory effects of PP188. A beneficial effect was also observed in patients who received hydroxyurea along with PP188. This could be due to a cooperative or even a synergistic effect between these 2 agents, one that might be a result of decreased adhesion of sickle erythrocytes to the microvascular endothelium or to some other less well-defined mechanism. Future studies of PP188 in sickle cell crisis would be useful to confirm the efficacy observed in children and to determine the nature of the interaction between PP188 and hydroxyurea.
http://jama.jamanetwork.com/article.aspx?articleid=194337
The "investor source" is looking at the primary endpoint in the JAMA study, "time to patient hospital discharge", which was a very muddy endpoint and based upon the availability of the treating ER physician to allow the patient to leave, which could of been many hours longer ( 5, 10, 20 hrs??)then necessary. Also in this study, the physician could keep the SCD patient hospitalized for any reason, SCD related or not. EPIC has a very pure primary endpoint that is driven by pain "time from last opioid use"(measured via patient controlled analgesia, PCA etc) not "time to discharge". EPIC has no mandatory pain scale measurements
Secondly, a healthy circulatory system is imperative in maintaining healthy organ function, and adequate bloodflow, this is especially important in Sickle Cell patients where blood flow in the microcirculation can often be comprised, especially during a Vaso Occlusive Crisis. Vepoloxamer is NOT a pain drug it is a drug that is designed to improve microvascular blood flow and hence to shorten the duration of the Vaso Occlusive Crisis which in turn should reduce organ damage (and perhaps increase survival materially over a lifetime?)
Yes Vepoloxamer (a rheologic agent) is administered for "only" 48 hours, but it adheres, seals (patches) and repairs the ruptured cell membranes, restoring the cells non adhesive properties and improving microvascular blood flow. It then releases from the membrane when density normalizes and it is cleared renally, unmetabolized. Vepoloxamer reduces the degree of adhesion to the walls of the vessels and to other ruptured red blood cells, which should lead to less occlusion and less pain. So a "delayed" response to the drug to fully engage seems not only plausible but totally reasonable. .
https://www.youtube.com/watch?v=wd4axOmxp8E
Publications (Vepoloxamer-Microvascular activity)
Vepoloxamer improved microvascular blood flow in sickle cell disease patients
during vasoocclusive crisis (prior Phase 3 sub-study) Double blind assessment of
red cell velocity (mm/s) measured in nine sickle cell patients with vaso occlusive
crisis (p=.00003)
http://www.ncbi.nlm.nih.gov/pubmed/15612454
https://ash.confex.com/ash/2015/webprogram/Paper84168.html
https://ash.confex.com/ash/2015/webprogram/Paper86647.html
http://masttherapeutics.com/wp-content/uploads/2015/07/JSCDH-S-15-00089.pdf
http://masttherapeutics.com/wp-content/uploads/2015/07/Is-There-a-Role-for-a-Rheologic-Agent-in-Transfusion-April-17-2013.pdf
http://masttherapeutics.com/wp-content/uploads/2015/07/MastThera_-2014-ASH-MST-188-Abstract.pdf
Has the "investor source" ever seen data showing that the Vepoloxamer "patch" becomes "unattached" after 48 hours from the damaged RBC membranes? Is it not possible that Vepoloxamer's RBC repair may well exceed the drugs half life of 4-6 hours? Is it possible Vepoloxamer has a durable and cumulative effect of improving microvascular blood flow and that's why it's working for SCD patients, especially kids and those on concurrent HU? Why does the "investor source" even assume that the assessment of the endpoint in the JAMA study was even allowed prior to completion of the 48-hr drug administration? Vepoloxamer is not WD-40, it is not just a lubricant, it repairs(patches) ruptured RBCs.
What about the P-188 Phase 2 trial which showed statistically significant shorter crisis and less opioid use?? (for which the placebo didn't even reach 96hrs) See subgroup 3, full dose patients N=31, duration of painful crisis 44hrs vs placebo 80 hrs, or a 36 hr decrease. P=.02.
http://www.bloodjournal.org/content/90/5/2041?sso-checked=true
What about Vepoloxamer in chronic heart failure which showed statistically significant improvements lasting up to two weeks! (I guess Vepo can have an effect after 80-120 hrs??)
"The Company previously announced that a single, two-hour infusion of MST-188 improved left ventricular systolic function that was significant immediately (at the end of MST-188 administration) and remained significant at one week (and, in some cases, at two weeks) after MST-188 administration. In particular, MST-188 demonstrated a statistically significant improvement in left ventricular ejection fraction, end-systolic volume, stroke volume and cardiac output."
http://masttherapeutics.com/investors/news/?releaseid=1900672
Why EPIC should be positive:
1)Vepoloxamer worked very well in the 1st failed phase 3 trial for children,(duration of crisis 21 hours less; P = .01) This makes sense because vessels are less damaged and more accessible in younger patients. After 250 patients enrolled in EPIC, 79% are children with average an average age of 15. The 1st failed Phase 3 only had 29% under 15 yrs old.
2) In the 1st failed phase 3 trial those patients taking concurrent Hydroxyurea (HU) +P-188 showed a duration of crisis of 16 hours less ; P =.02. In EPIC, 60% of patients are on Vepoloxamer +(HU) vs only 21% in the failed Phase 3. If 30% had been on HU in the 1st failed trial, the trial would of hit statistical significance on this one metric alone.
3) The first Phase 3’s endpoint was limited to a maximum of 168 hours. The JAMA exhibits shows that there was a clear, increasing separation between Vepoloxamer and placebo arms and that a majority of enrolled patients were not resolved after 168 hours, but marked as a censored value. It's very interesting to note that 72% of the peds in the placebo group were still in the hospital AFTER 168 hrs. It would appear vepoloxamer would have continued to show superiority after 168 hours, yet those results were not reflected in the first Phase 3. In EPIC there is no such cutoff, patients are marked when they leave the hospital.
JAMA Comments on the 168 hr cutoff:
"It is important to emphasize that in an earlier phase 2 study, even greater benefits with PP188 had been observed.19 This disparity may be explained at least in part by the assumptions used in our definition of crisis duration, the primary end point in this study. Specifically, we observed that fewer patients achieved crisis resolution within 168 hours than patients in the earlier pilot study had led us to anticipate.19 The current study used a very stringent definition of crisis resolution, one that required repeated assessments of pain throughout the entire hospitalization, including the period following discontinuation of parenteral analgesics. In a number of instances, patients were discharged from the hospital before pain relief had been confirmed by a second pain assessment. In still other instances, study patients were discharged before the criteria for crisis resolution had been met. In either case, the analysis plan required that these patients be considered as treatment failures and that the worst-case duration of crisis (ie, 168 hours) be imputed for them"
"Use of an extremely stringent definition of crisis resolution represented a very conservative approach to the analysis of the data. Because the proportion of patients achieving crisis resolution within 168 hours was lower than anticipated, the ability of this study to detect differences in the length of crisis was correspondingly smaller than expected.39 The work reported here also differed from the earlier phase 2 study in that treatment assignment was made according to the stratified dynamic randomization method of Pocock and Simon.28 For these reasons, the statistical analysis methods used in this study were conservative. While less conservative methods might have shown substantially greater differences between the study populations, such an analysis plan would have required taking into account the use of the randomization method.
4) EPIC was designed based upon the assumption that the mean duration of VOC would be 96 hours with a standard deviation of 51 hours. The interim look in October after 250 patients showed the mean duration of patients on I.V. Opioids to be 79 hours, with a standard deviation of 47 hrs. The three doctors on the recent expert calls all said, the 79 hour mean duration is "encouraging". If the 96 hour assumption holds up, EPIC results should be highly positive
FYI- (1998 hospital stay was 5.38 days and in 2008 was 5.18 days,(overall) Peds right at 96 hrs(see Figure F3))
http://europepmc.org/articles/PMC4177169
Evaluation of EPIC
http://masttherapeutics.com/wp-content/uploads/2015/07/EPIC-An-Ongoing-Pivotal-Phase-3-Study-in-Patients-with-Sickle-Cell-Disease-Aug-21-2013.pdf
http://www.twitlonger.com/show/n_1somifg
Study which shows Vepoloxamer is statistically efficient
Evaluation of Purified Poloxamer-188 (vepoloxamer) on Sickle Red Blood Cell (RBC) Membrane Function Properties
Jennell White, PhD*,1, Patrick C. Hines, MD PhD1, Ke Liu, PhD*,1, Lennette J. Benjamin, MD2, Xiufeng Gao*,1, and Martin Emanuele, PhD3
"Abstract
Background: Sickle erythrocyte adhesion and membrane fragility contribute to vaso-occlusion and downstream tissue and organ ischemia in sickle cell disease (SCD). Vepoloxamer is an amphipathic triblock copolymer with multi-mechanistic properties believed to improve these pathophysiologic consequences, by sealing damaged cell membranes and inhibiting hydrophobic cellular adhesive interactions. Vepoloxamer reduced both acute vaso-occlusive crisis duration and total opioid analgesic requirements in previous clinical studies. A phase 3 clinical trial of vepoloxamer in acute vaso-occlusive crises is ongoing. Currently, there are no standardized clinical assays to assess membrane properties such as adhesion and fragility that vepoloxamer is believed to target. We evaluated if and to what extent vepoloxamer affected adhesion, thrombosis, and membrane fragility in individual patient samples in our standardized microfluidic flow-based whole blood assays.
Methods: Blood was obtained from pediatric homozygous sickle cell patients at steady state (n=12). Patients were first characterized by measuring the extent of whole bloodadhesion to vascular cell adhesion molecule (VCAM-1) in a standardized microfluidic flow-based assay. Dynamic adhesive interactions (rolling or sliding) of whole blood and isolated leukocytes to P-selectin were assessed by measuring absolute rolling cell number, cell rolling flux (number of rolling cells per total number of flowing cells), and cell rolling velocity at 0.3dyn/cm2. Detachment assays were performed by exposing adherent cells to vepoloxamer (10 mg/mL) under physiological flow conditions. Erythrocyte membrane fragility was evaluated based on mechanical stress-induced hemolysis at 3 min (Hem3min, %).
Results: Vepoloxamer reduced whole blood adhesion to VCAM-1 at 0.1 mg/mL by 18% (p = 0.0015), at 1.0 mg/mL by 69% and at 10.0 mg/mL by 79% (in both cases, p < 0.001), and to HUVECs by >50% 0.1mg/mL (p=0.003, n=10). Vepoloxamer (10mg/mL) did not significantly affect cell-rolling flux in dynamic adhesion assays to P-selectin (p = 0.51 and 0.94, isolated leukocytes and whole blood, respectively). Vepoloxamer reversed established cell adhesion by > 30% in 3 or 10 patient samples tested, although the total average difference in percent detachment did not reach statistical significance (16.3%vs 29.6%, p=0.42, n=10). Finally, vepoloxamer reduced shear-induced hemolysis compared to untreated blood samples (35.2 % vs. 44.6% control, p =0.033).
Conclusion: Vepoloxamer can significantly reduce firm cell adhesion to both VCAM-1 and HUVECS under physiologic flow conditions. Shear-induced hemolysis is also reduced in a statistically significant manner, consistent with the proposed membrane protecting effects of vepoloxamer.] Interestingly, P-selectin mediated rolling adhesion was not significantly affected. This may suggest that vepoloxamer may have distinct inhibitory effects to VCAM-1 vs. P-selectin. The current findings suggest that combinatory assessment of the response of adhesive properties and membrane fragility to vepoloxamer treatment may facilitate selection of patients most likely to benefit from vepoloxamer therapy. The microfluidic flow-based platform presented in this study may have the potential to predict and monitor individual patient response to anti-adhesive therapies such as vepoloxamer. There are few reliable biomarkers that objectively predict and assess vaso-occlusive potential, thus further clinical study of this microfluidic flow-based platform are warranted."
http://www.bloodjournal.org/content/126/23/2180?sso-checked=true
I am back in. Reason: I am 100 % sure that Mast Therapeutics is able to improve the previous phase 3 trial for sickle cell from p=0.07 to p=.05 or lower. The company did significant adjustments (Hydroxurea, average age below 16 years, the biggest trial ever on sickle cell, ...) to succesfully complete this goal. Above that the FDA will be VERY happy that the opioid use and possible opioid addiction/abuse can be reduced by Vepoloxamer for sickle cell patients. It is a public secret that the FDA wants to get rid of opioids.
"What Adam Feuerstein really said about MSTX phase 3 trials
1. That two specialists are successfully using Vepoloxamer.
2. That an investor he knows, but not calls by name- an eskimo who spends money on Wall Street is an investor too- says he doesn't think (read 'think') Vepo will pass...
3. There is almost no risk in buying shares of MSTX b/c failiure is already priced i
4. There is absolutely no mention of the beneficial effect of hydroxyurea (used in more than 60% of the patients).
5. Adam F. doesn't mention the average age is 15 years, and VEPO has showed superior efficacy for mean age under 16 years
To summarize my opinion: The previous failed phase 3 trials score a modest efficacy with p=0.07, efficacy, so with the largest trial ever on sickle cell, more than 60% hydroxyurea and mean age below 16y, I think the chances will be high to score statistical efficiency with p below .05
With the changed study variables: age, hydroxyurea,the number of participants they only need to move p=.07 towards p=.05 or move from modest efficacy to statistical significant efficacy."
Author Alexander.johannes and Annicka Waechter from Yahoo finance
"Perfect...the conversations about opiates, SCD and the FDA...
This is one of my main points when corresponding with friends and associates in the medical and scientific communities.
The FDA has a underlying objective to rid the US of it's reliance on opiates. If you are a SCD sufferer...you are condemned to be an opiate addict. PERIOD. The pain is too intense that there is no way to off stave such a condemnation.
AF has no clue as to the FDA's secondary objective here to off stave the social ramifications of this disease.
Glad to see this HUGE note finally mentioned here...and so sorry to not have brought it up previously...being that such is a HUGE point.
There has been a lot of speculation on this board...but much of which is highly informed (Culley being Culley Besides). If this passes...he will be a rock star. If it fails, a monster.
The FDA and opiate concern is a big deal and if our results are even remotely "good"...we will have a huge friend of the FDA"
Author bpy03 on Yahoo finance
You may start buying now
I am out. Read my pitch to see why.
More great news:'The Company is filing this Post-Effective Amendment to withdraw and remove from registration the unissued and unsold shares of the Company’s common stock, par value $0.001 per share, shares of the Company’s preferred stock, par value $0.001 per share, the Company’s debt securities and the Company’s warrants, issuable by the Company pursuant to the Registration Statements.'
That my friends is great news. The Board Of Directors must expect great phase 3 results with possible partnerships, or is in negotiations for a buyout!
De-registration of securities:
http://ih.advfn.com/p.php?pid=nmona&article=71390765&symbol=MSTX
Ye$$$$$$ !
b/c Hedge funds aren't done buying yet.
Great!!! FNMA will be the court case AND stock of the century.
Once we passed the 200mda on a bullish manner, knowing that the court case is nearing to an end, you just know that Fannie Mae will be released from conservatorship.
I have adviced all my followers to buy a position into FNMA common shares
I agree with your reasoning and calculations. But is that realistic?
It is like knowing the right numbers of the next lottery jackpot,you just have to fill in the form. Since this week you just know FnF will be released and that the govt will need to pay billions of dollars back. You just know Fannie Mae will be worth at least $60/share when it is released. Selling now is just because you get manipulated that the share price isn't mobing up with 30% every day. Indeed how stupid can someone be to sell FNMA?
Could be halted at any time from now. FnF about to get released. Govt is checkmate.
It has broken the 50dMA in a bullish way. So not only based on fundamentals but also based on technical indicatoren this is a strong buy.
I agree.
Ok. Thank you
Can someone tell me the RT share price?
Indeed.
The volume says institutions are buying. Everbody knows that a settlement will come and commons will be trading again for at least $23/share according to Bill Ackman. Personally I think $60/share is more realistic.
Ackman gives commons a $23-47/share minimum target.
Shareholders will win the case. It is clear. Company should be valued at least $20/share. That would be very unfair, I think releasing Fnma with a market cap worth somewhere between $30-60/share would be a fair deal vs all common shareholders. Then it depends of the economic situation if the share price stays there or rises to $100/share
By a settlement for at least $60/share
Therefore the govt will be very happy if a settlement is agreed for only $60/share.
Settlement can come any day now.the government doesn't want any more secrets in this case to get unfolded. $60/common share is a fair settlement price.
What will be the minimum share price for a settlement? 60 billion dollar too much in dividends alone gives a value of $10/common share. Is $30/share a fair settlement price?
FNMA paid back 60 billion dollars in dividend above the money the government illegally borrowed. This 60 billion dollar is dividends on its' own gives FNMA corresponds to almost $10/share!
Mast Therapeutics Inc (MSTX) : Baker Bros. Advisors Lp scooped up 89,978 additional shares in Mast Therapeutics Inc during the Q4 period, according to a recent disclosure to the SEC. The investment management firm now holds a total of 4,797,442 shares of Mast Therapeutics Inc which is valued at $1.2 Million.Mast Therapeutics Inc makes up approximately 0.01% of Baker Bros. Advisors Lp’s portfolio.
Other hedge funds, including, Hightower Advisors boosted its stake in MSTX during the Q4 period, The investment management firm added 294,598 additional shares and now holds a total of 343,098 shares of Mast Therapeutics Inc which is valued at $84,745. Blackrock Advisors added MSTX to its portfolio by purchasing 15,428 company shares during the Fourth Quarter which is valued at $3,811.
http://sussexpilot.com/market-report/baker-bros-advisors-lp-buys-1-2-million-stake-in-mast-therapeutics-inc-mstx/26610
AEZS may generate $27/share annual revenues
In the US alone Zoptrex could generate $300 m annually. Macrilen in the US alone could generate upto $50m in the US alone. That is 350million/12.9 million outstanding shares = 27dollar/share as revenue for one year EXCLUDING Europe and China, EXCLUDING VALUES OF THE REST OF THEIR PIPELINE AND in licensed products.
Nice to see the increasing awareness that this stock is significantly undervalued.
Time for shorts to start worrying. Share price will keep on going North till$24/share before FDA news (see the sticky post).
That's not how I have read the conference call transcript.
Why $10 million more for only 3 millionshares
Brings to a total of 12,9 million outstanding shares. According to the AF biotech oncology rule that would gives AEZS a pre FDA-approval market cap of at least $300m between now and the next 12 months or at least $24/share.
Now why the need for $10m extra in cash?
1. To license additional products they can sell to increase their revenue base (listen or read the CC)
2. To prepare commercialization of Zoptrex, marketing efforts (listen or read to the CC)
3. To increase their sales force
4. To increase their negotiation position for more partnerships
5. To defend themselves against a hostile takeover
Where Does Wall Street See the Stock Going?
Research firms on the Street have price targets on the name ranging from $10 to $12 with a standard deviation of $0.816. The consensus target from the 4 analysts providing projections currently stands at $11. The mean target was last revised on 2016-03-21. These are short term projections for the next 12 months.
When taking a look at recommendations from analysts, investors can use the average brokerage recommendation score to determine the consensus take on a stock. The ABR is an average of the actual recommendations provided by research firms on a given equity. The ABR rank is displayed in the range of 1 to 5 where 1 represents a Strong Buy and 5 a Strong Sell. It’s important to note that analysts are often overly optimistic on their ratings and this should be considered when making investment decisions. Shares of AEterna Zentaris Inc. (NASDAQ:AEZS) currently have an ABR of 1.25, based on 4 recommendations.
http://www.uptickanalyst.com/aeterna-zentaris-inc-nasdaqaezs-analysts-take-on-earnings/
Incorrect.If that was the case he would be sued. $10m is to increase the capital structure which increases the negotiation position for partner deals and/or to license another product to sell and increase the revenue base.
I see this as very wise and bullish decision. Also see my sticky post.
AEZS should be worth at least $24/share after the ATM cash increase. It is a responsible capital increase. Much better than warrants. The company will gaan $10 million cash extra on only max 3 million shares. So the company will have max 12,9 million share outstanding. According to the AF biotech oncology rule, which says a company with positive P3 oncology results should have a market cap of $300m.AEZS should be worth $24/share prior to FDA Zoptrex approval not even calculating Macrilen clearance.