-Oligomannate, A New Oral Treatment For Mild To Moderate Alzheimer's Disease 
-The Only Approved Novel AD Treatment Globally Since 2003

Shanghai Green Valley Pharmaceuticals (Green Valley) today announced that 
China's National Medical Products Administration (NMPA) has approved 
Oligomannate (GV-971) as new drug for the treatment of "mild to moderate 
Alzheimer's disease (AD) and improving cognitive function." 

NMPA granted Oligomannate for fast-track review in November 2018.  It is the 
first novel drug approved for Alzheimer's disease globally since 2003. 
Oligomannate will provide a new treatment option to fight Alzheimer's disease 
for patients and is expected to be available in China by the end of 2019.

Study Results

The Phase 3 clinical trial is a multicenter, randomized, double-blind, 
placebo-controlled, parallel-group 36 week study led by Peking Union Hospital 
and Shanghai Jiaotong University Medical School Mental Health Center. The study 
was conducted in 34 Tier-1 hospitals across China. A total of 818 patients with 
the diagnosis of mild to moderate Alzhemer's disease completed the study. The 
trial was conducted in collaboration with IQVIA (formally Quintiles) and 
Signant Health (formerly Bracket) among other partners.

Trial results demonstrated that Oligomannate statistically improve cognitive 
function in mild-to-moderate AD patients as early as week 4 and the benefit was 
sustained at each follow-up assessment visit. The mean difference between 
Oligomannate and placebo groups in ADAS-Cog12 Score (a standard cognitive 
measure commonly used in AD studies) was 2.54 (p< 0.0001), with sustained 
efficacy from first month of treatment to the end of 9 months of treatment. 
Oligomannate was safe and well tolerated with side effects comparable to the 
placebo arm. 

"I have been doing research on Alzheimer's disease for 50 years, participated 
in multiple global multi-center studies of multiple drugs, and have never found 
a satisfactory treatment for Alzheimer's disease," said Professor Zhang 
Zhenxin, MD, a leading principal investigator of the phase 3 trial of 
Oligomannate and professor of Neurology at Peking Union Medical College 
Hospital in Beijing. "The result of the 9-month trial of Oligomannate is 
exciting. We finally see hope and dawn. I am sincerely happy for the patients 
and their families."

"There are only few drugs available to treat Alzheimer's disease, and none can 
delay or prevent progression of the disease," said Professor Xiao Shifu, a 
leading principal investigator of the phase 3 trial of Oligomannate at Center 
for Mental Health at Shanghai Jiaotong University Medical College. "The results 
of the Phase 3 clinical study showed rapid onset of efficacy of Oligomannate 
within 4 weeks, and that patients' cognitive function continued to improve. The 
treatment was safe during the 36-week clinical trial."

The cause of AD is not yet fully understood. Deposition of amyloid plaques and 
neurofibrillary tangles are among the proposed underlying etiologies; these are 
the common targets of many current investigational drugs.  Oligomannate has a 
mechanism of action distinct from other agents currently on the market and in 
clinical trials. As described by Professor Geng Meiyu, the leading inventor of 
the drug at the Chinese Academy of Sciences Shanghai Institute of Materia 
Medica, the preclinical studies show that Oligomannate reconditions dysbiosis 
of gut microbiota, inhibits the abnormal increase of intestinal flora 
metabolites, modulates peripheral and central inflammation, reduces amyloid 
protein deposition and tau hyperphosphorylation, and improves cognitive 
function. 

In the Research Highlight[1] about the preclinical study of Oligomannate 
recently published in Cell Research[2], Professor David M. Holtzman, chairmen 
of Department of Neurology and director of Hope Center for Neurological 
Diseases at Washington University in St. Louis and his colleagues wrote that 
the preclinical data "supports the emerging idea that modulation of the gut 
microbiome via treatments such as GV-971 or other strategies should be further 
explored as novel strategies to slow the progression of AD". 

Green Valley will launch Oligomannate very soon in China, and plan to submit 
the marketing authorization applications in selected countries following the 
China launch.  A multi-center global phase 3 clinical trial (GREEN MEMORY) with 
sites in the U.S., Europe and Asia is planned to be initiated in early 2020 to 
support global regulatory filing of Oligomannate.

"The phase 3 clinical trial of Oligomannate conducted in China showed a 
sustainable cognitive benefit. It was well tolerated. This is the first new 
therapy for Alzheimer's disease approved in many years and we applaud this 
innovation," said Jeffrey Cummings, MD, Vice Chair for Research and Research 
Professor of UNLV Department of Brain Health and Professor and director of 
Center for Neurodegeneration and Translational Neuroscience Cleveland Clinic, 
Lou Ruvo Center for Brain Health, and a scientific advisor to Green Valley. "We 
look forward to the global phase 3 trial of Oligomannate to investigate its 
clinical effects in larger and more diverse populations and to collect samples 
that will provide evidence of the agent's biological effects.

"I am encouraged by the cognitive improvement, safety and tolerability 
associated with Oligommanate in this initial clinical trial, as well as the 
potential to diversify the portfolio of promising treatments for our affected 
patients and families," said Eric Reiman, MD, Executive Director of Banner 
Alzheimer's Institute and a scientific advisor to Green Valley. "I am also 
encouraged by the plan to further evaluate clinical and biological effects of 
this drug in global trials."

"The preclinical observation that Oligomannate suppresses gut dysbiosis and 
harnesses neuroinflammation has resulted in improvement of cognitive 
impairment, as evidenced by the trial results," said Philip Scheltens, MD, PhD, 
professor of Neurologist and CEO of Alzheimer Center Amsterdam and a scientific 
advisor to Green Valley. "These results advance our understanding of the 
mechanisms that play a role in Alzheimer's disease and implies that the gut 
microbiome is a valid target for development of AD therapies."

"We are very excited that Oligomannate is the first new drug approved for 
treating Alzheimer's patients in the past 17 years, we are grateful to our 
patients and families who are the real heroes in the fight against this 
debilitating disease," said Mr. Lv Songtao, Chairman of Green Valley. "At Green 
Valley, we are committed to the mission of 'developing medicines that fulfill 
the biggest unmet medical needs for human health' and have finally succeeded 
after 22 years of unremitting efforts. We look forward to continuing this 
journey to bring new treatment to all patients around the world." 

About Green Valley

Shanghai Green Valley Pharmaceuticals is an innovative Chinese pharmaceutical 
company that pioneers new treatment strategies in the area of chronic and 
complex diseases. The company upholds the sacred mission of "developing 
medicines that fulfill the biggest unmet medical needs for human health", 
explores the pathogenesis of chronic and complex diseases with a holistic view 
of treatment, and focuses on breakthrough innovation in research and 
development of carbohydrate drugs. Green Valley is committed to becoming a 
global leader in carbohydrate drug innovation, providing safer and more 
effective drugs for patients with chronic and complex diseases, and providing 
better choice of treatment for diseases and improving the quality of life.

Green Valley Pharmaceuticals was founded in 1997 and is headquartered in 
Zhangjiang Science City in Shanghai, China. It is focused on advancing research 
programs in neuropsychiatric diseases, cancer, cardiovascular diseases, 
metabolic diseases and autoimmune diseases. It has 1,500 employees in China and 
operates a subsidiary in the United States. It has built the world's first 
large-scale carbohydrate compound library, the first carbohydrate drug API and 
processing facility, and the world's leading R&D pipeline for carbohydrate drug 
products.

About Alzheimer's disease

Alzheimer's disease is a progressive brain disorder marked by cognitive and 
behavioral impairment that significantly interferes with daily function. It is 
the third leading cause of disability and death in the elderly next to 
cardiovascular disease and cancer. According to the Alzheimer's InternationalS, 
there are about 50 million people in the world with dementia and about two 
thirds have Alzheimer's; the annual medical expense of the disease is estimated 
more than one trillion USD[3].

Forward Looking Statement

This news release may contain forward-looking statements based on current 
assumptions and forecasts made by Green Valley. Various known and unknown 
risks, uncertainties and other factors could lead to material differences 
between the actual future results, financial situation, development or 
performance of Green Valley and the estimates given here. These factors include 
those discussed in Green Valley's public reports, which are available on the 
Green Valley website at http://www.shgvp.com/En. Green Valley assumes no 
liability for the update of these forward-looking statements or the consistency 
between these forward-looking statements and future events or developments.

References

1. Seo DO, Boros BD, and Holtzman DM (2019) The microbiome: A target for 
Alzheimer disease? Cell Res. 29(10):779-780 
2. Wang X and Sun G et. al. (2019) Sodium oligomannate therapeutically remodels 
gut microbiota and suppresses gut bacterial amino acids-shaped 
neuroinflammation to inhibit Alzheimer's disease progression. Cell Res. 
29(10):787-803 
3. World Alzheimer Report 2018, published by Alzheimer's Disease International 
(ADI), London, 2018 



SOURCE: Shanghai Green Valley Pharmaceuticals