Arm 1: Phase 1 Study of monovalent CD123-Specific Adapter (SPRX002) and Universal CAR-Modified T cell (ARC-T Cells) for the Treatment of Patients with Relapsed or Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

The purpose of this study is to evaluate the safety and preliminary activity of ARC-T cells
and SPRX002 in participants with relapsed or refractory acute myeloid leukemia (AML) or
high-risk myelodysplastic syndrome (MDS)

Inclusion Criteria:

1. 18 years or older

2. Acute myeloid leukemia (AML) Subjects: WHO-confirmed AML (WHO AML Criteria 2016),
other than APL, with no standard treatment options available Relapsed or refractory
disease after 1 or 2 lines of therapy

1. Relapsed: Bone marrow blasts ≥ 5% following achievement of complete remission
(CR)/Complete remission with incomplete blood count recovery (CRi)/morphological
leukemia-free state (MLFS)

2. Refractory: Failure to achieve CR/CRi/MLFS with evidence of persistence leukemia
by blood and/or bone marrow after any of the following:

i. At least 2 cycles of 7+3 based therapy ii. At least 1 cycle of high or intermediate
dose cytarabine containing induction regimen iii. at least 2 cycles of venetoclax
(VEN)-based lower intensity therapy, e.g., with hypomethylating agents (HMA), or
low-dose Cytarabine (LDAC) or cladribine+LDAC iv. at least 4 cycles of HMA-based
therapy with venetoclax

3. Myelodysplastic syndrome (MDS) Subjects: Diagnosis of MDS and ≥ 10% bone marrow blasts
with indication of high-risk disease defined as those having resistant or refractory
disease to at least one course of therapy including HMA given at conventional regimen,
with or without venetoclax or other agents. Failure is defined as failure to attain a
response, or relapse after prior response to HMA therapy per the modified IWG
criteria. Patents relapsing after allogeneic hematopoietic stem cell transplant (HSCT)
>6 months prior are eligible if they have recovered from all transplant-related
toxicities and are off all immunosuppression for at least 6 weeks

4. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1

5. Adequate organ function, including renal and hepatic function based on last clinical
assessment performed within the screening period

1. Creatinine clearance ≥50 ml/min (Cockcroft-Gault or 24-hour urine collection in
cases in which Cockroft-Gault is unreliable or if preferred by physician) and not
on dialysis

2. Alanine aminotransferase <3 x upper limit of normal (ULN)

3. Aspartate aminotransferase <3 x the upper limit of normal (ULN)

4. Total bilirubin <2 x upper limit of normal (ULN) (except for patients with known
or suspected history of Gilbert's Syndrome where up to 3x ULN is allowed)

5. Left Ventricular Ejection Fraction (LVEF) ≥45% by echocardiography (ECHO) or
multigated acquisition (MUGA) scan

6. Pulse oxygenation ≥92% on room air

7. Prothrombin time test (PTT), prothrombin time (PT)/international normalized ratio
(INR) <1.5 x ULN, unless on a stable dose of anti-coagulant for thromboembolic
event (patients with any history of thromboembolic stroke; or history or Grade 2
(G2) or greater hemorrhage within 60 days are excluded)

6. Resolution of adverse events (AEs) from any prior systemic anticancer therapy,
radiotherapy, or surgery to Grade 1 or baseline (except G2 alopecia and G2 sensory
neuropathy)

7. Prior allogeneic stem cell transplant is allowed, provided the subject has recovered
from all AEs, there is no ongoing graft-versus-host-disease (GvHD) and subject is not
on taking any immunosuppressive medications to prevent GvHD

8. Male and females of childbearing potential must agree to use highly effective methods
of birth control through 6 months after the dose of study treatment

9. Patients must have an identified potential donor and transplant strategy/plan prior to
initiation of the lymphodepletion regimen to ensure availability of hematopoeitic stem
cells (HSCs) for potential urgent allogeneic HSC transplant (HSCT) if needed for
persistent bone marrow aplasia without evidence of residual leukemia. Transplant
decision making would be a discussion between subject and investigator due to
potential for treatment-related mortality and is not required

10. Willing to comply with and able to tolerate study procedures, including Long-Term
Safety Follow-up lasting up to 15 years

11. Subject's apheresis product from non-mobilized cells is received and accepted for cell
processing by manufacturing site. NOTE: apheresis will be accepted only after all
other eligibility criteria have been met

Exclusion Criteria:

1. Patients with acute promyelocytic leukemia (APL)

2. Patients with active CNS involvement. Subjects may be cleared of CNS involvement if
there has been no evidence of CNS involvement for at least 3 months prior to
enrollment

3. Hyperleukocytosis (≥25,000 blasts/μL) or rapidly progressive disease that in the
estimation of the investigator and sponsor would compromise ability to complete study
therapy. (Note: Subjects may be receiving or may receive hydroxyurea to maintain or
control hyperleukocytosis)

4. Previous treatment with an investigational gene or chimeric antigen receptor therapy
(Note: May be permitted after discussion with Medical Monitor)

5. Previous treatment with a directed therapy (T-cell engager or ADC) against the target
for the specific sparX protein in the specific arm for enrollment

6. Use of any anti-AML/MDS directed chemotherapy or targeted therapy, except hydroxyurea
therapy, within 14 days or 5 half-lives (whichever is shorter) prior to the date of
leukapheresis and use of any anti-AML/MDS directed monoclonal antibody within 28 days
prior to date of leukapheresis

7. Known infection with Human Immunodeficiency Virus or Human T-Cell leukemia/lymphoma
virus type 1 (HTLV-1)

8. A known hypersensitivity or severe allergy to study drug components including dimethyl
sulphoxide (DMSO) and human serum albumin

9. Contraindication to cyclophosphamide or fludarabine

10. Subject has systemic fungal, bacterial, viral or other infection that is exhibiting
ongoing signs/symptoms related to the infection without improvement despite
appropriate treatment

11. Severe uncontrolled intercurrent illness including:

1. Cardiovascular disease

2. Symptomatic congestive heart failure

3. Unstable angina, arrythmia, or myocardial infarction (MI) within 6 months prior
to screening

4. Significant pulmonary dysfunction

5. Uncontrolled thromboembolic events or recent severe hemorrhage

6. Any history of pulmonary embolism (PE) ever or deep vein thrombosis (DVT) within
3 months of screening. Therapeutic dosing of anticoagulants (e.g., warfarin, low
molecular weight heparin, Factor Xa inhibitors) is allowed for history of DVT if
greater than 3 months from time of screening) Note: Central line thrombosis not
requiring anticoagulation will not be excluded and will not require a 3-month
screening window

7. Autoimmune disease

12. Seropositive for and with evidence of active hepatitis B or C infection at time of
Screening

1. Subjects with a history of hepatitis B but have received antiviral therapy and
have non-detectable viral DNA for 6 months are eligible

2. Subjects seropositive because of hepatitis B virus vaccine with no signs or
active infection are eligible

3. Subjects who had hepatitis C but have received antiviral therapy and show no
detectable hepatitis C virus (HCV) viral RNA for 6 months are eligible

13. Any sign of active CNS pathology within 6 months of screening including history of
epilepsy, seizure requiring anti-seizure medications, paresis, aphasia, stroke, severe
brain injury, dementia, cerebellar disease, Parkinson's disease, organic brain
syndrome or psychosis. Subarachnoid hemorrhage or central nervous system (CNS) bleed
within 3 months of screening

14. Subject has active malignant tumors other than AML/MDS that requires active
antineoplastic or radiation therapy at the time of screening. Maintenance therapy or
hormonal therapy for well-controlled malignancy is allowed

15. Females who are pregnant or breastfeeding

16. Subjects with any significant medical condition, laboratory abnormality, or
psychiatric illness that would prevent the subject from participating in study (or
full access to medical records) as written including follow up, the interpretation of
data or place the subject at unacceptable risk are excluded