Traditionally, first-line therapy for inflammatory disorders involves immunosuppressive drugs. While this treatment can be effective for many diseases, it is often accompanied by unpleasant side effects. New strategies and agents would help improve therapeutic effectiveness.
With this goal in mind, a group of scientists at Temple University developed a proprietary drug discovery program that modifies naturally occurring bacterial metabolites to create patented formulations through the use of target-specific adjuvants. These individuals have founded SFA Therapeutics, which aims to use this technology to develop new immunomodulatory drug candidates that focus on restoring immune system balance.
Ira Spector, PhD, MBA
Chief Executive Officer and Co-founder
SFA Therapeutics
In this Innovation Spotlight, Ira Spector, chief executive officer and co-founder of SFA Therapeutics, discusses how he and his team strive to develop immunomodulatory drugs that can limit inflammation without halting overall immune function. Spector talks about the success story of SFA-002, a potentially promising agent for treating psoriasis.
Can you describe your proprietary drug development platform?
Many microbes exist in the human body through a symbiotic relationship, and their metabolites can play important roles in regulating immune function and maintaining homeostasis. Our process has been to take such metabolites and modify them with target-specific adjuvants to address specific disease states, improve their potency, selectivity, and safety, as well as ensure patentability.
How similar are these biosynthetic agents to naturally occurring molecules?
One of the key things that we do in the development of our biosynthetic compounds is to improve their specificity by making them more targeted than naturally occurring molecules. While we seek to engage multiple targets with each of our drug candidates, tailoring our molecules towards a group of specific targets allows us to correct specific disease states by re-balancing the immune system back to its natural state of homeostasis.
Improving the bioavailability of the molecules that we work with is also a critical aspect of our efforts. While many naturally-occurring metabolites have theoretical applications as therapeutic agents, their bioavailability and short-lived nature compromise their ability to act as practical treatments. What we do is to take these molecules that have strong potential as therapeutics and modify them through our proprietary drug development platform to improve their bioavailability and make their effects longer-lasting. This allows us to develop practical therapeutic agents that can have real effects in patients.
Finally, the abundance of naturally occurring microbes in the human body can vary greatly from individual to individual both in terms of quantity and with respect to the specific types of microbes. This leads to a high degree of variability in the types of metabolites produced as well as their overall levels within the body. By adapting specific metabolites into biosynthetic compounds and administering them in a known quantity, we are able to produce a tailored and standardized effect across patient populations.
What makes these agents potentially more efficacious, consistent, or safer than other options?
Although immunosuppressive drugs are often effective at the outset, their therapeutic benefits can diminish within a few months. These medications also increase susceptibility to infections and frequently cause side effects such as headaches, nausea, and fatigue. For some patients, the complexity of dosing schedules, the inconvenience of administration methods like injections or infusions, and the burden of side effects lead them to discontinue regular use. We are developing therapeutic candidates that limit the negative side effects associated with immunosuppressive drugs, as evidenced by the topline data readout of our Phase 1b oral drug candidate SFA-002, which was shown to produce no treatment related adverse events during the trial and may be taken orally to improve the patient experience.
How do these compounds potentially remove the need for consistent dosing over long periods of time?
By leveraging a multi-target strategy, we may engage with multiple disease-associated pathways to restore the overall system to a healthy baseline. The strategy is to break the cycle of cascading effects that lead to long-term immune dysfunction. The human body incorporates multiple parallel mechanisms to regulate normal cellular functions. When a single channel is downregulated, such as by a monoclonal antibody-drug, the other channels may increase to compensate, sometimes resulting in little effect on a disease. In the case of SFA-002, by targeting multiple known disease channels simultaneously, while immunomodulating and not immunosuppressing, we can effectively shut down the disease with fewer side effects.
Interleukin 10 is an immune-modulating cytokine that also serves as a potential basis for novel therapeutic agents.
iStock, vdvornyk
Can you describe SFA-002 and how it functions?
SFA-002, our interleukin (IL)-10 upregulator in immune cells for the treatment of psoriasis, may simultaneously affect multiple targets. It exerts anti-inflammatory effects while simultaneously blocking a number of inflammatory cytokines such as IL-6, tumor necrosis factor (TNF)-α, IL-17A, IL-17F, interferon (INF)-γ, IL-23, IL-6, and IL-12. This comprehensive approach allows SFA-002 to limit multiple inflammatory processes associated with psoriasis.
As an autoimmune disease, psoriasis pathology is driven by an overall state of immune dysfunction. By targeting multiple pathways of the disease within the immune system, we are able to tilt the scale back in favor of healthy immune function. In a recent clinical trial, treatment with SFA-002 was shown to produce statistically significant improvements in Psoriasis Area and Severity Index (PASI) percentage change and Investigator Global Assessment (IGA) score improvements compared to placebo.
What is next for SFA-002 and SFA Therapeutics?
Our primary focus is advancing SFA-002 into Phase 2 clinical trials for the treatment of psoriasis, where we see significant unmet need and therapeutic potential. While psoriasis remains at the forefront of our efforts, we are also building a broad pipeline of investigational therapies targeting inflammation and immune dysregulation. Recent patent protections strengthen our ability to explore future indications, including autoimmune diseases and hepatocellular carcinoma. Backed by a robust drug discovery platform, we are positioned to continue developing innovative treatments that address a range of immune-related conditions.
