Citrine Medicine Advances Efforts to Create the Very First Rare Disease Ecosystem in China Through Strategic Partnership with Bioprojet to License Exclusive Rights for the Use of Orphan Narcolepsy Therapy Wakix® (pitolisant) Citrine was founded by Eight Roads, F-Prime Capital, and Vivo Capital; and closed an $80 Million Series A nancing earlier this year Company is focused on bringing important rare disease therapies to China while accelerating the rare disease drug development process worldwide Wakix® will address high unmet medical need for the treatment of people with narcolepsy in China

NEWS PROVIDED BY Citrine Medicine  Oct 28, 2020, 07:00 ET

SHANGHAI and BOSTON, Oct. 28, 2020 /PRNewswire/ -- Citrine Medicine, a China-based rare disease therapeutics company, today announced that it has entered into a development and licensing agreement with Bioprojet SCR (Bioprojet), a private French company focused on the design, synthesis and development of novel classes of drugs for unmet medical needs. The partnership provides Citrine with exclusive rights to develop, register, market, and manufacture Wakix® (pitolisant) in China for the treatment of narcolepsy and obstructive sleep apnea.

/ Citrine is a therapeutics platform company that is developing the rst rare disease ecosystem in China by creating a new paradigm for helping patients, families, and physicians through the introduction of much-needed drugs for orphan diseases. In addition to developing and marketing rare disease drugs, the company aims to establish a patient- centric platform which educates people on rare diseases, trains doctors on diagnosis and treatment, and helps doctors develop a full disease management protocol. Citrine, founded by Eight Roads, F-Prime Capital, and Vivo Capital, recently closed an $80 million Series A nancing led by Quan Capital, a China-based, healthcare-focused rm. The three founding investors, together with 3H Health Investment and WU Capital, also participated in the round.

Rebecca Lin, Partner at Eight Roads Ventures and a member of Citrine's Board of Directors, stated: "At Eight Roads, our aspiration is to bring about positive change to society by backing innovative and meaningful businesses, and this mission underlies our founding investment in Citrine. We believe Citrine is well positioned to build an ecosystem in China to support patients suffering from rare diseases. The partnership with Bioprojet represents the company's rst effort to bring in validated medicines for patients in need. We look forward to supporting Citrine in its continued efforts to strengthen its capabilities and pipeline, while accelerating rare and orphan disease drug development both in China and globally."

Dr. Dandan Dong, a Managing Director at Vivo Capital and a co-founder of Citrine Medicine, said: "Vivo has long been a believer in the global orphan drug development effort, and we are strong supporters of companies that seek to help rare disease patients. In co-founding Citrine, we extended this belief to the Greater China market. We are pleased to see that Citrine is bringing Wakix® to China for use in people with narcolepsy, a disease with signicant unmet medical need. We will continue to support Citrine in bringing more rare disease therapies to Chinese patients."

"Great strides have been made in rare disease research and drug development in recent years; however, access to both knowledge and treatment options has been a barrier for rare disease patients in China," said Chong Xu, Ph.D., Principal at F-Prime Capital and a Citrine Medicine Board Director. "Recent regulatory reforms and policy changes in China are paving the way for an expedited drug approval pathway for rare disease drugs, and Citrine is poised to leverage this positive environment to deliver much-needed therapies to the people who need them. We believe the partnership with Bioprojet to bring pitolisant to patients in China is a great rst step towards that vision. F-Prime has long been committed to founding and

/ investing in companies that aim to transform healthcare, and we will continue to join forces with investors and founders to support Citrine in truly making a difference in the lives of individuals with rare diseases and their families in China."

Pitolisant is a selective histamine H3-receptor antagonist/inverse agonist that enhances the activity of histaminergic neurons and was developed after decades of research by Bioprojet co-founders Dr. Jeanne-Marie (J.M.) Lecomte and Prof. Jean-Charles Schwartz. Pitolisant increases the release of the brain chemical histamine to increase a patient's wakefulness and alertness. It is approved by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) to treat adults suffering from narcolepsy, a serious, chronic disorder characterized by excessive daytime sleepiness (EDS), with or without cataplexy.

Currently no drugs have been ofcially approved by the National Medical Products Administration (NMPA) in China for the treatment of narcolepsy. There is a high unmet medical need for the treatment of narcolepsy patients with and without cataplexy in China.

"We're excited that we are able to research, develop, and seek approval in China for Wakix®, a potential rst-in-class therapy to treat patients with narcolepsy," said Citrine CEO, Ben Wu. "In addition to working with the NMPA, Citrine will be working closely with healthcare providers, advocacy organizations, and other stakeholders to help address the unmet needs of the patient community."

"Bioprojet is proud to partner with Citrine to help bring pitolisant to additional patients in need. With our collaborative best-in-class approach, we plan to help bring much needed relief to thousands of people suffering from debilitating sleep-related disorders," said Prof. Schwartz, discoverer of the histaminergic neurotransmission in brain and of the H3 receptor. Prof. Schwartz is the co-founder of Bioprojet with Dr. J.M. Lecomte.

About Citrine Medicine Citrine (Shanghai) Co. Ltd. is a China-based biopharmaceutical therapeutics company dedicated to developing innovative therapies for patients with rare and intractable diseases by making diagnosis and essential treatments available and accessible for those who need them. Citrine is headquartered in Shanghai and has ofces in Beijing, China and Cambridge, Mass.

/ About Bioprojet SCR Bioprojet SCR is a research-based pharmaceutical company. Bioprojet is headquartered in Paris, France and its Research Center located in Rennes, France. Its activity is focused on the design, synthesis and development of novel classes of drugs for unmet medical needs. For more information visit http://www.bioprojet.com.

About Pitolisant Pitolisant is a selective histamine H3-receptor antagonist/inverse agonist which enhances the activity of histaminergic neurons. The drug was approved by the EMA in 2016 for the treatment of narcolepsy in adults with or without cataplexy and is marketed in major countries in Europe and was approved by the FDA in 2018. Cataplexy is characterized by sudden and uncontrolled muscle weakness or paralysis. Pitolisant has an orphan designation in the EU and the US for the treatment of narcolepsy. The drug pitolisant is distributed under the tradename WAKIX® in the European Union and the United States for the treatment of narcolepsy in adult patients with and without cataplexy.

About Narcolepsy Narcolepsy is a rare, chronic, debilitating neurological disorder characterized by excessive daytime sleepiness, cataplexy, a sudden loss of muscle control triggered by emotions, and hallucinations among other symptoms. Two types of narcolepsy are currently recognized according to the ICSD3 diagnostic criteria, Type 1 and 2. Type 1 is associated with cataplexy and a reduction in of hypocretin-1 levels, while Type 2 is not associated with cataplexy.

Important Safety Information In clinical trials conducted in patients with narcolepsy, the most frequent adverse drug reactions (ADRs) reported with pitolisant were insomnia (8.4%), headache (7.7%), nausea (4.8%), anxiety (2.1%), irritability (1.8%), dizziness (1.4%), depression (1.3%), tremor (1.2%), sleep disorders (1.1%), fatigue (1.1%), vomiting (1.0%), vertigo (1.0%), dyspepsia (1.0%), weight increase (0.9%), and upper abdominal pain (0.9%). Pitolisant is contraindicated in patients with severe hepatic impairment (Child-Pugh C) and in women breastfeeding their children.

About Eight Roads Eight Roads is a global proprietary investment rm backed by Fidelity. The exible nature of its capital means Eight Roads can back and build innovative and ambitious businesses looking to disrupt or lead their chosen markets. Eight Roads has over 20 years of venture

/ capital experience in China and has supported over 100 companies in the country's healthcare and technology sectors. In the past 10 years, the Eight Roads ecosystem has invested almost $6 billion USD globally.

About Vivo Capital Founded in 1996, Vivo Capital is a global investment rm focused on healthcare. Vivo has approximately $4.3 billion in , invested in over 250 public and private companies worldwide. Vivo provides a multi-fund investment platform, covering growth equity, including , venture capital, and public equity. The rm is headquartered in Palo Alto, California, with additional ofces in Asia.

About F-Prime Capital F-Prime Capital is a global venture capital rm investing in healthcare and technology. For the past 50 years, our independent venture capital group has had the privilege of backing great entrepreneurs building groundbreaking companies. With over two billion dollars under management and a global portfolio of more than 190 companies, we champion those dedicated to creating positive change in the world. F-Prime is headquartered in Cambridge, MA, with ofces in London, UK and San Francisco, CA.

Citrine Medicine Media Contacts:

Sarah Sutton Glover Park Group [email protected] 202-337-0808

Danielle Cantey Glover Park Group [email protected] 202-337-0808

SOURCE Citrine Medicine

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