Universal "modular" CAR-T: Innovent continues to develop cell therapy

On February 21, Innovent announced that the world's first universal "modular" Claudin18.

This new drug comes from the cooperation between Innovent and Roche on June 9, 2020

Recently, Innovent has gradually begun to enter into the development of multiple types of therapies including antibody-drug conjugates (ADC), immunostimulatory antibody conjugates (ISAC), and cell therapy through different cooperation models

IBI345: Universal "modular" CAR-T

As a generic "modular" CAR-T cell product, IBI345 consists of two components: an anti-Claudin18.

At the same time, "modular" CAR-T is versatile and can be combined with different antibodies to treat solid tumors with highly heterogeneous antigen expression or antigen deletion by sequentially or simultaneously administering more than one antibody targeting different antigen targets.

In January 2022, Innovent registered the first investigator-initiated clinical trial of IBI345 (IIT; NCT05199519) on ClinicalTrials.

CAR-T cells, as a new type of highly efficient and precisely targeted tumor cell immunotherapy drug modified by genetic engineering, have shown great therapeutic potential in the treatment of hematological tumors

On this basis, solid tumors and allogeneic general-purpose CAR-T are two important directions explored by many cell therapy companies.

Claudin18.

At present, no therapy targeting Claudin18.

However, for CAR-T therapy, currently only Keji Pharma is developing it in China, and its R&D code is CT041.

At ESMO 2021, Keji announced clinical results that as of April 8, 2021, the overall objective response rate (ORR) in 37 patients with digestive system tumors was 48.

Eighteen patients with gastric cancer had failed at least 2 previous lines of therapy and received 2.

The IBI345 developed by Cinda uses a general "modular" technology, which is different from the Claudin18.

IBI326: Application for listing in the first half of 2022

IBI326 is a second-generation fully human BCMA-targeted CAR-T therapy jointly developed by Innovent and Reindeer Medical

The product candidate uses lentivirus as a gene carrier to transfect autologous T cells.

In December 2021, Innovent and Reindeer Medical presented the results of the latest Phase 1/2 registrational clinical study of IBI326 in an oral presentation at the 2021 ASH Annual Meeting
.
This is a single-arm, open-label, multi-center clinical study conducted in China and enrolled patients with relapsed/refractory multiple myeloid who have received ≥ 3 lines of therapy, positive plasma cell membrane expression of BCMA, and ECOG score of 0-1 The primary endpoint of the study was overall response rate (ORR)
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As of October 12, 2021, a total of 79 subjects were enrolled, including 9 subjects participating in the investigator-initiated early exploratory study (IIT) and 70 subjects participating in the registration clinical study (NCT05066646)
.

The results showed that IBI326 had excellent and durable efficacy, with an ORR of 94.
9% and a complete remission/strict complete remission (CR/sCR) of 58.
2%, and the response had a tendency to deepen with the extension of follow-up time
.
The PFS at 6, 9 and 12 months after reinfusion was 78.
0%, 76.
0% and 71.
0%, respectively
.
It still has good efficacy for subjects who have previously received CAR-T therapy and relapsed.
The ORR of 13 subjects who received CAR-T therapy in the trial was 76.
9%, and 61.
5% achieved a very good partial response.
(VGPR) and above, CR/sCR was 46.
2%
.

The safety is also excellent and controllable.
Most of the patients have grade 1-2 cytokine release syndrome (CRS).
Only 2 subjects in the IIT stage have grade 3 or above CRS, and no grade 4/5 CRS
.
All subjects achieved remission of CRS and ICANS, 20% of whom were treated with tocilizumab and 34.
7% of whom were treated with glucocorticoids
.

This study is the first registered clinical trial in the world to enroll subjects who have failed previous CAR-T therapy, and is expected to address this unmet need for treatment
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The follow-up clinical development of this drug will also be advanced from four dimensions: front-line treatment, combination medication, indication expansion, and overseas layout
.

In February 2021, IBI326 was approved by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) as a "Breakthrough Therapy Drug" for the treatment of relapsed/refractory multiple myeloma
.
It is expected that after the listing, it is expected to obtain the priority review qualification and accelerate the listing process
.