A Multi-Center Study of SM-88 in Subjects With Pancreatic Cancer

Both investigator determined and independent blinded central review will be used for
determining outcomes.

Inclusion Criteria:

1. Biopsy-proven metastatic pancreatic adenocarcinoma with documented radiographic
disease progression on or after one or more systemic therapies. Chemotherapy given as
part of prior chemoradiation in the setting of non-metastatic pancreatic cancer does
not count as a line of therapy. Chemotherapy given for at least 4 months as adjuvant
after complete response is considered as a first line therapy.

2. Subjects must be unwilling or unable to tolerate other non-study systemic
chemotherapy.

3. Subjects must have measurable lesions (according to standard RECIST 1.1).

4. Subjects must have completed systemic therapy at least 28 days prior to first dose.

5. Subjects must have recovered from major side effects of prior therapies or procedures.

6. ≥18 years of age.

7. ECOG performance status ≤2.

8. Life expectancy >3 months, in the judgment of the investigator.

9. Adequate organ function defined as follows:

1. Hematologic: Platelets ≥100 x 10(9)/L; ANC ≥1.5 x 10(9)/L (without platelet
transfusion or growth factors within the 7 days prior to the screening laboratory
assessment)

2. Hepatic: aspartate transaminase (AST)/alanine transaminase (ALT) ≤2.5 x upper
limit of normal (ULN); total or conjugated bilirubin ≤1.5 x ULN

3. Renal: serum creatinine ≤1.5 x ULN or creatinine clearance (CrCl) ≥60 mL/min as
calculated by the Cockroft-Gault method

10. Coagulation: International normalized ratio (INR) ≤1.2 within 28 days of starting
study.

11. All acute toxic effects of any prior antitumor therapy resolved to Grade ≤1 before
baseline, with the exception of alopecia and neurotoxicity (CTCAE Grade 1 or 2
permitted).

12. Able and willing to provide written informed consent to participate in this study.

13. Subject is willing and able to comply with the protocol for the duration of the study
including undergoing treatment and scheduled visits and examinations including follow
up.

14. Subjects must be able to swallow whole capsule.

15. Female subjects must either be of non-reproductive potential, not breast-feeding or
must have a negative urine or serum pregnancy test within 28 days of study treatment,
confirmed prior to treatment on day 1.

16. Subjects of fertile potential who engage in heterosexual intercourse with partners of
childbearing potential must agree to use highly effective contraception while enrolled
in the study and for at least 6 months following the last dose of study drug

Exclusion Criteria:

1. Any screening laboratory, electrocardiogram (ECG), or other findings that, in the
opinion of the investigator or the sponsor, indicate an unacceptable risk for the
subject's participation in the study.

2. History or evidence of any clinically significant disorder, condition, or disease
that, in the opinion of the investigator or medical monitor would pose a risk to the
subject's safety or interfere with the study evaluations, procedures, or completion.
Examples include intercurrent illness such as active uncontrolled infection, active or
chronic bleeding event within 28 days of baseline, uncontrolled cardiac arrhythmia, or
psychiatric illness/social situation that would limit compliance with study
requirements.

3. History of a concurrent or second malignancy, except for adequately treated local
basal cell or squamous cell carcinoma of the skin, adequately treated superficial
bladder cancer, adequately treated Stage 1 or 2 cancer currently in complete
remission; or any other cancer that has been in complete remission for ≥5 years.

4. Subjects with MSI-H pancreatic cancer who have not previously received pembrolizumab.

5. Radiation to all target lesions within 12 weeks of study baseline,

6. No measurable target lesions.

7. Current use, or up to 14 days prior use, of certain prohibited medication or requires
any of these medications during treatment phase.

8. Major surgery, defined as any surgical procedure that involves general anesthesia and
a significant incision (i.e. larger than that required for placement of central venous
access, percutaneous feeding tube, or biopsy) within 28 days of the first dose of
study drug

9. Minor surgical procedures within 7 days of baseline, or not yet recovered from prior
surgery.

10. Any dysphagia, odynophagia, esophageal dysmotility or stricture, known GI
malabsorption syndrome, or intractable diarrhea that may significantly alter the
absorption of any of the components of SM-88, e.g., cirrhosis.

11. Known human immunodeficiency (HIV) virus infection.

12. Known hepatitis B surface antigen (HBsAg) positive.

13. Known hepatitis C virus (HCV) antibody positive.

14. Have previously been enrolled in this study or any other study investigating SM-88 or
who have previously received any component of SM-88 in a clinical trial.

15. History of any drug allergies or significant adverse reactions to any of the
components of SM-88.

16. Are currently enrolled in, or have discontinued within 30 days of screening, from a
clinical trial involving an investigational product or non-approved use of a drug or
device.

17. Subjects must not have any clinically significant and uncontrolled major medical
condition(s) including, but not limited to uncontrolled nausea/vomiting/diarrhea;
active uncontrolled infection; symptomatic congestive heart failure (New York Heart
Association [NYHA] class >= II); unstable angina pectoris or cardiac arrhythmia;
psychiatric illness/social situation that would limit compliance with study
requirements.

18. >10% weight loss over the 28 days prior to consent.

19. Subject has a variety of factors influencing oral drugs (such as unable to swallow,
nausea, vomiting, chronic diarrhea and intestinal obstruction, etc.).

20. Subjects with central nervous system metastasis; with the exception of subjects who
have stable brain metastases as defined as off steroids and no CNS progress for 6
months after CNS treatment.

21. Pregnant or lactating women.

22. History of psychiatric drug abuse that cannot be ended, or subjects with mental
disorders that will prevent compliance or evaluation including uncontrolled
schizophrenia, uncontrolled depression or other uncontrolled disorders.

23. Subjects with a history of hypersensitivity to phenytoin, its inactive ingredients, or
other hydantoins; or a history of prior acute hepatotoxicity attributable to
phenytoin.

24. Subjects exhibiting idiosyncratic reactions to psoralen compounds.

25. Subjects with a hypersensitivity to sirolimus.

26. Subjects with a history of the light sensitive diseases for which methoxsalen would be
contraindicated. Diseases associated with photosensitivity include lupus
erythematosus, porphyria cutanea tarda, erythropoietic protoporphyria, variegate
porphyria, xeroderma pigmentosum, and albinism.

27. Subjects treated, or anticipated to be treated, with delavirdine (due to potential for
loss of virologic response and possible resistance to delavirdine or to the class of
non-nucleoside reverse transcriptase inhibitors caused by phenytoin).

28. Subjects with melanoma or with a history of melanoma, invasive squamous cell
carcinomas, or aphakia (due to contraindication for use of methoxsalen).

29. Subjects with prior organ transplant or being treated, or anticipated to be treated,
with cyclosporine (because long-term administration of the combination of cyclosporine
and sirolimus is associated with deterioration of renal function).

30. Subjects with a seizure disorder that is not well controlled or who have required a
change in seizure medications within 60 days of enrollment to the trial.

31. Subjects treated, or anticipated to be treated, with a calcineurin inhibitor (because
concomitant use of sirolimus and a calcineurin inhibitor increases the risk of
calcineurin inhibitor-induced hemolytic uremic syndrome/thrombotic thrombocytopenic
purpura/thrombotic microangiopathy [HUS/TTP/TMA]).

32. Subjects with interstitial lung disease (ILD) (including pneumonitis, bronchiolitis
obliterans organizing pneumonia [BOOP], and pulmonary fibrosis).