PDC*vac: highly potent, versatile, off-the-shelf therapeutic cancer vaccines

PDC*line Pharma is developing cancer vaccines derived from a proprietary allogeneic human plasmacytoid dendritic cell line.

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Aug 21, 2019
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Following a feasibility clinical trial in melanoma, the company is actively expanding and diversifying its portfolio of cancer vaccines with a phase 1/2 trial in non-small-cell lung cancer.

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Based in Liege (Belgium) and Grenoble (France), clinical-stage biotech PDC*line Pharma is developing a novel class of off-the-shelf cancer immuno-therapies derived from PDC*line, a proprietary plasmacytoid dendritic cell line that can be engineered to display high levels of any cancer-antigen-derived, human leukocyte antigen (HLA)-A2-restricted peptide of choice. The resulting PDC*vac potently primes and boosts fully functional antitumor CD8* T cells to generate strong cytotoxic activity against tumor cells.

Compared with conventional, mostly autologous dendritic cell (DC)-derived vaccines, PDC*vac is off the shelf, easily scalable, up to ten times more economical, easily genetically modifiable and exhibits up to 200-fold higher potency. The antitumor activity of PDC*vac can be further increased by using it in combination with anti-programmed cell death 1 (PD-1) immune checkpoint inhibitors to achieve a synergistic effect.

“PDC*vac is derived from the only therapeutic plasmacytoid dendritic cell line available off the shelf and is ready to be used globally,” said Eric Halioua, CEO and president of PDC*line Pharma. “The first preclinical and clinical results are very encouraging, and the recent licensing deal we signed with leading Korean pharmaceutical company LG Chem further under¬scores the potential of our technology.”

In March 2019, PDC*line Pharma granted an exclusive license in South Korea and exclusive options in other Asian countries to LG Chem Life Sciences Company for the development and commercialization of the PDC*lung cancer vaccine. The total value of the deal is $123 million (€108 million) plus tiered royalties on net sales in Asia.

Giving cancer vaccines a PDC boost 

DC-derived cancer vaccines have been in development for close to three decades now, but despite some clinical success, there is a need for further improvement and optimization of the approach. Existing DC-based cancer vaccines are mostly autologous, which severely limits the scalability of the approach, and their efficacy is compromised by the challenge of obtaining a sufficient quantity of fully functional DCs and by external factors such as tumor-induced immune suppression.

PDC*line addresses these issues through its increased ability to prime and expand antigen-specific CD8* T cells compared with conventional (myeloid) DCs. PDC*line achieves this effect through an original mechanism of action involving (1) the activation of allogeneic CD4* T cells and (2) the expression of specific cytokines, which together help to fully activate and expand antitumor CD8* T cells.

In addition, the lack of expression of key costimu-latory molecules prevents the effective proliferation of allogeneic CD4* T cells, explaining the absence of allogeneic rejection of PDC*line both in vitro and in vivo.

Together, all these features lead to a boosted expansion of antigen-specific CD8* T cells, resulting in the potent antitumor activity of PDC*vac.

Fig. 1 | Development of next-generation plasmacytoid dendritic cell-based cancer vaccines. These allogeneic vaccines are derived from a potent plasmacytoid dendritic cell (PDC) line and can be engineered to present any cancer antigen-derived, human leukocyte antigen (HLA)-A2-restricted peptide of choice or neoantigen. ATMP, advanced therapy medicinal product.A PDC*vac for every need

PDC*line is a professional and universal antigen-presenting cell that is very easy to expand in large quantities. Following in vitro loading with the desired tumor antigen target, the resulting PDC*vac can be irradiated and stored frozen for years. The off-the-shelf product is thawed and directly injected to treat any patient with a cancer type expressing the selected antigens and HLA-A2. Because of the ease of transformation of the PDC*line cells, PDC*vac can be engineered to present different HLAs and/or any type of conventional antigen, neoantigen, shared antigen, peptide, mRNA or even viral vector (Fig. 1).

PDC*vac is currently available in the form of several cancer vaccine drugs.

  • PDC*mel: PDC*Pharma’s fi rst candidate for melanoma. PDC*mel completed a fi rst-in-human phase 1b feasibility clinical trial in 2017 assessing the safety of the product, the absence of rejection and its biological activity.
  • PDC*lung: the company’s leading candidate for non-small-cell lung cancer. PDC*lung targets widely expressed shared antigens. A phase 1b/2 trial evaluating its safety and biological activity, alone and in combination with anti-PD-1 immune checkpoint inhibitors, is being initiated.
  • PDC*neo: PDC*Pharma’s next candidate. PDC*neo is in preclinical development as a platform for expressing any kind of neoantigen.

According to Halioua, “with a workforce of 20 people, an experienced management team and a robust financial situation—looking to close a new round of financing of €11 million in 2019 following a previous raise of €17 million—PDC*line Pharma is in a strong position to advance its existing clinical programs and further develop its preclinical pipeline.”

Contact:

Eric Halioua, President and CEO
PDC*line Pharma
Liege, Belgium
Tel: +32 474 05 78 66
Email: e.halioua@pdc-line-pharma.com
Website: www.pdc-line-pharma.com

Go to the profile of PDC*line Pharma

PDC*line Pharma

Founded in 2014 as a spin-off of the French Blood Bank (EFS), PDC*line Pharma is a Belgian-French biotech company that develops an innovative class of active immunotherapies for cancers, based on a GMP-grade allogeneic therapeutic cell line of plasmacytoid dendritic cells (PDC*line). PDC*line is much more potent than conventional Dendritic Cell-based vaccines to prime and boost antitumor antigen-specific cytotoxic T-cells, including T cells specific for neoantigens, and is synergistic with checkpoint inhibitors. The technology can be applied to any type of cancer. Following a first-in-human phase I feasibility study in melanoma, PDC*line Pharma focuses on the development of PDC*lung, a candidate for non-small-cell lung cancer (NSCLC) and neoantigens (PDC*Neo). A phase Ib/IIa trial, aimed at evaluating safety and activity with and without anti-PD1, is being initiated in 2019 with PDC*lung. The company has a staff of 20 people, with an experienced management team. The company has so far raised €17M ($19.3M) including €7.6M ($8.6M) in equity and loans from Belgian investors (MeusInvest, Innodem3, InvestSud and SFPI) and several business angels, and €9.3M ($10.5M) of non-dilutive money (including grants from the Walloon region, Belgium and French entities). www.pdc-line-pharma.com

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