Concert Pharmaceuticals Advances Deuterated Drug CTP-543 into Phase 3 Trials for Alopecia Areata, Having Raised Over $300 Million to Date

Deuterium (D) is an isotope of hydrogen (H), commonly known as “heavy hydrogen.” Although deuterium is essentially identical to hydrogen in size and shape, the presence of an extra neutron makes the deuterium–carbon bond more stable than the hydrogen–carbon bond under the same conditions. Replacing some hydrogen atoms with deuterium in a drug molecule does not alter its fundamental pharmacological activity, but it does modify the metabolic rate and pathways, thereby changing its pharmacokinetic properties.This method is known as deuterium substitution technology.

Hydrogen-Carbon Chemical Bonds and Deuterium-Carbon Chemical Bonds (Image source: Concert Pharmaceuticals website)

Deuterium technology offers advantages such as enhanced and prolonged drug efficacy, reduced toxic side effects, shortened drug discovery and development timelines, and lowered R&D risks and costs, thereby garnering significant attention from the pharmaceutical industry both domestically and internationally. Numerous companies focused on deuterium-based new drug development have been established worldwide. Global pharmaceutical giants, including Pfizer, Novartis, Merck, AstraZeneca, Roche, Eli Lilly, and Bristol-Myers Squibb, have begun applying deuterium technology to develop new drugs. In China, pharmaceutical companies such as Zelt Bioscience, HaiChuang Pharma, Tongyuan Kang, and Chia Tai Tianqing are also accelerating their R&D efforts in deuterated drugs.

Concert Pharmaceuticals (NASDAQ: CNCE, hereinafter referred to as “Concert”) is also a member of the large cohort of companies engaged in the development of deuterated drugs.

Concert Pharmaceuticals was founded in April 2006, went public on the NASDAQ in the United States in 2014, and is headquartered in Lexington, Massachusetts. It is a publicly traded clinical-stage biopharmaceutical company.Concert has been deeply engaged in the field of deuterium technology for many years and is one of the earliest companies to research this technology. It is committed to leveraging its DCE Platform® (Deuterium Chemical Entity Platform) to develop innovative drugs for autoimmune diseases and central nervous system disorders.

Concert has been granted over 100 patents by the United States Patent and Trademark Office (USPTO), with multiple deuterated drugs acquired at high valuations by biopharmaceutical companies. It is currently developing a Phase III deuterated drug for alopecia areata. Concert’s long-term dedication and accumulated achievements in the field of deuterated drug development have positioned it as an industry leader.

Concert Pharmaceuticals collaborates with biopharmaceutical companies to apply its DCE platform to existing compounds with known therapeutic properties, including approved drugs, advanced clinical candidates, or previously studied bioactive compounds. Through this approach, Concert aims to achieve improved pharmacokinetic or metabolic profiles, thereby developing best-in-class therapeutics with enhanced clinical safety, tolerability, or efficacy.

Potential Advantages of Deuterium Technology (Source: Concert Pharmaceuticals Website)

Concert has established strategic partnerships with biopharmaceutical companies such as Avanir, Jazz Pharmaceuticals, Cipla Technologies, Processa Pharmaceuticals, and Vertex. Concert has licensed the development and commercialization rights of its deuterated drugs, including AVP-786, C-10323, JZP-386, CTP-354, CTP499, and VX-561 (formerly known as CTP-656), to the aforementioned biopharmaceutical companies, respectively, in exchange for milestone payments.

Among these, the asset purchase agreement between Concert Pharmaceuticals and Vertex amounted to nearly $300 million. In 2017, Vertex acquired the global development and commercialization rights to VX-561 (formerly known as CTP-656) and other assets related to the treatment of cystic fibrosis for $160 million in cash and $90 million in milestone payments. Subsequently, in 2021, Vertex paid an additional $32 million to acquire potential future milestones for VX-561, after which no further milestone obligations remained.

Strategic Partners (Source: Concert Pharmaceuticals Official Website)

Alopecia Areata (AA) is a common inflammatory, non-scarring hair loss condition, clinically characterized by well-demarcated, round or oval patches of hair loss. In severe cases, it can result in the complete absence of hair growth on the entire scalp or even the whole body.

Alopecia areata affects patients’ physical appearance, undermines their self-confidence, and leads to negative emotions such as anxiety and depression, thereby adversely impacting their mental health and quality of life. Furthermore, alopecia areata may be associated with various comorbidities, including allergic rhinitis, thyroid disorders, atopic dermatitis, and asthma.

Alopecia areata is currently believed to occur in the context of host genetic susceptibility, where factors such as oxidative stress, comorbid autoimmune diseases, neuropsychological factors, pathogens, immune checkpoint inhibitors, and microbiome dysbiosis can all contribute to the loss of hair follicle immune privilege and trigger autoimmune responses. Among these, the interferon-gamma (IFN-γ) storm mediated by the JAK/STAT signaling pathway plays a crucial role in the pathogenesis of alopecia areata. Janus kinases (JAKs) are a group of enzymes that play important roles in the immune system. Studies have shown that inhibiting JAKs may help treat certain immune-mediated diseases.

Concert Pharmaceuticals’ investigational candidate CTP-543 is a deuterium-modified form of the JAK1/2 inhibitor ruxolitinib, designed for the treatment of alopecia areata. Ruxolitinib has been approved in the United States and is marketed under the brand name Jakafi for the treatment of certain hematologic disorders. Deuterium modification of ruxolitinib can alter its human pharmacokinetics, thereby enhancing its therapeutic potential for alopecia areata.

The Phase 2 clinical trial of CTP-543 demonstrated its potential in the treatment of alopecia areata. This Phase 2 study was a double-blind, randomized, placebo-controlled, sequential dose-ranging trial that enrolled 149 patients to evaluate the safety and efficacy of CTP-543 in adults with moderate-to-severe alopecia areata. The results showed that patients treated with CTP-543 at doses of 8 mg or 12 mg twice daily achieved the primary efficacy endpoint: a ≥50% reduction from baseline in the Severity of Alopecia Tool (SALT) score at 24 weeks, which was statistically significant compared with placebo.

CTP-543 has been granted Breakthrough Therapy and Fast Track designations by the FDA. Concert Pharmaceuticals is now further evaluating the efficacy and safety of CTP-543 in adults with moderate-to-severe alopecia areata (≥50% scalp hair loss) as part of its THRIVE-AA Phase 3 clinical program.

The THRIVE-AA clinical program comprises two international Phase 3 studies, THRIVE-AA1 and THRIVE-AA2, both of which have completed enrollment. Concert Pharmaceuticals plans to report data from these trials in 2022. According to the current timeline, if both Phase 3 trials yield positive results, Concert Pharmaceuticals intends to submit a New Drug Application (NDA) for CTP-543 to the U.S. Food and Drug Administration (FDA) in early 2023 for the treatment of moderate-to-severe alopecia areata in adult patients.

Although Concert Pharmaceuticals has extensive experience in drug development, the process of developing new drugs is not always smooth sailing.

On February 1, 2021, Concert Pharmaceuticals announced that its investigational drug CTP-692 failed to meet primary and secondary endpoints in a Phase 2 study. CTP-692 is a novel deuterated D-serine for adjunctive treatment of schizophrenia.

The failure of CTP-692’s development inflicted significant damage on Concert. As of December 31, 2021, its closing stock price had fallen to $3.15.

According to the financial report released by Concert on March 3, 2022, the net profit attributable to common shareholders of the parent company for the fourth quarter of fiscal year 2021 was -$36.129 million, a year-on-year decrease of 61.36%.

However, as a biopharmaceutical company with 16 years of history, Concert’s potential in deuterated drug development continues to create significant opportunities for its future. As previously mentioned, Concert has been granted more than 100 patents by the United States Patent and Trademark Office (USPTO) and has established strategic partnerships with numerous biopharmaceutical companies through its portfolio of deuterated drugs.

Furthermore, the sustained investor confidence in Concert Pharmaceuticals underscores its value in drug development. Since its establishment in 2006, Concert has completed eight rounds of financing, raising a total of over $340 million.

The company name “Concert” can be deconstructed into three parts: CO, NCE, and RT. CO stands for “Company”; NCE refers to New Chemical Entity, commonly known as a “completely new drug” in the traditional sense; and RT represents Dr. Roger Tung, the company’s founder. Thus, the full company name can be interpreted as “Company of NCE by Roger Tung,” reflecting the founder’s expectation that the company would focus on the research and development of new drugs.

Dr. Roger Tung, a Vietnamese-American, has served as President and Chief Executive Officer and as a member of the Board of Directors since the founding of Concert Pharmaceuticals in 2006. Dr. Tung holds a Bachelor of Arts degree in Chemistry from Reed College and a Ph.D. in Medicinal Chemistry from the University of Wisconsin–Madison. Prior to founding Concert Pharmaceuticals, Dr. Tung held positions at several biopharmaceutical companies and institutions, including Vertex Pharmaceuticals, a multinational pharmaceutical company based in the United States; Shire plc, a global healthcare provider; Dompe Research Laboratories; and the Bristol-Myers Squibb Pharmaceutical Research Institute. Dr. Tung oversaw the research and development of five drugs for the treatment of HIV, hepatitis C, and cystic fibrosis, and is an inventor on several of these drug candidates.

Concert CEO Dr. Roger Tung (Image source: Concert official website)

Under Dr. Tung’s leadership, Concert Pharmaceuticals has traversed 16 years, evolving from an obscure small company into a leader in deuterated drug development, with Dr. Tung playing a pivotal role. Leveraging his decades of experience in the biopharmaceutical industry and the collective efforts of the team, Concert is poised to continue achieving new breakthroughs in novel drug development in the future.