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Tango, Finch, Indigo & More: The 2018 Xconomy Award Startup Finalists

Xconomy Boston — 

This year’s bumper crop of Xconomy Award startup finalists cover a wide range of technologies and approaches, from microbiome and gene therapy to regenerative medicine and emerging areas like chromatin biology. Some are early stage, some are already in the clinic and one even has products on the market. Here are brief profiles of the startup finalists. (To read about the CEO finalists, click here.)

Finch Therapeutics
Finch is one of several human microbiome startups, but its roots are unique. Before starting his company, Finch CEO Mark Smith and his collaborators launched a human stool bank in 2012, called OpenBiome, to collect stool donations, and provide screened and processed fecal material to hospitals for transplantation into patients with Clostridium difficile infection. Smith and his cofounders started Finch Therapeutics in 2014 to try to move beyond these fecal microbiota transplantations (FMT) and come up with rationally designed microbiome therapeutics.

In 2017, Finch merged with another microbiome company Crestovo, which was already testing in humans an orally administered drug containing a wide range of microbes from healthy donors for the treatment of C. difficile infection. The phase 2, 240-patient trial should generate data next year.

Finch brought its manufacturing capability to the merger with Crestovo. That capability is already proven: Finch makes OpenBiome’s FMT treatments, about a thousand each month.

This manufacturing know-how gives Finch the foundation to develop its next wave of designed microbiome therapeutics using clinical data. The company has helped dozens of academic groups do pilot studies of various microbiome treatments that are transplanted into patients from donors. In exchange for manufacturing and other services, Finch gets early access to data from these studies before they are published, or even access to patient and donor samples. Finch analyzes the clinical data or samples, using machine-learning algorithms to identify specific bacterial strains that might be providing important clinical benefits.

This “human-first” approach has led to a microbial cocktail, developed in partnership with Takeda Pharmaceutical, for ulcerative colitis that is moving toward human testing.

Foghorn Therapeutics
Foghorn is pursuing a new type of drug target in cancer: the genes that control how DNA is packaged inside the cell’s nucleus. The tightly packed web of DNA and proteins in the cell is called chromatin. The cell tweaks chromatin’s structure, opening up certain parts and making specific genes accessible so that they can be used to make proteins. Changing chromatin’s structure is another way the cell regulates which genes get turned on and when. Foghorn’s scientific cofounders, Cigall Kadoch of the Dana-Farber Cancer Institute (who’s also a finalist the Young Innovator category) and Gerald Crabtree of Stanford, have found that mutations in the system that controls this chromatin remodeling may be involved in up to 20 percent of cancers and in other diseases too.

Foghorn wants to find medicines that target the chromatin regulators that go awry in various types of cancer, and has its eye on neurology and immunology too. The company was founded in 2016 and has $50 million in financing from Flagship Pioneering to work on six discovery programs and more earlier stage ones.

Generation Bio
Generation Bio caught people’s attention when it raised $100 million in a Series B round of venture financing just one month after its launch early this year. What might be exciting investors is the company’s goal of developing next-generation gene therapies that could overcome some of the drawbacks of current ones. First generation gene therapies, such as one approved last year for a genetic form of blindness, can only be given once, because the immune system develops antibodies to the viruses that carry the gene to targeted cells. Moreover, gene therapy doses are difficult to control, making the long-term durability of gene therapies uncertain.

Generation Bio, founded in 2016, is using lipid nanoparticles to deliver genes, avoiding the use of viruses, which could allow for redosing if the beneficial effect wears off. The company’s vision is to treat patients with genetic diseases at birth and throughout their lives if needed.

Inside the nanoparticles are a kind of DNA called close-ended DNA (ceDNA), a key part of the company’s technology discovered by Robert Kotin while at the National Institutes of Health. (Kotin is a Generation founder and heads up its discovery efforts). Generation says ceDNA can enter the cell’s nucleus, carrying the therapeutic gene and other elements that allow the cell to use the ceDNA as a template to make the needed protein. The company says it can control the amount of ceDNA the patient gets, and adjust the dose with each treatment.
Generation is focused on targeting the liver with treatments for rare diseases, and is also looking at diseases of the eye, lung and central nervous system.

Indigo Ag
Human microbiome companies are years away from commercial products, but one microbiome company has already moved products to the market for agriculture in less than five years after being founded. Indigo Ag has raised more than $400 million and has microbial seed treatments for five different crops; the treatments are designed to boost crop yields by making plants more resistant to stress such as drought. The company, founded as Symbiota and renamed Indigo in 2016, developed the mixes of beneficial microbes by studying the microbes that normally live in plants and identifying the ones that most benefit the plant. Indigo then coats crop seeds with this mix of microbes, contracts with farmers to grow crops (corn, wheat, cotton, soy and rice) from the seeds, and then connects the growers with buyers (flour mills, for example) interested in buying non-genetically modified products at a premium. Data from Indigo’s field tests in Texas show that its seed treatments increased cotton yields by 14 percent in its second season after commercial release, up from 11 percent in its first year.

Indigo’s first products are intended to make plants more drought-resistant, and it’s looking to develop products that address other plant stresses such as pests and disease. It also wants to use microbes to make plants more efficient users of nitrogen, with the aim of reducing the need for nitrogen fertilizer.

Indigo’s rapid growth in just a few years can be credited in part to CEO David Perry, who is combining his previous experience creating and leading life science companies with his background growing up on a farm in Arkansas.

Semma Therapeutics
For nearly 20 years, Doug Melton has been trying to use stem cells to make replacement pancreatic cells to treat type 1 diabetes, which affects both of his children. In 2014, the time was finally ripe to move the results from his lab at Harvard University into a startup focused on making stem cell-based regenerative therapies for the disease. With that mission in mind, Melton, along with his former postdoctoral researcher Felicia Pagliuca, who made many of the seminal findings while in his lab, cofounded Semma Therapeutics.

The company has since received nearly $160 million in venture funding and is now scaling up its cell manufacturing process in preparation for human tests. Its goal is to develop a small, implantable device that contains insulin-producing cells derived from human embryonic stem cells. The device’s semi-permeable membrane is designed to protect the cells from immune attack so that patients wouldn’t have to take powerful immune-suppressing drugs. The hope is that the implant would provide insulin control over many years so that patients would no longer need to inject themselves daily with insulin. The company recently named Bastiano Sanna, who previously led some of the cell therapy and transplant programs at Novartis (NYSE: NVS), as CEO and president.

Tango Therapeutics
Tumors often have a genetic mutation that weakens them, but they’re still able to survive by relying on another key gene. Inactivating that second gene, however, can be the final, fatal blow to the cancer cells. This approach to targeting cancer, called synthetic lethality, is already the basis for a new class of drugs on the market called PARP inhibitors. Tango Therapeutics is looking for more synthetically lethal gene pairs in cancer and launched last year with $55 million in Series A investment after incubating for 10 months. Led by CEO Barbara Weber, the company says it’s starting first with specific subgroups of cancer patients who don’t have many treatment options. Tango scientists look at the DNA sequences of the patients’ tumors to find any key common mutations that are driving tumor growth, such as mutations in tumor suppressor genes. They then use CRISPR-based screening technology to search for the synthetically lethal partners of those mutated genes as potential drug targets.

Earlier this year, Tango researchers presented data in human cell lines as a proof of concept of their approach. They analyzed tumor data from patients with a type of ovarian cancer called clear cell carcinoma to look for the “Achilles heel” of cancer cells with a mutation in the ARID1A gene. They found that blocking a gene called EGLN1 in these cells caused them to die.

Tango features an all-star group of scientific founders, including Alan Ashworth of the University of California, San Francisco, whose research on synthetic lethality laid the groundwork for the development of the first PARP inhibitors, which are now on the market for certain types of ovarian cancer.

This is the second in a series of articles profiling the 2018 Xconomy Award finalists. Click here to learn about the CEO finalists. 

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