NEW YORK – Dutch biotech PamGene is moving forward with its diagnostics program and expects to launch its testing service for guiding lung cancer immunotherapy decisions on the European clinical market by next year.
A melanoma test service is also in PamGene's pipeline.
The company recently expanded its collaboration with Sanquin, the Netherlands' central blood bank, to support its diagnostic development activities.
"We are completing our validation on lung cancer, which means that we will have our first in vitro diagnostic product out in 2022," John Groten, PamGene's managing director, said. He noted that PamGene has in recent years shifted from being a pureplay discovery services company to adding diagnostics services, and has worked to align its activities with IVD guidelines and to obtain its ISO 13485 accreditation, which it gained in 2019. Getting its first test on the market will be a major milestone.
"It's quite something for a company that used to be a research services company," Groten said.
Established in 's Hertogenbosch, located in the south of Holland, in 2000, PamGene served the microarray market for years with its PamChip platform, seeking to capture a chunk of the then-fervent demand for gene expression profiling tools, competing with the Affymetrix GeneChip platform, GE Healthcare's Codelink Bioarrays, and a San Diego newcomer named Illumina.
Its platform consists of three-dimensional arrays composed of aluminum oxide, porous structures with interconnected capillaries, the diameters of which are on average 200 nm. Samples flowed through these capillaries, providing results the firm claimed were more sensitive and specific than rivals' offerings. The arrays are processed in batches of three on the company's PamStation and analyzed using its BioNavigator tool.
PamGene uses this platform today, though no longer for gene expression profiling. Instead, it recognized the ability of its system to profile the activity of proteins using multiplex peptide microarrays. Groten noted that the gene array market gradually was subsumed by whole-genome sequencing, which led PamGene to repurpose its platform into proteomics for profiling protein kinases, "very influential proteins in the body," which can be measured to gauge cell cycle effects, inflammatory response, and other cell signaling activities.
PamGene currently offers two protein kinase profiling chips: a phosphotyrosine kinase (PTK) array and a serine-threonine kinase (STK) array. Each chip contains four identical peptide arrays with either 144 STK or 196 PTK peptide sequences. These peptides include phosphorylation sites derived from literature or computational predictions, according to the firm.
"We are not trying to get at a subset, but to measure all of those kinases and activities," noted Groten. "You can really pinpoint any spot on a cell, measure the whole kinase family, and that makes for a very interesting technology."
Groten said the company has cultivated a client base of pharmaceutical companies and diagnostics firms that have relied on its protein kinase profiling services as part of drug or test development. This not only provided PamGene with income, but the idea to make tests itself.
"We were working for clients who were already working in tumor biology and on immune cell activation measuring kinases," said Groten. "That's probably why we started our diagnostics program in immune oncology."
IOpener and Sanquin
In 2016, PamGene partnered with Sanquin in the Netherlands to advance its plan of delivering to market a series of blood-based immunotherapy selection tests based on a 144-sequence peptide array. Other partners in the effort have been Erasmus University Medical Center in Rotterdam and Leiden University Medical Center. Together they have worked to develop and refine a blood-based kinase activity profiling assay that PamGene has dubbed IOpener, which can be used to predict response to immunotherapy in metastatic cancer and guide treatment selection.
Groten noted that immunotherapy for cancer patients is often hit and miss, with small subsets of patients benefiting. Clinicians, meantime, have relied on different approaches, from immunohistochemistry to genomics to try and distinguish who is benefiting from treatment.
"These types of biomarkers have not been shown to work on all patients due to tumor heterogeneity and that is maybe an understatement," Groten said. "Depending on tumor type and patient, you may benefit from using these markers," he added.
PamGene, therefore, worked to make its IOpener assay capable of providing a more comprehensive measurement of response via protein kinase activity. Sanquin assisted by providing peripheral blood mononuclear cells from the blood samples of cancer patients eligible for immunotherapy. Samples were sources from oncologists and academic centers in Holland.
Annelies Turskma, head of immunomonitoring services at Amsterdam-based Sanquin who has been involved in the project, noted that partnering with companies like PamGene is within its remit, as it engages in medical, diagnostic, and scientific research. Turskma said that partnering with PamGene fit with Sanquin's goal of providing better care for patients with the help of donors.
"As a blood bank we have a large cryostorage facility, where we not only store blood for transfusion but also store immune cells for clinical trials," noted Turskma. "Our collaboration with PamGene was an example of how we could extend and use our knowledge of immunology with our existing logistic facilities as a blood bank," she said.
These collaborations have allowed PamGene to hone IOpener's ability to guide immunotherapy treatment selection. The company has felt comfortable enough with its application in non-small cell lung cancer and melanoma to present data on these indications at conferences in recent years, demonstrating at the American Society of Clinical Oncology's annual meeting in 2018 , for instance, that the test could be used to measure clinical response to CTLA-4 and PD-1 blockade immunotherapy in a cohort of 140 patients.
A paper detailing the test in a new additional cohort of 160 lung cancer and melanoma patients appeared in the Journal for ImmunoTherapy to Cancer last year.
PamGene is now looking to roll out a service for lung cancer, to be followed by melanoma. Its diagnostics plans are linked to the shifting regulatory landscape for IVDs in Europe, but Groten assured that PamGene is working with the notified body Dekra, which has been accredited by European regulators to evaluate new test submissions under the new regulation, which comes into effect next May. Europe is PamGene's immediate market, and the company has been developing partnerships with oncologists in Switzerland and Germany to support its launch, but it hasn't taken its eye off the American market, where it will hope to partner with or establish a CLIA-compliant facility to offer its emerging menu of IOpener diagnostic services to the US.
One aspect of PamGene's diagnostic strategy is that it does not see IOpener as an end-all, be-all assay. Instead, it sees its offering as merely part of the mosaic of data that clinicians can access to make better treatment decisions for cancer patients.
"Biomarker development will not be a one by one case in the future," said Groten. "It will be a multimodal complex where you will need genomic endpoints, flow cytometry endpoints, and you will need proteomic endpoints too, like we offer with kinase screening," he said. "If you combine all of this knowledge, clinicians will have a beautiful idea before patients start therapy if they will have a clinical benefit or not."
PamGene is currently building out the patient-facing aspects of its service by working on dashboards and querying clinicians to make the reports it delivers back as easy to grasp as possible. "We are trying to make it simple," said Groten, "both for the patient and the physician."