How creative chemistry and collaboration synthesized a better drug strategy for Enterin

At Pfizer CentreOne, we are excited to collaborate with pioneering companies in navigating the drug development journey to bring their breakthroughs to market and patients.  Biotech company, Enterin, is one such innovator. Their mission is to become the first company in the world to develop a drug that repairs the dysfunctional gut-brain axis in patients with neurodegenerative disease.

Enterin is reshaping the understanding of the link between dysfunction of the enteric nervous system (ENS) of the gut and the early onset and chronic progression of neurodegenerative diseases such as Parkinson’s Disease. Enterin’s relationship with Pfizer CentreOne is an example of what a trusting and open collaboration with an experienced partner can accomplish.

Finding a Partner You Can Trust

Putting the life of your company and several years of work into the hands of a CDMO partner is a big decision. Biotech companies like Enterin need a trusted partner with the capabilities and expertise to deliver their molecules to patients and a strong commitment to protecting intellectual property and confidential processes.

Enterin completed the first human clinical trials for ENT-01 which demonstrated that oral administration of its treatment has restored function of the nervous system of the gastrointestinal tract in Parkinson’s patients.[i]

Enterin had specific requirements that made it even more important to choose the right CDMO. A key ingredient in ENT-01 is squalamine, which comes from an unusual class of steroidal molecules that are very complex and challenging to handle. Pfizer’s specialists’ knowledge of this kind of chemistry meant that it was the ideal partner for the job.

Dr. Michael Zasloff, Enterin’s CSO and founder, said, “The Pfizer CentreOne team is an extraordinarily creative and well-integrated group of people who know what they are talking about. To accompany this expertise, it was important to have access to the right facilities. Pfizer’s Kalamazoo site is the finest manufacturer of steroidal, cholesterol-based molecules in the world. Since squalamine’s synthesis originates from steroidal chemistry, the Pfizer CentreOne Kalamazoo site and local team were a perfect fit.”

Tackling challenges

Pfizer CentreOne supported Enterin at every step in the synthesis of ENT-01; from providing the initial starting intermediate through refinement of the steps, leading to the API. Whenever challenges appeared with the manufacture of the API, the team came up with creative solutions that showcased Pfizer CentreOne’s science and capabilities.

For example, the process that was originally used to create the polyamine tailpiece of the molecule, a vital component, was highly explosive. A new method was needed that was safe and suitable for scale-up.

The team at Pfizer CentreOne looked at the whole synthesis and completely revised how to create and attach the tailpiece, optimizing safety and successfully scaling up production. As a result of this innovative approach, Pfizer CentreOne already has enough of the material stored on site for when ENT-01 enters Phase III of development.

More than just manufacturing

The team at Pfizer CentreOne brought value to Enterin’s business through its expertise and creativity. Many CDMOs can replicate an existing process but discovering a novel approach and collaborating with partners is where the team delivered.

Speaking about the future of the relationship, Dr. Zasloff commented: “As ENT-01 is shown to be safe and effective, we will need to scale up production quickly. We are trusting Pfizer CentreOne to manufacture hundreds of metric tons from the small quantities we have made thus far.

This scale up is essential to reach patients around the world. Ultimately, Pfizer CentreOne will be responsible for the commercial manufacturing [launch] of the new drug, which we hope will represent a major new addition to treatment of neurological diseases.”

Building and maintaining the kind of relationship Pfizer CentreOne has with Enterin was essential to the success of ENT-01’sl drug development journey. If one thing the relationship has proven is that when both parties combine their knowledge with creative problem-solving and mutual respect it can accelerate project timelines fuel long-term market and patient success.


[i]  Targeting neurons in the gastrointestinal tract to treat Parkinson's disease, Clinical Parkinsonism & Related Disorders, International Association of Parkinsonism and Related Disorders (IAPRD)