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Natty Greene

 
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  • Which Chemotherapy Should OXiGENE Test Their Zybrestat+Avastin Combo Against? [View article]
    Bottom line is this:

    $39M market cap
    $32M in cash

    These drug assets are worth much more than $7 million.

    Strong buy at these levels ($1.90s)!
    Nov 17, 2014. 11:51 AM | 3 Likes Like |Link to Comment
  • Why Imminent Orphan Status Designation Will Attract Big Pharma To Mast Therapeutics [View article]
    Update:

    The October 7-9 COMP meeting report is out (http://bit.ly/1vhEUgM).

    The application, EMA/OD/117/14- For treatment of acute peripheral arterial occlusion - was not one of the 29 applications on the list which received a positive orphan status opinion.

    According to EMA, application EMA/OD/117/14 has been withdrawn.

    Therefore, the basis for the near term catalyst mentioned in this article is not happening. This was unexpected considering the MST-188 for treatment of ALI has already received orphan status in the US.

    When the full meeting minutes are published in about 60 days, we should know more details on what led to this application withdrawal decision.

    MSTX announced that EU orphan application (MST-188/ALI) was filed in Q2 - 2014. Now that application has been withdrawn. Now the company needs to provide an update on the timing of this application going forward. When will they reapply?

    Looking ahead, the following is still on the horizon for MSTX despite this EU orphan development which include:

    Phase 2 Study (heart failure): agreement with FDA on protocol
    Q4 2014

    Nonclinical Study (heart failure): data
    Q1 2015

    Nonclinical Study (embolic stroke): data
    Q2 2015

    Phase 2 Study (heart failure): initiate enrollment
    1H 2015

    Phase 2 Study (acute limb ischemia): complete enrollment
    Q4 2015

    EPIC Study (sickle cell disease): complete enrollment
    Q4 2015

    Phase 2 Study (WHO Group 2 pulmonary hypertension): data
    2H 2015

    Phase 2 Study (heart failure): data (interim analysis)
    2H 2015
    Oct 16, 2014. 09:21 AM | 1 Like Like |Link to Comment
  • Why Imminent Orphan Status Designation Will Attract Big Pharma To Mast Therapeutics [View article]
    FilmsGuy,

    Patience on this one...as many catalysts are on the horizon. This current valuation of $75M very much undervalues the company's drug asset potential.

    The EMA's Committee on Orphan Medicinal Products (COMP) is meeting as I type to give an opinion on MST-188 (ALI). With orphan status designation expected, this would give MSTX orphan status for MST-188 in US and in EU for two different indications (sickle cell & acute limb ischemia).

    The COMP meeting ends on Thursday, October 9, and they will issue a meeting report a few days after with their opinions on orphan status. The average time for this monthly report to be released in 2014 is 6 days after COMP meeting ends (October 15 in this case), but they have also issued report as soon as 2 days after meeting ends. Therefore, we could know as early as Monday, October 13.
    Oct 7, 2014. 09:24 AM | Likes Like |Link to Comment
  • Why Imminent Orphan Status Designation Will Attract Big Pharma To Mast Therapeutics [View article]
    Ponty,

    To inform your opinion of why "GSK dumped this", here is the full history of what is now known as MST-188. You'll notice that the new formulation is a second generation "purified" version....NOT the "unpurified" version used by GSK sub:

    Definitions

    RheothRx – A first-generation product with unpurified, excipient-grade poloxamer 188 as the active ingredient. Associated with elevated serum creatinine.

    MST-188 (formerly known as ANX-188, FLOCOR and CRL-5861) – A second-generation product with purified poloxamer 188 as the active ingredient. Certain low molecular weight substances present in excipient-grade poloxamer 188 that are associated with elevated serum creatinine are not present in MST-188. No clinically significant elevations in creatinine have been observed in clinical studies conducted with the purified material (>300 administrations).

    Early Development: The CytRx Corporation/Burroughs Wellcome Alliance

    Poloxamer 188 is a well studied compound. It was originally used as an emulsifying agent in topical wound cleansers and parenteral nutrition products. However, the therapeutic use of poloxamer 188 was largely conceived by Dr. Robert Hunter, MD, PhD (Distinguished Professor and Chairman, Department of Pathology and Laboratory Medicine, University of Texas Medical School at Houston). Dr. Hunter (then at Emory University) identified the compound’s rheologic, cytoprotective and antithrombotic activities through an extensive series of laboratory studies. His work led to the formation of CytRx Corporation, a start-up company that licensed Dr. Hunter’s inventions from Emory. CytRx conducted a wide range of pre-clinical and clinical studies with first-generation poloxamer 188, then known as RheothRx. These studies led to a major alliance with Burroughs Wellcome (today, GSK). Burroughs also performed an extensive series of nonclinical studies and 8 clinical trials, primarily focused on acute myocardial infarction (AMI). Early studies investigating RheothRx were promising. The largest AMI trial planned to enroll approximately 20,000 patients. However, during the 3,000-patient lead-in phase of this study, elevations in serum creatinine were observed, particularly in those patients aged 65 years and older and in subjects with elevated creatinine at baseline. This phenomenon was referred to as “acute renal dysfunction” and resulted in the discontinuation of the program by Glaxo, which had recently merged with Burroughs Wellcome.

    Addressing Renal Toxicity and Pursuing Sickle Cell Disease

    After Glaxo returned the RheothRx program, CytRx investigated the source of the renal dysfunction and determined the elevation in serum creatinine was attributable to preferential absorption of certain low molecular weight substances by the proximal tubule epithelial cells in the kidney. CytRx developed a proprietary method of manufacture based on supercritical fluid chromatography that reduced the level of these low molecular weight substances present in poloxamer 188, creating what is now known as purified poloxamer 188. Nonclinical testing of purified poloxamer 188 (now known as MST-188), demonstrated less accumulation in kidney tissue, less pronounced vacuolization of proximal tubular epithelium, more rapid recovery from vacuolar lesions, and less effect on serum creatinine. A full report of the differential effects of commercial-grade and purified poloxamer 188 on renal function has been published.1

    Subsequently, CytRx sought to re-introduce MST-188 into the clinic. However, CytRx lacked the resources to conduct a 20,000-patient heart attack study. Instead, they focused the development of MST-188 in sickle cell disease (SCD), a rare disease with a huge unmet need and in which RheothRx had demonstrated positive results in a pilot Phase 2 study conducted by Burroughs Wellcome. In that Phase 2 study (n=50), RheothRx significantly reduced the duration of crisis, pain intensity, and total analgesic use and showed trends to shorter days of hospitalization in the subgroup of patients who received the full dose of study drug (n=31). These data were reported more fully by Adams-Graves et al.2 Notably, CytRx conducted safety studies in both adult and pediatric sickle cell patients and, even at significantly higher levels of exposure than anticipated therapeutic doses, there were no clinically significant changes in serum creatinine observed and no acute kidney failure reported. Based on these promising Phase 1 and 2 results, CytRx subsequently launched a randomized, double-blind, placebo-controlled Phase 3 study of MST-188 in 350 patients with sickle cell disease. The primary endpoint was a reduction in the duration of a painful crisis. However, CytRx concluded the study at 255 patients, in part due to capital constraints. Nonetheless, the study demonstrated treatment benefits in favor of MST-188. However, it did not achieve statistical significance in the primary study endpoint (p=0.07). Mast believes that enrolling fewer than the originally-planned number of patients and key features of the study’s design negatively affected the outcome of the primary endpoint. In particular, the study assumed that most patients would resolve their crisis within one week (168 hours). However, a substantial number of patients did not achieve crisis resolution within 168 hours and were assigned a “default” value of 168 hours, which had a potentially significant effect on the primary endpoint. Notably, in a post hoc “responder’s analysis” of the intent-to-treat population (n=249), which analyzed the proportion of patients who achieved crisis resolution at 168 hours (excluding those who had been assigned the default of 168 hours), over 50% of subjects receiving MST-188 achieved crisis resolution within 168 hours, compared to 37% in the control group (p=0.02). Data from the Phase 3 study are reported more fully by Orringer et al.3 Following conclusion of the Phase 3 study, CytRx merged with a private company and modified its business strategy by discontinuing development of all of its existing programs (including MST-188) to focus on assets held by the private company with which it merged.

    SynthRx

    After the corporate reorganization at CytRx, a group of individuals, including Dr. Hunter, formed a private entity, which they named SynthRx, Inc., to acquire rights to the data, know-how, and extensive clinical and pre-clinical and manufacturing information necessary to continue development of MST-188. SynthRx developed new intellectual property and conducted additional analyses of the existing data. However, they were unable to raise capital to fund development of MST-188 during the “great recession.”

    Mast Therapeutics

    In 2010, Mast Therapeutics met with Dr. Hunter and his colleagues to negotiate the acquisition of SynthRx and continue the development of MST-188. The merger was finalized in April 2011.

    Since April 2011, Mast Therapeutics has re-established the unique manufacturing process through a partnership with Pierre Fabre (FRA) and met with the FDA multiple times to discuss a pivotal study protocol for MST-188 in sickle cell disease. In 2013, Mast initiated the EPIC study, a 388-patient pivotal Phase 3 trial of MST-188 in sickle cell disease, and, in 2014, Mast initiated its second MST-188 clinical program with a Phase 2, proof-of-concept study of MST-188 in combination with rt-PA in patients with acute limb ischemia. In addition, based on recent nonclinical study data showing improvements in cardiac ejection fraction and key biomarkers and prior studies showing MST-188 improved cardiac function without increasing cardiac energy requirements, Mast has announced its intent to pursue clinical development of MST-188 in heart failure.

    1. Emanuele, M. and Balasubramaniam, B. Differential Effects of Commercial-Grade and Purified Poloxamer 188 on Renal Function. Drugs in R&D April 2014. Available at http://bit.ly/YUus1P
    2. Adams-Graves P, Kedar A, Koshy M, et al. RheothRx (Poloxamer 188) Injection for the Acute Painful Episode of Sickle Cell Disease: A Pilot Study. Blood 1997;90:2041-6
    3. Orringer EP, Casella JF, Ataga KI, et al. Purified poloxamer 188 for treatment of acute vaso-occlusive crisis of sickle cell disease: A randomized controlled trial. JAMA 2001;286(17):2099-106
    Oct 2, 2014. 09:30 AM | 2 Likes Like |Link to Comment
  • Why Imminent Orphan Status Designation Will Attract Big Pharma To Mast Therapeutics [View article]
    ewmpsi,

    Yes, good day for GLYC, but still down 16% from intraday high just a week ago at $8.82 prior to news that Pfizer significantly delayed their PH3 trial.
    Oct 1, 2014. 04:09 PM | Likes Like |Link to Comment
  • Why Imminent Orphan Status Designation Will Attract Big Pharma To Mast Therapeutics [View article]
    JimHim,

    You are correct, it is PFE. I have submitted that edit the editors and it should be changed in article copy soon. Thank you.
    Oct 1, 2014. 04:05 PM | Likes Like |Link to Comment
  • Why Imminent Orphan Status Designation Will Attract Big Pharma To Mast Therapeutics [View article]
    Congrats on those picks. I agree on Franklin and also like that Baker Bros are involved (3M share position) in MSTX too. Definitely smart money there!
    Oct 1, 2014. 12:53 PM | 1 Like Like |Link to Comment
  • Why Imminent Orphan Status Designation Will Attract Big Pharma To Mast Therapeutics [View article]
    Glad you enjoyed the read. Not covered in the article is my opinion that significant institutional $ will begin to move into stock post EU orphan status opinion next week. With only 17% institutional ownership, there is a long runway of growth in that department. That expected wave of buying will be what really pushes the stock much higher in Q4. http://bit.ly/1qVCxd4
    Oct 1, 2014. 11:51 AM | Likes Like |Link to Comment
  • MannKind: Why The Short Argument Is Shortsighted [View article]
    Excellent article.
    Jul 25, 2014. 04:21 PM | 2 Likes Like |Link to Comment
  • Imminent District Court Ruling Should Propel Zogenix Higher [View article]
    Judge Zobel rules exactly as I predicted in this article. The only problem for Zogenix and the reason the stock is not moving up on this news is that Purdue news (competitive Hydrocodone ER given priority review by FDA) was released this morning too. ZGNX just can't catch a break!
    Jul 8, 2014. 03:40 PM | 2 Likes Like |Link to Comment
  • Imminent District Court Ruling Should Propel Zogenix Higher [View article]
    A 30,000 share buy on the open market is an insider buy in my book and even more notable because of who made the buy, Zogenix founder and chairman Cam Garner.
    Jul 2, 2014. 01:06 PM | Likes Like |Link to Comment
  • Imminent District Court Ruling Should Propel Zogenix Higher [View article]
    This is very helpful for Zogenix too with physicians....a supportive Zohydro statement from the American Academy of Pain Management,

    http://bit.ly/1rYdqsY
    Jul 2, 2014. 01:04 PM | 1 Like Like |Link to Comment
  • Imminent District Court Ruling Should Propel Zogenix Higher [View article]
    Agreed Rick.....this goes to $3 on favorable ruling by Zobel. Today's move (18%) is minor compared to what a favorable, precedent-setting ruling by the U.S. District Court would do.
    Jul 2, 2014. 01:01 PM | Likes Like |Link to Comment
  • Pitt Hyde & Mason Hawkins Buy >50% Stake In GTx Ahead Of Phase II Results [View article]
    I am always bothered by insider selling and this is no exception. I put much weight in my investment decisions based on insider buying and that was stressed in this article regarding Hawkins and Hyde. You'll just have to weigh whether you think this dump of 72K shares discounts the purchase of nearly 12M shares purchased at $1.78 mentioned in this article.
    Jun 11, 2014. 11:46 AM | Likes Like |Link to Comment
  • Pitt Hyde & Mason Hawkins Buy >50% Stake In GTx Ahead Of Phase II Results [View article]
    valuefinder,

    Yes, that is correct...PH2 breast cancer data is the key catalyst here.
    May 9, 2014. 12:17 PM | Likes Like |Link to Comment
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