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Geron Corporation Message Board

scistats 227 posts  |  Last Activity: Jul 5, 2016 10:03 AM Member since: Apr 5, 2009
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  • "The anti-tumor activity of MM-398 (Onivyde) was assessed in a pancreatic cancer model, a highly hypoxic preclinical tumor model...MM-398 reduces markers of hypoxia. Experiments were conducted in a human colon cancer cell (HT-29) model....shown in FIG. 3, MM-398 reduced markers of hypoxia."

    -United States Patent Application 20160074382

    Sentiment: Strong Buy

  • Reply to

    Merrimack's May 5th, 2016 Cartilage Patent

    by scistats May 7, 2016 8:24 AM
    scistats scistats May 8, 2016 4:23 PM Flag

    The technology itself may be something similar to this paper:
    "An artificial fusion protein between bone morphogenetic protein 2 and titanium-binding peptide is functional in vivo."

    Sentiment: Strong Buy

  • Reply to

    Merrimack's May 5th, 2016 Cartilage Patent

    by scistats May 7, 2016 8:24 AM
    scistats scistats May 8, 2016 4:17 PM Flag

    I think the answer is in the latest Form 10-Q: "We plan to apply our systems biology approach to multiple additional disease areas outside the oncology field. We expect to do so in some cases through the establishment of separately funded companies."

    Merrimack is a mighty river, but MACK's first attempt at a "disease area outside of oncology" was Silver Creek focused on heart disease using “Smart Growth Factors”. This has turned out to stink like a mighty big sewage trench. I found their website to be redirecting to a porn page until I posted about it on this board and obviously company staff corrected the hack. This went unnoticed because they did not even bother to check their own website. It took the initiative of an outside shareholder. Pretty pathetic.

    Anyway, MACK seems to be building a bone and joint health/musculoskeletal unit to try to redeem themselves.

    Sentiment: Strong Buy

  • Reply to

    Merrimack's May 5th, 2016 Cartilage Patent

    by scistats May 7, 2016 8:24 AM
    scistats scistats May 8, 2016 12:02 AM Flag

    Looking at the complementary Baxalta First Quarter 2016 Financial Results, they are committed to: Onivyde EU approval, ONIVYDE (MM-398) – Gastric, and growing their oncology presence in general, which is bullish. They have the new Precision BioSciences and Symphogen programs, indicating they are going long in a big way.

    I think Merrimack needs the milestone payment under their belt for EU approval, and if they get another liposome deal with Shire for antibody directed nanotherapeutic (ADN), it is going to start making more sense for Shire to own rather than lease. The AbbVie Stemcentrx deal may spur them.

    Sentiment: Strong Buy

  • CARTILAGE-BINDING FUSION PROTEINS
    United States Patent Application 20160122411
    Publication Date: 05/05/2016
    Filing Date: 03/28/2014
    Assignee: MERRIMACK PHARMACEUTICALS, INC. (CAMBRIDGE, MA, US)

    Abstract:
    Provided herein are fusion proteins comprising a first domain that specifically binds to the extracellular domain of a growth factor receptor, and a second domain that specifically binds to a cartilage matrix component, and pharmaceutical composition comprising these fusion proteins. Methods of treating musculoskeletal diseases using the fusion proteins and pharmaceutical composition disclosed herein are also provided.

    Sentiment: Strong Buy

  • Similar to the strategy described below, Merrimack is likely to focus on vasodilation combo for hypoxic tumor treatment.

    "In this work we will test a new treatment strategy composing of two different miceller drugs. The first micelle will encapsulate a nitric oxide donor drug, to cause vasodilation in the tumor blood vessels. We hope to show that vasodilation will then enhance the delivery of the second micelle, encapsulating the chemotherapeutic agent. We expect this system to overcome the difficulty imposed by the limited blood supply to pancreatic cancers, allowing us to successfully build up high enough anticancer drug levels inside the tumor to cure the patient."

    Reference:
    Welcome to the Otago School of Medical Sciences
    Testing a New Treatment Strategy for Pancreatic Cancer
    Dr. Khaled Greish and Dr. Greg Giles, 13 January 2014

    Sentiment: Strong Buy

  • scistats scistats May 5, 2016 12:07 PM Flag

    This sounds great!

    CEO Mulroy plans to focus on Immuno-Oncology (IO) for hypoxic tumors where current immune checkpoint inhibitors have limitations. He will use Antibody Directed Nanotherapeutic (ADN) loaded with what to achieve this?

    When he unveils MM-161 & MM-436, we may have our answer. He may also circle back to the old poster and talk about combining MM-141 with checkpoint inhibitors.

    Sentiment: Strong Buy

  • Italian30_2000 has suggested that CEO Mulroy will unveil an immune therapy at this years much anticipated Analysts Day on May 19th.

    Directly from Italian30_2000:
    "They mentioned on Q1 call that they will be discussing a next generation immunotherapy platform created using network biology. They are going to try and make immunotherapy better."

    If true, this would be in stark contrast to CEO Mulroy's fireside talk yesterday at Deutsche Bank Securities' 41st Annual Healthcare Conference where, by the fireside, CEO Mulroy all but pounded the embers with his fist and screamed that checkpoint inhibitors DO NOT work well in the hypoxic tumor environment.

    Merrimack obviously believes this to be true because they are currently refining a breast cancer diagnostic specifically for identifying the 20% of breast cancer tumors which are hypoxic. CEO Mulroy plans to target these hypoxic tumors with his Antibody Directed Nanotherapeutic (ADN) technology.

    In fact, it would appear that CEO Mulroy has looked at the list of where immune checkpoint inhibitors do not work, pointed to the cancers at the bottom of the list where they work the least well, and said this is Merrimack's territory, the hypoxic tumor.

    In a recent Merrimack paper this was stated: "Tumor hypoxia is strongly linked to aggressive disease progression and resistance to therapy..." EJNMMI Res 2015 5 57 Published online 2015 Oct 19

    Indeed, CEO Mulroy shunned checkpoint inhibitors, saying liposomes target hypoxic tumors best. This is at odds with the strategy of Aduro BioTech who are currently using their defanged, tumor antigen producing Listeria mononcytogenes CRS207 in combination with GVAX plus Bristol Myers Squibbs OPDIVO (nivolumab) an antiPD1 for pancreatic cancer.

    What does CEO Mulroy know or not know?

    Hopefully Italian will be correct. Liposomal therapeutic cancer vaccines have been widely investigated, and MM-161 & MM-436 might be just such creatures to be unveiled for a much needed partnership!

    Sentiment: Strong Buy

  • scistats scistats May 4, 2016 9:57 PM Flag

    A next generation immunotherapy platform would be great!

    Aduro is using Listeria mononcytogenes to deliver antigen inside the tumor. If this works in the hypoxic tumor environment, Merrimack will have to counter with what? Antigen filled liposomes?

    If it is Merrimack, you can bet it involves nanoliposomes targeting hypoxic tumors.

    The Analyst's Day is on May 19th. CEO Mulroy did seem excited about this. He mentioned this date several times.

    Sentiment: Strong Buy

  • scistats scistats May 4, 2016 9:45 PM Flag

    Novartis is a very strong endorsement of MM-121 as their LJM716 is going after the same target.

    MM-121 is ahead in the game. This is an extremely positive sign. Novartis is #2 or #3 by oncology sales in the world, just behind Roche.

    However Roche Genentech may be more viable for the following reason: "Genentech holds the U.S. patents for methods of producing certain types of recombinant antibodies. Those patents expire in 2018, Merrimack said in its IPO filing Friday with the Securities and Exchange Commission, but Merrimack may need to license the technology in order to produce its antibody, MM-121."

    Sentiment: Strong Buy

  • scistats scistats May 4, 2016 9:26 PM Flag

    I think we have to give up MM-141 being combined with a checkpoint inhibitor and accept CEO Mulroy at his word: Merrimack is indeed focused like a laser on hypoxic tumors for which checkpoint inhibitors do not work well.

    I will explain:

    They did mentioned MM-141 combined with a checkpoint inhibitors in an old poster, and I mentioned this several times on the board. I too was excited about this. However, they did not mention anything about this in the latest poster at the 2016 American Association for Cancer Research (AACR) Annual Meeting, April 16-20, 2016. So, I do not see this finding advancing.

    Go to time 00:19:02 on the Merrimack Pharmaceuticals at Deutsche Bank 41st Annual Health Care Conference Wednesday, May 04, 2016, 1:30 pm EDT talk .CEO Mulroy clearly states that MM-141 will be used on top of Onivyde or with the chemo it is being combined with in its current clinical trial: "A Phase 2 Study of MM-141 Plus Nab-paclitaxel and Gemcitabine in Front-line Metastatic Pancreatic Cancer"

    Again, Merrimack, based on what CEO Mulroy clearly stated, is a hypoxic tumor-focused oncology biotech. He has defined this as Merrimack's niche.

    Sentiment: Strong Buy

  • scistats scistats May 4, 2016 9:14 PM Flag

    This is the only competition that I am aware of.
    Its nice to be ahead of Novartis :)

    Sentiment: Strong Buy

  • scistats scistats May 4, 2016 8:05 PM Flag

    CEO Mulroy has Merrimack focused on hypoxic tumors and primed for a buyout to complement an established checkpoint inhibitor program. This would include almost all of big pharma. Merrimack is officially a sitting duck with product on the shelves.

    Sentiment: Strong Buy

  • scistats scistats May 4, 2016 8:01 PM Flag

    See Novartis clinical trial: "Open-Label Study Evaluating the Safety and Tolerability of LJM716, BYL719 and Trastuzumab in Patients With Metastatic HER2+ Breast Cancer"

    LJM716 targets HER3 and initial PoC was achieved.

    Sentiment: Strong Buy

  • scistats scistats May 4, 2016 7:52 PM Flag

    I want to stress CEO Mulroy's emphasis on hypoxic breast tumors. There is currently a trial underway focusing on metastatic breast cancer.

    Merrimack is trying to diagnose hypoxic breast tumors using Feraheme, an iron-oxide super-paramagnetic nanoparticle known to be taken up by macrophages abundant in the hypoxic tumor environment. Feraheme can be imaged because it has magnetic resonance imaging properties.

    These tumors represent 20% of the breast tumors out there. Merrimack thinks Onivyde will work well in these breast cancer tumor's hypoxic microenvironment.

    This will be Onivyde’s niche in breast cancer where checkpoint inhibitors do not work well. In addition, MM-121 will be used to take this one step further by blocking chemotherapy resistant HER3+ cancer cells.

    Also, "HER3 and downstream pathways are involved in colonization of brain metastases from breast cancer." -Da Silva et al. Breast Cancer Research, 2010

    Sentiment: Strong Buy

  • Based on today's fireside chat at Deutsche Bank Securities 41st Annual Healthcare Conference, CEO Mulroy stressed that immune checkpoint Inhibitors cannot effectively target hypoxic tumors. Instead, he says Merrimakc's nanoliposomes do it best.

    CEO Mulroy suggests that check-point inhibitors are not as effective in the hypoxic tumor microenvironment because of physical/biochemical barriers and a lack of abundant antigen and immune cells. These factors stymie the likes of blockbuster immune checkpoint inhibitors KEYTRUDA® (pembrolizumab)‎ and OPDIVO® (nivolumab).

    This belief is starkly at odds with the strategy of Aduro BioTech, Inc. who are currently using their defanged, tumor antigen producing Listeria mononcytogenes (CRS-207) in combination with GVAX + Bristol-Myers Squibb's OPDIVO® (nivolumab) (antiPD-1) for the very same hypoxic tumor microenvironment of pancreatic cancer tumors. Certainly CRS-207 is not a cure, but some patients have responded.

    CEO Mulroy, nevertheless, seems confident that Onivyde is definitely the way go away. He reinforced this belief by pointing out that instead of using Onivyde in combination with check inhibitors, MM-121 will be used in combination with Onivyde for HER3 receptor+ pancreatic cancer in the future in addition to other antibodies.

    In fact, he seems to believes that the entire Merrimack lineup of antibodies will be used to support Merrimack's Onivyde and antibody directed nanotherapeutics candidates for delivering traditional chemotherapy as well as novel molecules (or peptides, RNA, etc.) not yet disclosed. He stressed Merrimack is focused on hypoxic tumors where checkpoint inhibitors are at the bottom of the list for efficacy.

    Conclusion:
    CEO Mulroy Shuns checkpoint inhibitors and says Merrimack will continue to focus on liposomes targeting hypoxic tumors where checkpoint inhibitors fail. Merrimack's antibody program will enhance both Onivyde and the antibody directed nanotherapeutic (ADN) pipeline candidates.

    Sentiment: Strong Buy

  • scistats scistats May 4, 2016 5:02 PM Flag

    CEO Mulroy at Deutsche Bank Securities 41st Annual Healthcare Conference
    May 4, 2016
    1:30 PM

    1. UCSF convection-enhanced delivery of Onivyde for glioma (brain or spine tumors). This delivery will take advantage of the stability Onivyde’s shell that provides a long half-life.

    2. Trial underway on metastatic breast cancer hypoxic tumor diagnostic + Onivyde. Merrimack is trying to find hypoxic breast tumors with high macrophage content. Feraheme® (AMAG Pharmaceuticals) is an iron-oxide super-paramagnetic nanoparticle known to be taken up by macrophages abundant in hypoxic tumors and for exhibiting magnetic resonance imaging properties. These tumors represent 20% of breast tumors for which Onivyde is predicted to work best. This will be Onivyde’s niche where checkpoint inhibitors may not work well.

    3. Also targeting Onivyde for liposarcoma (LPS) another hypoxic tumor type. “Bone and soft tissue sarcomas are the main types of sarcoma. Soft tissue sarcomas can develop from soft tissues like fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues.”-American Cancer Society

    4. Coming soon. Onivyde + targeted therapies in hypoxic GASTRIC CANCER (GI cancers) tumors which lack the microenvironment for immune cells, specifically.

    5. Upshot: Merrimack thinks checkpoint inhibitors Keytruda and Opidvo cannot work in hypoxic tumors that lack the microenvironment needed for antigen and immune cells to jump start/stimulate an immune response. Onivyde is targeting these hypoxic tumors. Instead of teaming up with checkpoint inhibitors, they think they can avoid them.

    6. Emphasized will talk more on - Analyst's Day on May 19th.

    For MM-141, information he left out that is on poster:

    Istiratumab was designed, using an integrated Systems Biology‐based approach, to inhibit pro‐survival signaling in cancer cells by co‐blocking both IGF‐1R and ErbB3 receptors

    IGF‐1R, ErbB3 and/or their ligands can be identified in more than 95% of
    ovarian tumor samples

    Sentiment: Strong Buy

  • Reply to

    mgmt

    by dcorm05 May 3, 2016 10:27 PM
    scistats scistats May 4, 2016 2:01 PM Flag

    The conversion cleaned up the books considerably and is one less thing to deal with during an acquisition.

    And as Yasir said, it saves money, but not enough to buy time or stop the fuse from burning. There is nothing Merrimack can do to change the fact that they must be bought. This is a mathematical fact.

    "While in many cases issuing convertible debt is often easier to deal with than issuing equity, the one situation where this often becomes complex is an acquisition while the debt is outstanding."

    Google: "convertible-debt-conversion-in-a-sale-of-the-company"

    Sentiment: Strong Buy

  • Reply to

    mgmt

    by dcorm05 May 3, 2016 10:27 PM
    scistats scistats May 4, 2016 1:37 PM Flag

    If Dendreon had sold out to JNJ upon Provenge approval, we would be looking at Provenge version 10.0 by now. Instead, Dendreon decided to got it alone, and they got their nuts roasted. Valeant bought BK Dendreon for $495 million. They said, Provenge had been undermanaged and was a billion dollar product.

    Timing is key. CEO Mulroy has seen the light and understands that if he holds the Merrimack program back, it will stall and crash without helping anyone. A buyout is the definition of success for the majority of small biotechs.

    Sentiment: Strong Buy

  • Reply to

    mgmt

    by dcorm05 May 3, 2016 10:27 PM
    scistats scistats May 4, 2016 12:16 PM Flag

    Management was dodging questions about April Onivyde sales.
    They have a pretty good picture of the situation.

    I thought perhaps partnering MM-310 would help, but it would only be a drop in the bucket of the cash they need to compete. Either CEO Mulroy capitulates or he will rapidly take Merrimack BK.

    Dr. Al-Wakeel will orchestrate the buyout, and he has begun setting the stage with conversion of notes to shares.

    Big Pharma is not looking at month-to-month market trends, nor do they care about PPS fluctuations in the volatile small bio sector. They are looking at the competition and their position ten years down the road.

    Buyouts are happening now as seen with Stemcentrx which had the same manufacturing antibody directed nanotherapeutics (ADN) strategy as Merrimack. Discussions should already be underway if they know what is best.

    Sentiment: Strong Buy

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