Chinese Pharma and Biotech Companies Tap U.S. Talent

There’s little doubt that Chinese biotech and pharma companies see tremendous growth opportunities in the United States. Numerous companies with roots in China have established toeholds in the U.S. and other companies have been busy recruiting U.S. talent to bolster their ranks.

Multiple companies from China have made beachheads in the U.S., including BeiGene Co.,WuXi AppTec and others. As those companies moved into the U.S. it became easier to recruit top talent because there was no concern about the need to uproot people from the U.S. and move them to China. Over the weekend, the Wall Street Journal noted the growing number of U.S. researchers and executives who are working with Chinese companies and spearheading clinical research for them in the United States in hopes of gaining regulatory approval in the world’s top pharma market.

In its report, the Journal pointed to the explosive growth BeiGene has seen over the past few years in the U.S. The company now has more than 400 employees in the United States and has poached top talent from companies like Genentech. Eric Hedrick, a former medical director at Genentech Inc., now serves as chief medical officer of BeiGene and told the Journal that he helped recruit many of his former colleagues for the Chinese company.

Christian Hogg, chief executive of Hong Kong-based Hutchison China MediTech (Chi-Med) told the Journal that it is more economical to research a drug in China where salaries are lower and then test them in the U.S. in hopes of gaining regulatory approval. Chi-Med is currently testing two drugs in the U.S. and recently gained approval from the U.S. Food and Drug Administration to test two more, the Journal said. As a result, Chi-Med is doubling its U.S.-based headcount over the next year, Hogg said.

As more and more Chinese companies enter the U.S. market, the Journal said more U.S. researchers and pharma executives are expected to join the ranks of employees.

But, some Chinese companies are moving a little slower into the United States due to increased concern from the Trump administration over corporate espionage. Washington has been increasingly focused on Chinese investment in the United States, particularly in the areas involving intellectual property and biotech. Earlier this year the government strengthened the review powers of the Committee on Foreign Investment in the United States. The bill’s powers have been used to prevent an increase in Chinese investment in U.S.-based companies. In April, the White House ordered the Chinese majority owner of Massachusetts-based healthcare company PatientsLikeMe to sell his stake. The move has caused a decline in Chinese investment in U.S. companies.

That concern over Chinese involvement in U.S. pharma has also led to the ouster of several researchers from noted research centers, including Emory University and M.D. Anderson Cancer Center.

Still, the Sino-American relationship in pharma is a two-way street. While the U.S. is the top market for pharma, China is not far behind. Western companies have also made their own inroads in China, such as Roivant Sciences, which established Sinovant, as well as Takeda Pharmaceuticals.

Luring U.S. talent has been a fairly common pastime for Chinese firms. Last year, BioSpace noted that as more western pharma companies sought toeholds in China, a lucrative market particularly in oncology, the government of that nation sponsored research grants to U.S. and western scientists to finance their research. China’s “Thousand Talents Plan” is aimed at attracting top researchers from across the globe. The program targets individuals under the age of 55 who are willing to work in China full-time. Those selected for the program are given full professorships or the equivalent in universities and research institutes. The “Thousand Talents Plan” was created in 2010 with an aim to “gather global wisdom,” according to the plan’s website. In January though, the Chinese government tamped down on the promotion of the plan due to a backlash of concern from the U.S. government. Law enforcement leaders in the U.S. have characterized China’s plan as a program aimed more at the theft of intellectual property than an attempt to bolster its own scientific research programs.

https://www.biospace.com/article/chinese-pharma-and-biotech-companies-tap-u-s-talent/

Short report: ‘Evidence That Biohaven Is Overvalued’

Biohaven’s drugs under development are for migraines (rimegepant and BHV-3500), Alzheimer’s disease and anxiety disorders (troriluzole and sublingual riluzole) and multiple system atrophy (BHV-3241).

The success of Biohaven’s troriluzole depends on the metabolic superiority of troriluzole over riluzole, which the available data does not indicate.

The extent of rimegepant’s success is dependent on bringing it to market before Allergan’s ubrogepant, but Biohaven has yet to submit their NDA.

Trading at $62.01, Biohaven appears to be overvalued – for now.

Biohaven (NYSE:BHVN) is a clinical-stage company developing drugs for migraine treatment and prevention, glutamate dysfunction in Alzheimer’s disease (AD) and anxiety disorders, and multiple system atrophy. The value of a drug company depends on the estimated demand for their products. In the case of Biohaven, their drugs in development potentially treat increasingly prevalent conditions such as migraines, AD, and anxiety. However, the following information casts doubt that Biohaven will capitalize significantly on these drugs.

Biohaven is developing troriluzole (BHV-4157), a 3^rd generation prodrug of riluzole. Troriluzole is a prodrug because it has an additional dipeptide conjugated to riluzole that is cleaved by aminopeptidases in the blood to release riluzole. The prodrug allegedly slows liver metabolism and enables dosing with meals. Riluzole acts by augmenting the expression and function of excitatory amino acid transporters located on astrocytes, which increases glutamate uptake from the tripartite synapse. Riluzole has been used to slow Amyotrophic Lateral Sclerosis progression since 1995. Riluzole’s antiglutaminergic effect could also reduce the glutamate-related neuronal hyperactivity found in early AD. Supporting this, are preclinical studies, wherein riluzole improved memory in aged mice and AD mouse models.

Riluzole is currently being tested for AD in a Phase 2 trial sponsored by the Icahn School of Medicine, with a study end-date of 11/2020. Biohaven’s troriluzole trial enrolls patients with MMSE scores of 14-24 for 48 weeks of treatment, with a study end-date of 1/2020. Biohaven is also testing troriluzole for indications of anxiety (Phase 3), obsessive compulsive disorder (Phase 2/3) and spinocerebellar ataxia (Phase 3) with study end-dates of 10/2019, 11/2019, and 10/2020, respectively. Biohaven owns a patent for 2nd generation riluzole derivatives (9725427), but the application for the 3rd generation prodrugs, including troriluzole, is still pending at the US Patent Office. Although, an international search report has favorably indicated novelty for the 3rd generation prodrug variations.

There’s one issue – the proof of troriluzole’s superior metabolic profile is arguable. A paper published in 2018 reporting research that was funded by Biohaven, showed graphs comparing riluzole serum levels in rats after oral administration of a prodrug-riluzole and riluzole. However, the graphed extension times for the two drugs are different, which prevents an accurate assessment of the prodrug’s superiority. In fact, the graphs show that the prodrug slows the availability of riluzole which then drops almost 10-fold over 24 hours. Thus, the prodrug’s availability profile doesn’t appear suitable for daily dosing.

The intravenous administration, however, does appear to have improved pharmacokinetics, but intravenous administration is obviously less convenient. The paper also shows only a slight potency difference between the prodrug and riluzole in a mouse xenograft model of melanoma. While this recent paper doesn’t identify the prodrug as troriluzole, the prodrug was chosen as the best performing and the composition is included in the second patent application. Data for troriluzole in humans has only been described in Biohaven’s SEC filings, and does not include specifics on enhanced time to peak extension.

Biohaven’s patent applications also do not compare the time-concentration curves with riluzole to demonstrate superiority. My concerns are that the alleged improved metabolic profile will not justify insurance coverage (Medicare) since generic riluzole will be much cheaper. (The composition patent for riluzole expired in 2013.) Biohaven’s Phase 2 trial does not compare troriluzole to riluzole, but hopefully, the FDA will mandate that comparison for Phase 3, especially if Icahn’s Phase 2 trial results show riluzole with strong efficacy.

However, even if the prodrug’s metabolic profile and efficacy is superior, the assignor’s research was funded by the U.S. government, so Biohaven’s exclusivity is insecure. The U.S. government could license troriluzole to a third party if it deems a public need. In summary, while it appears promising, the indications are that troriluzole acceptance is unlikely and investors should focus on other Biohaven products for estimating value.

Biohaven has formulated riluzole for sublingual dosing in ALS patients with swallowing difficulty. Riluzole can be crushed and dissolved orally but has an unpleasant anesthetic effect, so there is a need for a more convenient and palatable option. Recently, a liquid suspension of riluzole, named Tiglutik, became available, so Biohaven’s sublingual riluzole would be competing with Tiglutik. Further, grant of the pending patent for Biohaven’s sublingual formulation is uncertain given the applicant’s faulty justification of surprise efficacy or a composition formula that teaches away.

Biohaven’s most valuable asset appears to be rimegepant. Rimegepant is used to prevent and treat migraines and has an estimated market size of $8B. Rimegepant, an oral cGRP antagonist, will compete with Allergan’s oral cGRP antagonist, ubrogepant. Allergan submitted their new drug application (NDA) for ubrogepant on March 11, 2019. Biohaven paid $105M for a priority review voucher from the FDA to expedite the review of rimegepant. The standard time for an NDA decision is 9-12 months and a priority review is 6 months.

Obviously, Biohaven was hoping to offer rimegepant before patients flock to and adopt ubrogepant. However, with Biohaven’s NDA still not submitted, it looks like Allergan’s ubrogepant will be first to market. Further, Allergan has brand identity with physicians and more manufacturing and marketing experience. Biohaven might end up having to offer rimegepant for substantially less than ubrogepant to woo prescribers.

Biohaven will also share the migraine market with companies selling cGRP targeting antibodies that are intravenously infused once a month. However, most patients will want to leave that experience and cost behind. Biohaven also has a small molecule inhibitor of cGRP (BHV-3500) in a Phase 2/3 clinical trial. BHV-3500 is structurally distinct from rimegepant and is being formulated for multiple ways of delivery.

Other drugs in Biohaven’s pipeline are BHV-5000 for Rett syndrome and complex regional pain syndrome (Phase 2), and verdiperstat for multiple system atrophy (Phase 3). Both drugs have been given orphan status by the FDA to incentivize their development.

Regarding Biohaven’s financials, they have 44.2 million shares outstanding and a market cap $2.97B. Biohaven’s 2019 10-Q filing shows $217M in cash and a monthly burn rate of $14.7M. Biohaven appears to have enough capital to manufacture and market rimegepant.

In summary, even if the troriluzole trial results are stellar, Biohaven may not be able to capitalize on it, and thus, Biohaven’s value appears to lay solely on rimegepant and BHV-3500. Because rimegepant and BHV-3500 are being offered much later and with less brand identity, they may never be the preferred prescription migraine treatment. All of this together, indicates that Biohaven’s stock is currently overvalued.

https://seekingalpha.com/article/4269864-evidence-biohaven-overvalued

FDA OKs non-insulin Type 2 diabetes drug for kids, first to hit market in 20 years

The U.S. Food and Drug Administration on Monday approved Novo Nordisk’sNVO, +0.01% Victoza, a liraglutide injection, for the treatment of young patients 10 years or older with Type 2 diabetes. Although Victoza has been FDA-approved to treat adults with Type 2 diabetes since 2010, it is the only non-insulin drug approved for children other than metformin, which was approved for pediatric use in 2000. “Victoza has now been shown to improve blood sugar control in pediatric patients with Type 2 diabetes. The expanded indication provides an additional treatment option at a time when an increasing number of children are being diagnosed with this disease,” said Lisa Yanoff, acting director of the Division of Metabolism and Endocrinology Products in the FDA’s Center for Drug Evaluation and Research. Type 2 diabetes occurs when the pancreas is unable to make enough insulin to keep blood sugar at normal levels. It’s the most common form of diabetes, normally occurring in patients 45 years or older. However, in the past two decades, its prevalence among younger patients has dramatically risen. More than 5,000 new cases of Type 2 diabetes are now diagnosed each year in the U.S. among people younger than age 20, according to the Centers for Disease and Control and Prevention.

https://www.marketwatch.com/story/fda-approves-non-insulin-type-2-diabetes-drug-for-kids-the-first-to-hit-market-in-20-years-2019-06-17

Calithera’s Kidney Cancer Drug Doubles Progression-Free Survival Vs. Chemo

Calithera Biosciences Inc CALA 18.13% shares were making a strong upward move Monday following a clinical trial readout from the company.

What Happened

Calithera, which develops novel small molecule therapies for cancer and other life-threatening diseases, announced positive top-line results from a Phase 2 study dubbed ENTRATA that is evaluating telaglenastat, or CB-839, in combination with the chemotherapy drug everolimus in patients with renal cell carcinoma.

Telaglenastat is the first glutaminase inhibitor to demonstrate clinical activity for treating cancer.

The enrolled patients were heavily pre-treated with a median of three prior lines of therapy for advanced metastatic disease, including immunotherapy and multiple tyrosine kinase inhibitors.

The enrollees demonstrated that the evaluated combo treatment doubled the median progress-free survival to 3.8 months compared to 1.9 months for everolimus alone, Calithera said.

The risk of disease progression or death was also reduced by 36% in the combo treatment arm.

The combination was well-tolerated.

The secondary endpoint of overall survival has yet to mature, according to the South San Francisco, California-based biotech.

Why It’s Important

Telaglenastat is Calithera’s lead product candidate and is being evaluated in several combinations for renal cell carcinoma as well as solid tumors.

Two separate trials for renal cell carcinoma in combination with the chemotherapy drug cabozantinib and with everolimus are in the most advanced stage of clinical development among its pipeline assets.

“The achievement of positive topline results in our first randomized trial is a significant milestone for Calithera because it provides clinical proof of concept for teleglenastat,” Calithera CEO Susan Molineaux said in a statement.

https://www.benzinga.com/general/biotech/19/06/13928847/calitheras-kidney-cancer-drug-doubles-progression-free-survival-vs-chemotherapy

Celgene dips out of deals ahead of mega-merger

• Celgene has agreed to pay $150 million to exit a two-year-old deal with BeiGene focused on developing and commercializing one of the Chinese biotech’s immuno-oncology drugs.
• As a result, BeiGene regains full global rights to tislelizumab, an anti-PD1 agent under investigation across more than half a dozen cancers, including lung, liver and blood. BeiGene has filed the drug for approval in China for both relapsed/refractory classical Hodgkin lymphoma and locally advanced or metastatic urothelial carcinoma, and expects the first approval decision later this year.
• Celgene has been a frequent partner to smaller biotechs, but Wall Street analysts said that may change if Bristol-Myers Squibb’s planned acquisition of the company goes through. In the last week, BeiGene and Mereo BioPharma each announced fizzled partnerships with Celgene.

The mega-merger between Bristol-Myers and Celgene may affect dozens of biotechs that partner with the companies. But even early on, BeiGene’s deal looked particularly vulnerable to change because it centered around immuno-oncology — an area Bristol-Myers has well-covered with its blockbuster PD-1 drug Opdivo (nivolumab).

Right after Celgene announced its takeover in early January, BeiGene shares fell more than 15%.

“We believe investor uncertainty regarding the ultimate disposition of tislelizumab, including potential extent and duration of research funding as a key overhang,” Andrew Berens, an analyst at SVB Leerink, wrote about BeiGene in a Jan. 3 note to clients.

BeiGene executives, meanwhile, maintain a more positive outlook. They noted earlier this year that the company already finances and runs most of the pivotal studies for tislelizumab. And in a June 17 statement, CEO John Oyler said BeiGene is “well-positioned” to further advance the drug.

Celgene in mid-2017 secured rights to develop tislelizumab in solid tumors for all markets outside Asia, with Japan being an exception. In exchange, the Chinese biotech received $263 million upfront and an exclusive license to commercialize Celgene’s cancer drugs Revlimid (lenalidomide), Abraxane ​(paclitaxe) and Vidaza (azacitidine) in China. Celgene also took a 5.9% equity stake in BeiGene, valued then at $150 million.

While Celgene is backing away from tislelizumab, BeiGene said it will hold onto the commercial license to Celgene cancer drugs in China.

Mereo BioPharma is also getting rights back from Celgene.

Last week, the London-based company said Celgene chose not to exercise an option to license etigilimab, an antibody that inhibits certain T cell immunoreceptors. According to Mereo, which got etigilimab through the recent acquisition of OncoMed, research suggests these immunoreceptors prevent T cells from attacking tumor cells.

The deal between Mereo and OncoMed carried contingent value rights (CVRs) based on etigilimab achieving certain milestones. But because of Celgene’s decision not to opt in on the drug, Mereo doesn’t expect CVR holders will receive associated milestone payments.

https://www.biopharmadive.com/news/celgene-dips-out-of-deals-ahead-of-mega-merger/557029/

CELYAD: presents new results

Celyad announced that the results of ongoing Phase I and Deplethink studies evaluating CYAD-01 for the treatment of refractory and / or recurrent acute myeloid leukemia (AMR r / r) and myelodysplastic syndrome (MDS) continue to support the clinical development of the product candidate CAR-T based NKG2D.

Preliminary data from cohort 10 of the Think trial evaluating a more dense CYAD-01 schedule without preconditioning showed better cell engraftment than bi-monthly injections of CYAD-01 without preconditioning.

The first results of the Deplethink trial evaluating a single CYAD-01 administration after preconditioning chemotherapy demonstrated that the treatment was well tolerated with better T-CSC engraftment over time compared to the segment of the Try to increase the dose with a cycle of three injections of CYAD-01.

https://www.zonebourse.com/CELYAD-SA-13479209/actualite/CELYAD-presente-de-nouveaux-resultats-28765196/

Roth Capital Starts Amarin Corporation (AMRN) at Buy

https://www.streetinsider.com/Analyst+Comments/Roth+Capital+Starts+Amarin+Corporation+%28AMRN%29+at+Buy/15616698.html