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Celldex Therapeutics, Inc. Message Board

long_vrts2 31 posts  |  Last Activity: Oct 20, 2016 9:58 PM Member since: Jul 12, 1999
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  • long_vrts2 long_vrts2 Oct 20, 2016 9:58 PM Flag

    "Hopefully Celldex will confirm this high expression rate in another PCNSL population and quickly begin a study."

    If they confirm I think it's a great opportunity for CLDX that came totally out of blue: ultra orphan indication, severe unmet need and a politically influential patient community (HIV/AIDS PCNSL pts) that could expedite the regulatory approval process.

    "Given the current stock price it will likely be the company that aquires Celldex that winds up performing this study. "

    CLDX valuation is in the dumps, despite evidence of efficacy and manageable AE profile for Glemba, Varli, CDX-301 and possibly 1401(?). 301+1401 data at SITC in a couple of weeks may be the catalyst to get things moving. I'd like to see more insider buying, they have a half-dozen highly compensated senior executives at the top, and only a couple have bought shares recently.

    Sentiment: Strong Buy

  • Reply to

    Varli & Atezo in bladder

    by btchinvstr Oct 19, 2016 9:21 PM
    long_vrts2 long_vrts2 Oct 20, 2016 9:39 PM Flag

    """Davis added though that Varli is also going to be pursued with Atezo in bladder, a new indication."

    As recently as 5 months ago, McDermott at Dana-Farber was saying that the "sole focus" was going to be RCC. Agree that something must've happened in the interim to also test Varli+Atezo in BC. For RCC there is evidence that Varli as mono therapy induced some durable responses, including completely clearing up lung mets in one adv RCC pt,; but I don't recall seeing anything re prior results regarding BC:

    "...A Double Whammy
    According to McDermott, using atezolizumab and varlilumab together combines two different approaches to targeting the immune system. The PD-L1 antibody has been shown to be effective in a variety of different tumor types by ‘releasing the breaks on the immune system’, whereas the antibody to CD27 acts as an agonist on T-cells, B-cells, and natural killer cells. “This is a novel approach that will hopefully amplify the immune response to cancer,” he says. “The CD27 antibody has been tested on its own, found to have some clinical activity, and is reasonably tolerable. The hope is that it can be safely combined with PD-L1 blockade for greater clinical effect.”
    Benefits in Kidney Cancer?
    According to Dr. McDermott, the varlilumab/atezolizumab combination may be particularly effective in renal cell carcinoma, which is the sole focus of the Phase II portion of the trial. The ligand for CD27, called CD70, can shut off activated T-cells, and is highly expressed on many kidney cancers. “Overexpression of CD70 may be a way that kidney cancers escape an immune response from the patient,” he says. “This combined approach may make particularly good sense for patients with kidney cancer, because it may break down a defense mechanism that allows these tumors to grow and to spread....” "

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Oct 18, 2016 2:09 AM Flag

    Couldn't agree more. This is one tough business, and there are no guarantees. At this point this is a great opportunity for CLDX that fell into their laps, but will require top notch effort to convert it into a marketed drug in a timely fashion.

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Oct 18, 2016 1:38 AM Flag

    Yes. It referenced a recent report from Japan which showed- for the first time- that 50%+ of CNS lymphomas and about 20% of diffuse large cell B lymphomas have a high expression of TIM-1. The overexpression of TIM-1 could be detected in the blood of patients which would make for a relatively straightforward diagnostic assay. There is no effective treatment for CNS lymphoma so there is a critical unmet need for this cancer. DLC B lymphomas can be treated effectively with Rituximab + chemo +/- radiation therapy. (Not sure if this is a case of history repeating itself, but the early to mid-stage clinical development of Rituximab was led by Tom Davis...if CDX-014 will have only a fraction of the success of Rituximab we'd be very happy campers...)

    Sentiment: Strong Buy

  • 1. CLDX already has CDX-014 anti-TIM-1 in PI/II clinical trial for kidney cancer.

    2. CNS lymphoma has no treatment options at this time. CNS lymphoma pts, oncologists and the FDA are very keen in finding a viable treatment option for this indication.

    3. CDX-014, as targeted ADC, could go into trials in CNS lymphoma definitely as a second line intervention, possibly first line. The ADC technology in CDEX-014 has been proven to work effectively in blood cancers with high response rates.

    4. CLDX already was looking to enroll CNS lymphoma pts in the Varli mono therapy PI/II so they've gone through the approval process once.

    5. The CNS lymphoma indication is a significant opportunity for CDLX in terms of orphan disease, targeted drug and unmet need. They have the right drug, funding and staff to push this- time to roll.

    Sentiment: Strong Buy

  • Mol Cancer Ther. 2016 Sep 26. [Epub ahead of print]

    Development of a Novel Antibody-drug Conjugate for the Potential Treatment of Ovarian, Lung and Renal Cell Carcinoma Expressing TIM-1.

    Thomas LJ1, et al

    1Celldex Therapeutics, Inc.
    3 Roswell Park Cancer Institute.

    T cell immunoglobulin and mucin domain 1 (TIM-1) is a type I transmembrane protein that was originally described as kidney injury molecule 1 (KIM-1) due to its elevated expression in kidney and urine after renal injury. TIM-1 expression is also upregulated in several human cancers, most notably in renal and ovarian carcinomas, but has very restricted expression in healthy tissues thus representing a promising target for antibody-mediated therapy. To this end we have developed a fully human monoclonal IgG1 antibody specific for the extracellular domain of TIM-1. This antibody was shown to bind purified recombinant chimeric TIM-1-Fc protein and TIM-1 expressed on a variety of transformed cell lines, including Caki-1 (human renal clear cell carcinoma), IGROV-1 (human ovarian adenocarcinoma) and A549 (human lung carcinoma). Internalization studies using confocal microscopy revealed the antibody was rapidly internalized by cells in vitro, and internalization was confirmed by quantitative imaging flow cytometry. An antibody-drug conjugate (ADC) was produced with the anti-TIM-1 antibody covalently linked to the potent cytotoxin, monomethyl auristatin E (MMAE), and designated CDX-014. The ADC was shown to exhibit in vitro cytostatic or cytotoxic activity against a variety of TIM-1 expressing cell lines, but not on TIM-1 negative cell lines. Using the Caki-1, IGROV-1, and A549 xenograft mouse models, CDX-014 showed significant anti-tumor activity in a clinically relevant dose range. Safety evaluation in non-human primates has demonstrated a good profile and led to the initiation of clinical studies of CDX-014 in renal cell carcinoma and potentially other TIM-1 expressing tumors.

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Oct 14, 2016 1:48 AM Flag

    "Why would BMY not want to release activity data?"

    Big bio's don't want to release results because they would rather keep the competition in the dark, especially in the early stages of drug development.

    "Is it a way for BMY to exert leverage over Celldex while CLDX's share price languishes?"

    Possibly, but it is the responsibility of CLDX management to maximize shareholder value. Right now the Street is a little skeptical- and rightly so- and it is up to CLDX to produce results and change investor sentiment.

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Oct 12, 2016 11:11 PM Flag

    Link for Nivo article:

    Sentiment: Strong Buy

  • I post these Nivo results because they illustrate how incremental cancer treatment advances are in recurrent, difficult to treat cancers and give some perspective on the Glemba results in Stage III/IV melanoma PII trial.

    1. 1st line in HNSCC is platinum chemo; patients who progress within 6 months have a median survival of about 5 months.

    2. Trial compared Nivo vs standard care (methotrexate/ docetaxel/cetuximab) in recurrent HNSCC pts.

    3. Nivo ORR =13.3% vs SOC = 5.8%

    Nivo wil replace current 2nd line SOC in HNSCC, and has a good chance to go 1st line after further testing.

    So Glemba at 11% ORR, used as 4th line (!) Tx in advanced melanoma, has relatively good efficacy. Combining Glemba with an immune response enhancer and moving it up to 2nd line (Glemba + checkpoint inhibitor and/or Glemba + Varli) will produce an ORR of 15% or greater and qualify Glemba for accelerated approval.

    Sentiment: Strong Buy

  • Reply to

    Glemba versus xeloda - prospects ?

    by nickdidomenico Oct 11, 2016 2:59 PM
    long_vrts2 long_vrts2 Oct 12, 2016 10:25 PM Flag

    Substantially. Eribulin is being tested in a slew of Tx combos in TNBC. Also, novel approaches like PARP inhibitors, CPI's and CDK inhibitors are being tested in dozens of TNBC trials. In the course of a couple of years, TNBC has gone from desolation valley to a teeming metropolis of drug candidates: good news for TNBC pts, challenging for trial sponsors.

    Yes, uveal melanoma trial will most likely complete by Jan '17. A relatively small market, but may offer the fastest way to first approval for Glemba due to a total lack of effective treatment options currently for met/rec uveal melanoma.

    Sentiment: Strong Buy

  • Reply to

    Glemba versus xeloda - prospects ?

    by nickdidomenico Oct 11, 2016 2:59 PM
    long_vrts2 long_vrts2 Oct 12, 2016 3:41 PM Flag

    Figure 2 where they list OS and PFS by receptor status: panel B, all the way at the bottom.
    The 2.3 mos PFS is in line with prior results with xeloda in TNBC pts.

    Sentiment: Strong Buy

  • Reply to

    Glemba versus xeloda - prospects ?

    by nickdidomenico Oct 11, 2016 2:59 PM
    long_vrts2 long_vrts2 Oct 11, 2016 7:15 PM Flag

    Most recent Xeloda (capecitabine) trial data that I'm aware of shows a PFS of 2.3 mos in TNBC in a population similar to the Glemba trial (also consistent with older trial results). Glemba needs to show a ~1.5 mo benefit for the difference to be stat significant- based on prior evidence, I would venture that high probability Glemba will hit it.

    Breast Cancer (Auckl). 2016 Jun 28;10:77-84.
    Subgroup Analyses from a Phase 3, Open-Label, Randomized Study of Eribulin Mesylate Versus Capecitabine in Pretreated Patients with Advanced or Metastatic Breast Cancer.
    Twelves C1,et al

    Our secondary analyses compared survival with eribulin versus capecitabine in various patient subgroups from a phase 3, open-label, randomized study. Eligible women aged ≥18 years with advanced/metastatic breast cancer and ≤3 prior chemotherapies (≤2 for advanced/metastatic disease), including an anthracycline and taxane, were randomized 1:1 to intravenous eribulin mesylate 1.4 mg/m(2) on days 1 and 8 or twice-daily oral capecitabine 1250 mg/m(2) on days 1-14 (21-day cycles).
    In the intent-to-treat population (eribulin 554 and capecitabine 548), overall survival appeared longer with eribulin than capecitabine in various subgroups, including patients with human epidermal growth factor receptor 2-negative (15.9 versus 13.5 months, respectively), estrogen receptor-negative (14.4 versus 10.5 months, respectively), and triple-negative (14.4 versus 9.4 months, respectively) disease. Progression-free survival was similar between the treatment arms.
    Patients with advanced/metastatic breast cancer and human epidermal growth factor receptor 2-, estrogen receptor-, or triple-negative disease may gain particular benefit from eribulin as first-, second-, and third-line chemotherapies.
    This study reports the subgroup analyses of eribulin versus capecitabine from a phase 3, open-label, randomized study (;

    Sentiment: Strong Buy

  • Reply to

    ESMO information just published

    by tina_astoria Oct 9, 2016 9:34 AM
    long_vrts2 long_vrts2 Oct 10, 2016 3:14 AM Flag

    Based on these updated PII results in metastatic melanoma, Glemba at 11% ORR is better than chemo (8%) and comparable to Yervoy and IL-2 (11-16%). So not a home run, more like a double. As monotherapy, I see Glemba as a 3/4th line of intervention in met melanoma. In combination with checkpoint inhibitors it could move up to 1/2 line (depending on BRAF status and tumor load of patient).

    On a side note, extrapolating the PFS of 4.4 mos in this trial to the TNBC trial is encouraging- in the BC trial Glemba needs to show a PFS of greater than ~3.75 mos to be successful vs active control (assuming that the control is consistent with historical results, not necessarily a given as we have seen...).

    It appears that Dr. Vahdat's nose for effective drugs is indeed good...

    Sentiment: Strong Buy

  • Reply to

    New Phase 1 Varli Study

    by fludyspnea Oct 5, 2016 11:29 PM
    long_vrts2 long_vrts2 Oct 6, 2016 10:20 PM Flag

    I would like to see them address a couple of issuesat SNO:
    - in ndGBM, do the survival curves start to separate after 2 years as would be expected from vIII becoming a significant risk factor at this time point. Is there a difference in % survival at 3, 4 and 5 yrs?
    - in rGBM: I checked recently with Mark Gilbert's group at NCI and they continue to actively recruit pts (pts also need to be on Avastin). So the question is whether there is some synergy between Rindo and Avastin in this pt population?

    Agree that the path forward- other than the current expanded access through NCI- will probably involve some type of research collaboration with an academic institution like the IMA950 study.

    Sentiment: Strong Buy

  • Reply to

    New Phase 1 Varli Study

    by fludyspnea Oct 5, 2016 11:29 PM
    long_vrts2 long_vrts2 Oct 6, 2016 10:09 PM Flag

    "I doubt we'll see 1401 without 301 going forward"

    Agree. In the PII in resected melanoma trial, 1401 in combo with 301 produced specific ESO-1 T-cell response in 100% of pts, whereas 1401 alone was around 72%. In general, need to get over a threshold of ~80% response to see improved clinical outcomes. It will be interesting to see the update at SITC on the combo.

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Sep 30, 2016 2:56 PM Flag

    If Glemba were already approved in another indication like TN breast cancer, then I would say yes. But for a first approval they may need to do another trial. The FDA is considering going to a "cancer target" approval model, i.e. Glemba would be approved for all GPNMB+ cancers, whatever the origin of that cancer may be (breast, skin, lung...), but that protocol hasn't been implemented yet.

    Sentiment: Strong Buy

  • The data published in the abstract are from earlier in the year (May'16), updated results will be provided at the time of presentation in October.

    1. Trial design:
    - Glemba, an ADC targeted against GPNMB which is expressed in approx 80% of melanomas.
    - Patient population: refractory to checkpoint inhibitor/BRAF inhibitor; 62 pts enrolled, 57 evaluated at time of abstract submission.
    - Primary endpoint: objective response rate (ORR).

    2. Results:
    - ORR = 14%, with 1 complete response and 7 partial responses.
    - 1 single time point PR (not included in ORR).
    - Stable disease = 46% (26 patients, duration 6-51 weeks with 11 ongoing as of 5/16).
    - adverse effects: consistent with an ADC, manageable.

    My take on these results:
    - Glemba ORR inferior to Keytruda/Opdivo immunotherapies, and targeted BRAF/MEK inhibitors.
    - comparable to Yervoy and IL- 2 which produce an ORR of 11-16% in similar melanoma patients.
    - Glemba has an advantage re toxicity because Yervoy produces life threatening effects in ~15% of pts plus long-term liver and GI problems, IL-2 very toxic during Tx to most organs and requires ICU setting in Tx.
    - superior to chemo which produces an ORR of ~8% in these pts (used mostly for symptomatic relief these days).

    - regulatory aspect: good probability of FDA approval based on efficacy, AE profile, mechanism of action and unmet need for advanced melanoma pts who progressed through checkpoint and BRAF/MEK inhibitors.

    - clinical indication: 2nd/3rd line intervention in BRAF mutant/GPNMB+ advanced melanoma pts with heavy tumor burden who progressed through BRAF/MEK inhibitors.

    Conclusion: Glemba has demonstrated clear evidence of efficacy in checkpoint/BRAF inhibitor refractory advanced melanoma patients. Relatively modest clinical market as 2nd/3rd line intervention in GPNMB+, advanced melanoma patients, CP/BRAF inh refractory. CLDX is testing Glemba+Varli in melanoma pts and this combo would need to produce a signify higher ORR for GV+V to become 1st line

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Sep 26, 2016 1:06 AM Flag

    There is significant potential for CLDX in cancers which don't have effective treatment options.
    For example, Glemba is being tested in uveal melanoma. An ORR of 10% would probably be sufficient to get AA because there are no good treatment options currently for this cancer.

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Sep 26, 2016 1:01 AM Flag

    "I'd really like to know more on their intended Varli strategy. "

    I think if Varli proves itself as an immune activator in combo with chemo, checkpoint inhibitors, vaccines, etc, in the current PI/II trials, then they will need to partner because the cost of testing the various permutations will be prohibitive for an R&D stage biotech like CLDX.

    On the other hand, big pharma is on the hunt for smaller bios with promising drug candidates. Wouldn't be surprised if we saw a Medarex 2.0, this time with CLDX, especially since BMY's trial with Opdivo as first line in NSCLC didn't pan out.

    Sentiment: Strong Buy

  • long_vrts2 long_vrts2 Sep 26, 2016 12:45 AM Flag

    Can't rule out the possibility of an oral presentation-yes, in that case we would have to wait until 10/5.

    Sentiment: Strong Buy

3.36+0.02(+0.60%)Oct 24 4:00 PMEDT