On April 13, 2023 Simcere Zaiming (Company), a pharmaceutical company focused on developing drugs to address unmet clinical needs for cancer patients around the globe, and subsidiary of Simcere Pharmaceutical Group Limited (2096.HK) (Simcere), a global pharmaceutical company, reported that two oral and six poster presentations will be presented on the Company’s preclinical programs at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, taking place April 14-19, 2023, in Orlando, FL (Press release, Jiangsu Simcere Pharmaceutical Company, APR 13, 2023, View Source [SID1234630061]).
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The AACR (Free AACR Whitepaper) annual meeting is one of the most influential oncology conferences of the year and attracts tens of thousands of scientists and clinical experts to share and discuss the latest progress in basic research, translational research, clinical research and prevention research in the field of oncology.
Today’s announcement marks a significant milestone for the company as it will be the first time Simcere Zaiming will participate in an international academic conference as an independent oncology entity with multiple studies, including on-site oral presentations. The eight studies cover several targets including SMARCA2, CBL-b, Polθ, SOS1, MUC17, USP1, SIRPα, GPRC5D, and involve multiple novel technologies such as targeted protein degradation, mutant fusion proteins, bispecific T engager and others.
Oral Presentations:
Title: Identification of a high selective SMARCA2 degrader which effectively suppresses the SMARCA4-deficient tumors M vitro and in Wvo
Session Type: Minisymposium
Session Category: Experimental and Molecular Therapeutics
Session Title: Innovative Therapeutic Approaches
Session Date/Time: Sunday Apr 16, 2023 3:00 PM – 5:00 PM
Location: Room W331
Abstract Presentation Number: 1137
Presenter: Dr. Zhengtao Li, Vice President, Simcere Zaiming
Targeting the "synthetic lethal" partner proteins SMARCA2/4 (human chromatin SWI/SNF- Related, Matrix-Associated, actin-dependent regulatory factor subfamily A member 2 and 4), SCR-9140 selectively degrades SMARCA2 to precisely kill SMARCA4-deficient tumors in preclinical studies while preventing damage to normal cells, thus exhibiting strong antitumor efficacy and favorable safety profile.
Title: Identification of the selective CBL-b inhibitors which effectively prevent T cells from exhaustion and demonstrate synergistic anti-tumor activity in combination with an anti-PD1 antibody
Session Title: Immune Checkpoints at Tumor Beds
Session Date/Time: Monday Apr 17, 2023 2:30 PM – 4:30 PM
Abstract Presentation Number: 3474
Presenter: Dr. Tamas Oravecz, Senior Vice President, Chief Scientific Officer, Simcere Zaiming
The E3 ubiquitin ligase CBL-b (Casitas B-cell lymphoma protein b) negatively regulates immune function and is considered a potential novel intracellular immune checkpoint. In preclinical studies, a group of Cbl-b inhibitor candidate drugs developed by Simcere Zaiming have demonstrated strong immune activation capabilities and synergistic effects with PD-1 inhibitors, suggesting strong potential for clinical application.
Poster Presentations:
Title: Identification of SS008871, a novel Polθ inhibitor that effectively inhibits tumors with homologous recombination deficiency in vitro and in vivo
Session Title: Experimental and Molecular Therapeutics, Novel Antitumor Agents 2
Session Date and Time: Sunday Apr 16, 1:30 PM – 5:00 PM
Location: Poster Section 18
Poster Board Number: 12
Abstract Number: 512
DNA polymerase θ (Polθ) is a key enzyme for DNA double-strand break repair and cell survival in homologous recombination-deficient tumors, and it is also a potential synthetic lethal new therapeutic target. The small molecule inhibitor of Pol θ, SS008871, has shown significant anti-tumor effect and good safety in various preclinical models.
Title: SCR-8388, a potent and selective SOS1::KRAS inhibitor, is effective in KRAS-addicted cancers
Session Title: Oncogenes and Tumor Suppressor, Genes as Targets for Therapy 2
Session Date and Time: Monday, Apr 17, 9 AM – 12:30 PM
Location: Poster Section 20
Poster Board Number: 21
Abstract Number: 1724
The most common oncogene, KRAS, was once regarded as the most difficult drug target, and there was a large unmet clinical need. SCR-8388 is a selective SOS 1 protein inhibitor that acts on the upstream pathway of KRAS and prevents KRAS activation. Preclinical studies have shown that SCR-8388 can significantly inhibit the growth of KRAS mutant tumors in both in vitro and in vivo models, and has a synergistic effect with EGFR antagonists.
Title: SCR-9171, a MUC17-targeted bispecific T cell engager molecule for gastrointestinal cancer
Session Title: Immunology, Therapeutic Antibodies 1
Session Date and Time: Monday Apr 17, 9:00 AM – 12:30 PM
Location: Poster Section 25
Poster Board Number: 21
Abstract Number: 1882
MUC17 is a transmembrane mucin that is often overexpressed in gastric cancer tissues and is also a potential target for gastric cancer therapy. SCR-9171 is a MUC17/CD3 bispecific T cell engager that precisely inhibits MUC17 expressing tumors with optimal CD3 affinity. In preclinical studies, SCR-9171 induces T cell activation, thereby potently killing MUC17-positive tumors, while releasing low level of cytokines that can lead to better treatment tolerability.
Title: A novel T cell engager targeting BCMA and GPRC5D showed promising preclinical activity with low toxic risk for multiple myeloma treatment
Session Title: Immunology, Therapeutic Antibodies 1
Session Date and Time: Monday Apr 17, 9:00 AM – 12:30 PM
Location: Poster Section 25
Poster Board Number: 22
Abstract Number: 1883
SCR-8572, a T-cell engager developed against two specific targets in multiple myeloma, BCMA and GPRC5D, demonstrated potent tumor-killing effects in preclinical in vitro and in vivo models, with preliminary good safety results. It is expected to become a candidate drug for clinical development.
Title: Identification of SP-002, a highly selective USP1 inhibitor effectively inhibits HRD tumor growth and displays low hematotoxicity risk
Session Title: Experimental and Molecular Therapeutics, DNA Repair / Molecular Classification of Tumors for Diagnostics, Prognostics, and Therapeutic Outcomes / Others
Session Date and Time: Wednesday Apr 19, 9:00 AM – 12:30 PM
Location: Poster Section 18
Poster Board Number: 3
Abstract Number: 6201
USP1 (ubiquitin-specific peptidase 1) is a synthetic lethal protein of HRD (homologous recombination deficient) tumors. As a highly selective USP1 inhibitor, SP-002 has significant anticancer activity against HRD tumors as a single drug or in combination with PARP inhibitors in preclinical in vitro studies. Furthermore, no significant hematological toxicity was observed.
Title: Generation of a mutant SIRPa fusion protein with highly-improved affinity and favorable safety profile
Session Title: Immunology, Immune Checkpoints
Session Date and Time: Wednesday Apr 19, 9:00 AM – 12:30 PM
Location: Poster Section 23
Poster Board Number: 1
Abstract Number: 6357
Interaction of the transmembrane glycoprotein CD47 with signal regulatory protein alpha (SIRPα) triggers "don’t eat me" signaling to the macrophage, thereby serving as a key immune checkpoint in a variety of hematological malignancies. SCR9168 is a SIRPα mutant protein fused with Fc, which has significantly improved CD47 affinity, and has good safety in various animal models including cynomolgus monkeys and has best-in-class potential of SIRPα mutant protein in the treatment of hematological tumors.