NEW YORK – Diagnostic and life science "company creation" specialist IV BioHoldings is betting on RNA as a general disease biomarker, recently unveiling its portfolio of companies developing RNA-based liquid biopsy tests for breast cancer, NAFLD, and lung cancer.
IVBH incubated the companies — LiquidLung, HepGene, and Mammogen — within this "bio innovation studio" to innovate tests aimed at improving diagnoses of high-impact diseases with significant unmet needs. Collectively, the companies are currently developing eight tests and expect to publish data from clinical studies within the next year and a half.
"All eight of our liquid biopsy tests will be commercialized as PCR-based laboratory-developed tests, with CLIA certification expected across all existing tests in 2023," Martin Keiser, founder and CEO of IVBH, said via email.
Keiser founded IVBH in 2018, following a career in investment management focusing on diagnostics and life sciences.
IVBH's decision to prioritize disorders with urgent unmet clinical needs that affect large populations of people led the company to incubate LiquidLung, HepGene, and Mammogen, which are developing liquid biopsies for lung cancer, non-alcoholic fatty liver disease, or NAFLD, and breast cancer, respectively. Each company plans to expand its test pipeline in the future.
"Solving these big problems is not only an opportunity to positively impact millions of people," Keiser said, "but the revenues generated in these big markets can be used to fund future innovation for diseases that may not affect as many people, but affect the people … as devastatingly as the diseases discussed above."
All three companies currently focus on non-tumor-derived RNA-based assays consisting largely of mRNA and miRNA targets, which enable relatively rapid readouts of disease responses and are better suited to detecting disease at multiple points, including at earlier stages, compared to circulating tumor DNA, which is more often shed later in a tumor's evolution when it undergoes necrosis.
RNA also provides, in Keiser's words, "a very rich environment for biomarker discovery."
"Commercially," he said, "RNA is easily measured in most biofluids and translates well to mature assay technologies such as PCR, which are platform-independent, affordable, reliable, scalable, portable, and require only a two-to-three-day turnaround time."
MiRNAs have attracted increasing interest as liquid biopsy biomarkers. Ma Jose Serrano, of the Liquid Biopsy Metastasis Research Group, in Granada, Spain, recently investigated their use as biomarkers of metastatic colorectal cancer, noting that miRNAs play an important role in cancer and they can be encapsulated with high stability into extracellular vesicles, or EVs, that are released in biological fluids.
"EV-miRNAs could become an important liquid biopsy tool to replace or complement the clinical relevance of [circulating tumor cells]," Serrano wrote in that study.
Once IVBH selects a disease area on which to focus, it spends months incubating a company around that topic.
"We do research on a clinical indication," Keiser explained, "identify and innovate around what we consider to be the fail points related to screening, diagnosis, and treatment for a particular disease state, and then we research and prioritize datasets that we feel provide us with the greatest potential to unlock new biological discoveries."
IVBH then mines Gene Expression Omnibus datasets for novel biomarkers, selecting those that demonstrate efficacy across at least two datasets. These form the scientific basis of the new company.
Of the three companies currently incubated by IVBH, Mammogen, headed by CEO Elizabeth Cormier-May, appears to have made the most progress toward test commercialization. Mammogen is exploring the use of mRNA and miRNA biomarkers for breast cancer, and recently closed an oversubscribed $2 million equity financing round to develop a pair of breast cancer liquid biopsies designed to identify women who would benefit from additional screening and to reduce the rate of unneeded breast tissue biopsies.
"[M]iRNA dysregulation may be reflected in the biological fluids of [breast cancer] patients including serum, plasma, and whole blood," Rihab Nasr, a researcher at the American University of Beirut who studies the role of microRNA in cancer pathogenesis, said in a recent review. "[M]iRNA are easily quantifiable, stable, and resistant to degradation in the extracellular environment, hence supporting their potential role as biomarkers for [breast cancer] screening and diagnosis."
Mammogen's tests address potential weaknesses in breast cancer testing guidelines that affect women under 40 years of age and those 55 and older.
Current guidelines do not recommend mammograms for women under 40, on account of lower breast cancer prevalence within this population, as well as generally denser breast tissue, which complicate accurate mammogram readings. Breast cancer incidence has been rising among younger women, however, and when it does occur, it is more likely to be aggressive.
Women 55 and older, on the other hand, experience a higher cancer incidence and are more likely to undergo breast tissue biopsies, of which an estimated 80 percent return negative. Knowing which patients don't need a more invasive biopsy is therefore of interest to both patients and healthcare providers.
Mammogen's genTRU-EDT (early detection testing) assay is designed to identify women between 18 and 40 years of age who might benefit from further evaluation. The genTRU-PID (post-imaging diagnosis) test is meant to reduce negative biopsies for suspicious nodules as a follow-on to traditional imaging, whether discovered incidentally or through routine screening.
Mammogen is planning several clinical studies to evaluate the performance of its breast cancer-related tests. Enrollment is anticipated to open in 2022, and the studies will integrate demographic and clinical risk factors, as well as clinical datapoints obtained from mammography, ultrasound, and magnetic resonance imaging.
"While our sensitivity and specificity in all studies completed to date are quite strong from biomarker measurements alone," Keiser said, "our expectation is that the inclusion of demographic and clinical variables, integrated along with our biomarker measurements, will further augment the sensitivity and specificity of the final commercial tests."
Meanwhile, HepGene's liquid biopsy assay measures 92 NAFLD-related RNA biomarkers, consisting of 60 mRNA and 32 miRNA markers. NAFLD has an estimated global incidence of approximately 1 billion people and is the leading cause of chronic liver disease in the US.
Finally, LiquidLung is exploring the same kind of tests in the lung cancer field, although IVBH declined to go into greater detail on the company at this time.
Keiser stated that all three IVBH companies are actively evaluating and preparing for all appropriate regulatory pathways, related to obtaining marketing approval for their respective tests.
He further noted that IVBH's recently announced partnership with P4 Diagnostix has enabled it to transition all eight diagnostics across lung cancer, NAFLD, and breast cancer from the R&D to the clinical phase. "We expect to publish data from multiple upcoming clinical studies within the next 12 to 18 months," Keiser said.