Press

The Institute for Systems Biology (ISB) and NED Biosystems (NED) will collaborate on an intriguing clinical trial that aims to use a cocktail of several marketed medications at low doses to reverse cancer’s onset or regrowth. Leroy Hood, MD, PhD, co-founder of ISB and Rebecca Lambert, founder and CEO of NED Biosystems, announced the deal at the end of October.

The Phase 1b/2 clinical trial will use NED-170, which was designed as a systems biology approach. The regimen combines repurposed, marketed drugs, and nutraceuticals that are documented to affect critical cancer disease-driver processes in people. It employs smaller doses in an effort to avoid toxicity and side effects.

“NED is a totally new type of therapy,” says Sui Huang, MD, PhD, an ISB professor. “We are pioneering a systems biology approach to cancer.”

The trial will use multi-dimensional monitoring of the tissue surrounding tumors using a blood test that employs the latest ultra-sensitive, hyper-personalized, proteomics technologies. This approach can measure traces of more than 3,000 distinct proteins at once that reveal many processes in the tumor tissue, thereby offering evidence about which of the individual agents in NED-170 will be useful for a particular patient.

“We use the Olink technology for proteomics, which changes everything,” says Huang, “With our omics expertise and these tools we can provide a truly systems view of what’s happening in patients.”

NED-170 was evaluated pre-clinically for tolerability and efficacy using a murine xenograft model. The company also has a compassionate expanded access program for patients with advanced tumors who either seek alternatives to standard-of-care (SOC) chemotherapy or whose tumors have progressed through available SOC options.

“A systems biology approach is paramount—NED-170 is the multi-pronged treatment required to subvert cancer’s complex system,” says Hood.

The trial is designed to treat patients undergoing standard of care who lack an option for targeted therapy based on tumor genome sequencing. It will cover three indications representing large unmet needs: cholangiocarcinoma, triple negative breast cancer, and ovarian cancer.

NED is initially targeting the 50% to 80% of cancer patients whose tumors do not carry mutations for targeted therapy. Based on observational data, NED believes its systems treatment, when combined with standard of care therapies, may afford patients extended survival and enhanced quality of life.

The data collected from NED’s initial trial and follow-on clinical trials will serve to develop a database for ISB’s large study utilizing proteomics and NED-170 to optimize the systems approach for suppression of cancer progression based on driver processes in subclasses of patients.

High-dimensional profiling of a patient’s blood biochemistry baseline, the team says, can provide information about how the tumor bed is preparing for outgrowth before a the cancer is clinically detectable, which can be a different process in different patients. It can also tell precisely which biological processes a particular tumor relies on most to (re)grow in a given patient. NED believes uncommon quality of life improvements (and cost savings) may be achieved when a cancer patient is treated with evidence-based agents efficacious against key pathways even at low doses.

“By moderating multiple cancer progressing pathways and cancer stem cells at once, NED-170 affords a comprehensive systems approach never before available to cancer patients,” says Lambert. “The comprehensive blood profiling utilized to measure NED-170’s impact on pathways advances a personalized measurement of each patient’s unique cancer signature.”

About Inside Precision Medicine
Inside Precision Medicine is the leading source of practical insights for pathologists, clinicians, researchers, and scientists working to translate important findings across the broad range of “omics” technologies to deliver on the promise of molecular and precision medicine for patients.

NED’s cancer treatment, NED-170, takes a systems approach that combines repurposed, oral agents that are well documented in humans to affect critical cancer disease-driver processes at doses that lack customary toxicity and side effects

SEATTLE – Leroy Hood, MD, PhD, co-founder of Seattle’s Institute for Systems Biology (ISB) and a pioneer in systems biology, and Rebecca Lambert, founder and CEO of NED Biosystems, Inc. (NED), a public benefit corporation that is developing the first oral “systems treatment” for cancer, have entered into a memorandum of understanding to collaborate on a clinical trial to show how cancer’s onset may be reversed.

NED’s cancer treatment, NED-170, takes a systems approach that combines repurposed, oral agents that are well documented in humans to affect critical cancer disease-driver processes at doses that lack customary toxicity and side effects.

“A systems biology approach is paramount – NED-170 is the multi-pronged treatment required to subvert cancer’s complex system,” said Hood, who is inventor of the DNA Sequencer, technology which enabled the Human Genome Project.

The collaborative trial’s objective is to gather intelligence through a multi-dimensional monitoring of the tissue in which a tumor grows. A simple blood test utilizes the latest ultra-sensitive hyper-personalized proteomics technologies to measure the traces of more than 3,000 distinct proteins at once that reveal many processes in the tumor tissue, thereby offering an assessment of the specific efficacy of the individual agents in the multi-pronged approach.

NED-170’s Phase 1b/2 clinical trial is designed to treat patients concomitant to standard of care who lack an option for targeted therapy based on tumor genome sequencing in three indications representing large unmet needs: cholangiocarcinoma, triple negative breast cancer, and ovarian cancer.

NED is initially targeting the 50 percent to 80 percent of cancer patients whose tumors do not carry mutations for targeted therapy. Based on observational data, NED believes its systems treatment, when combined with standard of care therapies, may afford patients extended survival and enhanced quality of life. The data collected from NED’s initial trial and follow-on clinical trials will serve to develop a database for ISB’s large study utilizing proteomics and NED-170 to optimize the systems approach for suppression of cancer progression based on the driver processes in subclasses of patients.

“A truly comprehensive approach to a complex adaptive system like cancer, as the war on global terror has taught us, must be a multi-pronged approach that moderates, without adding stress, the various behaviors that promote cancer and allows the tissue to re-establish the balance of a normal cell community,” said Sui Huang, MD, PhD, and ISB professor, cancer cell dynamics expert, and NED Biosystems Systems Advocate.

The envisioned high-dimensional profiling of a patient’s blood biochemistry baseline can inform doctors about how the tumor bed is preparing a tiny tumor for outgrowth before a tumor is clinically detectable, which can be different in different patients. It can also tell us precisely which biological processes a particular tumor relies on most to (re)grow in a given patient. Uncommon quality of life improvements (and cost savings) may be achieved when a cancer patient is treated with evidence-based agents efficacious against key pathways at doses that lack toxicity and side effects.

“By moderating multiple cancer progressing pathways and cancer stem cells at once, NED-170 affords a comprehensive systems approach never before available to cancer patients,” said Lambert. “The comprehensive blood profiling utilized to measure NED-170’s impact on pathways advances a personalized measurement of each patient’s unique cancer signature.”

About ISB

Institute for Systems Biology (ISB) is a collaborative and cross-disciplinary non-profit biomedical research organization based in Seattle. We focus on some of the most pressing issues in human health, including aging, brain health, cancer, COVID-19, the human microbiome, as well as many infectious diseases. Our science is translational, and we champion sound scientific research that results in real-world clinical impacts. ISB is an affiliate of Providence, one of the largest not-for-profit health care systems in the United States. Follow us online at isbscience.org, and on YouTube, Facebook, Instagram, LinkedIn and Twitter.

About NED Biosystems

Based in Cambridge, Mass., NED Biosystems is a clinical-stage biotech company founded by Rebecca Lambert to develop safe, efficacious, and comprehensive “systems” treatments for complex disease, beginning with the development of the patented NED-170 for treatment of cancer. Ease of oral dosing, favorable storage conditions and cost-effectiveness of the treatment supports the company’s mission to provide revolutionary, efficacious treatment solutions to patients not only in the U.S. and other developed nations but also in the developing world. Visit NEDbiosystems.com.

Hennessy’s Highlights – The Latest Oncology News from Mike Hennessy, Jr., President – OncLive.com

April 2019

Biotechnology company NED Biosystems is developing a novel therapeutic that integrates 7 compounds into a single orally administered treatment regimen for patients with late-stage cancer. The company, based in Cambridge, Massachusetts, has landed a patent from the US Patent and Trademark Office that it believes is the first issued to protect the composition of matter for a formulation containing this number of components.

The therapeutic, NED-170, consists of the FDA-approved chemotherapy drugs cyclophosphamide, metformin, and naltrexone combined with the naturally occurring compounds curcumin, melatonin, α-lipoic acid, and genistein. Investigators for NED Biosystems hypothesize that these 7 components, when combined in a regimen involving particular doses and timing, offer a new treatment option for patients with advanced cancers that progressed through standard therapy.

The patent, which will remain in force until at least 2034, includes claims to the unique combination of NED-170 components, providing protection to any NED-170 drug product or kit, as well as claims for its use in late-stage ovarian cancer. Specifically, the patent details an ovarian cancer regimen consisting of least 1 dose per day of metformin (range, 500-1000 mg), cyclophosphamide (50 mg), naltrexone (range, 1.5-4.5 mg), α-lipoic acid (1200 mg), curcumin (range, 750-4500 mg), genistein (500 mg), and melatonin (10 mg).

The combination regimen simultaneously targets essential physiological processes driving all latestage cancers, including angiogenesis, reduced apoptosis, differential cancer cell metabolism, and evasion of immune response, according to NED Biosystems.

“Patients who have exhausted standards of care have limited treatment options. They can go into phase I clinical trials, they can recycle chemotherapy drugs, or they can opt for the palliative care pathway,” Edward Garmey, MD, chief medical officer and chairman of the scientific advisory board at NED Biosystems, said in an interview. “NED170 has been created with the view that there needs to be another pathway available for these patients that is predicated on tumor control combined with quality-of-life preservation.

“It’s a big goal, and it certainly represents a paradigm shift for what’s currently offered to [patients with] late-stage cancer, but we feel it’s an achievable goal,” Garmey added.

Garmey said the company is finalizing the protocol for a phase I/IIA clinical trial to investigate the safety and efficacy of NED-170 in 10 patients with treatment-refractory triple-negative breast cancer and 10 with refractory cholangiocarcinoma. The FDA allowed the company to bypass the typical dose escalation required in phase I studies because the drugs involved have been demonstrated to be safe and effective in clinical trials. NED Biosystems expects to begin enrollment in the second half of 2019.

The company eventually plans to investigate the combination in other types of cancers, including breast, head and neck, and leiomyosarcoma.

See full story here: http://www.bioworld.com/report/BWT02082019NED.pdf

By Michael Fitzhugh, News Editor, BioWorld Volume 30, No. 27

February 8, 2019

NED Biosystems Inc., a Cambridge, Mass.-based venture developing a seven-agent combination therapy for cancer, has secured a U.S. patent for the treatment, called NED-170. The oral regimen, which comes in a daily seven-pill pack, targets both angiogenic and immune response pathways for the potential treatment of several types of cancers. If successful, it could potentially help not only extend lives, but also drive down the costs of cancer care in certain cases.

The company’s name is pronounced letter-by-letter as an acronym for “no evidence of disease.” It was founded in 2013 by Rebecca Lambert, whose younger sister was diagnosed with stage IV leiomyosarcoma and told that she had less than a year to live, a prognosis made especially heartbreaking since she had a young son. Lambert, who was working on Wall Street at the time, quit her job to help her sister, eventually connecting in that mission with Harvard University’s Judah Folkman, a late scientist known for his research on tumor angiogenesis. With his help, Lambert built a team that put together a regimen of drugs that helped her sister live for nine years, a refinement of which now forms the heart of NED-170.

Lambert, now chairman of NED’s board, told BioWorld that “my goal for my sister’s therapy in 2001 is identical to ours at NED today, to chronically control cancer’s growth and spread, permit patients to significantly extend life and live life with the full quality we associate with health each day.”

To support that work, the company has raised more than $3 million out of an anticipated $10 million series B it expects to close before the end of the second quarter. An earlier series A round provided the company with $1.5 million in 2015.

As patented, NED-170 contains a mix of three generic drugs, cyclophosphamide, metformin and naltrexone, and four GMP-grade natural products, alpha-lipoic acid, curcumin, genistein and melatonin. “The seven compounds are all selected so that they have very specific biological activity because we want multiple driver processes of cancer,” CEO Marc Blaustein told BioWorld. Each is given at a dose that’s known to be well-tolerated and has been selected to avoid drug-drug interactions, he said. Taken together, the medicines act to target two fuel supplies of growing tumors — angiogenesis and metabolism — while simultaneously aiming to boost immune response and apoptosis.

To test expectations for the combination, the company is gearing up for a small phase I/II trial which its team hopes to begin around the middle of this year. The open-label study is designed to enroll 10 patients in each of two arms, one focused on the rare cancer cholangiocarcinoma and the second testing the regimen in triple-negative breast cancer. Blaustein said he expects the trial to take about 18 months to run. In addition to safety data, investigators will also be looking for additional tumor response using RECIST criteria, progression-free and overall survival.

If successful, the company will decide whether to seek a partner to proceed with its work, raise additional capital or potentially go public, Blaustein said. Initial plans also include running a registration-directed cholangiocarcinoma trial to support a 505(b)2 new drug application while also looking ahead to phase III studies in other indications or potentially a basket trial.

The company announced Thursday that the U.S. Patent and Trademark Office has awarded it U.S. Patent No. 10,195,219 for NED-170, a protection that expires no earlier than 2034. Blaustein said his team is also pursuing intellectual property protections in other major markets.

As a Delaware Public Benefit Corporation, the company is also aiming to make a positive impact on the world by providing an at-home, low-toxicity therapy. “That goes with our quality-of-life focus,” he said. “But it also means that the costs that you typically associate with cancer care, including managing intense side effects and special delivery at infusion centers, you should be able to avoid with NED-170, meaning it could be very effective for overall cancer treatment.”

Another part of the company’s long-term vision, Lambert said, is to provide cancer treatments to under- and unserved patients in the developing world. “Requiring neither sophisticated clinical infrastructure nor cold chain management, NED-170 is uniquely suited to make cancer treatment possible in the developing world where today most patients lack any treatment,” she said.