HemoShear's Human Disease Model Validated By Takeda NASH Deal

Emerging Company Profile: HemoShear thinks its REVEAL-tx platform can identify novel targets and validate drug candidates better than existing bench research methods. Japan’s Takeda is betting in a new collaboration that HemoShear can deliver novel targets in NASH.

HemoShear LLC obtained both substantial financial backing and validation of its technology platform on Oct. 17 through a collaboration with Takeda Pharmaceutical Co. Ltd. to identify novel targets for non-alcoholic steatohepatitis (NASH).

The deal in a big liver disease indication is an important endorsement for HemoShear's REVEAL-tx disease-modeling platform, which the Charlottesville, Va.-based company created based on a goal to develop better bench research tools than cells in petri dishes or animal models. HemoShear will use the technology under its three-year agreement with Takeda – announced just days before the start of the American Association for the Study of Liver Diseases (AASLD) annual meeting – to identify new therapeutic targets that its partner has an option to license for internal NASH drug discovery and development.

Although no specific financial terms were revealed, HemoShear will receive an upfront payment and research funding, and it may earn milestone fees of up to $470m plus royalties. Being able to announce the deal as the AASLD meeting gets under way is especially significant for the company, because its REVEAL-tx technology has received four Presidential Awards from the organization based on publications that demonstrate the platform’s ability to replicate many clinical observations from drugs already in the clinic.

NASH, a primary focus of the upcoming AASLD conference, is a chronic liver disease characterized by inflammation and accumulation of fat in the liver that can progress to fibrotic disease, cirrhosis, liver cancer and the need for liver transplant. Thought to affect 16m people in the US, the disease has no approved drug therapy, although a host of companies led by Intercept Pharmaceuticals Inc., Genfit SA, Gilead Sciences Inc. and Allergan PLC – each in Phase III – are developing potential therapies for it. (Also see "Genfit's Enrollment Delay In NASH May Aid Intercept's First-To-Market Goal" - Scrip, 25 Apr, 2017.)

HemoShear was founded in 2009 and based its technology on research started at the University of Virginia. The company has been funded mainly by National Institutes of Health (NIH) grants and backing from individual private investors. The biotech also has earned income from contracting its platform technology to biopharma companies, but CEO James Powers told Scrip that to this point its work in NASH has been limited to in-house exploration of the disease and evaluation of other companies' therapeutic candidates. Beyond the Takeda collaboration, HemoShear also hopes to develop its own pipeline of drugs for rare pediatric diseases.

“This agreement is a huge milestone for us in terms of a validating partnership in the eyes of the industry and the investment community,” Powers said. “We spent a number of years building and validating a series of organ and disease models that closely replicate human biology with our proprietary technology. In recent years, we identified some opportunities to put that technology to work to generate greater value for patients and for investors by focusing on NASH and on children’s rare metabolic diseases.”

HemoShear CEO James Powers

Source: HemoShear LLC

Having accumulated $18m in NIH Small Business Innovation Research (SBIR) grants to date, as well as $23m in private investment, the exec said his company does not plan to seek venture capital financing until it is ready to advance one or both of its rare disease programs into the clinic. HemoShear hopes to bring candidates for propionic and methylmalonic acidemia – fatal genetic disorders that prevent the proper metabolizing of proteins – into preclinical development in 2018 and human testing in 2019.

While the announcement of the collaboration with Takeda says it will focus on liver diseases including NASH, Powers said the focus truly is on NASH and fatty liver disease. “For the foreseeable future, there’s a lot of work to be done,” he said. “We’ve already got study plans developed and we are going to be committing a significant amount of our resources just on NASH and fatty liver diseases.”

The deal is based on Takeda’s strategic decision to take a deep dive into understanding NASH and thinking about novel targets while other companies “are in a rush to get something out there,” Powers added. (Also see "The NASH Pipeline: Replete With Targets And New Compounds" - Scrip, 29 Aug, 2016.)

A Human Model With All Attributes Of Late-Stage NASH

This made the Japanese pharma an ideal partner for HemoShear, explained Co-founder and Head of Innovation Brian Wamhoff, because of how the biotech had been using the REVEAL-tx platform to evaluate the NASH drug-development race. After HemoShear developed its technology, its board of directors pushed beyond using it to screen drugs for safety and to focus it on unmet medical needs, for which clinically relevant disease models pose significant deficiencies, he said.

“That’s what landed us in NASH and ultra-rare diseases in children, for which there are very few animal models, and the [existing] animal models really don’t mimic human disease for the ones we study,” Wamhoff said. “Ultimately, what we created was a human liver model that has all of the attributes of early to late-stage NASH, validated against human clinical biopsy samples. It was the first time this had ever been done.”

Then, under an NIH grant, HemoShear began using REVEAL-tx to evaluate every NASH drug candidate it knew of, he noted.

HemoShear Head of Innovation Brian Wamhoff

Source: HemoShear LLC

“We took every drug in the preclinical space and in the clinical space, whether they were in the clinic or had failed in the clinic, and we ran those NASH sets through the system and we were able to predict what was happening with those drugs in the clinic – even some of the success that is being seen with obeticholic acid (Intercept’s Ocaliva), as well as some of its deficiencies, like the increase in cholesterol that’s produced by the liver.”

Takeda then was among a slew of potential partners HemoShear spoke with about collaborating in NASH, Wamhoff said, but the Japanese pharma emerged as its partner of choice.

“This is not merely from an economic standpoint, but how they think about NASH, how they want to use the platform, the fact that they really want to go after first-in-class, best-in-class drugs in that space, thinking about targets that no one has thought about, and to do that you really need a human-relevant model to pull those precious targets from,” he said.

HemoShear’s role in the partnership will take it up to identifying and nominating novel targets, Powers explained, with Takeda then having the option to launch a discovery program to chase the target(s). “It’s possible that HemoShear may run that chemistry program or it’s possible that Takeda would, but at this point, that’s a few years off, and right now what we want to do is interrogate the disease and nominate a set of targets for launching drug discovery programs,” he added.

REVEAL-tx’s basis is in reflecting how a drug candidate might act in an actual human patient’s blood flow, explained Wamhoff. He noted that there are about 40 mouse models right now for NASH, and asserted that none of them may prove adequate to deliver a truly optimal therapy for the disorder.

“What we set out to do in 2005 as faculty at UVa was that instead of putting human primary cells in a dish, if we could recreate the three-dimensional context that they’re in in vivo as well as physiological forces they experience in vivo, one could argue that that would recreate that in vivo-like biology on the bench,” Wamhoff said.

They ended up with a model that mimics where blood flow interfaces with cells and where drugs are metabolized, he added. “A lot is going on there from fundamental metabolism to drug metabolism to getting toxicants out of the body and we were able to bring those liver cells into a three-dimensional format and then re-apply hemodynamic blood flow and transport to those cells using our technology.”

“When you do that, the cells go from thinking they’re in a petri dish, which is a cell that’s really in crisis – you’re doing everything you can to keep it alive for your experiment – to literally thinking they’re back at home.” Wamhoff continued. “That was validated by a wealth of publications correlating responses back to in vivo clinical data and human data.”