CARsgen Therapeutics Presents Updated Data for CT041 Claudin18.2 CAR T-cells in Solid Tumors at ASCO 2022

SHANGHAI,June 6,2022 -- 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,announces that at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting,the Company presented two posters with study results for CT041,an autologous CAR T-cell product candidate against protein Claudin18.2 (CLDN18.2). The two posters included (1) results from the multicenterPhase 1b CT041 trial in the U.S. for patients with advanced gastric and pancreatic adenocarcinomaand (2)the safety and preliminary efficacy results from the Phase Ib/II CT041 study in China for patients with advanced gastric/gastroesophageal junction adenocarcinoma.

The abstracts of the posters are listed below:

Abstract #2538: Multicenter Phase 1b Trial of Salvage CT041 CLDN18.2 – specific Chimeric Antigen Receptor T Cell Therapy for Patients with Advanced Gastric and Pancreatic Adenocarcinoma

A single-arm,open-label,Phase 1b trial (NCT04404595) was conducted in six centers in the U.S. CLDN18.2 positive patients who had gastric cancer or gastroesophageal junction cancer (GC/GEJ) with ≥ 2 prior lines of systemic therapy or pancreatic cancer (PC) with ≥ 1 prior line were eligible for the study. A preconditioning regimen with fludarabine,cyclophosphamide,and nab-paclitaxel (100 mg or 100 mg/m2; FNC) was given prior to CT041 infusion. Adverse events (AEs) were graded per CTCAE v5.0. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded by ASTCT criteria. Tumor response was assessed per RECIST 1.1.

As of May 6,2022,14 patients had enrolled (5 GC/GEJ,9 PC) with a median of 3 prior lines of therapy (range 1-5) and had received 18 total cycles of CT041. Fourteen patients were given by three dose levels (DL) including DL1 of 2.5-3.0×108 cells (n=6),DL2 of 3.75-4.0×108 cells (n=6) and DL3 of 6.0×108 cells (n=2).

Safety

No dose-limiting toxicities or treatment-related deaths were observed. No ≥ Grade 3 CRS or ICANS was observed. No gastrointestinal bleeding or acute gastric mucosal injury were reported. One patient did not have CRS. Among the 13 patients with CRS,11 patients had Grade 1 and 2 patients had Grade 2.

Efficacy

In a subgroup of patients with GC/GEJ, an objective response rate (ORR)of 60% was reported,and one patient achieved complete response (CR). Additionally,tumor shrinkage was observed in 80% (4 of 5) of patients with stable disease (4 patients with PC). Median duration of response (mDOR) and progression-free survival (mPFS) have not been reached. Two patients who received DL3 did not have tumor response assessments by the data cutoff date. Dose-dependent responses were observed in DL1 and DL2. An ORRof 16.7% and a disease control rate (DCR)of 50% was observed in DL1. An ORR of 33.3% and a DCR of 83.3% were observed in DL2. Tumor response details are listed in the table below.

Tumor response by tumor type

GC/GEJ (n=5)

n (%)

PC (n=7)

n (%)

Complete response

1 (20)

0 (0)

Partial response

2 (40)

0 (0)

Stable disease

1 (20)

4 (57.1)

Progressive disease

1 (20)

3 (42.9)

Note: GC/GEJ= gastric canceror gastroesophageal junction cancer; PC=pancreatic cancer.

Conclusion

In heavily pre-treated gastric cancer,CT041 CLDN18.2 CAR T cells may have significantly improved antitumor activity compared to historical treatment regimens.

Abstract #4017 Safety,Tolerability and Preliminary Efficacy Results in Patients with Advanced Gastric/Gastroesophageal Junction Adenocarcinoma from a Phase Ib/II Study of CLDN18.2 CAR T-cell Therapy (CT041)

This multicenter,Phase Ib/II study (NCT04581473) was conducted to evaluate the safety and efficacy in Chinese patients with GC/GEJ. In Phase Ib,CT041 dose levels of 2.5×108 and 3.75×108 cells were investigated using a 3 + 3 design.

Keyeligibility criteria for the Phase Ib study: patients with CLDN18.2-positive expression confirmed by immunohistochemistry (IHC) staining (2+/3+ in ≥40% tumor cells),advanced GC/GEJ adenocarcinoma who were refractory to or intolerant of at least 2 prior treatments are eligible for this study. HER2–positive patients should have received standard anti–HER2 therapy.

As of December 22,2021,14 eligible patients with GC/GEJ were enrolled in Phase Ib,among which 57.1% had ≥ 3 metastatic organs and92.9% had peritoneal dissemination. Most of the patients (85.7%) had received 2 prior treatments or a triple combination of fluoropyrimidine,oxaliplatin and paclitaxel. 35.7% of the patients had been exposed to PD-1/PD-L1 inhibitor. The baseline characteristics are shown in the table below.

Demographics and baseline characteristics

Total (N = 14)

Median age (range),year

44.5 (23–71)

Male,n (%)

6 (42.9%)

Eastern Cooperative Oncology Group performance status=1,n (%)

12 (85.7%)

Lauren classification,n (%)

Intestinal type

3 (21.4%)

Diffuse type

9 (64.3%)

Mixed type

2 (14.3%)

Signet ring cell carcinoma,n (%)

9 (64.3%)

Claudin18.2 staining,n (%)

2+

2 (14.3%)

3+

12 (85.7%)

HER2 expression,n (%)

Positive

1 (7.1%)

Negative

12 (85.7%)

Unknown

1 (7.1%)

Numbers of metastatic organs,n (%)

< 3

6 (42.9%)

≥ 3

8 (57.1%)

Peritoneal metastasis,n (%)

13 (92.9%)

Liver metastasis,n (%)

3 (21.4%)

Numbers of prior lines,n (%)

2*

12 (85.7%)

≥ 3

2 (14.3%)

Prior systemic therapies,n (%)

Fluorouracil

14 (100%)

Platinum

14 (100%)

Paclitaxel / nab–paclitaxel

13 (92.9%)

PD–1/PD-L1 inhibitor

5 (35.7%)

Tyrosine–kinase inhibitor

2 (14.3%)

* Five patients received a triple combination of fluoropyrimidine,oxaliplatin and paclitaxel as first line treatment.

All 14 patients received 1 cycle of bridging chemotherapy determined by the investigators,including 13 patients (92.9%) received FOLFIRI,and only 1 received 5–FU plus intraperitoneal nab–paclitaxel. All patients received preconditioning treatment (fludarabine 25 mg/m2 on d1–2,cyclophosphamide 250mg/m2 on d1–3 and nab–paclitaxel 100 mg on d2) before CT041 infusion. All patients received at least one infusion (11 received 2.5×108 cells and 3 received 3.75×108 cells) of CT041 and 7 patients received two infusions. For the 7 patients who received two infusions,the median interval between infusions was 132 days (range 49–252 days).

Safety

No patients haddose–limiting toxicities or AEs leading to death. Thirteen patients had Grade 2 CRS,and only one patient had Grade 4 CRS,which was related to the patient's disease burden,who fullyrecovered after corticosteroid treatment. No ICANS or gastrointestinal mucosal injury were reported.

Efficacy

Thirteen patients were evaluable and one patient withdrew from the studybefore any tumor assessment was performed. Eight of 14 (57.1%) patients achieved partial response at the first tumor assessment after the first CT041 infusion. Based on the investigators' assessment,the ORR and DCR were 57.1% and 78.6% respectively.

While the median follow-up time was 8.8 months,the mPFS and median overall survival were 5.6 months and 10.8 months respectively. Seven patients were still alive bythe cutoff date.

Conclusion

These preliminary results suggest that CT041 had manageable safety/tolerability profile and promising efficacy in patients with previously treated advanced GC/GEJ adenocarcinoma. This study is ongoing with further investigation of CT041 in confirmatory Phase II underway.

Dr. Raffaele Baffa,Chief Medical Officer of CARsgen Therapeutics Holdings Limited,said,"Solid tumors,including gastric cancer,are of high incidence globally. As treatment options for gastric cancer are still limited,there is a strong need for more innovative therapies. The updated clinical data of CT041 at ASCO 2022 are very encouraging in pre-treated GC/GEJ and PC patients,demonstrating significant efficacy and excellent tolerability,including the impressive ORR of 60% and a case of CR. We look forward to the continuing development of CT041 and we believe it can help more patients."

Dr. Zonghai Li,Founder,Chairman of the Board,Chief Executive Officer,and Chief Scientific Officer of CARsgen Therapeutics Holdings Limited,"It is the first time that we presented the data for CT041 from registrational trials in China and the U.S. Following the publication of the results of an investigator-initiated trial of CT041 in Nature Medicine earlier in May,the updated results announced at ASCO 2022 further demonstrated the promising therapeutic efficacy and favorable safety of CT041. CT041 is currently the only CAR T-cell product candidate entering a confirmatory Phase II clinical trial for the treatment of solid tumors. We will spare no efforts to continue driving the global clinical development of CT041 to benefit more cancer patients worldwide."

About CT041

CT041 is an autologous CAR T-cell product candidate against the protein CLDN18.2 that has the potential to be the first-in-class globally. CT041 targets the treatment of CLDN18.2 positive solid tumors with a primary focus on GC/GEJ and PC. CT041 has demonstrated promising therapeutic efficacy and favorable safety in ongoing clinical trials. CARsgen believes that CT041 has the potential to become a backbone therapy for GC/GEJ and PC in the future and benefit a large population of patients worldwide.

As of the date of the announcement,CT041 is the only CLDN18.2-targeted CAR T-cell product candidate globally that is being studied in clinical trials with IND/CTA approvals from the FDA,the NMPA and Health Canada.

Active trials in CARsgen include investigator-initiated trials,a Phase Ib clinical trial for advanced GC/GEJ and PC and a confirmatory Phase II clinical trial for advanced GC/GEJ in China (CT041-ST-01,NCT04581473),and a Phase 1b/2 clinical trial for advanced gastric or pancreatic adenocarcinoma in North America (CT041-ST-02,NCT04404595). CARsgen also intends to conduct a pivotal Phase 2 clinical trial in North America in 2022.

In May 2022,the phase I trial interim results of an investigator-initiated trial of CT041 have been published in Nature Medicine. In this largest clinical trial for solid tumors to date,the CAR T-cell therapy showed unprecedented efficacy against solid tumors.

In 2020 and 2021,CT041 received Orphan Drug designation from the U.S. FDA for the treatment of GC/GEJ and Orphan Medicinal Product designation from the EMA for the treatment of advanced gastric cancer. In November 2021,CT041 was granted PRIME Eligibility by the EMA for the treatment of advanced gastric cancer. In January 2022,CT041 was granted Regenerative Medicine Advanced Therapy (RMAT) Designation by U.S. FDA for the treatment of advanced gastric orgastroesophageal junction adenocarcinoma with CLDN18.2 positive tumors.

About CARsgen Therapeutics Holdings Limited

CARsgen is a biopharmaceutical company with operations in China and the U.S. and is 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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