For those working in the area of cancer today, it’s impossible to attend a meeting or scientific session without hearing about genetically targeted therapies or efforts in the increasingly hot immuno-oncology space. But a small firm out of Boston has a different view when it comes to cancer therapy.
“We’re going after embryonic and pluripotent targets,” said Mike Schopperle, founder and CEO of Curemeta LLC, which, as its name suggests, aims to cure metastatic disease. Cancer is a “much more fundamental disease than just a disease of genetic mutations. Most [companies] focus today on genetic mutations or oncogenes, turning on or turning off something that makes cells grow. But if you look at the last two decades, targeted therapy doesn’t work [and] precision medicine is never going to work.” Immuno-oncology, meanwhile, has generated “a lot of hype” but “doesn’t help that many people.”
Curemeta’s approach is based on the notion that cancer results from cellular stress – whether that stress can be attributed to genetic mutations, age, diet or environmental causes, for example. “We think of it as a reprogramming disease,” Schopperle told BioWorld Today, involving a “cell in your body that is unhappy, for whatever reason.”
That “unhappy and stressed out cell says, ‘I don’t want to do this anymore,’” and begins to differentiate back into its embryonic form, acquiring stem cell-like properties. So Curemeta is working on a “simple approach,” developing antibodies and antibody-drug conjugates designed to go after embryonic targets expressed in cancer and not found in healthy tissue, Schopperle said.
“Cancer isn’t sophisticated,” he added. “It’s just a bug that’s spreading and growing, a rogue cell that has given up on the human body and is out there looking for food.”
The idea that cancer involves something other than a mutation might go against the grain of much of the current work being done in the space, but it is gaining some traction. “Five years ago, you would have been escorted out by armed security guards” for suggesting an alternative to genetic mutations at a scientific meeting, Schopperle joked, though he noted more seriously that much of the research to date has focused on developing drugs targeting a handful of mutations.
“In this business everyone focuses on the same targets,” he said. “People don’t like new targets; it’s a funny thing.”
Meanwhile, the idea of going after embryonic targets isn’t brand new. But it’s going to take establishing clinical proof of concept to get skeptics on board, and that is what Curemeta hopes to prove.
“When you start in this business, it’s kind of egotistical to think you’re going to cure cancer,” Schopperle said. “My goal was to do something good that would make all the other cancer companies go, ‘Wow, we should be going after this.’”
Curemeta launched roughly five years ago, with operations in Boston’s Seaport District, and boasted seven full-time employees when Schopperle arrived at the BIO-Europe Spring meeting in Barcelona in March.
Its first two years were spent developing a lead molecule, a goal it achieved in April 2013, during the week of the Boston Marathon bombing. “We named it bstrongximab,” he said, a reference to the “Boston Strong” slogan that emerged in the wake of the bombing.
“It has excellent preclinical in vivo and in vitro” data and appears to be targeting the portion of cancer causing the disease, he said. “So we want to bring in a really potent payload, more potential than is out there now.”
Curemeta is working with payload linker specialists and will pick the best payload for the job, he explained. After that, it’s off to the clinic, aiming for proof of concept.
“We hope to be in the clinic with a lead antibody-drug conjugate in 2019,” he said. Curemeta will initially target cancers such as colon, pancreatic, gastroesophageal and cholangiocarcinoma – all gastrointestinal diseases. The lead target, TRA, is expressed “in all cancers we looked at,” he said. “Gastrointestinal had the highest levels.”
The company, which has raised roughly $8 million to date, will have a lot riding on the early clinical work.
“We’re not Pfizer; we’re not Merck,” Schopperle said. “We’re going to get one shot.”
That said, he’s not opposed to bringing in a co-developer, “who has experience we don’t in clinical trials; that would increase our chances,” he said. “But the first real valuation point is the clinical trial.”
And Schopperle hopes to reach that goal not only quickly but cost-efficiently. “One of my goals is to debunk this myth that developing a drug costs $2 billion,” he said.
Curemeta also is likely to buck another popular trend in cancer drug development, opting against combination treatment, at least for now.
“I’m not a big fan of combinations,” Schopperle said, which he described as “taking two drugs that don’t work very well,” and running the risk of increasing the side effects. Curemeta is going after the stem cell differentiation that is causing cancer – the stem cells are believed to be the source of the metastasis that leads to patient deaths – “so we want proof of concept for these targets.” Eventually, it might make sense to look at combining the approach with a drug designed to debulk the primary solid tumor, but “we like our chances; we don’t believe we’ll need combination,” he said.
And cancer might not be the only use for Curemeta’s approach. One of the risks linked to treatment with embryonic stem cell-based therapy, which has potential in regenerative medicine, is the possibility of tumor formation. An ability to mitigate that risk with an antibody-drug conjugate capable of acting against differentiated cells could be a boon to the space. Schopperle said the firm is filing for a grant to support work studying that use, though its priority will remain on cancer.
“We’re small, so we have to stay focused,” he said. “We’re a cancer company right now.