December 2, 2015
By Mark Terry, BioSpace.com Breaking News Staff
Checkmate Pharmaceuticals, located in Cambridge, Mass., is built on discoveries made by the company’s chief executive officer, Art Krieg, in 1994. Working with synthetic DNA, he discovered what he describes as “a more powerful immune activator than I’d ever encountered before.” Ultimately what he found was that the immune system, which does a pretty good job of detecting bacterial and viral infections, also is capable of detecting DNA that isn’t present in our own cells. Changes in human DNA, called methylation, make just enough structural change to human DNA to differentiate it from viral and bacterial DNA.
In 1997 Krieg founded Coley Pharmaceutical Group to take four novel CpG oligonucleotides into clinical development. In 2008 Pfizer bought Coley, and Krieg became the head of Pfizer’s Oligonucleotide Therapeutics Unit. Pfizer abandoned the field in 2011 and Krieg then co-founded RaNA Therapeutics, acting as its chief executive officer through 2013, and then as chief scientific officer for Sarepta Therapeutics until July 2014.
Krieg’s technology may have been a little bit ahead of its time. At the time he founded Coley, researchers felt that the way to treat cancer with immunotherapy was to activate the immune system in a powerful way. Since the CpG oligonucleotides did that, it seemed like a sure fit. What wasn’t discovered until later was that cancer cells have what are called checkpoints—they essentially are a set of brakes that stop the body’s immune system from attacking the cancer cells. This discovery has led to a new class of molecules called checkpoint inhibitors, which take the brakes off. Mixing an immune activator with a checkpoint inhibitor is like simultaneously pushing the gas pedal on the immune system while taking the foot off the brake.
“The approach of Checkmate,” said Krieg, “is to couple the very powerful immune activator I discovered 20 years ago—a new and improved version of it—with checkpoint inhibitors. The cells have maybe a 20 percent response rate and what we hope to do is increase it, double it or triple it. We’ll know very soon.”
Company Leadership
In addition to Krieg as chief executive officer and founder, Checkmate is run by Chuck Abdalian, the company’s chief financial officer, Norm Greenberg, as senior vice president of Translational Medicine, Frank Hennecke as executive vice president of Drug Development, Ramani Varanasi as chief business officer, and Chuck Yon as general counsel.
Art Krieg—chief executive officer and founder of Checkmate Pharmaceuticals. Krieg received his MD from George Washington University and trained as a rheumatologist at the University of Minnesota and at the National Institutes of Health before he became a professor of internal medicine at the University of Iowa.
Chuck Abdalian—chief financial officer. He was formerly a partner with Coopers & Lybrand, a predecessor to PricewaterhouseCoopers. He has an extensive background in initial public offerings, mergers, acquisitions and life science licensing deals. He is currently managing director of CFGI’s Life Sciences Financial Consulting practices. He has held chief financial officer positions with Coley Pharmaceutical Group, BG Medicine, Knomem, Molecular Insight and W.R. Grace Health Care.
Norm Greenburg—senior vice president of Translational Medicine. He is the president and chief scientific officer of NMG Scientific Consulting and previously the vice president for global oncology research at MedImmune . He was also senior director at Pfizer Oncology.
Frank Hennecke—executive vice president of Drug Development. He has led the process development department of Cytos Biotechnology, developing CpG oligonucleotides for asthma and allergy immunotherapy since 1998. He also runs Hennecke Biotech Consulting.
Ramani Varanasi—chief business officer. She runs her own strategy and business development consulting practices and has held research and senior level positions in various companies, including Merck , Millennium (Takeda), Momenta Pharmaceuticals , Archemix and RXi Pharmaceuticals.
Chuck Yon—general counsel. He was the senior vice president, general counsel and secretary at Coley Pharmaceutical Group from 2001 through 2008. Before that he was senior vice president and general counsel for Astra Pharmaceutical Products.
Company Financing
In August 2015 Checkmate announced a Series A financing round of $20 million from Sofinnova Ventures and venBio. “I think the $20 million is all we need to prove the concept and run three clinical trials,” Krieg said. “The first trial will be in advanced melanoma, where we will be combining the CpG oligonucleotide with an anti-PD1 antibody.”
Pipeline
The company filed an investigational new drug (IND) application for CYT003, since renamed CMP001, in late 2015 and expects to enter the clinic in early 2016, possibly in January. Krieg indicated he expects to know if the combination is working or not in 2016.
In addition, Checkmate has several other compounds and formulations they are developing, although CMP001 is the most advanced.
Market Competition
The biopharma industry has been buzzing with advances in immune-oncology. Numerous big pharma companies, such as AstraZeneca , Sanofi and Novartis are working in this area, although primarily on the commercial side of things, as opposed to discovery. In October 2015, for example, Swiss company Novartis bought Admuen Therapeutics, located in Danvers, Mass., to acquire the company’s IL-15 agonist program, which is in Phase I clinical trials for metastatic cancer. Novartis also bought the rights to Spanish company Palobiofarma’s PBV-509, an adenosine receptor antagonist in Phase I clinical trials for non-small cell lung cancer.
Krieg indicated that Checkmate’s direct competitors working at developing CpG oligonucleotides in conjunction with checkpoint inhibitors are Dynavax and Idera Pharmaceuticals . Dynavax recently inked a deal with Merck to initiate two clinical trials with Merck’s anti-PD-1 therapy, Keytruda, and Dynavax’s MK-1966, an anti-interleukin-10 (anti-IL-10) immunomodulator and its toll-like receptor 9 (TLR9) agonist, SD-101. Idera announced in November that it had new preclinical data of its IMO-2125, a synthetic oligonucleotide-based agonist of Toll-like receptor 9 in combination with an anti-PD-1 monoclonal antibody for colon cancer. The company expects to start its first clinical study by the end of 2015.
Dollars and Deals
Aside from the recent Series A round, Checkmate acquired a clinically validated virus-like particle (VLP) platform from Cytos Biotechnology, which included CYT003 and other technologies.
What to Look For
The company’s focus is on proving that its technology and theories work, and all eyes will be on its clinical trial for CMP001. “As I look at the cancer immunotherapy space, what has really revolutionized things is the checkpoint inhibitors. I look at CAR-T cells and all the excitement, which is really justified, because they cause a response in patients who otherwise don’t respond, " Krieg said. “But it’s a very complex individualized therapy and what makes us excited about our approach compared to CAR-T and other individualized therapies that other companies are talking about is we’re a more universalized, one-size-fits-all approach without having to purify T cells from a patient without having to sequence their tumors and identify the antigens in the tumor…. That’s our theory and we hope to have clinical data on whether we’re right in the next year.”
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