BioMarin partners with local senior center for new lab expansion project

BioMarin is proposing three new buildings at the former PG&E site, with two for R&D and offices, and one combining housing and a senior center. (Pixabay)

BioMarin Pharmaceutical has teamed up with a local senior center in San Rafael, California, to advance a development project that would turn an old environmental cleanup site downtown into new laboratory and office space, as well as provide affordable housing and an activities center for the elderly.

The rare disease pharmaceutical company has submitted designs to the city for the expansion, proposing three new buildings: two for BioMarin’s R&D and general offices, plus a five-story building combining housing and the senior center, to be run by the non-profit Whistlestop.

BioMarin did not disclose the planned costs for its share of the new construction, located a five-minute walk from the company’s headquarters in San Rafael, with both about eight miles away from its manufacturing offices in nearby Novato.

Before BioMarin took possession of the lot—formerly home to a Pacific Gas & Electric manufacturing plant for decades—tens of thousands of cubic yards of contaminated soil were removed and trucked away, during a year-long cleanup project under a fully-enclosed tent, according to the Marin Independent Journal.

After the city’s design review phase, the two companies plan to submit a full construction application in September, Whistlestop CEO Joe O’Hehir told the San Francisco Business Times. “We needed a new location. They needed to show community benefit,” O’Hehir told the Business Times, describing the pairing that first launched in 2016.

https://bit.ly/2NrJ2IM

Controlling CRISPR and gene therapy with an amino acid switch

Gene editing and gene therapy have a range of potential applications, from editing out disease-causing mutations to treating spinal cord injuries. But the ability to control these treatments is a key concern, as they may stay switched on after they have had their intended effect, causing unwanted side effects. Scientists from the University of Bath and Cardiff University have created a switch that controls protein expression in cultured cells and mouse embryos and could one day be used in human gene therapies, the researchers believe.

The team tested the switch, an amino acid called BOC, in mice that had been genetically engineered to glow green under ultraviolet light. They used a method called genetic code expansion to create mouse embryos whose fluorescence gene had been edited out—but only in the presence of BOC. Edited embryos that were exposed to BOC were able to develop into mice that did not glow, but those not exposed to BOC remained green.

BOC is cheap and nontoxic and “should work in any protein in any species,” the researchers said in a statement. Many of the switch’s most immediate applications are environment-related—it could be used to keep the mosquito population down by propagating a gene that makes them infertile, they said. But it could also be used to control Cas9 proteins used in CRISPR-Cas9 gene editing. The study is published in Scientific Reports.

Adding switches to gene therapies is not a new idea, but current approaches have kinks that need to be addressed before they can be used in humans. Researchers from King’s College, for example, are working to treat spinal cord injuries using a gene therapy with an antibiotic-based “off” switch. The treatment triggers production of an enzyme that breaks down scar tissue, allowing neurons to regenerate. The antibiotic doxycyline is delivered after treatment to trigger the “off” switch.

While the treatment restored some hand function to rats that had suffered a spinal cord injury, a small portion of the targeted gene remained active even after the therapy had been switched off. The King’s team is working to shut off the gene completely and move into trials in larger animals.

As for gene editing, several approaches are in development to address the possibility of runaway editing. A team from the Salk Institute devised an “epigenetic CRISPR-Cas9” tool that edits DNA without cutting it as traditional CRISPR does, breaking the DNA and making it vulnerable to off-target mutations. The system is based on dead, or inactivated, Cas9. And the Broad Institute is using a CRISPR-based system dubbed REPAIR to edit RNA and bring about reversible changes in DNA. CRISPR pioneer Feng Zhang and colleague David Liu launched their startup, Beam Therapeutics, in May, which will use REPAIR and other technologies to edit nucleotide bases and correct point mutations.

Others are also focusing on enzymes to make CRISPR safer. Scientists at the Institute of Bioorganic Chemistry in Poland used a variant of Cas9 that cuts one strand of DNA rather than both strands.

The U.K. team sees the potential for BOC in several scientific and clinical settings. In addition to controlling gene therapy, the switch could be used to switch on and off proteins in cells to study aging, or to enhance regenerative medicine. The researchers now plan to “iron out wrinkles” in the system before testing it in broader applications, they said in a statement.

https://bit.ly/2KPuqBf

Beleave Unit Agrees to Lease Land in Colombia

Beleave Inc. (CSE: BE) (OTCQX: BLEVF) (“Beleave” or the “Company“) today announced that its Colombian subsidiary, Procannmed S.A.S. (“Procannmed“) has reached a land-lease agreement that will allow for the development and expansion of Procannmed’s cultivation of cannabis for sale and extraction purposes.

Under the agreement, Procannmed will lease up to 27 hectares (roughly 67 acres, or 2.9 million sq ft) of private land for a nominal monthly fee of $100 USD per hectare. The term of the agreement is for five years, with an option to renew for an additional five years.

Last month, Beleave announced it had acquired 51% of Procannmed for a combination of cash and Beleave common shares. The transaction stemmed from a lengthy due diligence process in which members of the Beleave team visited Colombia to speak with Procannmed representatives and various government and industry-related parties. This land deal is a direct result of those meetings and subsequent acquisition.

“This is an example of how we’re creating value beyond the immediate benefits of our growing and distribution activities,” says Beleave CEO, Andrew Wnek. “Now we can all look forward to the next stages of project development, and the tremendous potential this land offers to create value for shareholders.”

https://bit.ly/2IVIrf5

Bristol-Myers seeking buyer for French OTC drug unit

Bristol-Myers (BMY) has hired Deutsche Bank (DB) and Jefferies (JEF) to find a buyer for its French over-the-counter drugs business, which could be valued at over 1 billion euros, according to Reuters, citing sources familiar with the matter

https://bit.ly/2u6VzIM

Prana doses 1st patients in Phase 1 Parkinson’s trial

• Prana enrols and doses its first cohort of healthy volunteers in its Phase I clinical trial
• Evidence supports activity of PBT434 to prevent α-synuclein accumulation and neuron loss in experimental animal models of parkinsonian diseases
• Transition to human trials is a milestone for the Company building on its well-established scientific foundations
• Highly experienced drug development team, based in San Francisco, leading the program

Prana Biotechnology Ltd (ASX PBT: NASDAQ PRAN) is pleased to announce the first cohort of volunteers in its Phase I clinical trial have been administered PBT434, an experimental drug under investigation for the treatment of Parkinsonian diseases.

The trial conducted in Melbourne, Australia is recruiting and dosing healthy adult and elderly volunteers, to ascertain the optimal drug dose. The primary goal of the Phase 1 clinical trial is to demonstrate the safety and tolerability of PBT434, with a secondary endpoint of pharmacokinetic measures assessing and understanding how the drug is absorbed and metabolised in the human body.

PBT434 is the first of a new generation of small molecules designed to inhibit the aggregation of alpha(α)-synuclein and tau, critical intracellular proteins that are implicated in neurodegenerative diseases such Parkinson’s disease and atypical parkinsonism. PBT434 has been shown to reduce the pathological accumulation of these proteins in animal models of disease and has excellent potential to treat various forms of atypical parkinsonism, such as Multiple System Atrophy (MSA) and Progressive Supranuclear Palsy (PSP).

Prana’s Chief Medical Officer and Senior Vice President, Clinical Development Dr David Stamler, MD, said: “The first human administration of PBT434 is a major milestone for Prana. MSA and PSP are devastating diseases with no effective treatments and this is an important first step in developing a therapy for individuals with these diseases.”

The development program for PBT434 is being led by Dr Stamler from Prana’s San Francisco office. Dr Stamler and his team are highly experienced and have brought several new drugs to market, including deutetrabenazine for the treatment of Huntington’s disease chorea and Tardive dyskinesia, both of which were approved by the U.S. Food and Drug Administration (FDA) in 2017. This was the second neurological agent that Dr Stamler has led through the approval process with the FDA.

https://yhoo.it/2lV6ba0

Zynerba shifts gears to save cash after trial fail

• Zynerba Pharmaceuticals on Thursday announced negative topline results from a Phase 1 safety and dosing study of its transdermal tetrahydrocannabinol patch ZYN001, sending shares down as much as 15% in early morning trading.
• The results showed the patch was unable to achieve target blood levels of 5 to 15 ng/ml of tetrahydrocannabinol. There were no serious adverse events or discontinuations during the study.
• Based on the findings, Zynerba has chosen to shift its focus to ZYN002, which is being developed in Fragile X syndrome, developmental and epileptic encephalopathy and adult refractory epilepsy.

Zynerba made the decision to shift resources away from ZYN001 to conserve cash. The company now has cash and equivalents of about $52 million, and expects this will sustain operations through the second half of 2019.

Had ZYN001 delivered, the drug was expected to start a Phase 2 study in Tourette’s syndrome. Those plans have now been scrapped.

“The miss raises some question marks about efficacy of the transdermal delivery system and leaves ZYN002 as the company’s sole clinical asset, which has always accounted for our entire valuation,” wrote Jefferies analyst Biren Amin in a Thursday note to clients.

The company will now try to carry ZYN002 over the finish line. But with limited resources and a number of failures in the drug’s past, it will be a difficult task. Last summer, the company announced the drug failed in a mid-stage study for patients with adult epilepsy and focal seizures.

ZYN002, a synthetic transdermal cannabidiol gel, also failed to demonstrate a statistically significant reduction in knee pain for osteoarthritis patients last summer.

The movement comes after competitor GW Pharmaceuticals late last month won Food and Drug Administration approval for its cannabis-based epilepsy treatment Epidiolex (cannabidiol). While this marked the approval of the first plant-derived cannabis-based drug, the FDA was quick to point out that the data supporting approval of Epidiolex was unique and does not support the approval of any other cannabinoids.

https://bit.ly/2MQxca5

Gilead JAK inhibitor may be key to turnaround: Jefferies

Gilead Sciences is eagerly awaiting phase 3 data for its rheumatoid arthritis drug filgotinib in the next few weeks that could be an antidote for the biotech’s hepatitis C hangover.

That’s according to analysts at Jefferies, who see JAK inhibitor filgotinib as a $2 billion to $3 billion product for Gilead if the pivotal data show comparable efficacy to current drugs in the class, led by Pfizer blockbuster Xeljanz (tofacitinib), along with a clean safety profile.

Both Xeljanz and Eli Lilly’s recently approved Olumiant (baricitinib) are saddled with black-box safety warnings that could give Galapagos-partnered filgotinib a chance to quickly catch and possibly overtake its rivals.

Data from the FINCH-2 trial of filgotinib in RA patients who have failed biologics are due imminently and, if positive, could set up another phase 3 win in ulcerative colitis. The latter represents another $2 billion-plus market for the drug, say the analysts in a research note.

They suggest filgotinib’s greater JAK1 selectivity means it is less likely to affect platelets than its rivals, and so could have less risk of clotting side effects. And as it doesn’t appear to decrease hemoglobin levels and natural killer cells it could be less likely to cause other toxicities such as low red cell counts and infections.

That said, if all goes as hoped and filgotinib hits the top-line objective of a 20% to 30% improvement on the ACR 20 symptom scale after 12 weeks—depending on the dose—it could still be the fourth JAK inhibitor to reach the market for RA, behind Xeljanz, Olumiant and AbbVie’s much-touted upadacitinib.

“Filgotinib could be ‘best in class’ although fourth to market—and we acknowledge rebating will also be key here in the competitive market, as we note the street currently already appears unclear about how it will play out, hence not enough credit yet for the franchise.”

Of course, Gilead is looking for multiple new growth drivers now that sales of its hepatitis C franchise are in freefall, and filgotinib isn’t its only iron in the fire. Jefferies also points to nonalcoholic steatohepatitis (NASH) candidate selonsertib that is due to generate results in the first half next year, although it’s worth noting NASH is viewed as a tricky indication with a lot of companies in the race to market, so it’s a high-risk project.

And while there is a lot of bullishness about the biotech’s pipeline at the moment, there’s also a lot riding on both of these trial read-outs, and sentiment toward the company could be quickly dented if all doesn’t go to plan.

Nevertheless, Jefferies says Gilead “remains our top large-cap idea for a turnaround story and the most under-owned large cap in our coverage universe.”

Their turnaround projection is based in the near term on strong demand for three-in-one HIV drug Biktarvy, which has yet to make any meaningful contribution, as well as gradual increases for CAR-T therapy Yescarta and a bottoming out for hepatitis C product sales.

https://bit.ly/2NuPZc3