A Phase 1/2, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of INX-315 in Patients with Advanced Cancer

Incyclix Bio (Incyclix) is developing INX-315 as an oral, small molecule inhibitor of
cyclin dependent kinase 2 (CDK2) for the treatment of human cancers. This first-in-human
study is designed to evaluate the safety, tolerability, pharmacokinetics (PK) and
preliminary antitumor activity of INX-315 in patients with recurrent advanced/metastatic
cancer, including hormone receptor positive (HR+)/Human Epidermal Growth Factor Receptor
2 Negative (HER2-) breast cancer who progressed on a prior cyclin-dependent kinase 4/6
inhibitor (CDK4/6i) regimen, and CCNE1-amplified solid tumors who progressed on standard
of care treatment. The study will be conducted in 3 parts: Part A (INX-315 monotherapy
dose escalation and combination therapy with fulvestrant), Part B (ovarian cancer INX-315
monotherapy dose expansion), and Part C (INX-315 combination therapy with abemaciclib [a
CDK4/6i] and fulvestrant [a SERD] in advanced/metastatic breast cancer; dose escalation
and expansion).

Inclusion Criteria:

1. Advanced unresectable or metastatic ER+/HER2- BC that has progressed following
treatment with a CDK4/6 inhibitor

2. Advanced/ metastatic platinum-resistant or platinum-refractory epithelial ovarian
cancer (including fallopian tube cancer/primary peritoneal cancer) CCNE-1 amplified
tumors that progressed after standard systemic therapy

3. Advanced or metastatic solid tumor with known amplification of CCNE-1 that has
progressed after standard therapy, been intolerant to or is ineligible for standard
therapy

4. At least one measurable lesion as defined by RECIST v1.1 that has not previously
been irradiated

5. ECOG performance status score of 0 or 1.

6. Adequate organ function as demonstrated by the following laboratory values:

1. Hemoglobin ≥ 9.0 g/dL

2. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L

3. Platelet count ≥ 100 × 109/L

4. Estimated glomerular filtration rate (eGFR) of ≥60 mL/min

5. Part A and B: Total bilirubin ≤ 1.5 × ULN; AST and ALT ≤ 2.5 × ULN; ≤ 5 × ULN
in the presence of liver metastases Part C: Patients with GIlbert's syndrome
with a total bilirubin ≤ 2.0 × ULN and direct bilirubin within normal limits

7. Negative pregnancy test

Exclusion Criteria:

1. Have received previous therapy with a CDK2/4/6 inhibitor or CDK2 inhibitor.

2. Have central nervous system (CNS) metastases or spinal cord compression that is
associated with progressive neurological symptoms or requires corticosteroids
(within 4 weeks of enrollment) to control the CNS disease.

3. Have known intracranial hemorrhage and/or bleeding diatheses.

4. Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis.

5. Have clinically active ongoing interstitial lung disease (ILD) of any etiology,
including drug-induced ILD, and radiation pneumonitis within 28 days prior to
initiation of study treatment.

6. Resting QTcF > 470 msec, a history of prolonged QT syndrome or Torsades de pointes,
or a familial history of prolonged QT syndrome.

7. Uncontrolled, cardiovascular disease (including hypertension) with or without
medication

8. History of other malignancies, except for the following: (1) adequately treated
basal or squamous cell carcinoma of the skin; (2) curatively treated a) in situ
carcinoma of the uterine cervix, b) prostate cancer, or c) superficial bladder
cancer; or (3) other curatively treated solid tumor with no evidence of disease for
≥ 3 years.

9. Known HIV infection, including AIDS-related illness, or have active, uncontrolled
infection (viral, bacterial, or fungal), including tuberculosis, hepatitis B virus,
hepatitis C virus, or COVID-19 infection (symptoms and a positive test result).

10. Requires treatment with a prohibited medication or herbal remedy that cannot be
discontinued at least 2 weeks before the start of study drug administration.

11. Have planned or anticipation of the need for major surgical procedure within 28 days
of the first dose of study drug (procedures such as central venous catheter
placement, tumor needle biopsy, and feeding tube placement are not considered major
surgical procedures).

12. Unwilling or unable to comply with scheduled visits, study drug administration plan,
laboratory tests, or other study procedures and study restrictions.

13. Radical radiotherapy within 28 days prior to study entry or palliative radiotherapy
within 2 weeks prior to study entry.

14. Systemic anti-cancer therapy within 28 days or at least 5 half-lives, whichever is
less, prior to the first dose of the study drug

15. Prior irradiation to > 25% of the bone marrow

16. Previous high-dose chemotherapy requiring prior stem cell transplant

17. Participation in other studies involving investigational drug(s) within 4 weeks
prior to study entry.

18. Known or suspected hypersensitivity to active ingredient/excipients in INX-315 or
fulvestrant or abemaciclib.

19. Known difficulty in swallowing or tolerating oral medications, or conditions which
would impair absorption of oral medications such as active inflammatory
gastrointestinal disease, uncontrolled nausea or vomiting (i.e., CTCAE ≥ Grade 3
despite antiemetic therapy), ongoing gastrointestinal obstruction/motility
disorder/active inflammation, malabsorption syndrome, chronic diarrhea, known
diverticular disease or previous gastric resection or lap band surgery.

20. Has a serious and/or uncontrolled pre-existing medical condition(s) that, in the
judgment of the Investigator or the Sponsor, would preclude participation in this
study (for example but not limited to, interstitial lung disease, severe dyspnea at
rest or requiring oxygen therapy, history of major surgical resection involving the
stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a
preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea)