Study to Evaluate Safety and MTD of Epidural Resiniferatoxin Injection for Treatment of Intractable Cancer Pain

All subjects who received RTX will be included in the analyses and summaries of safety,
efficacy, PD, and PK assessments.

Inclusion Criteria:

- Histologically confirmed advanced cancer or metastasis, which has not responded to
standard therapy, producing intractable chronic pain in any area below the
mid-thoracic level.

- Male or female subjects must be at least 18 years of age.

- Must have a worst pain score ≥6 on the NPRS at Screening visit.

- Subjects not seeking or receiving potentially curative therapies for cancer.
Palliative therapy is acceptable if the therapy started and is stable prior to IP
administration.

- Sexually active female subjects of childbearing potential and male subjects capable of
fathering a child must be willing to use an effective method of contraception to avoid
pregnancies.

- Must be willing and capable of understanding and cooperating with the requirements of
the study.

- Must be able to understand and complete study-related forms and adequately communicate
with the investigator and/or site staff.

- Must have provided written informed consent prior to participating in any
study-related activity.

- Subjects able to complete the study duration.

Exclusion Criteria:

- Subjects with leptomeningeal metastases in lumbar area.

- Undergoing or have plans to undergo changes to current cancer treatment during the
study through the Day15 assessment.

- Had prior lumbar spine surgical procedures that could impair the ability to perform
the injection.

- Evidence of brain pathology or increase intracranial pressure.

- Presence of an IT shunt.

- Has evidence or a coagulopathy or hemostasis problem.

- Subjects with a total neutrophil count <1500 cells/mm3.

- Subjects with serum creatinine ≥1.5 mg/dL.

- Is febrile or has other evidence of an infection within 7 days of planned injection.

- Has an allergy or hypersensitivity to chili peppers, capsaicin, or radiographic
contrast agents.

- Female subjects who are pregnant, are planning on becoming pregnant, or are currently
breastfeeding.

- Subjects with any medical condition that could adversely impact study participation or
assessments.

- Subjects who have received new anti-cancer treatments and there is less than one week
or four half-lives of the investigational drug, whichever is greater, between the last
dose of the new drug and the planned day of IP administration; or had a change in the
dose or schedule of the anti-cancer treatments within one week or four half-lives,
whichever is greater, between the last dose of the anti-cancer treatment and the
planned day of IP administration; or are scheduled to receive a new anti-cancer
therapy or investigational product prior to completion of the Day 15 visit.

- Subjects with additional loci of pain above the mid-thoracic level or other pain
disorder due to non-cancer etiology, unless both the investigator and the subject are
clearly able to distinguish the additional pain from the target pain due to cancer.

- Liver cirrhosis or severe hepatic impairment, with liver function test 3 times above
ULN.

- Sensory/peripheral neuropathy of CTCAE Grade 2 or higher.

- Nonstudy related minor surgical procedure ≤5 days or major surgical procedure ≤21 days
prior to Screening visit.

- Subjects who have not completely recovered from any toxicities from previous
chemotherapy, hormone therapy, immunotherapy, or radiotherapies that are CTCAE Grade 3
or higher.

- Arterial thrombi (including stroke), myocardial infarction, admission for unstable
angina, cardiac angioplasty, or stenting within 3 months prior to Screening visit.

- Corrected QT using Fridericia's formula (QTcF) prolongation.

- Evidence or history of bleeding disorder within 4 weeks prior to IP administration.

- Known HIV or acquired immunodeficiency syndrome-related illness, acute or history of
chronic hepatitis B or C.