Safety and Preliminary Efficacy of OBT076 in Recurrent/Metastatic CD205+ Solid Tumors

Inclusion Criteria:

1. Subject is ≥ 18 years of age (at the time of signing the ICF) with non-curativerecurrent and/or metastatic solid tumors for which a standard therapy is notavailable or is no longer effective.

2. Subject has histologically and/or cytologically confirmed solid tumors.

3. Subject with Breast cancer:

4. Subject with hormone-receptor positive (as per local laboratory) recurrentlocally advanced or metastatic breast cancer, regardless of HER2 status, musthave received at least two prior lines of endocrine therapy in the adjuvant ormetastatic setting, either as monotherapy or in combination with targetedtherapy

5. Subject with recurrent locally advanced or metastatic non-curative HER2negative breast cancer (based on most recently analyzed biopsy), HER2 status isdefined as per ASCO-CAP guidelines as negative, if in situ hybridization testor IHC status is 0, 1+, or 2+.

6. Subject with triple negative breast cancer are eligible after at least oneprior line of cytotoxic chemotherapy in the metastatic setting.

7. Subject with prior adjuvant or neoadjuvant chemotherapy allowed.

8. Subject has received a maximum of two prior lines of cytotoxic chemotherapy in themetastatic setting. Subject who received three up to five prior lines of cytotoxicchemotherapy in the metastatic setting are eligible, if the last administration ofcytotoxic chemotherapy was at least 12 weeks prior to Cycle 1 Day 1

9. Subject has tumor that is positive for CD205 antigen by IHC staining

10. Subject has an ECOG performance status of 0-1.

11. Subject has radiological documented measurable disease (i.e., at least 1 measurablelesion as per RECIST Version 1.1).

12. Subject has adequate organ function

13. Subject has adequate bone marrow function

14. Subject understands and voluntarily signs an ICD prior to any study-relatedassessments/procedures are conducted.

15. Subject is able to adhere to the study visit schedule and other protocolrequirements.

16. Subject who is a female of childbearing potential (defined as a sexually maturewomen, has not undergone hysterectomy (the surgical removal of the uterus) orbilateral oophorectomy (the surgical removal of both ovaries) or 2) has not beennaturally postmenopausal for at least 12 consecutive months and is using anyadequate form of birth control must:

17. Have a negative pregnancy test within 1 week before first dose of study drug.

18. Use highly effective method(s) of birth control consistently and correctlyduring the study and for at least 4 months after the last dose of study drug.

19. Agree to not donate eggs (ova, oocytes) for the purposes of assistedreproduction during the study and for at least 4 months after the last dose ofstudy.

20. Agree to no plan to breastfeed and no plan to become pregnant during the studyand for at least 4 months after the last dose of study drug.

21. Subject who is a sexually active male must agree to use a condom, not to donatesperm and have no plans to father a child during the study and for at least 4 monthsafter the last dose of study drug.

Exclusion Criteria:

1. Subject has received any chemotherapy within 28 days prior to Cycle 1 Day 1.

2. Subject has received any other systemic anticancer therapy within 28 days or 5half-lives of Cycle 1 Day 1.

3. Subject has symptomatic visceral crisis requiring chemotherapy per Investigatorjudgment for non TNBC.

4. Subject with colorectal cancer and pancreatic cancer are not eligible for the study.

5. Subject with peritoneal involvement, i.e., peritoneal carcinomatosis, are noteligible for the study.

6. Subject has not recovered from the acute toxic effects (CTCAE grade ≤ 1) of prioranticancer therapy, radiation, or major surgery/significant trauma (except alopeciaor other toxicities not considered a safety risk for the subject at theInvestigator's discretion).

7. Subject has had major surgery within 14 days prior to starting study treatment orhas not recovered from major side effects.

8. Subject has had radiotherapy ≤ 4 weeks prior to starting study drug.

9. Subject has a history of, or current symptomatic brain metastasis.

10. Subject has any other malignancy within 5 years prior to randomization

11. Subject has a known or suspected hypersensitivity or other contraindication to anyexcipients used in the manufacture of OBT076.

12. Subject has significant medical condition, laboratory abnormality, or psychiatricillness that would, in the Investigator's judgment, contraindicate patientparticipation in the study (e.g., history of thromboembolic event, cardiacdysfunction, chronic pancreatitis, chronic active hepatitis)

13. Subject has severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine <7days before Cycle 1 Day 1

14. Subject has any condition that confounds the ability to interpret data from thestudy.

15. Subject is lactating or breastfeeding.

16. Subject has a past medical history of or ongoing clinically relevant interstitiallung disease, drug-induced pneumonitis or severe/very severe COPD.

17. Subject has active or chronic corneal disorder or Sjogren's syndrome.

18. Subject has any ongoing skin disorders not controlled by specific treatment.

19. Subject has significant active cardiac disease within the previous 6 monthsincluding unstable angina or angina requiring surgical or medical intervention,significant cardiac arrhythmia, or NYHA class 3 or 4 congestive heart failure, orpatients with QTc interval >470ms at screening.

20. Subject has a known history or current diagnosis of HIV infection, unless on tripleantiviral treatment with undetectable viral load.

21. Subject who is female of childbearing potential

22. Subject who is unable or unwilling to take folic acid or vitamin B12supplementation.

23. Subject with a history of allogeneic organ transplant.

24. Subject with grade 3 or 4 immune-related adverse reactions during any prior line ofcheckpoint inhibitor containing therapy. Patients with immune-related thyroiditiscontrolled with substitution, or prior asymptomatic lipase increases are eligiblefor the study.

25. Subject with active autoimmune disease or history of autoimmune disease thatrequired systemic treatment within 3 years of the start of study treatment.

Additional inclusion criteria specific for Part E:

1. Patients with stage IV NSCLC or stage III/stage IV urothelial cancer who have progressed on standard treatments or for whom a standard therapy is not available, standard therapy is no longer effective, or who have no satisfactory treatment options.

Additional exclusion criteria for Part E:

1. The presence of any contraindication to gemcitabine as per applicable Summary ofProduct Characteristics/label.

2. Patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalent) within the 14 days prior to the first dose ofstudy treatment or another immunosuppressive medication within the 30 days prior tothe first dose of study treatment. Inhaled or topical steroids, and adrenalreplacement steroid doses )\ mg daily prednisone equivalent) are permitted in theabsence of active autoimmune disease.

3. Patients with urothelial cancer and any history or current CNS metastasis.

4. Patients who were hospitalized during screening for infectious complications orrequired IV antibiotics in the 14 days prior to Cycle 1 Day 1.

5. Patients who presented in the 14 days prior to or on Cycle 1 Day 1 with one or moreof the following:

• ANC of <1.5 x 109 cells/L

• Platelets of < 100 x 109 cells/L

• Hemoglobin of < 9 g/dL

6. Patients who received G-CSF in the 14 days prior to Cycle 1 Day 1

7. Patients who had febrile neutropenia during the previous line of therapy or duringthe last line of therapy containing cytotoxic chemotherapy.

8. Patients who are primary refractory to anti-PD-(L)1 directed therapy.

9. Patients with NSCLC and more than 2 prior lines of systemic anti-cancer therapy inthe locally-advanced/metastatic disease setting; and who received more than oneprior line of cytotoxic chemotherapy in the locally-advanced/metastatic setting.

10. Patients with urothelial cancer who received more than 3 prior lines of systemicanti cancer therapy in locally-advanced/metastatic disease setting. Priorneoadjuvant or adjuvanttherapy is not counted.