On February 21, Innovent announced that the world's first universal "modular" Claudin18.
2 chimeric antigen receptor T cell (CAR-T) injection (development code: IBI345) developed by Innovent was used in the treatment of advanced Claudin18.
2 positive entities.
The first patient was dosed in a clinical trial of cancer
This new drug comes from the cooperation between Innovent and Roche on June 9, 2020
In this collaboration, Innovent can develop 2:1 bispecific T-cell antibodies and general-purpose CAR-T therapy for hematological and solid tumor treatment using Roche's patented technology, and is responsible for product development, manufacturing and commercialization , the specific transaction amount was not disclosed
Roche, on the other hand, has the option to develop products based on the platform outside of China.
If the option is exercised, it will pay Cinda a down payment (up to US$140 million), milestone payments (up to US$1.
96 billion) and double-digit sales.
IBI345 is the first product to enter clinical development based on this strategic collaboration and innovative technology platform
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
Taking cell therapy as an example, Innovent not only obtained new platform technologies through cooperation with MNC to support early R&D, such as Claudin18.
2 CAR-T IBI345, which entered the clinic this time; it also directly introduced potential pipelines, such as with Reindeer Medical.
Collaborative BCMA CAR-T IBI326
IBI345: Universal "modular" CAR-TIBI345: Universal "modular" CAR-T
As a generic "modular" CAR-T cell product, IBI345 consists of two components: an anti-Claudin18.
2 antibody and a "modular" CAR-T cell
Compared with traditional CAR-T cells, on the one hand, IBI345 can increase anti-tumor efficacy through the dual effects of antibodies and cells, and use the "targeting" effect of antibodies to amplify the antigen target signal, guide CAR-T cells into tumors and initiate recognition.
On the other hand, the activity of CAR-T cells can be regulated by regulating antibody administration, so as to achieve the purpose of controlling toxic and side effects
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.
Therefore, it is expected to achieve a breakthrough in CAR-T treatment of solid tumors, reduce the cost of CAR-T cell therapy, and improve the accessibility of CAR-T cell therapy for patients
In January 2022, Innovent registered the first investigator-initiated clinical trial of IBI345 (IIT; NCT05199519) on ClinicalTrials.
gov for the first time to explore the safety, tolerability, pharmacokinetics and preliminary efficacy of IBI345.
The clinical dosing dose and schedule provide clinical data support for the follow-up formal IND application (Insight previous reports: Innovent Bio's 2nd CAR-T starts clinical! Multi-target in-depth layout)
Today, Innovent announced the completion of the first subject dosing, and enrollment is still in progress
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
According to statistics from the Insight database, 5 CAR-T therapies have been approved in the United States, all of which are autologous CAR-T therapies for third-line and later hematological tumors
However, according to the financial report information released by various MNC pharmaceutical companies in 2021, the total global sales of CAR-T therapy for the whole year has exceeded 1.
7 billion US dollars, and the year-on-year increase of more than 20% has been increasing year by year
In China, 2021 can be described as the "first year" of cell therapy.
Two CAR-T therapies have been approved for marketing, making the field of CAR-T therapy marketed in China to break zero
On this basis, solid tumors and allogeneic general-purpose CAR-T are two important directions explored by many cell therapy companies.
A broader patient population coverage and higher availability of drug delivery are expected to help cell therapy achieve greater success.
In addition to solid tumor exploration, Claudin18.
2 is one of the most favored targets by pharmaceutical companies
2, a member of the Claudin protein family, is a highly tissue-specific protein expressed only in differentiated epithelial cells on the gastric mucosa under normal physiological conditions
Studies have shown that Claudin18.
2 is highly expressed in many gastric cancer, pancreatic cancer, esophageal adenocarcinoma, colorectal adenocarcinoma and other tumors, especially in patients with advanced gastric cancer and pancreatic cancer.
An ideal target in the field of cancer
At present, no therapy targeting Claudin18.
2 has been approved for marketing globally, but pharmaceutical companies have rushed to develop monoclonal antibodies, double antibodies, ADCs and cell therapies targeting this target
Among them, monoclonal antibody accounts for the majority.
According to the Insight database, there are 12 Claudin18.
2 monoclonal antibodies in clinical development in China alone, and 5 and 6 of double-antibody and ADC have entered the clinic respectively
However, for CAR-T therapy, currently only Keji Pharma is developing it in China, and its R&D code is CT041.
Phase Ib/II clinical trials have been initiated for patients with advanced gastric/esophagogastric junction adenocarcinoma and pancreatic cancer
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.
6% (95%CI, 31.
), the ORR of 28 gastric cancer patients reached 57.
1% (95% CI, 37.
Eighteen patients with gastric cancer had failed at least 2 previous lines of therapy and received 2.
5×108 CAR-T cell infusion (44% [8/18] of patients had previously received anti-PD-(L)1 monoclonal antibody)
The overall ORR in this population was 61.
1% (11/18), the median progression-free survival (mPFS) was 5.
4 months (95% CI, 2.
6, NE), and the median overall survival (mOS) was 9.
5 month (95% CI, 5.
The efficacy results have preliminarily confirmed the potential of Claudin18.
The IBI345 developed by Cinda uses a general "modular" technology, which is different from the Claudin18.
2 CAR-T currently under development.
We look forward to the data disclosure of the follow-up IIT research
Gastric cancer and pancreatic cancer are both malignant tumors of the digestive system that seriously endanger human life and health.
According to the WHO report, gastric cancer will be the third largest cancer type in China in terms of morbidity and mortality in 2020, with 480,000 new cases and 480,000 deaths.
370,000; pancreatic cancer incidence and mortality ratio is 1:0.
89, also known as "the king of cancer"
It is hoped that the development of CAR-T therapy will improve the treatment status and bring more benefits
IBI326: Application for listing in the first half of 2022IBI326: 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
According to the information disclosed by Innovent, it is expected to submit a new drug marketing application for IBI326 in the first half of 2022, which is expected to become the first CAR-T therapy targeting BCMA in China
The product candidate uses lentivirus as a gene carrier to transfect autologous T cells.
The CAR contains fully human scFv, CD8a hinge and transmembrane, 4-1BB co-stimulatory and CD3ζ activation domains
Based on rigorous screening and comprehensive in vitro and in vivo functional evaluation, the IBI326 CAR-T product candidate has potent and rapid efficacy with outstanding durability
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)
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% and 71.
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.
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
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