NEW YORK – Artificial intelligence biopharmaceutical company BPGbio is validating a breast cancer diagnostic test with help from the US Department of Defense and other collaborators that it hopes to commercialize in the next couple of years.
The Framingham, Massachusetts-based company has been working with the DoD for nearly nine years, and the new breast cancer panel comes after previous work to develop a prostate cancer screening test using BPGbio's technology, the company's President and CEO Niven Narain said. BPGbio uses artificial intelligence to analyze tissue and blood samples and differentiate between healthy and cancerous samples. It then utilizes the novel biomarkers it discovers to create diagnostics and screening tests, such as for prostate and breast cancer.
The basis of the firm's technology is its Interrogative Biology platform, which combines artificial intelligence with BPGbio's extensive biobank of patient samples to discover potential biomarkers. That biobank has been built up over 12 years through partnerships with hospitals and medical schools and includes blood samples, tissues, and demographic data, Narain said.
Biomarkers are identified de novo from data generated through in-house analysis combined with the firm's analytics tools, said Michael Kiebish, the firm's VP of platform and translational sciences. Depending on how the markers are connected in the data knowledge graphs developed by the company, they are then further explored for potential diagnostic utility. The markers are also investigated to determine whether they are impacted by demographics, comorbidities, or concomitant medications, he noted.
The markers being evaluated are diverse, encapsulating genetic mutations, gene expression, protein measurements, structural lipids, signaling lipids, metabolites, and post-translational modifications of proteins, such as phosphorylation or acetylation, Kiebish said.
Primarily a biopharmaceutical and drug discovery company, the firm has also stepped into the diagnostic testing development arena as well.
Its original partnership with the DoD began with prostate cancer diagnostics, and the Prostate Health Diagnostic Panel that was developed out of that partnership is nearing commercialization, Narain said. To develop the mass spectrometry-based blood test, the company analyzed tissue and samples collected every three months for more than 20 years from enlisted soldiers and discovered a novel biomarker, filamin-A, that could differentiate between benign prostate hyperplasia and aggressive prostate cancer in patients with elevated levels of prostate specific antigen.
Filamin-A directly interacts with the androgen receptor, which is tied to prostate cancer proliferation and progression, and is involved in calcium signaling, which activates pathways for prostate cancer progression, Kiebish said.
Filamin-A's relationship to prostate cancer has been the focus of various research. A 2021 paper published by Italian researchers in Cell Death and Disease found that the androgen receptor/filamin-a complex drives migration and invasiveness of cancer-associated fibroblasts, while a team from the Veterans Affairs Northern California Health Care System found that filamin-A can affect the growth and survival of prostate cancer. Multiple research groups from China have also investigated the role of filamin-A in prostate cancer.
Narain noted that the assortment of data it has received from the DoD allows the company to "really understand at the clinical level, at the demographic level, at the biological level what's going on in patients at certain time points — it's not a static analysis."
"In some cases, we have the ability to look at the biological profiles of patients before, during, and after they have cancer," he added, and that "allows us a unique lens into the components and the trigger points towards cancer."
In addition to providing samples, the agency encouraged the company to focus on African American men due to the higher incidence of prostate cancer, particularly aggressive cancers, in the population, Kiebish added.
Late-stage clinical trials for that test have been completed, including a study published in 2021 in Scientific Reports, and the firm is currently assessing the best path toward commercialization in both the US and abroad, particularly in Latin America and India. The company plans to offer the assay as a laboratory-developed test, and the commercial team is determining pricing and reimbursement right now, he said.
Although the DoD and its partners helped with the development of the test, Narain noted that the company is solely in charge of commercialization.
Once the clinical trials for the prostate cancer test were completed, Narain said the DoD — through its Clinical Breast Care Project — requested that the company use its technology to see if it could replicate its success in breast cancer. The panel it has designed — with help from collaborators like the DoD's Uniformed Services University of the Health Sciences, the Windber Research Institute, and the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF) — is intended to identify women who are diagnosed with ER-positive breast cancer but don't respond to hormone therapy.
According to Joseph Caravalho, HJF's president and CEO, the collaborators wondered whether by drawing on patients' clinical histories, there was a way to use computing power to make better predictions and determine more efficient courses of action.
In its research, the company discovered 34 genes that may provide more insight into the cancer's metastatic potential than pathology, he noted. Knowledge of those genes can encourage clinicians to treat patients more aggressively, since they know hormone therapy will likely not be effective. The panel has one shared gene with Agendia's Blueprint test and Prosigna's PAM50 test, but the remaining genes are unique, Kiebish said.
Unlike the prostate cancer test, which is nearing commercialization, the next-generation sequencing-based breast cancer panel is in the prospective validation stage. The company has been given access to additional tissue samples from the DoD that it will use to validate the 34-gene panel to ensure those genes "are as predictive as we've seen in the retrospective cohort," he said. The DoD samples are all from enlisted soldiers, but Narain said that the validation studies for both tests have also been done on non-military civilians. Kiebish added that the commercial panel will most likely include all 34 genes, as well as other genes to normalize the signature.
BPGbio is also developing diagnostic tests for pancreatic cancer and Parkinson's disease, Narain noted. The pancreatic cancer test will also be blood-based, and the Parkinson's test will use blood and urine samples, he added. Both tests were developed using similar approaches to the prostate and breast cancer tests, Kiebish said. The Parkinson's test has been validated in a CLIA-certified laboratory and is ready to be deployed as a laboratory-developed test, while the pancreatic cancer test is in analytical development with the company validating its biomarkers, he said.