CanWell has antibody-drug conjugate (ADC), small molecule-drug conjugate (SMDC) and immune-stimulating antibody conjugate platforms, which have collectively yielded several products in preclinical and clinical development. All are designed to address the toxicity of established systemic chemotherapies by releasing their payloads only once they have reached a specific tissue.
Antibody-drug conjugates
StarLinker: CanWell’s ADC platform
CanWell’s ADCs are based on StarLinker, the company’s linker technology platform which makes it easy to maximize the therapeutic window by tailoring payload combinations and ratios. StarLinker is differentiated by its simplicity and flexibility – based on small molecule chemistry for which CMC is relatively easy, the technology can accommodate up to four payloads and is compatible with several conjugation methods including cysteine conjugation and click chemistry. Its linkers are hydrophilic, which reduces aggregation and improves stability and pharmacokinetics compared with hydrophobic linkers, and can be used with native antibodies, obviating the need for any antibody engineering.
CAN016
CAN016 is an ADC targeting HER2 developed using CanWell’s StarLinker platform and distinguished by its integration of two distinct MoA cytotoxic agents within a single antibody construct – a design expected to counter the resistance mechanisms that limit the efficacy of conventional single payload ADCs by enhancing anti-tumor activity through complementary mechanisms. In preclinical studies, CAN016 effectively delivered dual cytotoxic payloads into tumor cells leading to synergistic tumor cell killing, inhibition of proliferation, and apoptosis. It has also demonstrated potent anti-tumor activity in multiple CDX and PDX models, including those resistant to currently approved HER2-targeted ADC therapies. CAN016 is in Phase I to treat solid tumor patients who
have experienced disease progression following prior ADC therapies.
Small molecule-drug conjugates
CanWell’s SMDCs comprise a small molecule drug linked to a binder of tumor microenvironment proteins, limiting systemic exposure of the SMDC.
CAN1012
CAN1012 is a small molecule drug-conjugate and selective TLR7 agonist that activates plasmacytoid dendritic cells leading to an anti-tumor response including proinflammatory cytokine production and the priming of cytotoxic T-lymphocytes. Compared with other TLR7/8 drugs in clinical development, CAN1012 is differentiated by its superior solubility, potency, tissue retention and safety, selectively inducing efficacy-favorable cytokines over toxic cytokines and promoting a Th1 immune response by increasing CD4 and CD8 T cells while reducing myeloid-derived suppressor cells (MDSCs) and M2 macrophages. Clinical studies of CAN1012 as a monotherapy and in combination with checkpoint inhibitors targeting PD1 and CTLA4 are enrolling advanced cancer patients in both the US and China.
CAN2109
CAN2109 is a small molecule-drug conjugate that kills tumor cells both directly and by releasing tumor neoantigens that elicit adaptive immune activity, turning the tumor into an endogenous vaccine against itself. Administered intratumorally, CAN2109 is retained in the tumor microenvironment with minimal release to systemic circulation. CAN2109 entered Phase I in 2023.
Immune-stimulating antibody-drug conjugates
TLR agonists have shown encouraging antitumoral activities in clinical trials, although their safety and efficacy are limited. CanWell has developed several TLR-ADC conjugates with varying TLR7 or 8 selectivities using our proprietary TLR molecule library. Preclinical studies strongly demonstrate proof-of-concept results on molecule selectivity, chemistry conjugation, stability, in vivo PK, and efficacy in mouse tumor models.
Collaborations
