The “valley of death” — the hurdle between a promising basic biological discovery and an approved drug available to patients — is a major barrier to the development of new therapeutics. Research at this stage is high-risk, costly, and time consuming. Promising drug candidates are often lost in the “valley” due to the risks inherent in the clinical trial process, so funding is hard to secure. In Crohn’s disease, this challenge is exacerbated by a poor understanding of disease pathophysiology and the clinical complexities of a chronic disease with fluctuating symptoms.
Helmsley’s Crohn’s Disease Program is committed to supporting new therapies for Crohn’s disease, which can be a severe and debilitating condition. Current treatments have many limitations and often do not do enough to alleviate symptoms. They are not fully effective in everyone and may lose effectiveness over time. They often require painful and cumbersome injections or time spent in an infusion center, and some have unwanted side effects. The most effective options suppress the immune system, leaving people susceptible to infections or malignancy. Despite therapeutic advances, most patients eventually require surgery. There is clearly a large unmet need for new therapies to improve the lives of those with Crohn’s disease, which has driven Helmsley’s interest in providing funding support to get novel therapies across the valley of death.
While traditional drugs to reduce inflammation essentially turn off the “on” switch of the immune system and target pro-inflammatory molecules, another therapeutic goal that has not been realized is to turn on the “off” switch. This off switch, or the “resolution of inflammation,” was characterized in the 1990s by Dr. Charles Serhan at Harvard Medical School and colleagues. Pro-resolving mediators such as Resolvins are a class of lipids that anchor active biological pathways in humans to resolve host-protective inflammation and promote tissue healing. Researchers have shown that deficiencies in these pathways contribute to pathological inflammation in a number of diseases, including Crohn’s disease, and that therapeutic use of Resolvins may be able to activate these pathways to turn on the “off” switch.
Not surprisingly, there has been great interest in targeting these pathways in inflammatory diseases, autoimmune diseases, and even cancer, but there have been great challenges in translating early discoveries to the clinic. Thetis Pharmaceuticals, an early-stage biotech, has promising technology that could make the resolution of inflammation pharmacologically accessible in inflammatory bowel disease (IBD). Early studies indicate that Thetis’ proprietary HEALER™ technology platform for its oral preparation of Resolvin E1 overcomes challenges related to stability, manufacturing, and formulation. Despite this promise, due to the high-risk and high cost of studies at this stage, it is difficult for a small biotech like Thetis to acquire sufficient funding to get it past the valley. Recognizing Thetis’ promising technology, Helmsley recently directed a Program-Related Investment at Thetis to support its early clinical studies in IBD.
Helmsley’s Crohn’s Disease Program aims to use this as a model to continue to support innovative treatments at risk of abandonment due to lack of funding, to ultimately advance our mission of improving the lives of people with Crohn’s disease. As a philanthropy, we have a responsibility to fund these high-risk projects. If not us, who?