H3 Biomedicine: Health, Hope and Heaps of Japanese Funding

[ Drug Discovery ] With a $200 million commitment from Eisai Co., cancer drug start-up has clear path ahead.

January 10, 2012 | CAMBRIDGE, Mass.—The ‘H3’ in the name of the new oncology drug company H3 Biomedicine stands for “Human. Health. Hope.”

It might also stand for the heaps of Japanese investment—up to $200 million—that it is receiving from Eisai Co., Japan’s fourth largest pharma company. It is an interesting and possibly unique funding model that spares the company the travails of seeking venture finance or short-term licensing deals, says co-founder Stuart Schreiber, professor of organic chemistry at Harvard University and the Broad Institute.

One year after H3 Biomedicine’s official launch in December 2010, it formally dedicated its pristine research laboratories in the heart of Kendall Square, Cambridge, with a ribbon-cutting ceremony held in a swanky new restaurant—fittingly named Catalyst—in the same building. Joining president and CEO Markus Warmuth were dignitaries from Massachusetts state and local government, as well as Haruo Naito, president and CEO of Eisai.

“When I first heard of this company’s name, H3 Biomedicine, I asked what the abbreviation stands for,” said Naito. “I was expecting my name Haruo to be included in that. ‘Human, health…’ I definitely believed ‘Haruo’ comes last. But it is ‘hope’—a great disappointment!” he joked.

Eisai is not just writing a handsome check but providing ready access to its drug discovery and development resources.  Several Eisai chemists have already moved to the U.S. to join H3 Biomedicine’s 30 or so current employees in the gleaming new laboratories (see “Lab Life”).

H3’s philosophy marries expertise in cancer genomics—the forte of co-founder Todd Golub—with discovery-oriented organic synthesis, a field in which his Broad Institute colleagues Stu Schreiber is an authority.

Clean Slate

“This is an exciting time in cancer research,” said H3’s CEO Markus Warmuth, a German oncologist. “15 years ago, our knowledge was limited to a few genes. Today, we have data on hundreds of cancer genomes, and it is increasing super-exponentially on a daily basis.”

“We have a clean slate, we can look at what we learned from cancer genomes, and try to develop drugs for patients from here. That’s why I decided to join H3 Biomedicine,” Warmuth continued.

“We’re trying to be very focused; we’re not opportunistic, it’s not a random walk in the park,” he said. “We’re trying to combine new insights into the pathogenesis of cancer, derived from actual patients’ cancer genomes, to bring new small molecules to patients in need… We have to be very patient to be successful in developing drugs.”

Warmuth said that H3’s success would be greatly aided by having “investor pressures” off its back, “so we can focus on real scientific questions and move forward developing drugs,” he said. “We’re very happy to have the investor [Eisai] in the background, who has given us a tremendous amount of money to really alleviate the pressure and enable us to take a long-term [approach] at a time that many other companies are trimming down their research budgets.”

Warmuth noted that the company’s two co-founders conveniently had their offices at the Broad Institute, just two minutes walk from H3’s location. Schreiber is a renowned chemical biologist who is the co-founder of Vertex, Ariad, and Infinity Pharmaceuticals. Todd Golub is the founding associate director of the Broad Institute and also the co-founder of Foundation Medicine, among others.

H3 will be tackling cancer in general, not focusing on any specific therapeutic areas. “We’re looking at the cancer genome, no matter if its lung cancer or breast cancer or liver cancer. We’re looking for the best opportunities—we’re not trying to just make lung cancer drugs or breast cancer drugs. Let’s look at what the cancer genome actually tells us.”

Eisai CEO Haruo Naito noted that his company has long-standing roots in the Boston area, having established the Eisai Research Institute in 1988 in Andover, Mass. Two of the four founding scientists are still present, under the leadership of Yoshito Kishi, a Harvard chemistry professor and colleague of Schreiber’s.

The pharmaceutical prowess of Kishi and colleagues was demonstrated in the synthesis of Halaven, approved by FDA in late 2010 for late-stage metastatic breast cancer. “It is the first time a drug is proven to extend life of such late-stage cancer patients,” said Naito.

The development of Halaven took 16 years from early discovery. The compound is found in an “ugly black sea sponge” that lives off the coast near Tokyo. Scientists collected 600 kg of the sponge to produce 1 mg of anti-tumor agent. Kishi’s group synthesized the highly complicated structure in a tour-de-force 61-step synthesis (accommodating 19 chiral carbon atoms that resulted in more than 500,000 potential compounds).

“I hope, Markus, in your case, it won’t take 16 years!” joked Naito. “‘H3’ means three years!” The most important ingredient in H3’s ultimate success, he said, would be “the fighting challenging spirit to do something new.”

“We want to be very fast and focused,” Warmuth concluded. “I’d be perfectly OK if we only ever work on three projects, if they are all successful and produce good drugs.” •

Lab Life

Construction of the first phase of H3’s lab space was completed last July, with 48,000 square feet currently, including spotless labs for synthetic chemistry, bacterial, and tissue culture, and genome analysis. The design offers a hybrid between open office space with glass frontage and respect for scientists’ privacy. “I think it’s important that sometimes you can shut the door and think about a problem,” said Warmuth.

The common room/coffee break area is surrounded by four modern seminar rooms, each named hope in a different language: Esperanza, Amal, Hope and Kibou. A planned expansion will include a brainstorming room with no projection capabilities, just wall-to-wall white boards and music.

“It’s absolutely terrific to work in an environment like this,” said chemist Dominic Reynolds, who trained at Cambridge University with Steven Ley. The fume hoods are surprisingly quiet and split into two, so maximizing safety while minimizing energy expenditures. Evaporation equipment is housed in ventilation hoods, with circulating ethylene glycol to cool reactions.

Every chemist is equipped with a lab laptop providing access to electronic literature and Eisai databases and resources. They also have access to a walk-up mass spectrometer and a 400-MHz Bruker NMR machine in a specially vaulted room. “It’s really a privilege to have a piece of equipment like this,” said Reynolds.

“We want to take advantage of modern synthetic methods to generate proprietary chemical libraries that take us into chemical space not occupied by anyone else,” said Reynolds. The emphasis is on quality, not quantity, with the goal of generating chemical libraries containing a relatively modest 15,000 or so novel compounds a year.

“We’re embracing old combinatorial methods, but we’re not in an Arqule-style, 300,000-compounds-a-year mode,” he said. “We’re looking for privileged novel scaffolds that we can decorate and access and screen quickly.”

One of the key differentiators of the new company, Reynolds explained, is that H3 is performing chemical syntheses in solution phase, in contrast to programs at say Infinty Pharmaceuticals (another biopharma that has featured Schreiber’s diversity-oriented synthesis expertise) or the Broad Institute, which run polymer-supported chemistry to facilitate the generation of massive numbers of compounds. “Here, the chemistry is much more tailored to each core, hence the smaller numbers… so it’s all solution based and HPLC-purified at the end, which is really important for the medicinal chemists,” said Reynolds.

Liverpudlian Peter Smith, previously at the Dana Farber and Millennium, said he had a blank slate to buy the right equipment “to prosecute the biology side of the project.” Assays will include protein levels and phosphorylation, DNA manipulation and transformation, and tissue culture—creating cell lines with different genetic backgrounds to help understand which patients will respond to various drugs.

“We’ll take different levels of genetic information and mutation status, and we’ll look for fusions of genes and epigenetic changes. We’re not just focusing on one particular aberration but building the importance of those genetic aberrations to find the right target,” said Smith.

Smith said the goal is essentially to define the experiment on day one, to understand what needs to be done in the patient and replicate that through enzymology, cell biology, animal models, and ultimately into the patient. “Knowing the question at the outset helps us prosecute efficiently, so we should get the answer quickly when we go into clinical studies,” he said. •

This article also appeared in the January 2012 issue of Bio-IT World magazine.

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