Aaron Goldman

Drug development is a long, costly, and risky process. Even with extensive preclinical testing, the failure rate of clinical trials is startlingly high—upwards of 90 percent. Addressing the problem of drug safety and efficacy has been top of mind for Aaron Goldman, PhD, a principal investigator at Mass General Brigham and an associate bioengineer at Brigham and Women’s Hospital, since he started his lab in 2015.

At the Brigham, Goldman has studied how cancer cells develop drug resistance, blending bioengineering, mathematics, and cancer biology. But now, in addition to uncovering cancer’s vulnerabilities, Goldman seeks to exploit them. In the past few years, his lab has developed and patented several cancer drugs, from small molecules to cell therapies. His team also uses organoids, three-dimensional tissue cultures derived from stem cells, to create effective drug screening tools.

Having worked in academic science and participating in various consulting and advisory opportunities with industry, Goldman is keenly aware of the gap between the bench and the clinic. That’s why his lab recently began working with Pluristyx, a Seattle-based biotechnology company that distributes induced plruipotent stem cell (iPSC) and embryonic stem cell products, in hopes of making even bigger strides toward better clinical models and clinically effective drugs.

“We’re really hopeful we can bring more effective drugs to patients, and much faster too,” he said.

Ironing out the kinks in the drug development process

Goldman wears many hats. Besides running a lab at the Brigham, he is also an Operating Partner on a consulting basis at BroadOak Capital, an investment firm. BroadOak is an investor in Pluristyx. That’s how he got to know Benjamin Fryer, the CEO of Pluristyx. “Ben introduced me to the PluriPartner program, in which an academic lab can get essentially unfettered use of their materials, their know-how, their resources, and their consultation to develop new therapies.”

The Goldman lab’s use of Pluristyx’s materials will allow them to address major hurdles of developing drugs that are both safe and effective. Goldman explained that drugs may fail in clinical trials because the drug development process can introduce variability. This is true for cell therapy development, he said, which is a multi-step process that’s typically carried out in stages, and often by multiple people or groups. His lab, for example, has typically been involved in the later stages of creating cell therapies for cancer, like screening CAR T cells for therapeutic potential. The earlier stages, like selecting which stem cells get made into the therapy in the first place, are typically done by companies like Pluristyx. This can add variability, and this variability can hamper the efficacy of drugs in clinical trials.

Goldman hopes to overcome these challenges through the PluriPartner program with Pluristyx. “Working with Pluristyx’s materials will enable us to be in control of the whole drug product developed,” Goldman said. This means that the lab will be able to develop and test more consistent drug products.

Screening for safer, more effective drugs

Besides the variability introduced during the drug development process, there’s another issue that might hamper the translatability of promising drugs: Preclinical models, especially animal models, don’t allow researchers to accurately predict how safe a drug will be for people. Researchers can use human cells, too, but cell models often lack the complexity of organs and aren’t the best way to test drugs for safety.

To begin to tackle this issue, Goldman will leverage the Pluristyx materials to engineer new organoid-based drug screening technologies and devices. Stem cells can be induced to create 3D tissue-like cultures called organoids, which have some of the properties of real organs.

Goldman is also moving beyond cancer with his organoid work. Using Pluristyx’s tools, specifically, their panCELLa platform, Goldman is collaborating with Luke P. Lee, PhD, of Medicine the Department of Medicine at the Brigham, to develop brain and blood-brain barrier-like organoids that can help researchers screen for drugs that can potentially treat neurological diseases, like ALS. “Luke’s group has become really critical in a lot of the engineering aspects of the translational research that we do.” Goldman is also planning to working with Joe Bonventre, MD, PhD, chief of the Division of Renal Medicine at the Brigham, to create multi-organ drug screening platforms to test the safety of kidney drugs.

Spawning new collaborations

Goldman said that researchers at the Brigham are uniquely positioned to make an impact. “The really special thing about the Brigham is that not only are we making discoveries, but we’re focused on making them work for patients,” he said. He hopes that his collaboration through the PluriPartner program with Pluristyx spawns collaborations with other researchers at the Brigham.

Another advantage of the collaboration is the speed at which Goldman’s lab might be able to bring drugs to the clinic. Academic science is focused on exploration and making breakthroughs, Goldman explained, but industry can make products at a bigger scale and take them into the clinic more quickly. “It could shrink the amount of time to make a therapy from 10 years down to three or four years,” he said. “It’s what I think is going to be a game-changer.”

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