More well thought out work can be found at — https://axial.substack.com/

Who leads Novome?

Novome is led by Blake Wise (CEO) with the founders being Liz Shepherd, Will DeLoache, Weston Whitaker, and Zachary Russ. Blake is the former CEO of Achaogen (a great case study on the current status of antibiotic businesses), and the founders were graduate students from Stanford and UC Berkeley. The idea originated out of research in the Sonnenburg Lab at Stanford developing new tools to engineer Bacteroides in the microbiome.

What does Novome do?

Novome develops engineered microbial therapeutics what they call genetically engineered microbial medicines (GEMMs). The premise is to produce microbes that can colonize the human gut through oral delivery and be precisely controlled. With this platform, Novome focuses on one of the most abundant strains in the microbiome, Bacteroides, and programs them to perform key functions to treat diseases with mapped out mechanisms-of-action.

The first indication they are pursuing is secondary hyperoxaluria (excessive secretion of oxalate; Allena is a competitor here), which ultimately leads to kidney stones. This disease is well-understood, without an approved medicine, and has a strong connection to the microbiome - something many of microbial therapeutics lack. Novomes GEMM colonizes the gut then breaks down oxalate to reduce the symptoms of hyperoxaluria. The company is completing IND-enabling studies. Their second indication is irritable bowel syndrome.

What makes Novome unique?

Novome has a unique technology and business model. Its GEMM platform so far has shown the ability to colonize the gut of models through oral delivery. The ability to successfully deliver a microbial therapeutic through an oral formulation would be transformational for the modality. The second part is Novome’s focus on secondary hyperoxaluria. This gives them better odds for clinical success because they have a clear connection between the microbiome and oxalate breakdown; however, the market size is too small for Novome to rely on soley. Hyperoxaluria (primary and secondary) has a patient population of maybe 200K; so it’s technically a rare disease. This plays well for Novome’s pace in the clinical trial but pricing of their medicine is unlikely to match other curative medicines due to the standard-of-care (drinking a lot of water) working. The market size in secondary hyperoxaluria for Novome is somewhere between $50M-$100M. After validation here, the company will need to expand to a larger market as quickly as possible.

Why I like what Novome is doing?

The key drive for Novome’s success will be its ability to translate its proof-of-concept data into humans. The key experiment is the ability of Novome’s GEMMs to colonize the human gut via an oral drug:

This figure shows Novome’s ability to control their GEEM in the gut of a mouse. In part A the experimental design is laid out with two groups of mice: the control (RF) and mice with different human gut communities (Hum-1/2). Their guts were equilibrated with the same diet of 7 days and given Novome’s GEMM, NB001 that was engineered for a porphyran locus that enables use of the carbohydrate as a food source. Then the mice were switched to diets that either had the polysaccharides, inulin or porphyran. The following curves measure the abundance of NB001 with C for inulin and D for porphyran. The rescue experiments show the company’s ability to induce fixation of NB001 in the microbial population through the addition of a single polysaccharide.

Over the next year or two, we will see if this premise translates well into humans and brings the first engineered microbial therapy to approval.

You can find Novome here.