Study of ASN003 in Subjects With Advanced Solid Tumors

The study will be conducted in two parts. Part A is a dose escalation study to determine a
safe and tolerable dose of ASN003 for subjects with advanced solid tumors. Part A will also
characterize the pharmacokinetics and pharmacodynamics of ASN003 through blood sampling and
optional biopsies.. Part B will only enroll subjects in three groups:

Group 1: subjects who have metastatic or recurrent melanoma with the BRAFv600 mutation.

Group 2: subjects who have advanced or metastatic non-small cell lung cancer, or colorectal
cancer with the BRAFv600 mutation.

Group 3: subjects who have advanced or metastatic cancers with phosphatidylinositide
3-kinases (PI3K) mutations, or phosphatase and tensin homolog (PTEN) loss mutation. Subjects
will be treated with the highest safe and tolerable dose determined in Part A of the study to
determine preliminary efficacy. Subjects may continue to receive ASN003 for up to 1 year in
the absence of severe side effects or disease progression.

Inclusion Criteria:

- written informed consent obtained prior to any study-related procedures.

- Eastern Cooperative Oncology Group Performance Status: 0-1

- Part A only: Histologically or cytologically confirmed metastatic and/or advanced
solid tumors with documented progressive disease for whom no further standard therapy
is indicated.

- Part B only: 5. Histologically or cytologically confirmed, molecularly selected (i.e.
BRAFV600 positive and/or PI3K mutation positive) advanced solid tumors. Prior
molecular characterization should be based using a regulatory approved assay or
analytically validated assay.

- Group 1: BRAFV600 positive metastatic or recurrent melanoma after failure of
prior treatment with standard therapy such as a checkpoint inhibitor and an
approved B-RAF inhibitor (vemurafenib or dabrafenib)

- Group 2: BRAFV600 positive metastatic colorectal carcinoma (CRC), or advanced
non-small cell lung carcinoma (NSCLC) after failure of at least two lines of
prior standard therapy or for whom no further standard therapy is indicated.

- Group 3: Advanced solid tumors with PI3K pathway alterations (PIK3CA mutation or
PTEN loss) after failure of at least one line of prior standard therapy or for
whom no further standard therapy is indicated. Prior treatment may not include
inhibitors of the PI3K pathway.

- Screening hematology values of the following: absolute neutrophil count ≥ 1000/μL,
platelets ≥ 100,000/μL, hemoglobin ≥ 10 g/dL (without transfusion support);

- Screening chemistry values of the following: alanine aminotransferase (ALT) and
aspartate transaminase (AST) ≤ 3.0 × upper limit of the normal reference range (ULN),
total bilirubin ≤ 2 × ULN, creatinine ≤ 1.5 × ULN, fasting blood glucose < 140 mg/dL,
hemoglobin A1C ≤ ULN, albumin ≥ 2.8 g/dL.

- Screening fasting lipid panel: LDL cholesterol < 190 mg/dL, triglycerides < 300 mg/dL

- Subject is willing and able to comply with all protocol required visits and
assessments, including biopsy if assigned to the MTD expansion cohort;

Exclusion Criteria:

- Have received prior chemotherapy, other investigational therapy, or major surgery
within 4 weeks of Day 1;

- Have received oral anti-cancer therapy with oral tyrosine kinase inhibitors within 14
days or 5 half-lives, whichever is longer.

- Have received prior treatment with monoclonal antibodies within 6 weeks of first dose
of Day 1;

- Subject has received a live virus vaccine within the previous 8 weeks.

- Have known central nervous system metastasis or primary tumor (Part A).
Previously-treated, CNS metastasis is permitted in Part B. CNS metastasis must be
small, discrete metastasis; stable for at least 30 days without the need for
concomitant prednisone for symptom management. No leptomeningeal disease is allowed.
Is receiving therapeutic doses of corticosteroids (>20 mg prednisone daily or
equivalent);

- Has a serious concurrent medical condition such as:

- history of Diabetes Mellitus, type 1 or type 2,

- known autoimmune disease, known bleeding diathesis, history of congestive heart
failure New York Heart Association (NYHA) class III or IV;

- uncontrolled hypertension (systolic BP ≥ 139 mmHg or diastolic BP ≥ 89 mmHg) at
screening, despite optimal antihypertensive therapy,

- clinically significant heart disease including but not limited to: myocardial
infarction, or arterial thrombotic events in the past 6 months, severe or
unstable angina, or known cardiac ejection fraction measurement of < 50 %;

- history or family history of long QT syndrome; 12-Lead electrocardiogram (ECG)
abnormalities considered by the investigator to be clinically significant or QTcF
≥ 450 milliseconds, regardless of clinical significance, at screening. Abnormal
ECG may be confirmed with one repeat assessment. For subjects with QTcF ≥ 450
msec on initial ECG, the mean of the two QTcF assessments will determine
eligibility;

- uncontrolled psychiatric illness;

- serious persistent infection within 14 days prior to the start of study
medication;

- known gastrointestinal disease or condition which may affect the absorption of
ASN003;

- known active or symptomatic viral hepatitis, chronic liver disease or liver
cirrhosis;

- known glaucoma or other pre-existing ocular conditions that may put the patient
at risk for ocular toxicities.

- any known condition or situation which may put the patient at significant risk,
may confound the study results, or may interfere significantly with subject's
participation in the study

- Female subjects who are pregnant or breast feeding