INTRODUCTION

• The T cell antigen coupler (TAC) is a novel, proprietary chimeric receptor that facilitates the re-direction of T cells to tumor cells and activates T cells by co-opting the endogenous T cell receptor complex, with the goal to elicit a safe and durable anti-tumor response. In preclinical models of cancer, TAC-engineered T cells effectively eradicate tumor cells in vitro and in vivo without TAC-related toxicities.

• TACTIC-2 (NCT04727151) is an open-label, multicenter phase I/II study that aims to establish safety, maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), pharmacokinetic profile, and efficacy of TAC01-HER2 in patients with HER2-positive solid tumors (i.e. breast, lung, pancreatic, colorectal, gastric, endometrial, ovarian, and others) whom have progressed on prior anti-cancer therapies.

• We present a clinical update from Cohorts 1 & 2 (8 participants) that highlights safety and efficacy data; the study further elucidates potential therapeutic impact to patients with HER2 overexpressed solid tumors.

TAC01-HER2 SCIENCE

Key features of TAC01-HER2 technology:

• TAC01-HER2 functions independently of MHC
• TAC01-HER2 requires endogenous TCR for T cell activation
• TAC01-HER2 incorporates the co-receptor and recruits the TCR complex, mimicking natural TCR activation

The TAC receptor interacts directly with the TCR-CD3 epsilon domain.

The TAC receptor also binds directly to the tumor antigen. Initiating the first step in T cell activation, which then leads to full T cell activation.

The TAC receptor then signals through the CD3-TCR complex.

TRIAL DESIGN & MANUFACTURING

This ultimately results in tumor cell lysis.

(1+, 2+ & 3+) HER2 Positive Breast Cancer Planned Enrollment of 23 Patients; 2nd Line + Seeing
(1+, 2+ & 3+) HER2 Positive non-Breast Cancer Planned Enrollment of 35 Patients; 2nd Line + Seeing

Lymphodepleting Chemotherapy: 3 consecutive days of fludarabine (Flu) IV (30 mg/m2) and cyclophosphamide (Cy) IV (300 mg/m2) with/without Mesna IV

PHASE I TRIAL ENROLLMENT

Primary Endpoints

Safety: DLTs, MTD

Secondary Endpoints

Efficacy: ORR, DOR, PFS, OS, RP2D, AEs

Eligibility Criteria

Patients with advanced, metastatic, unresectable solid tumors which express HER2 after at least 2 lines of therapy, at least 1 measurable lesion per RECIST version 1.1, ECOG performance score 0-1, grade 1 or baseline for any prior treatment related toxicities.

Cohorts 1 & 2: Demographic & Tumor-Intrinsic Characteristics

| Median Age (Range), by Year | | 65.5 (42-70) | Tumor Type (%)GastricColorectalGastroesophageal JunctionGall BladderEsophagealRectosigmoid | | --- | --- | --- | --- | --- | --- | | Sex: Male/Female (%) | M | 5(62.5%) | Tumor Type (%)GastricColorectalGastroesophageal JunctionGall BladderEsophagealRectosigmoid | | | | Sex: Male/Female (%) | F | 3(37.5%) | Tumor Type (%)GastricColorectalGastroesophageal JunctionGall BladderEsophagealRectosigmoid | | | | Race (%) | White | 7(87.5%) | Tumor Type (%)GastricColorectalGastroesophageal JunctionGall BladderEsophagealRectosigmoid | Previous Anti-Cancer Therapy Median (Range) | 4.5(2-12) | | Race (%) | Other | 1(12.5%) | | Previous Anti-Cancer Therapy Median (Range) | 4.5(2-12) | | ECOG PS (%) | 0 | 4(50.0%) | Previous Lines of HER2 Therapy Median (Range) | 2(0-9) | | | ECOG PS (%) | 1 | 4(50.0%) | Previous Lines of HER2 Therapy Median (Range) | 2(0-9) | | | HER2 Expression (%) | 3+ | 7(87.5%) | Previous HER2 Therapy Types (%)TrastuzumabTrastuzumab DeruxtecanInvestigative | 5(62.5%) | | | HER2 Expression (%) | 2+/ISH+ | 1(12.5%) | Previous HER2 Therapy Types (%)TrastuzumabTrastuzumab DeruxtecanInvestigative | 3(37.5%)5(62.5%) | |

PHASE I SAFETY DATA

Baseline Domain

Day 0 Summary of Adverse Events by Incidence

Summary of Adverse Events by Incidence

Safety Summary

Frequency

No Observed Cytokine Release Syndrome (CRS) in Cohorts 1 & 2

No Observed Immune Eector Cell-Associated Neurotoxicity (ICANS) in Cohorts 1 & 2

BIOMARKER DATA: FIRST PATIENT RESPONSE

All Serious Adverse Events are Confirmed to be Unrelated to TAC-01 HER2 Infusions

Blood Pharmacokinetics

Blood PK Data from Patient 0203-0021

Low but definitive presence TAC01-HER2 cells indicated by elevated TAC copies at day 15 marker. Compared against average (+/- SEM) of other cohort 1 & 2 patients (n=6).

Pt. 0203-0021
Avg (+/-SEM) of other cohort 1&2 pts. (n=6)

Cytokine Data from Patient 0203-0021 Serum cytokine analysis indicates slightly elevated levels in patient 0203-0021 vs others. Absence of IL-6 confirms lack of CRS. This is subtle, but intriguing biomarker data that corroborates safe response in patient 0203-0021.

EFFICACY: DOSE LEVEL 2 RESPONSE

Dose Level 2 (6-8 x 10^5 cells/kg) Day 28 Change in Lesion Sizes from Baseline

Partial Response Observed in Patient 0203-0021 42 year old male with IHC 3+, HER2+ stage IVb metastatic gastric adenocarcinoma. Previously treated with 2 lines of HER2-directed targeted + chemotherapy & palliative radiation.

TUMOR REGRESSION: FIRST PATIENT RESPONSE

Gastrohepatic Lymph Node in Patient 0203-0021

Baseline Day 0 (2.00 cm)

Gastrohepatic Node Reduction Perioportal Mass Reduction

Lymph Node Reduction

There has been overall interval decreased size of previously noted metabolically active lymph nodes associated with the mass, however with persistent intense metabolic activity in most of them.

*Despite SUVmax increase the lesions shows more extensive photopenic areas, representing cystic/necrotic change cancer cell death. ** There was also a stable cystic/necrotic node cancer cell death.

SUMMARY & CONCLUSIONS

SAFETY

EFFICACY

Interim results from the Phase I TACTIC-02 study suggest that TAC-01 HER2 is safe and well tolerated, supported by the absence of DLTs and events of special interest such as CRS & ICANS.

Demonstrated early signals of clinical activity, highlighting a partial response in a stage IVb gastric cancer patient and a disease control rate of 75% in cohort 2.

TRIAL PROGRESS

Disclosures: Dr. Benjamin L. Schlechter has no conflicts of interest to report.
Sponsorship: This Phase I/II Clinical Trial has been fully funded by Triumvira Immunologics Inc.
Contact: dadib@triumvira.com, benjamin_schlechter@dfci.harvard.edu

This study is ongoing with further investigation of TAC-01 HER2 in the remaining phase I trial, with enrollment in dose level 3 & patients consented for dose level 4. Phase II enrollment begins in 2023.