0001485003
false
0001485003
2023-09-01
2023-09-01
iso4217:USD
xbrli:shares
iso4217:USD
xbrli:shares
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported):
September 1, 2023
Carisma Therapeutics Inc.
(Exact Name of Registrant as Specified in its
Charter)
Delaware |
|
001-36296 |
|
26-2025616 |
(State or other jurisdiction of incorporation) |
|
(Commission File Number) |
|
(IRS Employer Identification No.) |
|
|
|
|
|
3675 Market Street, Suite 200 Philadelphia, PA |
|
|
|
19104 |
(Address of Principal Executive Offices) |
|
|
|
( Zip Code) |
Registrant’s telephone number, including
area code: (267) 491-6422
(Former Name or Former Address, if Changed
Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended
to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction
A.2 below):
¨ |
|
Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
¨ |
|
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
¨ |
|
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
¨ |
|
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
|
|
|
|
|
Title of each class |
|
Trading Symbol(s) |
|
Name of exchange on which registered |
Common Stock, $0.001 par value |
|
CARM |
|
The Nasdaq Stock Market LLC |
Indicate by check mark whether the registrant is an emerging growth
company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities
Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ¨
If an emerging growth company, indicate
by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial
accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨
Item 8.01. Other Events.
On September 1, 2023, Carisma Therapeutics Inc. (the “Company”)
issued a press release announcing preliminary findings from the first five patients enrolled in group 2 of the Company’s Phase 1
clinical trial of its lead product candidate, CT-0508, a human epidermal growth factor receptor 2 (“HER2”) targeted chimeric
antigen receptor macrophage for the treatment of HER2 overexpressing cancers. The Company will provide an overview of the group 2 data
during a presentation at the 8th Annual CAR-TCR Summit on September 1, 2023. A copy of the press release and an excerpt from
the presentation are attached hereto as Exhibits 99.1 and 99.2 and are incorporated herein by reference.
The Company is providing the following supportive data for the Phase
1 clinical trial:
The Company initiated a second group to evaluate the safety of bolus
dosing of patients, and five patients have been successfully dosed to date with a single-day bolus infusion. Consistent with results from
group 1 of the trial, based on preliminary results assessed to date from these five patients enrolled in group 2, CT-0508 has been generally
well-tolerated after infusion with no dose-limiting toxicities, was successfully manufactured using macrophages obtained from heavily
pre-treated, advanced solid tumor patients, and has shown high CAR expression, viability, and purity. While the results from this early
clinical trial data are both preliminary and limited, the Company believes the combined group 1 and group 2 results support the previously
presented preliminary results from this trial indicating that CT-0508 can potentially lead to remodeling and activation of the tumor microenvironment
(“TME”) and induce anti-tumor adaptive immunity. In group 1, a best overall response (“BOR”) of stable disease
was seen in 4 out of 9 patients, and in group 2, the best overall response was progressive disease. Translational analyses combining group
1 and group 2 demonstrated a correlation between TME activation, T cell activation, and HER2 status with BOR of stable disease.
The single-agent arm of the study remains open and up to four additional
patients may be enrolled. However, given the clinical findings observing T cell exhaustion as a potential limiting factor, and pre-clinical
data demonstrating robust synergy upon combining CT-0508 with T cell checkpoint inhibition, the Company expects to focus its ongoing efforts
primarily on enrolling patients in its sub-study administering CT-0508 in combination with pembrolizumab.
Item 9.01. Financial Statements and Exhibits.
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934,
the Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
|
CARISMA THERAPEUTICS INC. |
|
|
|
|
By: |
/s/ Steven Kelly |
Date: September 1, 2023 |
|
Steven Kelly |
|
|
President and Chief Executive Officer |
Exhibit 99.1
Carisma Announces Latest
Data from Phase 1 Clinical Trial of CT-0508 at 8th Annual CAR-TCR Summit
Group 2 data available
to date support primary safety and feasibility endpoints of single-day bolus dosing of CT-0508
New translational analyses
combining group 1 & group 2 continue to support CAR-M mechanism of action, demonstrating a correlation between biomarkers and best
overall response
PHILADELPHIA, PA – September 1, 2023
– Carisma Therapeutics Inc. (Nasdaq: CARM) (“Carisma” or the “Company”), a clinical stage biopharmaceutical
company focused on discovering and developing innovative immunotherapies, will present findings today at the 8th Annual CAR-TCR
Summit from its Phase 1 clinical trial of the Company’s lead product candidate, CT-0508, a human epidermal growth factor
receptor 2 (“HER2”) targeted chimeric antigen receptor macrophage (“CAR-M”) for the treatment of advanced/metastatic
HER2 overexpressing cancers.
The presentation includes data from
group 1 (n=9) and group 2 (n=5). Patients in both groups received the same total dose (up to 5x109 CT-0508) either via a
fractionated, multi-day infusion regimen (group 1) or via a single-day bolus infusion (group 2). The
data are drawn from the ongoing clinical trial led by Kim A. Reiss, MD, principal investigator of the Phase 1 clinical trial
and an associate professor of Hematology-Oncology in the Perelman School of Medicine at the University of Pennsylvania.
In the presentation, Michael Klichinsky, PharmD,
PhD, Co-Founder and Chief Scientific Officer at Carisma, will present data demonstrating that, in both groups, CT-0508 was successfully
manufactured for patients and that the administration of CT-0508 was well-tolerated after infusion with no dose-limiting toxicities reported
to date.
“As the CT-0508 trial progresses, it
is promising to see consistent results supporting the safety profile, feasibility, and mechanism of action of this first-in-class CAR-M
investigational therapy,” commented Dr. Klichinsky. “We look forward to results from the CT-0508 combination sub-study with
pembrolizumab and continued development of CAR-M and CAR-Monocyte therapies.”
Previously, Carisma presented findings from
group 1 showing that CT-0508 remodeled and activated the tumor microenvironment (“TME”) and initiated anti-tumor T cell immunity.
Translational analyses combining group 1 and group 2 show that various biomarkers including metrics of TME activation, T cell activation,
and HER2 status correlate with best overall response (“BOR”) of stable disease, providing further evidence of the CT-0508
mechanism of action.
The Phase 1 study translational analyses further
demonstrate an increase in exhausted CD8 T cells on treatment, supporting the ongoing combination sub-study with Merck’s anti-PD1
therapy KEYTRUDA® (pembrolizumab). This latest data readout follows the dosing of the first patient in the ongoing sub-study
of the Phase 1 clinical trial of CT-0508 in combination with pembrolizumab for the treatment of HER2 overexpressing cancers.
The Company is filing a Current Report on
Form 8-K today with the U.S. Securities and Exchange Commission disclosing the new data from its Phase 1 clinical trial of CT-0508, including
an excerpt of the presentation being made at the 8th Annual CAR-TCR Summit.
Editor’s Note: Carisma has licensed certain Penn-owned
intellectual property from the University of Pennsylvania, and Penn’s Perelman School of Medicine receives sponsored research and
clinical trial funding from the company. Penn may be entitled to receive additional financial benefits from technologies licensed and
optioned to Carisma. In addition, Penn is a co-founder of the company and holds equity in Carisma.
About CT-0508
CT-0508 is a human epidermal growth factor receptor 2 (HER2) targeted
chimeric antigen receptor macrophage (CAR-M). It is being evaluated in a landmark Phase 1 multi-center clinical trial that focuses on
patients with recurrent or metastatic HER2-overexpressing solid tumors whose cancers do not have approved HER2-targeted therapies or
who do not respond to treatment. Carisma is selecting participants who have tumors of any anatomical origin, but with the commonality
of overexpressing the HER2 receptor on the cell surface, which is the target for our CAR-M. The Phase 1 clinical trial marks the first
time that engineered macrophages are being studied in humans. The trial continues to enroll patients at seven clinical sites in
the U.S., including (i) Penn Medicine’s Abramson Cancer Center, (ii) the University of North Carolina Lineberger Comprehensive
Cancer Center, (iii) the City of Hope National Medical Center, (iv) the MD Anderson Cancer Center, (v) the Sarah Cannon Cancer Research
Institute, (vi) Oregon Health & Science University and (vii) Fred Hutchinson Cancer Center.
About Carisma
Carisma Therapeutics Inc. is a clinical stage biopharmaceutical company
focused on utilizing our proprietary macrophage and monocyte cell engineering platform to develop transformative immunotherapies to treat
cancer and other serious diseases. We have created a comprehensive, differentiated proprietary cell therapy platform focused on engineered
macrophages and monocytes, cells that play a crucial role in both the innate and adaptive immune response. Carisma is headquartered in
Philadelphia, PA. For more information, please visit www.carismatx.com.
Cautionary Note on Forward-Looking Statements
Statements in this press release about future expectations, plans and
prospects, as well as any other statements regarding matters that are not historical facts, may constitute "forward-looking statements"
within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements
relating to Carisma’s business, strategy, future operations, cash runway, the advancement of Carisma’s product candidates
and product pipeline, and clinical development of Carisma’s product candidates, including expectations regarding timing of initiation
and results of clinical trials and ability to replicate in later clinical trials positive results found in preclinical studies and early-stage
clinical trials of its product candidates. The words "anticipate," "believe," "contemplate," "continue,"
"could," "estimate," "expect," "goals," "intend," "may," "might,"
"outlook," "plan," "project," "potential," "predict," "target," "possible,"
"will," "would," "could," "should," and similar expressions are intended to identify forward-looking
statements, although not all forward-looking statements contain these identifying words.
Any forward-looking statements are based on management's current expectations
of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely
from those set forth in, or implied by, such forward-looking statements. For a discussion of these risks and uncertainties, and other
important factors, any of which could cause Carisma's actual results to differ from those contained in the forward-looking statements,
see the "Risk Factors" set forth in the Company's Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission
on August 10, 2023, as well as discussions of potential risks, uncertainties, and other important factors in Carisma's other recent filings
with the Securities and Exchange Commission. Any forward-looking statements that are made in this press release speak as of the date of
this press release. Carisma undertakes no obligation to revise the forward-looking statements or to update them to reflect events or circumstances
occurring after the date of this press release, whether as a result of new information, future developments or otherwise, except as required
by the federal securities laws.
Media Contact:
Julia Stern
(763) 350-5223
jstern@realchemistry.com
Investor Contact:
investors@carismatx.com
###
Exhibit 99.2 | HARNESSING THE POWER OF
ENGINEERED MACROPHAGES
Michael Klichinsky, PharmD PhD
Co-Founder & Chief Scientific Officer
CAR-TCR
September 2023 |
| 2
Cautionary Note Regarding Forward-Looking Statements
Regarding Carisma
Statements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may
constitute "forward-looking statements" within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to,
statements relating to Carisma’s business, strategy, future operations, cash runway, the advancement of Carisma’s product candidates and product pipeline, and
clinical development of Carisma’s product candidates, including expectations regarding timing of initiation and results of clinical trials. The words ““anticipate,”
“believe,” “contemplate,” “continue,” “could,” “estimate,” “expect,” “goals,” “intend,” “may,” “might,” “outlook,” “plan,” “project,” “potential,” “predict,” “target,” “possible,”
“will,” “would,” “could,” “should,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain
these identifying words.
Any forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could
cause actual results to differ materially and adversely from those set forth in, or implied by, such forward-looking statements. These risks and uncertainties include,
but are not limited to, (i) Carisma’s ability to obtain, maintain and protect its intellectual property rights related to its product candidates; (ii) Carisma’s ability to
advance the development of its product candidates under the timelines it anticipates in planned and future clinical trials; (iii) Carisma’s ability to replicate in later
clinical trials positive results found in preclinical studies and early-stage clinical trials of its product candidates; (iv) Carisma’s ability to realize the anticipated benefits
of its research and development programs, strategic partnerships, research and licensing programs and academic and other collaborations; (v) regulatory
requirements or developments and Carisma’s ability to obtain and maintain necessary approvals from the U.S. Food and Drug Administration and other regulatory
authorities; (vi) changes to clinical trial designs and regulatory pathways; (vii) risks associated with Carisma’s ability to manage expenses; (viii) changes in capital
resource requirements; (ix) risks related to the inability of Carisma to obtain sufficient additional capital to continue to advance its product candidates and its
preclinical programs; and (x) legislative, regulatory, political and economic developments. For a discussion of other risks and uncertainties, and other important
factors, any of which could cause the Carisma’s actual results to differ from those contained in the forward-looking statements, see the "Risk Factors" set forth in
Exhibit 99.3 to Carisma’s Current Report on Form 8-K filed with the Securities and Exchange Commission on August 10, 2023, Carisma’s Annual Report on Form
10-K for the year ended December 31, 2022 filed with the Securities and Exchange Commission on February 28, 2023, Carisma’s Quarterly Report on Form 10-Q
for the quarter ended June 30, 2023 filed with the Securities and Exchange Commission on August 10, 2023, as well as discussions of potential risks, uncertainties,
and other important factors in Carisma’s most recent filings with the Securities and Exchange Commission. Any forward-looking statements that are made in this
presentation speak as of the date of this presentation. Carisma undertakes no obligation to revise the forward-looking statements or to update them to reflect events
or circumstances occurring after the date of this presentation, whether as a result of new information, future developments or otherwise, except as required by the
federal securities laws.
9/1/2023 |
| Lead Program
CT-0508
Anti-HER2 CAR-M Phase I Trial |
| 10
CT-0508: HER2 Targeted CAR-Macrophage
First-in-class & first-in-human engineered macrophage
Cells: Autologous monocyte derived macrophages
Vector: Ad5f35
Phenotype: M1
Target: HER2
CAR: 1st Generation
Single Agent Days 1 / 3 / 5 Dosing (n=9)
Single Agent Day 1 Bolus Dosing (n=up to 9)
CT-0508 + Pembro Combination (n=9)
Study Summary
• Pts pre-mobilized with G-CSF
• Dose: 1 to 5 x 109 cells
• No pre-conditioning
• Endpoints
• Feasibility
• Safety
• PK and MOA
Program Overview
• HER2 2+/3+ metastatic solid tumor basket trial
• Phase I multi-center, open-label study open at 7 US sites
• Cohorts:
• Group 1 (Fractionated dosing): Complete – data
presented at ‘22 SITC
• Group 2 (Bolus dosing): Enrolling – Early data included
today
• CT-0508 + pembrolizumab: Enrolling
Cohorts
9/1/2023 |
| 11
• Source: autologous mobilized
peripheral blood monocytes
• Mfg time: ~1 week
• Vein to vein: ~3 weeks
• Vector: Ad5f35
• Process: Automated
• Format: Cryopreserved
• Successful manufacturing:
-
CAR-M Manufacturing
Process
Manufacturing Partners:
Viability mean % 86%
Purity mean % 89%
CAR+ mean % 79%
Total cells based on label
(cells) 2.06E+09
9/1/2023 |
| 12
Successful CT-0508 Manufacturing:
Functional M1 Polarized CAR-M Generated
High viability, purity, and CAR expression
Patient Derived CT-0508
Healthy Donor Derived CT-0508
P
atie
nt
H
e
alth
y
D
o
n
or
0
20
40
60
80
100
%
Via
ble
P
atie
nt
H
e
alth
y
D
o
n
or
0
20
40
60
80
100
%
Pro
d
u
ct P
urity
P
atie
nt
H
e
alth
y
D
o
n
or
0
20
40
60
80
100
%
C
A
R
E
x
pre
s
sio
n
All patient CT-0508 batches show M1 polarization
Monocytes CT-0508
M1 signature score
9/1/2023 |
| 13
Patient CT-0508 CAR-dependent cytokine secretion
Patient CT-0508 are functional in vitro:
Each batch demonstrated target killing, phagocytosis, M1 polarization, and cytokine release
M
SLN
HER2
0
500
1000
1500
TNFα
p
g/ml
✱✱✱✱
M
SLN
HER2
0
500
1000
1500
2000
IL-6
p
g/ml
✱✱✱✱
M
SLN
HER2
0
50
100
150
IL-1β
p
g/ml
✱✱
M
SLN
HER2
0
100
200
300
400
500
IL-18
p
g/ml
✱✱✱✱
M
SLN
HER2
0
10000
20000
30000
40000
50000
MIP-1α (CCL3)
p
g/ml
✱✱✱✱
M
SLN
HER2
0
10000
20000
30000
40000
MIP-1β (CCL4)
p
g/ml
✱✱✱✱
M
SLN
HER2
0
10
20
30
40
GM-CSF
p
g/ml
✱✱✱
All CT-0508 batches kill HER2+ tumor cells
0 24 48 72
0.00
0.25
0.50
0.75
1.00
1.25
SKOV3 (ovarian cancer)
N
orm
aliz
e
d to
T
u
m
or B
urd
e
n
0 24 48 72
0.00
0.25
0.50
0.75
1.00
1.25
Time (hr)
N
orm
aliz
e
d to
T
u
m
or B
urd
e
n
0 24 48 72
0.00
0.25
0.50
0.75
1.00
1.25
AU565 (breast cancer)
N
orm
aliz
e
d to
T
u
m
or B
urd
e
n
0 24 48 72
0.00
0.25
0.50
0.75
1.00
1.25
Time (hr)
N
orm
aliz
e
d to
T
u
m
or B
urd
e
n
9/1/2023 |
| 14
CT-0508 Study 101 patient demographics (n=14)
Summary of Participant and Tumor Characteristics
Characteristic N = 14 Characteristic N = 14
Median age (range), years 58 (45, 81) Tumor Type, n (%)
Breast Cancer
Esophageal Cancer
Salivary Carcinoma
Cholangiocarcinoma
Ovarian Cancer
8 (57.1)
2 (14.3)
2 (14.3)
1 (7.1)
1 (7.1)
Gender, n (%)
Male
Female
4 (28.6)
10 (71.4)
Race, n (%)
White 14 (100)
Median Number of Prior Cancer Therapies,
n (range) 5 (2, 12)
ECOG PS, n (%)
0
1
9 (64.3)
4 (28.6)
Median Number of Prior Anti-HER2
Therapies, n (range)
Subjects with Prior Anti-HER2 Therapy
2 (0, 9)
13 (92.9)
HER2 Overexpression, n (%)
IHC 3+
IHC 2+/FISH+
9 (64.3)
5 (35.7)
Prior Radiotherapy, n (%)
Yes 9 (64.3)
Microsatellite Instability (MSI)*
MSS/MSI-Low
MSI-High
Unknown
13 (92.9)
0 (0)
1 (7.1)
Tumor Mutational Burden (TMB)*
Low (<10 mut/Mb)
High (≥10 mut/Mb)
Unknown
11 (78.6)
2 (14.3)†
1 (7.1)
* MSI-high and TMB high are known biomarkers associated with improved response to immune checkpoint
† 1 patient had received 11 lines of prior therapy and 1 patient has demonstrated HLA-A and HLA-C loss of Heterozygosity 9/1/2023 |
| 15
CT-0508 is Well Tolerated with No Dose Limiting Toxicities
Similar safety profile between Group 1 and Group 2
9/1/2023
Majority of Adverse Events were Grade 1-2
Group 1 & Group 2 Combined
• No dose limiting toxicities.
• No severe CRS or ICANS.
• All SAEs related to treatment were due to hospitalization for
monitoring of either Grade 2 CRS or Grade 2 infusion
reaction.
Group 1 Group 2 Combined
Patients Treated N=9 (%) N=5 (%) N=14 (%)
Infusion Reaction 2 (22.2%) 1 (20.0%) 3 (21.4%)
Grade 1 1 (11.1%) 0 (0.0%) 1 (7.1%)
Grade 2 1 (11.1%) 1 (20.0%) 2 (14.2%)
CRS (cytokine release
syndrome) 6 (66.7%) 3 (60.0%) 9 (64.2%)
Grade 1 4 (44.4%) 1 (20.0%) 5 (35.7%)
Grade 2 2 (22.2%) 2 (40.0%) 4 (28.6%)
Grade 3-4 (Severe) 0 (0.0%) 0 (0.0%) 0 (0.0%)
ICANS 0 (0.0%) 0 (0.0%) 0 (0.0%)
SAEs Related To Treatment 2 (22.2%) 3 (60.0%) 5 (35.7%)
# of events
Similar safety profile between Group 1 and Group 2 |
| 16
Transient Elevations of Pro-Inflammatory Cytokines
Day 1 Day 3 Day 5 Day 7
Concentration (pg/mL)
Day 1 Day 3 Day 5 Day 7 Day 1 Day 3 Day 5 Day 7
9/1/2023 |
| 17
CT-0508 rapidly extravasates from peripheral blood and were
detected in the tumor of 8/9 patients
CT-0508 detection in the TME:
CT-0508 was detected in the
TME of 8/9 pts.
CT-0508 peripheral blood pharmacokinetics:
Rapid egress out of peripheral blood following each dose.
ND
Infusion
Infusion
Infusion
Infusion
ND
CT-0508 Transgene
(copy number/µg of DNA)
9/1/2023 |
| 18
Best Overall Response of Stable Disease
Change in Target Lesion From Baseline (%)
Evaluated Participants N = 14*
Best Overall Response (RECIST 1.1) Stable Disease: 4 (28.6%) Change in Target Lesion From Baseline (%)
Best Overall Response
Change in Tumor Burden Over Time Best Overall Change in Tumor Burden
9/1/2023 |
| 19
HER2 expression (3+) correlated with Best Overall Response*
Correlation between HER2 status and Best Overall Response
* Per RECIST 1.1
Trend toward decrease in
HER2+ tumor cells in pts
with SD
Evaluated Participants N = 14*
HER2 2+ SD: 0/5 (0.00%)
HER2 3+ SD: 4/9 (44.4%)
Screening Day 8 Week 4
HER2 mRNA Expression (Log2)
Best Overall Response
n=5 PD n=4 SD n=5 PD
HER2 2+ HER2 3+
SD: n=4
PD: n=5 PD: n=5
9/1/2023
RNA Seq |
| TME remodeling correlated with Best Overall Response*
Immune Cell Recruitment Related Genes
Tumor Inflamed Signature Related Genes**
Antigen Presentation Machinery Related Genes
Best Overall Response
* Per RECIST 1.1 **
18 gene Tumor Inflammation Signature developed by Nanostring
T cell activation Related Genes
9/1/2023 20 |
| 21
TME remodeling correlated with Best Overall Response*
Best Overall Response
* Per RECIST 1.1
**Calculated using gene set variation analysis (GSVA) using the gene sets presented on the previous slide
9/1/2023
T cell
activation
Immune cell
Recruitment
Tumor inflamed
signature
Antigen presentation
machinery
0
1
-1
Score change (screening to week 4)** |
| 22
T cell expansion in the blood & TME correlated with Best
Overall Response*
Expansion of T cell clones in blood correlates w/ BOR
* Per RECIST 1.1
# of clones
Best overall response
# of clones
Expanding
clones
Emergent
clones
Accumulation of peripherally expanded clones in the TME Sum frequency Sum frequency
Expanding
clones
Emergent
clones
Blood TME
9/1/2023 |
| 23
CT-0508 increased T cell clonality in TME and activated
dominant clones suggesting epitope spreading
Expanding clonotype:
T Lymphocytes
Repertoire clonality
Blood
Repertoire clonality
TME
CT-0508 increased T cell clonality
Best Overall Response |
| Naïve-like
Central Memory
TEMRA
Effector Memory
Exhausted
Proliferating
24
CT-0508 increased the frequency of central memory, effector
memory, and exhausted CD8 T cells in the TME
0
Naïve-like Central Memory Effector Memory TEMRA Exhausted Proliferating
Screening
Week 4
Screening
Week 4
Screening
Week 4
Screening
Week 4
Screening
Week 4
Screening
Week 4
9/1/2023
0 |
| 25
Early trends suggest improved baseline T cell fitness*
correlates with Best Overall Response
SD PD
0
2
4
6
CD4/CD8 in Aph
C
D
4
/
C
D
8
r
a
tio
o
f
A
p
h
e
r
e
sis
(
F
r
o
m
CIT
E
-
S
e
q
)
SD PD
0
20
40
60
CD8+CD27+CD45RO- of CD8 in Aph
%
C
D
2
7
+
C
D
4
5
R
O
-
o
f
C
D
8
T
c
ells
(F
r
o
m
CIT
E
-
S
e
q)
CD4/ CD8 ratio Frequency of CD8 Tscm
Higher CD4/CD8 ratio and % of CD8 Tscm associated with improved T cell fitness
* Based on peripheral blood T cell CD4/CD8 ratio and frequency of CD8+ T stem central memory in apheresis material 9/1/2023 |
| FEASIBILITY
• CT-0508 was successfully
manufactured from
autologous mobilized
monocytes
• Patient product demonstrated
high CAR expression, purity,
viability, M1 polarization and
confirmed functionality
• No lymphodepletion
26
CT-0508 Study 101 Interim Data Supports CAR-M Hypothesis
and Combination with Pembrolizumab
MECHANISM OF
ACTION
• CT-0508 tumor infiltration
detected
• TME remodeling correlates with
clinical outcome
• T cell expansion and fitness
correlates with clinical outcome
• Exhausted T cells increase on
treatment
PRELIMINARY
CLINICAL PROFILE
• No dose limiting toxicities
• No severe CRS, no ICANS,
and no major organ system
toxicity observed
• Best overall response of SD
• SD in HER2 3+ population
44.4% (n=4/9); SD in HER2
2+ population 0% (n=0/5)
• Group 2 enrolling
9/1/2023 |
v3.23.2
X |
- DefinitionBoolean flag that is true when the XBRL content amends previously-filed or accepted submission.
+ References
+ Details
Name: |
dei_AmendmentFlag |
Namespace Prefix: |
dei_ |
Data Type: |
xbrli:booleanItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionFor the EDGAR submission types of Form 8-K: the date of the report, the date of the earliest event reported; for the EDGAR submission types of Form N-1A: the filing date; for all other submission types: the end of the reporting or transition period. The format of the date is YYYY-MM-DD.
+ References
+ Details
Name: |
dei_DocumentPeriodEndDate |
Namespace Prefix: |
dei_ |
Data Type: |
xbrli:dateItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionThe type of document being provided (such as 10-K, 10-Q, 485BPOS, etc). The document type is limited to the same value as the supporting SEC submission type, or the word 'Other'.
+ References
+ Details
Name: |
dei_DocumentType |
Namespace Prefix: |
dei_ |
Data Type: |
dei:submissionTypeItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionAddress Line 1 such as Attn, Building Name, Street Name
+ References
+ Details
Name: |
dei_EntityAddressAddressLine1 |
Namespace Prefix: |
dei_ |
Data Type: |
xbrli:normalizedStringItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionAddress Line 2 such as Street or Suite number
+ References
+ Details
Name: |
dei_EntityAddressAddressLine2 |
Namespace Prefix: |
dei_ |
Data Type: |
xbrli:normalizedStringItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- Definition
+ References
+ Details
Name: |
dei_EntityAddressCityOrTown |
Namespace Prefix: |
dei_ |
Data Type: |
xbrli:normalizedStringItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionCode for the postal or zip code
+ References
+ Details
Name: |
dei_EntityAddressPostalZipCode |
Namespace Prefix: |
dei_ |
Data Type: |
xbrli:normalizedStringItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionName of the state or province.
+ References
+ Details
Name: |
dei_EntityAddressStateOrProvince |
Namespace Prefix: |
dei_ |
Data Type: |
dei:stateOrProvinceItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionA unique 10-digit SEC-issued value to identify entities that have filed disclosures with the SEC. It is commonly abbreviated as CIK.
+ ReferencesReference 1: http://www.xbrl.org/2003/role/presentationRef -Publisher SEC -Name Exchange Act -Number 240 -Section 12 -Subsection b-2
+ Details
Name: |
dei_EntityCentralIndexKey |
Namespace Prefix: |
dei_ |
Data Type: |
dei:centralIndexKeyItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionIndicate if registrant meets the emerging growth company criteria.
+ ReferencesReference 1: http://www.xbrl.org/2003/role/presentationRef -Publisher SEC -Name Exchange Act -Number 240 -Section 12 -Subsection b-2
+ Details
Name: |
dei_EntityEmergingGrowthCompany |
Namespace Prefix: |
dei_ |
Data Type: |
xbrli:booleanItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionCommission file number. The field allows up to 17 characters. The prefix may contain 1-3 digits, the sequence number may contain 1-8 digits, the optional suffix may contain 1-4 characters, and the fields are separated with a hyphen.
+ References
+ Details
Name: |
dei_EntityFileNumber |
Namespace Prefix: |
dei_ |
Data Type: |
dei:fileNumberItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionTwo-character EDGAR code representing the state or country of incorporation.
+ References
+ Details
Name: |
dei_EntityIncorporationStateCountryCode |
Namespace Prefix: |
dei_ |
Data Type: |
dei:edgarStateCountryItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionThe exact name of the entity filing the report as specified in its charter, which is required by forms filed with the SEC.
+ ReferencesReference 1: http://www.xbrl.org/2003/role/presentationRef -Publisher SEC -Name Exchange Act -Number 240 -Section 12 -Subsection b-2
+ Details
Name: |
dei_EntityRegistrantName |
Namespace Prefix: |
dei_ |
Data Type: |
xbrli:normalizedStringItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionThe Tax Identification Number (TIN), also known as an Employer Identification Number (EIN), is a unique 9-digit value assigned by the IRS.
+ ReferencesReference 1: http://www.xbrl.org/2003/role/presentationRef -Publisher SEC -Name Exchange Act -Number 240 -Section 12 -Subsection b-2
+ Details
Name: |
dei_EntityTaxIdentificationNumber |
Namespace Prefix: |
dei_ |
Data Type: |
dei:employerIdItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionLocal phone number for entity.
+ References
+ Details
Name: |
dei_LocalPhoneNumber |
Namespace Prefix: |
dei_ |
Data Type: |
xbrli:normalizedStringItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionBoolean flag that is true when the Form 8-K filing is intended to satisfy the filing obligation of the registrant as pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act.
+ ReferencesReference 1: http://www.xbrl.org/2003/role/presentationRef -Publisher SEC -Name Exchange Act -Number 240 -Section 13e -Subsection 4c
+ Details
Name: |
dei_PreCommencementIssuerTenderOffer |
Namespace Prefix: |
dei_ |
Data Type: |
xbrli:booleanItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionBoolean flag that is true when the Form 8-K filing is intended to satisfy the filing obligation of the registrant as pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act.
+ ReferencesReference 1: http://www.xbrl.org/2003/role/presentationRef -Publisher SEC -Name Exchange Act -Number 240 -Section 14d -Subsection 2b
+ Details
Name: |
dei_PreCommencementTenderOffer |
Namespace Prefix: |
dei_ |
Data Type: |
xbrli:booleanItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionTitle of a 12(b) registered security.
+ ReferencesReference 1: http://www.xbrl.org/2003/role/presentationRef -Publisher SEC -Name Exchange Act -Number 240 -Section 12 -Subsection b
+ Details
Name: |
dei_Security12bTitle |
Namespace Prefix: |
dei_ |
Data Type: |
dei:securityTitleItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionName of the Exchange on which a security is registered.
+ ReferencesReference 1: http://www.xbrl.org/2003/role/presentationRef -Publisher SEC -Name Exchange Act -Number 240 -Section 12 -Subsection d1-1
+ Details
Name: |
dei_SecurityExchangeName |
Namespace Prefix: |
dei_ |
Data Type: |
dei:edgarExchangeCodeItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionBoolean flag that is true when the Form 8-K filing is intended to satisfy the filing obligation of the registrant as soliciting material pursuant to Rule 14a-12 under the Exchange Act.
+ ReferencesReference 1: http://www.xbrl.org/2003/role/presentationRef -Publisher SEC -Name Exchange Act -Section 14a -Number 240 -Subsection 12
+ Details
Name: |
dei_SolicitingMaterial |
Namespace Prefix: |
dei_ |
Data Type: |
xbrli:booleanItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionTrading symbol of an instrument as listed on an exchange.
+ References
+ Details
Name: |
dei_TradingSymbol |
Namespace Prefix: |
dei_ |
Data Type: |
dei:tradingSymbolItemType |
Balance Type: |
na |
Period Type: |
duration |
|
X |
- DefinitionBoolean flag that is true when the Form 8-K filing is intended to satisfy the filing obligation of the registrant as written communications pursuant to Rule 425 under the Securities Act.
+ ReferencesReference 1: http://www.xbrl.org/2003/role/presentationRef -Publisher SEC -Name Securities Act -Number 230 -Section 425
+ Details
Name: |
dei_WrittenCommunications |
Namespace Prefix: |
dei_ |
Data Type: |
xbrli:booleanItemType |
Balance Type: |
na |
Period Type: |
duration |
|
Carisma Therapeutics (NASDAQ:CARM)
過去 株価チャート
から 8 2024 まで 9 2024
Carisma Therapeutics (NASDAQ:CARM)
過去 株価チャート
から 9 2023 まで 9 2024