Issue:October 2020

EXECUTIVE INTERVIEW – Enteris BioPharma: Pioneers in Oral Formulation Development

Breaking down the barriers to oral delivery of peptides and small molecules is no easy task, but it holds the key to enhancing myriad drug products and treatment paradigms. Presently, many of these therapies can only be administered parenterally due to poor oral bioavailability or permeability, which can limit market opportunities for the drug maker and reduce patient compliance with treatment regimens. Enteris BioPharma, an emerging biotechnology company based in Boonton, NJ, offers a solution to these challenges.

Founded in 2013, Enteris has established itself as a pioneer in the oral peptide market, utilizing its proprietary drug delivery technology, Peptelligence®, and its manufacturing capabilities to develop and produce oral formulations of BCS class III and IV compounds, including peptides, peptidomimetics, and small molecules. Through Enteris’ own internal R&D program and external partnerships, Peptelligence is now the subject of several pre-clinical and clinical development programs. Drug Development & Delivery recently interviewed Dr. Rajiv Khosla, Chief Executive Officer of Enteris BioPharma, to discuss how Enteris’ innovative oral formulation technology is helping the pharmaceutical industry overcome the hurdle of low bioavailability to reshape treatment categories and expand market opportunities with minimal financial and regulatory risks.

Q: Dr. Khosla, you were appointed CEO of Enteris BioPharma in May. What drew you to the company?

A: From its founding in 2013, Enteris has established itself as a leader in the oral peptide market, yet I believe the company has only begun to realize its vast potential. The Peptelligence oral delivery technology is a potential game changer for pharmaceutical companies that offer the opportunity to not only enhance myriad drug candidates, but also reshape therapeutic categories and treatment paradigms in ways that can fill unmet medical needs and provide improved treatment options for patients. For the CEO of a specialty drug delivery company, that is quite an opportunity.

This is a growing company with a number of value-creating opportunities on the horizon. The acquisition of Enteris last year by SWK Holdings (Nasdaq: SWKH) provided a strong validation for Peptelligence and the company’s future prospects. With SWK’s commitment, Enteris now has a partner who shares our excitement for the technology’s potential and is willing to invest capital and other resources to advance the company’s internal and external development pipelines, bolster our management team, strengthen our business development activities, and fund a major expansion of our manufacturing capabilities.

Q: Enteris’ Peptelligence platform is designed to enable the oral delivery of peptides, peptidomimetics, and other BCS class III and IV molecules. Can you explain the significance of this capability and Enteris’ approach?

A: The oral delivery of peptides, peptidomimetics, and other BCS class III and IV molecules are often hampered by low bioavailability and permeability. As such, these drugs are typically administered by injection, which limits market penetration and patient compliance. Oral formulations, however, can improve patient adherence to drug regimens. Afterall, who would not choose to swallow a tablet rather than endure a painful injection. For drug makers, it can expand the market for newly discovered molecules and is an excellent lifecycle management strategy for commercial products nearing the end of their life cycles.

There are other advantages. Perhaps one of the most underappreciated is the reduced regulatory risk facing drug makers. The reformulation of an existing drug can open the door to the 505(b)(2) regulatory pathway through the U.S. FDA, which allows a drug maker to take advantage of existing safety data. This can reduce the financial cost of drug development and minimize the regulatory risk when compared to the costs and risks associated with the development of a new chemical entity (NCE).Yet, the value of the 505(b)(2) regulatory pathway, in my opinion, has not been fully explored by the broader biopharmaceutical industry.

Through our licensing agreements and partnerships with other drug makers, Peptelligence is now the subject of several active externally sponsored pre-clinical and clinical development programs. Among these programs is an oral formulation of Cara Therapeutics’ KORSUVATM, a potent peripheral kappa opioid receptor agonist with a primary focus for the treatment of pruritus associated with kidney failure, liver disease, and atopic dermatitis. Cara is currently advancing three oral KORSUVA clinical programs for these three distinct treatment indications. Enteris is also harnessing Peptelligence to develop its own internal clinical pipeline of orally delivered therapeutics that have been previously marketed as injectable-only formulations.

Q: The backbone of Enteris’ business is partnering with companies to design and advance oral tablet formulations of the partner company’s peptide or small molecule drug product. What sets Enteris apart from its rivals? What makes you the preferred partner for pharmaceutical companies?

A: There are many factors that set Enteris apart from our competitors, but these encapsulate what I believe are of greatest value to our current partners and prospective future partners: the strength of our technology and what it can accomplish, strong intellectual property protection, a collaborative approach with a focus on customization and our manufacturing expertise.

The Peptelligence oral formulation technology utilizes several patented oral bioavailability-enhancement techniques, using a variety of conventional pharmaceutical formulation methods and pharmaceutical excipients. We do not offer a single off-the-shelf technology but work with our partners to develop formulations that are specifically bespoke and optimized for their active pharmaceutical ingredient (API). We closely examine the characteristics of the API, the potential indications, the status of the development program, and the feasibility of oral delivery. It is typical for Enteris to provide three or more formulation prototypes to partners to demonstrate the feasibility of the Peptelligence oral formulation technology.

Peptelligence enhances bioavailability by solubilizing and improving the permeability of APIs across a wide range of molecular weights. The result: Peptelligence enables the oral bioavailability of APIs that previously had zero oral absorption or enhances by up to 11-fold APIs with poor bioavailability. Moreover, Peptelligence has been validated in more than 15 clinical trials and benefits from robust clinical and safety experience.

The Peptelligence pharmaceutical manufacturing process is a highly scalable and straight forward procedure that uses methods, such as dry blend and direct compression, to produce dosage forms that readily satisfy in-process controls and release testing. And finally, our partners benefit from robust intellectual property protection in the U.S. and internationally in key markets through 2036.

Q: Adding to Enteris’ strength as a development partner is the company’s manufacturing capabilities. What manufacturing expertise do you bring to the table that differentiates Enteris? Why is the expansion of Enteris’ manufacturing capabilities important to the company’s growth?

 A: The formulation, development, and manufacturing of oral, peptide-based drugs is a complex business and requires specific skills and expertise. Enteris is uniquely positioned with the capabilities and expertise to meet an array of manufacturing needs within this niche. We are especially proud of our established track record spanning over 23 years with a history of quality focus and regulatory compliance.

We are experts in handling and processing high-potency APIs. We have experience working with biopharmaceutical companies of all sizes. Our CDMO operations are housed in a growing 32,000-sq-ft facility in Boonton, NJ, with the capability to scale-up and cGMP manufacture optimized oral formulations to meet clinical trial needs from feasibility to Phase 2, and provide analytical development and stability testing, with a proven enteric-coated tablet formulation that is scalable and readily transferable.

An expansion project has been underway at our manufacturing facility. Completion is expected in the short-term and will enable us to manufacture Phase 3 clinical trial material (CTM), and commercial-level production. This will allow us to pursue deeper manufacturing relationships with developmental clients and allow us to remain a trusted and reliable manufacturer as client programs progress through each stage of drug development.

Q: Enteris is also advancing its own internal pipeline of oral peptide and small molecule therapeutics. What is the company’s strategy and what are your lead programs?

A: We believe that developing an internal pipeline that leverages the Peptelligence platform will enhance the value of the technology. Enteris has developed a strong regulatory strategy involving the use of the 505(b)(2) regulatory pathway. But our goal is not to become a commercial drug company, but rather to seek partnerships and out-licensing opportunities and use that capital to fund future growth.

Our most advanced clinical-stage drug candidate, Ovarest®, is a Phase 2b-ready oral formulation of the peptide leuprolide that we are developing for the treatment of orphan indications. It is followed by TobrateTM, an oral tablet formulation of tobramycin, now in Phase 1 development for the treatment of uncomplicated urinary tract infections (uUTIs).

These are attractive development opportunities. In the U.S., urinary tract infections affect approximately 10 million women annually. Leuprolide, on the other hand, is an effective and widely used therapy, but has significant limitations in both convenience and tolerability due to its depot injection delivery method.

Q: Looking ahead, what do you see as the key opportunities for Enteris over the next 6 to 12 months?

A: We entered 2020 with a great deal of momentum and continue to target multiple growth opportunities. To that end, we are excited about the ongoing expansion of our manufacturing facilities. Completion is expected in the short-term and will enable us to manufacture Phase 3 CTM and commercial-stage compounds.

Meanwhile, Enteris continues to pursue new external licensing and partnership opportunities for Peptelligence and advance its internal and partnered pipeline assets.

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