Celldex Therapeutics Presents Positive Preclinical Data from Inflammatory Bispecific Antibody Program CDX-622 at AAAAI 2025
Rhea-AI Summary
Celldex Therapeutics (NASDAQ:CLDX) has presented positive preclinical data for CDX-622, their novel bispecific antibody targeting inflammatory and fibrotic disorders, at the AAAAI 2025 Annual Meeting. The antibody works by targeting both thymic stromal lymphopoietin (TSLP) and stem cell factor (SCF) pathways.
The preclinical studies demonstrated that CDX-622 effectively neutralizes both SCF and TSLP, reducing tissue mast cells and inhibiting Type 2 inflammatory responses. Key findings show the antibody inhibits inflammatory activities with similar potency to existing treatments, preferentially targets soluble SCF, and demonstrates favorable pharmacokinetic properties.
A Phase 1 study in healthy volunteers, initiated in November, is currently ongoing with initial data expected later in 2025. The compound showed strong safety profile in toxicology studies, with no adverse effects observed even at the highest dose level of 75 mg/kg.
Positive
- Positive preclinical efficacy data showing dual pathway inhibition
- Clean safety profile with no adverse effects at highest dose (75 mg/kg)
- Phase 1 trial actively enrolling
- Similar potency to existing treatments
Negative
- Still in early development phase
- Clinical efficacy in humans yet to be demonstrated
Insights
Celldex's CDX-622 represents a scientifically compelling approach to inflammatory disease treatment. The bispecific antibody design targeting both TSLP and SCF pathways is particularly noteworthy as it addresses two critical mechanisms simultaneously - inhibiting Type 2 inflammation via TSLP neutralization while reducing tissue mast cells through SCF blockade.
The preclinical data demonstrates several important strengths: CDX-622 maintains potency comparable to individual antibodies against each target, shows preferential inhibition of soluble SCF (potentially minimizing off-target effects on other KIT-dependent processes), and produces significant mast cell depletion across multiple tissues. The clean toxicology profile with no observed adverse effects even at high doses (75 mg/kg) is encouraging for clinical development.
This dual-mechanism approach could potentially offer advantages over existing single-target therapies like tezepelumab (anti-TSLP) in conditions where both pathways contribute to pathology. The skin explant model results suggest particular relevance for dermatological conditions, though applications could extend to respiratory and other inflammatory disorders where mast cells and Type 2 inflammation play significant roles.
With the Phase 1 study already underway in healthy volunteers, we should watch for initial clinical data expected later this year to confirm target engagement and early safety signals in humans. This will provide important validation of whether the impressive preclinical profile translates to clinical applications.
This preclinical data announcement represents meaningful pipeline progress for Celldex, building on their expertise in mast cell biology while expanding their inflammation portfolio. The company is strategically leveraging their scientific strengths across programs, as CDX-622 builds upon knowledge gained from their barzolvolimab program.
The progression to clinical testing with an ongoing Phase 1 study demonstrates solid execution on development timelines. Expected data readout later this year will provide important early validation of the approach. However, investors should recognize this remains an early-stage program with significant development milestones still ahead.
The dual-targeting mechanism potentially differentiates CDX-622 in the competitive landscape of inflammatory disease therapeutics. By addressing both TSLP (a validated target with approved therapies) and mast cell depletion via SCF inhibition, Celldex is pursuing a scientifically rational combination approach that could potentially offer improved efficacy in conditions where both pathways contribute to disease.
This program diversifies Celldex's pipeline beyond their lead assets while maintaining focus on immunology applications. The preclinical toxicology results showing no adverse effects at doses up to
For Celldex investors, this program represents pipeline progression that could create additional value beyond their more advanced clinical assets, reinforcing the company's capabilities in developing novel immunology therapeutics.
- CDX-622 inhibits SCF and TSLP-dependent inflammatory signatures in human skin -
- Phase 1 study in healthy volunteers ongoing -
HAMPTON, N.J., March 03, 2025 (GLOBE NEWSWIRE) -- Celldex Therapeutics, Inc. (NASDAQ:CLDX) announced today positive preclinical data from CDX-622, a novel bispecific antibody that targets two non-redundant, complementary pathways implicated in inflammation and fibrosis—thymic stromal lymphopoietin (TSLP) and mast cell depletion via stem cell factor (SCF) starvation.
The data demonstrate that CDX-622 neutralizes both SCF and TSLP, reducing tissue mast cells and inhibiting Type 2 inflammatory responses, supporting its potential to improve clinical activity over single target inhibition in inflammatory diseases and fibrotic disorders. The data were presented by Diego Alvarado, PhD, Vice President of Research at Celldex Therapeutics, in a poster presentation (#708) as part of the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting 2025.
“We are pleased to present these data which demonstrate the exciting potential of CDX-622,” said Tibor Keler, Ph.D., Executive Vice President and Chief Scientific Officer of Celldex Therapeutics. “We believe dual neutralization of SCF and TSLP can potentially deliver profound clinical benefit for patients with inflammatory and fibrotic disorders where both mast cells and TSLP play a pathogenic role. Based on these preclinical findings, last November, we initiated a Phase 1 study in healthy volunteers that is actively enrolling and look forward to presenting initial data from this important clinical program later this year.”
In the poster presented, preclinical studies demonstrate that CDX-622:
- Inhibits TSLP and SCF-dependent activities in vitro with similar potency as its parental mAbs as well as tezepelumab and barzolvolimab
- Preferentially inhibits the soluble over the membrane form of SCF, which may lead to differential impact on KIT-dependent processes
- Inhibits both SCF and TSLP-dependent inflammatory signatures in a human skin explant model
- Exhibits mAb-like PK properties and leads to significant reduction in skin mast cell signatures
- Was well tolerated in a GLP toxicology study at all dose levels, with no observed adverse effect level, including at the highest dose level tested (75 mg/kg) and led to a profound mast cell depletion in several tissues
About CDX-622
CDX-622 is a bispecific antibody that targets two complementary, clinically validated pathways that drive chronic inflammation, potently neutralizing the alarmin thymic stromal lymphopoietin (TSLP) and depleting mast cells via stem cell factor (SCF) starvation. SCF activation of the KIT receptor is required for mast cell survival and plays a key role in their activation, maturation and tissue recruitment. Combined neutralization of SCF and TSLP with CDX-622 is expected to simultaneously reduce tissue mast cells and inhibit Type 2 inflammatory responses to potentially offer enhanced therapeutic benefit in inflammatory and fibrotic disorders. A Phase 1 randomized, double-blind, placebo-controlled, dose escalation study designed to assess the safety, pharmacokinetics, and pharmacodynamics of single ascending doses (Part 1) and multiple ascending doses (Part 2) of CDX-622 in up to 56 healthy participants is actively enrolling.
About Celldex Therapeutics, Inc.
Celldex is a clinical stage biotechnology company leading the science at the intersection of mast cell biology and the development of transformative therapeutics for patients. Our pipeline includes antibody-based therapeutics which have the ability to engage the human immune system and/or directly affect critical pathways to improve the lives of patients with severe inflammatory, allergic, autoimmune and other devastating diseases. Visit www.celldex.com.
Forward Looking Statement
This release contains "forward-looking statements" made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements are typically preceded by words such as "believes," "expects," "anticipates," "intends," "will," "may," "should," or similar expressions. These 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 or that those goals will be achieved, 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 successfully complete research and further development and commercialization of Company drug candidates, including barzolvolimab (also referred to as CDX-0159), in current or future indications; the uncertainties inherent in clinical testing and accruing patients for clinical trials; our limited experience in bringing programs through Phase 3 clinical trials; our ability to manage and successfully complete multiple clinical trials and the research and development efforts for our multiple products at varying stages of development; the availability, cost, delivery and quality of clinical materials produced by our own manufacturing facility or supplied by contract manufacturers, who may be our sole source of supply; the timing, cost and uncertainty of obtaining regulatory approvals; the failure of the market for the Company's programs to continue to develop; our ability 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; our ability to continue to obtain capital to meet our long-term liquidity needs on acceptable terms, or at all, including the additional capital which will be necessary to complete the clinical trials that we have initiated or plan to initiate; and other factors listed under "Risk Factors" in our annual report on Form 10-K and quarterly reports on Form 10-Q.
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.
Company Contact
Sarah Cavanaugh
Senior Vice President, Corporate Affairs & Administration
(508) 864-8337
scavanaugh@celldex.com
Patrick Till
Meru Advisors
(484) 788-8560
ptill@meruadvisors.com
FAQ
What are the key findings from CDX-622's preclinical trials presented at AAAAI 2025?
When did Celldex (CLDX) begin Phase 1 trials for CDX-622 and when are results expected?
What is the maximum dose tested for CLDX's CDX-622 in toxicology studies?
How does Celldex's CDX-622 bispecific antibody work?
