By Shannon Ellis
Staff Writer
Tuesday, March 22, 2016
SHANGHAI – Canbridge Life Sciences Ltd., a privately held biopharma in Beijing, has in-licensed AV-203 , a clinical-stage ErbB3 (HER3) inhibitory antibody candidate from Aveo Oncology Inc., of Cambridge, Mass. While the candidate has been tested in numerous tumor models, Canbridge will develop AV-203 in esophageal squamous cell cancer (ESCC), the most prevalent form of esophageal cancer especially in China where half of all new cases arise.
A virtual biopharma with a team of 20, Canbridge has a China-focused strategy by seeking out global candidates that can meet a specific unmet need in China or Asia. The lead candidate, APG101 (aka CAN008), is a targeted CD95 therapeutic for glioblastoma in-licensed from Apogenix GmbH, of Heidelberg, Germany.
In this deal, Aveo will receive a $1 million up-front payment with the potential to receive $133 million downstream if all goes according to plan. Terms also call for Aveo to receive a tiered royalty with a percentage range in the low double digits on net sales.
In return, Canbridge has the right to develop AV-203 (aka CAN017) globally, excluding North America, for numerous indications although ESCC is the top priority.
“This is not a regional deal; it is worldwide outside of North America,” James Xue, Canbridge CEO, told BioWorld Today. “When you come to a valuation, you build in both geographies as well as indications. Because it is our decision to investigate esophageal carcinoma first, but it has potential in other types of tumors where squamous cell is dominant or has a significant presence, we feel to show our seriousness a modest up-front payment was appropriate.”
Canbridge will cover the costs for developing CAN017 for squamous cell esophagus cancer to demonstrate proof of concept including additional in-China manufacturing requirements, preclinical and clinical studies all the way to phase IIa.
The two sides leave open the option of working more closely to co-develop the candidate once Canbridge completes proof of concept in China.
“This agreement allows us to further advance AV-203 development by leveraging the resources of a motivated partner in Canbridge,” said Michael Bailey, Aveo’s president and CEO. “Importantly, it also allows us to retain North American rights for future development for a third clinical stage drug candidate, providing Aveo with a robust portfolio of oncology therapeutics.”
THE GENZYME CONNECTION
Aveo and Canbridge share an influential master connector in common: Henri Termeer, the former CEO of Genzyme, a unit of Sanofi SA, of Paris. Termeer is the chairman of Aveo and also Canbridge’s chief advisor. (Before branching out on his own, Xue was the China general manager for Genzyme.) Having Termeer on the team has been a boon for Canbridge in making ties with the U.S. and Europe.
“We talked about how Canbridge has an interest in Asian disease and whether in their pipeline there was something where we could leverage our strengths, and it came to the AV203,” said Xue. “Aveo had already completed a phase I study in the U.S. but because of their priorities, they probably will not have any immediate plans for post-phase I development. We took a closer look and saw the relationship with squamous cell type carcinoma. We moved pretty quickly after determining that since Asia has over half the world prevalence of esophageal cancer.”
For its part, Aveo has had a bumpy ride after its lead candidate, tivozanib for renal cell carcinoma, ran into costly regulatory complications with the FDA during phase III trials. The company has had to cut its research team and has been monetizing its pipeline in order to refocus efforts on tivo. (See BioWorld Today, Feb. 18, 2014.)
TOO MANY PICKLED VEGETABLES
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A China-focused statistical review published in Thoracic Cancer estimated there were 287,632 new cases of ESCC diagnosed and 208,473 deaths in 2010. Esophageal cancer incidence ranked fifth of all cancer types in China, with a rate of 21.88 per 100 000. For both incidence and mortality, men living in rural areas were most likely to be affected, peaking at the age 80 to 84.
In certain rural areas in Henan, Hebei and Shanxi, the incidence rate shoots to the highest in the world, greater than 100 cases per 100,000 according to a study in the Journal of Epidemiology. Other high incidence areas are found in the provinces of Sichuan, Anhui, Jiangsu, Hubei, Fujian, Guangdong and Xinjiang.
Studies show there is a complex interaction between genetic factors when combined with alcohol consumption, smoking and poor nutrition that can cause ESCC. It is believed diets containing a high quantity of pickled vegetables (with nitrosamine content) are also to blame.
ERBB3 (HER3)
ErbB3 belongs to a family of four proteins that also includes EGFR (HER1) and HER2 tyrosine kinase receptors. ErbB3 stimulates cancer growth and its overexpression generally correlates with poor prognosis.
AV-203 selectively targets the receptor ErbB3 and demonstrated preclinical activity in a number of different tumor models including breast, head and neck, lung, ovarian and pancreatic cancers. The preclinical data further showed the potential for heregulin, the only known ligand for ErbB3, to serve as a biomarker predictive of AV-203 anti-tumor activity.
Aveo completed a phase I study showing no dose-limiting toxicities at a maximum dose of 20 mg/kg.
Plans are already under way at Canbridge to make use of PDX mice models to continue testing CAN017 in tumors from Chinese squamous cell esophageal cancer patients. Company execs expect to be ready to submit an investigational new drug application next year, and take advantage of China’s new guidelines for innovative drugs.
“We are going to start a human trial in China first and hope to take advantage of the green channel approach. Because it is [CAN017 targets] a major malignant tumor, has a Chinese specificity, and we are going to manufacture the product in China, it will allow us to tap into the national guidance,” said Xue.
CHINA AS A LAUNCHPAD TO THE WEST
Meeting China’s significant unmet medical needs is the stated aim of many of China’s most promising biopharmas, in large part because there is such a gap between the drugs available in developed markets and in China – with only about 30 percent drugs available in China.
“The big multinational companies have set their center of gravity and development capabilities mostly in the West,” explains Xue. “Many products are successfully launched with Western populations as a priority. If they happen to be able to address a disease in the Asian population then it is perfect. However, if prevalence in Asia is much greater than in the West and you are still using this algorithm to the do the global launch then it will be quite a missed opportunity for those companies. That is where companies like Canbridge can come in.”
But with Canbridge’s first foray into a global rights deal, the company is joining a small band of companies that are hoping to pull the center of gravity slowly their way.
“Once the data generated in China begins to look very promising, we have strong confidence that we can replicate the data in the West,” said Xue. “We can utilize Asia as a base to develop innovative therapies for the global patient, instead of the other way around.”