Celldex Therapeutics Reports Positive Results from Rindopepimut Phase 2 Brain Cancer Study at SNO 2010

Celldex Therapeutics Reports Positive Results from Rindopepimut Phase 2 Brain Cancer Study at SNO 2010
-- Trial Met Primary Efficacy Endpoint; Randomized Phase 3 Trial to Initiate in 2011 --
-- Management to Host Conference Call on Monday, November 22, 2010, at 8:30 am --
NEEDHAM, Mass., Nov 20, 2010 (BUSINESS WIRE) --

Celldex Therapeutics, Inc. (NASDAQ: CLDX), today announced the presentation of complete data for the primary endpoint of ACT III, a multi-center, single arm, Phase 2 clinical trial of rindopepimut (CDX-110) in patients with newly diagnosed glioblastoma multiforme (GBM). The data showed 66 percent of patients were progression-free at 8.5 months from diagnosis or 5.5 months from start of vaccination, a statistically significant increase over a predetermined progression-free rate (PFR) estimate. These data are consistent with previous studies (ACTIVATE and ACT II) with rindopepimut in GBM conducted at M.D. Anderson and Duke University. The data were presented at the Annual Meeting of The Society for Neuro-Oncology (SNO) in Montreal, Quebec, Canada. Rindopepimut is an investigational immunotherapeutic vaccine that targets the tumor-specific molecule, epidermal growth factor receptor variant III (EGFRvIII).

"These data suggest that rindopepimut is extending survival well beyond what we have seen historically in this patient population," said Rose Lai, M.D., Assistant Professor of Neurology in the Division of Neuro-Oncology, Department of Neurology, Columbia University Medical Center, and lead investigator on the ACT III study. "The consistency of data from three separate studies is impressive and clearly supports the plan to conduct a controlled pivotal study in GBM."

"This exciting data from ACT III is an important milestone in this fatal disease setting and we look forward to initiating an international, randomized, placebo-controlled Phase 3 clinical trial, which we anticipate will begin in the second half of 2011," said Anthony Marucci, President and Chief Executive Officer of Celldex Therapeutics.

The ACT III data will be discussed in a conference call and webcast presentation on Monday November 22, 2010, from 8:30 to 9:30 am Eastern Time. Lead investigator, Dr. Rose Lai, will participate in the call.

ACT III Results

The multi-center Phase 2 trial enrolled 65 patients with newly-diagnosed and optimally resected EGFRvIII-expressing GBM. Patients started vaccination with rindopepimut at approximately 3 months post-diagnosis. The results for the predefined primary endpoint (66% Progression Free Rate or "PFR" at approximately 8.5 months post-diagnosis) show a statistically significant improvement (p=0.0168, 95% CI) over a predetermined estimate of 53%, which is beyond the range of expected progression-free survival for GBM patients receiving standard of care (SOC), consisting of radiation + temozolomide (TMZ). Published results for SOC, and from matched historical controls, are 45% and 29%, respectively, for PFR at 8.5 months post-diagnosis.

  Median PFS from
diagnosis (months)
  Median OS from
diagnosis (months)
  OS at
24 Months

ACT III (n=65)   12.3x  24.3*   50%* 
ACT II (n=22)   15.3   24.4   50% 
ACTIVATE (n=18)   14.2   24.6   50% 
Matched historical control (n=17)#  6.4   15.2   6% 
Standard of care radiation/TMZ+ (n=287)   6.9   14.6   27% 

x Change in median PFS not statistically significant from ACTIVATE and ACT II.
* Overall survival data for ACT III are estimated and not yet final.
# Sampson, et al. J Clin Oncol. 2010 Nov 1;28(31):4722-9.
Historical controls were treated at M.D. Anderson and matched for eligibility (EGFRvIII-positive, KPS greater-than or equal to 80%, complete resection, radiation/TMZ and without progression through ~ 3 months post-diagnosis).
+ Stupp, et al. N Engl J Med 2005;352:987-96.

Importantly, rindopepimut showed a similar benefit in patients whether or not they expressed an active DNA repair gene (MGMT) that has been shown to limit the benefit from TMZ treatment. In ACT III, the number of patients who were expected to be resistant to the TMZ chemotherapy appeared to do better with vaccination than the numbers observed in the historical data. Patients who have an active DNA repair gene, MGMT, generally have a worse outcome, presumably because they do not gain much benefit from TMZ as reported in the literature. Patients with a methylated MGMT promoter in their tumor do not express MGMT and have a more favorable outcome to TMZ treatment. Patients with methylated tumors (n=25) that were treated with the rindopepimut regimen experienced a median PFS of 17.2 months, which compares favorably with the published data from the SOC of radiation plus TMZ (R+TMZ) of 10.3 months. Those with unmethylated tumors (n=40) treated with the rindopepimut regimen experienced a PFS of 11.2 months, which compared favorably to the PFS with SOC of 5.3 months in this patient population. Thus, rindopepimut would appear to benefit both methylated and unmethylated MGMT patients.

Study Design

The ACT III Phase 2 trial studied rindopepimut in combination with maintenance TMZ in 65 patients with newly-diagnosed EGFRvIII-expressing GBM who had undergone surgical (gross total) resection followed by conformal radiation therapy with concurrent oral TMZ (75 mg/m2 per day) without tumor progression. Rindopepimut mixed with granulocyte-macrophage colony stimulating factor (GM-CSF) (~150 mcg) was administered intradermally. Patients received rindopepimut bi-weekly for three doses prior to starting maintenance TMZ and monthly thereafter on day 21 of each TMZ cycle until disease progression. The primary endpoint was PFR at 5.5 months from first vaccination/study day 0 (~ 8.5 months from diagnosis).

The ACT III Phase 2 trial began as a Phase 2b/3 randomized open-label, two-arm trial comparing rindopepimut combined with TMZ to TMZ alone in patients with newly diagnosed GBM. It was amended to a single arm design when 14 of 16 control arm patients declined further participation after notification of randomization assignment. When the patients randomized to the control arm withdrew from the study, the trial could no longer achieve the planned statistical goals due to the absence of a control arm.

Vaccination with rindopepimut was well tolerated in combination with maintenance TMZ, with local injection site reactions being the most common treatment-related adverse events. Serious treatment-related adverse events occurred in three patients, including:

one case of toxic epidermal necrolysis (possible dapsone hypersensitivity syndrome) which resolved within 12 days of admission;
one grade 2 hypersensitivity reaction (pruritus, erythema, flushing and mild shortness of breath), occurring within 10 minutes of dosing and fully resolved within one hour of antihistamine and corticosteroid;
one urticarial rash (or hives)

Eighty-two percent of the evaluable vaccinated patients developed a specific anti-EGFRvIII antibody response that was maintained at a significant level in most patients.

About Rindopepimut

Rindopepimut is an investigational immunotherapeutic vaccine that targets the tumor-specific molecule epidermal growth factor receptor variant III (EGFRvIII). EGFRvIII is a mutated form of the epidermal growth factor receptor (EGFR) that is only expressed in cancer cells and not in normal tissue and is a transforming oncogene that can directly contribute to cancer cell growth. It is reported to be present in 25-30 percent of GBM tumors.

Conference Call and Presentation Webcast

The conference call and presentation will be webcast live over the Internet and can be accessed by logging on to the "Presentations" page of the "Investors" section of the Celldex website at www.celldextherapeutics.com. The call can also be accessed by dialing 866-730-5770 (within the United States) or 857-350-1594 (outside the United States). The passcode for participants is 76849635.

A replay of the call will be available approximately two hours after the live call concludes through December 5, 2010. To access the replay, dial 888-286-8010 (within the United States) or 617-801-6888 (outside the United States). The passcode is 70523463. The webcast will also be archived on the Company's website.

About Celldex Therapeutics, Inc.

Celldex Therapeutics is the first antibody-based combination immunotherapy company. Celldex has a pipeline of drug candidates in development for the treatment of cancer and other difficult-to-treat diseases based on its antibody focused Precision Targeted Immunotherapy (PTI) Platform. The PTI Platform is a complementary portfolio of monoclonal antibodies, antibody-targeted vaccines and immunomodulators used in optimal combinations to create novel disease-specific drug candidates. For more information, please visit http://www.celldextherapeutics.com.

Safe Harbor Statement Under the Private Securities Litigation Reform Act of 1995: This release contains "forward-looking statements" made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including those related to the Company's strategic focus and the future development and commercialization (by Celldex and others) of rindopepimut (CDX-110), CDX-1307, CDX-011, CDX-1135 (formerly TP10), CDX-1401, CDX-1127, Belinostat, Rotarix(R) and other products. Forward-looking statements reflect management's current knowledge, assumptions, judgment and expectations regarding future performance or events. Although management believes that the expectations reflected in such statements are reasonable, they give no assurance that such expectations will prove to be correct and you should be aware that actual results could differ materially from those contained in the forward-looking statements. Forward-looking statements are subject to a number of risks and uncertainties,including, but not limited to, our ability to obtain additional capital on acceptable terms, or at all; our ability to adapt APC Targeting TechnologyTM to develop new, safe and effective vaccines against oncology and infectious disease indications; our ability to successfullycomplete product research and further development of our programs, including rindopepimut, which, effective November 1, 2010, is at our cost; the uncertainties inherent in clinical testing; our ability to manage research and development efforts for multiple products at varying stages of development; our strategy and business plans concerning the continued development and commercialization of rindopepimut; our ability to successfully complete the transition of rindopepimut from Pfizer to Celldex; the uncertainties of any future payments with respect to Belinostat, as the development and commercialization of Belinostat is completely outside of Celldex's control; the uncertainties of any future royalty payments with respect to Rotarix(R), as the commercialization of Rotarix is completely outside of Celldex's control; the timing, cost and uncertainty of obtaining regulatory approvals; the failure of the market for the Company's programs to continue to develop; ourability to protect the Company's intellectual property; the loss of any executive officers or key personnel or consultants; competition; changes in the regulatory landscape or the imposition of regulations that affect the Company's products; and other factors listed under "Risk Factors" in our annual report on Form 10-K.

All forward-looking statements are expressly qualified in their entirety by this cautionary notice. You are cautioned not to place undue reliance on any forward-looking statements, which speak only as of the date of this release. We have no obligation, and expressly disclaim any obligation, to update, revise or correct any of the forward-looking statements, whether as a result of new information, future events or otherwise.

SOURCE: Celldex Therapeutics, Inc.

Celldex Therapeutics, Inc.Anthony S. Marucci, 781-433-0771President and CEOorAvery W. Catlin, 781-433-0771Chief Financial [email protected] Media:BMC Communications GroupMatthew Driscoll, 212-477-9007 [email protected]