Who’s the boss? For SFA Therapeutics’ CEO and co-founder Ira Spector it’s patients, and his sights are set on changing the course of treatment for chronic inflammatory disease.
A 30-year industry veteran with extensive drug development expertise running clinical trials at Wyeth (now part of Pfizer), Allergan and ICON, Spector could be sitting comfortably on a beach somewhere. But he said retirement is overrated.
“I tried to retire twice and hated it both times,” he said. “There’s so much unmet need out there that I just couldn’t feel comfortable retiring. Do I try to go to the beach? Sure. Do I try and relax? Sure. But I’ve discovered that I just can’t. I’m wired to do this.”
Wired indeed — Spector has overseen more than 500 clinical trials and 34 NDAs during his career. His latest venture, SFA Therapeutics, boasts a “completely new approach to drug discovery and development.” That’s a pretty bold statement, but Spector believes he and his co-founders are onto something special: a development platform that intersects chronic inflammation and cancer.
“We call ourselves a fourth-generation microbiome company,” Spector explained. “We’re not first generation, which is fecal transplant. We’re not doing probiotics, which we don’t think get to the targets that do any good. We’re not doing bacterial colonies, which we think requires personalized medicine. We are using substances that are created by bacteria in the body and figuring out how to turn those into drugs. We’ve discovered that these substances have exquisitely important roles in modulating the immune system.”
Because the science relies on “bacterial metabolites” found in humans, there is no genotoxicity, which can lead to faster clinical development and safer treatments.
“The platform was so compelling and different (from) anything else out there, it demanded we build a company around it,” Spector said.
The SFA of SFA Therapeutics
Spector met Mark Feitelson — the “F” of SFA — by chance at a luncheon in 2015. During the course of their conversation, Feitelson shared that he had co-developed a drug to “block the progression of hepatitis B to liver cancer,” but he couldn’t find a taker.
“I told him, ‘I’ve been in drug development for 30 or so years. I’ll come to your lab and look at your data,’” Spector recalled.
After visiting the lab, Spector was impressed by the data supporting Feitelson’s science, which targets a “master switch in key pathways involved in inflammation and cancer.” Buoyed by the results, Spector knew Feitelson was onto something big.
“(Feitelson’s) data showed outstanding results in transgenic animals — half the animals developed no liver cancer and the other half developed tiny tumors — a profound effect,” he said.
Spector recognized that the potential of Feitelson’s findings could extend well beyond cancer.
"Do I try to go to the beach? Sure. Do I try and relax? Sure. But I’ve discovered that I just can’t. I’m wired to do this.”
CEO, co-founder, SFA Therapeutics
“I told him he has a platform I could pick targets (from) and match to different diseases,” Spector said.
The next step was to prove the science based on human models. Enter the “A” in SFA: Alla Arzumanyan. As Feitelson’s co-inventor, Azrumanyan got to work on the translational research. A year later, SFA Therapeutics was born.
Now six years in, SFA has identified six small molecule drug candidates from this platform, including drugs for major indications such as psoriasis, rheumatoid arthritis, Crohn’s disease, IBS and more. Altogether, the company is examining the potential of 85 different chronic inflammatory disease targets.
“Imagine drugs that are developed from substances found in the human body, substances that have evolved with humans over eons and that have no carcinogenicity, that have very low side effects and without which, we can’t function,” Spector said. “We discovered that patients who have a number of autoimmune diseases lack these substances or don’t make them properly, because they often have GI issues as well as their underlying autoimmune disease. But if we provide these microbiomes as a drug, which is not so simple, by the way, then we can have a profound effect on patients, just like insulin is provided to Type 1 diabetics, because they can’t make them internally.”
Earlier this month, the FDA cleared SFA’s application for an IND to investigate SFA-001N in patients with NASH (non-alcoholic steatohepatitis) with or without fibrosis. The condition, which currently has no approved therapies, affects between 1.5% and 6.5% of adults in the U.S., 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 transplantation by 2030.
“This IND clearance represents a significant milestone for SFA Therapeutics,” Spector said. “By expanding our pipeline to a new therapeutic area, we have the opportunity to demonstrate that our novel microbiome-derived drug development platform has the potential to address a wide range of autoimmune and chronic inflammatory conditions in multiple organs.”
Spector added that the IND validates the initial thesis and allows SFA to “tailor our original discoveries to specific diseases by matching specific bacterial metabolites … and in doing so, we’re essentially manipulating cytokines up and down various pathway, which we’ve been doing now for six years before the public even knew what a cytokine was.”
SFA Health also received an orphan drug designation for its original drug SFA-001 for blocking the progression of hepatitis B to hepatocellular carcinoma, which Spector said is a huge issue, particularly in Asia where it’s considered endemic.
“Some 300 million-plus people suffer from hepatitis B in Asia,” he said. “In the U.S., about 54,000 people die from the sequelae, which is hepatocellular carcinoma. But in Asia, especially in China, it’s the second-leading cause of liver cancer after gastric cancer.”
Up and running at speed
Transitioning from company inception to clinical trials in six years requires a lot of know-how, and Spector is relying on the many lessons of his career, including how to be efficient and leaning into what matters, when it matters.
“One of the things that we did at Wyeth, which has always stayed with me, is if you analyze the steps required to develop a drug, there are must dos and there are just-in-time dos,” he said. “Meaning, there are things you don’t have to do upfront that you can do later.”
According to Spector, many pharma companies still use a drug development approach that he said is “20 to 25 years out of date.”
“This includes doing a lot of things upfront that don’t necessarily have to be done upfront,” he explained. “Our focus is on: How do we prove that this works? Where’s the signal? How big is the signal? Is this translatable? Can we formulate it? We’ve stripped the entire drug development process down to these essentials. And then we’ve worked to be very efficient in how we design what I call ‘elegant experiments,’ which include a minimum number of patients and the right data to answer the right questions. There are lots of other things that will need to be done downstream, but they didn’t have to be done up to this point.”
As with any small company, the difficulty is funding clinical research, no matter how efficiently the trials are set up. So in 2017, the company pivoted to focus on psoriasis to show proof of concept. Spector and team believe this indication is the gateway to treating autoimmune disease because of the multiple cytokines and multiple targets that can be down regulated.
"We have an extraordinary opportunity and extraordinary responsibility to take what we have forward."
CEO, co-founder, SFA Therapeutics
“We started with psoriasis, because with the skin we can see the treatment effect fairly quickly and we don’t need to develop sophisticated biomarkers,” Spector explained. “SFA-002 came from that work — it simultaneously down regulates IL-17, IL-23, TNF-alpha, interferon gamma and upregulates anti-inflammatory IL-10.”
Spector’s understanding of TNF-alpha stems back to his days at Wyeth, where he was part of the team that developed the blockbuster Enbrel for autoimmune diseases.
“Enbrel, which became an $18 billion drug, focused only on TNF-alpha, so imagine a single drug that focuses on all the primary channels associated with autoimmune disease and what that could do?” Spector mused. “That’s why we put all of our focus on SFA-002, which is now in its second trial, a phase 1b with 30 subjects and two cohorts, the first cohort is already enrolled. And then we will broaden our portfolio in the first quarter of 2023 by going into the clinic for SFA-001 for NASH and fibrosis. We’re pretty pleased with what we’ve done; we have nine patents issued and we’re expecting our 10th.”
Over the course of his career, Spector has seen the fluctuations in the biotech space, and within the current environment he said there’s still a lot of capital available for companies that can strongly “differentiate by showing the ability to do something that’s never been done before that can change the course of disease for patients.”
“It’s great to have a theory, but we actually have outstanding data from our first phase 1a,” he said. “Six out of six patients showed a meaningful clinical response. We’re now seeing data in the phase 1b, which is an open label. And we’re very excited by the responses we’re seeing. And when we complete this trial, which we hope to have a data read-out hopefully end of first quarter or at least end of first half of 2023, those data are really what will be critical.”
For the PharmaVoice honoree, SFA Therapeutics is the result of everything he’s learned over his career, including getting his Ph.D.
“This is the ultimate thing I’ve done,” he said. “I’m using what I learned during my Ph.D. program and over my career to build this company. I won’t say it’s the last thing I’m going to do because I already have the next idea. Our vision is to change medicine, which is a very big goal. We have an extraordinary opportunity and extraordinary responsibility to take what we have forward. I think if I was sitting on the beach, I’d feel very guilty, because we think what we have has that kind of potential.”