The purpose of this research was to better understand the patient experience living with
DPNP, uncover the unmet treatment needs in treatment and management of DPNP, and
incorporate these learnings into the development of the pilavapadin phase 3 clinical trial
program.

Diabetic Peripheral Neuropathy (DPN) adversely affects patient quality of life including
interference with daily function, sleep disturbances, chronic pain syndromes, depression, loss of
sensation, and lower extremity infections, ulcerations, and amputations (1). Painful DPN (DPNP)
affects an estimated 30% of patients with type 1 diabetes (T1D) and 50% of patients with type 2
diabetes (T2D)(1,2). The most prevalent form of DPNP is distal symmetric polyneuropathy, which
is characterized by burning pain, tingling, numbness, paresthesia, hyperalgesia and allodynia (2).
These debilitating symptoms significantly impact quality of life, including depression, sleep
disturbance, and daily functioning. Many challenges exist in management of DPNP, most notably
a lack of timely diagnosis. This presents a large unmet need highlighting the necessity for
innovative therapeutic approaches. Pilavapadin is a potent, highly selective, orally administered
inhibitor of a novel target, adapter protein-2 associated kinase1 (AAK1). Inhibition of the AAK1
receptor has been shown to reduce pain via the alpha-2 adrenergic receptor pathway,
independent of the opioid pathway. Pilavapadin 10 mg QD was shown to be efficacious in
reducing pain as evaluated by the Average Daily Pain Score (ADPS) in a Phase 2 proof-of-concept
study (RELIEF-DPN-1) and a Phase 2b dosing ranging study (PROGRESS) in patients with
DPNP. The purpose of this research was to better understand the patient experience living with
DPNP, uncover the unmet treatment needs in treatment and management of DPNP, and
incorporate these learnings into the development of the pilavapadin phase 3 clinical trial
program.

A disease-level, patient-focused survey was created for digital dissemination by the Medidata
Patient Insights Diabetes Advocates Board. The survey aimed to garner patient perspectives
on all aspects of living with DPNP and was conducted from June 3, 2024, to June 28, 2024.
The survey was shared across 36 independent patient advocacy partnerships and social
media.

Two hundred fifty-three respondents took the survey and 38 were screened out. Of the 215
respondents surveyed, 66.5% were female, 76.7% had T2D, 22.3% had T1D, and 96.3% had
DPNP symptoms for greater than 1 year. The most experienced DPNP symptoms were:
(81.7%) pins/needles, (77.9%) tingling, (73.1%) burning pain, (58.1%) stabbing pain, (57.2%)
electric-shock. DPNP symptoms significantly or severely impacted preforming normally daily
activities and ability to continue to work in 39.9% and 44.2% of respondents, respectively.
DPNP significantly or severely impacted sleep in 30.7% and 12.5% of patients. The majority of
respondents (85%) reported use of an OTC pain reliever with 41.2% reporting daily use.
Despite this OTC drug utilization, 43.5% reported OTC pain reliever efficacy as only somewhat
effective and 42.9% reported not so effective. Many respondents (74.8%) reported use of
pregabalin or gabapentin, with 72% reporting daily use. However, respondents reported its
efficacy as somewhat effective (43.2%) and (22.6%) not so effective. Use of prescription
opioid pain relievers to relieve DPNP symptoms was reported in 35.2 % of respondents. Daily
or a few times a week frequency of prescription opioid pain reliever use was reported in
20.8% and 18.1%, respectively. Fifty percent of respondents reported the efficacy of
prescription opioid pain reliever as somewhat effective. While 29.2% reported the efficacy of
prescription opioid pain reliever as effective.

The presented patient-level survey analysis demonstrates the vast unmet medical need and
profound disease burden faced by patients living with diabetic peripheral neuropathy pain.
These DPNP symptoms negatively impacted normal daily activities, including the ability to
work and sleep, in an overwhelming majority of respondents. Despite the use of available
OTC, prescription non-opioid, and opioid pain relievers, a significant proportion of patients
report limited symptom relief. These survey results lend to the existing literature highlighting
a critical gap in effective DPNP management. The insights from this patient survey will guide
the real-world patient needs in the design of the phase 3 pilavapadin clinical trial program.