Last stock offering underwriters paid $24, Bristol's up-front payment was small relative to upfront payments made by big pharma and big biotechs in the past year, but the real benefit to Celldex is in the renegotiation of its license with Medarex and the potential to cozy up more closely with Bristol's promising oncology business.
CDX-1135 was the fourth maybe fifth most talked about product in Celldex's pipeline last year. It was being tested to treat a disease that affects just 300-500 patients in the U.S., and for this indication has very limited fundamental upside. Yet, it's similar to Alexion Pharmaceuticals's (ALXN) Soliris, which is what made it so attractive.
Soliris is a complement modulator, and works by binding to a component called C5, which has been linked to several genetic and blood diseases. Alexion Pharmaceuticals has grown to a $35 billion company with just this one single FDA approved drug, which earned $1.55 billion in sales last year. Currently, Soliris is approved to treat a life-threatening genetic disorder atypical hemolytic uremic syndrome and the blood disease paroxysmal nocturnal hemoglobinuria, but is being studied to treat five additional conditions. If successful at treating all diseases, some analysts predict peak sales reaching $5 billion worldwide due to Alexion's ability to price the drug sky-high in treating these ultra-rare conditions.
Now, back to Celldex: CDX-1135 works in the same way, binding to the exact same component. The only difference is that it also binds to the C3 component, which is why many long-term investors, including myself, believe that CDX-1135 is a secret value buried deep within the company's pipeline. Because after all, given the success of Soliris, conventional wisdom implies that CDX-1135 could be tested to treat various rare diseases, could be priced high, and would support an Alexion-like premium multiple once CDX-1135 is proven successful in clinical trials.
Three Phase 2 trials of rindopepimut have been completed in newly diagnosed EGFRvIII-positive glioblastoma patients with consistent results—ACTIVATE, ACT II, ACT III —and multiple patients continue to be followed for survival. Across all three studies, rindopepimut has been generally well tolerated with generation of robust, specific and durable immune responses.
DCVax-L DMC Phase III due 2-7-14 per the biopharmcatalyst site.
Soon will have $20 range...
CDX-011 is a vaccine used to treat patients with advanced/metastatic breast cancer who express the protein GPNMB. The FDA has granted Fast Track designation to CDX-011 for the treatment of advanced, refractory/resistant GPNMB-expressing breast cancer.
What’s impressive about CDX-011 is that it was proven effective on patients who had no longer responded to a median of five-six prior therapies; meaning most difficult to treat. Yet, of the 120 patients treated with CDX-011, 33% had a response rate compared to no response in patients using chemotherapy. Moreover, CDX-011 slowed the growth of tumors by 100% compared to its control arm.
Due to the stage of the disease, such progress is considered incredible. The technology used is equally impressive, as the success from the trial proves that targeting GPNMB is highly effective in treating such violent diseases. Thus, investors are excited that this protein is also expressed in multiple tumors such as melanoma and glioma.
Moving forward, the question is not whether the drug will be approved, but rather when it will be approved. The FDA is already showing favoritism towards the drug, and has a history of rapidly approving drugs for life-threatening cancers. As a result, there’s a lot to like when it comes to Celldex.
Meaning of PR from MD Anderson is that - IN OPEN LABLE UNBLINDED STUDY - MD ANDRSON will disclose results only at the end of the study. But if company wants to disclose they can at their discretion and results are documented in patients file.
Reason No. 1
Celldex's most advanced clinical candidate, rindopepimut, is indicated as a potential treatment for glioblastoma multiforme, a particularly aggressive and difficult-to-treat form of brain cancer. What's key to understand is that numerous experimental treatments for glioblastoma have failed in clinical trials over the years. Roche's Avastin was the first pharmaceutical approved by the Food and Drug Administration to treat any form of glioblastoma in over a decade, and even it can only claim marginal clinical benefits for this terrible disease.
Although rindopepimut did show encouraging signs of improving survival rates and progression-free survival compared to historical benchmarks in a mid-stage study, we have seen similar results from other drugs that went on to fail in late-stage studies. Put simply, shorts are betting that rindopepimut will ultimately fail in its quest to become a breakthrough treatment for this devastating form of cancer.
Reason No. 2
The company's second most advanced clinical candidate, Glembatumumab vedotin, is based on Seattle Genetics' (NASDAQ: SGEN ) promising antibody-drug conjugate, or ADC, technology that consists of a human monoclonal antibody linked to a potent cellular toxin. Glembatumumab is being tested as a potential treatment for breast cancer and melanoma.
Although Roche, Seattle Genetics, and others have invested heavily in this technology for nearly two decades, we have only seen a handful of approvals so far. Moreover, the first ADC to be approved, Mylotarg, was withdrawn from the market due to serious adverse events.
The problem is that off-site toxicity issues haven't been completely resolved and researchers are still working on ways to improve tissue targeting for ADCs. So while Celldex is pursuing a hot-ticket item in oncology research with Glembatumumab, the technology is far from perfect. The short thesis would thus appear to be that Glembatumumab won't succeed where the majority of experimental ADCs have failed. Time will tell.
For all patients treated at the maximum dose level, tumor shrinkage was seen in 62% (16/26) and median PFS was 9.1 weeks. A subset of 10 patients had "triple negative disease," a more aggressive breast cancer subtype that carries a high risk of relapse and reduced survival as well as limited therapeutic options due to lack of over-expression of HER2/neu, estrogen and progesterone receptors. In these patients, 78% (7/9) had some tumor shrinkage, 12-week PFS rate was 70% (7/10), and median PFS was 17.9 weeks. Tumor samples from a subset of patients across all dose groups were analyzed for gpNMB expression. The tumor samples from most patients showed evidence of stromal and/or tumor cell expression of gpNMB.
We are heading for better results on DCVax Direct and its better than ICPT which open $440 after close at $70 in March 2014
Solaris $1.5Billion Sales in 2013 - Mkt Cap for ALXN $32Billion = CLDX atleast expected to be $20Billion Mkt Cap Management guidance is that final results on ReACT will be available in 2H, 2014. ... comparable to Alexion's (ALXN) $1.5 billion blockbuster drug Solaris. .... Read more on Alternative Investing
Celldex Therapeutics, Inc. (NASDAQ: CLDX) announced that data from its Phase 1 study of varlilumab, a fully human monoclonal antibody targeting CD27, will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2014 in Chicago. The abstracts accepted for poster presentation are listed below. In addition, the data will be discussed during a Poster Highlight Session entitled "Modulating the Anti-tumor Immune Response" by Dr. Cassian Yee of The University of Texas MD Anderson Cancer Center on Monday, June 2, 2014 from 5:15 to 5:30 p.m. CDT.
-- (# 3024) Data from the hematologic malignancy dose-escalation arm will be presented by Stephen M. Ansell, MD, PhD, Professor of Medicine, Mayo Clinic, in a poster entitled "Phase 1 Evaluation of an Agonist Anti-CD27 Human Antibody (CDX-1127) in Patients with Advanced Hematologic Malignancies" on Monday, June 2 from 1:15 to 4:15 p.m. CDT.
-- (# 3027) Data from the solid tumor expansion cohorts in metastatic melanoma and renal cell carcinoma will be presented by Jeffrey R. Infante, MD, Director, Drug Development Program, Sarah Cannon Research Institute, in a poster entitled "Immunologic Activity of an Activating Anti-CD27 Antibody (CDX-1127) in Patients with Solid Tumors" on Monday, June 2 from 1:15 to 4:15 p.m. CDT.
Data contained in the published abstracts was current as of the submission deadline of February 4, 2014. Data to be presented in the poster sessions will include comprehensive data from the trials as of May.
Fast Track, Breakthrough Therapy, Accelerated Approval and Priority Review
Expediting Availability of New Drugs for Patients with Serious Conditions
Speeding the development and availability of drugs that treat serious diseases are in everyone's interest, especially when the drugs are the first available treatment or have advantages over existing treatments. The Food and Drug Administration (FDA) has developed four distinct and successful approaches to making such drugs available as rapidly as possible: Priority Review, Accelerated Approval, Fast Track Designation, and breakthrough therapy designation. Because each of these approaches implies speed, there can be confusion about the specific meaning of each and the distinctions among them.
The following summary describes each element, how they differ, and how they complement each other.
Positive data from this study will not only strengthen the validity of such combination studies but also contribute to the validation of varlilumab as a clinically potent enhancer of anti-tumor immune response. A combination of these two drugs to treat tumors is backed by scientific rationale that varlilumab will activate immune response against the tumor while nivolumab will simultaneously preventing the shutting down of the immune response by the tumor cells.
Together, a combination of these two drugs is expected to exert a synergistic effect in cancer patients. Celldex retains the right to use varlilumab in other combinations with their internal assets as well as with external assets that are not pure-play PD-1, such as PDL-1.
Harry Boxer predicted CLDX is ready to move to $22 ... FDA grants accelerated approval to cancer drug Beleodaq (belinostat); CLDX
What your agenda Adam Fraudestein with NWBO? While SRPT is a known fraudster with only 2 patients clinical results which they claimed to be in phase 2 without legit FDA clinical findings still enjoys $1.4Billion Mkt cap and many competitors already are in phase3 and results would be out before 2014 ends. CEO has as many as 50 class action lawsuits for security fraud , but still AF favours out rightly. SRPT also has no possibility to get into Europe because of Prosensa already has patents registered. AF giving false hope for investors about SRPT also he did the same many other companies in the past which URL is being removed completely by The Street so that nobody can scoop such records in past.
NWBO has no records of any security fraud or class action law suits as of today. Legit DCVax-L phase3 Trials and DCVax Directs has encouraging outcomes so far. Many company failed with their Phase3 trials but that's what the trials are.
The Wall Street Journal news department was not involved in the creation of this content.
BETHESDA, Md., May 27, 2014 /PRNewswire/ -- Northwest Biotherapeutics (NASDAQ: NWBO) (NW Bio), a biotechnology company developing DCVax(R) personalized immune therapies for solid tumor cancers, today provided a summary of initial data to date in its ongoing Phase I/II clinical trial of DCVax-Direct for all types of inoperable solid tumors. The Company reported that over 50% of the patients who have completed at least half of the 6 treatments in the trial are already showing preliminary signs of cancer cell death, tumor shrinkage and/or stabilization (i.e., stopping the progression) of their advanced cancer.
Further information will be available at the Company's exhibit booth at the upcoming ASCO conference. The Company also plans to conduct a conference call to discuss the initial preliminary data.
The Company's Phase I/II trial of DCVax-Direct is treating patients with advanced, inoperable cancers involving multiple metastases (including metastatic colon cancer, pancreatic cancer, sarcoma, melanoma and others). Although these patients have such advanced metastatic disease, only one tumor is being injected in each patient because the current trial is a first-in-man study. In future studies, the Company plans to inject DCVax-Direct into multiple tumors in each patient.
The Phase I portion of the trial includes 36 patients. To date, 19 patients have completed at least half of the 6 treatments with DCVax-Direct, which are spread over 8 months. None have yet completed all 6 treatments.
Among the 19 patients who have received at least half of the 6 treatments, 11 patients have already shown some preliminary positive responses to the treatments, including the following:
-- 8 of the 11 patients have shown signs of tumor necrosis (cell death) and
immune cell infiltration, as well as stabilized disease that has stopped
progressing, following the injections of DCVax-Direct.
-- For all of these 8 patients, biopsies indicated substantial to
extensive tumor necrosis, as well as substantial accumulations of
immune cells infiltrating into and around the patients' tumors,
following the DCVax-Direct injections.
-- For 6 of these 8 patients, imaging scans also indicated either
tumor shrinkage or no disease progression following the
-- For the other 2 of these 8 patients, imaging scans seemed to
indicate some enlargement of their tumors. However, the needle
biopsies revealed that the tumor was filled with necrosis (dead
tumor cells) and infiltrating immune cells, as noted above. In
addition, these patients have reported significant improvement in
their physical condition and clinical symptoms.
-- The other 3 of the 11 patients have shown stabilized disease, with no
growth in their advanced and aggressive tumors following the DCVax-Direct
injections, but have not yet shown definitive necrosis or infiltration of
immune cells into their tumors.
Among the remaining 8 of the 19 patients who have received at least half of the 6 injections in the trial:
-- 1 of these 8 patients requires more data before a preliminary assessment
can be made;
-- 7 of these patients have shown progression of their disease.
The Phase I/II DCVax-Direct clinical trial includes a total of 60 patients: 36 in the Phase I portion and 24 in the Phase II portion. The DCVax-Direct trial began treating its first patients in Q3 of last year.
As is often the case with first-in-man studies, the Company's DCVax-Direct trial was required, as a regulatory matter, to proceed slowly until safety considerations could be assessed. The Company was required to treat just one patient with at least 2 of the 6 treatments in the overall regimen, then wait 2-3 weeks before treating the next single patient in the same way, and so on, treating just one patient at a time.
By March, the Company was permitted to begin enrolling without such pacing limitations. In the period between March and May, most of the remaining slots in the 36-patient Phase I trial have been enrolled or completed screening. (Enrollment occurs after both the screening and the product manufacturing have been completed for that patient.)
The DCVax-Direct treatment regimen in the clinical trial includes a total of 6 injections: initially at Day 0, Day 7 and Day 14, followed by injections at Week 8, Week 16 and Week 32.