UNITED STATES
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FORM
CURRENT REPORT
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Item 8.01. Other Events.
On April 10, 2024, during presentations at the American Association for Cancer Research 2024 Annual Meeting and the Annual Needham Virtual Healthcare Conference, Carisma Therapeutics Inc. (the “Company”) will provide preliminary data from the Company’s Phase 1 clinical trial of its first product candidate, CT-0508, a human epidermal growth factor receptor 2 (“HER2”) targeted chimeric antigen receptor macrophage for the treatment of HER2 overexpressing cancers, as well as preliminary data from the first three patients treated in the Company’s sub-study utilizing CT-0508 in combination with pembrolizumab. An excerpt from the presentation is attached hereto as 99.1 and is incorporated herein by reference.
The Company is providing the following data:
Based on preliminary results assessed to date from the 14 patients enrolled in group 1 and group 2 of the Company’s monotherapy treatment clinical trial, 40.7% of all target lesions had reduced in size on at least one scan across all anatomic sites.
The Company has enrolled six patients in its sub-study utilizing CT-0508 in combination with pembrolizumab. Based on preliminary results assessed to date from the first three patients treated in the sub-study, whose demographics are consistent with the 14 patients enrolled in group 1 and group 2 of the monotherapy clinical trial, the combination therapy has been generally well-tolerated after infusion with no dose-limiting toxicities. The first two of the initial three patients enrolled in the combination study were treated with corticosteroids after receiving a CT-0508 infusion and prior to pembrolizumab administration. The Company believes that systemic corticosteroids have the potential to reverse the activity of CT-0508. Based on in vitro studies, corticosteroids lead to CT-0508 cell death. The Company observed a best overall response of progressive disease in the first two patients and stable disease in the third patient per RECIST 1.1 criteria. In an individual case study presented, the third patient in the combination study, who achieved stable disease despite high baseline T-cell exhaustion, presented the greatest increase in peripheral blood T cell clonality seen to date across all seventeen patients treated to date with CT-0508 and had one out of two target lesions reduced by approximately 46%. The results from this early data are both preliminary and limited.
Item 9.01. Financial Statements and Exhibits.
|
Exhibit Number |
Description | |
| 99.1 | Excerpt from Company Presentation, dated April 2024. | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). | |
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: April 10, 2024 | Steven Kelly | |
| President and Chief Executive Officer | ||
Exhibit 99.1
1 CT - 0508 Study 101 Monotherapy Patient Demographics (n=14) Heavily pre - treated pts with HER2 2+/3+ solid tumors 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
2 4/9/2024 40.7% of all target lesions had reduced in size on at least 1 scan Anatomic Location Frequency of tumor lesions that reduced on treatment on at least 1 scan Breast 1/1 (100%) Liver 4/5 (80%) Lung 1/7 (14.3%) Lymph Node 4/8 (50%) Other 1/4 (25%) Skin/Subcutaneous 0/2 (0%) All Lesions 11/27 (40.7%) Best changes in individual target lesions by anatomic site: Target lesion reduction by anatomic site: Each column represents a single target tumor lesion, not a patient.
3 CT - 0508/ Pembro Sub - study: Regimen Level 1 Demographics Patient Demographics were consistent with Group 1 and Group 2 Summary of Participant and Tumor Characteristics Characteristic N = 3 Characteristic N = 3 Median age (range), years 62 (50, 73) Tumor Type, n (%) Breast Cancer Esophageal Cancer Ovarian Cancer 1 (33.3) 1 (33.3) 1 (33.3) Gender, n (%) Male Female 1 (33.3) 2 (66.7) Race, n (%) White 3 (100.0) Median Number of Prior Cancer Therapies, n (range) 6 (5, 7) ECOG PS, n (%) 0 1 0 (0.0) 3 (100.0) Median Number of Prior Anti - HER2 Therapies, n (range) Subjects with Prior Anti - HER2 Therapy 4 (0, 5) 2 (66.7) HER2 Overexpression, n (%) IHC 3+ IHC 2+/FISH+ 2 (66.7) 1 (33.3) Prior Radiotherapy, n (%) Yes 2 (66.7) Microsatellite Instability (MSI)* MSS/MSI - Low MSI - High 3 (100.0) 0 (0) Tumor Mutational Burden (TMB)* Low (<10 mut/Mb) High (≥10 mut/Mb) 2 (66.7) 1 (33.3) † * MSI - high and TMB high are known biomarkers associated with improved response to immune checkpoint † patient has demonstrated HLA - A, HLA - B and HLA - C loss of Heterozygosity
4 CT - 0508/ Pembro Sub - study: Well Tolerated, No Dose Limiting Toxicities, Similar Safety Profile to CT - 0508 Monotherapy CT - 0508 Monotherapy Group 1: Fractionated Dosing CT - 0508 Monotherapy Group 2: Bolus Dosing CT - 0508 + Pembrolizumab Regimen 1 Patients Treated N=9 (%) N=5 (%) N=3 (%) 1 Any treatment - emergent AEs (TEAE) 9 (100) 5 (100) 3 (100) Grade 1 - 2 4 (44) 2 (40) 1 (33) Grade 3 - 4 5 (56) 3 (60) 2 (66) Any TEAEs related to CT - 0508 8 (89) 4 (80%) 3 (100) Any TEAEs related to pembrolizumab N/A N/A 1 (33%) Any treatment - emergent SAEs (TESAE) 4 (44) 3 (60) 3 (100) Any TESAEs related to CT - 0508 2 2 (22) 2 (40) 3 (100) Any TESAEs related to pembrolizumab N/A N/A 0 (0) Cytokine release syndrome (CRS) 6 (67) 3 (60) 2 (67) Grade 1 - 2 6 (67) 3 (60) 2 (67) Grade 3 - 4 0 (0) 0 (0) 0 (0) Immune effector cell - associated neurotoxicity syndrome (ICANS) 0 (0) 0 (0) 0 (0) 1. 2 of the 3 patients in the combination study were treated with corticosteroids post CT - 0508, prior to pembrolizumab 2. All TESAEs related to CT - 0508 were due to hospitalization for monitoring of either Grade 2 CRS or Grade 2 infusion reaction. Similar safety profile between CT - 0508 as monotherapy & in combination with pembrolizumab No severe CRS or ICANS
5 CT - 0508/ Pembro Sub - study : Regimen Level 1 (n=3) Summary First two patients received corticosteroids prior to pembrolizumab Patient Steroids Given Prior to Pembro Best Overall Response Disease HER2 Status Additional Treatment Details Patient 1 Yes PD Stage IV Breast Cancer HER2 2+ • Treated with dexamethasone due to G2 CRS post CT - 0508 infusion, prior to pembrolizumab administration Patient 2 Yes PD Stage IV Ovarian Cancer HER2 3+ • Treated with methylpredinosolone due to G3 Infusion reaction post CT - 0508 infusion, prior to pembrolizumab administration • Triple HLA Class I loss of heterozygosity (HLA - A, B and C deletion in tumor genome). Patient 3 No SD (One out of two target lesions reduced by ~46%) Stage IV Esophageal Cancer HER2 3+ • Missed an early cycle (2nd infusion) of pembrolizumab due to medical issues unrelated to therapy • Patient had brain metastasis and progressed per RECIST 1.1 week 14 due to new brain met Additional Information on Corticosteroids and CT - 0508 • Systemic corticosteroids have the potential to reverse the activity of CT - 0508. • Based on in vitro studies, corticosteroids lead to CT - 0508 cell death. • Steroids were given post CT - 0508, pre - pembrolizumab.
6 CT - 0508/ Pembro Sub - study: Patient Case Study Patient #3: HER2+ Esophageal Adenocarcinoma w/ 6 prior lines of therapy and refractory to Enhertu Patient 3 - Prior Line Prior Therapy Start Time End Time Best Overall Response 1 Neoadjuvant carboplatin/paclitaxel Feb 2019 April 2019 CR 2 Adjuvant Capacitabine , oxaliplatin, trastuzumab Nov 2020 Nov 2020 Unknown 3 Fluorouracil, folinic acid, oxaliplatin, trastuzumab Dec 2020 April 2021 PR 4 Fluorouracil, trastuzumab May 2021 March 2022 SD 5 Paclitaxel, ramucirumab, trastuzumab, tucatinib May 2022 Jan 2023 SD 6 Enhertu Feb 2023 April 2023 PD * BOR: Best Overall Response CR: Complete Response; PR: Partial Response; SD: Stable Disease; PD: Progressive disease Cancer type: Stage IV Esophageal adenocarcinoma (EAC), HER2 3+ Prior history: 6 Prior lines of therapy; Most recent prior line: achieved BOR* of PD and DC’d Enhertu in 2 months Pembrolizumab clinical studies in EAC: • EAC is resistant to pembrolizumab monotherapy (KEYNOTE 180) • ORR 5% • PFS 1.5 months • Pembrolizumab did not show a survival benefit over SOC chemotherapy in PDL1+ EAC (KEYNOTE 181)
7 CT - 0508/ Pembro Sub - study: Patient Case Study Patient #3: 46% reduction in 1 of 2 target lesions Paratracheal LN Target Lesion: 46% reduction by week 13 Baseline Week 8 Week 13 Dosing • Patient received 3.10E+ 09 cells • Patient missed the 2nd cycle of pembrolizumab Tumor assessments • Paratracheal target lesion reduction of 46% by week 13; 21.9mm to 11.8mm • Mediastinal mass target lesion grew 31% by week 13; 26.9 to 35.3mm Outcome Comparators PFS Patient 3 – Regimen 1 CT - 0508 / Pembro 3.25 months Patient 3 – 6 th Line of Therapy on Enhertu 2.0 months Pembrolizumab monotherapy in KEYNOTE 180* 1.5 months *KEYNOTE 180: Efficacy and Safety of Pembrolizumab for Heavily Pretreated Patients With Advanced, Metastatic Adenocarcinoma o r S quamous Cell Carcinoma of the Esophagus. JAMA Oncology. 2019. Clinical assessments • Achieved a BOR of SD per RECIST 1.1 • PD per RECIST at week 13 due to new CNS metastasis • PFS of 3.25 months (13.3 weeks)
8 CT - 0508/ Pembro Sub - study: Pt 3 had high baseline peripheral CD8 T cell exhaustion
9 CT - 0508/ Pembro Sub - study: Individual Case Study Patient 3: Greatest increase in peripheral blood T cell clonality seen to - date across all 17 patients treated with CT - 0508 Increased T cell clonality in the peripheral blood T cell clonality (Fold change over screening) Monotherapy Pt #3 - SD Pembrolizumab combo – cohort 1