News & Media

2018 – Diseased and Normal Human Cell Platform Technologies

DBM has found its niche in this above marketplace. DBM creates and establishes human cell platforms and designs and invents bioassays using the same human cell platforms as key ingredients. And even though it is a new year, DBM carries with it the same bedrock vision it held when the company was founded in 2007 – better results through leveraging diseased human cell platform technology. We look forward to continue to serve the biotechnology sector locally, regionally, nationally, and internationally with our expertise, know-how and innovative assays.

Although many of our clients are confidential, we thank them all for their patronage. We are gratified to have extended work with many of them. We see an increased interest in ‘humanizing” drug discovery and profiling within industry and academia and DBM is gratified that our core principle is gaining traction among our clients and in the marketplace.

DBM is proud to announce continued progress in one “Fast Track” SBIR award supported by the NIH ORIP focused on the creation of genotyped human ADPKD cell platforms and 3D cystogenesis bioassays using such diseased human kidney cell platform technology. We are humbled by the receipt of a new “Fast Track” SBIR award supported by the NIH NIEHS focused on the creation of normal human kidney cell platforms for cytotoxicity testing. Both SBIR awards focus principally on DBM’s strong suits – designing cell platforms for real world and applied science experimental applications. They are also quite complementary. DBM intends to use these monies to develop additional novel cell platforms that will be useful in cytotoxicity testing, drug discovery and lead compound and drug profiling. DBM is also self-funding an effort to create new diabetic kidney cell platforms and already has established primary cultures isolated from diabetic kidney tissue.

DBM is also developing human cell platforms for the taste bud and taste sensory physiology, an important initiative for us. We are also developing diseased and normal human skin cell platforms for our bioassay services work and we have keen interested in 3D growth format diseased cell platforms in cancer and PKD as well as in normal tissues. Finally, we have become facile in custom cell immortalization services with multiple genetic strategies. Our creativity is driving these efforts.

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2017 in Review – A Year of Growth and Addition of Key Team Members at DBM

As DBM reflects on a strong 2017 and hello to a promising 2018, DBM said hello to several new faces in both its labs and offices. In the past year, DBM has added new staff and new capabilities.

In early 2017, DiscoveryBioMed hired Matthew Redmann, PhD to the post of Head of Business Development and Senior Scientist. As a recently graduated Ph.D. from the University of Alabama at Birmingham (UAB), Matthew brings with him a quality publication record and substantive interests in the business of science and how to translate discoveries at the bench to useful applications in the world. Matt is originally from Appleton, WI.

Shortly after, Lawrence Greer, J.D., LLM was appointed as Chief Financial Officer to oversee and manage the increasing complexity of DBM’s financial dealings. Lawrence earned his J.D from the University of Alabama School of Law and brings with him significant legal and business experience in the biotechnology and finance realms. Lawrence is originally from Birmingham, AL.

Alongside these additions, DBM promoted a long-term and valued intern, Albert “Os” Nakayama, to Staff Scientist. He continues to add value to scientific team in bioassay performance, scientific support, and data analysis and presentation. He is also a PowerPoint artist that has assisted on important slide deck presentations to potential partners and investors. Os is originally from Birmingham, AL.

Additional appointments include Dr. Doug Hay being added to DiscoveryBioMed’s Board of Directors. Doug brings decades of valuable biotech and pharmaceutical management experience and will be a boon to DBM as it seeks to expand its reach and navigate ever-volatile biotechnology markets. DBM has been and remains a valued consultant to DBM in Drug Discovery and Development. Doug is originally from Scotland and resides in Philadelphia.

DBM has a team with great chemistry in terms of leadership, business development and science and that will serve the company well in 2018.

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Update: Human ADPKD Kidney Cell Platforms – Progress to Date

This post is meant to serve as an abbreviated version of an internal White Paper and is provided as an update to our efforts here at DiscoveryBioMed, Inc. (DBM, Inc.) to continue to optimize and develop human ADPKD kidney cell platforms. We are ‘learning by doing’ as always, and we wanted to present some new findings and current status of products in development.

A Mixed Cell Population Is Key to “Cystogenesis Functionality”
One confounding issue in the practice of isolating, growing, genotyping and characterizing single cyst-derived primary cultures and multicystic/microcystic tissue-derived primary cultures is that not all of the primary cultures from individual kidneys form cysts or are capable of cystogenesis. This is puzzling in light of the fact that they all derive from the same human ADPKD donor kidney tissue. Having said that, with each donor, we do have primary cultures that indeed form cysts. During the characterization of all primary cultures from a given donor in 3D Biogels, we also seed some cells from each culture on TC plastic so as to image and assess whether there is a single cystic epithelial cell type in the culture or if there is more than one cell type in the culture. In the context of this work, there is a uniform phenotype that a mixed cell population appears necessary in a given huADPKD primary culture to form cysts.

Not only do we observe routinely both small and large cystic epithelial cells in these ‘cystogenesis capable’ cultures, but we also observe a small number of fibroblasts as well. There are typically not enough fibroblasts in these cultures to overgrow and overwhelm these cultures and this is tested for in quality control to ensure consistency between cultures. Interestingly, a common practice in epithelial cell culture (cystic or non-cystic) is to eliminate fibroblasts from the cultures to generate a ‘pure’ population of epithelial cells. DBM believes this may be short sighted. For example, we have separated ‘pure’ populations of epithelial cells and fibroblasts from a given primary culture. However, before we separated the cell types, the culture formed cysts in 3D, whereas after separation, cystogenesis failed to occur, suggesting an indispensable role of fibroblasts in this process. It is also possible that these fibroblasts are actually progenitor cells and one academic investigator in Europe believes that this may be the case. Taken together, there is more than one type of cell in these cultures and multiple types of epithelial cell and we and others continue to define them going forward.

Current Iteration of the 3D Cystogenesis Bioassays
DBM can perform three different types of cystogenesis assays with coded and blinded client LTAs. Cystogenesis occurs in our DBM RenalCyte media only and does not require stimuli at significant concentrations. More recently, we have begun to test different stimuli with forskolin and arginine vasopressin accelerating cyst formation and increasing cyst number. Growth factors do not seem to accelerate the system, suggesting that the cells themselves may produce and secrete necessary growth factors endogenously in the Biogels.

First, the “Cyst Attack” assay tests a candidate therapeutic LTA on cysts that have already formed and become an ideal size to determine whether the LTA stops further cyst enlargement, shrinks the cysts, causes them to collapse into a spheroid, or rupture altogether. Imaging is performed daily over time in these custom assays where cyst number per well and cyst size can be measured. Overall viability is measured via 3D CellTiterGLO cell quantification (based on cytosolic ATP from live cells) at the conclusion of the experiment.

Second, the “Cyst Prevention” assay tests a candidate therapeutic LTA on Biogels where cysts have just begun to form, so as to determine whether they attenuate or prevent cyst formation versus untreated and vehicle-treated controls.

Third, in “Cyst Suppression” assays, one can treat from the initial seeding of the cells into the Biogels (versus controls) and prevent the appearance of any cysts from time 0 or Day 0 for a prescribed period of time. Similar endpoints to the “Cyst Attack” assay can be captured.

Recently, DBM procured a BioTek Cytation 5 high content imaging and light-based high-throughput screening imaging system so as to image the huADPKD cells growing in 3D Biogels in 96-well and 384-well microtiter plates. This effort seeks to ‘miniaturize’ the assay from the current 48-well plate format. DBM has been successful in observing cystogenesis from key primary and immortalized huADPKD cell cultures in 96-well full area well plates, 96-well half area well plates and in 384-well plates. This effort seeks to increase the throughput of the assay and also allows for implementation of automated robotic light-based bioassays and high-content imaging in the future for our clients. The use of fluorescent dyes are currently being investigated to enhance image acquisition and quality.

Current Status of Immortalized huADPKD Cell Cultures
In 2017, DBM began by challenging cystogenesis competent cells from three of our six donor cultures, two of which have mutations in PKD1 and one which has a mutation in PKD2. From these cultures, we derived immortal cell cultures using both SV40T and hTERT. These immortalized mixed cultures are still being characterized, but at early passage form 3D cysts in Biogels similar to their primary progenitors. We are continuing to passage these cells to observe phenotype and if the hTERT immortalized cultures maintain growth and phenotype, we will select them with neomycin. We are also employing additional immortalization strategies.

Please enquire to learn more about either our primary or immortal ADPKD cell cultures and assays.

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Q2 2017 Update: DBM Sends Delegates to BIO and RESI Conferences in San Diego

As mentioned in the Q1 2017 update, it is an exciting year thus far for DiscoveryBioMed with the acquisition of a BioTek Cytation 5 anchored automated system. In order to market these new capabilities and build new relationships with potential clients and partners, DBM sent a team of delegates to both the BIO International Convention and at RESI (hosted by Life Science Nation) in San Diego this past July.

Last year at BIO 2016, DBM was invited to exhibit at the BIO Innovation Zone with other select companies that are pushing the boundaries on scientific innovation and translation to the marketplace. Last year at the BIO Investor Forum, DBM was sponsored by the NIH NIDDK to present the latest data from our Adiponectin Inducer program.

This year in an effort to further increase DBM’s reach, delegates looked outside the formal BIO convention for additional meetings and attended another conference called RESI. Between these two conventions and over the course of two and a half days, DBM’s delegates Erik Schwiebert, Lawrence Greer, and Matthew Redmann had over 35 meetings with potential clients and future partners. This volume matched the activity at last year’s BIO convention.

DiscoveryBioMed is always expanding its CRO services portfolio. However, its core focus remains tightly rooted in a humanized drug discovery philosophy – meaning utilizing the most relevant humanized cellular platform as possible, regardless of whether that process is for our clients or for our own R&D programs. If you or your company are in need of custom services, especially in renal, respiratory, dermatology and metabolic diseases areas, submit a request through our online store.

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Q1 2017 Update: DBM Invests in Cytation 5 Anchored Automated System

Discovery BioMed prides itself on utilizing the latest technology platforms and offering services based on these advanced systems. In H1 2017 DBM invested in a BioTek Cytation 5 anchored automatic robotics system supported by BioTek’s BioSpa 8 and a BioTek plate washer. Together this system provides high-content automated fluorescence, luminescence, brightfield imaging and plate reading modalities.

After an initial period of set-up and optimization, DBM is now utilizing this platform for both its CRO services and R&D arms. One service that has proven popular with our large biopharma clients, leverages DBM’s expertise in renal biology and is a demonstration of the types of assays we offer is DBM’s in vitro 3D cyst formation assay. This is assay is directed towards clients and researchers with a principle interest in human renal diseases that exhibit cystogenesis as part of their pathology.

As with all research projects undertaken by DBM, we base the assay on human tissue platforms. This enables greater translatability of the results and a better likelihood of eventual clinical success. This assay in particular relies upon our ethically obtained human normal and autosomal dominant polycystic kidney disease cell platforms. DBM is currently expanding its cryovial repository of these cells with mutations in either PKD1 or PKD2 available as platforms. These primary cells are seeded into Biogels where they form bone fide cysts in culture and can be exposed to therapeutic assets.  Using our robotics line, cyst size can be tracked over several days or weeks. Images can be automatically captured daily and viability measured at the experiments conclusion.

It is important to note that this is just one example and DBM’s CRO arm remains focused on custom assay and platform development.

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Q4 2016 Update – DBM Participates at BIO’s 2016 International Conference and BIO’s 2016 Investor Forum, Continues an Active Intern Program

In June 2016, DBM’s Dr. Erik Schwiebert and Dr. John Streiff, with support from our long-time consultant, Dr. Douglas Hay, traveled to San Francisco to participate in the annual BIO International Meeting. There, DBM met with over 40 companies within and outside the BIO Partnering Forum. The NIH NIDDK also nominated and supported DBM at the convention with an Exhibit Kiosk in the NIH Innovation Zone. DBM was humbled and grateful for this opportunity. DBM was also an active partner in the BioAlabama exhibit.

Additionally, DBM was nominated by the NIH NDDK to participate in the Annual 2016 Bio Investor forum. And, in October, DBM traveled to San Francisco, once again, to present the results from an in vivo study with lead compounds from its Metabolic R&D program. DBM’s presentation was well received and its presence made possible by an NIDDK administrative supplement to an active SBIR award for registration and travel funds. DBM’s Dr. Schwiebert declared that “DBM continues to be honored and grateful for the deep support from the NIDDK in our partnering and business development efforts.”

Over the past year, DBM has been host to productive and outstanding interns. UAB students Cherie Verbal, Ophelia Johnson, and Albert Nakayama performed active work for DBM part-time from January through August 2016. Albert is continuing work with DBM going forward for the next 6-9 months as nearly full-time employee at present. These outstanding student interns were part of a Master’s program in Biomedical Engineering at UAB focused on Design and Commercialization. DBM is assisting Cherie in finding employment in the Huntsville area, while DBM is supporting in part Ophelia’s time in London where she has a prestigious fellowship in biomedical engineering and commercialization. In addition to this, DBM hosted 9 UAB Ph.D. students in exposure and immersion experiences at DBM and has identified a handful of promising candidates to join us and/or allied companies that we are helping as new startups.

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DiscoveryBioMed, Inc. Declares a Sharpened Focus on Renal Cell Biology and Physiology and on Renal Diseases

Through both natural evolution of our R&D programs and within our CRO services business, DiscoveryBioMed, Inc. (DBM, Inc.) has identified a sharpening focus in Renal or Kidney Cell Biology and Physiology and in Renal Diseases over the last year, in 2016, and going forward.

We invite interested parties to view our newly redesigned website where this focus is declared and apparent.

It is ironic that DBM’s founder, Dr. Erik Schwiebert, first worked on Renal Cell Physiology while a lab technician, first year Ph.D. student, and Ph.D. candidate while in Dr. Bruce Stanton’s laboratory at Dartmouth. “In my very first memories of culturing rodent and human cells, I was involved in establishing primary cultures and growing those cultures and immortal cell lines from the nephron of the kidney so as to study the regulation of epithelial sodium and chloride channels in collecting duct-derived cells,” Erik explained. “I am very familiar with establishing and growing kidney cells as well as studying them and characterizing them. It is therefore not surprising that DBM has also gravitated to that although it was not overtly intentional.”

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It is who we are – It is what we do

Since the ‘light bulb idea moment’ in 2006 and the pre-launch and launch periods in 2007, DiscoveryBioMed, Inc. (DBM, Inc.) has held the solid core principle of Humanized Drug Discovery, the use of intact, living human cells in culture as the biologically-relevant and disease-relevant cell platforms on which to perform meaningful small molecule discovery and critical hit-to-lead and lead compound profiling. This core principle holds for both our internal R&D programs and our contract research organization (CRO) services business.

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