The 2024 AACR meeting wrapped up successfully in California, USA, showcasing the latest in innovative agents poised to enter clinical trials for cancer treatment.
The spotlight was on key targets such as CDK, KRAS, and WRN, covering various types of cancers and therapeutic approaches. Dominating the conversation were small molecule drugs, thanks to their versatility and ease of use, claiming half the market for anti-cancer therapies. “Radionuclide” drugs are getting more attention, and antibodies along with ADC macromolecule drugs made a significant impact at this conference. One may wonder, which antitumor agents stood out the most at this event? |
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| “First in class (FIC)” and “Best in class (BIC)” small molecules |
| Highlighting the event were FIC and BIC small molecules, known for their groundbreaking therapeutic potential and competitive edge in the oncology drug development landscape. This year’s AACR gathering saw the unveiling of numerous such innovations by various pharmaceutical companies[1]-[4]. |
| Drug Name |
Sponsor |
Target |
Conditions |
Clinical Trials |
Grade |
| RMC-9805 |
Revolution Medicines |
KRASG12D(ON) |
PDAC、
CRC、NSCLC |
Phase 1 |
FIC |
| ORIC-944 |
ORIC |
PRC2 |
MPC |
Phase 1/1b |
BIC |
| BBO-8520 |
BridgeBio Pharma |
KRASG12C |
NSCLC |
Phase 1a/1b |
FIC |
| CC-94676 (BMS-986365) |
Bristol Myers Squibb |
AR |
mCRPC |
Phase 1 |
FIC |
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| Biomolecules should not be underestimated: ABBV-303 and M3554 |
| At this year’s AACR meeting, AbbVie reported on ABBV-303, a novel c-Met targeted multispecific NK cell engager, currently in Phase 1 research. It was well tolerated in preclinical multiple-dose safety studies in non-human primates[5][6]. Merck reported on M3554, a novel anti-GD2 antibody drug conjugate, with preclinical data showing that M3554 demonstrated strong anti-tumor activity in PDX models of neuroblastoma, osteosarcoma, or glioma[7]. |
| The radiopharmaceuticals continue to heat up: Actinium-225-PSMA-Trillium (BAY 3563254) |
| Therapeutic radiopharmaceuticals—especially Radionuclide Drug Conjugates (RDCs)—are poised to revolutionize cancer treatment. Novartis has already introduced two RDCs to the market. At the conference, Bayer reported Actinium-225-PSMA-Trillium (BAY 3563254) for treating advanced metastatic castration-resistant prostate cancer through PSMA binding and subsequent radiation emission. Currently in Phase 1 trials, BAY 3563254 has undergone its initial evaluations for safety and imaging in humans[8]. |
| In addition, the AACR unveiled five promising small molecule anti-tumor drugs—AZD8421, ARV-393, NST-628, VVD-214, and PF-07220060. These compounds have demonstrated effective anti-tumor activity in vivo across various cancer models, including breast, colorectal, and prostate cancers [9]-[13]. |
MedChemExpress (MCE) continues to support cancer research by offering an extensive portfolio of over 25,000 Cancer Related Bioactive Molecules
and Cancer Related Compound Libraries, underlining the continuous innovation and development in the fight against cancer. |
| Product Name |
Description |
| RMC-9805 |
A highly selective covalent inhibitor of KRASG12D (ON). |
| PF-07220060 |
A selective CDK4 inhibitor. |
| ORIC-944 |
A selective, orally active, allosteric inhibitor targeting the EED subunit of polycomb repressive complex 2 (PRC2). |
| ARV-393 |
An orally active PROTAC that utilizes the ubiquitin-proteasome system to target the degradation of BCL6. |
| AZD8421 |
A selective CDK2 inhibitor. |
| BBO-8520 |
A direct small molecule covalent inhibitor targeting KRASG12C. |
| M3554 |
A novel anti-GD2 ADC. |
| BMS-986365 |
A selective heterobifunctional ligand-directed degrader (LDD) targeting the androgen receptor (AR). |
| Ac-PSMA-trillium |
A non-radioactive form of Actinium-225-PSMA-Trillium (BAY 3563254). |
| ABBV-303 |
A multi-specific NK cell antibody targeting c-Met. |
| VVD-214 |
A synthetic lethal allosteric inhibitor of WRN helicase. |
| NST-628 |
A brain-permeable MAPK pathway molecule glue that inhibits RAF phosphorylation and MEK activation. |
| PSMA binder-1 |
A ligand for PSMA and can be used to synthesize Ac-PSMA-trillium. |
| Lys(CO-C3-p-I-Ph)-OMe |
A pharmacokinetic modifier (PK modifier) that can improve the PK properties of PSMA ligand molecules. |
| Lys(CO-C3-p-I-Ph)-O-tBu |
A pharmacokinetic modifier (PK modifier) that can improve the PK properties of PSMA ligand molecules. |
| PSMA binder-2 |
A ligand for PSMA and can be used to synthesize Ac-PSMA-trillium. |
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References:  |
[1] Cancer Res 1 April 2023; 83 (7_Supplement): 526.
[2] https://clinicaltrials.gov/study/NCT05413421?term=ORIC-944&rank=1
[3] https://clinicaltrials.gov/study/NCT06343402?term=BBO-8520&rank=1
[4] Cancer Res 1 April 2024; 84 (7_Supplement): ND02.
[5] https://clinicaltrials.gov/study/NCT06158958?term=ABBV-303&rank=1
[6] Cancer Res 1 April 2024; 84 (7_Supplement): ND01.
[7] Cancer Res 1 April 2024; 84 (7_Supplement): ND08.
[8] https://clinicaltrials.gov/study/NCT06217822?term=BAY3563254&rank=1
[9] Cancer Res 1 April 2024; 84 (7_Supplement): ND06.
[10] Cancer Res 1 April 2024; 84 (7_Supplement): ND05.
[11] Cancer Discov. 2024 Apr 8.
[12] Cancer Res 1 April 2024; 84 (7_Supplement): ND11.
[13] Cancer Res 1 April 2024; 84 (7_Supplement): ND12. |
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