(Picture: Vikram Sudarsan, Ph.D., CEO and president of Engrail Therapeutics)
안녕하세요 보스턴 임박사입니다.
Engrail Therapeutics는 Neuroscience Drug Discovery를 전문으로 좋은 Asset을 Acquisition을 통해서 성장하는 것을 목적으로 하는 회사입니다. Vikram Sudarsan 박사는 Cipla Technologies의 CEO 였는데 Pulmatrix에 2019년에 인수되었습니다.
그리고 Engrail Therapeutics를 창업했는데 중국의 Nan Fung Life Sciences (NFLS) 이라는 VC Firm의 전폭적인 지원 속에 현재까지 왔습니다. 1년 후 $32 Million Series A를 받았습니다. ENX-101이라는 GABA-A Modulator를 개발하는 중이었습니다.
Engrail Therapeutics nabs $32M series A for CNS work – Fierce Biotech 6/19/2020
San Diego-based biotech Engrail Therapeutics has raised $32 million as it looks to kick-start its first clinical work for its central nervous system med.
Nan Fung Life Sciences (NFLS), the global investment platform of the Nan Fung Group, led the round, which will see the cash funneled into its first pipeline asset, ENX-101, a sub-type selective GABA-A modulator. On top of this, it’s also looking to beef up its pipeline with more asset deals penciled in for the future.
The biotech, which launched last year, says it wants to buy up more assets with “validated mechanisms, ultimately catalyzing a diverse portfolio of therapies to treat diseases of the nervous system.” Its business model includes licensing, co-development and company buyouts—big ambitions for such a young startup.
Vikram Sudarsan, Ph.D., CEO and president of Engrail, said the cash should be there for its ambitious plans. “With these resources and a long-term commitment from NFLS to invest $1.5 billion in the life sciences sector, we will leverage our unique, flexible transaction model to build a world-class neuroscience company,” he said in a release.
Neuroscience is a notoriously tough R&D area, however, with billions of research dollars spent and lost on projects that simply couldn’t make the grade, especially in areas like Alzheimer’s disease.
Sudarsan, former chief at Cipla Technologies before it was bought by Pulmatrix last year, is confident the industry may be past the peak of these failures.
“Neuroscience is making massive strides. As the brain’s complexities and molecular mechanisms have become clearer, we are better able to identify disease targets, which has also a supported a resurgence in funding neuroscience drug development,” he said.
“These factors have contributed to recent clinical and commercial success across the industry. However, significant unmet needs persist, placing immense disease burden on patients. Our goal is to build a leading neuroscience company fueled by a robust pipeline. We are focused on the acquisition, development and commercialization of patient-centric neuroscience therapeutics. ENX-101 represents the first milestone in this effort.”
Just what it will be leading is being kept under wraps; Its MAO, GABA, is however the major inhibitory transmitter controlling synaptic transmission and neuronal excitability. It is present in a high percentage of neurons in the CNS and also present in the peripheral nervous system, and it acts to maintain a balance between excitation and inhibition.
A number of targets have been in development using this approach including epilepsy, anxiety and sleep disorders.
그리고 2021년에 NeuroCycle Therapeutics를 인수했는데 ENX-101과 같은 기전의 Drug candidate를 가지고 있는 회사였습니다.
Engrail Therapeutics Acquires NeuroCycle Therapeutics – Press Release 2/2/2021
Engrail Therapeutics™ (Engrail) today announced that it has acquired NeuroCycle Therapeutics, a company focused on sub-type selective GABA-A modulation. The acquisition strengthens Engrail’s presence in the GABA-A space and provides a strong platform for initiation of clinical trials with multiple assets in 2021.
“We believe Engrail represents the ideal company to carry on the work NeuroCycle started given their focus and experience in the GABA-A space. We look forward to seeing them bring novel medicines to patients that need them.”
“Our flexible transaction model and science-first approach allows us to acquire high-quality assets with a lower-risk path to market where significant patient need still exists,” said Vikram Sudarsan, Ph.D., CEO and president, Engrail Therapeutics. “We combine a comprehensive view of clinical development strategy, regulatory considerations and intellectual property to find differentiated assets with validated mechanisms of action. GABA-A is a well validated target and modulators of this receptor have therapeutic effect across a broad range of neurological and psychiatric conditions. We now have multiple sub-type selective GABA-A modulators with strong profiles and look forward to rapidly advancing development.”
Dr. Sudarsan continued, “We remain committed to building a leading, patient-centric neuroscience company with a growing pipeline through licensing, co-development and acquisitions. Our goal is to build a diverse pipeline of neuroscience therapeutics over the next several years, and the acquisition of NeuroCycle represents another important step on this path. We expect 2021 to be a busy year as we consider additional transactions to expand our portfolio.”
Jed Hubbs, Ph.D., CEO and president, NeuroCycle Therapeutics said, “We believe Engrail represents the ideal company to carry on the work NeuroCycle started given their focus and experience in the GABA-A space. We look forward to seeing them bring novel medicines to patients that need them.”
NeuroCycle을 인수한 이후에 Series A extension으로 총 $64 Million을 받게 됩니다. ENX-101은 임상1b에 있었고 ENX-102는 임상1a에 있는 상태였습니다.
Engrail Therapeutics Extends Series A Financing to $64 Million – Press Release 8/3/2021
Engrail Therapeutics™ (Engrail) (the Company), a neuroscience company focused on the acquisition, development and commercialization of patient-centric therapies, today announced the close of a $32 million extension of its Series A financing round, which brings the total round to $64 million. Nan Fung Life Sciences (NFLS), the global investment platform of the Nan Fung Group, led this round following their leadership of the original Series A raise. The Company will use the proceeds to finance the advancement of their diverse pipeline, including its lead assets, ENX-101, ENX-102 and internal preclinical programs. Engrail’s lead compounds are subtype-selective GABA-A modulators with compelling pharmacological profiles that possess wide ranging therapeutic utility.
“We are excited to support this team as it continues acquiring high-quality assets and advances them through clinical development.”
“Earlier this year, we initiated a Phase 1b study for ENX-101 and Phase 1a study for ENX-102. This funding will help advance these assets, as well as our earlier-stage pipeline, as rapidly as possible while continuing to build out our clinical development capabilities,” said Vikram Sudarsan, Ph.D., CEO and president of Engrail Therapeutics. “Additionally, NFLS has made a long-term commitment to invest $2 billion in the life sciences sector, enabling us to continue leveraging our flexible transaction model to acquire assets with validated mechanisms to treat diseases of the nervous system through licensing, co-development and company acquisitions. We continue to pursue transactions that will grow our pipeline and cater to major unmet needs in the neurosciences.”
Engrail has assembled a diverse portfolio of assets with validated mechanisms through its dynamic model for advancing drugs aimed at treating life-limiting diseases of the nervous system. By adopting a ‘science-first’ approach, combined with a comprehensive view of clinical development strategy, regulatory considerations and intellectual property, the Company can find differentiated assets with validated mechanisms of action for diseases where significant patient need still exists.
“Engrail has demonstrated impressive progress in the past year since its founding with the initiation of two Phase 1 studies for its lead candidates,” said Peter Bisgaard, managing director of NFLS and chairman of Engrail’s board of directors. “We are excited to support this team as it continues acquiring high-quality assets and advances them through clinical development.”
About Engrail Therapeutics
Founded in 2019, Engrail is forging a new direction to reduce the enormous burden of diseases that impact the nervous system. We unite biological insights with clinically meaningful solutions to build and catalyze a diversified portfolio of transformative medicines. Harnessing our rigorous scientific approach to identify the most promising therapies, we leverage our flexible transaction model to advance assets with validated mechanisms and efficiently move them through development to commercialization. Engrail is supported by a long-term capital commitment from Nan Fung Life Sciences. For more information, visit www.engrail.com.
About Nan Fung Life Sciences
Nan Fung Life Sciences is a global life sciences investment platform with a long-term capital commitment from the Nan Fung Group. Our team possesses diverse experience with long track records in company formation, venture capital, growth/buyout investments, and drug discovery and development. Through direct investments via Pivotal bioVenture Partners US and Pivotal bioVenture Partners China as well as fund investments, we cover the full spectrum of the life sciences industry including therapeutics, medical devices and diagnostics and across all development stages. To learn more, visit www.nanfunglifesciences.com.
2022년에 ENX-101 임상1b 결과를 발표했습니다. 대체적으로는 긍정적인 발표였는데 어떤 이유인지 파이프라인에서는 결국 사라졌습니다.
ENX-101 exhibited a favorable safety and pharmacokinetic profile in healthy volunteers
• ENX-101 was well tolerated following once-daily oral administration with no dose titration
• Translational biomarker data indicated target engagement consistent with anti-seizure activity
• Engrail plans to initiate the ENACT phase 2 trial in epilepsy
SAN DIEGO – June 7, 2022 – Engrail Therapeutics™ (Engrail) (the Company), a precision neuroscience company focused on the acquisition, development, and commercialization of transformational therapies, has announced positive results from a phase 1b clinical trial of ENX-101, a subtype-selective GABA-A positive allosteric modulator (PAM). The phase 1b clinical trial data were presented on June 6, 2022, at the 2022 Epilepsy Pipeline Conference in Santa Clara, California. Following these results and recent interaction with the US FDA that included alignment on the phase 2 development program, Engrail plans to initiate the ENACT Trial, an international multi-center phase 2 clinical trial to evaluate the efficacy and safety of ENX-101 in patients with focal epilepsy.
“We are excited to announce that repeated administration of ENX-101 showed a highly favorable safety and tolerability profile in healthy volunteers across a wide range of doses,” said Kimberly Vanover, Ph.D., chief scientific officer of Engrail Therapeutics. “Moreover, translational biomarker data provided strong evidence of target engagement by ENX-101 that we believe are predictive of positive clinical benefit in patients with epilepsy as well as other disorders of the central nervous system.”
ENX-101, administered orally once daily for ten days, was safe and well tolerated in healthy volunteers. There were no dose-related, clinically meaningful changes in vital signs, electrocardiograms, physical exams, or clinical laboratory values. Treatment-emergent adverse events (TEAEs) were generally mild and transient. There were no serious adverse events or severe adverse events reported. The most frequent TEAE associated with ENX-101 administration was mild and transient somnolence that occurred primarily during the first few days of dosing. ENX-101 exhibited predictable dose-related exposure with a half-life of approximately 20 hours.
ENX-101 exhibited activity across pharmacodynamic biomarkers confirming target engagement. Notably, ENX-101 decreased saccadic peak velocity, consistent with centrally acting GABA-A PAM pharmacology, and increased beta power of quantitative electroencephalogram (qEEG) recordings. ENX-101 exhibited little to no adverse effect on alertness, psychomotor function, or sustained attention with repeated administration. Additionally, ENX-101 did not show a sedative-like increase in qEEG delta power, rather, ENX-101 decreased delta power. Moreover, there was no evidence of tachyphylaxis to functional target engagement or tolerance to the central nervous system inhibitory effects of ENX-101 with repeated administration. Taken together, the data are consistent with a GABA-mediated pharmacodynamic profile that is distinct from sedative benzodiazepines and other non-selective GABA-A PAMs.
“The data generated to date with ENX-101 are highly encouraging. I look forward to seeing the translation of these results into outcomes in patients suffering from therapy resistant epilepsy – an inherently tough disease in need of better treatment options,” said Jacqueline French, M.D., professor of Neurology at NYU Langone Health’s Comprehensive Epilepsy Center.
Vikram Sudarsan, Ph.D., chief executive officer and president of Engrail added, “the positive ENX-101 phase 1b clinical results are just one of many important outcomes we expect to see from the organization over the coming years. We founded Engrail in 2019 with the aspiration of becoming a leading neuroscience company. Our stellar and experienced team has built a deep and differentiated pipeline spanning six unique programs, including two programs rapidly advancing to phase 2. We built this pipeline through thoughtful business development as well as internal drug discovery efforts and are now focused on advancing our entire portfolio.”
About the ENX-101-004 Phase 1b Trial
ENX-101-004 was a randomized, placebo-controlled multiple ascending dose trial conducted in healthy volunteers. ENX-101 or placebo was administered orally once daily in the morning for 10 days. Five cohorts (N=9; 6:3 active:placebo in each cohort) evaluated doses of 5, 10, 15, 25, and 50 mg ENX-101. The primary objective of the study was to evaluate the safety and tolerability of ENX-101 following repeated administration. Secondary objectives included the evaluation of the effects of ENX-101 on electrocardiogram (ECG) parameters, pharmacokinetic (PK) parameters, and a battery of pharmacodynamic biomarkers such as saccadic eye movement, quantitative electroencephalographic (qEEG) parameters, visual analog scales, and cognitive performance.
Following a Screening Period (Day -28 to Day -3), healthy volunteers meeting inclusion criteria were admitted to an inpatient clinical research center for a Baseline Period (Day -2 to Day -1). Study treatment was administered on Days 1 through 10 and participants were followed for an additional three days following the cessation of treatment and discharged on Day 13. The extensive biomarker battery was collected at Baseline and on Days 2 and 9. Safety and tolerability were assessed daily.
About ENX-101
Targeting the gamma-aminobutyric acid A (GABA-A) receptor is a well-validated pharmacological approach for the treatment of epilepsy, anxiety, pain, and other centrally-mediated disorders. However, conventional, non-selective GABA-A modulators, such as benzodiazepines, have several liabilities limiting chronic use, primarily driven by GABA-A α1 subunit containing channels. ENX-101 is an investigational precision targeted GABA-A PAM that enhances neurotransmission in receptors containing α2, α3, and α5 subunits while blocking α1. This profile is thought to contribute to anti-seizure efficacy and a favorable safety profile while minimizing the undesirable effects associated with α1-mediated GABAergic neurotransmission. ENX-101 has been well-tolerated in clinical trials with once daily oral dosing and does not require dose titration.
2023년 7월에 ENX-102의 임상2상을 시작했다고 발표를 했습니다. 아마도 ENX-101 임상을 중단하고 ENX-102로 바뀐 것 같습니다.
Engrail Therapeutics™ (Engrail) (the Company), a precision neuroscience company focused on the acquisition, development, and commercialization of transformational therapies, today announced initiation of a multi-center phase 2 clinical trial, the ENCALM Trial, to evaluate the efficacy and safety of ENX-102 in patients with generalized anxiety disorder (GAD). ENX-102 is an investigational, highly selective GABA-A α2,3,5 positive allosteric modulator (PAM) and antagonist at α1-containing GABA-A channels. ENX-102 represents a first-in-class approach to the treatment of GAD.
“Translational and phase 1 clinical data indicate central target engagement with a highly differentiated safety and tolerability profile for ENX-102 vs. non-selective GABA-A PAMs such as benzodiazepines. ENX-102 exhibits a long half-life and can be dosed once daily without titration. These data support further evaluation of ENX-102 for efficacy in generalized anxiety disorder,” said Kimberly Vanover, PhD, chief scientific officer of Engrail.
“While there are a variety of options for treating GAD, they all have significant drawbacks – particularly limiting safe and tolerable long-term use. Engrail’s approach of selectively targeting GABA-A α2, α3, and α5 subunits holds promise for providing strong anxiolytic effect while reducing the risk of sedation and abuse potential,” said Charles Nemeroff, MD, PhD, chair and professor with the Department of Psychiatry and Behavioral Sciences at the Dell Medical School, University of Texas at Austin.
Vikram Sudarsan, Ph.D., chief executive officer and president of Engrail added, “We are excited by the best-in-class profile of ENX-102 and look forward to further elucidating its efficacy and safety profile in phase 2. The initiation of phase 2 and further advancement of the rest of our precision neuroscience pipeline makes 2023 a hallmark year for the organization.”
For more information on the ENCALM Trial, visit clinicaltrials.gov.
About ENX-102
Targeting the gamma-aminobutyric acid A (GABA-A) receptor is a well-validated pharmacological approach for the treatment of anxiety and other centrally-mediated disorders. However, broad-spectrum GABA-A modulators, such as benzodiazepines, have several liabilities limiting chronic use, primarily driven by GABA-A α1 subunit containing channels. ENX-102 is an investigational subtype-selective GABA-A PAM acting to enhance GABA neurotransmission in receptors containing the α2, α3, and α5 subunits while blocking α1. This profile is thought to contribute to anxiolytic efficacy and result in a favorable safety profile without the undesirable effects associated with α1.
얼마전에 $157 Million의 펀딩을 받았습니다. ENX-102의 임상을 더 집중할 수 있는 규모일 것같습니다.
Engrail Raises $157M in Oversubscribed Series B to Move Neuro Pipeline Forward – Biospace 3/19/2024
San Diego-based Engrail Therapeutics has closed a $157 million oversubscribed Series B funding round to support the development of its therapeutic assets for the treatment of anxiety disorders, depression, post-traumatic stress disorder and rare neurodegenerative diseases.
New investors, including Forbion, F-Prime Capital, and Norwest Venture Partners, led the funding. Other participants included RiverVest Venture Partners, Red Tree Venture Capital, Ysios Capital, Longwood Fund, Eight Roads Ventures and Pivotal Life Science.
Proceeds from the financing round will be used to support the advancement of Engrail’s pipeline through clinical development.
“With strong financial backing from highly sophisticated and dedicated life science investors, we are well-positioned to deliver multiple value-creating milestones. Notably, we look forward to completing our ongoing ENX-102 Phase II study in generalized anxiety disorder and advancing the rest of our pipeline into clinical development,” Engrail CEO Vikram Sudarsan said in a statement. “Engrail was fortunate to have been incubated under a tremendous commitment from Pivotal Life Sciences. We are excited to start the next chapter of our journey with some of the best thought partners in neuroscience and life sciences investing in our success.”
Engrail emerged in 2020 with a $32 million Series A financing round singularly funded by Nan Fung Life Sciences, which was designed to advance its first pipeline asset. Known as ENX-101, the drug was a sub-type selective GABA A modulator but the drug has since been removed from the company’s website. The Series A was extended to $64 million in 2021. Since 2019, the biotech has raised over $220 million.
“We see tremendous potential in Engrail’s pipeline and management team and are excited to participate in their development of transformative therapies for patients,” Stacie Weninger, board member and president of F-Prime Biomedical Research Initiative, said in a statement.
Engrail is among several biotechs that have recently secured funding. ProfoundBio, a Seattle-based antibody-drug conjugate company, raised $112 million in its Series B round in February 2024 to move four candidates forward.
In January 2024, Beijing Avistone Biotechnology, which is focused on precision oncology treatments, also completed a 1 billion yuan ($140 million) Series B round.
2024년 1Q의 Corporate Presentation은 아래에 링크합니다.
BOSTON DR LIM 