Synlogic Pivots After First Clinical Failure
Executive Summary
The synthetic biotics company is discontinuing development of SNYB1020, its first clinical-stage product, which failed to lower blood ammonia in cirrhosis patients.
Synlogic Inc. is discontinuing development of its first clinical-stage asset, SYNB1020 for the treatment of hyperammonemia, after it failed to show a benefit in a Phase Ib/IIa study. The development is a disappointing one for the company, which has been pioneering the development of a new class of synthetic biotic medicines that work in the microbiome since it was established in 2014.
The Cambridge, Mass.-based company is pivoting to focus on advancing two other early clinical-stage programs instead: SYN1618 for the treatment of phenylketonuria (PKU) and SYNB1891 for solid tumors.
"The study was done in a very rigorous way and that enabled us to make a clear decision," CEO Aoife Brennan said in an interview. "Unfortunately, that decision was that while the preclinical data was very promising and the human data looked like we were going in the right direction, it just wasn't going to translate into a benefit for patients."
"We believe we have a lot of really interesting programs that do have potential to benefit patients and would prefer to focus our efforts there," she added.
The early data result for a clinical-stage asset in the microbiome space raises more questions about an area of drug development that has captured the industry's interest but hasn't delivered substantially. Synlogic's drug platform works differently from that of some other companies working in the microbiome space. Synlogic is focused genetically modifying microorganisms to manipulate the microbiome, while some other companies are developing small molecules that target the microbiome.
"We do not view this as indicative of the potential success of other microbiome-based therapeutics companies in this space given the unique and complex nature of the synthetic biotics platform, which genetically modifies bacteria to degrade harmful metabolites in the gut – a significantly different approach from other players," Jefferies analyst Chris Howerton said in a 20 August research note.
He also noted that despite the disappointing efficacy data with SYNB1020, there are still reasons to be optimistic about the '1618 program, given its different mechanism of action and positive results from a signal-finding Phase I/II trial in patients with PKU.
Synlogic's Brennan also said there is little overlap in the programs outside of safety. "What we have learned applies to this pathway and this indication, and there is no read through," she said.
In July, Synlogic announced positive top-line clinical data from a Phase I/IIa study of '1618, showing a statistically significant increase in biomarkers activity related to its ability to consumer phenylalanine. The full data from the study will be presented at the symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM) on 3-6 September.
The company is initiating a clinical trial now with a new solid oral dosage form of the drug; the initial study involved a liquid formulation.
The company is also collaborating with Roche to study SYNB1891, a non-pathogenic strain of E.coli engineered to express STING agonist and stimulate the innate immune system, in combination with Roche's PD-L1 checkpoint inhibitor Tecentriq (atezolizumab) in patients with advanced solid tumors. Synlogic expects to move forward with a monotherapy trial first before testing the combination.
Synlogic, spun out of research from the Massachusetts Institute of Technology, has focused initially on the development of synthetic biotics for rare genetic metabolic diseases, which it has viewed as a relatively straightforward path to market. (Also see "Synlogic Moves Synthetic Biotics To The Clinic For Rare Metabolic Disease" - Scrip, 30 Oct, 2017.) The company separately has a development deal with AbbVie to discover synthetic biotics for the larger but more complex area of inflammatory bowel disease. (Also see "Synlogic Links Up With AbbVie For IBD Microbiome Therapies" - Scrip, 10 Feb, 2016.) The partnership with AbbVie has continued to move forward, Brennan confirmed, but the company is not at liberty to disclose information about the targets that are being studied.
The company raised $29.4m in a Series A round in 2014, led by Atlas Venture and new Enterprise Associates, and went onto raise a total of $112m in three financing rounds. The company went public in 2017 through a reverse merger with Mirna Therapeutics Inc. in 2017. (Also see "Finance Watch: Two More US Biopharma IPOs And Two New European VC Funds" - Scrip, 20 May, 2017.) The company's stock has lost much of its value in the last two years. It opened on 28 August, 2017 at $10.30 following the completion of the reverse merger, but opened on 21 August at $3.19.
SYNB1020 was in development for the treatment of hyperammonemia in diseases like urea cycle disorders (UCD) and hepatic encephalopathy (HE). It is a synthetic biotic engineered to remove excess ammonia from the blood with the hope it would compensate for defects in patients with UCDs.
But data from an interim analysis of the randomized, double-blind, placebo-controlled Phase Ib/IIa trial in 23 patients with cirrhosis and elevated blood ammonia showed treatment did not result in blood ammonia lowering or changes in other exploratory endpoints relative to placebo.
The company had cash and equivalents of $149.1m as of 30 June, enough money to run the company into 2021, the firm has forecast. Brennan said Synlogic would be providing investors with updated financial guidance following the disappointing data read out.