The string of recent clinical successes for the antibody zolbetuximab has not only been welcome good news at AstraZeneca and Astellas, it has also buoyed biotechs working on their own Claudin-targeting therapies.
Chief among them is Alentis Therapeutics, which rode the wave of increased interest in the modality to attract blue chip investors in its Claudin-1 antibodies for organ fibrosis and tumors. Armed with $105 million from an oversubscribed series C funding round co-led by Novo Holdings and RA Capital—along with previous supporter Jeito Capital—the biotech is focused on pushing these therapies through the clinic.
Drawing “deep pocket, blue chip investors” behind the biotech was possible due to the “tailwinds” from zolbetuximab’s progress, Alentis CEO Roberto Iacone, M.D., Ph.D., told Fierce Biotech in an interview. “That demonstrated that now the Claudin space can be targeted, in particular in gastric cancer patients, with a remarkable effect in terms of overall survival,” Iacone said.
Not only does bringing Novo Holdings and RA on board offer “validation” for Alentis’ Claudin-1 approach, but the amount raised is “remarkable in this market situation,” the CEO said. The funds will go toward building out what Iacone described as “Alentis 3.0.”
Part of this new phase of Alentis means further expanding the team. When Iacone joined the company in 2020, Alentis comprised just four employees. Now, the workforce spans over 25 staff spread across its headquarters in Basel, Switzerland, as well as an R&D subsidiary in France and clinical operations in the U.S. “Maybe we’ll make more appointments at the C-level,” Iacone suggested, adding that the company will eventually start to think about commercialization.
Claudin-1 is a protein that maintains a barrier between epithelial cells, which line the surfaces of the body including the liver. Despite the protein having a much broader expression profile than the Claudin 18.2 targeted by AstraZeneca’s zolbetuximab, “nobody cracked the way to target Claudin-1,” Iacone said.
The company’s priority for the year will be expanding human trials for its two lead Claudin-1 molecules. One of these assets, ALE.F02, has already undergone a phase 1 study in healthy volunteers, with some of today’s funding going toward a phase 2 trial in kidney, lung and liver fibrosis patients. The other asset is ALE.C04, which will enter a phase 1 study as potentially the first treatment to target Claudin 1-positive tumors.
As those trials get underway and begin to read out, the company is preparing for a “very intense newsflow” over the next 18 months, Iacone said.
Further back in development, Alentis is also applying its Claudin-1 tech to antibody-drug conjugates (ADCs) and bispecific antibodies. The thinking behind pushing into these well-travelled areas is to maintain the company’s pioneer status, the CEO explained.
“We are today the leader of Claudin-1 biology, and there is a huge support from the board and from myself to remain the leader in the future,” he said. “That means part of the proceeds will be used for ADCs for Claudin-1 in oncology and for bispecifics for both organ fibrosis and cancer.”
With “promising” preclinical results on both fronts, there is a “huge sense of urgency” at the company to “bring this new modality to the patient as quickly as possible.” While Iacone wouldn’t commit to when these ADC and bispecific programs will enter the clinic, he branded it a “top priority.”
These big ambitions will require big money, but Iacone revealed that the biotech still has a “substantial part” of the $67 million series B raised in 2021 available. Combined with the latest funds, it means the company has plenty of cash to fuel its plans over the next two years.
Beyond that point, “we cannot exclude that in the future there will be more support from other investors as well,” he added.