Enosi: COVID-19 adds to autoimmune challenges

COVID-19 can be a particularly difficult disease to treat even in patients with no underlying conditions. When the patient in question is already dealing with cancer, an autoimmune disease or other diagnosis, fighting the virus becomes even more of an obstacle.

Outsourcing-Pharma (OSP) recently connected with Marc Feldmann (MF), cofounder of Enosi Life Sciences, and discussed the singular difficulties associated with treating such patients, and how research is progressing.

OSP: Could you please tell me a little bit about yourself and your work with Enosi Life Sciences?​

MF: Along with Dr. H. Michael Shepard, I am a co-founder and Board Member of Enosi Life Sciences, a drug research and development company focused on providing industry-leading therapeutics for autoimmune disease, cancer, and acute inflammation. Dr. Shepard was instrumental in the development of Herceptin, as I was in the development of Remicade.

By combining our backgrounds in oncology and anti-inflammatory therapeutics, we feel we can target the common denominator present in acute inflammatory diseases and cancer – inflammation – to improve upon what have been some of the most successful therapeutics in history. 

OSP: Specifically, please tell us about your work with COVID-19, inflammation challenges in C19 patients, and the types of therapeutics you and your colleagues have been exploring.​

MF: When a virus like COVID-19 attacks the lungs, the body releases tumor necrosis factor (TNF) to fight the infection. Too much of this pro-inflammatory cytokine creates a “cytokine storm,” causing inflammation that could lead to severe respiratory distress or death.

Scientists have used anti-TNF antibodies for more than two decades to treat severe cases of autoimmune inflammatory disease, like rheumatoid arthritis. With the timeline unclear for a successful COVID-19 vaccine, researchers should consider a range of viable therapeutic candidates, including anti-TNF therapeutics.

Anti-TNF therapeutics have been successful, but their shortfall is that they block both TNF receptors: TNFR1 and TNFR2. Enosi Life Sciences is focused on improving upon those therapeutics by developing new and improved therapeutics that inhibit the inflammatory TNFR1 without blocking the natural anti-inflammtoryTNFR2. We believe this will preserve immune system function and improve patient outcomes.

OSP: What are some of the benefits in the strategy of targeting inflammation in C19 patients?​

MF: One characteristic of deteriorating lung function in COVID-19 patients is capillary leak, which is often a product of inflammation driven by several key inflammatory cytokines, two of which are IL-6 and TNF. Knowing this, some researchers have tried to block cytokines, specifically IL-6, to treat COVID-19 but have been unsuccessful so far.

Anti-TNF therapy has a strong track record of reducing inflammation, so because the inflammatory cytokines blocked by anti-TNF therapy are also present in COVID-19 patients, researchers believe that anti-TNF therapy could reduce the capillary leak present in COVID-19 patients and in turn, reduce the need for oxygen and ventilation, as well as the mortality rate, in COVID-19 patients.

OSP: Could you please explain the unique challenges faced by COVID-19 patients already diagnosed with autoimmune diseases?​

MF: In addition to the elevated risk of COVID-19-related complications in patients with autoimmune conditions, they may be more prone to pneumonia, cytokine storms, and extreme inflammatory complications such as lung and blood vessel protective lining failure.

OSP: What are some of the long-term effects C19 is having on such patients?​

MF: As a reaction to COVID-19 infection, patients can suffer continued lung inflammation, even after fighting the virus. Some individuals continue to encounter symptoms after their initial recovery, including those who have had mild versions of the disease.

We know that COVID-19 attacks the lungs, causing inflammation. This may leave survivors with persistent shortness of breath. This can also be troubling as inflammation in the heart can lead to long-lasting cardiac disease and failure.

Much is still unclear about how people will be affected over time by COVID-19. However, many physicians will closely monitor individuals who have recovered from COVID-19 to see if issues persist after recovery.

OSP: To date, what therapeutic approaches have medical professionals treating C19 patients (especially immunocompromised patients) been taking?​

MF: Early observational clinical data suggests that there is potential for anti-TNF therapies in treating COVID-19 patients. The relationship between anti-TNF therapy and COVID-19 deaths and hospital admissions is inverse. In arthritis patients, those who are undergoing anti-TNF treatment do well, seeing a 30% lower likelihood of hospitalization than those not on anti-TNF.

OSP: Please share the limitations on current-generation anti-inflammatory drugs in treating C19​

MF: Less than half of patients treated with TNF blockers respond well to treatment, and more than a quarter of patients fail treatment after 12 months. It is evident that existing TNF blockers do a lot of good for patients, but it is still possible to improve these very successful pharmaceuticals.

Researchers have learned that two different TNF receptors are present, each of which triggers its own reaction: TNFR1, which causes inflammation, and TNFR2, which is antiinflammatory. Consequently, blocking the receptor that keeps inflammation under control (TNFR2) may suppress other functions of the immune system, increasing the risk of opportunistic infections as well as cardiac and respiratory disorders.

Current anti-TNF therapeutics are not specific, and block both TNFR1 and TNFR2. Feldmann, Shepard and other researchers are developing therapeutics to do so.