Systemic Lupus Erythematosus (SLE) or Lupus is a systemic autoimmune disease affecting and estimate 400,000 Americans, 90% of whom are women.  The most common symptoms are skin rash and joint pain, although serious potentially life-threatening involvement of organs such as the kidneys and lungs occur in a smaller percentage of lupus patients.

The underlying biological abnormalities include a break in self-tolerance with the development of autoantibodies.  Numerous different autoantibodies have been characterized in lupus patient sera.  These commonly include antibodies to double-stranded DNA and RNA-containing autoantibodies.  Similar to the underlying pathology in Sjogren’s syndrome, circulating extracellular RNA triggers the production of type I interferons which drives chronic inflammation in these patients.

Pathogenic RNA is known to drive interferon production in SLE by binding to RNA sensors such as TLR7.  Furthermore, the expression of TLR7 is increased in many women with SLE because of incomplete X chromosome inactivation.  Resolve is pioneering a completely new approach to the treatment of Sjogren’s by removing extracellular RNA from circulation thereby preventing it from activating type I interferons.  Our lead product candidate is RSLV-132 which is a biologic drug composed of human RNase1 fused to the Fc domain of human IgG1.  The drug is engineered to remain in circulation for approximately one month and is not taken up into cells to prevent it from causing damage to healthy cellular mRNA, only pathogenic RNA circulating in the blood is removed.  This approach may provide clinical benefit to SLE patients with active systemic disease as described in a randomized, placebo-controlled phase 2a clinical trial in patients with SLE, the results were published in Lupus Science & Medicine a leading Rheumatology Journal.

Post-acute sequelae of COVID-19 (PASC) is a post-viral illness resulting from infection with SARS-CoV-2 RNA.  A 2022 CDC survey reported that 18 million Americans are suffering from PASC with women making up a larger proportion of PASC patients.  The most common symptoms are severe debilitating fatigue, post-exertional malaise (PEM), and autoimmune like disease with the development of autoantibodies.  Additional symptoms include cognitive dysfunction, brain fog, cardiovascular symptoms, respiratory symptoms, loss of taste or smell, and neurological symptoms such as anxiety or depression.  The pathogenesis of the disease is unknown, but many reports demonstrate the presence of viral RNA reservoirs months following infection.  An increase in interferon, analogous to autoimmune diseases has also been described in PASC patients.  Resolve has recently completed a randomized, placebo-controlled clinical trial in 105 participants with PASC symptoms for at least 6 months and severe fatigue.  The results are currently under review at a top scientific Journal and will soon be made public.

According to a 2015 Institute of Medicine comprehensive report on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), up to 2.5 million Americans are suffering with this post-viral disease, and of those patients up to 10-20% are completely housebound.  The etiology of the disease is unknown, but the prevailing view is that a viral infection of enterovirus triggers the disease.  In addition to severe debilitating fatigue, the cardinal symptom of the disease is PEM.  ME/CFS has a well-established sex bias with up to 80% of the patients being women.  There is a large overlap in symptoms between ME/CFS and PASC and many patients diagnosed with PASC also meet the Canadian Consensus Criteria for ME/CFS.  There are no validated biomarkers aiding diagnosis and no approved therapy for patients suffering from ME/CFS.  Until very recently patients’ symptoms have in many cases been dismissed by physicians who did not understand or recognize the disease, adding additional frustration and suffering for these patients.  In addition to the presence of autoantibodies and immune system dysregulation, several scientific reports highlight abnormalities in non-coding RNA molecules.