Monoclonal antibodies? So passé. Cancer metabolism drugs are emerging as the therapeutic to watch, or so says Cornerstone Pharmaceuticals CEO Steve Carchedi.
Cornerstone’s approach is to develop anticancer drugs that target mitochondrial metabolism – in essence cutting off the energy supply that allows cancer cells to grow and develop. Its lead candidate, CPI-613, inhibits two enzymes that are critical for cancerous cells to replicate, Carchedi said.
“By targeting enzymes that are highly selective to cancer cells, we don’t harm healthy cells,” Carchedi said. “And our drug attacks a broad spectrum of cancers – pancreatic, lung, breast – so we’re really not locked in to treating just one indication.”
The 15-year-old New Jersey company is now aiming to raise its profile in the wake of competitor Agios going public – and hitting a $4-plus billion market cap. Agios, also in the cancer metabolism space, is in the midst of Phase 1’s, but Cornerstone has quietly progressed to several Phase 2’s, Carchedi said – making it the most advanced in this promising new space.
What’s notable about Cornerstone, Carchedi says, is that its earliest clinical testing includes a handful of profoundly curative moments. He told the story of a 19-year-old girl with Burkitt’s lymphoma – a particularly aggressive cancer in which cancer cells double in size within 24 hours, and patients tend to have a short lifespan that’s measured in weeks or months.
After being refractory to a number of different treatments, including a stem cell transplant, Carchedi says she was told she should go home, get her affairs in order. But as a sort of last-ditch effort, the girl was enrolled in Cornerstone’s Phase 1 safety and dosing trial for CPI-613.
After two cycles, she responded to Cornerstone’s treatment. And after 17, her tumor had reduced to the point that she could get surgery. And after that, there was no residual disease at all. Cured, more or less.
A Deep-dive Into Specialty Pharma
A specialty drug is a class of prescription medications used to treat complex, chronic or rare medical conditions. Although this classification was originally intended to define the treatment of rare, also termed “orphan” diseases, affecting fewer than 200,000 people in the US, more recently, specialty drugs have emerged as the cornerstone of treatment for chronic and complex diseases such as cancer, autoimmune conditions, diabetes, hepatitis C, and HIV/AIDS.
Results may vary, of course. In the first Phase 1 trial, 38 percent of patients received some sort of positive clinical benefit from Cornerstone’s therapy.
“But these are the sickest of the sick – they were salvage therapies,” Carchedi said.
The company just kicked off a Phase 1 clinical trial using CPI-613, treating patients with refractory B-cell Non-Hodgkin lymphoma. They’ll be treated with rituximab and bendamustine as well. These are all the trials that Cornerstone has underway:
- Phase II of CPI-613 in patients with relapsed or refractory small cell lung cancer
- Phase II of CPI-613 in patients with advanced and/or metastatic solid tumors
- Phase II of CPI-613 in patients with relapsed or refractory myelodysplastic syndrome
- Phase II of CPI-613 in patients with locally advanced or metastatic pancreatic cancer
- Phase I/II of CPI-613 in patients with advanced cholangiocarcinoma (bile duct cancer)
- Phase I/II of CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer
- Phase I of CPI-613 in combination with high doses of Cytarabine and Mitoxantrone in patients with relapsed or refractory acute myeloid leukemia
Cornerstone has raised “well over $50 million” since its 1999 genesis, Carchedi said. The company’s now receptive to the ideas of acquisition or going public, as it readies itself for wrapping up a wave of Phase 2 trials next year.
Like many a biotech CEO, he claims the next generation of cancer treatment lies in the IP portfolio of his own company, which in this case is targeting cancer metabolism.
“We’re obviously past the chemotherapy era,” Carchedi said. “What followed was the biotech era where monoclonal antibodies, vaccines and immunotherapy ruled – but that’s wrapping up now. Cancer metabolism is the next new wave of drug development.”
