TT11 / Tessa Therap, UNC Lineberger Comprehensive Cancer Center, Baylor Scott & White Research Institute - LARVOL DELTA

Autologous CD30.CAR-T-cell therapy in patients with relapsed or refractory classical Hodgkin lymphoma – long term update of the chariot trial (ASH 2025) - "Methods The phase 2 trial was a single arm, multi-center study, enrolling pts (12-75 years) with cHL progressionafter at least 3 lines of therapy, including chemotherapy, brentuximab vedotin, and anti-programmed celldeath (PD)-1 antibodies. Pts were treated with CD30.CAR-T cells, after bendamustine and fludarabinelymphodepletion...ORR after CD30.CAR-T single infusion was 75% (n=9) with complete response (CR) rate of 50% (n=6).CD30.CAR-T treatment was well tolerated with only one pt experiencing grade 1 CRS which resolved with1 dose of tocilizumab...Potential strategies to improve long termresponses could include increasing cell doses, alternative lymphodepletion regimens, further engineeringof the product or the addition of novel therapeutic agents to enhance CD30.CAR-T effectiveness in r/rcHL. Further data on CAR-T kinetics will be available at presentation."

CAR T-Cell Therapy • Clinical • Classical Hodgkin Lymphoma • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Infectious Disease • Lymphoma • TNFRSF8

LCCC 1606-ATL: Study of CAR-T Cells Expressing CD30 and CCR4 for r/r CD30+ HL and CTCL (clinicaltrials.gov) - P1 | N=43 | Active, not recruiting | Sponsor: UNC Lineberger Comprehensive Cancer Center | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2041 ➔ Nov 2039 | Trial primary completion date: Sep 2026 ➔ Dec 2025

Enrollment closed • Trial completion date • Trial primary completion date • B Cell Lymphoma • Classical Hodgkin Lymphoma • Cutaneous T-cell Lymphoma • Dermatology • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Oncology • Sezary Syndrome • Skin Cancer • T Cell Non-Hodgkin Lymphoma • CCR4 • TNFRSF8

Study of CD30 CAR for Relapsed/Refractory CD30+ HL and CD30+ NHL (clinicaltrials.gov) - P1/2 | N=38 | Active, not recruiting | Sponsor: UNC Lineberger Comprehensive Cancer Center | Recruiting ➔ Active, not recruiting | Trial completion date: Aug 2038 ➔ Nov 2039 | Trial primary completion date: Sep 2027 ➔ Dec 2025

Enrollment closed • Trial completion date • Trial primary completion date • Cutaneous T-cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • TNFRSF8

CD30 CAR for CD30+ NSGCT (clinicaltrials.gov) - P2 | N=2 | Active, not recruiting | Sponsor: UNC Lineberger Comprehensive Cancer Center | Recruiting ➔ Active, not recruiting | N=18 ➔ 2 | Trial completion date: Aug 2030 ➔ Dec 2030 | Trial primary completion date: Sep 2026 ➔ Dec 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Germ Cell Tumors • Testicular Non-seminoma

CD30 CAR for CD30+ NSGCT (clinicaltrials.gov) - P2 | N=18 | Recruiting | Sponsor: UNC Lineberger Comprehensive Cancer Center | Active, not recruiting ➔ Recruiting | Trial primary completion date: Sep 2025 ➔ Sep 2026

Enrollment open • Trial primary completion date • Germ Cell Tumors • Testicular Non-seminoma

CD30 CAR for CD30+ NSGCT (clinicaltrials.gov) - P2 | N=18 | Active, not recruiting | Sponsor: UNC Lineberger Comprehensive Cancer Center | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2026 ➔ Aug 2030 | Trial primary completion date: Dec 2026 ➔ Sep 2025

Enrollment closed • Trial completion date • Trial primary completion date • Germ Cell Tumors • Testicular Non-seminoma

Study of CD30 CAR for Relapsed/Refractory CD30+ HL and CD30+ NHL (clinicaltrials.gov) - P1/2 | N=40 | Recruiting | Sponsor: UNC Lineberger Comprehensive Cancer Center | Trial completion date: Aug 2040 ➔ Aug 2038 | Trial primary completion date: Aug 2025 ➔ Sep 2027

Trial completion date • Trial primary completion date • Cutaneous T-cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • TNFRSF8

ATLCAR.CD30.CCR4 for CD30+ HL ATLCAR.CD30.CCR4 Cells (clinicaltrials.gov) - P1/2 | N=31 | Recruiting | Sponsor: UNC Lineberger Comprehensive Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • IO biomarker • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

CD30 CAR for Relapsed/Refractory CD30+ T Cell Lymphoma (clinicaltrials.gov) - P2 | N=20 | Recruiting | Sponsor: UNC Lineberger Comprehensive Cancer Center

Trial completion date • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • TNFRSF8

Administration of T Lymphocytes for Prevention of Relapse of Lymphomas (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: UNC Lineberger Comprehensive Cancer Center

Trial completion date • Cutaneous T-cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • ALK • TNFRSF8

ATLCAR.CD30.CCR4 for CD30+ HL ATLCAR.CD30.CCR4 Cells (clinicaltrials.gov) - P1/2 | N=31 | Not yet recruiting | Sponsor: UNC Lineberger Comprehensive Cancer Center

IO biomarker • New P1/2 trial • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

Study of CD30 CAR for Relapsed/Refractory CD30+ HL and CD30+ NHL (clinicaltrials.gov) - P1/2 | N=40 | Recruiting | Sponsor: UNC Lineberger Comprehensive Cancer Center | Trial completion date: Aug 2038 ➔ Aug 2040 | Trial primary completion date: Aug 2023 ➔ Aug 2025

Trial completion date • Trial primary completion date • Cutaneous T-cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • TNFRSF8

Singapore’s Top-funded Biotech Start-up Announces Liquidation Following Failure of Fundraising (GeneOnline) - "Despite being backed by Singapore’s top investors including Temasek Holdings and the government-linked EDBI, Tessa Therapeutics Ltd. still failed to raise more capital to sustain operations and develop its cell therapies for cancers. As a result, this Singapore-based biotech start-up has announced to its shareholders the intent of initiating liquidation procedures in the near future...Last September, TT11X even won recognition in the 'Most Promising Off-the-Shelf Therapies' category at the Asia-Pacific Cell & Gene Therapy Excellence Awards 2022....Tessa’s other leading pipelines include TT11, an autologous CD30 CAR T-cell therapy for R/R Classical Hodgkin lymphoma, as well as TT16, a combination therapy utilizing HER2-specific autologous CAR VST and an oncolytic virus."

Financing • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Solid Tumor

Tessa Therapeutics Announces Positive Results from CD30 CAR-T Combination Study with Nivolumab in 2nd line Hodgkin Lymphoma (GlobeNewswire) - P1 | N=15 | ACTION (NCT05352828) | Sponsor: Tessa Therapeutics | "Tessa Therapeutics Ltd...presented encouraging safety and efficacy data from a combination study of its autologous CD30 CAR-T therapy (TT11) with Bristol Myers Squibb’s nivolumab at the 17th International Conference on Malignant Lymphoma taking place from June 13-17, 2023, at Lugano, Switzerland....Circulating tumor ctDNA-MRD (minimum residual disease) was assessed with PhasED-Seq (Foresight Diagnostics) in 3 patients with complete responses at End of Treatment (EOT). All 3 patients (100%) had undetectable ctDNA-MRD demonstrating deep molecular response. Additional patient samples are currently under assessment."

P1 data • Hematological Malignancies • Hodgkin Lymphoma • Oncology

Combined autologous CD30.CAR-T cells and nivolumab in patients with relapsed or refractory classical Hodgkin Lymphoma after failure of frontline therapy (ACTION study) (ICML 2023) - "Two patients had cytokine release syndrome (Grade 1), which resolved without use of steroid or tocilizumab. Preliminary data demonstrated favorable safety profile and promising anti-tumor responses of CD30.CAR-T combined with nivo in r/r cHL patients after failure of frontline therapy. Evaluation of 15 patients enrolled is ongoing, and the clinical and ctDNA-MRD data will be presented at the meeting."

CAR T-Cell Therapy • Clinical • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • TNFRSF8

Tessa Therapeutics’ Autologous and Allogeneic Cell Therapy Data to be Featured at the 17th International Conference on Malignant Lymphoma, Lugano (GlobeNewswire) - "Tessa Therapeutics Ltd...announced two presentations featuring clinical data from the company’s autologous CD30.CAR-T therapy TT11 and off-the-shelf CD30 CAR EBVST therapy (TT11X) will be featured at the 17th International Conference on Malignant Lymphoma taking place from June 13-17, 2023, at Lugano, Switzerland."

Clinical data • P1 data • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology

CERTAIN: Phase 1 Study of Autologous CD30.CAR-T in Relapsed or Refractory CD30 Positive Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1 | N=21 | Active, not recruiting | Sponsor: Tessa Therapeutics | Trial primary completion date: Mar 2023 ➔ Nov 2022

Trial primary completion date • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • TNFRSF8

ACTION: Autologous CD30.CAR-T in Combination With Nivolumab in cHL Patients After Failure of Frontline Therapy (clinicaltrials.gov) - P1b | N=15 | Active, not recruiting | Sponsor: Tessa Therapeutics | Recruiting ➔ Active, not recruiting

Checkpoint inhibition • Combination therapy • Enrollment closed • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • TNFRSF8

Updated Results and Correlative Analysis: Autologous CD30.CAR-T-Cell Therapy in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma (CHARIOT Trial) (ASH 2022) - "Methods This is a Phase 2 single arm, multi-center study, enrolling patients (12-75 years) with cHL progression after at least 3 lines of therapy, including chemotherapy, brentuximab vedotin, and anti-programmed cell death (PD)-1 antibodies...The patients were treated with CD30.CAR-T cells, after lymphodepletion chemotherapy using bendamustine and fludarabine, with an allowable dose range of 2.0 to 2.7 × 108 CD30.CAR-T cells per m2...The CD30.CAR-T cells showed good expansion and persistence after infusion. The efficacy, safety and exploratory biomarkers of CD30.CAR-T will be further evaluated in the Pivotal segment of this Phase 2 study."

CAR T-Cell Therapy • Clinical • IO biomarker • Hematological Malignancies • Hodgkin Lymphoma • Immunology • Inflammation • Lymphoma • Oncology • IL15 • TNFRSF8

Clinical Activity of Anti-PD-1 Therapy Following CD30 CAR-T Cell Therapy in Relapsed Hodgkin Lymphoma (ASH 2022) - P1, P1/2 | "The anti-PD-1 antibodies nivolumab and pembrolizumab have both been studied in phase II studies in patients with r/r cHL with ORR ranging between 65-87% and median progression free survival (PFS) ranging from 13-15 months...This study is the first to describe CD30.CAR-T expansion following anti-PD-1 therapy. While further analysis is warranted to assess for CD30.CAR-T functionality after anti-PD-1 exposure, our data suggest that anti-PD-1 therapy may rescue CD30.CAR T cells, supporting further investigations in patients with cHL."

CAR T-Cell Therapy • Clinical • Bone Marrow Transplantation • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • Transplantation • CCR4 • TNFRSF8

Ultrasensitive Circulating Tumor DNA (ctDNA) Dynamics after Autologous CD30.CAR-T Cell Therapy for Relapsed or Refractory (r/r) Classical Hodgkin Lymphoma (CHARIOT Trial) (ASH 2022) - P2 | "A single infusion of CD30.CAR-T therapy rapidly induces MRD negativity in a significant subset of patients at Day 42. ctDNA as exploratory biomarker will be further evaluated in Pivotal part of the study."

CAR T-Cell Therapy • Circulating tumor DNA • IO biomarker • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • TNFRSF8

CAR T-Cell Therapy in Hodgkin Lymphoma (SOHO 2022) - P1 | "Material and Methods To assess the safety and activity of banked CD30 CAR EBVSTs, we are treating patients with multiply relapsed or refractory CD30-positive lymphomas in a phase 1 dose escalation study using 4×107, 1×108 or 4×108 CD30.CAR EBVSTs infused after lymphodepletion with cyclophosphamide and fl udarabine...Patients had received a median of 5 prior therapies, including potentially high dose chemotherapy with autologous stem cell rescue, checkpoint inhibitors and brentuximab vedotin, and all had active disease at time of CAR-T cell infusion...J Clin Oncol. 2021 Feb 10;39(5):514-524."

CAR T-Cell Therapy • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • CD19

Phase 1b/2 Study of Autologous CD30.CAR-T Cells in Combination with Nivolumab in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma after Failure of Frontline Therapy (ACTION) (ASH 2022) - P1, P1/2, P1b | "The efficacy and safety profile of programmed death (PD)-1 checkpoint inhibitors, nivolumab and pembrolizumab, in cHL have been well demonstrated (Chen et al., 2017; Kuruvilla et al., 2021; Younes et al., 2016), with FDA approval for r/r cHL. PD-1 checkpoint inhibitors, in combination with CD30-directed antibody therapy (brentuximab vedotin) or other chemotherapies, have also shown high efficacy in this setting (Advani et al., 2021; Mei et al., 2022; Moskowitz et al., 2021)...Following a leukapheresis procedure for manufacture of CD30.CAR-T cells, patients will be treated with 4 cycles of nivolumab every 4 weeks (Q4W), and a single infusion of CD30.CAR-T cells (given between nivolumab Cycles 2 and 3, and after lymphodepletion with bendamustine and fludarabine)...The key secondary objective is to evaluate potential anti-tumor activity, as assessed by the CR rate of autologous CD30.CAR-T in combination with nivolumab at EOT in 14 evaluable patients, as per..."

CAR T-Cell Therapy • Clinical • Combination therapy • IO biomarker • P1/2 data • Bone Marrow Transplantation • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • Pediatrics • Transplantation • TNFRSF8

Longitudinal Dynamics of Clonal Hematopoiesis in Patients Receiving Anti-CD30 CAR T-Cell Therapy (TCT-ASTCT-CIBMTR 2023) - P1 | "The recurrence of DNMT3A and PPM1D mutations indicates the selective influence of prior chemotherapeutics. Given the increasing number of patients receiving CAR-T therapy, further work must determine if high CH prevalence in this cohort is predictive of increased long-term complications in survivors."

CAR T-Cell Therapy • Clinical • IO biomarker • Cardiovascular • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Oncology • Transplantation • DNMT3A • PPM1D • TNFRSF8

Evaluating the Safety and Clinical Efficacy of Off-the-Shelf CD30.CAR-Modified Epstein-Barr Virus-Specific T Cells in Patients with CD30-Positive Lymphoma (TCT-ASTCT-CIBMTR 2022) - P1 | "To assess the safety and clinical activity of banked CD30.CAR EBVSTs, we enrolled patients with multiply relapsed (median of 4 prior lines of therapy; range 3-5) or refractory CD30-positive lymphomas in a Phase 1 dose escalation study using 4 × 10 7 , 1 × 10 8 or 4 × 10 8 CD30.CAR EBVSTs infused after cytoreduction with cyclophosphamide and fludarabine...In summary, banked CD30.CAR EBVSTs can safely be given to allogeneic recipients and may cause significant tumor responses including complete remissions. These cells may be a suitable platform for other “off-the-shelf” CAR-T cell therapies."

Clinical • Epstein-Barr Virus Infections • Graft versus Host Disease • Hematological Malignancies • Immunology • Inflammation • Lymphoma • Oncology • Transplant Rejection • TNFRSF8