THE CASE FOR CONCARLO: CLEANING UP WHAT PRECISION ONCOLOGY LEAVES BEHIND

Advances in precision oncology have made the outlook for those with cancer more hopeful than ever. Through molecular profiling and genetic sequencing, medical professionals are now matching patients with the treatments that stand the highest likelihood of success. For example, if a woman has breast cancer that expresses high amounts of the estrogen receptor, she is a candidate for newer, more effectively targeted therapies such as the aromatase inhibitor Femara® or the estrogen receptor downgrader Falsodex®. Yet, despite this great progress, more than 600,000 patients continue dying each year in the U.S. from cancer. Sadly, even the most optimistic post-procedure patient meetings still end with an awkward discussion about the realities of what may have been left behind.

 

As a scientist who has studied cell-cycle and cancer biology for more than 25 years, and as someone with many brave, cautious “survivors” in my close circle of friends, a few years ago I found myself asking, “Is this as good as it gets?” And the follow up was, “If not, what are you going to do about it?” I had worked in the cell cycle/cancer biology field for several decades and in 2017, I founded Concarlo Therapeutics because I saw the possibility to leverage my expertise in p27Kip1 (p27) biology as a uniquely powerful pathway for cleaning up what precision oncology leaves behind. Concarlo is named after my three kids (Connor, Carly and Logan) as a reminder of why I do what I do: to change outcomes for their generation. 

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At its most basic description, cancer is a disease of uncontrolled cell growth. Cells normally receive signals to start or stop growing, but a cancer cell ignores those signals and proliferates constantly. The oncology field has generated numerous drugs that create blockades that target the top or middle of what I call the “oncogenic funnel” –  the series of signals that flow from the cell surface to the cell’s brain or nucleus, where the real “motors” of proliferation lie. But, by targeting at the top or the middle, these drugs frequently leave room for the tumor to evolve through mechanisms toward the bottom of the funnel, which can evade those blockades. Targeting at the bottom of the funnel is always going to be best, the same way it is always easier to pinch off the bottom of a water funnel. The “motors” exist in the bottom of the funnel and are an ensemble of proteins called CDK4/6, CDK2 and their regulator, p27. At Concarlo, we are developing inhibitors to p27, which will in turn inhibit CDK4/CDK6 and CDK2, which are the three main drivers of cancer and drug resistance. The p27 target is a highly unique cell-cycle protein: it has the ability to control both CDK4/CDK6 and CDK2, it is relatively rare in the cancer genome, so there is less cross reactivity of p27-targeting drugs with other proteins, resulting in less toxicity than other approaches. Concarlo has developed both large molecule, biologic, and small molecule approaches to drug this target. Our goal is to become the world leader in p27 biology as a way to combat drug resistance across numerous tumor types. 

 

Our lead therapeutic, IpY.20, is currently in manufacturing with the goal of beginning our FIH clinical trial within two years. During this time, we will perform safety/toxicity studies, design our clinical trial, and produce our GMP batches to initiate our IND application. In 2021, sales of CDK4i drugs topped $7 billion, and, regrettably, most of the 37,000 eligible metastatic patients using these therapies became resistant. 

 

We intend to enter the market as an alternative to chemotherapy for metastatic drug-resistant breast, ovarian, uterine and pancreatic cancer patients. Our IpY.20 therapeutic has important differentiators to impact outcomes among these patients: 

  1. High selectivity for the p27 target resulting in low toxicity; 

  2. The ability to kill-not just stop the growth of-tumor cells, which results in tumor regression; and 

  3. The ability to combine with other targeted therapies to clean up what precision oncology leaves behind. 

 

We have shown preclinical efficacy in metastatic breast cancer, ovarian, uterine and pancreatic cancer models, demonstrating the potential wide clinical utility of this approach. We have raised $6.6M to date and are currently raising $4M in a pre A round at $25M pre-money with the goal of finishing CMC of IpY and validation of our small molecule hits.

 

As a female-founded organization, we are intensely driven to achieve our mission, which holds such promise for women, who are disproportionately affected by many of these cancers. We have assembled a world-class team of scientists, drug developers, and scientific advisors with the intellectual capital and expertise to transform the treatment landscape of drug resistant cancers. Now, as we scale-up clinical trial material for our first-in-human clinical trials with our lead therapeutic candidate, we invite you to learn more about our work and how you can aid us in our important mission. Together, we look forward to creating a world of possibility and time, where cancer is a very treatable, manageable and survivable condition. Join us. www.concarlo.com