Deepath Medical Diagnostics (DeePath MDx), Inc. is an early-stage clinical diagnostics company developing novel technologies for detection, quantification, and characterization of hematologic cells that impact cancer. The SCALPEL cell-based test is a highly informative assay based on single cell profiling of oncogenic signaling characteristics. Characterizing the pertinent features of cancer cells provides information which can guide treatment decisions. The test is designed to analyze the cellular ecosystem, including the cancerous cells and cell types comprising the anti-tumor immune response. An integral goal is to accurately detect actionable disease through detection of activated cell types. The Eyelis analytics aim to support high dimensional data analysis and visualization to derive cell-specific protein expression profiles.

In acute and chronic leukemia, the test can more accurately identify and characterize the signaling aberrations in post-therapy residual leukemic progenitors. In allergic conditions, the phenotypic profile of activated basophils can predict the severity of symptoms. Predictive models will be derived from targeted protein and gene expression analysis.

~Jitakshi De, M.D.

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Jitakshi De, President & CEO

MD, FCAP, FASCP

Dr. De is a Physician Scientist / Pathologist and Entrepreneur, Chief Executive and Technology Officer, and Founder of Deepath Medical Diagnostics (DeePath MDx), Inc. She earned her M.D. from Duke University and holds a Bachelors in Biology from University of North Carolina at Chapel Hill. De completed her residency in Anatomic and Clinical Pathology from University of Texas at Houston (’03 – ’07) and a fellowship in Hematopathology from University of Michigan (’08 – ’09).

Her clinical and translational research experiences include:

’93-’94: Use of a dicentric chromosome breakage assay in S. cerevisiae for identification of kinetochore proteins of functional significance.
’97-’98: Cloning of the unusual class of ARE mRNA-regulating CCCH tandem zinc finger proteins in X. laevis, including identification of a novel vertebrate member, XC3H-4.
’00-’02: LC-MS/MS analysis to compare the cell surface proteome of FACS-purified peripheral blood CD4 and CD8 T cell subsets.
’04-’05 Assessment of prognostic factors relevant in chronic lymphocytic leukemia (CLL) treated with a combination chemoimmunotherapy.
’06-’07: Identification of an immunophenotypic correlate (i.e. diminished aberrant CD19 expression) of KIT-activating mutations in acute myeloid leukemia with t(8;21)/AML1-ETO.
’07-’08: Phospho-specific immunocytochemistry analysis of growth factor-induced signaling pathway activation in FACS-purified CD133+ hematopoietic stem cells.
’08-’09: Morphoproteomic analysis of survival pathways in classical Hodgkin lymphoma (cHL) cells and microenvironment.
’12-’15: Immunophenotypic characterization of activated signaling pathways in chronic myeloid leukemia (CML) progenitor cell types by highly multiplexed cytometry.
’13-present: Development of advanced software analysis tools for highly multiparametric cytometry based on time-of-flight mass spectrometry detection of rare earth metal-conjugated antibodies.

She brings valuable industry experience in flow cytometry and mass spectrometry-based immunophenotyping with high dimensional analytics for both biomarker discovery and cancer diagnostics.

Dr. De was a recipient of the Howard Hughes Medical Institute Student Research Fellowship (1997 – 1998), CAP Fellowship in Hematopathology (06/06 – 07/06), and the Becton Dickinson Biosciences Stem Cell Research Award (Summer 2013) . Her research interests include functional identification of cell types and the immunologic response in neoplastic conditions. She is a Fellow of the American Society of Clinical Pathology and the College of American Pathologists. Click here for De’s CV

Ramani Aiyer, PhD, MBA VP, Research and Development (R&D)

Ramani Aiyer heads Shasta BioVentures, a Life Sciences R&D and Business Development consultancy offering strategic advisory and project management services. He has over 20 years’ experience in the biopharmaceutical and clinical diagnostics industries, with major roles in R&D strategic planning, mentoring scientists and leading project teams. He is a member of the California Life Sciences Association Fellows All-Star Team (FAST) advising biotech start-ups. He has a PhD in Biochemistry from Harvard, did post-doctoral research at Stanford and Dana-Farber Cancer Institute, and has an MBA from University of California, Berkeley. Earlier, he was Chief Scientific Officer at Actis Biologics, a start-up bio-therapeutics company, and prior to that Senior VP, R&D Strategic Planning at Piramal Life Sciences. His other roles have included management consulting, and senior positions at Genentech, TransMed Biotech, LifeScan acquired by Johnson & Johnson), and Sugen (acquired by Pharmacia/Pfizer).

Paul H. Kane, BSEE Lead Algorithm Engineer

Paul Kane comes with an extensive background in signal processing and analysis of biomedical data from magnetic resonance spectroscopy and mass spectrometry. His expertise is in continuous problem solving through the application of advanced techniques combining signal and data processing, image analysis and analytical mechanics. He applies intuition and a solid background in engineering and physics fundamentals for pattern classification of high dimensional cytometry data.


BOARD OF ADVISORS

John K. Choi, MD, PhD

John Choi is an Associate Faculty of St. Jude Children’s Research Hospital. He completed his medical education and post-doctoral studies from University of Pennsylvania, and was on faculty at Children’s Hospital of Philadelphia prior to joining St. Jude hospital. His research interests include the study of mechanisms by which mutated E2A promote precursor B lymphoblastic leukemia, and ways to more precisely evaluate minimal residual disease (MRD) in acute myeloid leukemia by flow cytometry.

Rajen J. Mody, MD, MS

Rajen Mody is an Associate Professor in the Department of Pediatrics Hematology/Oncology at University of Michigan. Dr. Mody has an extensive experience in supervising investigator-initiated as well as group wide early-phase clinical trials as a principal investigator of several local and international clinical trials through the Children’s Oncology Group (COG). His research interests include studying the role of precision medicine in high risk pediatric malignancies through use of translational genomics and next-generation sequencing technology. In addition, his clinical research interests include use of innovative early-phase clinical trials for development of new agents against pediatric malignancies. He has also received formal training in clinical trials design and Biostatistics through a masters degree (M.S.) from the School of Public Health at the University of Michigan.

Bruce H. Davis, MD

Bruce Davis is an expert hematopathologist with experience in the development and validation of fluorescence cell-based diagnostic assays for clinical cytometry and laboratory hematology. He has led R&D of new diagnostic products, in particular, the Leuko64 assay for the detection of infection and sepsis. Dr. Davis has authored and co-authored over 100 peer reviewed publications, and serves on the editorial boards for journals in cytometry and laboratory hematology, and as Chairman of the Clinical and Laboratory Standards Institute. He earlier served as the Director of Hematopathology at the Dartmouth Hitchcock Medical Center and at US Labs (subsidiary of LabCorp). He received his BS in Biology from Cornell University in New York and his MD from University of Connecticut.

I. Elaine Allen, PhD

Dr. Allen is a Professor of Epidemiology & Biostatistics at UCSF. She founded and led several biotechnology companies including MetaWorks, an Evidence-Based Medicine firm; and Stat Systems, a diagnostic company. She previously held faculty positions at the University of Pennsylvania, Medical College of Pennsylvania, and Babson College. She is Co-Director of the Babson Survey Research Group and is actively involved in design and conduct of surveys on online education and entrepreneurship. Dr. Allen has published widely on statistical issues in meta-analysis, analytics, survey research, and clinical research methods.

ISAC '14 pic

ASCP’s 40 under 40 pathologists and laboratory professionals (2014)

BD Biosciences Stem Cell Research Award (Summer 2013)

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Validation of fluorescence flow cytometry assays: post-analytic considerations Cytometry Part B 2013, 84B: 309-314.

Morphologic and immunophenotypic description of an unusual acute myeloid leukemia-associated translocation (8;19)(q24;q13.1) SH-EAHP Case of the Quarter, May 2013.

Morphoproteomic analysis of survival pathways in classical Hodgkin lymphoma IJCEM 2010, 3(1): 55-68.

Immunophenotypic features predictive of KIT activating mutations in t(8;21)/AML1-ETO acute myeloid leukemia AJCP 2007, 128: 550-557.

A teaching database for diagnosis of hematologic neoplasms using immunophenotypic by flow cytometry Arch Pathol Lab Med-Vol 132, May 2008.

For additional publications, visit the ResearchGate site here

The SCALPEL (Single Cell Analysis of Limited Protein Expression Levels) assay is a multiplexed cell-based biomarker assay that measures signaling activities in target cell types to identify pathologically activated cells in certain “difficult to cure” cancers and allergic/immunologic disorders.

When a growth factor or cytokine binds to its cell surface receptor, a cascade of tightly regulated signaling events ensues inside the cell through proteins within signaling cascades that get altered and activated by the addition of phosphate groups by kinases. Deregulated oncogenic pathways result from multiple protein kinases that get sequentially phosphorylated transmitting the signal into the nucleus, ultimately promoting unabated gene and protein expression. Pathologic activation can also result as an immune response to exogenous triggers. With the SCALPEL test, detailed characterization of the proliferative clone(s) or pathologically activated cells can be performed by massively multiplexed immunophenotypic analysis that derives the cell-specific profiles of regulatory proteins within activated networks.

SCALPEL is a clinical and research application of high parameter cytometry for identification, quantification, and characterization of functionally activated cell types. Data analysis is performed by Eyelis high-dimensional analysis and visualization software.

The assay is designed to identify refractory stem/progenitor cells in leukemia, and to decipher certain relevant components of immune response in leukemic and non-leukemia conditions. The SCALPEL results are integrated with routine diagnostic work-ups to guide treatment strategy and monitor for minimal residual disease (MRD). In chronic myeloid leukemia (CML), it can potentially determine the eligibility and outcome of patients who discontinue treatment with TKIs.

The Eyelis analysis software algorithms enable feature selection and automated pattern-based classification of cells identified by high parameter cytometry. The software improves sensitivity and accuracy of cell identification, and generates intuitive data displays to ease interpretation.

ICSH/ICCS Working Group Practical Guidelines Meeting on Cell-based Fluorescence Assays for Laboratory Developed Tests (LDTs) – Part IV – Postanalytic Considerations 2011; Lucerne, ME. Cytometry Part B 2013; 84B: 309-14.

Personalized Medicine World Conference (PMWC) ’13, January 28-29; Mountain View, CA.

Mass Cytometry Analysis of Primitive Cell Subpopulations in Previously Treated Chronic Myeloid Leukemia in Chronic-Phase. Cancer Research: April 15, 2013; 73; 4118. Proceedings: AACR 104th Annual Meeting 2013, April 6-10; Washington, DC.

Functional characterization of Lymphoid Progenitor Cells in Chronic Myeloid Leukemia by Mass Cytometry Phos-flow Analysis. Podium Presentation (abstr. 25) International Society for Advancement of Cytometry CYTO XXVIII Annual Meeting ’13, May 19-22; San Diego, CA.

Multidimensional Data Visualization Tools for Multiparameteric Analysis of Signaling Pathways by Mass Cytometry Analyses of Chronic Myeloid Leukemia Specimens. Multimedia abstract (Program 128/B7) International Society for Advancement of Cytometry CYTO XXVIII Annual Meeting ’13, May 19-22; San Diego, CA.

Next Generation Diagnostics (Dx) Summit 2013, August 20-22, Capitol Hill; Washington, DC.

11th Annual Discovery on Target 2013, September 24-26; Boston, MA.

2013 Shanghai International Symposium on Cancer Stem Cells, October 17-19, Tongji University; Shanghai, China.

Multidimensional Single Cell Analysis of Diverse Cell-Types Comprising Malignant Neoplasms Using Mass Cytometry. Emerging Cell Technologies: Podium Presentation CMCB 2014 – BIT’s 4th Annual World Congress of Molecular and Cell Biology, April 25-28; Dalian, China.

Bio-IT World Conference & Expo ’14, April 29 – May 1, World Trade Center; Boston, MA.

Automated Analysis of High Parameter Cytometry Datasets to Classify and Characterize Distinct Cell Types in Biologic Samples of Cancerous and Inflammatory Disorders. Multimedia abstract (Program 140/B2) International Society for Advancement of Cytometry CYTO XXIX Annual Meeting ’14, May 17-21; Fort Lauderdale, FL.

Eyelis Software-Assisted Analysis of Proliferative Stem/Progenitor Cell Types Detected by the SCALPEL Assay in a Blood Sample with Relapsed Chronic Myeloid Leukemia. Diagnostics Section (Program 197/B66) 30th Congress of the International Society for Advancement of Cytometry CYTO Annual Meeting ’15, June 26-30; Glasgow, Scotland.

A Novel SCALPEL Cell-based Assay for Residual/Relapsed Disease Detection in Chronic Myelogenous Leukemia. International Clinical Cytometry Society Annual Meeting ’15, Oct 11-13; Denver, CO.

Automated Identification of Novel Cell Types Based Upon Signaling Characteristics in Chronic Myeloid Leukemia. Multimedia Abstract in Hematologic Disorders (B2). 31st Congress of the International Society for Advancement of Cytometry CYTO Annual Meeting ’16 , Jun 11-15; Seattle, WA.

Targeted analysis of public phospho-mass cytometry datasets to analyze the phenotypic variability in activated basophil subset in subjects with peanut allergy. 32nd Congress of the International Society for Advancement of Cytometry CYTO Annual Meeting ’17, Jun 11-14; Boston, MA.

A novel approach to activated cell cluster identification by high dimensional phospho-mass cytometry using stable intracellular attributes in Eyelis-based auto-classifier. 32nd Congress of the International Society for Advancement of Cytometry CYTO Annual Meeting ’17, Jun 11-14; Boston, MA.

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DeePath Medical Diagnostics, Inc.

895 Dove St., Ste 300
Newport Beach, CA 92660

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Quotes from renowned experts in CML about the rising costs of TKI therapy and the need for biomarkers:

This Forum reflects the views of a large group of CML experts who believe that the current prices of CML drugs (1) are too high, (2) are unsustainable, (3) may compromise access of needy patients to highly effective therapy, and (4) are harmful to the sustainability of our national health care systems. These concerns reflect the spiraling prices of cancer drugs in general. Of the 12 drugs
approved by the FDA for various cancer indications in 2012, 11 were priced above $100 000 per year. Cancer drug prices have almost doubled from a decade ago, from an average of $5000 per month to >$10 000 per month.
~Experts in Chronic Myeloid Leukemia, Blood online, April 25, 2013; DOI 10.1182/blood-2013-03-490003

Patients with sustained undetectable transcripts by PCR is the cohort that would be considered potentially eligible for treatment discontinuation. You would expect that grossly half would relapse and half would not, so the biomarker should have grossly that distribution.. Patients with low levels of detectable disease (e.g., MR4) either sustained while on therapy or who have relapsed after treatment discontinuation but still at low levels. You would expect that most of these patients would express the biomarker.. Patients that have discontinued therapy and have not relapsed, ideally after at least 6 months. The risk of relapse after 6 months is low so you would expect that none or not more than very few would express the biomarker.
~Jorge Cortes, M.D. at MD Anderson Cancer Center. 01.04.2017

It has been observed in clinical trials that molecular recurrence occurs in about half of the patients who stopped TKI after having reached a deep molecular response (DMR, based on very low or undetectable BCR-ABL, i.e. 4 log or greater reduction). Factors predicting recurrence are currently lacking, with more patients having to take a 2G-TKI to reach the goal of DMR for TKI discontinuation, though successful discontinuation is also possible on IM.
~Michael Deininger, M.D. at Huntsman Cancer Institute. 01.06.2017

Importantly, patients with longer and deeper molecular responses are thought of now as potentially cured. Unfortunately, clinical trials have shown that about half of these patients relapse after cessation of TKIs. At this time, this is not recommended strategy for these patients unless on a clinical trial. There is as yet no good biomarker to predict those 50% of patients who will or will not relapse.. The discontinuation strategy also brings up the importance of the initial treatment choice. The second-generation TKIs, which have higher chances of achieving a deeper response might emerge as the preferred choice. Apart from the traditional biomarkers (PCR for BCR/ABL), we need novel biomarkers that can predict long-term remission/cure for these patients for TKI discontinuation. In addition, targeting CML stem cells could also emerge as a “curative” strategy.
~Amitkumar Mehta, M.D. at University of Birmingham, Alabama, ASCO Reading Room. 01.25.2017