Engrail, the 'biotech' that aims to treat anxiety with the support of Ysios

To respond to the needs of patients with neuropsychiatric disorders and life-limiting rare diseases through innovative treatments. This is the objective of the American biotechnology company Engrail Therapeutics, which recently raised 157 million dollars in a financing round that included a significant investment from Ysios Capital.

The venture capital firm, with offices in Barcelona and San Sebastián, has bet on the company due to its varied pipeline of drugs and the promising expectations of its main and most advanced investigational treatment, which is in development for generalized anxiety disorder. Engrail's scientific expertise in molecular mechanisms and the neurocircuits underlying nervous system disorders is the lever on which its work has been based since its founding in 2019.

Since its inception, the biotech had a clear focus: neuroscience, in a context where large pharmaceutical companies reduced it due to the high resources it requires and the high risk it entails. "We recognized that there was an opportunity to approach neuroscience drug development with greater precision and generate significant value for patients, physicians, and our investors," explains to The New Barcelona Post Engrail's President and CEO, Vikram Sudarsan, along with Ysios Capital partner Guillem Laporta and Engrail's Head of Commercial Strategy, Camilla Gomiero.

With four drugs in development, Engrail works with a varied pipeline focused on neuropsychiatric disorders and rare diseases

Thus, finding an effective treatment for anxiety disorders without severe consequences represents an "unmet medical need," on which Ysios focuses its work, as Laporta recalls. The partner of the management company, familiar with Vikram's work from a previous investment in a pharmaceutical company of which the neuroscientist was a part, highlights that the results of the preclinical phase of Engrail's drug yielded encouraging results, which were reproduced in the first phase of the clinical study. Thus, pending definitive results to be obtained in current and future phases, ENX-102 "seems to have a very favorable profile and represent a promise for the future."

Currently, the drug is in phase II, during which its effects on large numbers of patients will be evaluated, and results will be available in 2025. The biotechnology company, which has raised 220 million dollars since its foundation, focuses this drug especially on patients with chronic anxiety, as Gomiero explains. This is because benzodiazepines can only be administered for short periods of time due to their addictive power, while, according to the results obtained so far, the addictive potential of ENX-102 is much lower.

The dependence they generate is not the only limiting side effect of benzodiazepines, which also cause cognitive impairment, dizziness, weakness, and drowsiness. This implies that these drugs increase the probability of suffering a traffic accident by 60%, so contributing to reducing their use would not only benefit specific patients but society in general, as Laporta highlights. These effects are notably intensified when combined with alcohol, while the drug being developed by Engrail appears not to have the same interaction with its consumption.

ENX-102 is included in a pipeline of drugs being developed by Engrail that address neuropsychiatric disorders and rare neurodevelopmental diseases. ENX-104 aims to combat a core component of severe depression, anhedonia. According to Gomiero, anhedonia consists of the "inability to feel pleasure," which the drug addresses by increasing dopamine release. Current therapies do not specifically treat anhedonia: "Depression is generally treated in a standard way instead of adapting therapy to the specific symptoms patients experience. It is important to differentiate patients and address their specific needs," says Gomiero. Also in the neuropsychiatric field, Engrail is developing ENX-105, which has a unique profile and carries significant potential for the treatment of post-traumatic stress disorder, bipolar disorder, and anxious depression.

Combating the deadly Menkes disease

Neuropsychological disorders are not Engrail's only target. Based on research published in 2020, the biotech recognized the potential of a drug for Menkes syndrome, an extremely rare and fatal neurodegenerative disease. The disease is of genetic origin, so it mainly affects children, whose life expectancy is reduced to very early ages due to this syndrome. It is caused by a genetic defect that causes copper to be abnormally distributed in the body, leading to serious consequences including cognitive impairment and reduced neurological development, decreased strength and muscle capacity, and ultimately, death.

Engrail is developing ENX-103 with the aim of improving copper distribution in the brain and the rest of the body to promote neurological development and prolong life. And in this process, a particularly relevant Spanish patient is playing a significant role. Through special government authorization, this patient began treatment with the components of ENX-103 more than two years ago and, so far, has shown very promising signs of improvement.

"He is playing an immense role in the work to understand the role of this drug in humans," Sudarsan highlights in recognition of the patient and his family, as well as research centers in Spain that are involved in the process. "Barcelona has contributed greatly to the understanding of this disease, and Spain in general has a great role to play in terms of rare diseases." In this sense, Sudarsan believes that the authorities have "humanized the approach to patients and these diseases, from a practical perspective." And it is that patients with orphan diseases desperately require treatments, which is why the collaboration of regulators is necessary to move them as quickly as possible.

For Ysios, "it is crucial that this willingness of regulatory authorities exists," Laporta emphasizes. The partner of the venture capital firm highlights the importance of investing not only in areas that affect a large number of patients, but "in areas where there is an immense unmet need, even if few are affected." Laporta has valued the fact that Engrail also focuses on this area, and has praised the diversity of its pipeline. "Investing in Engrail is like placing the investment in multiple companies, due to the variety of its drugs." Thus, this investment contributes to diversifying the portfolio of Ysios, which has invested in the Californian company through its third fund. This is Ysios BioFund III, through which the manager has so far made 14 investments.

Engrail, which was focused on developing its programs and also on raising funding until it closed this 157 million round, will now fully focus on advancing these therapies for the benefit of patients. Currently, the pharmaceutical company has 20 employees and will efficiently expand its workforce to support clinical development, as well as other functions: "We are a very efficient company. We are very effective in execution: a small team can do a great job," Sudarsan claims.

Ysios Capital, founded in 2008, currently has more than 400 million euros in assets under management