BeBetter Med is founded in 2012 by US scientists and aims to create advanced novel medicines to treat cancers and other severe diseases. Key developments include the first-in-class PI3K/HDAC dual inhibitor BEBT-908, in the NDA stage for refractory and recurrent DLBCL, the primary CDK4 inhibitor BEBT-209 and the Pan-EGFR inhibitor BEBT-109, in phase III clinical trials for advanced/metastatic breast cancer and NSCLC. Additionally, four other programs are in Phase I/II clinical trials.

BEBT-209 primarily inhibits CDK4 with a potency that is six times greater than CDK6, aiming to reduce the hematological toxicities inherited by broader CDK4/6 inhibitors. Phase II results in metastatic triple-negative breast cancer (mTNBC) patients with prior systemic therapy demonstrate a 43.5% objective response rate (ORR) and 6.7 mo progression-free survival (PFS), outperforming Sacituzumab Govitecan-hziy (SG, 31.0% ORR, 4.8 mo PFS), with comparable adverse events when combined with chemo. We plan to launch a global Phase III trial for mTNBC in 2025.

BEBT-503 is a potent and well-balanced pan-PPAR agonist, designed mainly for diabetes management in patients with metabolically dysfunction-associated fatty liver disease (MAFLD). Preclinical trials in a CDAHFD mouse model of diabetes with MAFLD indicated that BEBT-503 lowers baseline blood glucose, enhances glucose tolerance, and notably, does not cause weight gain. Phase I clinical trials in healthy individuals have been completed in Australia, revealing an excellent safety profile and good oral bioavailability. Phase Ib/II trials are underway for patients with diabetes, MAFLD, and primary biliary cholangitis.

BEBT-809 is a first-in-class, oral 20-HETE/GPR75 pathway inhibitor that demonstrates favorable efficacy and safety compared to GLP-1 drugs in animal models. Unlike GLP-1 agonists, which are injectable and primarily reduce body weight through food intake reduction, BEBT-809 effectively decreases body weight by up to 45% in diet-induced-obesity (DIO) mice without significantly altering food consumption. Additionally, it minimizes body weight rebound, enhances insulin sensitivity, and preserves lean muscle mass while reducing white adipose tissue. BEBT-809 also offers a significant safety advantage with over 200-fold safety margins, showcasing its potential as a novel, more compliant, cost-effective, and efficacious therapy for obesity and diabetes compared to GLP-1 drugs.

BeBetter Pharma is a US subsidiary of BeBetter Med. BeBetter Pharma leverages siRNA’s advantages in low off-target toxicity, high specificity, and long duration to deliver next-generation therapeutics for complex diseases. The company’s proprietary siRNA delivery platforms include: Peptide-Oligonucleotide Conjugates (POCs) and GalNAc Dual Oligonucleotide Conjugates (GDOCs). Current POC programs specifically bind to neuron proteins or renal cell receptors, silencing targeted gene(s) for precision treatment of central nervous system disorders and renal diseases. GDOCs enhance therapeutic impact by targeting multiple genetic pathways of multifactorial diseases.

Kidney-specific POC Platform enables selectively delivering an siRNA to renal proximal tubule epithelial cells (PTECs), offering a promising approach for treating various kidney-related diseases.  The siRNA therapeutics targeting URAT1 (BEBT-730) and EGLN1(BEBT-733) are designed to treat hyperuricemia/gout and chronic kidney disease (CKD)/anemia, respectively. 

BEBT-730 is specifically designed to deliver URAT1-targeting siRNA to PTECs, where URAT1 plays a central role in uric acid reabsorption.  It reduces URAT1 mRNA in the kidney cells up to 93% reduction at 10 nM and downregulates URAT1 protein in PTECs, improving uric acid levels and kidney functions in a diseased mouse model. No changes in body weight, food intake, liver, or kidney function markers are observed after repeat doses in non-GLP toxicity study in CD1 mice.

BEBT-733 is specifically designed to deliver EGLN1-targeting siRNA to PTECs, aims to reduce hypoxia-inducible factor (HIF) degradation, and mitigates kidney injury and anemia.  In an acute kidney injury (AKI) model, a single 5 mg/kg dose reduced EGLN1 mRNA levels by approximately 66.6% and improved serum creatinine and urea levels. In a chronic kidney disease (CKD) model, it improved hemoglobin (HGB) and hematocrit (HCT) levels. 

CNS-specific POC Platform enables selectively delivering an siRNA to brain neurons and offers a promising approach for treating various neuron-related diseases. The siRNA therapeutics targeting APP/MAPT (BEBT-756) and SNCA (BEBT-758) are designed to treat Alzheimer’s and Parkinson’s diseases, respectively.  

BEBT-756 is designed to deliver dual APP/MAPT siRNAs specifically to neurons to treat Alzheimer’s disease. Preclinical studies demonstrate significant gene silencing of APP and MAPT (tau) in key brain regions, addressing two critical hallmarks of Alzheimer’s pathology. This dual siRNA targeting approach offers the potential for enhanced efficacy by simultaneously inhibiting both pathways, potentially slowing disease progression more effectively. Furthermore, siRNA therapeutics may complement amyloid-targeting antibodies, which primarily block downstream pathological aggregates formed during advanced, irreversible stages of the disease. By reducing APP and MAPT mRNA levels, siRNA therapy tackles the root cause, directly decreasing the production of these culprit proteins.

BEBT-758 selectively silences the SNCA gene to reduce alpha-synuclein expression. Preclinical studies in mice demonstrate significant suppression of SNCA in critical brain regions, including the cerebral cortex, brainstem, hypothalamus, and cervical spine. Unlike SNCA antibodies that target late-stage pathological aggregates, BEBT-758 siRNA acts upstream by reducing SNCA mRNA, decreasing alpha-synuclein production at its source. This upstream intervention prevents misfolding, oligomerization, and aggregation, aiming to halt the disease's pathological cascade.

GDOC platform is designed to simultaneously silence two related individual mRNA targets, offering a promising approach for treating complex multi-pathway diseases such as metabolic disorders, in contrast to the requirement of combined single-targeting GalNAc-siRNA therapeutics to address multifactorial diseases.

BEBT-701 employs proprietary GDOC technology to target validated genes associated with hypertension (angiotensinogen, AGT) and hyperlipidemia (Proprotein convertase subtilisin/kexin type 9, PCSK9), offering a dual-action therapeutic approach. This innovative design harnesses the synergy of modulating multiple pathways with a single therapeutic molecule. Preclinical studies show that BEBT-701 achieves significantly higher efficacy than single siRNA therapies, with durable effects observed in both rodents and monkeys. Notably, non-GLP toxicity studies demonstrate a favorable safety profile, supporting its potential as a transformative treatment for cardiovascular and metabolic diseases.

 BEBT-720 leverages dual siRNA technology to target CIDEB and HSD17B13, introducing a multi-mechanism strategy for liver disease treatment. CIDEB plays a critical role in lipid droplet formation and metabolism, while HSD17B13 is associated with steroid metabolism and has protective effects against liver disease. By simultaneously silencing both genes, BEBT-720 addresses key drivers of liver pathology. Preclinical in vitro and in vivo studies demonstrate that BEBT-720 significantly reduces CIDEB and HSD17B13 expression, leading to a marked decrease in lipid droplet accumulation and liver fibrosis in MASH mouse models. These findings underscore the potential of BEBT-720 to mitigate liver damage and enhance overall liver health.