US-China Xynomic preps broad push for HDAC cancer drug after new financing

U.S.-China biotech Xynomic Pharma has raised additional funding to take an HDAC inhibitor in-licensed last year into seven new cancer trials.

The company hasn’t revealed the amount of the series B financing but says it will be enough to start trials of abexinostat—originally developed by Pharmacyclics—in blood cancers and solid tumors over the next 12 months. It will also fund initial clinical testing of XP-102, a pan-RAF inhibitor licensed from Boehringer Ingelheim in a $502 million deal last November, in colorectal cancer and melanoma.

Four of the seven abexinostat trials will be pivotal studies that could support registration, saysXynomic, including a multicountry study testing the drug as a monotherapy for follicular lymphoma and a similar trial in China. The other pivotal studies include a Chinese trial of abexinostat in diffuse large B-cell lymphoma (DLBCL) and a multicountry combination trial pairing the drug with Novartis’ Votrient (pazopanib) in patients with locally advanced or metastatic renal cell carcinoma.

The other three nonpivotal studies include a phase 1/2 assessment of abexinostat with Johnson & Johnson’s Imbruvica (ibrutinib) in DLBCL and mantle cell lymphoma, a phase 1b trial of the drug alongside Merck & Co.’s Keytruda (pembrolizumab) in multiple solid tumors, and a combination study in estrogen receptor-positive breast cancer.

Xynomic acquired exclusive rights to abexinostat in February 2017, without revealing any financial details or even who it had licensed the drug from. While Pharmacyclics originated the drug, it was initially licensed to French drugmaker Servier, which gave back rights to it in 2014 ahead of Pharmacyclics’ $21 billion takeover by AbbVie the following year.

The HDAC inhibitor class has come under pressure of late after an ASCO abstract for one of the leaders in the category, Syndax’s entinostat, revealed less-than-stellar results in a Keytruda combination trial which spooked investors and led to a dip in the company’s share price.

Meanwhile, Xynomic says it launched a dedicated R&D center in Shanghai last month that will focus on the discovery and early-stage development of small-molecule drugs focused on kinase inhibition, immuno-oncology and epigenetic modification. It’s already working on two candidates, says the biotech, namely XP-103, a TRK/Fra-1 inhibitor, and XP-104, a RET inhibitor.

Northern Light Venture Capital, Zhongshan Bison Healthcare Investment and Hakim Unique Internet Company led the round, with Xynomic’s existing investors—including Prosperico Ventures and the company’s founder and chairman Yinglin Mark Xu—also taking part.

https://bit.ly/2sqf3YI

Small molecule quells cancer-driving RNA, previously undruggable targets

Despite all the excitement gene-editing systems like CRISPR have generated, there have been challenges when it comes to delivering the technology. Viral vectors are commonly used but can lead to off-target editing and side effects such as cancer. Researchers from The Scripps Research Institute have been working on an alternative: a small molecule that can selectively target RNA and could pave the way to a pill that can treat genetic diseases.

DNA-targeting CRISPR has dominated the gene editing landscape, but RNA-focused systems are on the rise. These systems target RNA to bring about reversible changes to DNA, but are delivered in much the same way—via injection.

Matthew Disney, a professor at Scripp’s Florida campus, has been working on small molecules that target RNAs, which have historically been considered undruggable due to their small size and relative lack of stability. What’s more, it is difficult to selectively target RNAs because they are made of just four ingredients: the nucleotide bases A, T, G and C. Proteins, on the other hand, are composed of many different amino acids.

Disney’s approach combines an RNA-degrading enzyme with a druglike molecule that binds selectively to a specific RNA. The complex, dubbed RIBOTAC (ribonuclease-targeting chimeras) is designed to latch onto and destroy an “undesirable gene product,” such as a disease-causing RNA, according to a statement from Scripps.

The team tested their technology against miRNA-96, a microRNA oncogene that fosters cancer cell proliferation. They tethered the RNA-degrading enzyme RNase L to Targaprimir-96, a molecule they created in 2016 to bind with miRNA-96. The treatment selectively cleaved the miRNA-96 precursor in cancer cells, silencing the oncogene. It “derepressed” the transcription factor FOXO1, unleashing cell death in triple-negative breast cancer cells, but not in healthy breast cells. The findings appearin the Journal of the American Chemical Society.

Others have tried to target RNA with an antisense approach, using strands of DNA or RNA to knock down specific molecules of RNA and treat disease. Ionis Pharma has licensed out antisense treatments to Roche, AstraZeneca and Janssen in deals targeting Huntington disease, kidney disease and gastrointestinal disease, for example.

On the flip side, Accent Therapeutics launched this year to drug RNA-modifying proteins (RMPs), which have been linked to certain cancers. The biotech is working to understand which proteins are involved in which cancer indications and to identify the patients who would be most likely to respond to treatment.

Accent has selected 20 RMPs it believes have “strong implications” in specific cancer indications and prioritized them according to unmet medical need and what it knows about the biology of those targets, including whether they are likely to be a druggable. Of these, it has picked four targets and is working to identify chemical matter for each one, Chief Scientific Officer Robert Copeland told FierceBiotech.

Awakening the body’s ability to kill its own cancer by exploiting cells’ RNA degradation system offers a novel approach to attacking cancer, says Disney of Scripps.

Scripps intends to apply its technology to hard-to-treat cancers, genetic disorders and other diseases for which there are no known cures. “The applications range from cancer to incurable disease—basically any disease where RNA is a key driver,” Disney told FierceBiotechResearch in an email.

https://bit.ly/2xxXgnE

STAAR Surgical (STAA) Short Interest Update

STAAR Surgical (NASDAQ:STAA) was the recipient of a large decline in short interest during the month of May. As of May 15th, there was short interest totalling 494,547 shares, a decline of 49.1% from the April 30th total of 971,594 shares. Approximately 1.2% of the shares of the stock are short sold. Based on an average daily trading volume, of 872,862 shares, the short-interest ratio is currently 0.6 days.

https://bit.ly/2xv8JEm

Amgen latest drugmaker with Herceptin biosimilar sidelined by FDA letter

Amgen, in a two-sentence announcement today, said it received a complete response letter for the biosimilar of Roche’s cancer med Herceptin it developed with Allergan. It marks the third Herceptin biosimilar that has been stalled by the FDA but has won approval in Europe.

The Thousand Oaks, California-based drugmaker offered no insight into what the FDA found lacking in its version. “We will work closely with the FDA to bring this important medicine to patients in the U.S. We do not expect this to impact our U.S launch plan,” it said in the announcement.

Biosimilar makers have been hot to develop their own versions of Roche’s Herceptin, a long-in-the tooth oncology drug that still raked in $2.5 billion in U.S. sales last year and $7 billion worldwide. Mylan and partner Biocon, Pfizer and now Amgen have all had their initial applications rejected by U.S. regulators. Pfizer just today won an European Medicines Agency approval for its Trazimera.

None of the drugmakers have provided much detail as to what triggered their CRLs, so it is unknown whether there has been a common theme for the denials or what the hangup is for the FDA that has not bothered the EMA. FDA concerns about Biocon’s Indian plant figured into the rejection of the version from Mylan and its Indian partner.

Mylan and Biocon won an FDA thumbs-up for their Herceptin biosimilar in December, but only after a three-month delay in which the FDA looked over some new technical data that had resulted from changes made in their manufacturing operations. When the partners got their CRL it looked like they would go from the front of the line to the back of the line as the FDA considered applications from other drugmakers. But the partners ended up being the first to win approval as competitors also had their versions sidelined.

These delays have allowed Roche to continue to go to the Herceptin cash machine. Despite recent approvals for biosimilars in the EU, Herceptin sales worldwide were up 3% last year to about $7 billion on higher sales in the U.S. and Brazil. While most of those sales come from the U.S., $2.7 billion, EU revenue is also significant, at $2.1 billion.

While regulatory and manufacturing stumbles have protected Roche’s Herceptin sales, the Swiss drugmaker is also throwing up roadblocks. Last fall, Roche sued Pfizer for infringement on 40 Herceptin patents, asking a court to block a potential biosim launch. Pfizer said it will defend its “position vigorously and in the appropriate venue.”

https://bit.ly/2syTVPt

Medtronic recalls HeartWare HVAD over electrical disconnection

Medtronic is recalling the HeartWare HVAD because of the possibility for an interruption to occur in the electrical connection between the system’s power source and the HVAD controller, the FDA said in a statement on its website. The agency added, “Interruptions to the electrical connection could cause unintended intermittent electrical disconnection, which could result in a pump stop. A pump stop could cause patient harm such as exacerbation of heart failure symptoms, or symptoms such as mild weakness, dizziness, anxiety, nausea, loss of consciousness, or death.”

https://bit.ly/2JkqlHT

Theranos investors cannot pursue class action: U.S. judge

A U.S. judge has ruled that investors who claimed that Theranos Inc defrauded them into investing indirectly in the company by touting revolutionary blood-testing technology that never existed cannot pursue their claims as a class action.

The ruling late on Thursday by U.S. Magistrate Judge Nathanael Cousins in San Jose, California, is a setback for investors who might otherwise recover more by suing Theranos, Chief Executive Elizabeth Holmes and former Chief Operating Officer Ramesh “Sunny” Balwani as a group.

The proposed class had included more than 200 people who invested in funds between July 29, 2013, and Oct. 5, 2016 for the purpose of buying shares in Theranos, once a star of Silicon Valley.

Cousins, however, said individual lawsuits were appropriate because some investors might be unable to show they relied on the blood-testing company’s alleged misrepresentations.

“It is easy to imagine, for example, that someone invested simply because a friend suggested it, or because all that percolated down the grapevine was vague insight that Theranos was a fast-growing company, or had promising (but unspecified) technology,” Cousins wrote in a 34-page order.

Reed Kathrein, a lawyer for the plaintiffs, said he may appeal or seek reconsideration.

“It is too early to say anything other than we are very disappointed,” ahead of the scheduled depositions of Holmes and Balwani and completion of discovery this month, Kathrein said in an email.

Indirect investors in private companies such as Theranos cannot sue under federal securities laws, which address the integrity of public markets. The Theranos investors sought to avoid this by suing under California state law.

Michael Mugmon, a lawyer for Theranos, said: “We are pleased by the court’s ruling, as it brings the company a step closer to resolving its outstanding legal issues.”

Lawyers for Holmes and Balwani did not immediately respond to requests for comment.

Once valued at $9 billion, Theranos’ fortunes darkened amid reports that its technology, which offered hope that one drop of blood could help Americans control their health, did not work.

On March 14, the U.S. Securities and Exchange Commission charged Theranos, Holmes and Balwani with running a “massive fraud” by exaggerating the technology while raising more than $700 million from investors.

Holmes settled by agreeing to cede majority control, pay a $500,000 fine, and not serve as an officer or director of public companies for 10 years. Balwani did not settle.

Theranos also faces a criminal probe into whether it misled investors, The Wall Street Journal said in April.

The case is Colman et al v Theranos Inc et al, U.S. District Court, Northern District of California, No. 16-06822.

https://reut.rs/2JgMC9B

ASCO stand on Trump drug price proposals

A leading U.S. group of cancer doctors is wary of new Trump administration proposals for lowering drug prices, particularly if new negotiation tools are introduced that will mean the U.S. government no longer routinely pays for all cancer drugs in the Medicare health program for older people.

The rising cost of cancer care will be in focus during an annual meeting of the American Society of Clinical Oncology (ASCO) that begins Friday in Chicago. In recent years, potent new immunotherapies and treatments that target genetic mutations underlying cancer have successfully curbed the disease in some patients.

But they have come with ever-rising price tags, spurring new questions about how much individuals, corporations and the government in the United States, already the world’s most expensive health system, will pay for these breakthroughs.

President Donald Trump last month unveiled a “blueprint” to reduce drug prices by promoting the entry of cheaper rivals to existing drugs and giving private insurers more scope to negotiate prices.

In private health insurance plans, insurers have tools to negotiate prices on the drugs they cover for their members. In exchange for manufacturer discounts, insurers may lower the patient co-payment below competing treatments, or drop coverage of a rival drug altogether, to increase prescriptions.

The Trump proposal includes the possibility that the government would stop covering all approved drugs for certain illnesses, including cancer, in the Medicare program. It has requested feedback from the industry on this and other ideas.

“It is a balancing act, because we do think that there should be an ability to negotiate price, but we are always driven by our belief that patients should not be denied the most effective drugs for their condition,” ASCO’s chief executive officer, Dr. Clifford Hudis, told Reuters.

Another idea is to change Medicare’s reimbursement of doctors including a fee calculated as a percentage of a drug’s price. Critics say the payments encourages physicians to use the most expensive drugs. Hudis said ASCO is not opposed to changing the formula, but argues that oncology practices will still need to be reimbursed for handling specialized cancer medicines delivered by infusion or injection.

ASCO, the nation’s leading association of cancer physicians, said it will publicize its full response after submitting feedback to the Trump administration by a July 16 deadline.

EFFECTIVENESS VS PRICE

U.S. spending on cancer drugs reached almost $50 billion last year – nearly doubling since 2012 – and is projected to double again to $100 billion in five years, according to IQVIA, which collects drug sales data.

Expensive new cancer treatments like Merck & Co’s $162,000-per-year immunotherapy Keytruda and Gilead Sciences Inc’s $373,000 blood cancer therapy Yescarta, which have helped some patients survive previously untreatable disease, are contributing to the increase.

But so are less effective drugs without competitors whose prices are raised by manufacturers each year. Oncologists and other specialists benefit from price increases on drugs that are administered in their offices.

Without percentage-based fees, oncology practices would lose “their ability to make considerable sums off their relationship with the pharmaceutical industry,” said Dr. Peter Bach, director of Memorial Sloan Kettering’s Center for Health Policy Outcomes in New York. ASCO and other institutions have proposed their own methods for reducing healthcare costs, but stopped short of urging drugmakers to lower prices. ASCO has recommended ranking drugs on their comparative clinical value, including relative efficacy and side effects, but not price. The group has also suggested that the price of a cancer drug could vary depending on how effective it is for a specific indication, or how well an individual patient fares after the treatment.

The association does not support moving to a flat fee for treating cancer patients, including drugs, an approach that is being used in other specialties. That “could force providers to make suboptimal or lower-value choices,” the organization said. At ASCO’s annual meeting, which runs from June 1-5, cancer researchers will provide new data on survival rates with Keytruda, on the emerging class of CAR-T cell treatments for blood cancers and on genetically targeted therapies.

Some research will address the cost question, including a comparison of treatment costs and outcomes for colon cancer patients in the United States and Canada.

https://reut.rs/2LegmB5