Phase 1/2 Study to Evaluate Vosilasarm (EP0062) as Monotherapy and in Combination in Patients With Advanced or Metastatic AR+/HER-2-/ER+ Breast Cancer

Inclusion Criteria:

1. Women 18 years or older at the time of informed consent

2. Histologically proven diagnosis of breast cancer with evidence of metastatic orlocally advanced breast adenocarcinoma as defined by the American Joint Committee onCancer/Union for International Cancer Control/Tumour Node Metastases (AJCC/UICC TNM)staging classification (8th Ed, 2017) and where no conventional therapy is availableor considered appropriate by the Investigator or is declined by the patient

3. Availability of archival tumour sample (formalin-fixed, paraffin-embedded block(s)or slides from a primary tumour or biopsy of a metastatic tumour lesion or lesions);in the absence of an archival tumour sample, or if only archival bone tissue isavailable, a fresh biopsy will need to be collected

4. Biopsy-proven AR+ and ER+ breast cancer

• For Module A, AR+ breast cancer is defined as ≥ 10% AR nuclei staining bycentral immunohistochemistry (IHC) using the Ventana assay

• For Modules B and C, AR+ breast cancer is defined as ≥ 30% AR nuclei stainingby central IHC using the Ventana assay

5. HER2-negative breast cancer, defined as negative by fluorescence in situhybridisation (FISH) or IHC score of 0 or 1+. If IHC is equivocal at 2+, a negativeFISH test (HER2/Amplification of the centromeric region of chromosome 17)CEP17 ratioof <2.0) is required

6. Postmenopausal, as defined by at least one of the following:

7. Age over 60 years

8. Amenorrhea > 12 months at the time of informed consent and an intact uterus,with follicle-stimulating hormone (FSH) and oestradiol in the postmenopausalranges (as per local practice)

9. FSH and oestradiol in the postmenopausal ranges (as per local practice) inwomen aged <55 years who have undergone hysterectomy

10. Prior bilateral oophorectomy

11. Module B arm 1: patients who have progressed on ≤ 2 prior lines of endocrinetherapy, including a prior CDK4/6 inhibitor.

12. Module B arm 2: patients who have progressed on ≤ 2 prior lines of endocrine therapyin advanced/metastatic setting, including prior CDK4/6 inhibitor

Exclusion Criteria:

Patients with any of the following will not be included in the study:

1. Prior anti-cancer or investigational drug treatment within the following timewindows:

• Any chemotherapy within 21 days prior to the first dose of study drug

• Any non-chemotherapy investigational anti-cancer drug < 5 half-lives (28 daysfor biologics) or < 14 days for small-molecule therapeutics or if half-life isnot known

• Tamoxifen and aromatase inhibitors within 14 days prior to the first dose ofstudy drug

• Fulvestrant or other investigational Selective Estrogen Receptor Degraders (SERDs) within 21 days prior to first dose of study drug

2. Currently taking testosterone, methyltestosterone, oxandrolone, oxymetholone,danazol, fluoxymesterone, testosterone-like agents (e.g., dehydroepiandrosterone,androstenedione, and other androgenic compounds, including herbals), orantiandrogens

3. Radiation therapy within 14 days prior to the first dose of study drug and scheduledto have radiation therapy during participation in this study. Short courses ofpalliative radiation therapy during the study might be allowed following discussionwith and approval by the Medical Monitor. Palliative radiotherapy within 6 weeksprior to first dose of study drug is permitted

4. Unresolved or unstable serious toxic side effects of prior chemotherapy orradiotherapy, i.e., ≥ Grade 2 per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, except fatigue, alopecia, and Grade 2 chemotherapy-induced neuropathy

5. Confirmed Corrected QT Interval by Fridericia (QTcF) > 470 ms on screening ECG, orhistory of torsades de pointes (TdP), or history of congenital long QT syndrome, orimmediate family history of long QT syndrome, unexplained sudden death at a youngage, or sudden cardiac death

6. Any other clinically important abnormalities in rhythm, conduction, or morphology onresting ECG (e.g., complete left bundle branch block, third-degree heart block);rate-controlled atrial fibrillation is permitted

7. Concomitant medications that prolong the corrected QT interval and/or increase therisk for TdP that cannot be discontinued or substituted with another drug within 5half-lives or 14 days before the first dose of study drug, whichever is longer

8. Congestive heart failure Grades II-IV according to the New York Heart Association atthe time of screening

9. Myocardial infarction or unstable angina within the previous 6 months

10. Patients receiving medications that are known to be strong inhibitors or inducers ofCYP3A4 within 5 half-lives or 14 days, whichever is longer, before the first dose ofstudy drug

11. Prior treatment with selected combination agent