Microbiome Report for Week Ending 10/6/18

Rebiotix Clinical, Microbiome Data From First-In-Class Microbiota Restoration Therapy to Be Presented at IDWeek 2018

Rebiotix Inc., part of the Ferring Pharmaceuticals Group, announced on 10/1/18 that data new from their Microbiota Restoration Therapy (MRT) drug development platform will be presented at the annual Infectious Disease conference, which will be held October 3-7 in San Francisco.

Each data set highlights the company’s continued leadership in the microbiome field, providing new insight into the durability of RBX2660 months after use as treatment in their recent Open-Label trial, to be presented by Rebiotix’s Associate Director of Clinical Research, Sarah Mische, PhD. Additionally, the company will share findings from the novel application of their Microbiome Health Index™, which has been developed as platform to quantify changes in patient microbiome profiles; Rebiotix’s Chief Scientific Officer, Ken Blount, PhD, will present the latest developments.

The titles of the presentations are:

Prevention of Recurrent Clostridium difficile at Six Months following Treatment with Microbiota-based Therapy RBX2660: Durability Results from a Phase 2 Open-Label Study

Evaluating a Prototype Microbiome Health Index (MHI) as a Measure of Microbiome Restoration Using Data Derived from a Published Study of Fecal Microbiota Transplant (FMT) to Treat Recurrent Clostridium difficile Infections (rCDI)

RBX2660  is derived from human stool and includes spore and non-spore-forming microbes and is administered via ready-to-use enema. It has received FDA Fast Track, Breakthrough Therapy and Orphan Drug Designations

LNC Therapeutics Launches New Obesity Clinical Trial with Stablor
Announced on 10/1/18 the launch of a new clinical trial with Stablor, OBEMINALE 2, and the treatment of the first patient. This new clinical study is intended to obtain 13.5 health claim from the European Food Safety Authority, EFSA. The final results are expected in the fourth quarter of 2019.

Stablor is a medical nutrition product that addresses a major public health issue, obesity. Its composition, protected by international patents, combines specific fractions of milk proteins with selected amino acids. What is unique about Stablor® is its ability to target the metabolic and nutritional disorders linked to obesity.

A first clinical trial, OBEMINALE 1, completed by LNC, has demonstrated the clinical efficacy of Stablor on visceral fat loss and cardio metabolic risk factors in obese patients with a metabolic syndrome. The trial also highlighted the ability of Stablor to modulate gut microbiome and more specifically, a family of bacteria known for its anti-obesity potential.

In March of 2017 the EFSA (European Food Safety Authority) rejected LNC's bid to gain an approved health claim for Stablor. The agency rejected 3 of 4 studies for a lack of controls.

Seres Therapeutics to Present New Data Supporting SER-109 Clinical Activity at IDWeek 2018
Seres Therapeutics, Inc. (Nasdaq:MCRB) today announced it will present new data for SER-109, a microbiome candidate in Phase 3 development, at the IDWeek 2018 conference being held from October 3-7 in San Francisco, CA. The findings, highlighted in two presentations, provide support for SER-109 as a potential new treatment option for individuals suffering from recurrent C. difficile infection. The company will also host a symposium on the development on novel microbiome therapeutics for C. difficile infection.

“These additional SER-109 data provide valuable information about the potential mechanism of action of microbiome therapeutics, an emerging new field of medicine. Our results provide additional evidence supporting the continued development of SER-109 in patients with recurrent C. difficile infection. In addition, these new data suggest that SER-109 may have important broader public health benefits by reducing the spread of antibiotic resistance,” said Matthew Henn, Ph.D., Executive Vice President, Microbiome Research and Development at Seres Therapeutics.

Synlogic Appoints Industry Vet Aoife Brennan MD as President and Chief Executive Officer
Synlogic, Inc. (Nasdaq: SYBX) announced on 10/2/18 the appointment of Aoife Brennan, M.B., B.Ch., as president and chief executive officer of Synlogic, effective immediately. Dr. Brennan joined Synlogic as chief medical officer in 2016 and has served as interim president and chief executive officer since May 2018.

“After conducting a thorough search process, it was clear to the board of directors that Aoife is the right person to lead Synlogic at this time in the company’s evolution,” said Peter Barrett, chairman of Synlogic’s board of directors. “Aoife stepped into the interim role and rapidly demonstrated her effectiveness. Her broad experience across multiple stages of drug development and therapeutic areas, her demonstrated leadership abilities, and her ambitious vision for Synlogic, make her uniquely qualified for the job. We are confident that under her leadership, Synlogic will be well-positioned to deliver Synthetic Biotic medicines to patients.”

Prior to joining Synlogic, Dr. Brennan spent six years at Biogen in roles of increasing responsibility, most recently as vice president and head of the Rare Disease Innovation Unit, which included programs ranging from pre-clinical to commercial. She has also led programs across multiple therapeutic areas including the late-phase development of nusinersen for spinal muscular atrophy and treatments for Hemophilia B and Hemophilia A, ALPROLIX® and Eloctate. Earlier, Dr. Brennan was director of clinical development at Tolerx, a start-up biotech company focused on immunotherapy for Type 1 diabetes. Dr. Brennan holds a medical degree from Trinity College Dublin, Ireland and completed her post-graduate training in internal medicine, endocrinology and metabolism at the Royal College of Physicians in Ireland.

Vedanta Biosciences Announces Successful Ph I a/b Data  for Lead Microbiome Consortia Candidate, VE303
Vedanta Biosciences announced on 10/4/18 preliminary results from the Phase 1a/1b clinical study in healthy volunteers for its lead, orally-administered live biotherapeutic product (LBP) candidate for recurrent Clostridium difficile infection (rCDI), VE303. With these Phase 1 data to support dosage selection, Vedanta Biosciences expects to begin a Phase 2 study before the end of the year to evaluate the safety and efficacy of VE303 in patients with rCDI. Additional exploration of VE303 in healthy volunteers to inform dose selection in other indications is ongoing.

Summary of Key Findings:
1. Single and multiple doses of VE303, after vancomycin administration, ranging up to 1.1 x 1011 total colony forming units (CFU), were safe and well-tolerated. Adverse events related to VE303 administration occurred in less than one third of study volunteers and all were Grade 1.
2. Abundant colonization of VE303 strains that lasted for at least 12 weeks was detected at all doses.
3. Repeated dosing led to increased robustness of strain colonization (i.e., a majority of VE303 strains colonized in a majority of volunteers).
4. VE303 accelerated microbiota recovery after vancomycin administration in a dose-dependent manner compared to recovery without VE303, demonstrating proof of mechanism.

Unlike single strain approaches to microbiome modulation, Vedanta Biosciences is developing consortia of bacterial strains designed to effect robust and durable therapeutic changes in a patient's gut microbiota. Unlike fecal transplants or administration of fecal fractions, Vedanta Biosciences' consortia are defined compositions of bacteria manufactured from pure, clonal cell banks, bypassing the need to rely on direct sourcing of fecal donor material of inconsistent composition. VE303 is the first product candidate, to the Company's knowledge, consisting of a rationally-defined bacterial consortium in lyophilized powder form to be clinically investigated.

VE303 is an orally-administered investigational live biotherapeutic product (LBP). It is produced from pure, clonal bacterial cell banks, which yield a standardized drug product in powdered form and bypasses the need to rely on direct sourcing of fecal donor material of inconsistent composition. VE303 consists of a defined consortium of live bacteria designed to restore colonization resistance against gut pathogens, including C. difficile. In 2017, Vedanta Biosciences received a $5.4 million research grant from CARB-X (Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) to support clinical studies of VE303. VE303 was granted Orphan Drug Designation in 2017 by the United States Food and Drug Administration (FDA) for the prevention of recurrent C. difficile infection (rCDI).