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Celldex Therapeutics, Inc. Message Board

long_vrts2 49 posts  |  Last Activity: 2 hours 58 minutes ago Member since: Jul 12, 1999
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  • Editorial podcast by Dr. Connelly highlights:

    1. gpMB an attractive cancer target:
    - gpNMB an independent risk factor for worse outcome in BC
    - 40-60% of BC's overexpress gpNMB
    - 29% of TNBC pts gpNMB+++

    2. Glemba melanoma trial:
    - 15% ORR in all pts
    - 28% ORR in high gpNMB

    3. Glemba PI/II trial in BC pts:
    - primary endpoint met
    - few treatment related adverse effects

    4. EMERGE PII trial in BC/TNBC/high gpNMB pts:
    - controlled trial against "Investigator's Choice"
    - Glemba superior to IC w/ ORR of 19% vs 14%
    - Glemba adverse effect profile superior to IC, better tolerated with fewer side effects
    - Statistically significant Glemba improvement in ORR/PFS over IC for TNBC and TNBC/high GPNMB pts

    5. Going forward:
    - if METRIC successful, Glemba will be first targeted therapeutic in TNBC
    - certain kinase inhibitors increase gpNMB expression and make cancer cells more sensitive to Glemba

    Glemba PI/II trial in advanced melanoma:
    1. Study design:
    - 117 non-resectable, Stage III-IV melanoma pts
    - divided into 3 regimens
    2. Dose optimization:
    - 1.88 mg/kg every 3 weeks gives best balance of efficacy and low toxicity
    - ORR ranged from 15% to 33% depending on dosing
    - 3 deaths in doses exceeding MTD
    (My take on toxicity: these were MTD exceeding doses in advanced Stage IV melanoma pts, relevance somewhat of a moot point because these doses will not be used clinically)

    Glemba PI/II trial in locally advanced/metastatic BC:
    1. MTD was established for PII:
    - 1.88 mg/kg was optimal
    2. Primary endpoint for efficacy met:
    - PFS12 of 33%
    - median PFS of 9.1 wks for all pts, 17.9 wks for pts with TNBC, and 18.0 wks for pts with gpNMB
    3. Safety profile:
    - acceptable, with relatively mild toxicity
    4. Conclusion:
    - Glemba active in BC
    (confirmed in EMERGE PII randomized trial)

    Sentiment: Strong Buy

  • This Editorial podcast accompanies the Glemba report in TNBC.

    By Dr. Roisin Connelly of Sidney Kimmel Cancer Center/Johns Hopkins, leading clinical investigator in breast cancer clinical trials. Worth listening to, let me know if not accessible without subscription, I'll post details. Very encouraging for Glemba, CLDX and TNBC pts.

    Sentiment: Strong Buy

  • Sep 8, 2014 CATLIN AVERY W Officer 10,000 Direct Option Exercise at $4.50 per share. 45,000

    Sentiment: Strong Buy

  • long_vrts2 by long_vrts2 Sep 30, 2014 1:24 AM Flag

    Sep 25, 2014 ARYEH JASONDirector 20,300 Direct Option Exercise at $6.82 - $17.88 per share.

    (It appears that he didn't sell...)

    Sentiment: Strong Buy

  • World J Gastroenterol. 2014 Sep 21;20(35):12517-12521.
    Eltrombopag in chronic hepatitis C.
    Mihăilă RG, Cipăian RC.
    Author information

    Abstract
    Chronic hepatitis C is a public health problem worldwide. Unfortunately, not all patients may benefit from antiviral therapy due to thrombocytopenia. Its causes are represented by portal hypertension and platelet sequestration in the spleen, decreased serum levels or activity of thrombopoietin, the bone marrow suppression induced by hepatitis C virus and a possible adverse effect of interferon. Thrombopoietin receptor analogs may contribute to increase platelet counts in these patients. Eltrombopag binds to another region of the thrombopoietin receptor compared to endogenous thrombopoietin and stimulates the proliferation and maturation of megakaryocytes and the platelet production in a dose-dependent manner. Eltrombopag has proven its effectiveness for the treatment of patients with primary immune thrombocytopenia. Its indication for other hemopathies or situations (like thrombocytopenia secondary to chemo- or radiotherapy, acute leukemia, myelodysplastic syndroms, acquired and hereditary bone marrow failure, and platelet donors) is under study. Eltrombopag may be particularly useful in patients with advanced chronic hepatitis or liver cirrhosis who require antiviral treatment. We present a minireview on the results of treatment with eltrombopag in patients chronically infected with hepatitis C virus, highlighting the benefits and mentioning possible adverse effects. In some studies eltrombopag increased the number of virological responses after clasical antiviral treatment of patients with chronic hepatitis C and reduced the transfusional requirements of those who had to be subjected to invasive surgery. Eltrombopag is a solution for many of these patients, which allows them receiving antiviral therapy and sometimes getting a sustained virological response, but they must be well monitored to prevent possible thromboembolic

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Sep 26, 2014 12:30 AM Flag

    Yes, the Rindo+CDX-301 combo would be controlled against Rindo alone. Looks like CLDX is planning to expand the 301 program to cancer immunotherapy, based on comments by Tom Davis, and since he mentioned internal programs, I think Rindo, Glemba and 1401 are all candidates (1401 combo already underway in melanoma):

    "CDX-301 has broad potential to support and control immune function across multiple indications including cancer immunotherapy, marrow disorders like sickle cell disease, immunosuppression from trauma, burns and radiation, and even autoimmunity. We look forward to assessing the activity of CDX-301 in this initial setting and expanding the program, including in combination with a number of internal programs, over time."

    Sentiment: Strong Buy

  • CD-Melphalan is licensed to SPPI for a royalty rate of 15%-25%. Below is part of an article on CE-Melphalan from Street:

    "But something much bigger could happen soon for Spectrum, and that is Melphalan. Melphalan is a type of chemotherapy that has been around since 1984. It's nothing new. Its annual global sales are $130 million. The problem is, in order to administer Melphalan, a chemical called propylene glycol is needed, and this chemical is known to poison the kidneys and cause cardiac trouble. It severely limits the dosage of Melphalan a cancer patient can take.

    What Spectrum has is a new form of Melphalan that no longer needs propylene glycol as a delivery mechanism, upping the dosage patients can take in a sitting with less toxicity. In this case, you have a drug with an established sales record since the mid 1980s, reformulated and tested for bioequivalence already established; Orphan status granted; and a New Drug Application (NDA) to be submitted by the company next month.

    Will Spectrum's new Melphalan be a blockbuster? No, but there is little reason that its new, less-toxic formulation of the same drug can't simply supplant most, or perhaps even all Melphalan sales. The bottom-line numbers here are significant, and they are much more certain. This approval, unlike Beleodaq, will more likely lead to significant revenue increases."

    Sentiment: Strong Buy

  • (CDX-301 is currently in clinical trial in combination with CDX-1401 in melanoma, and in combination with low-dose radiotherapy for low grade lymphoma. An interesting potential combination would be with Rindo for vIII+ GBM, where robust immune response correlates with increased OS).

    J Exp Med. 2014 Aug 25;211(9):1875-91. doi: 10.1084/jem.20131397. Epub 2014 Aug 18.
    Classical Flt3L-dependent dendritic cells control immunity to protein vaccine.

    Anandasabapathy N1, Feder R2, Mollah S3, Tse SW4, Longhi MP2, Mehandru S2, Matos I2, Cheong C2, Ruane D2, Brane L2, Teixeira A2, Dobrin J2, Mizenina O2, Park CG2, Meredith M2, Clausen BE5, Nussenzweig MC2, Steinman RM2.
    Author information

    Abstract
    DCs are critical for initiating immunity. The current paradigm in vaccine biology is that DCs migrating from peripheral tissue and classical lymphoid-resident DCs (cDCs) cooperate in the draining LNs to initiate priming and proliferation of T cells. Here, we observe subcutaneous immunity is Fms-like tyrosine kinase 3 ligand (Flt3L) dependent. Flt3L is rapidly secreted after immunization; Flt3 deletion reduces T cell responses by 50%. Flt3L enhances global T cell and humoral immunity as well as both the numbers and antigen capture capacity of migratory DCs (migDCs) and LN-resident cDCs. Surprisingly, however, we find immunity is controlled by cDCs and actively tempered in vivo by migDCs. Deletion of Langerin(+) DC or blockade of DC migration improves immunity. Consistent with an immune-regulatory role, transcriptomic analyses reveals different skin migDC subsets in both mouse and human cluster together, and share immune-suppressing gene expression and regulatory pathways. These data reveal that protective immunity to protein vaccines is controlled by Flt3L-dependent, LN-resident cDCs.

    Sentiment: Strong Buy

  • Prev Rank -
    Location La Jolla, Calif.
    Industry Pharmaceuticals
    Sector Health Care
    F1000 Rank -
    G500 Rank -
    Current Streak -
    LGND

    This biotechnology firm generates most of its revenue in two ways—by partnering with other pharmaceutical companies, which pay royalties and license fees for use of Ligand’s drugs, and through sales of the company’s “drug reformulation technology,” Captisol. Acquired by Ligand in 2011, Captisol enables the creation of new/improved drugs by improving the solubility, stability and dosing of active pharmaceutical ingredients (to date, six have been approved by the FDA). It also contributed $19 million of the company’s $49 million total revenues last year, and accounted for just over half of 2013 revenue growth. —N.S.

    Revenue, Net Income $ millions
    Revenue Past Four Quarters 53
    Net Income Past Four Quarters 12

    Growth Rates %
    EPS 3 yr Annual Growth Rate Pct 66
    Rev 3 yr Annual Growth Rate 33
    Total Return 3 yr Annual Rate 73
    Beat S&P 3 yr Annual Growth Rate? YES

    Sentiment: Strong Buy

  • Reply to

    LV

    by cldx_58 Sep 20, 2014 2:20 PM
    long_vrts2 long_vrts2 Sep 21, 2014 11:52 PM Flag

    I don't see a buyout happening at this stage. An ITMN type scenario is more likely, with Rindo and/or Glemba successfully completing pivotal trials- big pharma prefer a sure thing, even if they have to pay several fold over current valuation.

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Sep 19, 2014 2:45 PM Flag

    frank,

    If they increase the patient enrollment to ~70 pts per group, then yes, I think there is the possibility of getting conditional FDA approval. It seems that CLDX is going in this direction based on their enrollment plans for the 2 respective groups in ReACT.

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Sep 19, 2014 12:51 AM Flag

    whip,

    I think it's a combination of having some- or likely most of- Rindo data from ReACT & compassionate use in hand, and waiting on some final results:

    1. From Group 1 (avastin naive) in the ReACT trial: they have RR and PFS and are waiting for final OS results. The OS results that still need to be finalized are likely the high-titer Rindo pts (n=8), 100% of whom were alive at 18 months.

    2. From Group 2 (avastin refractory): they have final PFS and OS, may need to finalize responses. In this group we already know the "High titer" (n=13) vs "Low Titer" (n=11) results, with "High titer" showing a doubling in median OS (6.6 mos vs 3.2 mos) and an approx 4-fold increase in 6 month OS (69% vs 18%).

    3. From compassionate use, they have the results in hand based on previous positive comments from Tom Davis, and the fact that they submitted an abstract to SNO. Since the abstract was chosen for podium presentation, and as lead-in for Michael Weller's overview presentation on the prospects of immunotherapy for GBM, I would venture that the results will be positive.

    Add to the mix the high institutional ownership of over 90%, and valuation over $1 Billion, and I think the probability is high that the anticipated newsflow will be positive.

    Sentiment: Strong Buy

  • Phase I Study of 30-Minute Infusion of Carfilzomib As Single Agent or in Combination With Low-Dose Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma.
    Papadopoulos KP1, Siegel DS2, Vesole DH2, Lee P2, Rosen ST2, Zojwalla N2, Holahan JR2, Lee S2, Wang Z2, Badros A2.
    Author information
    Abstract
    PURPOSE:

    Carfilzomib is an irreversible inhibitor of the constitutive proteasome and immunoproteasome. This phase I study evaluated the maximum-tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of carfilzomib administered as a 30-minute intravenous (IV) infusion. Safety and efficacy of carfilzomib as a single agent or in combination with low-dose dexamethasone were assessed.

    RESULTS:

    Thirty-three patients were treated with single-agent carfilzomib. Dose-limiting toxicities in two patients at 70 mg/m2 were renal tubular necrosis and proteinuria (both grade 3). The MTD was 56 mg/m2. Nausea (51.5%), fatigue (51.5%), pyrexia (42.4%), and dyspnea and thrombocytopenia (each 39.4%) were the most common treatment-related toxicities. Overall response rate (ORR) was 50% (56-mg/m2 cohort). Increasing carfilzomib dosing from 20 to 56 mg/m2 resulted in higher area under the plasma concentration-time curve from time zero to last sampling and maximum plasma concentration exposure with short half-life (range, 0.837 to 1.21 hours) and dose-dependent inhibition of proteasome chymotrypsin-like activity. In 22 patients treated with 45 or 56 mg/m2 of carfilzomib plus low-dose dexamethasone, the ORR was 55% with a safety profile comparable to that of single-agent carfilzomib.

    CONCLUSION:
    Carfilzomib administered as a 30-minute IV infusion at 56 mg/m2 (as single agent or with low-dose dexamethasone) was generally well tolerated and highly active in patients with relapsed and/or refractory MM. These data have provided the basis for the phase III randomized, multicenter trial ENDEAVOR.

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Sep 17, 2014 12:56 AM Flag

    ACTIV is powered to show a 3 months statistically significant difference with 0.79 hazard ratio, so it looks like CLDX wants to assure some cushion in the stats, based both on RTOG0525 and 2 recent studies from Germany and UK focusing on EGFRvIII GBM pts.

    The results from the compassionate use should give us an indication of the efficacy of Rindo in both newly diagnosed and recurrent GBM (assuming they break up the data into those categories for the presentation)- it appears that residual tumors are less of a factor than previously thought, so it may be possible to extrapolate directly from the compassionate use setting.to the controlled trial. At any rate, even if they present the results as pooled new GBM+ recurrent GBM, Rindo efficacy in this pt population would point to equal (or, more likely, greater) efficacy in the newly diagnosed GBM population that comprises ACTIV pts.

    Sentiment: Strong Buy

  • Reply to

    MNKD - long_vrts

    by swissmilkcow_10 Sep 16, 2014 3:23 PM
    long_vrts2 long_vrts2 Sep 17, 2014 12:29 AM Flag

    swiss,
    I sold after the positive Adcom meeting when MNKD doubled, and haven't looked back. My concerns over MNKD's prospects are regarding the uptake of Afrezza, and the deal with Sanofi not being advantageous to MNKD. I'd watch this one for awhile and see how evolves before putting any money into it.

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Sep 16, 2014 1:44 AM Flag

    The compassionate use Rindo presentation is the lead-in for an overview presentation by Dr. Michael Weller entitled "Current status of immunotherpy for gliomas". Michael Weller is one of the leading authorities on glioma immunotherapy , he's a co-investigator in the ReACT trial and co-author in the Rindo compassionate presentation. I think there is a pretty high probability that the lead-in for his presentation will be positive.

    Sentiment: Strong Buy

  • Cancer Chemother Pharmacol. 2014 Sep 13. [Epub ahead of print]
    Clinical study of the novel cyclin-dependent kinase inhibitor dinaciclib in combination with rituximab in relapsed/refractory chronic lymphocytic leukemia patients.

    PURPOSE:
    Dinaciclib is a novel selective inhibitor of cyclin-dependent kinase (CDK)1, CDK2, CDK5, and CDK9. We conducted a phase I study to investigate the effects of dinaciclib when administered with rituximab.
    METHODS:
    In this phase I nonrandomized dose-escalation 3 + 3 trial, patients with relapsed/refractory chronic lymphocytic leukemia (CLL) were treated with dinaciclib and rituximab. Dinaciclib was administered intravenously (IV) over 2 h on days 1, 8 and 15 in cycles 2-13 (28-day cycles). Rituximab 375 mg/m2 was administered IV on days 1, 8, 15 and 22 in cycle 1 (28-day cycle) and on day 1 during cycle 3-13. Rituximab was not administered in cycle 2. Rituximab and dinaciclib were given alone in cycles 1 and 2, respectively, and in combination in cycles 3-13. Primary objectives included determination of the recommended phase II dose of dinaciclib and evaluation of pharmacokinetics (PK) when administered with rituximab.
    RESULTS:

    Five patients completed the study due to early termination. All presented with drug-related adverse events (AEs), but no dose-limiting toxicities were observed. The most commonly observed toxicities included hematological, digestive and metabolic AEs. However, no tumor lysis syndrome has been reported in the study. Four patients achieved stable disease, and one patient achieved complete response according to 2008 iwCLL criteria at cycle 3. PK samples were collected from 5 patients, and no obvious interaction between dinaciclib and rituximab was observed.
    CONCLUSIONS:Limited data from this study shows dinaciclib in combination with rituximab was well tolerated and revealed encouraging clinical activity in relapsed/refractory CLL patients.

    Limited data from this study shows dinaciclib in combination with rituxim

    Sentiment: Strong Buy

  • Reply to

    Long VRTS are you playing this....

    by frankfrazzano Sep 12, 2014 2:21 AM
    long_vrts2 long_vrts2 Sep 15, 2014 1:03 AM Flag

    I'm a little apprehensive of CTIX, their management and pipeline doesn't inspire a lot of confidence. Not familiar with Melinta. LGND should be a solid investment for the next 5 years IMO.

    Sentiment: Strong Buy

  • Reply to

    Long VRTS are you playing this....

    by frankfrazzano Sep 12, 2014 2:21 AM
    long_vrts2 long_vrts2 Sep 13, 2014 1:59 AM Flag

    I think delafloxacin is going to be a successful antibiotic. Yes, I'm a LGND shareholder, have done really well with this pharma, and IMO prospects continue to look v. solid.

    Sentiment: Strong Buy

  • Reply to

    CLDX at Morgan Stanley: notes:

    by long_vrts2 Sep 9, 2014 1:57 AM
    long_vrts2 long_vrts2 Sep 12, 2014 1:56 AM Flag

    Agee- a safe way to play the immunotherapy revolution. I think it will do well over the next 4-5 years.

    Sentiment: Strong Buy

CLDX
12.37-0.59(-4.55%)Oct 1 4:00 PMEDT

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