ConcarloTherapeutics
Combating Drug Resistance with Innovation

Although breast cancer is treatable in all stages—even stage 4, when it is widespread to various body parts—there is a pressing need to develop better, more effective treatments as the disease is the world's most prevalent women’s cancer, with over 7.8 million women diagnosed in the last seven years. The recent development of CDK4i drugs—a class of medicines that target the CDK4/6 pathway, which has been linked to a variety of cancers—has had a substantial impact on the quality of cancer care provision. However, despite initial extended durations of remission, most patients develop intrinsic resistance towards such therapeutics. At this juncture, Concarlo has developed IpY and a companion diagnostic, ApY, to effectively overcome CDK4i resistance and roll out a more tailored therapy approach for improved patient results.

With a comprehensive suite of drug development experts, Concarlo is a precision-medicine oncology firm that focuses on identifying and treating breast cancer using an innovative method to target a specific cellular target known as p27Kip1. "It is a woman-founded and run organization that is working toward revolutionizing the metastatic breast cancer field," says Dr. Stacy Blain, the company's Co-founder, & Chief Scientific Officer.

Concarlo's innovative and patented IpY, a novel therapeutic peptide, will be the first to address CDK2 resistance and the first to target p27 and inhibit both CDK4 (a common driver of cancer) and CDK2. Owing to its homology with other key targets, inhibiting CDK2 has proven problematic due to toxicity. Additionally, despite advances in available drugs, current treatments for cancer driven by CDK4 do not cause the durable arrest of tumors.

This is because patients become resistant to the drug, and as a result, for many patients, their overall survival rate does not change that significantly. The median overall survival rate for metastatic breast cancer patients hovers around 5 years.

Concarlo targets a specific cellular protein to kill tumor cells rather than slowing their proliferation. The company relies on the role of p27Kip1 — a vital "ON-OFF" switch that regulates the activities of major cancer-related proteins such as CDK4, CDK6, and CDK2. By targeting CDK4/6 and CDK2 with high specificity, Concarlo's solution avoids both resistance and toxicity. The precision-medicine oncology firm has demonstrated that as IpY is delivered to target cells, the therapeutic protein is released and binds to its target protein— p27Kip1. IpY inhibits proliferation in ER-positive breast cancer cell lines (MCF7 and T47D) and triple-negative (TN) breast cancer cell lines resistant to Palbociclib, suggesting its broader efficacy. In vivo, IpY is effective at treating Palbociclib-resistant breast cancer cell line xenograft models.

Many drug developers worldwide are trying to produce drugs that target CDK2 with different modalities. However, Concarlo uses a unique approach in producing a less toxic drug and can also cause tumor regression. The company also believes that the drug can be used as an alternative to chemotherapy. The oncology firm has conducted drug trials on mice with hormone receptor-positive breast cancer and triple-negative breast cancer. The results from these trials have been promising in improving efficacy and reducing toxicity.

However, as Concarlo is still in the preclinical stage, they need to conduct a series of studies and improve efficacy levels to get approval from the FDA to start testing the therapy in humans. Concarlo aims to have its first clinical trial done in 18 to 24 months. At present, the company has secured grants from SBIR (Small Business Innovation Research) and is on the lookout for colleagues, stakeholders, and investors to help the organization with its development and expansion visions. In line with its ideology of creating a cutting-edge 21st-century approach to cancer care that focuses on targeted therapies and diagnostics, Concarlo has also signed a contract with the NIH Nanoparticle Characterization Laboratory to conduct some IND-Enabling studies.