CinCor Pharma, Inc. ($INC): Founded in 2018. CinCor focuses on cardiovascular, metabolic and kidney diseases. The main development of the company is CIN-107, which is aimed at the treatment of hypertension and other diseases associated with high blood pressure.
CinCor is a biopharmaceutical company operating at the clinical stage and specializing in the development of a clinical drug, CIN-107, for the treatment of hypertension and other cardiovascular diseases. CIN-107 is a highly selective oral low molecular weight inhibitor of aldosterone synthase, an enzyme responsible for the synthesis of aldosterone in the adrenal glands. CIN-107 was developed to use a differentiated mechanism of action, direct inhibition of aldosterone synthase production, in order to provide improved treatment for patients suffering from hypertension or high blood pressure. Despite the widespread availability of several antihypertensive drugs, there remains a significant unmet medical need, as more than half of the 108 million patients with hypertension in the United States do not achieve blood pressure control.
The company evaluates the efficacy and safety profile of CIN-107 as a potential treatment for a wider population of hypertensive patients, including various subpopulations of patients with hypertension who failed to achieve blood pressure control despite treatment. The company is conducting a Phase 2 clinical trial of CIN-107 called BrigHtn in patients whose blood pressure is not controlled despite treatment with three antihypertensive agents, including a diuretic called therapeutically resistant hypertension or rHTN, and recently initiated a separate phase 2 clinical trial called HALO in patients with elevated aldosterone levels whose blood pressure is not controlled despite treatment with a single hypotensive agent, which is called uncontrolled hypertension or uHTN. In addition to hypertension, the company is developing CIN-107 for the treatment of primary aldosteronism, or PA, and is studying its usefulness for relieving complications of chronic kidney disease or CKD. Earlier this year, the company began Phase 2 clinical trials of CIN-107 in patients with confirmed PA, which is called the Spark-PA study, and it is planned to launch a phase 2 clinical trial in patients with CKD who have uncontrolled blood pressure in the first half of 2022.
Hypertension, which is defined by the American College of Cardiology and the American Heart Association as resting blood pressure above 130/80 mmHg, is generally considered the most common preventable risk factor for premature death worldwide. Although hypertension is often asymptomatic, it significantly increases the risk of heart disease, stroke and kidney disease, as well as other diseases. It is estimated that up to 20% of the world's population suffers from hypertension, and the US CDC estimates that up to 108 million Americans may have hypertension, and that hypertension costs the United States about $131 billion a year. Patients who fail to maintain blood pressure at 130/80 mm Hg. despite the fact that it corresponds to at least three antihypertensive agents, one of which is a diuretic, it is considered that it has rHTN. The population of patients with rHTN is approximately 17% to 20% of the total population of hypertensive patients in the United States, or approximately 12-15 million individuals. For these patients, treatment options are limited and the current standard of treatment is to add an MRA agent to their antihypertensive regimen. Patients with rHTN have approximately five times more cardiovascular events per 100 patient-years than patients with hypertension with blood pressure control.
Uniqueness of the idea and competitive advantages
Direct suppression of aldosterone synthesis has long been a goal in the development of therapeutic drugs, since the relationship between elevated aldosterone levels and the progression of many diseases has been well studied. However, the problem was to develop a molecule that could safely inhibit the production of aldosterone without adversely affecting the synthesis of cortisol. The main enzymes responsible for the synthesis of aldosterone and cortisol have approximately 93% similarity in amino acid sequences, therefore a highly selective inhibitor of aldosterone synthesis is required. Multiple programs developed by others have been discontinued over the past few years due to insufficient selectivity of their candidate products, which led to simultaneous inhibition of both aldosterone and cortisol. Inappropriate suppression of cortisol leads to a decrease in stress and immunological response, an adverse effect on metabolic functions and an increased risk of death.
The CIN-107 was designed with high selectivity specifically to solve this problem. In particular, CIN-107 selectively targets aldosterone synthase, which is encoded by the CYP11B2 gene. It is important to note that it has a low affinity for 11ß-hydroxylase, the enzyme responsible for the synthesis of cortisol, which is encoded by the CYP11B1 gene. In several preclinical studies in vivo, CIN-107 significantly reduced aldosterone levels, without affecting cortisol levels, in a wide range of doses. Similar observations were made in several phase 1 clinical trials on healthy volunteers. The company observed a dose-dependent decrease in plasma aldosterone levels in patients receiving a 10 mg dose, showing a decrease of approximately 85% to 90% in a single dose increasing trial, and in patients receiving a dose range of 1.5 mg to 5 mg, showing a 65% decrease. up to 71% reduction of the multiple ascending dose test. These decreases were compared with baseline levels measured the day before the initial intake and were not observed in placebo recipients. It is important to note that no effects on cortisol levels were observed at doses up to 360 mg, the highest of the estimated doses. In a trial of multiple increasing doses for doses up to 5 mg once a day administered for 10 days, no suppression of cortisol synthesis was observed.
To date, several phase 1 clinical trials of CIN-107 have been conducted on healthy volunteers to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of CIN-107. CIN-107 has been well tolerated by healthy volunteers in all Phase 1 clinical trials conducted to date, without serious adverse events or SAE, or adverse events occurring during treatment, or TEAE, leading to the cancellation of treatment associated with CIN-107.
In addition, a phase 1 clinical trial was conducted with subjects with varying degrees of renal function. One SAE unrelated to CIN-107 was observed in this trial.
Based on the currently available preclinical and clinical data, the company develops CIN-107 for multiple diseases in which aldosterone plays a significant role in the pathophysiology of diseases, including hypertension and PA. The company is also studying its usefulness for relieving complications in CKD.
The development and commercialization of new drugs is highly competitive. The company may face competition from large pharmaceutical companies, specialty pharmaceutical companies and biotech companies from around the world. Potential competitors also include academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection and create joint mechanisms for research, development, production and commercialization.
In particular, the company is facing competition from companies in the pharmaceutical, biotechnology and other related markets that are developing treatments for hypertension, PA and CKD. Competitors include Minerals Therapeutics, Damian Pharma AG, Dorsai Ltd., Quantum Genomics, Ionic Pharmaceuticals, Inc., Alnylam Pharmaceuticals, Inc., Sihuan Pharmaceutical and KBP BioSciences. More established companies may have a competitive advantage due to their larger size, resources, and institutional expertise. In particular, these companies have extensive experience and knowledge in providing cost recovery, government contracts and relationships with key opinion leaders, conducting trials and clinical trials, obtaining and maintaining regulatory approvals and relationships with distributors of products and approved medicines on the market. These companies also have significantly greater research and marketing capabilities.
The company was incorporated in March 2018 as a subsidiary of Cinr Pharma, LLC, a biotech company specializing in the development of new therapeutic drugs, or CinRx. Since its foundation, the company has focused primarily on raising capital, organizing and staffing the company, business planning, as well as acquiring and promoting the main product candidate, CIN-107, through clinical development after obtaining a compound license from F. Hoffmann-La Roche. Ltd and Hoffmann La-Roche Inc.
The company does not have candidate products approved for sale, and the company does not receive revenue from the sale of products. From its inception until September 30, 2021, the company financed its activities mainly through equity financing and received a total of about $185 million in gross proceeds from the sale of preferred shares.
In order to sell any product outside the United States, a company must comply with numerous and various regulatory requirements of other countries regarding safety and efficacy, as well as regulate, among other things, clinical trials, marketing authorization, commercial sales and distribution of the product. For example, in the European Union, it is necessary to obtain permission to apply for a clinical trial or CTA in each member state in which the company intends to conduct a clinical trial. The approval process varies from country to country and may include additional product testing and additional periods of administrative review. The time required to obtain a permit in other countries may differ from the time required to obtain an FDA permit, and may be longer than it is required. Regulatory approval in one country does not guarantee regulatory approval in another, but refusal or delay in obtaining regulatory approval in one country may negatively affect the regulatory process in others.
Marc de Garidel has been Chief Executive Officer and member of the Board of Directors since July 2021. Prior to his appointment as Chief Executive Officer, he served as Chief Executive Officer of AZTherapies, Inc. from September 2020 to April 2021. Mr. de Garidel serves on the Board of Directors of AZTherapies, Inc. and Claris Biotherapeutics, Inc. Until September 2020, Mr. de Garidel served as Chief Executive Officer of Corvidia Therapeutics, Inc. from January 2018 until their acquisition by the company. Novo Nordisk A/S in August 2020. Mr. de Garidel also served as CEO of Ipsen SA from November 2010 to July 2016, and since November 2010 - Chairman of the Board of Directors of Ipsen. Mr. de Garidel started his career at Eli Lilly Pharmaceutical Group in 1983, where he held various positions of responsibility before joining Amgen Inc. in 1995 as CFO in Europe. Mr. de Garidel graduated from the Ecole Spéciale des Travaux Publics and received a Master's degree in International Management from the Thunderbird School of Global Management.
Mary Teresa Coelho, MBA, has held the positions of Executive Vice President, CFO and Director of Business Development since November 2021. Ms. Coelho previously served as Executive Vice President, CFO and Treasurer of BioDelivery Sciences International, Inc. from January 2019 to October 2021. and as CFO and Treasurer at Balchem Corporation from October 2017 to October 2018. In addition, she also served as Chief Operating Officer of Diversey, Inc. From September 2017 to October 2017 and held senior financial positions in the Diversey Care division of Sealed Air Corporation from October 2014 to August 2017, including as CFO and Vice President of Global Commercial Excellence. She has been on the Board of Directors of First Wave BioPharma Inc. since August 2021 and currently serves as Chairman of the Audit Committee and member of the Compensation Committee at First Wave BioPharma Inc. Ms. Coelho received a Master's degree in Finance from Ibmec in Brazil and a Bachelor's degree in Economics and International Relations with honors from the American University School.
Catherine Pierce, MBA, D.HSc., co-founder of the company since 2018 and Chief Operating Officer since May 2019. Ms. Pierce previously served as Chief Operating Officer of CinRx and Vice President of Strategic Alliances at Medpace from September 2015 to August 2021. Ms. Pierce also served as Vice President of Research and Development at Teva Pharmaceutical Industries Ltd. from April 2013 to September 2015. Ms. Pierce holds a Bachelor's and Master's degree in Business Administration from Xavier University and a PhD from Nova Southeastern University.
Mason Freeman, MD, has been Executive Vice President for Clinical Development since August 2021, and a member of the Scientific Advisory Board since June 2019. Dr. Freeman is also a venture partner at 5AM Venture Management, LLC. May 2008. In addition, Dr. Freeman is the director of the Center for Translational Research at Massachusetts General Hospital. Previously, Dr. Freeman was a member of the Board of Directors of scPharmaceuticals Inc. from July 2018 to December 2020 and Crinetics Pharmaceuticals, Inc. from November 2015 to July 2019. Dr. Freeman holds a bachelor's degree from Harvard College and a Doctor of Medicine from the University of California, San Francisco.
Shareholders of the company
Sofinnova Venture Partners X, Sofinnova Capital IX, 5AM Ventures VI, CinRx Pharma, General Atlantic.