Issue:June 2021

DRUG DEVELOPMENT EXECUTIVE - Enteris BioPharma: How to Build a Preferred CDMO Partner

Since its founding in 2013, Enteris BioPharma, a clinical-stage biopharmaceutical company based in Boonton, NJ, has grown into an important player in the drug development and delivery market by utilizing its proprietary drug delivery technologies, Peptelligence® and ProPermaTM, to develop and produce oral formulations of BCS class III and IV compounds, including peptides, peptidomimetics, and small molecules. These pioneering platforms hold the potential to radically alter treatment paradigms. Many of these drugs can only be administered parenterally due to poor oral bioavailability, which can limit market opportunities for the drug maker and reduce patient compliance with treatment regimens. In addition to its proprietary technology, Enteris is also investing heavily in its contract development and manufacturing capabilities, which have evolved into a key pillar of the company’s business strategy.

Recently, Enteris completed a major expansion project at its 32,000-sq-ft manufacturing facility, providing the company with the wherewithal to take clients from the laboratory bench through commercial launch. The unveiling of its new and improved CDMO operations marks a major milestone for Enteris and is no small accomplishment given that the company completed the construction despite the disruptions brought on by COVID-19. Drug Development & Delivery recently interviewed Dr. Paul Shields, Chief Operating Officer of Enteris BioPharma, to discuss the changing face of the CDMO industry and how Enteris plans to leverage its newly expanded CDMO operations to take advantage of a variety of growth opportunities to build deeper partnerships.

Q: What role does contract development and manufacturing play in Enteris’ business strategy?

A: I cannot overstate the importance of our CDMO operations to the future of Enteris. The backbone of our business has been partnering with pharmaceutical companies to use our core Peptelligence and ProPerma drug delivery technologies to design and advance oral tablet formulations of peptide or BCS class II, III, and IV small molecule products, and this has not changed. Yet the specific expertise needed to successfully develop and manufacture these oral formulations is every bit as valuable as the technology itself.

Contract manufacturing has been a key source of revenue for Enteris, yet we are only now about to begin to realize its full potential. Enteris recently announced the expansion of its Boonton, NJ, manufacturing facility and the launch of its CDMO business segment, providing custom solutions to the formulation, development, and manufacturing of solid oral doses for difficult-to-formulate BCS III and IV compounds, including peptides and highly potent compounds. Enteris now provides bench-to-market development services, including the development, manufacture, testing, and release of Phase 1 to Phase 3 clinical trial supplies, as well as commercial production. We believe this will bolster our strength as a development partner and play a key role in our ongoing business development efforts. To be sure, near- and medium-term licenses involving Peptelligence and ProPerma are expected to bring lucrative upfront, milestone and royalty payments. These partner programs, however, also have the potential to generate development and manufacturing revenue that will fuel future growth and enhance our value as a company.

Q: How does Enteris’ CDMO capabilities add to the company’s strength as a development partner?

A: The formulation, development, and manufacturing of oral, peptide-, and small molecule-based drugs is a tricky business and requires specific skills and expertise. Enteris provides total integrated CMC service support, including preformulation, formulation, analytical research and development, quality assurance, and clinical and commercial manufacturing of solid, oral dosage formulations while keeping our partners’ product vision the highest priority. As such, we are uniquely positioned within this niche with the capabilities and expertise to meet an array of development and manufacturing needs under a single roof, which can save our clients time and money.

The idea of a CDMO as a one-stop-shop has been a growing trend in the industry, and for good reason. When pharmaceutical companies work with multiple contract services organizations during the drug development and manufacturing process, it can cost them in terms of money, time, and risk. Projects can become difficult to manage, whereas if the majority of the work is handled in one place, information flow improves, and it alleviates concerns about time and risk mitigation. This can be especially important when transferring between late-stage clinical to commercial production. While some CDMOs have the capability to manufacture clinical trial materials up through Phase 1 or Phase 2, transferring a complex formulation to another CDMO can prove costly and time consuming. With our expanded CDMO capabilities, Enteris can remain a trusted and reliable manufacturer as client programs progress through each stage of drug development.

Q: What expertise do you bring to the table that differentiates Enteris from other CDMOs?

A: On the manufacturing side, we have considerable expertise in technologies to improve solubility and permeability, and we specialize in applying aqueous film coats at scale. We value and emphasize analytical development and validation. Our quality assurance and control systems are fully compliant with the FDA, EMA, and ICH. It is important to note that regardless of whether we are working with a solid oral dose developed using our Peptelligence or ProPerma technologies, or another formulation technology, Enteris can ensure optimal manufacturing of a client’s clinical and commercial supplies.

But CDMO is about more than manufacturing. We have an unparalleled team of industry-leading scientific subject matter experts in the areas of formulation, analytical research and development, quality control, quality assurance, and manufacturing. We apply a risk-based, phase-appropriate approach to cGMP analytical activities, such as specification setting, analytical method development, and analytical validation. What’s more, we have thorough experience with high-potency active pharmaceutical ingredients (HPAPIs), industry-leading expertise in enteric coatings, and extensive experience working at small batch sizes, sometimes fewer than 100 units, in instances where API supplies are limited due to cost, scarcity, or other factors.

Q: Why was it important for Enteris to invest in the expansion of its Boonton, NJ, manufacturing facilities?

A: Enteris is a growing company with a number of value-creating opportunities on the horizon. Following the acquisition of Enteris in 2019 by SWK Holdings Corporation (Nasdaq: SWKH), we initiated an aggressive business development and marketing program designed to identify and secure potential licensing opportunities with pharmaceutical companies seeking to develop orally delivered versions of their peptide and small molecule products. The expansion of our manufacturing capabilities goes hand in hand with those efforts, allowing us to pursue deeper manufacturing relationships with developmental clients.

Q: What capabilities do you have now that you did not have before?

A: Enteris now has the ability to provide bench-to-market development services, including the development, manufacture, testing, and release of Phase 1 to Phase 3 CTM. We also have the ability to handle production for commercial launch.

The renovated 32,000-sq-ft manufacturing facility includes 6,000 sq ft of cleanroom space with approximately 2,500 sq ft dedicated to the containment and processing of HPAPI. The facility also includes 1,700 sq ft of flexible suite space that can be adapted to a partner’s development and manufacturing needs.

Q: Enteris completed the expansion projects amid a global pandemic. What challenges did you have to overcome?

A: Delivering on a construction timetable amid the COVID-19 pandemic was no easy feat, and the team at Enteris is to be congratulated for meeting the challenge. There were hurdles along the way that we needed to work around, such as renovating one part of the facility while maintaining production capacity in another. Throughout the project, our team found creative solutions to address the specific challenge, which reflected the same ingenuity we bring to the production of pharmaceuticals.

Interestingly, there were some advantages to conducting a large-scale construction project during the lockdown in that with most of our employees working from home, there was little disruption to their activities as a result of the construction. The build-out could occur during the normal workday rather than scheduling heavy construction for off-hours or weekends.

Q: Speaking of COVID-19, the pandemic shined a light on the shortcomings of the global supply chain. How do you see it changing the CDMO industry?

A: The disruption caused by COVID-19 caused significant challenges with drug shortages and increased production costs. It made clear the need to reduce our industry’s reliance on overseas markets for key materials, as well as the actual manufacturing of medications prescribed to millions of Americans. Given this dynamic, we see more demand for US-based CDMOs with the ability to handle complex manufacturing needs for specialty pharmaceutical and biotechnology companies.

Q: What should a drug developer look for from a CDMO?

A: Obviously, much depends on the specifics of a project and the drug developer’s needs. Topping the list of criteria should be a proven track record with a history of quality focus and regulatory compliance, the company’s core competencies, and the breadth of the services it provides to clients. Does the CDMO provide bench-to-market development services, including the development, manufacture, testing, and release of all stages of CTM and commercial production? For complex drug products, drug makers should look for a partner skilled in highly specialized formulation, manufacturing, and process technology areas. And if your API is expensive, potent, or challenging to source, it will be important to find a CDMO with a proven ability to manufacture small scale batches.

Another issue to consider is the size of the CDMO and how your company might be prioritized. Understandably, companies that cater to larger drug makers often allocate more resources to those clients. It’s smart business. However, this can result in smaller drug makers and their projects falling through the cracks. We recognize there is a growing trend in the market in which small organizations and small and mid-size biotechnology companies are developing their assets to commercial launch. As a nimble and highly specialized CDMO, Enteris is very cognizant of their needs, and has the experience and abilities to ensure these companies receive our dedicated and bespoke service.

Q: Looking ahead, what do you see as the key opportunities for Enteris’ contract manufacturing operations over the next 12 months?

A: We see considerable opportunities in 2021, subject to any COVID-19 constraints, to leverage our newly enhanced manufacturing capabilities.

Under our CEO Rajiv Khosla, Enteris has increased the business development pipeline for the Peptelligence and ProPerma technologies. In addition, we will actively pursue new high-value relationships with companies seeking CDMO capabilities in the US, such as manufacture of CTM, formulation development, and analytical method development, including for HPAPIs, regardless of whether the product is a solid oral formulation using our proprietary oral formulation technologies or other tablet technology.