Microbiome Report for Week Ending 5/4/19

May 10, 2019

Axial Biotherapeutics Presents New Preclinical Data from AB-2004 Program Demonstrating Reduction of Microbiome-Derived Metabolites in Autism Mouse Models
Axial Biotherapeutics, a biotechnology company dedicated to building a unique class of gut-targeted programs for neurodegenerative diseases and neurodevelopmental disorders, announced on 5/2/19 that it presented new preclinical data on AB-2004 on, its orally administered, drug candidate that has demonstrated the ability to repair leaky gut and improve repetitive behavior, anxiety, and ASD-related sensorimotor gating deficits by removing key microbial metabolites in animal models with Autism Spectrum Disorder (ASD). The Company presented the data in a poster presentation at the International Society for Autism Research (INSAR) 2019 Annual Meeting in Montreal, Canada.

“We are pleased to present additional preclinical data which substantiates the potential of our platform to remove microbial based metabolites, by which we can restore gastrointestinal (GI) function and improve behavior associated with CNS and gut-derived diseases,” said David H. Donabedian, Ph.D., Co-founder and CEO of Axial Biotherapeutics. “We believe that altered microbial metabolite profiles can drive ASD symptoms, including behavior abnormalities, leaky gut and other GI issues. We believe that AB-2004 has the potential to alter these symptoms and we look forward to continuing patient screening for our Phase 1b/2a program and progressing this product further into the clinic.”

The main highlights from the poster presentation titled, “Characterization of GI barrier integrity and gut microbiome-derived metabolites in BTBR, Shank3 and Cntnap2 mouse models of ASD and demonstration of AB-2004 as a potential mitigating therapeutic” include:

  • The Cntnap2-/- mouse model accurately recapitulated the leaky gut phenotype and elevated levels of the gut microbiome-derived metabolite 4-EPS that have been reported in ASD patients
  • Treatment with AB-2004 effectively restored GI integrity and reduced elevated 4-EPS levels in Cntnap2-/- mice
  • The Cntnap2-/- model has been identified as a promising and translationally relevant animal model for the development of microbiome-inspired therapies for the effective treatment of GI and behavioral dysfunctions in ASD

These data support the development of AB-2004 as a treatment for GI dysfunction in ASD and potentially behavioral symptoms through reduction of pathologically active microbiome-derived metabolitesAxial is currently screening ASD adolescents for its Phase 1b/2a clinical trial of AB-2004.

Synlogic Presents Data Describing a Solid Oral Formulation for Synthetic Biotic Medicine for the Treatment of PKU
Synlogic, Inc., (Nasdaq: SYBX) a clinical stage company applying synthetic biology to beneficial microbes to develop novel, living medicines, announced on 4/30/19 that data demonstrating its development of a robust and reproducible process to generate a solid oral formulation of its Synthetic Bioticmedicine, SYNB1618, are being presented today at the 22nd Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT). Synlogic is developing SYNB1618 for the treatment of phenylketonuria (PKU).

“We have developed a process to generate a solid formulation of SYNB1618 for oral use that makes it more patient-friendly and provides a stability profile suitable for eventual commercialization,” said Antoine Awad, Synlogic’s head of technical operations. “The data presented at the ASGCT meeting demonstrate that we can generate a solid preparation of SYNB1618 with minimal impact on cell viability and activity and improved quality attributes compared to the liquid formulation that is being used in our ongoing clinical trial. We plan to apply our solid formulation expertise across our pipeline products.”

Synlogic’s Synthetic Biotic platform leverages the tools and principles of synthetic biology to engineer a strain of probiotic bacteria (E. coli Nissle) to perform or deliver specific functions lost or damaged due to disease. SYNB1618 is designed to metabolize Phe and was engineered by inserting specific genetic circuits including a bacterial gene that encodes phenylalanine ammonia lyase (PAL). PAL is an enzyme that breaks down Phe to generate trans-cinnamic acid (TCA), which is converted to hippuric acid (HA) in the liver and excreted in urine. Thus, plasma TCA and urinary HA levels can serve as biomarkers of PAL and, therefore, of SYNB1618 activity in vivo.

As described in the ASGCT presentation, Synlogic’s scientists have successfully developed a process that demonstrates:
batch to batch reproducibility in cell viability and activity at the 30L production scale
improved physical quality attributes of the product; and
a solid formulation that:
is similarly active to frozen liquid in terms of consumption of Phe or production of TCA/HA in an in vitro gut simulation model and in vivo in non-human primates and a mouse model of disease
in initial studies is stable for >90 days at 2-8◦C and >30 days at room temperature (Synlogic intends to generate shelf-life data over two years).

As a solid oral formulation with improved stability and convenience SYNB1618 has potential as a new therapy for managing blood Phe levels in patients with PKU.

Assembly Biosciences Announces Changes to Senior Leadership Team
Assembly Biosciences, Inc. (NASDAQ: ASMB), a clinical-stage biotechnology company developing innovative therapeutics targeting hepatitis B virus (HBV) and diseases associated with the microbiome, announced on 5/2/19 the appointment of David R. Houck, Ph.D., as Senior Vice President Product Development and Portfolio Management, and the departure of Graham Cooper, Chief Financial Officer and Chief Operating Officer.

“As Assembly’s pipeline of novel core inhibitors for HBV and rationally-designed live biotherapeutics from the microbiome platform continue to mature, we are delighted to welcome David to the Company. His decades of experience in pharmaceutical development will provide important insight over the coming years,” said Derek Small, President and Chief Executive Officer of Assembly. “With the additions of David and Steve Knox, our recently announced Senior Vice President of Clinical Development, we continue to strengthen our leadership team with experienced drug developers who have the necessary skills to advance our clinical candidates for patients.”

Dr. Houck has more than 35 years of experience in the pharmaceutical and biotechnology industries, from drug discovery through submission of Investigational New Drug applications and New Drug Applications for both small molecules and biologics, with particular experience in anti-infective agents including Hepatitis C virus and HIV. Throughout his career, Dr. Houck has been responsible for product development, including nonclinical development, manufacturing and quality control. Additionally, he has had extensive interaction with various regulatory agencies, including the U.S. Food and Drug Administration and the European Medicines Agency. Prior to Assembly, Dr. Houck was Chief Development Officer at Aptinyx, and before that was Vice President of Drug Development and Quality at Naurex. Previously, Dr. Houck served as Chief Executive Officer at Pharmakey LLC, a provider of regulatory, chemistry, manufacturing and controls (CMC), nonclinical, and translational medicine services to biopharmaceutical companies. Earlier in his career, he held senior positions at Merck & Co., Sterling Winthrop, Sanofi, OSI Pharmaceuticals, and SCYNEXIS. Dr. Houck received a B.S. from Alma College, an M.S. from Purdue University, a Ph.D. in chemistry from Ohio State University, and served as a postdoctoral fellow at the Los Alamos National Laboratory.

The Company also announced that Graham Cooper is leaving to pursue other interests. The Company has initiated a search for a new Chief Financial Officer, and Michael Samar, Assembly’s Vice President Finance and Business Operations, has been appointed to serve as principal accounting officer and has assumed certain of Mr. Cooper’s responsibilities.

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