7:23 PM
Feb 28, 2019
 |  BC Innovations  |  Product R&D

Mapping microbiome manufacturing

Why making microbiome drugs will require reinventing bacterial manufacturing

Microbiome companies have been squeezed by the scarcity of contract manufacturers willing to work with tough bacterial strains. While contractors are starting to engage, it could take a big clinical win for them to fully take the plunge.

Manufacturing is one of the biggest bottlenecks faced by microbiome companies. Despite decades of experience growing bacteria to produce biologics, the biotech industry is ill-equipped to produce live bacterial therapies.

One reason is that manufacturers have historically had little concern for the state of the bacteria, so long as enough protein product is made.

“You don’t really care how fit the cells are, how many of them are dead or alive at the end of the process, it’s really just about yield from the protein perspective,” said Aoife Brennan, CEO and CMO of Synlogic Inc., which is using synthetic biology to engineer live microbial therapeutics.

The lack of manufacturing capacity is especially acute for companies developing intestinal microbiome strains, which represent the lion’s share of the field. This is because many gut microbes require low-oxygen culture conditions and produce hard-to-kill spores that readily contaminate other cultures.

“It’s a new class of therapeutics, no one’s really done it before,” said Duncan Peyton, CEO of 4D pharma plc., which is developing products based on single microbiome strains.

“I think manufacturers will move when they start to say, ‘there’s a real base of business there’.”

Wende Hutton, Canaan Partners

Some companies have responded to the challenge by building capabilities to manufacture in-house.

Others are waiting for more proof-of-concept data before investing in infrastructure, and are outsourcing to the few contract manufacturing organizations (CMOs) willing to accommodate live microbiome therapies.

Mark Smith, CEO of Finch Therapeutics Group Inc., said the short supply of CMOs that can handle gut microbes has created “long lead times and high prices,” though that is partly because the field is still in its infancy.

“Our expectation is that over time, the market is going to equilibrate, and there’ll be more supply. More CMOs are coming into the space now, and I expect that trend to continue,” said Smith.

Canaan Partners’ Wende Hutton believes a step change won’t come until the microbiome space sees a large pharma acquisition or drug approval. “I think manufacturers will move when they start to say, ‘there’s a real base of business there’.”

At least six Phase II or Phase III studies of live intestinal microbial therapeutics should start to read out top-line data by mid-2020 (see Table: “Bug Reports”).

In addition, while FDA updated a guidance document on live biotherapeutic products (LBPs) in 2016, and the European Pharmacopoeia Commission published three documents on quality requirements for LBTs in April, the regulatory path is still relatively uncharted (see Box: “Live Regulation”).

Table: Bug reports

Trials of at least six live intestinal microbiome therapeutics are expected to reach “primary completion” of Phase II or Phase III trials by the middle of next year, meaning top-line data may be announced. Data excludes probiotic products. Source: ClinicalTrials.gov

CompanyProductIndicationStatusPrimary completion
Seres Therapeutics Inc. (NASDAQ:MCRB) / Nestle S.A. (SIX:NESN)SER-109Recurrent Clostridium difficile infection (CDI)Ph III (2 trials)Feb. 2019;April 2019
Ferring Pharmaceuticals A/SRBX2660Recurrent CDIPh IIIJune 2019
Finch Therapeutics Group Inc.CP101Recurrent CDIPh IIJuly 2019
MaaT Pharma S.A. MaaT013Steroid-resistant acute graft-versus-host disease (GvHD)Ph IISept. 2019
Vedanta Biosciences Inc.VE303Recurrent CDIPh IINov. 2019
Seres Therapeutics Inc. (NASDAQ:MCRB)SER-287Ulcerative colitisPivotal Ph IIbJuly 2020

Sidebar: Live regulation

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