정재준 대표이사 세계적인 제약업계 저널 SCRIP 인터뷰
2019년 9월 19일 영국에서 발행되는 대표적인 세계 제약업계지인 스크립(SCRIP)에 (주)아리바이오의 정재준 대표님의 인터뷰가 실렸습니다. "(주)아리바이오 대표는 다중기작의 약물인 AR1001로 알츠하이머병과 혈관성 치매를 치료할 수 있을 것으로 기대하고 있다고 전했다. AR1001은 아리바이오만의 신약개발 플랫폼인 ARIDD (Advanced, Rapid and Integrated Drug Development)를 통해 개발된 약물로 개발과정을 가속화시켰을 뿐만 아니라 임상의 성공 가능성도 극대화 시킬 수 있는 장점을 가지고 있다."
ARIBIO Counts On Multi-Modal Drug For Alzheimer's And Vascular Dementia
ARIBIO CEO tells Scrip how the South Korean biotech is aiming to develop a multi-modal drug for both Alzheimer’s disease and vascular dementia using its innovative platform technology, which can cut development periods and costs and better predict clinical trial success.
Source: ARIBIO ARIBIO CEO MATTHEW JAI JUN CHOUNG SAYS PARADIGM SHIFT NEEDED FOR DEMENTIA DRUG DEVELOPMENT
Amid continued failures in clinical trials of new drugs for Alzheimer’s disease (AD), researchers are beginning to have doubts about whether the "one drug, one target" paradigm is the way to go. Biogen Inc./Eisai Co. Ltd.'s BACE inhibitor elenbecestat has just become the latest late-stage failure in the field, after showing an unfavorable risk-benefit ratio. (Also see "BACE Hopes Finally Fizzle As Biogen/Eisai End Elenbecestat Alzheimer's Studies " - Scrip, 13 Sep, 2019.)
Those calling for a different approach include the CEO of South Korean venture ARIBIO, Matthew Jai Jun Choung, who believes that the traditional drug discovery model needs to change to successfully develop an effective and safe drug for the disease. While the exact cause of Alzheimer's is still unknown, Choung told Scrip in an interview that the best option for the disease, for now, is to focus on developing a multi-mechanism product that can save neurons and effectively rebuild memory.
ARIBIO has a rare business model somewhere between a “no research, development only” company and classical drug development operation. The venture licenses in new drug compounds after the lead optimization stage, but conducts its own preclinical and clinical studies to validate data and reduce toxicity risks. So far it has licensed in 15 compounds, but after screening the candidates it is focusing on three major pipeline assets – AR1001 for dementia, AR1003 for sepsis and AR1008 for obesity, all conditions for which the venture sees few effective treatments or existing drugs have serious side effects. AR1001 and AR1003 are small molecules while AR1008 is a natural product-derived candidate.
ARIDD Tech Cuts Development Periods, Costs, Failures
ARIBIO is focusing on developing multi-mechanism molecules using innovative platform technology developed by Choung and based on his experience in the development field. The company's Advanced Rapid and Integrated Drug Development (ARIDD) technology enables the company to screen in-licensed compounds, go through in-house evaluation and pre-development work and select strategic drug candidates. These will then go through clinical development and be licensed out.
“Our endpoint is to seek partnerships after conducting clinical trials. We base our development strategy on this from the beginning,” the CEO explained. At the molecular level, the platform uses orbitrap mass spectrometry to analyze samples to identify drug targets and biomarkers. It also uses a unique toxicity test system that can conduct histopathological analyses for 27 internal organs at one time. The company also designs its own clinical trials but assigns these to contract research organizations to reduce development risks in the early stages.
“We conduct clinical trials after securing the safety of the compound to a certain level. This could reduce risks of side-effects,” the executive said. “This is our strength. We can accelerate development periods, predict clinical trial failures and cut costs.” After completing Phase I and II trials, ARIBIO determines whether a compound will be developed as a disease-modifying or symptomatic drug. It also explores the compound’s potential for combination therapy. As a result, once a candidate is approved, it may have multiple functions.
Multi-Modal Drug Protects Neurons, Recovers Synapse Function
In dementia, ARIBIO’s strategy is to develop a multi-modal or multi-target drug that can protect neurons and help recover synapse function. AR1001 has the potential to fundamentally slow the progression of AD through a multi-pronged mechanism of action that includes stimulation of neurogenesis, inhibition of neuronal death and restoration of synaptic plasticity. Furthermore, studies have shown the molecule helps clear toxic amyloid beta oligomers via autophagy activation and increased cerebral blood flow.
“Preclinical studies have so far shown that this mechanism is working," Choung said. "It prevented neurons from dying and generated new neurons. We have secured data that show increased synaptic plasticity and autophagy activity.”
A Phase II clinical trial of AR1001 is underway at 20 centers in the US. Of the 210 patients, more than a third have begun to receive the drug. “We are very excited. So far, there haven’t been any safety issues and this is huge,” the CEO said. “Our dream is to develop a drug that is effective for both Alzheimer’s disease and vascular dementia.” A Phase II study in the latter indication is set to begin next year and has already received IND approval from the US FDA. Meanwhile, top line Phase II data for AD will be available late next year.
South Korea and Eastern Europe are known to have a relatively higher proportion of vascular dementia patients versus countries like the US. “In vascular dementia, the key is how fast we can recruit patients. This is why we are including South Korea and Europe as well as the US for clinical trials,” he said. ARIBIO plans to begin a Phase II clinical trial of obesity candidate AR1008 in South Korea initially, as regulations for natural product-derived drugs are relatively relaxed in the country.
ARIBIO plans to seek partners for its AD candidate, but likely after the Phase II trial data are released. It may seek an orphan designation in another (undisclosed) indication and also consider developing combination therapies.
“As there are no fundamental drugs for AD, we believe more new approaches should be tried to treat the disease, so that patients can maintain their quality of life,” Choung said. ARIBIO is also pursuing the development of back-up programs to prepare for completion of Phase II studies. As for financing, the venture is preparing for an initial public offering late this year or next year, depending on the stock market conditions. ARIBIO has so far raised KRW15bn ($12.5m) up to a Series B round, from South Korean investors including venture capital funds, the state-run Korea Development Bank and others.
INTERVIEWS (19 Sep 2019) : Jung Won Shin (Jungwon.Shin@informa.com)