WiNK Therapeutics Is Using RNA Tech to Tackle Insulin Dependence at the Source

MIT and Duke-trained engineer Warren D. Marcus, PhD, has teamed up with researcher Paolo Serafini, PhD, to develop a way to use RNA technology to reverse the causes of Type 1 diabetes and insulin-dependent Type 2 diabetes. While still in the preclinical stage, WiNK’s research offers a ray of hope for millions suffering from diabetes.

Challenge

“My earliest childhood memory is finding out that my grandmother lost her sight.”

Warren D. Marcus grew up in Florida with his maternal grandmother, sharing a room with her until he was ten years old. After her vision went, he remembers retrieving things for her, getting her water, helping her with her food. She had insulin-dependent Type 2 diabetes and endured one complication after another.

First she experienced kidney failure and they started her on dialysis. Then she lost one leg to amputation, followed by the next. After that, she suffered a heart attack.

“Basically everything that could go wrong with diabetes went wrong with her,” Marcus explains.

Between ages six to 14 — in essence, his entire childhood — Marcus and his family cared for his grandmother through all her setbacks and emergencies. He remembers it now, but for years, he actually suppressed some of these painful memories. It was only when he grew up and came across the research of Paolo Serafini, an associate professor of microbiology and immunology at the University of Miami, that they came flooding back.

Why? Because Serafini’s work proposed a viable way to use RNA to tell the body to replace the lost insulin-producing cells and could also signal the body to block the autoimmune attack that destroys insulin-producing cells in Type 1 diabetics. It was, in essence, a game-changing breakthrough in addressing diabetes — a possible cure. As Marcus vetted the work, checking and double checking Serafini’s findings, he marveled at what this technology could mean to people living with Type 1 diabetes or insulin-dependent Type 2 diabetes. And that’s when he remembered his grandmother and what he watched her go through and what this could have meant to her.

Origin Story

Marcus encountered Serafini’s novel technology while looking for assets to form his own company after years working for an oncology-focused biotech company. Although he didn’t know it at the time, his journey towards this decision started soon after his grandmother passed, when at age 16, he won the Florida Power and Light Scholarship, helping him to gain a spot in the engineering program at MIT.

“At the time, I had to choose between mechanical or electrical engineering. I was a kid; I didn’t know what I wanted to do, so I flipped a coin mentally and mechanical won.”

While at MIT, he quickly realized he didn’t want to stay in the pure mechanical engineering space. He was interested in combining mechanical engineering with biology, creating tools and solutions for health problems. After undergraduate, Marcus pursued a PhD in cellular and biosurface engineering from Duke, did a postdoc in biophysics while at Georgia Tech, and then spent years in a research position at Arizona State University working on potential diagnostics and therapeutics for Alzheimer’s disease.

After moving into the biotech industry in 2006, Marcus headed the cloning group for Altor BioScience Corporation, overseeing the plasmid construction and initial protein production of new molecules for the development of two lead cancer-fighting immunotherapy products. He was one of the scientists responsible for the discovery and development of ALT-803 — an immunotherapeutic agent that has been noted by the Director of the Cancer Immunotherapy Trials Network as one of the top agents likely to cure cancer.

This discovery took on a highly personal significance to Marcus, who lost his uncle and paternal grandmother to cancer right around the time he began his work on it, and then, over the course of his 12 years at the company, lost three more uncles to cancer.

“When I started thinking about building my own company, developing therapeutics for cancer was first and foremost on my mind.”

Using his experience as both a researcher and a business development lead, Marcus began searching around for the right innovation or research to develop into a product. He wanted an idea that was early enough to raise the necessary funding for the IP costs, but far enough along in its research and funding to be viable. At first, he pursued an interesting oncology-focused asset at the University of Miami, but in the process of vetting that asset, he learned that its primary researcher, Paolo Serafini, was also working on a diabetes intervention.

“As I looked more and more into it, I realized it was an absolute game changer. I talked to someone at Pfizer who had worked in diabetes for 20 years and she said, ‘honestly, this is the holy grail.’ It’s around then that all those memories of my grandmother came rushing back. I realized that if I had a real opportunity to make a difference in this disease, I wanted to do it.”

The Product

Serafini’s innovation in treating Type 1 and insulin-dependent Type 2 diabetes is two-fold. First, he developed an RNA construct which consists of an aptamer that delivers the strand of genetic material to the right place: in essence, he created a ‘molecular Uber’ that gets the information where it needs to go. Now that the ‘Uber’ has allowed for delivery specifically to the insulin-producing cells, there are two different genetic payloads that are delivered: one that tells the cells to start to reproduce themselves and another signals the cells to make protective proteins on the surface of the cell to stop the hallmark autoimmune attack in Type 1. It’s a two-pronged approach that both creates new insulin-producing cells (needed for Type 1 diabetes sufferers and insulin-dependent Type 2s) and protects them (needed for Type 1s).

RNA is notoriously unstable and difficult to work with, which meant that other investors shied away from Serafini’s work. But Marcus looked into the science and saw that Serafini managed to modify the RNA to make it more thermostable. It lasts long enough to deliver its message via the aptamer (molecular Uber) and then it’s gone. The aptamer Serafini built also binds exclusively to the islet cells it targets and not to other human tissue, making it a targeted, safe intervention.

Marcus was in. In December 2021, he and Serafini signed an agreement and became the co-founders of WiNK Therapeutics, a preclinical stage biotech company using RNA aptamers for drug delivery. They’ve already tested the impact on human insulin-producing islet cells engrafted in mice with great success — the mice in the studies both regenerated human islet cells and highly expressed the protein on the surface that is known to protect these cells from autoimmune attack.

“It’s such a novel approach to use RNA this way,” Marcus emphasizes. “And the beautiful thing about our patent is that it blocks anyone else from using an RNA aptamer to target the specific proteins we target.”

If all continues to go well, they will likely initiate clinical trials in patients within three years. They are also exploring other applications of the technology, including implications for fighting cancerous cells, the research that initially drew Marcus to Serafini’s work. Another type of aptamer could work to deliver targeted chemotherapy to precisely where it needs to go in the body. Compared to antibodies, these RNA aptamers are relatively inexpensive and non-immunogenic, meaning the body won’t treat this drug-delivery system like a foreign invader and launch a counter-attack.

For now, the focus is on diabetes, and the company has spent the last year making sure their drug is optimized for manufacturing and bringing on team members and advisors to help accelerate the process of getting their solution to the people who so desperately need it. On the research and manufacturing side, they’ve enlisted Mark Tracy, who, among other things, oversaw the manufacturing of the first RNAi therapeutic to be approved by the FDA. Marc Rudoltz leads their Clinical/Regulatory division, bringing years of leadership experience in the clinical development, regulatory, and commercial aspects of multiple drugs.

In a full circle moment for Marcus, one of their advisors is Jay Skyler, MD, an endocrinologist from the University of Miami and former president of the American Diabetes Association. When Marcus mentioned Skyler to his family, his dad told him the name sounded familiar. It turns out that Skyler was a doctor who treated Marcus’s grandmother at one point all those years ago when he was a boy sharing a room with her. And Skyler remembers treating his grandmother, back in the early 80s.

“When I told my mom what I was working on, what we were building for people living with diabetes, she said, ‘Are you kidding me?’ You can feel the excitement in my family to address this thing we lived with.”

Our Take

WiNK Therapeutics combines novel technology that uses RNA to effectively target islet cells, with a founding team that understands what it takes to bring a new drug to market. It’s a potent combination, especially when you consider the possibilities for this RNA aptamer drug delivery system beyond the scope of their initial diabetes work. WiNK Therapeutics’ president Warren D. Marcus, PhD, is no stranger to moonshot thinking and is eager to use the tools and community at StartUp Health to quicken the pace of getting his technology to patients. As he put it, “This kind of collaborative spirit is really important and I know we can accelerate this type of development and push therapies forward quickly together.” We can’t wait to watch their growth in the years ahead.

→ Learn more & connect with WiNK Therapeutics

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WiNK Therapeutics Is Using RNA Tech to Tackle Insulin Dependence at the Source was originally published in StartUp Health on Medium, where people are continuing the conversation by highlighting and responding to this story.

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