BTX-1188, our lead product candidate, is a rationally designed dual-targeting molecular glue degrader of GSPT1 and IKZF1/3 that we are developing for the treatment of acute myeloid leukemia and solid tumors. We believe that the combination of degrading GSPT1, a promising oncology target, and IKZF1/3, clinically validated immunomodulatory targets, provides advantages relative to GSPT1-only degradation.

We have a broad discovery program leveraging parallel in silico and in vitro approaches to identify novel neosubstrates that could be degraded by Cereblon-based molecular glues. This effort has already identified several potential new targets previously considered undruggable and with relevance across a range of cancers. We look forward to translating these efforts into novel molecular glue programs in the future.

We are developing degraders of Son of Sevenless 1 (SOS1), an important upstream target in the Kirsten rat sarcoma virus (KRAS) pathway. We are also in early stages of discovery in developing degraders directly targeting KRAS. KRAS is the most frequently mutated cancer-causing oncogene and is mutated in over 20% of all human cancers, including an estimated 90% of pancreatic tumors, 45% of colorectal tumors, and 30% of lung tumors. In preclinical models, we have demonstrated that our lead candidates rapidly and potently degraded SOS1 by up to 90% with inhibition of pan-KRAS mutant cancer cell lines.

We are developing degraders of cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6), important targets for a range of cancers and clinically validated in the context of breast cancers. In preclinical breast cancer models, our lead candidates potently degrade CDK4 and CDK6, resulting in robust inhibition of phosphorylated Rb and cell cycle arrest. We believe our degraders of CDK4 and CDK6 will enable treatment of the up to 20% of patients with intrinsic resistance and the up to 70% of patients with acquired resistance to CDK4 and CDK6 inhibitor approaches.

In addition to our degraders of cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6), we are also developing degraders with additional degradation of cyclin-dependent kinase 2 (CDK2), which we believe will broaden the potential patient populations that could be addressed by our CDK-targeting degraders. Upregulation in the CDK2/4/6 pathway is a key driver of a range of cancers, including 30% of breast and esophageal cancers, 50% of pancreatic and 40% of bladder cancers. In preclinical models, we have shown that our degraders can potently and selectively degrade CDK2, CDK4 and CDK6, avoiding important off-target CDKs such as cyclin-dependent kinase 1 (CDK1) and Aurora kinase.

We are developing degraders of Phosphodiesterase 4 (PDE4), a validated target for auto-immune and inflammatory diseases such as psoriasis. Our first-in-class degraders are highly selective for PDE4 degradation and have shown greater potency than PDE4 inhibitors in terms of inhibition of key cytokines such as TNF-α, IFN-γand IL-1β in preclinical models.