Motivation, Driving Force and Unmet Medical Need:

My daughter developed something called Complex Regional Pain Syndrome (CRPS) following a delicate right-hand wrist surgery. She is right-handed. She remains in constant pain, often debilitatingly intense and has limited use of the right wrist. It is heart-breaking to see her in such pain and not be able to do much to help.

Complex regional pain syndrome, with a prevalence of about 1:2,000, is a chronic inflammation and pain condition experienced by humans. It is a severe post-traumatic pain disorder. CRPS is usually triggered by trauma to the distal regions of a limb and is further associated with limb-restricted edema; sensory, vasomotor, sudomotor, motor, and trophic abnormalities; and profound sensory central nervous system (CNS) reorganization.

While most patients with CRPS show an improvement within months, either with or without treatment, 20% of patients develop persistent pain, often lasting for years or even through their lifetime. This type of persistent pain is intrusive and results in among the lowest quality of life scores in medical conditions. There is no cure. Current treatments are either short-lived, ineffective or just plain unsuccessful. Since many patients cannot be successfully treated, the treatment of CRPS remains an important unresolved problem and a major unmet medical need.

At DNX, we had been working for a few years on mechanisms of more effectively blocking the activity of a master pro-inflammatory cytokine. This pro-inflammatory cytokine and its natural antagonist have evolved over a billion years to check and countercheck each other. When all is well in the human body, both molecules are in balance. In the event of trauma, some inflammation is good as it alerts the body’s natural defense mechanisms to swing into action. Unfortunately, in cases when the ‘check-countercheck’ mechanism is thrown off balance, for any number of reasons – as in the case of my daughter – there is nothing to stop the master pro-inflammatory cytokine from continuing its action, without an effective countercheck, resulting in “dysfunctional-,” “smoldering-,” or chronic inflammation.

The natural antagonist molecule has a very short half-life in the human body. Thus, when the balance is thrown off, the natural antagonist molecule is unable to mount a continuously elevated countercheck to the actions of the pro-inflammatory cytokine. Therefore, the natural antagonist must be injected daily and, in some cases, even possibly 2-3 times per day, depending upon the indication and severity of the condition. This is most inconvenient to patients.

DNX has developed a genetically modified, long-acting version of the natural antagonist, which has demonstrated in preclinical testing a dramatic improvement in efficacy (4x to 50x), greatly reduced dosing frequency (1 per week to 1 per two weeks to 1 per month versus daily or multiple daily) and without sacrificing safety.

Promising Treatment Option for CRPS:

Medical researchers at the Universities of Manchester, Sheffield and Liverpool in the UK and the Universities of Pecs and Budapest in Hungary, published a breakthrough paper in the July 26, 2019 edition of the Proceedings of the National Academy of Sciences (PNAS), in which they were successfully able to create an animal model of CRPS and subject it to treatment by the natural antagonist molecule. The team discovered that ‘blocking’ of the pro-inflammatory cytokine with the natural antagonist helped to both ‘prevent and reverse’ all of the changes in the animal model of CPRS. Their results indicate that persistent CRPS is often contributed to by autoantibodies and highlight, for the first time, the promise of a potential therapeutic use of the antagonist to ‘prevent or treat’ CRPS by blocking the actions of the pro-inflammatory cytokine!

The preliminary results of the PNAS study is extraordinarily encouraging to me personally and to the Team at DNX. The lead researcher from this study is planning a clinical trial at the University of Liverpool. My daughter hopes to be a participant in such a clinical trial.

Collaboration:

From a successful funding round, DNX will aim to collaborate with the lead researcher from the study in advancing our proprietary molecule for testing in CRPS. A positive outcome may not only help my daughter and all the other patients who struggle with CRPS daily, but it additionally has the potential of treating several other rare diseases, especially those of pediatric origin that arise from dysfunctional inflammation.

The Link Between Dysfunctional Inflammation and Cancer:

There is a growing body of evidence from a multitude of proof-of-concept clinical trials that smoldering-, or dysfunctional inflammation drives normal cells and tissue to malignancy. Implicated at the heart of these early findings is the complex activities of the master pro-inflammatory cytokine. DNX believes it may even be possible to catch and stop cancers from developing early in the process by cutting-off chronic inflammation ‘at the pass.’ Now that, in our opinion, may well qualify as the “greatest thing since sliced bread!”

The Inflammation Spectrum:

It is said that the longer you can keep inflammation at bay, the longer you will live! The inflammation spectrum is linked to a host of disease indications – from rare, orphan indications to gout to several cancers to cardiovascular diseases. The DNX proprietary molecule has the potential to positively impact some of these diseases and change the life trajectory of patients.

We invite you to join us in our journey to providing essential solutions to some tough health problems.