Corporate Presentation - October 2021 Engaging the TCR to Transform the Treatment of Solid Tumors - Investors - TCR2 Therapeutics
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Engaging the TCR to Transform
the Treatment of Solid Tumors
Corporate Presentation
October 2021
1
Forward Looking Statements
This presentation has been prepared by TCR2 Therapeutics Inc. (“we,” “us,” or “our”) and gavo-cel will not support further development and marketing approval; the risk that we
contains forward-looking statements within the meaning of the Private Securities Litigation may be unable to gain approval of gavo-cel and our other product candidates on a timely
Reform Act of 1995 and other federal securities laws. Forward-looking statements are basis, if at all; the risk that we have over-estimated the potential patient population for our
neither historical facts nor assurances of future performance. Instead, they are based on product candidates, if approved; the risk that the current COVID-19 pandemic will impact
our current beliefs, expectations and assumptions regarding the future of our business, our clinical trials and other operations; and the other risks set forth under the caption “Risk
future plans and strategies, our development plans, our clinical results and other future Factors” in our most recent Annual Report on Form 10-K for the year ended December
conditions. All statements, other than statements of historical facts, contained in this 31, 2020, as filed with the SEC on March 16, 2021, as updated in our most recent
presentation, including express or implied statements regarding our expectations for the Quarterly Report on Form 10-Q for the quarter ended June 30, 2021, as filed with the SEC
Phase 1/2 clinical trials of gavo-cel, our expectations for the safety and efficacy of our on August 5, 2021, and in our future filings with the SEC available at the SEC’s website at
product candidates and enhancements, including gavo-cel, compared to current T-cell www.sec.gov. New risks and uncertainties may emerge from time to time, and it is not
therapy approaches, our expectations regarding the estimated patient populations and possible to predict all risks and uncertainties. You should not place undue reliance on any
related market opportunities in gavo-cel’s targeted indications, and our expectations forward‐looking statements, which speak only as of the date they are made.
regarding manufacturing of our product candidates are forward-looking statements. These
statements are based on management’s current expectations and beliefs and are forward- While we may elect to update these forward-looking statements at some point in the
looking statements which involve risks and uncertainties that could cause actual results to future, we assume no obligation to update or revise any forward-looking statements
differ materially from those discussed in such forward-looking statements. except to the extent required by applicable law. Although we believe the expectations
reflected in such forward-looking statements are reasonable, we can give no assurance
Such risks and uncertainties include, among others: uncertainties inherent in clinical that such expectations will prove to be correct. Accordingly, readers are cautioned not to
studies and in the availability and timing of data from ongoing clinical studies; whether place undue reliance on these forward-looking statements. No representations or
interim results from a clinical trial will be predictive of the final results of a trial; the warranties (expressed or implied) are made about the accuracy of any such forward-
possibility that positive results from preclinical studies and correlative studies may not looking statements.
necessarily be predictive of the results of our planned clinical trials, including the Phase
1/2 clinical trials of gavo-cel; the risk that the results from the Phase 1/2 clinical trials of
2
Powering Our Vision
Building a Solid Tumor Focused Cell Therapy Company
Versatile TRuC Platform Emerging Innovative TRuC-T Pipeline
▪ Lead clinical program: gavo-cel
▪ Novel solid tumor targets: MSLN, CD70, GPC3, NECTIN-4
▪ First enhancement IND filing for TC-510, gavo-cel with
Solid Tumor Allogeneic
Enhancements PD-1 Switch, anticipated in 1Q22
Franchise Platform
▪ POC for lead allogeneic development candidate
MSLN, CD70, GPC3, PD-1 Switch, IL-15, Dual
POC for Lead Candidate
NECTIN-4 TRuCs
Established Leadership & Strategy
▪ Deep operational, clinical and research expertise in cell
therapy and immuno-oncology
World Class, In-House
Manufacturing ▪ Capital efficient manufacturing strategy
Cell Therapy
Leadership Capabilities ▪ State-of-the-art commercial-scale facility in Rockville, MD
cGMP production ready in 2023
~$317M
Cash as of 2Q21
3
TRuC, T Cell Receptor Fusion Construct; MSLN, mesothelin; POC, proof of concept
Advancing a Diverse Pipeline of Solid Tumor Programs 4 MSLN, mesothelin; NSCLC, non-small cell lung cancer; MPM, mesothelioma; GvHD, Graft versus Host Disease
Evolving the Natural Power of the TCR
Advancing a New Cell Therapy Modality to Create Life-Transforming Medicines
TRuC® Platform
(T Cell Receptor Fusion Constructs)
Harnessing the TCR Complex TRuC® construct integrates into the TCR
replacing the native CD3ε subunit
Comprehensive T cell activation to tackle
solid tumors α β
ε δ γ ε
No HLA restriction supports broad patient
access ζ ζ
Versatile platform with flexibility to add
enhancements
Potential across oncology and autoimmune
in multiple high-value indications
Cytotoxic TRuC-T Cells TRuC Treg Cells
Solid Tumors Autoimmune Diseases
Hematological Malignancies Transplant Rejection
5
gavo-cel
Stage of Development: Phase 1/2
6
Mesothelin Solid Tumors Represent a Significant Market
Initial gavo-cel Indications Expansion Opportunities
Population: 80,000 patients Population: 163,000 patients
Malignant Pleural Mesothelioma Esophageal Cancer
Population: 2,100 76% 30% Population: 5,000
✓ Orphan Drug Designation
Potential Accelerated Approval
Triple Negative Breast Cancer
36% Population: 15,000
Non-Small Cell Lung Cancer
Population: 61,000 31%
Pancreatic Cancer
66% Population: 38,000
Cholangiocarcinoma
Population: 4,000 50% Gastric Cancer
✓ Orphan Drug Designation 40% Population: 11,000
Potential Accelerated Approval
Endometrial Cancer
Ovarian Cancer 20% Population: 13,000
Population: 13,000
58%
Colorectal Cancer
55% Population: 81,000
Percent of Patients with Mesothelin Surface Expression
7
Refs: Inaguma 2017, SEER Statistics 2020, Morello 2016, Tozbikian 2014
Ongoing gavo-cel Phase 1/2 Trial in MSLN+ Solid Tumors
PHASE 1: Dose Finding PHASE 2: Expansion
4 Dose Level 7 (+ LD)
NSCLC
n=8
NSCLC
n=12
(1x109 cells/m2) + anti-PD1
Dose Level 6 (- LD)
3 Dose Level 5 (+ LD) Ovarian Cancer
(5x108 cells/m2) n=10
Dose Level 4 (- LD)
RP2D
2 Dose Level 3 (+ LD) Cholangiocarcinoma
(1x108 cells/m2)
Dose Level 2 (- LD) n=10
Indications with potential
1 Dose Level 1 (+ LD)
for accelerated approval
(5x107 cells/m2) MPM
Dose Level 0 (- LD) n=10
(‒ LD) Cohorts = 1 patient
(+ LD) Cohorts = 3 patients
Each Ph. 1 dosing cohort consists of: Primary Endpoints
▪ Phase 1: Safety
+14 +14 1 Patient
+28 o determine recommended Phase 2 dose (RP2D)
Days Days Days
+ LD ▪ Phase 2: Efficacy:
1 Patient 1 Patient Next Dose o response rate (RECIST v1.1)
- LD + LD Level
1 Patient
+ LD
8
LD, Lymphodepletion; RP2D, Recommended Phase 2 dose; MPM, Malignant Pleural/Peritoneal Mesothelioma; NSCLC, Non-Small Cell Lung Cancer
Key Takeaways from gavo-cel Phase 1 Trial
3/3 Clinical Activity in All
Tumor Types Treated
RECIST ORR MTD Identified at
5x108/m2 + LD
6 Partial Responses by
Target Lesion Assessment
31%
38%
ORR
ORR
Approaching RP2D
4 RECIST PRs in
MPM (3) & Ovarian Cancer (1)
25%
ORR
Orphan Drug Designation
81% Disease Control
Rate (DCR)
for Mesothelioma and
Cholangiocarcinoma
5.9 Median PFS (months)
for MPM Patients 46%
Patients Eligible for
gavo-cel Based on
Mesothelin Threshold
All gavo-cel MPM
11.2 Median OS (months) for
MPM Patients
Patients + LD (gavo-cel
+ LD)
9
LD, Lymphodepletion; PR, Partial Response; ORR, Overall Response Rate; MTD, maximum tolerated dose; ODD, orphan drug designation; MPM, CCA
Patient Tumor Characteristics
Dose Level DL 0 (no LD) DL 1 DL 2 (no LD) DL 3 DL 4 (no LD) DL 5
Overall
(gavo-cel dose) 5x107/m2 5x107/m2 1x108/m2 1x108/m2 5x108/m2 5x108/m2
No. Patients n=1 n=6 n=1 n=5 n=1 n=3 n=17 (%)
Age, median (range) 61 69 (36-84) 46 46 (31-63) 67 52 (37-66) 57 (31-84)
1 MPM, 12 MPM
5 MPM
Diagnosis 1 MPM 1 MPM 3 Ovarian 1 MPM 3 MPM 4 Ovarian
1 Ovarian
1 Cholangio 1 Cholangio
MSLN 2+/3+ 90 81 (55-100) 90 60 (50-90) 60 65 (65-73) 73 (50-100)
Median No. Prior Rx 8 4 9 6 7 4 5 (1-9)
Prior ICI, n (%) 1 (100) 4 (67) 1 (100) 2 (40) 1 (100) 2 (66) 11 (65)
Prior anti-MSLN
1 (100) 1 (17) 1 (100) 1 (20) 0 1 (33) 5 (29)
therapy, n (%)
Bridging Therapy,
0 4 (67) 0 4 (80) 1 (100) 1 (33) 10 (59)
n (%)
Data Cutoff – June 30, 2021
10 MSLN, mesothelin; ICI, immune checkpoint inhibitor; MPM, malignant pleural/peritoneal mesothelioma; Cholangio, cholangiocarcinomaGrade ≥3 Treatment Emergent Adverse Events
DL 0 (no LD) DL 1 DL 2 (no LD) DL 3 DL 4 (no LD) DL 5
Overall
Adverse Event 5x107/m2 5x107/m2 1x108/m2 1x108/m2 5x108/m2 5x108/m2
n=1 (%) n=6 (%) n=1 (%) n=5 (%) n=1 (%) n=3 (%) n=17 (%)
Hematologic
Lymphopenia 1 (100) 6 (100) 0 5 (100) 1 (100) 3 (100) 16 (94)
Neutropenia 0 6 (100) 0 5 (100) 0 3 (100) 14 (82)
Thrombocytopenia 0 2 (33) 0 1 (20) 0 2 (67) 5 (29)
On Target / On Tumor
CRS 0 2 (33) 0 1 (20) 0 3 (100) 6 (35)
Neurotoxicity 0 0 0 0 0 0 0
On Target / Off Tumor
Pericarditis /
Pericardial effusion
0 0 0 0 0 0 0
Pleuritis /
Pleural effusion
0 0 0 0 0 0 0
Peritonitis/Ascites 0 0 0 0 0 0 0
Other
Pneumonitis 0 1 (17)* 0 0 0 0 1 (6)
Sepsis 0 1 (17) 0 0 0 0 1 (6)
Hemorrhage 0 0 0 0 0 1 (33)* 1 (6)
Data Cutoff – June 30, 2021
11 * Dose Limiting ToxicityConsistent Tumor Regression in Patients with gavo-cel
Overall Response Rate 25%, Disease Control Rate 81%
48
50
40
CHOLANGIO
30 gavo-cel
All
20 + LD
MPM
MPM
MPM
MPM
MPM
MPM
MPM
MPM
MPM
MPM
MPM
OVA
OVA
OVA
OVA
OVA
10
DCR 81% 77%
0
-10 -5 ORR
-20 -13 -12 -10 -9 25% 31%
(independent)
-30 -23 -20
-40 -25 -25 ORR
31% 38%
* (investigator)
-50
-60
*
-56 -55 MPM ORR 27% 38%
-70
-67 -64 -61
DCR = PR or SD lasting at least 3 months
-80 -75 gavo-cel w/o LD
-90 gavo-cel w LD
-100
4 2 3 5 14 15 8 13 6 1 12 16 11 9 7 10
* PR by Investigator Assessment Patients Data Cutoff – June 30, 2021
12 MPM, malignant pleural/peritoneal mesothelioma; OVA, ovarian cancer; CHOLANGIO, cholangiocarcinoma; DL, dose level;
LD, lymphodepletion; DCR, disease control rate; ORR, overall response ratePatient Response and Follow-Up
Overall Response Rate 25%, Disease Control Rate 81%
Patient (Indication)
DL0 1 (MPM)
2 (MPM)
3 (MPM)
4 (MPM)
DL1 5 (OVA)
6 (MPM)
7 (MPM)
DL2 8 (MPM)
9 (MPM)
DL3 10 (OVA)
11 (OVA)
DL4 12 (MPM)
13 (OVA)
DL3 14 (CHO)
15 (MPM)
DL5 16 (MPM)
17 (MPM)
DL3* 18 (MPM)
DL3.5a* 19 (MPM)
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Lymphodepletion: LD No LD Months Data Cutoff – June 30, 2021
Response: SD PR CR PD Alive (ongoing) Deceased Survival post-PD
13 *Post-Data CutoffCase Study: Patient 14 - Cholangiocarcinoma
Tumor Regression (56%*)
Baseline Week 4 Week 8
16mm 7mm Not Measured
63-year-old female,
Target Lesion 1
Metastatic intrahepatic cholangiocarcinoma
Mediastinal
▪ Mutated KRAS and RB1
▪ Failed to respond to 5 prior lines of therapy
Week 8
14mm
Enrolled in gavo-cel Clinical Trial Study
▪ March 2021: Lymphodepletion with Flu/Cy followed
New Lesion
by gavo-cel at 1x108/m2
Liver
Baseline Week 4
SUV 7.2 SUV 1.2
Liver Lesion
PET Scan
14 * PR by Investigator AssessmentCase Study: Patient 15 - Mesothelioma
Partial Response (RECIST v1.1), Tumor Regression (55%)
Baseline Week 4 Week 8 PET SCAN
66-year-old female, 23mm 0mm 0mm
Baseline Week 4
Relapsed pleural mesothelioma
Target Lesion 1
Lymph Node
▪ Failed 4 prior lines of therapy, including
nivolumab/ipilimumab and anti-MSLN
ADC
Baseline Week 4 Week 8
Enrolled in gavo-cel Clinical Trial 21mm 13mm 13mm
Study
Target Lesion 2
▪ April 2021: Lymphodepletion with
Lung
Flu/Cy followed by gavo-cel at 5x108/m2
Baseline Week 4 Week 8
23mm 14mm 14mm
Target Lesion 3
Lung
15Case Study: Patient 5 - Ovarian Cancer
Partial Response (RECIST v1.1), Significant Tumor Regression (61%)
Baseline Week 4 Week 12 Week 24
70-year-old female, 19mm, 7.6cm3 14mm, 4cm3 10mm, 2.3cm3 9mm, 1.3cm3
Target Lesion 1
High grade, Stage IV serous ovarian cancer
Lymph Node
▪ TP53R248Q, CCNE1 amplified, wild type BRCA1/2
▪ Failed 6 prior lines of therapy
▪ Platinum resistant Baseline
27mm, 24cm3
Week 4
14mm, 3.3cm3
Week 12
9mm, 2.9cm3
Week 24
10mm, 1.7cm3
Enrolled in gavo-cel Clinical Trial Study
Target Lesion 2
Lymph Node
▪ April 2020: Lymphodepletion with Flu/Cy followed
by gavo-cel at 5x107/m2
Response Post gavo-cel Week 24
▪ Target Lesions: PR (at months 1, 2, 3, 6) 19mm
▪ Non-target Lesions: CR (at months 1, 2, 3, 6)
Lymph Node
New Lesion
▪ Best overall assessment: PR (at month 3)
▪ Overall: PD (new lymph node lesion)
16Survival of Patients with Mesothelioma
gavo-cel in Patients with MPM: ORR 38%, PFS 5.9 Months, OS 11.2 Months
gavo-cel Progression Free Survival gavo-cel Overall Survival
Median 5.9 months Median 11.2 months
Data Cutoff – June 30, 2021
Second Line MPM
(Post Platinum-Based Frontline Therapy)
Monotherapy n ORR (%) PFS (mo) OS (mo)
Vinorelbine 98 3.1 4.2 9.3
vs
Supportive Care1 56 1.8 2.8 9.1
Pembrolizumab 73 22 2.5 10.7
vs
Vinorelbine or Gemcitabine2 71 6 3.4 12.4
1. Fennell et al Phase 2 VIM Study. ASCO 2021
2. Popat et al Phase 3 PROMISE-meso Study. Ann Oncol 2020
17Malignant Pleural Mesothelioma Benchmark
~$600M Consensus* Global Peak Sales of Gavo-cel
1L MPM
FDA Approval: IPI - NIVO
Prevalence ORR PFS 2 yr. PFS 2 yr. OS
U.S. Population: 2,100 Monotherapy n (%) (mo) (%) OS (mo) (%)
Est. Gavo-cel Opportunity: 1,300 Ipilimumab + Nivolumab 303 40 6.8 24 18.1 41
Non-Epithelioid 74 - - - 18.1 38
EU Population: 3,000 Epithelioid 229 - - - 18.7 42
Est. Gavo-cel Opportunity: 1,900 Pemetrexed + Cisplatin
or 302 43 7.2 7 14.1 27
Carboplatin
Non-Epithelioid 75 - - - 8.8 8
Mesothelin Expression
Epithelioid 227 - - - 16.5 33
1. Baas et al Phase 3 CheckMate 743 Study. Lancet 2021
2L MPM
~70% of Epithelioid MPM Patients 90% of MPMs are
Epithelioid MPM Limited Options Post Platinum-Based Regimens
with Mesothelin Surface Expression
Monotherapy n ORR (%) PFS (mo) OS (mo)
2+ or 3+ in ≥50% Tumor Cells
Vinorelbine 98 3.1 4.2 9.3
vs
Supportive Care1 56 1.8 2.8 9.1
Pembrolizumab 73 22 2.5 10.7
vs
Vinorelbine or Gemcitabine2 71 6 3.4 12.4
1. Fennell et al Phase 2 VIM Study. ASCO 2021
2. Popat et al Phase 3 PROMISE-meso Study. Ann Oncol 2020
Refs: gavo-cel Phase 1/2 clinical trial, Inaguma 2017,
18 Footnote
SEER Statistics 2020, Morello 2016, Tozbikian 2014 *Consensus based on average analyst estimates covering the companyOvarian Cancer Benchmark
~$1.5B Consensus* Global Peak Sales of Gavo-cel
Prevalence Platinum Refractory / Resistant Ovarian Cancer
U.S. Population: 13,000
Est. Gavo-cel Opportunity: 4,900 Monotherapy n ORR (%) PFS (mo) OS (mo)
EU Population: 9,100 Olaparib (BRCA mutated)1 193 31 7 16.6
Est. Gavo-cel Opportunity: 3,400
Chemotherapy2 181 13 3.4 13.3
Mesothelin Expression
1. Kaufman Journal of Clinical Oncology 2015
2. Pujade-Lauraine Journal of Clinical Oncology 2014
~60% of Serous OC Patients with 70% of 90% of OCs are
Epithelial OCs Epithelial OC
Mesothelin Surface Expression
are Serous OC
2+ or 3+ in ≥50% Tumor Cells
19 Refs: gavo-cel Phase 1/2 clinical trial, Inaguma 2017,
SEER Statistics 2020, Morello 2016, Tozbikian 2014 *Consensus based on average analyst estimates covering the companygavo-cel Clinical Development Plan
Phase 1 Phase 2
Registrational Studies
Dose Escalation Expansion Cohorts
o Cohorts of 10-20 patients for
o At least 4 patients per cell dose
each indication
o Ovarian, MPM, NSCLC and o Single arm
o 50% MSLN 2+/3+ expression
Enrollment cholangiocarcinoma
cutoff o MSLN cut-off as per Phase 2
o 50% MSLN 2+/3+ expression studies
o Potential exploration of other
cutoff
MSLN expression cut-offs
o Monotherapy and αPD-1 combo o RP2D + LD in all patients
o Monotherapy
Dosing o RP2D + LD in all patients o αPD-1 combo if supported by
o Escalating cell dose +/- LD
o Potential for redosing Phase 2 studies
o Efficacy: ORR, PFS, OS o Generate data for regulatory
o Evaluate safety of gavo-cel approval via Fast Track or
Goals o Safety and efficacy of αPD-1 Breakthrough Designation
o Determine RP2D
combinations pathways
Expected Current 2021 2022+
Timing
20
LD, Lymphodepletion; RP2D, Recommended Phase 2 dose; MPM, Malignant Pleural/Peritoneal Mesothelioma; NSCLC, Non-Small Cell Lung CancerTC-510: PD1xCD28 Switch
Stage of Development: IND-Enabling
21Enhancing gavo-cel with a PD1xCD28 Switch Receptor
▪ PD1xCD28 switch designed to convert PD-
L1/L2 inhibitory function into a potent
costimulatory signal
▪ Costimulation occurs only in a PD-L1/2 rich
tumor microenvironment upon TRuC and PD-1
ligation resulting in a more targeted signal
enhancement
▪ Mesothelin-targeting TRuCs that co-express a
PD1xCD28 switch in vivo featured:
o Enhanced early TCR downstream signaling
o Significantly increased proliferation
o Prevented exhaustion upon repeated antigen
stimulation
o Enhances efficacy of gavo-cel against PD-L1
overexpressing tumors
Inhibition
Activation Activation
22Elucidating TC-510’s Mechanism of Action
Costimulatory Signaling vs. PD-1 Dominant Negative Receptor (DNR)
TC-510
gavo-cel gavo-cel + PD1xCD28Mut gavo-cel + PD1 DNR
gavo-cel + PD1xCD28
X
PD1xCD28 PD1xCD28
No Activation No Activation
Activation
TRuC Signaling Yes Yes Yes Yes
Co-Receptor No Active Signaling and Decoy Function Decoy Function
Decoy Function
23Against Tumors with High PD-L1 Expression, TC-510 Shows
Superior Efficacy to gavo-cel In Vivo
NT TC-210
MSTO-M/PDL1 MODEL
Tumor Volume (mm3)
Tumor Volume (mm3)
2000 Non-transduced 2000 gavo-cel
1500 1500
Tumor Volume (mm3)
2000 Vehicle
Vehicle 1000 1000
NT
NT
500 500
1500 TC-210
gavo-cel
1.5 x106 0 0
T cell dose PD1TM
TC-510 Switch 0 5 10 15 20 25 0 5 10 15 20 25
1000
Mutant+ PD1xCD28Mut
gavo-cel Study Day Study Day
PD1TM Switch
500 TC-510
Tumor Volume (mm3)
2000
0 1500
0 5 10 15 20 25 1000
500
0
0 5 10 15 20 25
Study Day
24
AACR 2020, A Chimeric PD1-CD28 Switch Receptor Enhances the Activity of TRuC-T CellsTC-520: IL-15 Enhancement
Stage of Development: IND-Enabling
25CD70 Population is Large and Spans a Diverse Set of Tumors
Up to 141,000 CD70+ patients in the US alone
Examples of Tissue Staining
CD70+ Tumors (% Positive) CD70+ U.S. Patients
RCC Melanoma
AML 95% 20,000
Renal Cell Carcinoma 80% 15,000
Thymic Carcinoma 80% 2,000 Breast cancer Tonsils
(and other EBV+ cancers)
Nasopharyngeal
Carcinoma
80% 400
DLBCL 50% 9,000
Mesothelioma 50% 1,100 MCL CTCL DLBCL
CLL 50% 10,000
NSCLC 40% 80,000 Flieswasser et al., Cancers 2019
GBM 35% 3,500
(Higher in certain subtypes)
0% 20% 40% 60% 80% 100%
26 Sources: SEER, Flieswasser et al., Cancers 2019, Agathanggelou et al., Am J Pathol. 1995, Riether J Exp Med 2017CD70: Highly Attractive Target with an Innate Fratricide Challenge
Tumor Cell
▪ Versatile tumor target: expressed in hematological
malignancies (AML, lymphoma) and solid tumors
(RCC, NSCLC, OC)
o Expression in normal cells limited to a subset of activated T cells,
B cells, and dendritic cells
o Expression in activated T cells renders CD70-directed T cell
therapies susceptible to fratricide
▪ Clinically validated: POC demonstrated in AML with
αCD70 mAb in AML (argenx)
▪ Path to first-in-class autologous CD70 cell therapy
o Most advanced CAR-T programs by Allogene and CRISPR are
allogeneic targeting RCC
27
AML, acute myeloid leukemia; RCC, renal cell carcinoma; NSCLC, non-small cell lung cancer; OC, ovarian cancerTC-520 Exhibits Potent and Persistent In Vivo Efficacy
Orinigal
Orinigaltumor (rightflank)
tumor (right flank)
2500
2500
Tumor volume (mm3)
Vehicle
Tumor volume (mm3)
Vehicle
2000 NT
2000 NT
1500 Fratricide prone
1500 #1 Fratricide prone
TC-520
1000
#1
1000500 T cell 786-O
injection (RCC)
500 0
-10 0 10 20 30 40 50 60 70
0 Study Day
-10 0 10 20 30 40 50 60 70 CD70
Study Day
28
RCC, renal cell carcinomaIL-15 Enhancement Improves TC-520 Phenotype and Function
NT TC-520 mbIL-15fu
TRuC+CD4+ TRuC+CD4+
TRuC+CD8+
120 120
120 Naive
Percentage (%)
Percentage (%)
Percentage (%)
TRuC+CD4+ 100 Naive
100
100 TCM
Naive
Naïve/ TCM TEM
TEMRA 80 8080 TCM
Tscm TEM TEMRA
60 60 TEM
60TEMRA
TEMRA
TEM TCM 40 4040
TRuC+CD8+
20
2020
CD45RA
One-hit 786-O E:T=5:1 0 0
CD45+ Cell count 0
T fu
uC
T
fu
uC
N
15
N
TR
T
fu
uC
15
L-
TR
N
5
15
bI
L-
70
TR
TRuC+
70
bI
L-
D m
m
70
bI
D
C
Fold Expansion
4
C
m
D
C
CCR7 3
In Vivo Efficacy at Suboptimal Dose in CD70 low H1975 NSCLC model
Unstimulated 2 80
786-O repeated stimulation NT
Tumor Volume (mm3)
T Cell count
Autonomous Persistence Repeated
1 Stimulation 1200
Fold Expansion
CD45+ Cell count
80 60 CD70 TRuC
TC-520
1.0 NT 15 0 1000
mbIL-15fu
Fold Expansion
CD70 TRuC
TC-520 0 5 10 15 20
Fold Expansion
60
0.8 Days 800 40
Fold Expansion
mbIL-15fu
10 786-O added
0.640 600 106 T cells
20
0.420 400
5
0.2 0 0
200
0 2 4 6 8 10 0 2 4 6 8 10
0.0 0
Days Days
0 4 8 12 16 0 5 10 15 0 CD70
Days Days 0 10 20 30
Days Post-Infusion
29Allogeneic TRuCs
Stage of Development: Lead Optimization
30Allo TRuC-T Cells are Generated in a Two-Step Process
Natural TCR TRuC TCR
(Alloreactive) (Not alloreactive)
Natural TCRαv and βv
domains sdAb binder
γ δ
1 Knocking-out TRAC locus to delete TCR
TRAV TRAJ TRAC
X
CRISPR/Cas
2 Introduction of mouse TCRα/β or human TCRγ/δ
constant regions to enable TCR assembly
31Optimization and Selection of Allo TRuC Designs
AUTOLOGOUS ALLOGENEIC
αβ αβ αβ αβ γ δ
Short linker Long linker
Murine TCR α/β constant domains
Human TCR α/β Human TCR γ/δ
constant domains constant domains
▪ The re-expression of murine TCR α/β or γ/δ constant domains avoids mis-pairing with the endogenous
human TCRβ subunit thereby enhancing the restoration of the TCR
32Equivalent Anti-Tumor Activity of gavo-cel with Allogeneic TRuC-T Cells
NT Autologous gavo-cel
Tumor Volume (mm3)
Tumor Volume (mm3)
2500 2500
2000 2000
1500 1500
1000 1000
500 500
0 0
0 10 20 30 40 50 0 10 20 30 40 50
Study Day Study Day
mTCRα/β; hCD3ε tether mTCRα/β tether (SL) mTCRα/β tether (LL) hTCRγ/δ tether
2500 2500 2500 2500
Tumor Volume (mm3)
Tumor Volume (mm3)
Tumor Volume (mm3)
Tumor Volume (mm3)
2000 2000 2000 2000
1500 1500 1500 1500
1000 1000 1000 1000
500 500 500 500
0 0 0 0
0 10 20 30 40 50 0 10 20 30 40 50 0 10 20 30 40 50 0 10 20 30 40 50
Study Day Study Day Study Day Study Day
33Building Commercial Scale Capacity
Quality, Consistency, Capital Efficiency
CDMOs ▪ World renowned expertise, state-of-the-art facilities
▪ Capacity to produce for initial planned clinical trials
▪ Full control of process and timelines; establishes
CGT independence
Catapult UK
▪ cGMP gavo-cel clinical production anticipated to come
online in 2022
▪ Leverages state-of-the-art facility, technical expertise in
ElevateBio cell therapy TCR2 Commercial-Scale Manufacturing Facility; Rockville, MD
BaseCamp ▪ cGMP gavo-cel clinical production anticipated to come
online in 2022
TCR2 US ▪ ~85,000 sq. ft built-to-suit, state-of-the-art facility for
Commercial- commercial and clinical manufacturing in Rockville, MD
Scale Facility ▪ Accelerates commercial-scale timelines with cGMP
production anticipated in 2023
ElevateBio BaseCamp; Waltham, MA Cell & Gene Therapy (CGT) Catapult UK; Stevenage, UK
34Engaging the TCR to Transform the Treatment of Solid Tumors Thank You 35
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