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With $21M, Retooled Blend Whips up Mini-Smart Bombs For Cancer

Xconomy Boston — 

Sometimes in biotech, you go in with one plan, and an unexpected discovery changes everything. That’s the case with Blend Therapeutics, which has morphed into a company trying to use nanotechnology to create a new type of cancer therapy.

Watertown, MA-based Blend is announcing today that it has raised $21 million in new equity and debt funding from existing backers New Enterprise Associates, Flagship Ventures, NanoDimension, and Eminent Venture Capital. Added to its $16 million Series B round three years ago, Blend has now raised $39.8 million since inception.

An unspecified institutional investor is providing the debt piece. Company officials wouldn’t disclose just how much debt there is, or who is providing it—co-founder and chairman Omid Farokhzad would only say the backer is an “A+ institutional investor.”

It’s unusual for a company without a drug even in clinical trials, let alone generating revenue, to take on debt. But Farokhzad says Blend’s new focus—developing nanoparticle drugs it calls “Pentarins”—allows it to take that risk.

“This was a perfectly great strategy for where we are today,” Farokhzad says.

Pentarins are essentially tinier versions of antibody-drug conjugates, or ADCs, which are a relatively new drug type that uses antibodies armed with toxins. Only three ADCs have been approved in the U.S., and one was taken off the market for safety reasons.

With their small size and nanoparticle coating, Pentarins are meant to overcome certain ADC limitations, such as a difficulty getting deep into solid tumor tissue. This isn’t to say ADCs can’t effectively treat solid tumor-based cancers—Roche/Genentech and ImmunoGen’s ado-trastuzumab emtasine (Kadcyla), for instance, is approved for breast cancer. But Blend’s president of R&D, Richard Wooster, nonetheless notes that size is an “inherent limitation” of ADC technology; Blend is trying to prove that its tinier Pentarins are a step up over existing approaches.

The first Pentarin, BTP-277, is expected to be ready for its first clinical trial in 2016, according to Wooster.

This isn’t the route Blend initially intended to pursue. The company was launched in 2012 based on the work of three local scientists: Farokhzad, and MIT’s Stephen Lippard and Bob Langer. It had a two-pronged plan. One was to build on Lippard’s work into platinum-based cancer chemotherapy drugs; to develop next-generation versions of these drugs (like cisplatin, for instance) that were more targeted, rather than “sledgehammers” that kill cancer and healthy cells alike.

The other, as the company’s name suggests, was to “blend” disparate therapies together using nanoparticle technology, which is Farokhzad and Langer’s specialty.

Blend raised $16 million for the work, and in 2012 hired Mark Iwicki, a longtime Sunovion Pharmaceuticals executive, to lead the company. The cash was meant to get its first drug to the precipice of its first clinical trial. Even though a drug candidate called BTP-114—which uses cisplatin—has emerged from that effort, the trial hasn’t happened yet. Farokhzad says that’s because of an unexpected “aha” moment that changed Blend’s direction.

ADCs were becoming a mainstay in the pipelines of many pharmaceutical companies. Those drugs effectively link an antibody to a toxin (like Seattle Genetics’s brentuximab vedotin (Adcetris)), with the antibody guiding a drug to a tumor, and then releasing it when it gets there—like a smart bomb. They’re more effective treating blood cancers, however, because they typically have a hard time penetrating solid organs, or solid tumors very well, Wooster says. So Blend—which was essentially making conjugated drugs anyway—figured it had the solution. Why not, according to Farokhzad, use nanotechnology to create “an ADC specifically engineered and designed for solid tumors”?

Blend pored through the scientific and patent literature, and couldn’t find anything that would stop it from trying. So it went “into lockdown mode” to work on the concept.

Blend is only now unveiling its discovery and new focus. Unlike ADCs, Pentarins don’t link a toxin to an antibody, but to a peptide ligand—a much smaller signaling molecule. They’re then stuffed into a polymer nanoparticle.

The nanoparticle is meant to shepherd the drug through the body to its target cell, the way an antibody would for an ADC. Once it gets there, it slips into the cell and unloads the drug. The proposed advantage here is that a Pentarin should be small enough to penetrate deep into tumor tissue the way larger ADCs can’t. Wooster notes that the toxin, or drug payload, can be the same size as the one an ADC carries; it’s the targeting mechanism (the peptide) that’s smaller.

BTP-277 is Blend’s first effort along these lines. Wooster wouldn’t name the specific target receptor or the toxin BTP-277 is armed with, but its first indication will be non-small cell lung cancer.

Blend will use the cash to gear up for its first study for BTP-277, and BTP-114, and develop more Pentarins.

It’ll also need some of those dollars to find a new CEO. Iwicki left in January 2014 to run Civitas Therapeutics, which was sold to Acorda Therapeutics for $525 million a few months ago. Blend has been without a CEO for a year. With two drugs now heading towards clinical trials, it’s ready to staff back up.

“We feel very good about our position,” Farokhzad says. “[But] we temporize our own excitement and wait for clinical data to demonstrate proof of concept.”