HAMPTON, N.J., April 01, 2019 (GLOBE NEWSWIRE) -- Celldex Therapeutics, Inc. (CLDX) presented promising data from the Company’s growing bispecific and TAM (Tyro3, Axl, MerTK) receptor programs during poster sessions today at the American Association for Cancer Research (AACR) Annual Meeting 2019.
“Our research and discovery efforts have yielded multiple promising candidates that address important needs in cancer immunotherapy and complement our pipeline,” said Tibor Keler, Ph.D., Executive Vice President and Chief Scientific Officer of Celldex Therapeutics. “CDX-527 joins two powerful pathways in the immune system, PD-1 blockade and CD27 costimulation. The data we presented at AACR demonstrate that this bispecific antibody candidate has greater activity than the combination of the two individual antibodies and support advancing the program into IND-enabling studies. In addition, we also presented data on our lead candidate antibodies targeting the TAM receptors, which act as checkpoints on myeloid cells. We have uncovered a unique mechanism for antibody-mediated activation of dendritic cells and macrophages and demonstrated that a surrogate MerTK mAb promotes anti-tumor immunity alone and enhances the activity of PD-1 blockade. We look forward to continuing to progress both CDX-527 and our TAM program over the course of the year,” concluded Keler.
Poster #2392: CDX-527: A novel bispecific immune-modulating antibody targeting CD27 and PD-L1 (Vitale, et. al)
The use of bispecific antibodies provides opportunities to engage two independent pathways involved in controlling immune responses to tumors. Preclinical and clinical studies support the safety and benefit of combining PD-1 blockade with a CD27 agonist.
The bispecific CDX-527 combines a novel and potent PD-L1 antibody for blocking the PD-1 checkpoint pathway with the binding domains of a CD27 agonist antibody for CD27-mediated costimulation of T cells.
CDX-527 demonstrated potent inhibition of PD-1 signaling and T cell activation using in vitro models with reporter cell lines and human primary cell cultures.
Anti-tumor activity was tested with a surrogate bispecific molecule that binds mouse PD-L1 and human CD27 in human CD27-expressing transgenic mice. The bispecific demonstrated potent anti-tumor activity in a BCL1 lymphoma model and was significantly more effective than the combination of the CD27 and PD-L1 monoclonal antibodies (mAbs).
A pilot study in non-human primates suggests that CDX-527 demonstrates good pharmacokinetic properties and no toxicities were observed.
Based on the promising data observed to date and the PK/PD profiles, Celldex has initiated manufacturing activities and investigational new drug (IND) enabling studies to support clinical studies of CDX-527.
Poster #1555: Monoclonal antibodies targeting the TAM family of receptor tyrosine kinases (Alvarado, et al)
TAM receptors (Tyro3, Axl, MerTK) are receptor tyrosine kinases (RTKs) expressed in innate immune cells. These receptors have been gaining importance in the immunotherapy field due to their role as checkpoint molecules on macrophages, dendritic cells, and other immune cells, where they can negatively regulate anti-tumor immunity.
Celldex presented data showing that lead candidate mAbs targeting MerTK, Axl or Tyro-3 activate myeloid cells, including monocytes, macrophages and dendritic cells, enhancing pro-inflammatory cytokine release, increasing expression of costimulatory molecules and enhancing T cell activation in mixed lymphocyte reaction (MLR) assays.
Celldex demonstrated that the potent activity of the TAM-specific antibodies are dependent on a unique coupling of the TAM receptors with Fc receptors.
Celldex’s most advanced program targets MerTK, where the Company has demonstrated that antibody targeting of MerTK in mice elicits an inflammatory cytokine response similar to that observed in the human cells and in MerTK deficient mice and has anti-tumor activity when dosed alone or in combination with a PD-1 inhibitor in a colon cancer model.
These data support development of anti-TAM mAbs as therapies to activate innate immune responses with a potential for systemic dosing. The Company intends to advance potential candidates into development activities this year.
About Celldex Therapeutics, Inc.
Celldex is developing targeted therapeutics to address devastating diseases for which available treatments are inadequate. Our pipeline includes immunotherapies and other targeted biologics derived from a broad set of complementary technologies which have the ability to engage the human immune system and/or directly inhibit tumors to treat specific types of cancer or other diseases. Visit www.celldex.com.
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Celldex Therapeutics, Inc.