CARsgen Presents Updated Research Results on BCMA CAR T-cell Product (CT053) at 2021 ASH Annual Meeting

SHANGHAI,Dec. 13,2021 -- CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK),a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors,today announces that at the 2021 American Society of Hematology ("ASH") Annual Meeting,the Company presented two posters with study results for CT053,an autologous CAR T-cell product candidate against B-Cell Maturation Antigen (BCMA),which include (1) the sustainable efficacy and safety results from the Phase I/II study in China (LUMMICAR-1) and (2) an integrated analysis in participants with relapsed and/or refractory multiple myeloma (R/R MM) by high-risk factors. Details are listed below.

Poster #2821: Sustainable Efficacy and Safety Results from LUMMICAR STUDY 1: A Phase 1/2 Study of Fully Human B-Cell Maturation Antigen-Specific CAR T Cells (CT053) in Chinese Subjects with Relapsed and/or Refractory Multiple Myeloma

BCMA is a promising therapeutic target in multiple myeloma (MM). CT053 is an autologous CAR T-cell product candidate incorporating a fully human BCMA-specific single-chain variable fragment with fine-tuned binding affinity and a high monomer ratio.

LUMMICAR STUDY 1 is a multi-center,open-label Phase I/II clinical trial in China. The primary endpoint of this trial is to evaluate the safety and tolerability of CT053 and to identify the recommended Phase II dose. Secondary endpoints are to evaluate efficacy,safety and pharmacokinetics. Efficacy is assessed according to the International Myeloma Working Group (IMWG) 2016 criteria.

As of July 8,2021,14 heavily treated participants with R/R MM received CT053 infusion. Three participants received 1.0×108 CAR+ T cells,and 11 participants received 1.5×108 CAR+ T cells. All participants had received at least 3 prior regimens,with a median of 6 prior regimens. 50.0% (7/14) of the participants had high risk cytogenetic abnormalities,14.3% (2/14) of the participants had extramedullary disease (EMD),and 14.3% (2/14) of the participants had International Staging System (ISS) III.

Safety

CT053 was generally well-tolerated. No ≥Grade 3 cytokine release syndrome (CRS) or neurotoxicity was observed. No dose limiting toxicity (DLT) and no treatment-related death was reported. No immunogenicity was identified.

Efficacy

As of July 8,the median follow-up time was 13.6 months (range from 4.2 months to 22.4 months). The overall response rate (ORR) was 100% (14/14). Of these patients,78.6% (11/14) achieved stringent complete responses (sCR) with minimal residual disease (MRD) 10-5 negative,and 9 patients reached sustained CR/sCR for more than 12 months. A total of 92.9% (13/14) of patients achieved at least very good partial responses (VGPR). The 12-month progression-free survival (PFS) rate was 85.7% (12/14). The median duration of response (mDOR) and the median progression-free survival (mPFS) had not been reached. For patients without EMD,the CR/sCR rate was 91.7% (11/12) and the 12-month PFS rate reached 100%,which demonstrate better treatment trends.

Conclusion

These results demonstrate that CT053 CAR T cells achieved a deep and durable response,with an acceptable safety profile in patients with R/R MM (50% of patients had high risk cytogenetic abnormalities).

Poster #1751: Integrated Analysis of B-cell Maturation Antigen-Specific CAR T Cells (CT053) in Relapsed and Refractory Multiple Myeloma Subjects by High-Risk Factors

Prior results from studies of CT053 (three investigator-initiated trials [IITs]) and the LUMMICAR STUDY 1 demonstrated deep and durable responses in heavily treated patients with R/R MM as reported at the 2020 ASH Annual Meeting. Here,we summarized and analyzed the integrated efficacy and safety from these studies stratified by high-risk factors,including EMD,high-risk cytogenetic abnormalities,and ISS III.

The data cut-off for the IIT studies and the LUMMICAR-1 study were June 30,2021 and July 8,respectively. A total of 38 patients received CT053 infusions (1 patient received 0.5×108,4 patients received 1.0×108,32 patients received 1.5×108,and 1 patient received 1.8×108 CAR+ T cells). All patients had received ≥2 prior regimens against multiple myeloma with a median of 6 prior regimens (range 2-12). A total of 31.6% of the 38 treated patients had EMD,50.0% had high-risk cytogenetics,and 28.9% had ISS stage III disease.

Efficacy

In the 13.9 months median follow-up time,the ORR was 92.1% (35/38),with 78.9% (30/38) of patients achieving CR/sCR and 86.8% (33/38) of patients achieving at least VGPR. The mPFS and mDOR were 22.7 months and 24.0 months,respectively.

Based on the results of the analysis stratified by high-risk factors,the CR/sCR rate,mPFS,and mDOR were 58.3%,9.3 months and 9.2 months,respectively,in patients with EMD,whereas the measures in patients without EMD were 88.5%,25.0 months and 24.0 months,respectively. The mPFS and mDOR in patients with high-risk cytogenetics were 15.6 months and 18.3 months and were both 13.3 months in ISS III patients,while mPFS and mDOR had not been reached in patients without these two high-risk factors. These results suggest that the presence of the high-risk disease characteristics of EMD,high-risk cytogenetics,and ISS stage III at baseline might affect the clinical benefits. See the following table for details.

EMD status

High-risk cytogenetics

ISS stage

EMD

(n = 12)

Non-EMD

(n = 26)

HR-cyto

(n = 19)

Non-HR-

cyto

(n = 19)

ISS III

(n = 11)

Non-ISS III

(n = 27)

Total

(N=38)

Median follow-

up time,months

9.3

14.9

12.9

15.4

12.2

15.4

13.9

ORR,n (%)

11

(91.7%)

24

(92.3%)

16

(84.2%)

19

(100%)

9

(81.8%)

26

(96.3%)

35

(92.1%)

CR/sCR,

n (%)

7

(58.3%)

23

(88.5%)

14

(73.7%)

16

(84.2%)

8

(72.7%)

22

(81.5%)

30

(78.9%)

mPFS,months

(95%CI)

9.3

(2.8,NR)

25.0

(15.6,NR)

15.6

(10.1,25.0)

NR

(11.2,NR)

13.3

(0.9,NR)

NR

(15.6,NR)

22.7

(13.3,

NR)

mDOR,months

(95%CI)

9.2

(2.8,NR)

24.0

(14.8,NR)

18.3

(9.2,NR)

NR

(10.3,NR)

13.3

(7.6,NR)

NR

(14.8,NR)

24.0

(13.3,

NR)

Abbreviations: EMD,extramedullary disease; HR-cyto,high-risk cytogenetic abnormalities; NR,not reached; ISS,international staging system.

Safety

No DLT or treatment-related death occurred. The incidence of Grade 1 or 2 CRS was 73.7%,and no ≥Grade 3 CRS occurred. One (2.6%,1/38) patient with ISS stage III and EMD developed Grade 3 neurotoxicity (epilepsy),which fully resolved after methylprednisolone treatment.

Conclusion

The results demonstrate that CT053 represents a promising treatment option for patients with R/R MM,including those with high-risk disease,and it is generally well-tolerated.

Dr. Zonghai Li,Founder,Chairman of the Board,Chief Executive Officer,and Chief Scientific Officer of CARsgen Therapeutics Holdings Limited,pointed that,"Thanks to Dr. Wenming Chen and Dr. Chengcheng Fu for sharing the study results of CT053 at the ASH Annual Meeting. Thanks to all researchers dedicated to this project. I hope that CT053 can reshape the treatment paradigm for multiple myeloma and become a foundational treatment for multiple myeloma patients,and thus benefit patients as soon as possible."

About CT053

CT053 is an upgraded fully human,autologous BCMA CAR T-cell product candidate for the treatment of R/R MM. It incorporates an upgraded CAR construct engineered by CARsgen that features a fully human BCMA-specific single-chain variable fragment with lower immunogenicity and increased stability,which reduces the self-activation of CAR T-cells in the absence of tumor associated targets.

CARsgen has completed the Phase I trials and is conducting the pivotal Phase II portions of a Phase I/II clinical trial (LUMMICAR STUDY 1) in China and a Phase 1b/2 clinical trial (LUMMICAR STUDY 2) in North America to evaluate the safety and efficacy of CT053 for R/R MM. CARsgen plans to submit for marketing approval to the NMPA in the first half of 2022 and to the U.S. FDA in the first half of 2023. The Company also plans to conduct additional clinical trials to develop CT053 as an earlier line of treatment for MM.

CT053 received Regenerative Medicine Advanced Therapy (RMAT) and Orphan Drug designations from the U.S. FDA in 2019,as well as the PRIority MEdicines (PRIME) and Orphan Medicinal Product designations from the European Medicines Agency (EMA) in 2019 and 2020,respectively. CT053 also received Breakthrough Therapy designation from the NMPA in 2020.

About CARsgen Therapeutics Holdings Limited

CARsgen is a biopharmaceutical company with operations in China and the U.S. focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors. The Company has built an integrated cell therapy platform with in-house capabilities that span target discovery,antibody development,clinical trials,and commercial-scale manufacturing. CARsgen has internally developed novel technologies and a product pipeline with global rights to address major challenges of CAR T-cell therapies,such as improving the safety profile,enhancing the efficacy in treating solid tumors,and reducing treatment costs. The Company's vision is to become a global biopharmaceutical leader that brings innovative and differentiated cell therapies to cancer patients worldwide and makes cancer curable.

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