Ariel Fernandez is a chemist and mathematician specialized in rational drug design and molecular biophysics. Some of his most celebrated contributions may be described as translational. They harness fundamental advances in basic science and flesh them out into innovative therapeutic agents. Ariel Fernandez's consultancy focuses on hit-to-lead and lead optimization phases of drug discovery. Learn more.
Our focus on cancer evolution in a therapeutic context
Ariel Fernandez Consultancy is mostly focus on the role of cancer evolution in the design of timed oncotherapies. Endowed with the evolutionary substrate of genomic instability, cancer adapts and develops resistance to therapy, constituting a moving target. Current therapies select for resistance and therefore do not seem to deal with this hurdle. Efforts by Ariel Fernandez and coworkers squarely address this problem. We develop dynamic immunotherapies that evolve concomitantly with the disease and steer the tumor into resistance pathways leading to extinction.
At Ariel Fernandez Consultancy we recognize that even immune checkpoint inhibitors (ICIs), the most promising therapeutic agents today, do not provide lasting cure, not even for the subpopulation of responsive patients. Immune surveillance imposes selection pressure on the tumor and the genomic instability induced by priming epigenetic agents promotes cancer evolution and adaptation. This scenario leads to patterns of immune resistance that ultimately lead to relapse of the disease. Thus, it becomes imperative that the immunotherapy avoids maintaining a fixed selection pressure. Ariel Fernandez Consultancy addresses this imperative and develops paradigmatic solutions to the moving target problem.
Our solutions are somewhat akin to synthetic lethality but the therapeutic context is very different. Parallels between our timed immunotherapies and targeted therapies based on collateral sensitivity also exist but the therapeutic context is again different. At Ariel Fernandez Consultancy we perform computational analysis of clonal dynamics of immune evasion under the selection pressure imposed by our proprietary immunotherapies. Our results are validated in preclinical experimental models. At that juncture, we typically license out our inventions and aid our licensees as they move the invention through clinical evaluation and development.
The clinical implementation of evolving therapeuties developed at Ariel Fernandez Consultancy relies on a clinical evaluation of the immune-evasion phenotype at critical junctures. We assist in such evaluations that will ultimately dictate the choreography of the treatment and the calibration of clinical endpoints vis-à-vis expected target outcomes. We at Ariel Fernandez Consultancy are keenly aware that evolving therapies will surely be harder to implement than conventional treatments. However, our research supports the view that therapy must lead and not follow vis-à-vis cancer evolution.
Ariel Fernandez
Scientist - Consultant
COVID 19
In these papers, Ariel Fernandez outlines plausible routes to defuse COVID19:
Ariel Fernández: “Viewpoint: Structural impact of mutation D614G in SARS-CoV-2 spike protein: enhanced infectivity and therapeutic opportunity”. ACS Medicinal Chemistry Letters 11, 1667-1670 (2020). https://pubs.acs.org/doi/10.1021/acsmedchemlett.0c00410
Ariel Fernández: “VIEWPOINT: Therapeutically targeted destabilization of the quaternary structure of the spike protein in the dominant G614 strain of SARS-CoV-2.” ACS Pharmacology and Translational Science 3, 1027-1029 (2020). https://pubs.acs.org/doi/10.1021/acsptsci.0c00114
Ariel Fernández: “VIEWPOINT: Achilles' heel of SARS-CoV-2 structure.” ACS Pharmacology and Translational Science 3, 1030-1031 (2020).
https://pubs.acs.org/doi/10.1021/acsptsci.0c00128
Ariel Fernández: “Defusing Sars-CoV-2: Emergency brakes in a vaccine failure scenario.” ACS Pharmacology and Translational Science 3, 1425-1426 (2020). https://dx.doi.org/10.1021/acsptsci.0c00152
Ariel Fernández: “Targeted Disassembling of SARS-CoV-2 as It Gets Ready for Cell Penetration.” ACS Medicinal Chemistry Letters 11, 2055–2057 (2020)
Ariel Fernández: “COVID-19 Evolution in the Post-Vaccination Phase: Endemic or Extinct?”. ACS Pharmacology and Translational Science, published online December 31, 2020. DOI: https://pubs.acs.org/doi/10.1021/acsptsci.0c00220
Ariel Fernández: “Glycosylation of SARS-CoV-2 Steers Evolutionary Outcomes in the Postvaccination Phase”. ACS Pharmacology and Translational Science, published online January 21, 2021. DOI: https://pubs.acs.org/doi/10.1021/acsptsci.1c00015
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