Innovent to Present Preclinical Data of Multiple Novel Molecules at the 2024 AACR Annual Meeting
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Late-Breaking Research: Experimental and Molecular Therapeutics 1
Topic: IBI3001: a potentially first-in-class site-specific glycan-conjugated B7-H3/EGFR bispecific ADC for multiple solid tumors
Abstract Number: LB055
Presentation Form: Poster
Presentation Time: Sunday Apr 7, 2024 1:30 PM - 5:00 PM
Location: Poster Section 53
Presenting Author: Dr. Kaijie He
IBI3001 is a potentially first-in-class bispecific ADC against B7-H3 and EGFR that is site-specifically glycan-conjugated using the clinically validated SYNtecanE® platform.
IBI3001 has multiple anti-tumor mechanisms of action: (1) enhanced EGFR signaling blockade; (2) EGFR- and B7-H3-aided payload internalization and cytotoxicity; and (3) potent bystander killing effects of ADC. The optimized B7-H3 arm not only enhances the EGFR signaling blockade but also reduces EGFR on-target toxicities.
IBI3001 showed strong anti-tumor efficacy in vitro and in vivo across multiple solid tumors and is well tolerated with the therapeutic index at 40.
Topic: IBI334, a novel ADCC-enhanced B7-H3/EGFR bispecific antibody, demonstrated potent pre-clinical efficacy in solid tumors
Abstract Number: LB056
Presentation Form: Poster
Presentation Time: Sunday Apr 7, 2024 1:30 PM - 5:00 PM
Location: Poster Section 53
Presenting Author: Dr. Kaijie He
IBI334 is an afucosylated bispecific antibody against B7-H3 and EGFR that is constructed using Innovent's proprietary Innobody platform.
With the aid of B7-H3, IBI334 showed better tumor growth inhibition in vitro and in vivo than EGFR monoclonal antibody and c-met/EGFR bispecific antibody benchmarks.
IBI334 has a favorable safety profile with the highest non-severely toxic dose (HNSTD) in cynomolgus monkeys at 120 mg/kg and a large therapeutic window of > 200 folds.
As a promising bispecific antibody against multiple solid tumors, IBI334 is currently under clinical evaluation.
Topic: Discovery and preclinical characterization of IBI343, a site-specific glycan-conjugated anti-Claudin18.2 ADC for treating solid tumors
Abstract Number: LB057
Presentation Form: Poster
Presentation Time: Sunday Apr 7, 2024 1:30 PM - 5:00 PM
Location: Poster Section 53
Presenting Author: Dr. Kaijie He
IBI343 is a potentially first-in-class anti-Claudin 18.2 ADC that is site-specifically glycan-conjugated to cytotoxin exatecan via Synaffix's GlycoConnect® technology.
It demonstrated Claudin 18.2-specific in vitro cytotoxicity on a series of cancer cell lines at varying levels of target expression, and potent in vivo efficacy in multiple xenograft models. The glycan-based conjugation technology leads to enhanced stability of the ADC molecule. IBI343 displayed good safety profile in GLP toxicology study in rhesus monkey and was well tolerated up to 30 mg/kg.
IBI343 has favorable pre-clinical efficacy and safety, and it is currently in preparation for Phase 3 clinical trial for Claudin-18.2-positive HER2-negative gastric cancer.
Dr. Kaijie He, Vice President of Innovent, stated: "We are pleased that the pre-clinical studies of our novel anti-cancer drugs are accepted for Late-Breaking Research poster presentation at the 2024 AACR conference. This is the result of dedicated work from scientists at Innovent Academy with the aim to tackle cancers with innovative drugs that are more effective and safer. With careful design and optimization, our molecules can achieve favorable therapeutic windows of 40 to more than 200 times. We look forward to their performance in clinical settings and hope that these innovations can eventually benefit cancer patients."
Poster Session: Immunology - Single Target and Bispecific Antibodies
Topic: A novel TROP2-targeted immune stimulating antibody conjugate (ISAC) with potent anti-tumoral activity and acceptable safety
Abstract Number: 2718
Presentation Form: Poster
Presentation Time: Monday Apr 8, 2024 1:30 PM - 5:00 PM
Location: Poster Section 6
Poster Board Number: 9
Presenting Author: Dr. Huizhong Xiong
Immune stimulating antibody conjugates (ISACs) are a unique class of ADC in which antibodies recognizing tumor antigens are conjugated with immune agonists. ISACs target tumor tissue and specifically activate intra-tumoral myeloid cells, unleashing downstream immune response. Like the other immune agonists, balance between efficacy and safety remains a challenge for ISACs.
Here we describe a potential first-in-class TROP2 ISAC with rationally selected antibody and TLR7/8 agonist linker-payload. The anti-TROP2 antibody elicited robust ADCP of TROP2+ tumor cells by macrophages. In-vitro, TROP2 ISAC mildly activated myeloid cells only in the presence of TROP2+ tumor cells. In-vivo, the molecule potently suppressed tumor growth in different TROP2+ xenograft tumors, and effectively enhanced killing of an ADC. In terms of safety, the ISAC was tolerated in both WT and hTROP2KI mice, and, importantly, in monkeys.
Taken together, our data demonstrate a novel TROP2 ISAC with outstanding efficacy and manageable safety profile, which may benefit patients with TROP2+ tumors.
Poster Session: Immunology - Immune Modulation Employing Agonist or Co-Stimulatory Approaches
Topic: Tumor targeted-CD28 bispecific antibody with optimized potency, robust anti-tumoral activity and stringent CD3-dependence
Abstract Number: 5295
Presentation Form: Poster
Presentation Time: Tuesday Apr 9, 2024 1:30 PM - 5:00 PM
Location: Poster Section 3
Poster Board Number: 4
Presenting Author: Dr. Huizhong Xiong
We reported a rationally screened CD28 agonist antibody and its PSMAxCD28 bispecific format, IAR038.
IAR038 has minimal activity in the absence of CD3, even under stringent conditions, different from benchmark antibody in clinical development. It demonstrated moderate activity in vitro in a CD3-dependent and PSMA-dependent manner. Notably, IAR038 elicited superior tumor killing in vivo and combined effectively with anti-PD1 antibody.
In addition, it had an improved half-life compared with the Benchmark antibody. These features may translate to a wider therapeutic window and improved safety for CRPC patients.
Dr. Huizhong Xiong, Senior Director of Immunology of Innovent, stated: "We keep pushing for deeper understanding and more rational design of agonistic and costimulatory molecules. Our work on tumor targeted TLR7/8 agonist and tumor targeted CD28 antibody demonstrates the capability of our biology-driven drug development to achieve better balance between efficacy and safety, made possible by our advanced technology platforms."
About Innovent
Innovent is a leading biopharmaceutical company founded in 2011 with the mission to provide high-quality biologics that are affordable to all. The company discovers, develops, manufactures and commercializes innovative medicines that treat some of the most intractable diseases. Its pioneering therapies treat cancer, cardiovascular and metabolic, autoimmune and eye diseases. Innovent has 10 products in the market, 3 new drug applications under the NMPA review, 5 assets in Phase III or pivotal clinical trials and 18 more molecules in early clinical stage. Innovent partners with over 30 global healthcare leaders, including Eli Lilly, Roche, Sanofi, Adimab, Incyte and MD Anderson Cancer Center.
Guided by the motto, "Start with Integrity, Succeed through Action," Innovent maintains the highest standard of industry practices and works collaboratively to advance the biopharmaceutical industry so that first-rate pharmaceutical drugs can become widely accessible. For more information, visit www.innoventbio.com, or follow Innovent on Facebook and LinkedIn.
Statement: Innovent does not recommend the use of any unapproved drug (s)/indication (s).
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SOURCE Innovent Biologics
FAQ
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