Who is the real boss? For Ira Spector, CEO and co-founder of SFA Therapeutics, the answer is the patient. His focus is on changing the treatment path for chronic inflammatory diseases.

Spector has 30 years of industry experience, having led clinical trials at companies such as Wyeth (now part of Pfizer), Allergan, and ICON, accumulating deep expertise in drug development. By all accounts, he could be relaxing on a beach enjoying retirement, but he says retirement is overrated.

"I tried retirement twice and hated it both times," he says. "There is so much unmet medical need out there that I just can't retire with a clear conscience. Do I want to go to the beach? Of course. Do I want to relax? Of course. But I find I just can't do it. I was born for this."

Indeed—Spector has overseen more than 500 clinical trials and 34 New Drug Applications (NDAs) over his career. His latest venture, SFA Therapeutics, claims to have "a completely new approach to drug discovery and development." That's a bold statement, but Spector believes he and his co-founders are working on something special: a development platform linking chronic inflammation to cancer.

"We call ourselves a fourth-generation microbiome company," Spector explains. "We're not first-generation (fecal transplants), we don't do probiotics (we don't think they reach effective targets), and we don't do bacterial colonization (which requires personalized medicine). We use substances produced by bacteria in the human body and study how to turn them into drugs. We've found that these substances play an extremely important role in regulating the immune system."

Because this science relies on "bacterial metabolites" found in the human body, there is no genotoxicity, which can accelerate clinical development and lead to safer treatments.

"This platform is so compelling and unique that it demands we build a company around it," Spector says.

The "SFA" in SFA Therapeutics

Spector happened to meet Mark Feitelson—the "F" in SFA—at a lunch in 2015. During their conversation, Feitelson mentioned that he had co-developed a drug aimed at "blocking the progression of hepatitis B to liver cancer," but had been unable to find a partner.

"I told him, 'I've been in drug development for about 30 years, let me come to your lab and look at the data,'" Spector recalls.

After visiting the lab, Spector was impressed by the data supporting Feitelson's scientific theory, which targeted "a master switch in key pathways of inflammation and cancer." Encouraged by the results, Spector realized that what Feitelson was working on was significant.

"(Feitelson's) data showed remarkable effects in transgenic animals—half of the animals didn't develop liver cancer, and the other half only developed tiny tumors—the effect was very significant," he says.

Spector recognized that Feitelson's discovery had potential far beyond cancer.

"I told him he had a platform from which I could pick targets and match them to different diseases," Spector says.

The next step was to validate the science in human models. That's where the "A" in SFA—Alla Arzumanyan—came in. As Feitelson's co-inventor, Arzumanyan began working on translational research. A year later, SFA Therapeutics was born.

Now six years into the company's existence, SFA has identified six small-molecule drug candidates from this platform, including drugs targeting major indications such as psoriasis, rheumatoid arthritis, Crohn's disease, and irritable bowel syndrome. In total, the company is studying the potential of 85 different targets for chronic inflammatory diseases.

"Imagine drugs derived from substances found in the human body that have co-evolved with humans for thousands of years, are not carcinogenic, have extremely low side effects, and without which we couldn't even function properly," Spector says. "We've found that many patients with autoimmune diseases lack these substances or can't produce them properly because they often also have gastrointestinal issues in addition to their underlying autoimmune disease. But if we can provide these microbiomes as a drug (which, by the way, is not simple), then we can have a profound impact on patients, just like giving insulin to type 1 diabetes patients because they can't produce it themselves."

Earlier this month,the FDA approved SFA's applicationto conduct an Investigational New Drug (IND) application, investigating SFA-001N in patients with NASH (nonalcoholic steatohepatitis) with or without fibrosis. This disease, which currently has no approved therapies, affects 1.5% to 6.5% of U.S. adults and can progress to cirrhosis or liver cancer. By acting on multiple molecular pathways simultaneously, SFA-001N has the unique potential to address the inflammatory and fibrotic responses associated with NASH, which is projected to become the leading cause of liver transplants by 2030.

"This IND approval is a significant milestone for SFA Therapeutics," Spector says. "By expanding our pipeline into new therapeutic areas, wehave the opportunityto demonstrate that our novel microbiome-derived drug development platform has the potential to address a wide range of autoimmune and chronic inflammatory diseases across multiple organs."

Spector added that the IND validated the initial hypothesis and allows SFA "to tailor our initial discoveries to specific diseases by matching specific bacterial metabolites... In doing so, we are essentially upregulating and downregulating cytokines in different pathways, and we've been doing this work for six years, even before the public knew what cytokines were."

SFA Health also receivedorphan drug designationfor its original drug, SFA-001, which is used to block the progression of hepatitis B to hepatocellular carcinoma. Spector says this is a huge problem, especially in Asia, where it is considered endemic.

"In Asia, more than 300 million people have hepatitis B," he says. "In the U.S., about 54,000 people die from its sequelae, hepatocellular carcinoma. But in Asia, especially in China, it's the second leading cause of liver cancer after stomach cancer."

Getting up and running quickly

Going from company formation to clinical trials in just six years requires a lot of expertise. Spector is relying on many of the lessons he's learned throughout his career, including how to be efficient and focus on what matters at critical moments.

"One thing we did at Wyeth that I've always remembered is that if you analyze the steps needed to develop a drug, some are essential, while others are 'nice to do at the right time,'" he says. "Meaning, some things you don't need to do at the beginning; you can save them for later."

According to Spector, many pharmaceutical companies still use a drug development approach that he believes is "20 to 25 years out of date."

"This includes doing a lot of things at the start that aren't necessarily needed," he explains. "Our focus is: How do we prove this works? Where is the signal? How strong is the signal? Does it translate? Can we formulate it? We've streamlined the entire drug development process to these core elements. Then we work to efficiently design what I call 'elegant experiments'—using the fewest patients and the right data to answer the right questions. There are many other things that need to be done downstream, but they're not essential at this point."

As with any small company, the difficulty lies in funding clinical research, no matter how efficiently the trials are designed. So, in 2017, the company pivoted to focus on psoriasis to prove its concept. Spector and his team believe this indication is a gateway to treating autoimmune diseases because it allows for the downregulation of multiple cytokines and multiple targets.

"We started with psoriasis because through the skin we can see treatment effects fairly quickly, and we don't need to develop complex biomarkers," Spector explains. "SFA-002 came from this work—it simultaneously downregulates IL-17, IL-23, TNF-α, interferon-γ, and upregulates anti-inflammatory IL-10."

Spector's understanding of TNF-α stems from his days at Wyeth, where he was part of the team that developed Enbrel, a blockbuster drug for treating autoimmune diseases.

"Enbrel later became an $18 billion drug, but it only targets TNF-α. Imagine what it would mean if there were a single drug that could target all the major pathways associated with autoimmune diseases?" Spector muses. "That's why we've put all our energy into SFA-002, which is now in its second trial, a Phase 1b with 30 subjects and two cohorts, with the first cohort already enrolled. Then we'll expand our portfolio in the first quarter of 2023 to bring SFA-001 into clinical studies for NASH and fibrosis. We're very pleased with what we've achieved; we've been granted nine patents and are looking forward to a tenth."

Throughout his career, Spector has witnessed the ups and downs of the biotech sector. In the current environment, he says there is still plenty of capital available for companies that can achieve strong differentiation by "demonstrating unprecedented ability to change the course of a patient's disease."

"It's nice to have theories, but we actually have excellent data from our first Phase 1a," he says. "Six out of six patients showed meaningful clinical responses. We're now looking at the Phase 1b (open-label) data, and we're very excited about the responses we're seeing. When we complete this trial—and we hope to have a data readout by the end of the first quarter of 2023, or at least by the end of the first half—that data will be truly critical."

For this PharmaVoice honoree, SFA Therapeutics is the culmination of all the experiences in his career, including earning his PhD.

"This is the most important thing I've ever done," he says. "I'm using what I learned in my PhD program and career to build this company. I won't say this is the last thing I'll do, because I already have my next idea. Our vision is to change medicine, and that's a very ambitious goal. We have an extraordinary opportunity and an extraordinary responsibility to push what we have forward. I think if I were sitting on a beach right now, I'd feel very guilty, because we believe what we have has that kind of potential."