CIO Bulletin

Creating novel, innovative methods to combat drug-resistant and metastatic breast cancer—Concarlo Therapeutics

Cancer is the second leading cause of death in the US. In 2017 alone, about 1.7 million people were diagnosed with cancer, and 0.6 million people died from the disease. Drug resistance and the resulting ineffectiveness of the drug treatment are responsible for up to 90% of the cancer-related deaths

Drug resistance in cancer is a well-known phenomenon when cancer becomes tolerant to pharmaceutical treatment. Current treatments for cancer management include surgery, cytotoxic chemotherapy, targeted therapy, radiation therapy, immunotherapy, and endocrine therapy. Even though chemotherapy is central to the clinical management of cancer, failure in chemotherapy is not uncommon, mainly due to the dose-limiting toxicities associated with the occurrence of drug resistance. Resistance to anticancer drugs arises from various factors, such as genetic mutations or epigenetic changes, conserved but up-regulated drug efflux, and various other cellular and molecular mechanisms.

More and more targeted drugs have been developed to precisely target/block changes that drive growth and proliferation in recent decades.

One of the companies leading the charge of innovation for combating drug resistance in cancer is Concarlo Therapeutics. Concarlo Therapeutics is a Brooklyn, New York-based precision-medicine oncology company focused on diagnosing and treating cancer with an innovative approach to targeting a unique cellular pathway - p27Kip1. Concarlo targets the unique p27Kip1 cellular pathway to kill—not just stop the growth of— tumor cells. They use the p27Kip1 cellular pathway — a key “ON-OFF” switch that modulates the activities of critical proteins involved in many cancers: CDK4, CDK6, and CDK2 to avoid resistance problems toxicity by targeting the vital proteins with high specificity.

In conversation with Dr. Stacy Blain, Co-founder, Chief Scientific Officer, and acting CEO of Concarlo Therapeutics

Q. What makes Concarlo different from the crowd?

We are a founder- and women-led company addressing a crucial women’s issue: metastatic breast cancer.

Q. How is Concarlo the solution for breast cancer?

p27 is a novel target that controls the activity of CDK4/CDK6 and CDK2. Drugging CDK4/6/2 has been challenging due to the similarity of these targets with other proteins in the cell. Available drugs to CDK4/6 and CDK2 frequently have “off-target” effects, which leads to unwanted toxicity, preventing patients from staying on therapy. By targeting p27 instead of the highly conserved CDKs, Concarlo’s drug, IpY, inhibits the CDK4/6/2 targets precisely and with low toxicity. Additionally, instead of just slowing tumor growth, IpY kills tumor cells, causing tumor regression. It has activity in tumors that have become refractory to several first and second-line therapies, so it should be an effective alternative to chemotherapy for our patients.

Q. What is the hallmark of Concarlo’s R&D mission and technologies?

Concarlo is a pre-clinical oncology company developing therapies to combat drug resistance. We have multiple, unique approaches to drug p27, which has the distinct ability to inhibit CDK4/CDK6 and CDK2, three of the most critical drivers of cancer and resistance in the human body.

Q. What strategies do you use for marketing your business?

Concarlo is currently raising money to finish manufacturing our drug, IpY, to move to the Investigational New Drug (IND)stage of starting human clinical trials. We intend to take our medicine to Phase 1 and then actively seek strategic partners to help with the rest of the development pathway.

Q.How have your priorities changed from when you first started?

Our priority has remained the same: to deliver a new modality in the fight against metastatic breast cancer. What we have learned along the way is that our approach may have validity in other drug-resistant tumor types, so we are expanding our path to incorporate diagnosing and treating them too.

Q. What, according to you, are the qualities of a good entrepreneur?

A good entrepreneur is someone who has the vision and then actively seeks out the team to help carry that vision forward. They are also someone who can listen to and assimilate other people’s opinions to make data-driven decisions. Finally, they are someone who can sell the mission and opportunity to investors and MAKE the dream happen.

The innovator driving Concarlo Therapeutics to create new treatment methods to help people with cancer

Dr. Stacy Blain is the co-founder, Chief Scientific Officer, and acting CEO of Concarlo Therapeutics. Dr. Blain is a tenured faculty member at the State University of New York, an internationally recognized expert in the cell cycle and cancer biology, and studying the targets that Concarlo has been drugging for more than 25 years.

Her work has been published in top-tier journals; she has presented at numerous national and international meetings. She has received research funding from the NIH, the American Cancer Society, the Susan G. Komen Breast Cancer Fund, and the METAvivor Foundation. She is a decorated teacher, mentor, and educational leader. She has successfully led Concarlo from its academic inception to a company with pre-clinical assets, currently in manufacturing, with the goal of FIH in 2 years.

Dr. Blain and Concarlo have been finalists in the AIM HI Women’s venture competition, a winner of the RESI Innovator award, and the recipient of an SBIR Phase 1 award. Dr. Blain received her BA from Princeton University, her Ph.D. from Columbia University, and her postdoctoral work with Dr. Joan Massague at the Memorial Sloan-Kettering Cancer Center.