Business Concentrates PETROCHEMICALS
Nektar advances abuse-proof opioid Biotech firm uses PEGylation to stem euphoria effect Nektar Therapeutics is advancing a new drug that uses polymer chemistry to reach an elusive public health goal: relief from chronic pain with little potential for misuse. The San Francisco-based biotech firm has released results of a study showing that its developmental opioid, NKTR-181, provides pain relief without the high levels of euphoria that can lead to misuse and addiction with standard opioids. Nektar previously reported that the drug significantly reduces pain in people with chronic lower back pain. Pain, particularly back pain, is a big problem for millions of Americans. But misuse of opioid pain relievers is arguably a bigger problem. In 2014, nearly 2 million Americans either misused or were dependent on prescription opioid pain relievers, Nektar says. Marketers of oxycodone and other opioids have confronted misuse with formulas intended to make their pills resistant to crushing and snorting. But people who misuse drugs often find ways to thwart the controls and extract the pills’ active ingredients. Nektar’s approach is to covalently bond, through an ether linkage, a short-chain polyethylene glycol to a five-ring morphinan, explains Chief Scientific Officer Stephen K. Doberstein. The molecule, whose structure will be published in the coming weeks, crosses the blood-brain barrier
Nektar’s R&D labs in San Francisco. slowly, preventing the “rush” that people who misuse drugs seek. “The speed of onset is super important,” Doberstein says. Moreover, the ether linkage is more stable than the morphine ring, according to Doberstein. Thus, he says, a person can’t use chemistry to break the linkage without denaturing the molecule’s active half. NKTR-181 represents only the second example of a PEGylated small-molecule drug, Doberstein says. The first is naloxegol, a derivative of α-naloxol that Nektar licensed to AstraZeneca in 2009. FDA approved it in 2014 for the treatment of opioid-induced constipation. Nektar continues to study the longterm safety of NKTR-181 in a Phase III clinical trial. Given its potentially large market, the company will seek a partner with pain drug experience. “We are talking to multiple companies,” Doberstein says.—MICHAEL MCCOY
Biotech summer Billions flowed to pharma venture funds in June and July. Investment firm
Pivotal bioVenture Partners
Atlas Venture
Clarus Ventures
New Enterprise Associates
Amount
$300 million
$350 million
$910 million
$3.3 billion
Focus
Early-stage start-ups
Early-stage inhouse start-ups
Structured deals that support Phase III clinical trials
Technology and health care, including genetics start-ups
Sources: Companies
10
C&EN | CEN.ACS.ORG | JULY 24, 2017
Another try at Vietnam’s first cracker Vietnam may finally get its first ethylene cracker. Siam Cement, a big Thai chemical maker, says it will proceed with the construction of Long Son Petrochemicals, a $5.4 billion chemical complex in the south of Vietnam, about 100 km from Ho Chi Minh City. The venture plans to award building contracts before the end of the year. Scheduled to come on-line in 2022, Long Son will feature an ethylene cracker with an annual production capacity of 1 million metric tons. Using feedstocks including locally sourced ethane and imported naphtha and propane, the complex will produce basic plastics such as polypropylene and polyethylene. About 30% of the investment will go to build infrastructure, including a deep-sea port. The project will be owned 71% by Siam Cement and 29% by state-owned PetroVietnam. Over the past two decades, Vietnam has repeatedly invited international firms to build oil refineries integrated with petrochemical complexes. Starting in the mid-1990s, companies including Total, Petronas, and LG all tried to launch such a project in central Vietnam. The refinery eventually opened in 2009— minus the petrochemical complex. Siam Cement’s decision to go ahead with Long Son comes as a consortium of Idemitsu Kosan, Kuwait Petroleum, PetroVietnam, and Mitsui Chemicals gets ready to open the country’s second refinery. Located in northern Vietnam, the $9 billion project will produce refinery-derived chemicals but no ethylene. According to Asian Development Bank, Vietnam’s economy has been growing at an average rate of 5.9% per year since 2012. In 2016, Vietnam imported 2.3 million metric tons of basic polyolefin plastics, Siam Cement claims.—JEAN-FRANÇOIS
TREMBLAY
CR E D I T: N E KTA R
DRUG SAFETY
