Translating naturally evolved, bacteria-host pharmacological interactions into rationally selected, live biotherapeutics

Emerging insights into the pivotal role played by the gut microbiota in shaping our physiology and metabolism in health and disease have inspired a new class of therapeutics. Assembly Bio is a clinical-stage leader in the discovery and development of oral live microbial biotherapeutic products (LBPs) where the naturally evolved functions of gut bacteria are being harnessed to deliver clinical benefit in a wide variety of therapeutic areas.

Our rationally selected microbial consortia are intended to target a wide range of diseases that are modulated by gut microbe-mediated pharmacological and biological mechanisms and have wide-ranging systemic effects.

From concept to clinic:
integrated therapeutic discovery & development capabilities

Rationally selected live microbial biotherapeutic consortia

Assembly Bio has built a rich and diverse library of bacterial strains isolated from carefully screened healthy human subjects. Our research platform enables rapid identification and evaluation of clonal bacterial strains, using human cell-based functional assays and animal models that reflect immunological and cellular mechanisms fundamental to health and disease. Assembly selects the most promising bacteria with demonstrated intrinsic pharmacological, immunological and cell biological functions, based on the evolved interplay between microbe and host.

Each selected strain undergoes further detailed genetic and physiological evaluation to support functional characterization, downstream development and regulatory filing. Rationally selected therapeutic consortia are assembled, in which each microbe has been specifically chosen based on its in vitro and in vivo functions and ability to modulate disease biology. Our oral therapeutic strategy relies on functional engagement of consortium microbes with the gut microbe-host environment, rather than a microbiota repopulation approach. Our lead programs leverage naturally evolved bacterial mechanisms rather than genetic engineering of host strains for desired therapeutic functions.

Reliable development and scalable GMP manufacturing

Once isolated and selected, each pure bacterial strain is manufactured under reliable and scalable cGMP conditions. The bacterial strains are produced as individual drug substances in the form of viable dried materials (lyophilized). Multiple drug substance lots of individual bacteria comprising the consortium are then blended and encapsulated as drug products. Our in-house CMC/manufacturing team is expert at turning live microbial biotherapeutics into drugs for oral administration.

Assembly Bio has developed extensive development and manufacturing experience with a wide range of anaerobic bacteria, which can be applicable to the development of any type of bacteria. Our manufacturing expertise delivers lyophilized vegetative bacteria, plus prebiotics as needed, which are subsequently formulated for encapsulation. Importantly, our internal analytical development and quality control groups support the entire manufacturing process.

Gemicel® targeted drug delivery

The viable vegetative bacteria of each rationally assembled LBP consortium are formulated and encapsulated in our proprietary Gemicel® Targeted Oral Delivery System (ODS)—a novel dual-release technology ensuring region specific delivery of active drug within the gastrointestinal (GI) tract. The unique Gemicel capsule-in-capsule design helps maximize clinical utility through the release of drug into two separate, pre-designated regions of the GI tract, by taking advantage of variations in gut pH.

To learn more about the Gemicel Target Delivery System, please watch the accompanying short video and read more details below.

Overcoming challenges of targeted drug delivery to the GI tract

Each Gemicel® capsule is engineered with specialized polymeric coatings to facilitate drug release into two separate targeted regions of the GI tract. Gemicel technology makes it possible to use a single capsule to deliver identical or two different doses of a particular drug or combination of drugs, or to deliver two separate drugs into two pre-specified locations within the GI tract.

Assembly Bio has completed a clinical study of Gemicel ODS in human subjects which demonstrated the delivery of therapeutic boluses into two specific locations within the GI tract: (1) the distal ileum; and (2) proximal colon. The study used radioisotope-based scintigraphy to precisely image the drug delivery properties of Gemicel ODS. Such targeted delivery to two separate locations of the lower GI tract carries therapeutic advantage across several disease states.

A promising array of candidates to address a range of important medical conditions

Our therapeutic strategy and drug discovery & development platform offer great breadth and depth of opportunity—starting with live biotherapeutic candidates for Ulcerative colitis, Crohn’s disease, and Irritable Bowel Syndrome (each in partnership with Allergan).

We are also investigating other microbial consortia for clinical applications that reach beyond gastroenterology including oncology and immune-mediated and metabolic diseases.

In the clinic with first live biotherapeutic for Ulcerative colitis (UC)

Assembly Bio's first clinical trial of its lead investigational LBP candidate, ABI-M201, is ongoing in patients with mildly to moderately active UC. ABI-M201 is comprised of a defined consortium of gut commensal bacterial strains, specifically selected based on their functional attributes to target key aspects of disease biology.

This program serves as an endorsement of comprehensive capabilities to discover and manufacture high quality, rationally selected live biotherapeutic products —from clonal strain isolation & selection to CMC drug manufacture through targeted oral delivery via its proprietary Gemicel® capsule-in-capsule technology.