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Geron Corporation Message Board

end2war 450 posts  |  Last Activity: 16 hours ago Member since: Oct 31, 2003
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  • HP

    Since they already get 99% KD with 4 mg/kg on some of the NUC naive, why go higher? Now that they have some safety data at 4 mpk, they can explore the rest of the curve.

    I think they may be looking at the following::
    1. The shape of the KD curve, ie how linear and how steep, (eg does it hit max KD sooner with a larger dose, and does it sustain KD longer with a larger dose)?
    2. Will they get a better average or mean KD with a higher dose?
    3. The area of plateau, where more drug does not produce more KD ( or decreasing improvments)
    4. Whether SAEs start showing after 4 mg, in the range from 4 to 6 mpk, and if so the frequency of SAEs as they raise the dose. (hopefully they will have little or none in this range)
    5. Any previously undiscovered dose dependent outcomes.

  • We are not a single drug company. We are platform company with multiple drugs in the pipeline. Think of us as an RNAi platform play.

  • We have not only had our foot on the gas over the past few years, we’ve had it on
    the floor. Our lead programs, ARC-520, -AAT, and -521, are now at important
    points in their development when substantial value inflections are possible.
    Pushing through those points is critical to us as a company and we want to ensure
    that we have the capital for this, particularly during this time of uncertainty in the
    broader markets. In order to keep our foot on the gas with these more mature
    programs, we are easing up a bit on some of our earliest-stage programs. We
    created a flexible cost structure that enabled us to move quickly but also to dial
    down spending on a program-by-program basis, and we are taking advantage of
    that now in order to fully resource HBV and AAT. All earlier programs continue
    to move forward, but some will just move at a slower pace for now. This is a good
    strategy and we are quite confident that there will be ample opportunities to fully
    fund these and other programs through various shareholder friendly methods."

    1. He is not sure when funding will occur, so he is conserving on money use.
    2. There probably will be no large dilutive secondary, but a small private placement or something else to raise interim cash is not off the table.
    3. They eventually will have cash for their pipeline programs, but he is not able to project exactly when those programs can get going full bore because he does not know when the ARC-520 and/or ARC-AAT data will enable the cash raise, and he is not projecting another source of funding.
    4. It is hard to predict when CA will release Monarch data from this, but I still assume we will get something by July 1, 2016.
    5. There may be collaboration negotiations underway, and they may have given ROFN to Roche, but you cannot tell that from the above quote.

    Basically, don't lose sleep over money, but who knows when or how they will solve the problem. Timing, is one of the hardest things to understand here. Don't hold your breath, LOL.

  • Reply to

    I've got a good feeling boyos

    by tltrooper May 2, 2016 6:49 AM

    I have a good feeling too, but I think it will close the gap, LOL.

  • Reply to

    Just one approval...

    by postcalloff Apr 30, 2016 9:43 AM

    By the way, John, I really enjoyed your opening comments. Everyone's very focused on what you're going to do with your cash, BD, M&A. So I have, actually, one simple question, probably for John: would you be willing to go hostile? And if not, why not? How do you feel about that? Because clearly, what we're hearing is that the small companies won't engage right now because they don't like the valuations, but the large companies are very interested. Thank you.

    --------------------------------------------------------------------------------

    John Milligan, Gilead Sciences, Inc. - President and CEO [7]

    --------------------------------------------------------------------------------

    Hi, Mark. It's John. You know, mergers and acquisitions are always a process. And so the ability to go hostile is limited by how much data or how much corporation you need. So in each situation, you'd have to kind of think about -- what do I need to know about the pipeline, or about things that are not public about a company in order to be comfortable making sort of a public offer for the company?

    But that being said, we've never declared ourselves unwilling to go hostile. I do prefer a friendly process, but it would just depend on the situation itself.

  • end2war end2war May 1, 2016 8:13 PM Flag

    Jimmy That is right, unless your timing, direction, on understanding is off--which one can almost guarantee it is! Play with leverage at your own risk. For example, consider a few leaps.

  • Reply to

    ARC-521

    by dig_a_little_deeper_1 May 1, 2016 8:55 AM
    end2war end2war May 1, 2016 4:00 PM Flag

    2/9 CC:

    "ARC-521 uses the same DPC™ delivery vehicle as ARC-520 and ARC-AAT, so
    we have a good amount of experience with it clinically. To date it has been well
    tolerated at all dose levels studied, which gives us great confidence as we prepare
    to initiate clinical studies of ARC-521 during 2016. We have an aggressive plan
    for the development of ARC-521 that includes an accelerated first-in-man Phase
    1/2 design intended to get us into a multiple dose study in patients rapidly. We
    will talk more about this design as we get closer to initiating the study, which has
    planned regulatory submissions toward the end of second quarter 2016"

  • end2war end2war Apr 29, 2016 5:55 PM Flag

    Sorry, you need to Google the full article. I tried, but failed, to post the list of results.

  • end2war end2war Apr 29, 2016 5:53 PM Flag

    HP

    Look again at the "results" Ssection. The part I liked is that the DID say the failed to achieve sAG KD.

  • The largest ever investment bet by the storied venture firm Founders Fund has paid off.
    The drug company AbbVie, based in Massachusetts, said it would pay $5.8 billion in cash and stock to take over Stemcentrx, a little-known biotech backed by Founders Fund and whose strategy for treating cancer we first wrote about in September.
    The deal includes another $4 billion in cash payments if Stemcentrx’s experimental drugs, still in clinical trials, actually pan out. According to Business Insider, the full value would make it one of the very largest acquisitions of a private, venture-backed company in history, possibly trailing only the $19 billion acquisition of WhatsApp by Facebook.
    The head-turning price tag reflects intense demand for new cancer drugs, but AbbVie is also taking a big risk. “I think that this deal is going to end up looking either very smart or very stupid,” writes Derek Lowe, the well-known drug blogger. About $100 billion worth of cancer drugs are sold annually worldwide and new cancer treatments dominate the list of medicines in clinical trials.
    Stemcentrx was unusual because its financial backers weren’t well-known biotech VCs. Instead, its largest single investor was Founders Fund, better known for backing outfits like SpaceX and Palantir Technologies, but which believed it could improve the typically low odds of drug success. Brian Singerman, a partner at Founders Fund, tells Fortune the fund managers aren’t space experts either, but still invested in Elon Musk’s SpaceX.
    Now the biotech “dumb money” looks pretty smart, and that could tempt other venture funds to shift their cash away from social media and software and into biotech, too. "There’s a tsunami brewing," Stuart Peterson, a founder of Artis Ventures and an early investor in Stemcentrx, told Business Insider. "[Cancer] is a big problem that’s meaningful for us on a global basis. This is where we should be focused."

  • end2war end2war Apr 29, 2016 3:26 PM Flag

    Results

    In the monotherapy arms, the 100, 200, and 400 mg once-daily doses of NVR 3-778 produced small reductions in HBV DNA (

  • NVR 3-778, an experimental drug that interferes with hepatitis B virus (HBV) capsid assembly, led to reductions in HBV DNA, HBV RNA, and hepatitis B "e" antigen (HBeAg), showing greater activity when combined with pegylated interferon, researchers reported at the European Association for the Study of the Liver's International Liver Congress (EASL 2016) last month in Barcelona.

    NVR 3-778, being developed by Novira Therapeutics,is a first-in-class small molecule that directly targets the HBV core protein, which plays key roles in viral replication and persistence. It is responsible for assembly of the viral nucleocapsid and enables replenishment of HBV cccDNA.

    NVR 3-778 appears to inhibit HBV by multiple mechanisms, offering a new approach to hepatitis B treatment. Current therapy using nucleoside/nucleotide analog antivirals or interferon can suppress HBV replication long-term, but seldom leads to a cure as indicated by hepatitis B surface antigen (HBsAg) loss and development of anti-HBs antibodies.

    Researchers previously demonstrated that NVR 3-778 causes mis-assembly of the HBV core protein in vitro. Treating HBV-producing cells with NVR 3-778 blocked encapsidation of viral genetic material, preventing the production and release of functional infectious virus. Prior research showed that NVR 3-778 blocked replication of various HBV strains in a laboratory study. In genetically engineered mice with human hepatocytes, combining NVR 3-778 with pegylated interferon led to greater antiviral activity than either drug alone. An early human trial showed thatNVR 3-778 was generally safe and well-tolerated.

    Man-Fung Yuen from the University of Hong Kong and colleagues conducted a Phase 1b trial of the safety and efficacy of NVR 3-778, used alone and with pegylated interferon, in chronic hepatitis B patients.

    This study enrolled adults with HBeAg-positive chronic hepatitis B and baseline HBV DNA above 20,000 IU/mL. All but 3 were men, the median age was approximately 40 y

  • end2war end2war Apr 29, 2016 1:52 PM Flag

    bull,

    Thanks, I always thought that there were possibilities for territorial deals with the Asian markets. And, for me that usually focuses on large Japanese Pharma, but how to address HK and mainland China is another story. I hope ARWR gets a product that will deliver FCs and they have the problem of how to distribute it. First things first. Lets see them deliver FCs.

  • end2war end2war Apr 29, 2016 12:02 PM Flag

    I am not sure, but I think you are wrong to say they are independent. This is for a scientist like HP, or someone that understands better than me what they are doing. Here is a little info from wikipedia.

    "Apolipoproteins are proteins that bind lipids (oil-soluble substances such as fat and cholesterol) to form lipoproteins. They transport the lipids through the lymphatic and circulatory systems.

    The lipid components of lipoproteins are insoluble in water. However, because of their detergent-like (amphipathic) properties, apolipoproteins and other amphipathic molecules (such as phospholipids) can surround the lipids, creating the lipoprotein particle that is itself water-soluble, and can thus be carried through water-based circulation (i.e., blood, lymph).

    Apolipoproteins also serve as enzyme cofactors, receptor ligands, and lipid transfer carriers that regulate the metabolism of lipoproteins and their uptake in tissues."

  • end2war end2war Apr 29, 2016 11:44 AM Flag

    From ARWRs website on pipeline:

    "ARC-LPA

    ARC-LPA is designed to reduce production of apolipoprotein A, a key component of lipoprotein(a), which has been genetically linked with increased risk of cardiovascular diseases, independent of cholesterol and LDL levels. ARC-LPA is Arrowhead’s first drug candidate to use a subcutaneously administered delivery construct."

  • end2war end2war Apr 29, 2016 11:29 AM Flag

    “RNAi therapeutics for chronic HBV - Animal models” is being presented in the 5th Asian Conference on Hepatitis and AIDS (ACHA). They are doing a lot of the testing there and they seem to be moving forward with a full understanding that HBV studies are more important in foreign jurisdictions than the US. It does look like they may have some competition for GILD that comes out of Asia regarding cHBV licensing and distribution.

  • end2war end2war Apr 29, 2016 11:19 AM Flag

    Henry,

    I am going with CA on this. You should too. He said money is not going to be a problem. Believe him!!

    CA in the 2/9/16 CC:

    "I have always thought that we could get through anything as long as we could say 4
    things. They are:
    1. Our technology works;
    2. We are working to solve real medical problems;
    3. We have capital now; and
    4. We have access to additional growth capital.
    We believe that all of these are true today."

  • end2war end2war Apr 29, 2016 11:10 AM Flag

    Do you guys realize that 1/3 of the world dies from vascular disease? The aging process in humans causes a decline in vascular health. Standard practice now is to do lipid panel blood tests to detect conditions that are known to lead to heart and vascular problems and that includes clotting problems that cause heart attack, strokes and the buildup of arterial plaque. This can be modified slightly with good diet, and weight control, but the world now is overweight and does not eat right. Statins are a first line defense. But, it all starts with the liver making the unwanted lipids.

    What can RNAi do about it? Can it turn off the right genes to lower the production of unwanted colesteral? Is this another multi billion dollar opportunity for ARWR? Can we even get our hands around the potential here. Is this a sign of where RNAi science is going. Will it engulf all of medicine?

  • end2war end2war Apr 29, 2016 11:00 AM Flag

    An important aspect to be discussed is the use of radioactive or fluorescent labels, and the strategy for their incorporation.

    Although modified nucleotides are chemically distinct from the four major ribonucleotides, they typically are composed of a phosphate, a ribose and a pyrimdine or purine base, and thus display physicochemical properties which are, though different, still similar to a typical ribonucleotide. A prominent exception is the Y-base (wybutosine, Fig. 1A), whose three-ring aromatic sys-tem is concomitantly fluorescent and so lipophilic that it allows easy separation and detection of tRNAs carrying it.3 The rule for the vast majority of the remaining 100 or so modifications is, that a modified RNA cannot be easily distinguished from its unmodified counterpart, because a small modification such as e.g., a methylation does only minor changes to the RNA’s physi-cochemical properties. Therefore, many methods first break down the RNA chain by nuclease digestion,4 in some cases fol-lowed by a phosphatase treatment (shown in Fig. 2).5 The result-ing mixture of short oligonucleotides, nucleotides or nucleosides, which has essentially lost its sequence information, can then be separated by chromatography, capillary electrophoresis or mass spectrometry after specific ionization and mass analyzer transfer. Modifications are identified by their retention characteristics in chromatography and capillary electrophoresis, or by their charac-teristic mass-to-charge ratio (m/z), respectively.

  • Abstract
    RNA nucleotide modifications are typically of low abundance and frequently go unnoticed by standard detection methods of molecular biology and cell biology. With a burst of knowledge intruding from such diverse areas as genomics, structural biology, regulation of gene expression and immunology, it becomes increasingly clear that many exciting functions of nucleotide modifications remain to be explored. It follows in turn that the biology of nucleotide modification and editing is a field poised to rapidly gain importance in a variety of fields. The detection and analysis of nucleotide modifications present a clear limitation in this respect. Here, various methods for detection of nucleotide modifications are discussed based on three discriminating principles, namely physicochemical properties, enzymatic turnover, and chemical reactivity. Because the full extent of nucleotide modification across the various RNA species remains ill understood, emphasis is placed on high-throughput techniques with a potential to screen entire transcriptomes.

GERN
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