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Celldex Therapeutics, Inc. Message Board

long_vrts2 49 posts  |  Last Activity: Nov 23, 2015 12:56 AM Member since: Jul 12, 1999
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  • Amgen Inc. AMGN announced that Kyprolis gained approval in the EU in combination with Celgene Corporation’s CELG Revlimid (lenalidomide) and dexamethasone for the treatment of multiple myeloma patients who have received at least one prior therapy. This makes Kyprolis the first irreversible proteasome inhibitor to gain approval in the EU for use in combination for the treatment of patients with relapsed multiple myeloma.

    EU approval was largely expected as the Committee for Medicinal Products for Human Use had issued a favorable opinion this September.

    We note that Kyprolis had gained accelerated approval in the U.S. in 2012 for the treatment of patients with multiple myeloma who have received at least two prior therapies including Velcade and an immunomodulatory agent and have demonstrated disease progression on or within 60 days of completion of the last therapy. The FDA had expanded Kyprolis’ label further in Jul 2015 for its use in combination with Revlimid and dexamethasone in multiple myeloma patients who have received one to three prior lines of therapy.

    Amgen is working on expanding Kyprolis’ label further both in the U.S. and EU. The company is now looking to get Kyprolis approved in the EU for use in combination with dexamethasone in relapsed multiple myeloma patients, for which it intends to submit data from the phase III ENDEAVOR (RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma) study.

    Kyprolis is also under priority review in the U.S. for the same indication with a response from the FDA expected by Jan 22, 2016. The drug became a part of Amgen’s portfolio following its acquisition of Onyx and registered sales of $364 million in the first nine months of 2015.

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Nov 23, 2015 12:50 AM Flag

    "...its a nice pilot study that hints at efficacy..."

    Immunotherapy takes longer to kick in, and this is reflected in a modest (or "hint" if you will...) of improvement on Median OS. However, the long term survivor tail is unprecedented for any recurrent GBM trial of Avastin or Avastin combination treatment:

    - OS24: Rintega=25%, Avastin=0%
    - OS36: Rintega=25%

    This is what I meant when I said the update exceeded my expectations. I thought if they showed OS36 of 10% that would be very impressive....but 25%, with some pts still PFS at 36 mos? Yes, most definitely these results are "unprecedented", and they do "change the way we think about gliobastoma".

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Nov 23, 2015 12:29 AM Flag

    "On the flip side, control patients were older and had a lower KPS on avg."

    Actually, the control pts were younger and had higher KPS, so these favored the control arm. However, I agree with you that it's hard do say if the imbalances completely cancel each other.

    "however if ACT IV is stopped early next interim I can see them using ReACT to get simultaneous approval in new/recurrent gbm."

    Yes, this is what CLDX is planning to do. If ReACT results are good enough for simultaneous approval in a couple of months, aren't they good enough for Expanded Access right now, to give pts and their doctors this treatment option to improve survival, and equally importantly, quality of life?

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Nov 21, 2015 6:48 PM Flag

    If we lived in a world with normally functioning government institutions, the following would happen:

    1. Monday morning, 8 am (oops, forgot this is the bureaucracy that is the FDA, they get in at 9a, if at all, drink their coffees and eat their donuts, perhaps surf the web a little bit). OK, so maybe bright and early at 11a they should check the ReACT results.

    2. As a first step, the FDA should immediately approve Rintega for Expanded Access (also known as Compassionate Use). Recurrent vIII+ GBM is currently a death sentence, with no effective treatment options. Rintega is the first therapy that increases survival- markedly so- and it borders on the criminal to deny patients an effective treatment, with substantial evidence of efficacy/safety as demonstrated by Rintega.

    3. The FDA should then make a sustained effort- as in working full days, 5 days a week, yes, I know I'm asking for the moon here- to comprehensively analyze the data and give Accelerated Approval to Rintega in recurrent vIII+ GBM.

    4. Based on the results presented in May, I was convinced that the FDA was going to award accelerated approval to Rintega. I was flabbergasted when they didn't given that vIII GBM is an ultra orphan disease, severe unmet need, excellent safety/efficacy of Rintega. I will be even more flabbergasted if in the wake of Friday's ReACT data the FDA will not award Expanded Access, at least- or AA as it should- to Rintega.

    I would love to hear from shorts, naysayers, etc, why Rintega should not be approved for recurrent GBM after the SNO'15 results? Why deny this very safe and effective treatment to patients who otherwise face a very dire prognosis? Just give me one reason...

    Sentiment: Strong Buy

  • The long term ReACT results presented on Friday at SNO'15 exceeded my expectations:

    1. Mature Overall Survival data showed an improvement over results presented in May: there was a 10% improvement in Hazard Ratio (from .57 to .53), and more than a 2-fold improvement in p value (from 0.039 to 0.014). (Translated into plain English, this means that Rintega halves the risk of death in recurrent vIII+ GBM pts, with a probability close to 99% that this is due efficacy of Rintega and not due to chance.)

    2. % Survival: at 2 years: 25% of Rintega pts vs 0% control.

    3. Long-term survival (Kaplan-Meier curve in slide 11): this is the most remarkable finding from the trial. The 25% of Rintega pts who are alive at 2 years continue to be alive at 3 years, with no drop off. To put this in context: Rintega is being compared in this trial not to a sugar pill, but Avastin, which is standard-of-care in this indication. Avastin, either as monotherapy or in combination with other treatments, has been tested in dozens of prospective and retrospective trials in recurrent GBM. Only a couple of patients, out of thousands, have survived to 3 years (and these pts were not even stratified for vIII GBM, where the outcome is even worse- in the control arm of ReACT, no patient survived past 2 years). In the ReACT trial, from a relatively small sample, 25% of pts on Rintega survive to 3 years, and a few of them are even progression free at 3 years!

    So I completely agree with Dr. Reardon's "The long-term survival benefit observed in this study is unprecedented as it is exceedingly rare for patients with highly aggressive, EGFRvIII-positive glioblastoma—even in the newly diagnosed setting—to live beyond two years."

    4. Safety: Rintega continues to show an excellent safety profile, with injection site redness being the major adverse symptom.

    5. Quality of life: not only are pts on Rintega living remarkably longer, but the quality of life is significantly improved, with much less steroid use.

    Sentiment: Strong Buy

  • Adds to the positive buzz surrounding MK-8931:

    "Merck and inventors Jack D. Scott, Andrew W. Stamford, Eric J. Gilbert, and Jared N. Cumming will receive a patent award in the pharmaceuticals category for “Iminothiadiazine Dioxide Compounds as BACE Inhibitors, Compositions and Their Use” (U.S. Patent 8,729,071 B2). One of the compounds from this invention, verubecestat (MK-8931) is currently being evaluated in two Phase 3 clinical trials for the treatment of Alzheimer’s disease."

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Nov 17, 2015 1:31 AM Flag

    Yes. Material info.

    Sentiment: Strong Buy

  • We are initiating coverage of Viking Therapeutics, Inc. (VKTX) with a Buy rating and a $15.00 price target. Viking is a clinical stage biopharmaceutical company focused on developing treatments for metabolic and endocrine related disorders. We believe that Viking’s products represent potential best-in-class treatments due to their unique mechanisms of action and strong safety profile in early clinical testing. With a market cap of less than $50 million, we believe the market does not fully appreciate the multiple billion-dollar opportunities Viking is pursuing, thus representing a compelling investment opportunity.

    Sentiment: Strong Buy

  • Reply to

    SNO 2015 Abstract

    by flogonuzim Nov 9, 2015 9:57 AM
    long_vrts2 long_vrts2 Nov 10, 2015 1:38 AM Flag

    This abstract was submitted June 15. Dr. Reardon's presentation will bring us up to date with the most recent ReACT results, CLDX will issue a PR and perhaps hold a conference call. The number of long-term survivors on Rindo will be a critical piece of information because recurrent, Avastin treated pts don't survive past 32 months or so. Based on PFS at 30 months, it's probable that about 20% of pts in the Rindo arm are surviving past 32 months.

    Sentiment: Strong Buy

  • long_vrts2 by long_vrts2 Nov 10, 2015 1:28 AM Flag

    Looks like CLDX and its collaborators will have a pretty high profile at SNO:

    1. ReACT presentation: platform, first in session, presented by lead investigator David Reardon.

    2. Adult Clinical Research Award winner '15: David Reardon.

    3. Presidential address: David Reardon.

    4. Sponsored Symposium:

    Immunotherapy in Glioblastoma: Emerging Options in Precision Medicine
    Supported by a grant from Celldex Therapeutics
    Room: Salon HKL

    John H. Sampson, MD, PhD
    Duke University, Durham, NC

    Amy B. Heimberger, MD
    MD Anderson Cancer Center, Houston, TX

    Michael Weller, MD
    University Hospital of Zürich, Zürich, Switzerland

    5. Immuno-Oncology: Emerging Research in Primary and Secondary Brain Tumors
    Supported by Bristol-Myers Squibb
    Room: Salon E-F (Level 3 of Marriott Rivercenter)

    2 presentations by Rindo co-inventor John Sampson and 1 by ReACT lead investigator Reardon:

    Harnessing the Immune System in Cancer Research and Current Challenges in Treating CNS Tumors
    John Sampson, MD, PhD
    Duke University School of Medicine

    Emerging Clinical Investigations of Immunotherapy in Glioblastoma
    John Sampson, MD, PhD
    Duke University School of Medicine

    Future Considerations for Immuno-Oncology in Primary and Secondary Brain Tumors
    David Reardon, MD
    Dana-Farber Cancer Institute

    Should be interesting....

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Nov 9, 2015 1:51 AM Flag

    A lot depends on the Varli results. If Varli proves itself, then running all the PII's and III's is beyond CLDX's capability. They will have to partner, and one possibility will be Roche doing a Genentech type arrangement where they take big equity stake in CLDX. The advantage to CLDX would be that this would give them the funds to take Rindo, Glemba and 301 to market, and would have a deep pockets partner to advance Varli. The advantage for Roche would be that Varli would give it a dominant position in the IO space because Varli could be used with a variety of checkpoint inhibitors and potentially other immuno-oncolgy agents.

    Sentiment: Strong Buy

  • G&A was ~ $20M in '14 and will increase to ~ $30M in '15.
    About $2M of the increase is due to personnel costs (eg salaries) "as we prepare for potential product launches".
    The balance, or about $8M, will be spent on " RINTEGA and glembatumumab vedotin commercial planning costs".

    Unless they expect "knock your socks off" efficacy and statistical significance for the Rintega and Glemba trials, I hope they also allocate some funds for regulatory approval purposes. I feel that they didn't fight the good fight against the FDA to get accelerated approval for Rintega in recurrent GBM, despite having Breakthrough Therapy designation and consistent improvement in survival across Avastin naive, Avastin refractory and compassionate use. If the long-term Rintega survival data from ReACT show an OS improvement that exceeds previously reported results for Avastin pts- which would be an absolute improvement and potential imbalances in cohorts would be irrelevant- then CLDX should consider going back to the FDA and making a case for accelerated approval. Recurrent GBM pts whose prognosis without Rintega is so severe deserve no less.

    Sentiment: Strong Buy

  • SAN DIEGO, Nov. 3, 2015 /PRNewswire/ -- Viking Therapeutics, Inc. ("Viking") (VKTX), a clinical-stage biopharmaceutical company focused on the development of novel, first-in-class or best-in-class therapies for metabolic and endocrine disorders, today announced the initiation of dosing in the company's Phase 2 clinical trial of VK5211 in patients who recently suffered a hip fracture. VK5211, the company's lead program for muscle and bone disorders, is an orally available, non-steroidal selective androgen receptor modulator (SARM) designed to selectively stimulate muscle and bone formation with reduced activity in peripheral tissues such as skin and prostate. The company believes these characteristics may provide important benefits to patients recovering from hip fracture.

    The Phase 2 clinical trial is a randomized, double-blind, placebo-controlled, parallel group study designed to evaluate the efficacy, safety and tolerability of VK5211 in up to 120 patients recovering from hip fracture surgery. Patients will be randomized to receive once-daily VK5211 doses of 0.5 mg, 1.0 mg, 2.0 mg, or placebo for 12 weeks. The study's primary endpoint will evaluate the effects of VK5211 on lean body mass after 12 weeks of treatment. Secondary and exploratory objectives include assessments of functional performance, quality-of-life, and activities of daily living, as well as safety, tolerability and pharmacokinetics.

    "Initiation of this study represents a key milestone for Viking and our innovative SARM program as we work to rapidly advance the clinical development of VK5211," said Brian Lian, Ph.D., chief executive officer of Viking. "Our recently-completed Phase 1 safety and pharmacokinetic study of VK5211 in healthy elderly subjects reaffirmed previously-reported safety and tolerability characteristics of the compound, and we are excited to evaluate the treatment's efficacy in this Phase 2 trial. Patients recovering from hip fracture are known to lose bone and muscle at accel

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Oct 29, 2015 12:42 AM Flag

    ctn, good to hear from you. Yeah, I'm also in GILD, been in it for a long time- it's the best run biotech in the business, I'll wait for the next leg up and in the meantime reinvest the dividend. I picked up a few shares of early marketing biotechs MACK and SUPN, I think they are oversold and should be good for a 100% ROI over the next year.

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Oct 29, 2015 12:35 AM Flag

    I share in the disappointment regarding valuation. CLDX has lost close to 70% from its peak valuation. What is even more frustating is that it happened during a period when none of the clinical trials failed, and the institutional ownership is as solid as ever. I think brighter days are ahead as the pipeline advances on the regulatory path toward marketing.

    Sentiment: Strong Buy

  • In this study we used an in vitro system using human peripheral blood T cells to characterize the varlilumab-mediated costimulatory effects in combination with TCR stimulation in terms of phenotypic, transcriptional and functionality changes.


    T cells were isolated from normal volunteer PBMCs using magnetic bead isolation kits and stimulated in vitro with plate bound anti-CD3 Ab (OKT3) and varlilumab or control Ab for 72 h. Activation profiles were monitored by ELISA or Luminex-based testing cytokine/chemokine releases, cell surface phenotyping for costimulatory and coinhibitory markers and CFSE dye dilution by proliferating T cells and Tregs. Changes in gene expression and transcriptome analysis of varlilumab-stimulated T cells was carried on Agilent Human whole genome microarray datasets using a suite of statistical and bioinformatic software tools.


    Costimulation of T cells with varlilumab required continuous TCR signaling as pre-activated T cells were unable to produce cytokines with CD27 signaling alone. Analysis of T cell subsets further revealed that memory CD4+ and CD8+ T cells were specifically activated with a bias toward CD8+ T lymphocyte proliferation. Activation was accompanied by upregulated cell surface expression of costimulatory [4-1BB, OX40, GITR and ICOS] and coinhibitory [PD-1] molecules. Importantly, varlilumab costimulation did not activate purified Tregs as measured by cytokine production, proliferation and suppression of dividing non-Treg T cells. Analysis of changes in gene expression during varlilumab stimulation of T cells revealed modulation of pro-inflammatory signatures consistent with cellular activation and proliferation, with the IL-2 pathway showing the highest frequency of gene modulation.


    Altogether, the data reveal the requirements and T cell subtype-specific effects of CD27 costimulation, and helps select relevant biomarkers for studying the effects of varlilumab in patients.

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Oct 27, 2015 12:51 AM Flag

    CDLX acquired the rights to "develop and commercialize" Flt3L from Amgen in '09. From CLDX's Business Development website:

    "Amgen Inc. – Celldex acquired exclusive rights from Amgen to develop and commercialize two immune-stimulatory molecules known as FMS-like tyrosine kinase 3 ligand or Flt3L (now referred to as CDX-301) and CD40 ligand (CD40L). ..."

    Sentiment: Strong Buy

  • Cancer Discov. 2015 Oct 22. pii: CD-15-0510. [Epub ahead of print]

    Cancer immunotherapy with immunomodulatory anti-CD137 and anti-PD-1 monoclonal antibodies requires Batf3-dependent dendritic cells.

    Sanchez-Paulete AR1, Cueto FJ2, Martinez-Lopez M2, Labiano S1, Morales-Kastresana A1, Rodriguez-Ruiz ME3, Jure-Kunkel M4, Azpilikueta A1, Aznar MA1, Quetglas JI1, Sancho D2, Melero I5.


    Weak and ineffective antitumor cytotoxic T lymphocyte (CTL) responses can be rescued by immunomodulatory monoclonal antibodies (mAbs) targeting PD-1 or CD137. Using Batf3-/- mice, which are defective for cross-presentation of cell-associated antigens, we show that Batf3-dependent dendritic cells (DCs) are essential for the response to therapy with anti-CD137 or anti-PD-1 mAbs. Batf3-/- mice failed to prime an endogenous CTL-mediated immune response toward tumor-associated antigens, including neoantigens. As a result, the immunomodulatory mAbs could not amplify any therapeutically functional immune response in these mice. Moreover, administration of systemic sFlt3L and local poly-ICLC enhanced DC-mediated cross-priming and synergized with anti-CD137- and anti-PD-1-mediated immunostimulation in tumor therapy against B16-OVA-derived melanomas, whereas this function was lost in Batf3-/- mice. These experiments show that cross-priming of tumor antigens by Flt3L- and Batf3-dependent DCs is crucial to the efficacy of immunostimulatory mAbs and represents a very attractive point of intervention to enhance their clinical antitumor effects.

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Oct 23, 2015 1:32 AM Flag

    "its not like management would stop the trial if interim results made it clear that there was no chance of passing the final."

    Actually, the IDMC will advise termination of trial if they conclude that it's unlikely that the treatment will demonstrate a statistically significant difference at closing test (see Synta on Tuesday).

    I assign an approx 70% chance of success for Rindo second interim in ACTIV. I think Oppenheimer has projected 65% success, don't know about other funds.

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Oct 23, 2015 1:20 AM Flag

    "why not increase N to get the higher p value."

    Increasing the N value- as pointed out correctly by share- does not impact the p-value target. It does, however, increase the probability that you will hit your p-value target.

    Sentiment: Strong Buy

17.79-0.32(-1.77%)Nov 24 4:00 PMEST