Tryp Therapeuatics (TRYPF) Coverage Report

1;27(5):187-193). The development of FM treatments has been stymied by a high placebo response (Br Med Bull. 2021 Jul 23;ldab015). Phantom limb pain (PLP). Phantom limb pain is pain felt in a missing body part, such as a missing limb. There are ~1.9 million amputees in the US, with ~80% reporting PLP. Amputations can be caused due to diabetes mellitus, combat-related limb loss, trauma, and cancer. Mechanisms related to PLP involve neural relationships between the central (CNS) and peripheral nervous system (PNS). Exhibit 20: Cortical contributions to PLP Source: J Clin Invest. 2018; 128: 2168  Research suggests that PLP mechanisms in the PNS work in combination with changes in the CNS to cause PLP (J Clin Invest. 2018; 128: 2168).  The CNS is involved with cortical remapping, where cortical reorganization follows the loss of a limb. Following amputation, the cortical region that received input from the amputated limb may receive input from neighboring cortical regions, which eventually spread and include the region that previously controlled the amputated limb (Exhibit 20A).  The CNS is also involved in the role of proprioceptive memory where the brain has a memory of the position of the limb in space relative to the body. It may also play a role in cortical reorganization in the CNS to drive the PLP (Exhibit 20B).  The PNS is involved in PLP when abnormal and ectopic neuronal activity is transmitted along the spinothalamic pathway (Exhibit 21). The DRG axons terminate in the spinal cord. Post amputation, inflammation and sprouting can occur in the residual limb where neuromas develop. It is these injured axons along with leftover peripheral nerves that spontaneously generate abnormal electric signals and can cause PLP (Exhibit 21).  Current treatments include nonpharmacological approaches, including education, and cognitive-behavioral therapies, as well as surgeries, prosthetic supplies, and pharmacotherapy. However, these strategies are met with limited efficacy (Pain Rep. 2021; 6(1): e888). Michael Higgins 212.409.2074 Tryp Therapeutics, Inc. (TRYPF) Page 28