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Ironwood Pharmaceuticals, Inc. Message Board

big_pharma_coming 5 posts  |  Last Activity: Jul 6, 2016 3:30 PM Member since: Oct 4, 2011
  • big_pharma_coming big_pharma_coming Jul 6, 2016 3:30 PM Flag

    Med Tech letter has a great track record. 2 yrs ago Huberts stock letter rankings ranked them #1 of 267

    They will be right about ZIOP soon imo

  • big_pharma_coming big_pharma_coming Jul 6, 2016 3:29 PM Flag

    It is better - also lots of analyst reports and Med Tech letter ZIOP comments with original bold and slides and links posted that cannot be posted on Yahoo.

  • big_pharma_coming big_pharma_coming Jul 6, 2016 3:28 PM Flag

    Thanks for posting - better than guys blaming others for their failures. I agree with this - this deal makes partnerships or more likely a buyout near term almost certain. Its obvious what is going on here.

  • big_pharma_coming big_pharma_coming Jul 6, 2016 3:26 PM Flag

    I do think a deal is coming - there is no reason to cut this percentage now if you are not doing a deal also the change of control twenty day weighted avg makes a big pop very good for XON and Kirk on conversion. And the 1% per month is meant to give Big Pharma some urgency to get the deal done. My take is ZIOP has a buyout offer by the end of July. Good luck to the longs - there really has been nothing but good fundamental news and positive data and publications - ZIOP is stuck in the XON short attack and lies and the sector meltdown. Other small caps are down 85% or so - ZIOP is still up from the beginning of 2015 - not many other bios are. Adding

  • Stifel -Intrexon Update – Second Cohort Enrollment Completed for Ziopharm’s Ad-RTS-IL-12 Study in GBM


    June 28, 2016

    Intrexon Corporation

    XON – NYSE


    Target Price — $57.00


    Company Update

    Intrexon Update – Second Cohort Enrollment Completed for Ziopharm’s Ad-RTS-IL-12 Study in GBM

    Yesterday afternoon, Ziopharm announced updated enrollment in its ongoing Phase I trial of Ad-RTS-IL-12 + veledimex in glioblastoma – enrollment in the second cohort was completed and the third cohort is now open to patients. This news follows last month’s preliminary data, which showed the company’s gene therapy candidate was safe and showed signs of activity. Given historical controls, the interim results showing 10 of 11 patients are still alive at median of 6.2 months is interesting, and, pending final data, potentially compelling. In addition, in light of Amgen’s recently approved T-VEC and the expectation that many GBM patients undergo surgery, we believe Ziopharm’s Ad-RTS-IL-12 approach could be medically tractable, if efficacy is eventually compelling.

    Ad-RTS-IL-12 is another powerful IO approach. Much of oncology is currently

    focused on enticing the patient’s immune system to help destroy tumors. This goal

    is probably much less far fetched than it once seemed as it’s now clear that most

    tumors contain the remains of immune responses. It is thought that these

    anti-tumor immune responses arose to fight these semi-foreign growths (tumors),

    but were shut off by what is called the tumor micro-environment (thus allowing the

    tumor to grow). These ineffective immune cells that recognized the tumor but could

    not destroy it are called tumor infiltrating lymphocytes (TILs). Attempts to get TILs

    to finish their job have focused on checkpoint immunotherapies such as Ipilimumab

    (anti-CTLA-4) and Nivolumab (anti-PD-1) that block the activity of the

    immunosuppressive tumor microenvironment and thereby enhance the activity of

    the anti-tumor TILs.

    Ad-RTS-IL-12 + Veledimex. Ziopharm has taken an alternate approach to this

    problem and is attempting to activate TILs through expression of IL-12, a

    pro-inflammatory cytokine that activates the TIL’s and probably other T-cells

    resulting in stronger anti-tumor responses. However, a major problem with

    stimulatory cytokines, such as IL-12, is their significant tendency to cause side

    effects – so administering them systemically is problematic (the NCI has attempted

    this administration in humans and has not adopted a mode of administration using

    Intrexon’s technology, we believe). Ziopharm is approaching this problem using

    one of Intrexon’s most well-known tools – called the RheoSwitch. The RheoSwitch

    itself is a two part gene regulatory element controlled by the orally available drug

    veledimex. When veledimex is administered orally, tumors that have been injected

    with Ad-RTS-IL-12 start to express IL-12. The data here are not fully disclosed, but

    Ziopharm management has indicated that IL-12 can be measured systemically and

    that IL-12 side effects are reversibly observed after induction. Most importantly,

    when veledimex is withdrawn, the expression of IL-12 slows and then stops over

    the course of several hours. (continued...)

    It's probably still early days, but the goal of getting just enough IL-12 expression

    and concomitant TIL activation to fight the tumor, but not be too toxic for the

    patient seems reasonable.

    Ad-RTS-IL-12 in comparison Amgen’s Imlygic. Imlygic (T-VEC) seems an

    analogous therapeutic and takes a dual approach blocking the cellular protein

    ICP47 (allowing antigen to be presented) in addition to stimulating immune cells to

    attack tumor cells. In Imlygic, Amgen has altered the cold sore virus, made

    several genetic modifications, including increasing its selectivity for cancer cells,

    to generate a therapeutic that is directly injected into the tumor. Subsequently,

    macrophages are stimulated to secrete the GM-CSF cytokine and an anti-tumor

    response is invoked. When injected into melanoma, the drug has shown a 16.3%

    durable response rate in patients. Given that Imlygic is delivered via injection,

    Ziopharm’s approach of directly injecting the drug into tumors seems more

    medically acceptable. In addition, given the clear activity of Imlygic and possibility

    that Imlygic expresses the less powerful GM-CSF cytokine than IL-12 (used in

    Ad-RTS-IL-12), we find the Ziopharm program increasingly interesting.

    Interim Ad-RTS-hIL-12 Phase I results. In May, Ziopharm announced interim

    data from its ongoing single-arm, dose escalation, recurrent GBM study. In cohort

    one, 86% of patients remain alive with a median follow up time of 6.8 months

    (n=7). Additionally, in the May press release, the company noted that 91% of all

    11 patients were still alive with a median follow up time of 6.2 months (cohort two

    was not fully enrolled yet). We note all patients enrolled had high-grade, recurrent

    glioma and nine of these 11 patients had previously failed salvage therapy.

    Furthermore, Ziopharm notes that mOS for patients these settings is

    approximately 6-7 months and 3-5 months, respectively. Given these historical

    controls, we find the preliminary data interesting and potentially compelling.

    Ziopharm expects to present updated data later this year.

    Glioblastoma treatment paradigm. Treatment for GBM upon initial diagnosis

    typically involves surgery, radiation, and chemotherapy. Maximum tumor resection

    is considered the best option for those where surgery is possible/appropriate. We

    note carmustine wafers are approved as an adjunct to surgery/insert into the

    resection. In newly diagnosed GBM patients, the drug’s label lists a 12.9 month

    mOS for those on carmustine + radiation arm versus an 11.6 month mOS for

    patients on the placebo + radiation arm. In recurrent GBM patients, the drug’s

    label lists a 6.5 month mOS for those on carmustine + radiation arm compared to

    a 4.6 month mOS for patients on placebo + radiation arm.

    Temodar, an alkylating agent, is also approved for newly diagnosed glioblastoma

    patients and to be administered with radiation and subsequently as maintenance

    treatment. Temodar’s label lists a median OS for radiation therapy + Temodar of

    14.6 months versus 12.1 months on radiation therapy alone. Lomustine is another

    alkylating agent that is approved for patients with brain tumors. However this

    chemotherapy is approved only in those who have already undergone surgery

    and/or radiation therapy. Finally, we note Avastin is approved in glioblastoma as a

    single agent for adult patients with progressive disease following prior therapy.

    The drug’s label lists a 19.6% ORR and a 3.9 month median duration of response.

    Target Price Methodology/Risks

    We value the company via a sum-of-the-parts approach where some of the pieces

    of the company are valued via formal methods (principally DCF) and other, earlier

    stage parts of the company are valued principally based on competitor valuations.

    Overall, this approach results in a calculated market capitalization of $6.685 billion.

    Based on a current share count of 116.861 million, we arrive at a 12-month price

    target of $57.

16.10+0.59(+3.80%)Sep 27 4:00 PMEDT