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Hutch’s “Project Violet” Taps Crowd, Seeks $20M for Drug Discovery

Xconomy Seattle — 

Many scientists are dreaming these days about using crowdfunding to raise money for their projects, through platforms like Kickstarter. Usually the scientists seek to raise a few thousand bucks in the name of a fairly incremental advancement in our understanding of biology.

Jim Olson and his team at Seattle’s Fred Hutchinson Cancer Research Center are thinking way bigger than that.

Olson, probably Seattle’s most accomplished biotech entrepreneur of the past five years, has a team working on a new drug discovery platform that could have attracted $20 million in venture capital back in the go-go days of the early 2000s. That’s not a serious option in this time of venture capital scarcity and federal research cutbacks. So Olson and his team have crafted an alternate plan. It’s called “Project Violet,” and it draws its name and inspiration from a little girl with brain cancer that Olson, a pediatric oncologist, once treated. The project combines aspects of crowdfunding, social media, and video game-style engagement in the name of drug discovery.

If this plan pans out, Project Violet will scrape together $20 million from thousands of small and large donors, and keep them engaged in a drug discovery journey over the next few years. The money will help advance several drug candidates to the point where a company can more appropriately pick up the baton for development.

No one can say for sure whether this is a new model that will help fill empty biotech and pharma company pipelines, but Project Violet has so far attracted quite a bit of support. About 70 volunteers from Amazon have helped craft an Internet crowdfunding platform over the past year, and Project Violet has tapped the expertise of the region’s video game experts for advice on how to hold the attention of its donors throughout the long, difficult journey of drug development. With little publicity beyond a talk Olson gave earlier this year at TEDx Seattle, Project Violet has already raised enough to pay a few salaries for members of the project team.

“It’s an experiment, like everything we do,” Olson says.

Jim Olson, founder of Project Violet

Jim Olson, founder of Project Violet

Olson, who sees patients at Seattle Children’s and does research at the Hutch, has stepped up to this challenge after founding two new Seattle biotech companies—Blaze Bioscience and Presage Biosciences. Blaze is based on a technology called Tumor Paint, which uses a peptide that binds with, and lights up tumors, so that brain surgeons know which tissues they should cut out and which parts of the brain they should leave alone. Presage has a special probe that enables it to inject different drug candidates, or combinations of drug candidates, into a surgically removed slice of tumor so that researchers can see which drug is mostly likely to work for an individual patient. Both companies have had success raising money from angel investors, and Presage has secured a couple of partnerships with Celgene and Takeda Pharmaceuticals.

Project Violet essentially is a new idea that builds on what Olson’s team learned from the Tumor Paint experience. Peptides are short chains of about 30 to 40 amino acids in length, that can bind with specific targets in cells. Many researchers are interested in peptides as drugs, because they are lean enough to get inside cells where large-molecule antibodies can’t go, and they can reach difficult 3-D targets known as protein-protein interactions that are generally inaccessible to conventional small-molecule drugs. Cambridge, MA-based Aileron Therapeutics is one such venture-backed company built on the idea of coming up with new ways to engineer peptides to hit “undruggable” molecular targets. Another example is Ensemble Therapeutics, also in Cambridge, which has a different technology for pursuing undruggable targets.

Although a few peptide drugs are already on the market, such as exenatide (Byetta) for diabetes, most peptides have no real chance as drugs. For some, it’s because once they get absorbed, they get chewed up by enzymes in the body that render them useless within minutes. Or, maybe the peptide can only be derived from natural sources like scorpion venom or sunflowers—not exactly fountains for commercial-size quantities needed for drugmaking. The peptide used in Tumor Paint, for example, traces its origin to scorpion venom.

The team at the Hutch identified a series of technical hurdles standing in the way of drug discovery in a family of peptides known as knottins. Over the past year, Chris Mehlin and Colin Correnti in the Olson lab took the lead on work that knocked down most of the hurdles, Olson said. Suddenly, with a new scalable process, the team’s capabilities went from making about 10 new knottins per year to 10,000 in three weeks. The now eight-person team, plus students and postdocs, can do the work with equipment on campus, rather than turn to a more expensive contract manufacturer.

The new fast and cheap process, which produces knottins through recombinant (genetic engineering) techniques, means that Project Violet can create lots of different variations of molecules that could be made to hit a particular hard-to-reach molecular target of medical interest.

Here’s where the public engagement comes in. The idea is to try to engage the crowd of donors in the drug discovery process, by allowing them to “adopt” a specific peptide in discovery for $100. The donors will get a picture of roughly what their molecule looks like, and they’ll get to follow periodic blog updates from the scientists who can walk them through the key early steps of discovery. Without getting so specific that they’d lose their intellectual property, the scientists will share some of the ups and downs they go through in the lab when a molecule shows an ability to bind tightly with a target, when they pick their favorite (the “hit-to-lead” process) and when they use chemical tools to further tweak the ideal compound (lead optimization).

Veterans of drug discovery know that most drugs fail in this winnowing process, and even the very best compounds are still years away from entering their first clinical trial. So it’s reasonable to ask what will happen to Project Violet donors when they find out the hope for their adopted molecule has been dashed? Will they stay interested through such a long, winding, technically arcane process?

Members of the team say they are concerned about holding onto people’s attention, and have thought a lot about how to keep the interest up over time. Whenever a drug fails, the donor can simply get switched to a new one.

“We’re building in backup options so people will always have a horse in the race,” said Mehlin, a member of the project team and a former scientist at Amgen.

Since the Hutch is a nonprofit research center, collecting donations (not equity investments) for Project Violet, it can only go so far down the R&D continuum before it needs to be handed off to a commercial partner for further development, where drug candidates start to accumulate financial value. The plan is to take the best candidates from Project Violet as far as the studies necessary to begin clinical trials, also known as IND-enabling studies, Olson says.

The Hutch recently amended its collaboration with Blaze Bioscience so that the company will get the exclusive option to license optimized peptides from Project Violet. In return, the project team will get some development guidance from the Blaze team, the Hutchinson Center is getting an increased equity stake in the company, and the Hutch will collect payments from Blaze if the company in-licenses any of the drug candidates. The Hutch is also free to out-license any drug candidates that Blaze doesn’t take.

It’s clearly a heady time over at the Olson lab, as the team is seeking the kind of national media attention that could drive a lot of donors to Project Violet. Olson, rather than seeking the spotlight for himself, introduced me to the entire Project Violet team when I stopped by the office. There’s talk of Project Violet getting hooked into a national science competition, and trying to entice corporate sponsors to foot the bill so that 9,000 kids will each get to “adopt” their own drug, so they can learn about how a drug becomes a drug.

“This is an opportunity to get engaged with the community,” said Correnti, a member of the team with a PhD in biochemistry from the University of Washington. “Essentially what we’re doing is drug discovery at the most basic level. People see pharma as a scary large entity that doesn’t share a lot of information. We want to connect the community and get them involved from the beginning.”

For more information, see Olson’s TEDx Seattle talk on Project Violet.

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  • Thanks for writing about this project Luke. I wanted to capture the link to the discussion that it sparked over on Twitter about nonprofits, crowdfunding, maintaining focus, etc.