An Interview with Industry Veteran and Leader of Controlled Release Technologies Agis Kydonieus
Agis KydonieusAgis Kydonieus is the founder and president of Samos Pharmaceuticals LLC and cofounder of KAT Transdermals LLC and InteguRx Therapeutics LLC. He has 30+ years of extensive experience in preclinical as well as phase I–III clinical development and has launched several products in the marketplace. He has served as a consultant, scientific advisory board member, and executive for several companies in the fields of drug delivery—including oral (peptides), transdermal (passive and iontophoretic), implantable, injectable, buccal, and vaginal delivery—cancer chemotherapy, biopolymers, resorbable and nonresorbable medical devices, and tissue engineering including devices for orthopedics, adhesion prevention, ophthalmics, and wound and skin care. As a consultant, he also aids his clients in business plan preparation and venture financing, through venture groups and through strategic alliances and joint ventures.
Dr. Kydonieus secured a Ph.D. in chemical engineering in 1964 from the University of Florida and started his career as a chemical engineer at Union Carbide Corporation. In his early career, he joined Cooper Union Polytechnic Institute in New York as an assistant professor of chemical engineering, where he developed new families of polyurethane and polyester elastomers. He cofounded Chemtech, Inc., to commercialize the new polymers, which was later acquired by Morton Thiokol Inc. He joined Baxter Laboratories as an assistant director of corporate biomedical engineering before moving to HealthChem Corp., where he served as a board director, vice president, and later as president and founder for Hercon Laboratories Corporation. During his stay at Hercon Labs, company sales showed at least a 50% increase per year for over four years. During this time, he made over 50 presentations to stock exchange groups, pharmaceutical analysts, and institutional groups worldwide. His work was instrumental in obtaining a $20 million convertible debenture for HealthChem Corp. He finally served as vice president of corporate R&D at ConvaTec, a Bristol-Myers Squibb corporation.
His work in the field of controlled release technologies has been exemplary. He is the editor of 10 books on drug delivery including the first-ever three-volume treatise on
CRS officers during the banquet and awards ceremony at the 1984 annual meeting.transdermal delivery and has over 70 U.S. patents and patent applications, mainly in the field of transdermal and other drug delivery technologies. His academic and industrial findings have been key foundations to various technologies in the field of formulation science, polymer science (small/large organic molecules), and medical devices. For his contributions, he has been given recognition awards by the Controlled Release Society (1990), received the BMS Outstanding Corporate Contribution Award (1992), and was elected a Fellow of CRS (2010). He has served on scientific advisory boards of multiple companies including NexMed Inc., Kytogenics Pharmaceuticals, Transport Pharmaceuticals, and Valera Pharmaceuticals and on academic boards such as the New Jersey Center for Biomaterials and the MIT Biomaterials Consortium. He is one of the founders of CRS and has served as its president (1984), program chairman of the annual meeting (1982), board member, and trustee.
Q During your career, which stage (company) of your career was the most exciting part of this journey and why?
A Although I have worked in large companies and in academic environments, I loved working for small companies because there was not only freedom to innovate but also the need to innovate. In a way I consider myself a serial entrepreneurial kind of person, because I always reverted back to starting a new company to accomplish what I thought was needed to advance some part of the medical field. Perhaps the most exciting company I worked for was Chemtech, because I was young and wet behind the ears, and I left a rewarding academic position to chase a dream of developing new polymers for the medical field. It was scary but rewarding at the same time, and probably it showed me the way that I followed the rest of my career.
Q Please name a few projects (of all the research projects in your career) that you have found to be both intellectually and personally satisfying.
A It seems that some of the most exciting projects came early in my career. At HealthChem we were making a three-layered polymeric laminate (with a nylon scrim in between), with the two outside vinyl layers being glued together by a vinyl plastisol. This product was accepted in many fields because of its strength and tear resistance. However, when used in moist environments it allowed fungi to grow on it, which limited its market potential. The manufacturers of the vinyl films were not interested in incorporating antifungal agents in the films because that would contaminate their manufacturing plants. So in desperation we added the antifungal agent in the plastisol glue. Amazingly enough, the antifungal agent captan migrated from the plastisol glue to the outer films and made the laminate antifungal. Washing after washing and year after year the laminate remained antifungal! Nowadays, this would be known to every student in the pharmaceutical field, but in the late 1960s this was an amazing observation. The product found its way as the covering of mattresses in hospitals and geriatric facilities and became a multimillion dollar product for HealthChem. This observation allowed for the founding of the transdermal company Hercon Laboratories, the granting of more than a dozen patents for the controlled release of active agents, and the marketing of several multimillion dollar products containing fragrances, flavors, pheromones, insecticides, and of course drugs for transdermal patches.
Q There was a short period of time when you joined academia after spending a few years in industry. What led to that transition from industry to academia and back?
A I enjoyed academia and especially teaching the young students; however, my temperament was not only to innovate and teach but also to see the innovations translated into actual products. Nowadays professors can start companies using their innovations, which I applaud and consider totally appropriate. In the early 1970s this was not something that was possible to do and in some cases not even acceptable. This is the reason that my stay as a professor was short lived, although I kept on teaching at Cooper Union for several years as an adjunct professor.
Q What are some of the current technologies you are working on that you can see as making a good impact in the market?
A Samos is working on an oral technology platform that allows the delivery of drugs for an extended period of time, such as seven days, from the administration of a single tablet or capsule. The technology is based on the development of conjugates of three molecules: the drug to be delivered, the carrier molecule, which has long half-life in the intestinal tract, and a linker with the ability to chemically bond to both the drug and the carrier molecule. The bond between the linker and the drug is designed to cleave at desired time intervals under physiologic conditions. The conjugation chemistry is being developed in conjunction with the Chemistry Department of Rutgers University, and several of the conjugates have been tested in both pigs and beagle dogs with considerable success. One U.S. patent on the technology has been granted, and others are pending. By the way, Samos is a Greek island, which my family comes from and which can arguably be considered the most beautiful island in the Aegean Sea.
I am also the president of KAT Transdermals, where we are developing seven-day transdermal patches for CNS products. Our lead products are for depression and Parkinson’s diseases—with a twist, which involves drugs with different mechanisms of action. In addition, KAT has developed technologies that allow for the adhesion onto skin of any patch for a period of seven days, without concern for irritation.
InteguRx Therapeutics is also a transdermal company with proprietary technologies in the chemical enhancer area. Our first product is a transdermal gel for the prevention of nausea and vomiting in pregnancy. Patents have been granted for the product, and it has completed animal studies successfully. Unfortunately, I cannot say much more about the abovementioned products, because these are products in commercial development and trade secrets are critical for obvious reasons.
Q Where do you see the current research efforts in the pharmaceutical field being focused?
A Perhaps there are others with greater insight in this area, but my opinion is that new advances will come from point-of-care diagnostics and immunotherapy. New technologies from smart phones to lateral flow strip analyzers provide a rapid, convenient, and much less expensive way to diagnose diseases. For example, Columbia University’s “dongle” can provide in conjunction with a smartphone accessory immunoassay tests for sexually transmitted diseases including HIV and syphilis. Abbott’s i-STAT can conduct complete blood analysis at the point of care. Bionesa and others can provide analytic functions for infectious diseases, drug abuse, cardiac markers, blood analysis, and so on with 12 analytes being performed simultaneously, and all within 5–10 minutes. It is of course well known that the faster a disease is diagnosed the better the probability for a good outcome.
Small-molecule drugs accounted for 84% of pharmaceutical sales in 2014. However, I believe that the new research efforts and progress will now come mainly from large molecules such as antibody–drug conjugates and monoclonal antibodies that overcome suppression of the immune response and mainly for the treatment of cancer.
Antibody–drug conjugates consist of a cytotoxic drug connected by a linker to a monoclonal antibody that directs it to the target cancer cells due to the great number of cell surface-associated antigens. There are a few such drugs approved by the FDA, but there are at least 40 more such conjugates presently in clinical trials.
PD-L1 is a cell surface protein that binds to the receptors PD-1 and CD80 on activated T cells and B cells and thus inhibits T cell proliferation and inhibits immune response. Overexpression of PD-L1 on cancer cells allows these cells to avoid T cell detection and elimination. Monoclonal antibodies that block PD-L1 from binding to PD-1 and CD 80 overcome the suppression of T cell activation and allow the T cells to attack the cancer. There are PD-L1 inhibitor drugs in the market already, with many more in clinical trials. I am sure that the two approaches mentioned above will keep on making ever greater impact in the treatment of cancer in the coming years.
Q Please tell us about your involvement with organizations such as the Controlled Release Society. Please comment on the growth of the organization over the last few decades.
A I was involved during the prehistory and protohistory of the Controlled Release Society, being one of its founders. It all started in 1972 among seven or eight of us (N. Cardarelli, F. Wright, J. Mansdorf, J. Bakan, J. Montemarano, G. Janes, and me) who maybe accidentally found ourselves in the field of controlled release of active substances. We decided to run a symposium entitled the “International Controlled Release of Bioactive Materials Symposium.” The first symposium took place in 1974 at the University of Akron in Ohio, and it was a spectacular success. There were some 30 presentations and about 70 attendees. There was no money to operate, and the symposium was run out of the office of the Symposium Chair, with his secretary being the most important and hardest working CRS person. As a matter of fact, this continued for several years after CRS was established. We had a great number of annual meetings at the Baja Mar Hotel in Fort Lauderdale, Florida, and always in August because everything was on sale. Credit for this great innovation should be given to George Janes, who was the Arrangements Chairperson for many years. The symposium attendees reached the magic number of 100 during the fourth symposium in Corvallis, Oregon. The symposium until 1982 (320 attendees, 79 presentations) was all-inclusive, but less than 20% of the presentations and participants were in the field of drug delivery. In 1984 Joe Robinson, Bill Higuchi, Nick Peppas, and Daniel Vitaver (president of Riccar Labs, Argentina) joined the board (Linda Sanders of Syntex was also installed as CRS vice president), and CRS started to take its present trajectory.
Q What is your advice to the younger generations of aspiring scientists, managers, and entrepreneurs to achieve success in industry and academia?
A This is a difficult question, because every one of us has a different understanding of what success might be. Some suggestions might be 1) don’t be afraid of failure, because in the dust of failure resides the seed of success, and 2) consider that a job is nothing more than the continuation of your education. If the job becomes easy and routine, look for a promotion or a position with another company at a higher level of responsibility. To remain relevant, your career must be a continuous learning experience. Keep on learning new medical applications and technologies through course work or through job training.
Q Please tell us about your hobbies and your civic involvement. How have these interests helped in your personal development?
Oil painting of Hunter’s Farm in Lambertville, NJ.A Other than exercising, which I do religiously to keep fit, I have two major hobbies. My wife and I are avid collectors of Chinese art. Over the last 40 years we have acquired over 500 Chinese pieces of art all the way from the Neolithic era (4000 BC) to the Shang Dynasty (2000 BC) to the Chin Dynasty (1900 AD). Recently, my son said, “Hey, Dad, your home looks like a Chinese warehouse!”
My greatest love, however, is oil painting, mainly open-air painting in Bucks County, Pennsylvania, and in the nearby New Hope and Lambertville, New Jersey, areas. I also paint still lifes in the Impressionistic style.
In the spirit of giving back to the greater society, I recently started and funded a tax-exempt foundation, “The Kydonieus Family Samos Foundation,” which provides scholarships to students of Greek descent who attend or are interested in attending the University of Florida to study chemical engineering or the sciences.
These hobbies allow me to relax and see the beauty of nature and the greatness of the human spirit through the ages. I get equal enjoyment executing a great painting, getting a novel technological idea, or securing a great piece of art.
