A Study of TSC-100 and TSC-101 in AML, ALL and MDS in Patients Undergoing Allogeneic Peripheral Blood Stem Transplantation

Inclusion Criteria:

• Male or female aged ≥ 18 years at the time of signing the informed consent.

• Eastern Cooperative Oncology Group (ECOG)-PS ≤ 2 at the time of the screening visit.

• Contraceptive use by male and female participants must be consistent with localregulations regarding the methods of contraception for those participating inclinical studies.

• Male Participants:

• A male participant must agree to use a highly effective contraceptive as detailed inAppendix 4 of this protocol during the intervention period and for at least 12months after the last dose of study intervention and refrain from donating spermduring this period.

• Female Participants:

• A female participant is eligible to participate if she is not pregnant, notbreastfeeding, and at least one of the following conditions applies:

• Not a woman of childbearing potential (WOCBP) OR

• A WOCBP who agrees to follow the contraceptive guidance during the interventionperiod and for at least 12 months after the last dose of study intervention.

• Preparing to undergo allogeneic HCT for either of the following:

• AML

• MDS

• ALL

• Participants in the treatment arms must express HLA-A*0201. Participants in thecontrol arm may express any HLA type.

• Having the HA1+/- or HA-1+/+ (HA-1 positive) genotype to be eligible for TSC-100treatment.

• Having the HA2+/- HA-2+/+ (HA-2 positive) genotype to be eligible for TSC-101treatment.

• Having a haploidentical donor, MMUD, or MUD for HCT who is adequately HLA-matched byinstitutional standards and meets the donor inclusion criteria.

• Considered to be clinically indicated for haploidentical donor, MMUD, or MUDtransplantation at the discretion of the treating investigator.

• Considered to be clinically indicated for RIC at the discretion of the treatinginvestigator.

• Considered to be clinically indicated for peripheral blood stem cell transplantationat the discretion of the treating investigator.

• Organ function parameters for transplant eligibility are met per institutionalstandards.

• Capable of giving signed informed consent - which includes compliance with therequirements and restrictions listed in the ICF and in this protocol.

• Participants must provide consent for mandatory study procedures including bonemarrow biopsy and blood sampling for research analyses in the ICF.

• Participants must agree to participate in long-term follow-up for up to 15 yearspost initial product treatment if they are enrolled in the study and receive theinvestigational Tcell infusion.

Donor Inclusion Criteria :

• Male or female aged ≥ 18 years at the time of signing the informed consent.

• Able to undergo peripheral blood stem cell (PBSC) collection and up to 2 rounds ofleukapheresis (for TSC-100 or TSC101 manufacturing for treatment arms only, and ffor stem cell collection for both treatment arms and the control arm).

• Donors matched to TSC-100 participants should be HA-1-/- (negative) and/or negativefor all HLA-A*02 alleles

• Donors matched to TSC-101 participants should be negative for all HLA-A*02 alleles

• Capable of giving signed informed consent which includes compliance with therequirements and restrictions listed in the ICF and in this protocol.

Exclusion Criteria:

• Medical or psychological conditions that would make the participant an unsuitablecandidate for cell therapy including another concurrent uncontrolled malignancy oractive CNS disease.

• The presence of organ toxicities will not necessarily exclude participants fromenrolling on the protocol at the discretion of the PI; however, a delay in theinfusion of HA1/HA2 TCRT cells may be required at the discretion of the treatinginvestigator

• Participants with levels of donor-specific HLA antibodies that are considered by thetreating investigator to be high enough to warrant desensitization protocols and whohave no alternate donors.

• Participants who meet inclusion criteria for TSC-101 but who are also positive forHLAA*02:07.

• Participants with evidence of clinically significant infection or uncontrolled viralr reactivation of cytomegalovirus (CMV), Epstein-Barr virus (EBV), Adenovirus, BKvirus (BKV), or human herpesvirus 6 (HHV-6).

• Participants with active cardiac disease, defined as:

• Uncontrolled or symptomatic angina within the past 3 months.

• History of clinically significant arrhythmias (such as ventricular tachycardia,ventricular fibrillation, torsades de pointes). Atrial fibrillation with controlledventricular response on treatment is not an exclusion.

• Myocardial infarction < 3 months from study entry.

• Uncontrolled or symptomatic congestive heart failure.

• Prior allogeneic HCT.

• Participants who have a history of hypersensitivity to murine proteins.

• Enrollment on a concomitant trial with a novel investigational agent.

• Use of anti-thymocyte globulin, alemtuzumab, or other in vivo T-cell depletingagents from Day -14 through end of study.

Donor Exclusion Criteria :

• Donors for TSC-100 positive for any HLA-A02 allele would be excluded unless theyare HA-1 negative. If donors with any HLA-A02 allele are considered for patientseligible for TSC-100, the donor would undergo HA-1 testing to ensure that the donoris HA-1 negative (40% probability).

• Donors for TSC-101 positive for any HLA-A*02 allele are excluded regardless of HA- 2status.

• Donors who test positive for any of the following: HIV-1, HIV-2, humanT-lymphotropic virus (HTLV)-1, HTLV-2 seropositive or with active hepatitis B orhepatitis C virus infection, syphilis, West Nile virus through central lab testing.Donors who screen positive for risk of CreutzfeldtJakob disease or Zika virusinfection using donor history questionnaires will also be excluded. Donors withevidence of past CMV or EBV infections will be allowed.

• Related donor residing outside of the United States of America (USA). If the donorscreening, testing and leukapheresis can be performed at the same site where theparticipant is being treated, the donor is considered eligible.