Xylome Corporation: Pioneering Novel Drug Delivery Solutions

You are currently viewing Xylome Corporation: Pioneering Novel Drug Delivery Solutions
Tom Kelleher, Ph.D.

Xylome Corporation, a privately held C-corporation in Madison, Wisconsin, is driven by decades of expertise from two senior scientists: Tom Kelleher, Ph.D., CEO, and Tom Jeffries, Ph.D., President, who have known each other for 40 years, since their graduate school years at Rutgers. Focused on innovative drug delivery solutions like TopicOil™, Xylome harnesses non-conventional yeasts to revolutionize hydrophobic drug delivery systems.

Let’s delve into the interview details!

What inspired you to focus on innovative drug delivery solutions, and how did you get started in this field?

There are only 5 conventional industrial yeasts of economic significance. Xylome was founded with a mission to develop sustainable and innovative products using precision fermentations from the largely unexplored genomic and metabolic world of the other 1500 non-conventional yeasts.

Tom Kelleher’s industrial career, at Novo Nordisk, Cubist and Amgen, focused on delivering manufacturing processes for new classes of biologics to FDA for both clinical studies and final drug approvals. At Xylome, it was a natural transition to seek innovative biopharmaceutical products from the exploration of non-conventional yeasts.

Tom Jeffries’ academic career at the USDA and as a Professor Emeritus at the University of Wisconsin in Madison focused on the genomics of potentially useful nonconventional yeast. Jeffries’ insights were critical for selecting Xylome’s platform yeasts for the development of TopicOil™, Xylome’s drug delivery system.

The blend of industrial and academic talents resulted in an extraordinary team of scientists and engineers led by Dr. Joanna Bundus at our Madison laboratories, who have been working on scale-up, efficacy studies, Regulatory documentation, GMP/GLP manufacturing/analytical quality control and disposition of available inventory for Xylome’s drug delivery system.

What challenges do you face in the development and implementation of new drug delivery technologies?

Awareness and technical understanding of a very simple aqueous-feeling oil have emerged as a challenge to the initial adoption of TopicOil™. Surprisingly, is a difficult concept for seasoned formulation chemists to understand and accept the concept of a single-ingredient moisturizer in water that is composed solely of TopicOil™’s biological lipid bodies, which contain 87% oil. Currently, most oil-based formulations utilize emulsifying agents, surfactants and often 15-20 other ingredients to obtain a high-oil and high-hydrophobic drug content moisturizer.

Several decades ago, liposomes permitted the advancement of hydrophobic drugs with formulations that were less toxic. However, since the introduction of liposomes in the late 1970’s and hydrophobic liposomes in the 1990’s, there has been few innovations in the field of large entity carriers for hydrophobic drugs. The volume to surface ratio issue for drug delivery becomes even less useful when newer nanoparticle technologies are used for hydrophobic drug delivery. The large lipid bodies that comprise TopicOil™ open new possibilities for the delivery of high concentration hydrophobic drugs.

The lipidomics and proteomics of TopicOil™’s lipid bodies were conducted at the University of Wisconsin Bioanalytical Center and the findings can be shared under a confidentiality disclosure with Regulatory groups from pharmaceutical companies. Xylome has also reviewed medical and allergenicity databases for other important Regulatory information.

How do you ensure that your solutions meet regulatory standards and patient safety requirements?

Xylome is focused on topical administration of new classes of hydrophobic drugs for unmet medical needs, which can be addressed by a high-capacity delivery system. In the future, additional Regulatory applications will be prepared for oral and parenteral administration. However, Xylome’s initial focus is topical drugs, which minimize the number of Regulatory hurdles for our first drug programs. As expected, Xylome is adhering to or exceeding the current FDA guidelines for topical drugs and building the background requirements of full pharmaceutical GMPs with our Regulated contract manufacturing organizations. Finally, Xylome is utilizing the validated analytical services of a well-recognized GLP service lab for the disposition of TopicOil™.

On the patient safety side, Xylome has concluded an open-label human exposure study of our lipid body cream that had 579 human skin exposures on the face and hands of volunteer women between the ages of 28 and 65 over a 30-day period with an average exposure total of 27.5 exposures per subject. In the human exposure evaluation, there were no adverse events, and the exposure study supported the benign nature of the large (10-micron) lipid body, when used as a base moisturizer for hydrophobic loading. For pharmaceutical companies, who are developing specific drugs in TopicOil™, then human exposure studies will have to be repeated for each drug, but the patient safety of TopicOil™ has been preliminarily addressed by Xylome.

In your opinion, what trends are currently shaping the future of drug delivery systems?

Xylome recognizes that many on-market hydrophobic drugs have or will become generic. Under the scope of Xylome’s drug delivery intellectual property, we are working to create prototype TopicOil™ based formulations, which could open new applications and treatments for patients. Prototype formulations, assembled by Xylome, offer manufacturers an opportunity to monetize new applications, new strengths and new patient administration formats that have not existed previously.

The IP covered proprietary effort by Xylome is striving to meet market interests in new prototypes for generic and for new classes of drugs. TopicOil™ can provide high loading and low-ingredient number of TopicOil™ based products. Additionally, other benefits and properties of TopicOil™ such as being steam sterilizable, freezable and skin-barrier forming properties that can be used for the creation of innovative patient treatments, which are not easily achieved by liposomes or emulsions.

What advice would you give to startups looking to enter the drug delivery space?

For startups, it is Xylome’s experience that spending the years of technology development required for organizational depth and assembly of a proprietary toolbox is essential for bringing innovative products to pharmaceutical formulators and the drug delivery market. Xylome’s core competency is genetics and the development of the full range of genetic tools, transformation systems, and selection techniques in concert with a multidisciplinary approach to downstream processing are all requirements for successful development of new drug delivery systems.

Funding is critical and maximizing the amount of non-dilutive funding is essential. The consequence of avoiding debt and avoiding early irrational venture funding can be significant because accepting these latter funds can cause a difficult outcome for a startup. On the other hand, avoiding debt and maximizing non-dilutive funds/contracts will result in a more methodical corporate development. Unrealistic timeframes under the pressure from investors can undermine the flexibility to move to the best solutions as opposed to the fastest, often flawed, solutions.

Looking ahead, what are your goals for your company in the next few years regarding drug delivery innovations?

Xylome’s goal is to continue as a technology provider in the development of new classes of important hydrophobic drugs, which will be co-developed with the original academic scientists and inventors. The innovations in drug delivery will include topical, oral, and parenteral formats. These goals will be facilitated by Xylome’s growing Regulatory infrastructure. The company’s growth objective is to increase the utilization of TopicOil™ by drug formulators from the respective manufacturers of existing drugs. Using that same infrastructure, Xylome will create advantaged, generic-drug prototypes so that our customers can produce better therapies for patients.

Revolutionizing Hydrophobic Drug Delivery with TopicOil™

Xylome’s innovative product for drug delivery is TopicOil™. The scale-up and GMP production of TopicOil™’s patent pending, large, purified lipid bodies represent a significant step forward in improving the delivery of hydrophobic drugs. Xylome now has significant inventory and availability of this new drug delivery material for evaluation by pharmaceutical drug formulation scientists.

TopicOil™’s patent-pending large, purified lipid bodies do not occur in nature, but these structures are the result of genetic overexpression of native genes for lipid production in Xylome’s platform yeast. The naturally assembled lipid bodies have an internal oil content of neutral triglyceride oil that represents ~87% of the lipid bodies’ volume. That internal oil is a structured white palm-oil replacement, which feels like any other nice hand or facial moisturizer. However, TopicOil™ is a single ingredient in water, which is a novel entity for emulsifier-free, non-oily hydrophobic drug delivery, and a new paradigm in minimal-ingredient technology.

More importantly, TopicOil™’s large, purified lipid bodies have a significant volume-based physical advantage over liposomes, simply because of the size difference, with liposomes generally being only 30-100 nanometers in diameter, while TopicOil™’s large lipid bodies being about 10,000 nanometers in diameter. This is a 5-log difference in hydrophobic volume and a 10 to12-fold volumetric enhancement in carrying capacity for hydrophobic drugs, relative to liposomes. The large hydrophobic volume to surface ratio permits an increased ability to carry more drug in an equivalent applied volume, when used in a topical setting.