Aiming to rebound from blunders years ago, Celldex touts a Phase Ib win with sights set on Xolair
Following multiple high-profile missteps several years ago, the folks over at Celldex Therapeutics began charting a path to redemption that would take on Roche and Novartis’ blockbuster Xolair franchise. That path got a boost Friday with a data readout the company says positions it well against the pharma giants.
Celldex reported results from a Phase Ib study for their monoclonal antibody CDX-0159 to treat two conditions that cause severe and debilitating hives. The Hampton, NJ-based biotech said that among 19 patients who received a full dose of the antibody, 18 achieved a complete response and the 19th saw a partial response.
That stands in stark contrast to some of the response rates Celldex says patients see on Xolair, which fall around the 40% to 50% range. Those with such conditions also need to take multiple doses of Xolair, while Celldex’s data come from patients taking only one dose of CDX-0159, CEO Anthony Marucci emphasized.
“We’ve been antibody developers for a long time, both in oncology and non-oncology assets,” Marucci told Endpoints News. “Looking at this target and where we believed it worked, naturally the science took us to inflammation. That’s not to say we’ve abandoned oncology … but this target and the way we designed the molecule, to reduce infusion reactions and improve its half life, the data in our minds [are] spectacular even in the early stages.”
In the wake of the announcement, Celldex $CLDX shares were up 45% ahead of the bell Monday morning.
The diseases in question are two forms of chronic inducible urticaria. The first, called symptomatic dermographism, makes up more than half of cases. Patients can develop severe hives in response to little stimulation on the skin, such as putting on socks. The second condition, known as “cold urticaria,” makes up 16% of cases and causes hives outbreaks when skin is exposed below certain temperatures.
Within the Phase Ib study, nine of the 19 patients had symptomatic dermographism while the other 10 suffered from cold urticaria. Eight of the nine SD patients achieved complete response, including three who had previously been treated with Xolair, and all 10 with ColdU met their complete response.
On top of the response rates, Celldex said the treatments proved highly durable. The SD patients maintained their responses at a median of 57 days, and those with ColdU maintained the disease state for a median of 77 days.
CDX-0159 works by targeting mast cells by binding the receptor tyrosine kinase KIT. Mast cells mediate inflammatory responses in the body and KIT signaling controls mast cell differentiation. As such, Celldex’s theory involves tamping down on KIT in order to deplete the mast cells in the skin.
Celldex is continuing to study the drug in other forms of urticarias, including hives triggered by sweating in warm temperatures or from exercise, as well as urticarias that result in spontaneous hive outbreaks. Both of these datasets in the ongoing Phase Ib trial are expected in the first half of 2022.
Should everything turn out hunky dory, the program would mark a sharp turnaround for a biotech that culled multiple late-stage assets from its pipeline after Phase III failures. In 2016, a cancer vaccine program flopped a glioblastoma study, and 2018 brought a Phase IIb disaster in breast cancer — a miss that resulted in Celldex laying off about 40% of its workforce.
But now Celldex is engaging in a full court press to get CDX-0159 to patients, and Marucci hopes the company can expand the program into other diseases where mast cells are implicated. Celldex isn’t saying much yet, but researchers are looking at other indications in the respiratory, allergic, ophthalmic and GI areas.
Taking a bite out of the Xolair pie is proving to be an opportunity Celldex simply can’t pass up, Marucci said. Xolair netted about $3.3 billion in sales between Roche and Novartis in 2020 and continued to see growth in 2021’s first quarter, and analysts estimate that about $1.5 billion of that total comes from the spontaneous form of the disease.