This article was published in Pharmaceutical Technology Europe’s July 2023 print issue.
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A novel complement therapeutic CTx001 offers a novel approach to treating geographic atrophy.
Complement Therapeutics (CTx) is a Germany-based preclinical stage biotechnology company focusing on the R&D of novel therapeutic approaches to address unmet needs in disorders that affect the body’s immune system, known as the complement cascade. The complement cascade is a part of the immune system that enhances (or complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen’s cell membrane (1). When activated by one of several triggers, the complement system works in conjunction with other components of the immune system to clear invading pathogens (1).
Based on the research of the company’s founders, Simon Clark, Paul Bishop, and Richard Unwin from the University of Manchester, CTx aims to develop innovative and effective therapeutics to address unmet needs in complement-mediated diseases, particularly in the fields of age-related macular degeneration (AMD), kidney disease, and various haematological conditions. Through an extensive programme of translational research, the scientists have gained powerful new insights into the ways the complement cascade works and how it is dysregulated in AMD.
Founded in 2020, CTx has subsidiaries in the United Kingdom (UK), operating as Complement Therapeutics Ltd, and in the United States (US), trading as Complement Therapeutics Inc., as well as research laboratories in Stevenage, UK.
Research conducted by Tracxn Technologies indicates that CTx ranks fourth among 94 active competitors (2). CTx’s key competitors include: CureVac, a Germany-based biopharmaceutical company that develops messenger RNA (mRNA)-based therapeutics focused on prophylactic vaccines, cancer immunotherapies, and molecular therapies. CureVac was the world’s first company to successfully use mRNA for medical purposes (3); Rezolute Inc. (formerly Antriabio), a US-based biopharmaceutical company specialized in the development of drugs for metabolic and orphan diseases. A leading candidate under development is a plasma kallikrein inhibitor (PKI) designed to treat diabetic macular oedema (DME). This oral therapy, formulated to be administered once a day, is designed to reduce inflammation and vascular leakage caused by DME through targeting the kallikrein-kinin system (4); and Visus Therapeutics Inc., a US-based clinical-stage pharmaceutical company that specializes in developing therapeutic solutions for vision care. One of the company’s flagship products includes VT-1051, a novel, injectable, sustained-release delivery system that delivers a Ciliary neurotrophic factor (CNTF) analogue and a FAS/TNF-α inhibitor which has the potential to preserve photoreceptors, prevent programmed cell death, and improve vision in patients suffering from geographic atrophy (GA) (5).
CTx was spun out of the University of Manchester and has raised a total of €77 million over three rounds of financing according to data derived from Crunchbase (6). In 2021, CTx secured initial seed funding from BioGeneration Ventures (BGV), subsequently receiving a further €5 million in Round 2 seed funding from BGV and Forbion in February 2022. With this funding, CTx advanced its lead investigational product, CTx001 through pre-clinical proof-of-concept, and secured an Innovation Passport from the UK Medicines and Healthcare Products Regulatory Agency (MHRA) (7). CTx001 is a highly innovative adeno-associated virus (AAV) gene therapy designed for the treatment of GA secondary to dry AMD, which is a leading cause of blindness, and for which no licensed treatment currently exists.
Through the financing received from BGV and Forbion, CTx also initiated a one-year, natural history non-interventional i-GAIN (investigating Geographic Atrophy Insights) study in patients who have a confirmed diagnosis of GA in one or both eyes in the UK (8). The study is designed to evaluate the relationship between genetics, blood biomarkers, and phenotypic changes in the eye of people with GA. Data derived from the i-GAIN study is designed to support the clinical development planning for CTx001, particularly in enabling the identification and stratification of patients with complement-driven AMD for future interventional studies (8).
More recently in April 2023, CTx announced that it had successfully secured an additional €72 million in Series A financing. The third round of financing was led by Gimv, a Belgian-based private equity and venture capital fund, co-led by Forbion (as an existing investor), and further joined by BGV, Panakès Partners, Cambridge Innovation Capital (CIC), Hadean Ventures and Seroba Life Sciences (9).With this latest round of financing, CTx will continue the development, as well as complete a Phase Ib clinical proof of concept of its lead product CTx001. The novel therapy is expected to have the potential to offer superior efficacy compared to competitive drugs, as well as reduce the burden of treatment among patients through a “one and done” approach (10).
This article was published in Pharmaceutical Technology Europe’s July 2023 print issue.
CTx will also use the funds to expand its laboratory-based activities at its site in Stevenage, UK, as well as evaluate its pipeline assets for non-ocular indications. According to Rafiq Hasan, CEO and managing director at Complement Therapeutics GmbH, “the support of this broad syndicate enables us to generate additional data demonstrating CTx001’s unique and differentiated mechanism of action, with the potential to transform the treatment landscape in [GA]” (9).
The financing will also be used to further develop the company’s novel Complement Precision Medicine (CPM) platform, which enables the quantification of over 30 complement cascade proteins from a single systemically drawn blood sample (11). The CPM platform will also facilitate the stratification of patients with AMD and other conditions for enrolment into future clinical trials, and support the subsequent commercialisation of CTx’s assets. According to Cipriani et al. (2021), the CPM platform has been validated in normal human samples and two distinct disease cohorts (12).
Alongside the financing, Michaël Vlemmix (Gimv), Rob Woodman (Panakès), Anne Horgan (CIC), and Roger Franklin (Hadean Ventures) will join the CTx board as new members.
AMD is a chronic and progressive degenerative disease of the macula, the central part of the retina (or the light-sensitive tissue at the back of the eye) that controls sharp, straight-ahead vision (13). AMD is a common condition that blurs a patient’s central vision and is a leading cause of blindness for older adults. Research conducted by Guymer et al. (2023) estimates that AMD is present in 8.69% of the global population, affecting 196 million people in 2020; and its prevalence is expected to increase to 288 million by 2040 (14).
According to the US National Eye Institute (NEI), dry AMD has three stages: early, intermediate, and late, with the disease usually progressing slowly over several years. Also termed GA, there is currently no treatment for late dry AMD, which is driven by a combination of factors including genetic predisposition, natural ageing changes, and lifestyle factors, such as smoking and nutritional intake. Genetic and molecular studies have identified the complement system as a key driver of AMD onset and progression, and there is increasing evidence that complement inhibition can slow the progression of GA (15).
Over the past few years, R&D efforts in the field of complement-mediated diseases have received the support of the US National Institutes of Health (NIH), which has awarded grants worth US$837 million for research in this domain (16). With enhanced funding and growing recognition of the complement system as a multidimensional innate immune surveillance mechanism, it can be expected that more novel therapeutic targets will be discovered in the future. CTx is therefore well placed to take advantage of potential future opportunities by addressing unmet needs in complement-mediated diseases, particularly AMD, to which it can strive to achieve market dominance and leadership position. With the active involvement of big pharma players as well as new entrants, the drug development landscape of complement therapeutics is likely to expand further with the market poised to witness steady growth over the coming years.
Bianca Piachaud-Moustakis is a lead writer at PharmaVision.
Pharmaceutical Technology Europe
Volume 35, No.7
When referring to this article, please cite it as Piachaud-Moustakis, B. Frontrunner in Therapies for Complement-Mediated Diseases. Pharmaceutical Technology Europe 2023 35 (7).