NEW YORK – European biotech PDC*line Pharma and its partners are gearing up to study a bespoke neoantigen cancer vaccine in colorectal cancer after nabbing an €8.1 million ($8.8 million) funding award from the Belgian government earlier this month.
PDC*line Pharma, a 2014 French National Blood Service spinout, is spearheading the unique approach applied in the vaccine, dubbed PDC*neo+, which uses allogeneic dendritic cell lines loaded with peptides targeting tumor-specific neoantigens. The company, which has a presence in both La Tronche, France, and Liege, Belgium, has already been validating a non-personalized version of the vaccine that targets preselected neoantigens as a treatment for lung cancer and melanoma. Now, with the new funding, the firm and its collaborators are planning to take the tumor-specific version into Phase I trials as an adjuvant treatment for colorectal cancer patients.
Belgium's Walloon region and Wallonia health cluster BioWin awarded the $8.8 million grant to a collaborative group comprising members of industry and academia. The recipients include PDC*line Pharma, which received €4.7 million ($5.1 million) of the award; Belgium-based firms OncoDNA and SalamanderU; and two Belgian universities, IREC/MIRO (Institut de Recherche Expérimentale et Clinique/Molecular Imaging, Radiotherapy and Oncology) and ULB-BCTL (Université Libre de Bruxelles Breast Cancer Translational Research Laboratory). The total project budget is €12.5 million ($13.6 million).
OncoDNA will use its sequencing technology within the collaboration to identify patient-specific neoantigens, while SalamanderU will develop a compact isolator technology that ultimately allows the drug candidate, PDC*neo+, to be manufactured and administered through a decentralized, point-of-care model. The two Belgian universities will support translational research in clinical trials.
Differentiating with dendritic cells
PDC*Line Pharma CEO Eric Halioua believes his firm's therapy could have a leg up over other personalized neoantigen-based cancer vaccines thanks to PDC*neo+'s starting material: a subset of dendritic cells called plasmacytoid dendritic cells (PDCs) shown to powerfully prime and boost a patient's cytotoxic T cells.
The firm is eager to highlight the potential advantages of its PDC lines, especially as bigger drugmakers march along with further-advanced personalized neoantigen candidates.
"It's not a new story, this personalized [approach]," Halioua said, pointing to Moderna and Merck's messenger RNA candidate as one example. That personalized vaccine, combined with Merck's checkpoint inhibitor Keytruda (pembrolizumab), is now in Phase III trials as an adjuvant treatment for high-risk melanoma patients. Other companies, such as Swiss biotech Nouscom, are also pursuing personalized cancer vaccine programs.
But in Halioua's view, PDC*line Pharma's approach has the potential to get around limitations of other neoantigen cancer vaccines. "The majority of the other companies [developing personalized cancer vaccines] are infusing mRNA, DNA, or viruses," Halioua said. "We are infusing very potent dendritic cells. We have a direct approach."
According to Halioua, the mRNA and DNA approaches require a functional immune system, which is lacking in older patients with dysfunctional dendritic cells. As such, a vaccine that infuses patients with functional dendritic cells gives PDC*line Pharma a leg up, in his view.
Loading PDC lines for individual patients
Plasmacytoid dendritic cell lines are at the core of the company's drug development activities and what the "PDC" in its name stands for. The firm believes the PDC lines could eventually be loaded with peptides for any type of cancer.
The concept begins with the cell lines. The company loads synthetic peptides representative of tumor antigens — preselected or tumor-specific — that "stick onto the cells of the PDC lines," Halioua said. To identify these antigens, the firm first removes the tumor in surgery. "Then, we can get a big piece of the tumor, and based on the piece of this tumor, we identify the specific mutations that produce immune activity," he said. "These are the personalized neoantigens."
At this stage, for the adjuvant colorectal cancer trial, PDC*line Pharma plans to pursue around 12 patient-specific neoantigens, though Halioua said the firm might ultimately increase this number.
In an ongoing Phase I/II trial PDC*line Pharma has treated 67 lung cancer patients with the shared antigen-loaded asset, PDC*lung01, and the safety profile has been encouraging, Halioua said. Since the neoantigens are preselected in the PDC*lung01 product, it involves less logistical complexity than the bespoke vaccine.
Still, for Halioua, the high potential for responses with personalized therapies makes it worth entering the bespoke space. "There is definitely something there" with the bespoke approach, he said.
Toward a point-of-care model
The logistics are not as much of a challenge for PDC*line Pharma today as they could be down the line. Right now, the firm is planning to manufacture the bespoke vaccines in its own in-house good manufacturing practice (GMP)-approved facility in Belgium, not far from where the Phase I trial is launching. That trial will focus initially on enrolling between 15 and 20 colorectal cancer patients in up to five European countries. Most likely, he said, the trial will be based mostly in Belgium.
While a trial of this size, Halioua feels, will be "completely manageable," scaling the treatment to larger patient populations in later trials could require longer transit times for the personalized therapies, which presents a heightened challenge given the product needs to be shipped in subzero temperatures. Right now, it takes PDC*line Pharma nine weeks to go from biopsy to infusion, though Halioua said the firm could speed up timelines with decentralized systems in the future.
This is where it may benefit from its partnership with SalamanderU, which is helping PDC*line Pharma develop a closed-unit system that will enable the bespoke treatment to be fully manufactured at the site where the patient is treated. The firm is starting its clinical trials with the in-house centralized facility, but Halioua said SalamanderU is going to be simultaneously working on this new point-of-care technology, so it can be used in pivotal trials down the line.
The first study is expected to launch in 2025, then roughly 18 months later, Halioua expects the bespoke cancer vaccine to enter Phase II/III trials. At that point, he said the decentralized manufacturing processes will also be in place.
Tracking biomarkers of response
In the colorectal cancer trial, Halioua said he and his team at PDC*line Pharma are looking forward to tapping into the translational research expertise at partner institutions, IREC/MIRO and ULB-BCTL. Together with researchers in these academic centers, he said, the firm is hoping to use liquid biopsy-based approaches to track patients' recurrence and, ultimately, identify biomarkers that predict vaccine response and identify patients eligible for the therapy.
In a statement issued about the funding award, Christos Sotiriou, the head of ULB-BCTL, and Francesco Sclafani, a gastrointestinal oncologist and researcher at Institut Jules Bordet, Hopital Universitaire de Bruxelles (HUB) and Bordet Cancer Research Laboratory, said they will use "various omics technologies, such as single-cell RNA sequencing and spatial transcriptomics, [to] delve into the tumor microenvironment of colorectal cancers" to develop predictive biomarkers for vaccine response and help recruit patients for the clinical trial.
The collaboration is expected to last three years, and the priority will be to gauge the safety and feasibility of PDC*neo+ in colorectal cancer patients, an indication Halioua said his firm is focusing on given the unmet need. Ultimately, Halioua said his firm might consider expanding the personalized vaccine approach to melanoma and lung cancer, the indications in which PDC*line Pharma is developing its shared neoantigen therapies already. This could hinge on the level of activity the firm sees with the personalized approach in colorectal cancer.
"For us, it's important to have both the modalities," he said of the shared and bespoke vaccines in PDC*line Pharma's pipeline. "But it will be the clinical results that define what will be the priority in the future. Everything is possible."