BIND Nanotherapy Shows Early Cancer Efficacy In The Clinic
This article was originally published in The Pink Sheet Daily
Executive Summary
Strong preclinical data for BIND-014, docetaxel-carrying particles engineered using BIND’s Accurin platform, translated into positive results against tumors not usually vulnerable to the cancer drug, the company reported at a late-breaker poster session of the American Association for Cancer Research annual meeting.
CHICAGO – Early data on Bind Therapeutics Inc.’s BIND-014 indicate that the nano-oncologic can achieve durable responses at doses only 20% the strength normally prescribed for its docetaxel payload, according to data presented during a late-breaker poster session at the American Association for Cancer Research meeting in Chicago April 4.
The findings from 17 patients in an ongoing Phase I trial in heavily pretreated patients with a variety of tumor types showed durable responses of up to six months for patients taking the novel agent, which uses BIND’s Accurin technology to deliver docetaxel. BIND-014 works by binding prostate-specific membrane antigen, which is expressed on the surface of both cancer cells and on the neovasculature of many solid tumors. The roll of the receptor in this case is not to allow entry into the cell but to hold the nanoparticle in place while it diffuses its toxic payload into the environment surrounding the tumor cells. The effect is a high concentration of Accurins at the site and a high concentration of drug in the area of the tumor and away from other organs.
“We’re seeing patients respond at low doses in tumors known to be otherwise unresponsive to docetaxel therapy after a short number of treatments, including our cervical cancer patient, who has been on the drug for more than six months,” said market and business development head Dan Koerwer.
In fact, six of the 17 patients tested so far in the dose-ascending trial have achieved either stable disease or a partial response, while the study includes no breast, lung or prostate cancer patients – the populations docetaxel is approved to treat. “Our study is the opposite of enriched; it’s de-enriched for responders to docetaxel,” Koerwer said.
“The data strongly show a much more active agent [than docetaxel alone] and the reason it’s active is that it concentrates on the tumor,” said Omid Farakhzad, head of Harvard Medical School’s Laboratory of Nanomedicine and Biomaterials and a scientific founder of BIND. “The tumor is probably seeing a concentration of the drug that is equivalent to the higher doses.”
Preclinical and clinical data tracking the drug’s translation from bench to clinic were published the same day in Science Translational Medicine. “That’s the big story for us,” remarked Koerwer. “The platform is very robust, [we have a] very strong industrial process, and all the preclinical data that we have are now translating into the clinic.”
“It’s not just clinical data in isolation but the fact that they were so well predicted by their preclinical results.”
The ongoing Phase I dose-finding trial was designed to evaluate BIND-014 in patients with advanced or metastatic cancer for which no standard or curative therapy exists. It was administered once every three weeks by one-hour intravenous infusion. Doses up to 75 mg/m2 have been evaluated in seven female and 10 male patients with a median age of 62.
Transient grade 4 neutropenia was observed in two of seven patients at 60 mg/m2 and two of three patients at the 75 mg/m2 dose. No febrile neutropenia was observed. Non-hematological toxicities were mild to moderate and well-managed. “The known side effects of the drug are much milder than what you see in its conventional form,” Farakhzad said.
A Potential For Paradigm Change
While the delivery aspect of the nanotech process has led to comparisons of the Accurin technology and antibody drug conjugates (ADCs), such as ImmunoGen Inc./Roche’s investigational T-DM1 and Seattle Genetics Inc.’s newly approved Adcetris (brentuximab vedotin), ADCs “fall significantly short to be a comparator,” Farakhzad said.
ADCs may have paved the road for BIND to be able to tell its story more effectively, but the ability to concentrate a lethal dose of the drug at the site of action in a safe and effective way is unprecedented, and it will change cancer medicine in much the way the advent of drug-eluting stents changed the practice of cardiology, Farakhzad predicted.
He thinks that BIND’s platform will mean not just another way to treat cancer, like ADCs, but will be a paradigm shift for the way many diseases are treated.
Accurins are made of well-characterized synthetic polymers that are used in other medical applications. They are able to pass through the bloodstream undetected by the immune system because their outer surface includes a polyethylene glycol layer that recruits a shell of water, disguising the particle as a passing water drop.
According to Farakhzad, the particles can carry tens of thousands of copies of their drug payload, and they are not covalently bound, as with ADCs, so they don’t require changes to the API structure.
“It’s astonishing the number of ‘instructions’ these things have embedded in their design,” Koerwer said. The technology is very modular, and it could bind lots of different cell-surface markers by just changing the ligand, so it could be structured to do a therapeutic binding event or to simply to hold the particle in place, as with BIND-014.
While part of the speedy translation of BIND-014 from bench to bedside is owed to the well-characterized API it carries, BIND has formed partnerships with other companies in oncology that involve forming Accurins around proprietary compounds. The company hasn’t revealed the individual partners, but they are top-20 global pharma companies that want to combine Accurin technology with one of their clinical candidates, Koerwer said.
Despite being called molecularly “targeted,” many compounds under development by research-intensive global pharma companies “are quite promiscuous and have serious tox liabilities,” said Farakhzad. “In many cases, depending on the drug and the disease, they are well suited for this approach.”
While privately held BIND’s lead effort is in oncology, the Cambridge, Mass., start-up, which currently has only 35 employees, is looking ahead to moving a second Accurin compound through development. It could be in oncology, inflammation or a cardiovascular indication, Koerwer said, noting the company has published data on a model of vascular injury. Potentially, a particle could be bound through an active targeting ligand to a protein only expressed when a blood vessel is injured, similar to when it undergoes angioplasty, and deliver a cytotoxin to prevent pathological regrowth of the endothelium.
The Russian Deal
Rusnano, officially the Russian Corporation of Nanotechnologies, was the lead investor in BIND’s last funding round. The $10 billion investment fund, financed completely by the Russian government, is interested in establishing a “nano-valley” around Moscow, Koerwer said (Also see "To Russia, With Love: Selecta, BIND To Create Subsidiaries In Financing Deals With Rusnano" - Pink Sheet, 27 Oct, 2011.).
“We did a lot of due diligence in deciding to have them make this investment, and now it’s unrolling very well.”
In addition to Rusnano, the round was joined by existing and new investors that include Polaris Venture Partners LP, Flagship Ventures, Arch Venture Partners, NanoDimension, DHK Investments and . As part of the agreement with Rusnano, BIND is establishing an affiliate in Moscow that will do R&D in parallel with the organization in Cambridge.
BIND has made no commitment on partnering its drugs on a regional or a global basis, but “being in Russia has turned out to be very attractive to some of the companies we discuss this with,” Koerwer said. “Our presence there is attractive because it’s a means for some of our partners strengthening their presence there and making a strategic commitment to Russia.” The government has made it clear to global pharma companies that it wants them to be in the country building technology, building R&D and manufacturing facilities, he said. The Russian government has a strong interest in developing a local pharmaceutical industry (Also see "Novartis, AstraZeneca Pledge Support For Russia At St. Petersburg Economic Forum In Latest Big Pharma Move To Go Local" - Scrip, 17 Jun, 2011.).