Vectura hopes new respiratory device will breathe life into business

Vectura Group is pinning its future on a relatively new respiratory device aimed at treating several ailments beyond asthma, as the British drugmaker looks to revive its business after the costly acquisition of rival SkyePharma in 2016.

Vectura, which has partnerships with Bayer, Novartis and GSK, said on Thursday its 2018 adjusted core earnings would exceed analysts’ forecasts, citing rising sales of inhalers and improved margins.

Vectura’s shares, which fell more than 40 percent in 2018, closed 13 percent higher at 80 pence, giving the company a valuation of around 532 million pounds.

The company also said research and development expenses for 2019 would remain unchanged from its forecast of 45-55 million pounds, with 2018 investments at, or around, the bottom of the 55 million to 65 million pounds range.

Most of that cash is being spent on its “nebulised platform”, which is expected to treat common respiratory diseases such as asthma as well as other ailments, Chief Financial Officer Paul Fry told Reuters on Thursday.

Fry said the company’s new nebulised devices, which convert liquid medicine into mist that is inhaled by patients, would also focus on paediatric asthma, cardio pulmonary vascular disease and cystic fibrosis.

“We are looking to explore that platform in a number of different therapy areas like cystic fibrosis … we believe there is an important market opportunity and something that perhaps not many people are exploiting.”

Fry said Vectura was seeking a partner for its paediatric asthma treatment, but did not give details on any potential deal.

Vectura stopped developing a treatment for severe uncontrolled asthma in November after trials showed it failed to have a significant impact on the condition.

The company said then it would take an impairment charge related to the failure that would hit its 2018 pretax results by 40 million pounds.

While the company posted a 96.2 million pounds operating loss in 2017, due to an impairment charge related to previous acquisitions, it reported adjusted core earnings of 25.8 million pounds.

Fry said 2018 margins benefited as a larger proportion of sales of its biggest product Flutiform came from Japan and other high-margin regions.

Margins were also helped by fewer batches of products being written down and lower production costs due to changes in suppliers.

Fry added that Vectura’s deal with Hikma Pharmaceuticals for generic versions of GSK’s Ellipta portfolio also boosted revenue in 2018.

https://www.marketscreener.com/GLAXOSMITHKLINE-9590199/news/Vectura-hopes-new-respiratory-device-will-breathe-life-into-business-27816410/?countview=0

MIT Sloan professors’ model cuts liver transplant candidates’ deaths by 20%

Demand for liver transplants is much higher than organ supply, resulting in approximately 2,400 deaths every year. Also problematic is the current model used to identify and prioritize the “sickest” patients, which does not allow for equitable access to all waitlisted candidates, with a particular disadvantage to women. To address these issues, MIT Sloan School of Management Prof. Dimitris Bertsimasand Prof. Nikos Trichakis utilized machine learning to create a model that reduces mortality by 20%, averting nearly 400 deaths each year. Their model, Optimized Prediction of Mortality (OPOM), also provides a fairer and more equitable allocation to candidate groups, including women.

“There are many significant benefits to using this new model over the current system. Unlike the current system, which makes some arbitrary choices and results in bias against certain populations, OPOM’s methodology for prioritization is clear and understandable to surgeons — and it can save hundreds of additional lives every year,” says Bertsimas.

Trichakis noted, “OPOM fixes many of the current system’s problems because it was designed specifically for liver patients using real data. As a result, it can accurately prioritize patients across all populations without bias. This shows the potential of machine learning technology to help guide clinical practice and national policy on transplants.”

The researchers explain that the current model created in 2002 depends on the Model for End-Stage Liver Disease (MELD) score to rank disease severity and priority for receiving a liver transplant. As certain patient populations are at risk of death or of becoming too sick or unsuitable for transplantation based upon disease progressions that are not captured in their MELD score, the system arbitrarily grants them “exception” points. While the overall MELD score has led to a more objective ranking of candidates awaiting liver transplantation, the process of MELD exception point granting has resulted in inequitable and undesirable outcomes.

More specifically, the MELD exception points policy has disadvantaged women. “Data shows that women have historically had less access to liver transplantation and have had higher death rates on the wait list,” notes Trichakis. “This is due to the awarding of exception points to cancer patients, as more than 75% of those patients are men. Women also tend to have lower muscle mass and higher sodium levels, which lowers their MELD scores.”

Using a state-of-the-art machine learning method developed at the MIT Operations Research Center and real historical data from liver patients, the researchers sought a better way to prioritize the allocation of organs. With OPOM, they asked the question: What is the probability that a patient will either die or become unsuitable for liver transplantation within three months, given his or her individual characteristics?

They found that the OPOM allocation outperformed the MELD-based prediction method in terms of accuracy and fairness. In simulations, OPOM averted significantly more waitlist deaths and removed the bias against women. As a result, it allowed for more equitable and efficient allocation of liver transplants.

“Unlike MELD, which relies on an inexact approach of exception point assignment, OPOM allows for accurate prioritization of all candidates and removes bias for or against particular groups,” says Trichakis.

Bertsimas adds, “If we use this model to change how we measure mortality and allocate livers, the death rate will decrease by 20%, which is very significant. We’re hopeful that our findings will affect the national policy.”

Bertsimas and Trichakis are coauthors of “Development and validation of an Optimized Prediction of Mortality (OPOM) for candidates awaiting liver transplantation” with transplant surgeons Dr. Ryutaro Hirose of the University of California and Dr. Parsia A. Vagefi of the University of Southwestern Medical Center. Additional coauthors include MIT Sloan students Yuchen Wang and Jerry Kung. Their paper has appeared online in the American Journal for Transplantation.

https://www.biospace.com/article/mit-sloan-professors-model-decreases-liver-transplant-candidates-deaths-by-20-percent-/

DURECT Call to Provide Corporate Update on January 7, 2019

DURECT Corporation (Nasdaq: DRRX) invites interested parties to listen to a corporate update conference call that will be broadcast live over the internet on Monday, January 7, 2019 at 8:00 am Eastern Time (5:00 am Pacific Time).

A live audio webcast of the presentation will be available by accessing DURECT’s homepage at www.durect.com and clicking “Investor Relations.”  If you are unable to participate during the live webcast, the call will be archived on DURECT’s website under Audio Archive in the “Investor Relations” section.

https://www.biospace.com/article/releases/durect-corporation-announces-investor-call-to-provide-corporate-update-on-january-7-2019/

SCYNEXIS Provides Year-end Update and Outlines Plans for 2019

Initiated VANISH Phase 3 program of oral ibrexafungerp in acute VVC; top-line data expected in 1H 2020 with potential NDA filing in 2H 2020
Initiation of recurrent VVC Phase 3 trial planned for 1H 2019
Continued advancement of oral ibrexafungerp clinical development program in hospital-based invasive fungal infections
Received non-dilutive state incentive cash benefit of $6.7 million; approximately $51 million cash balance as of January 3, 2019, sufficient to ensure full funding of the VANISH Phase 3 VVC trials past top-line data

SCYNEXIS, Inc. (NASDAQ: SCYX), a biotechnology company delivering innovative therapies for difficult-to-treat and often life-threatening infections, today provided a year-end update and 2019 development plans for ibrexafungerp, an investigational antifungal agent and the first representative of a novel class of structurally-distinct glucan synthase inhibitors, triterpenoids.

“In 2018, we achieved multiple meaningful clinical milestones, most notably reporting positive data from our Phase 2b DOVE study evaluating oral ibrexafungerp for the treatment of vulvovaginal candidiasis (VVC),” said Marco Taglietti, M.D., President and Chief Executive Officer of SCYNEXIS. “The identification of a clinically and mycologically effective, well-tolerated oral dose of ibrexafungerp was a critical step for the initiation of our global Phase 3 program. The outcome of this registration program could be transformative for the millions of women with VVC not satisfied with existing therapies and also for SCYNEXIS, as ibrexafungerp could represent the first new antifungal class approved since 2001.”

Dr. Taglietti continued: “We are laser-focused on ensuring the efficient and timely completion of our VANISH Phase 3 trials to allow an NDA filing expected in the second half of 2020. We start 2019 with approximately $51 million in cash, sufficient to ensure the full funding of the VANISH Phase 3 trials past top-line results. We will continue to operate thoughtfully to progress the development of ibrexafungerp across multiple indications and to opportunistically explore commercial partnerships and other non-dilutive forms of cash injections, like the recent $6.7 million we received from the New Jersey Technology Business Tax Certificate Transfer (NOL) Program.”

Ibrexafungerp Development Update:

• Initiated VVC Phase 3 registration program. SCYNEXIS remains on track to report top-line data in 1H 2020, with potential New Drug Application (NDA) filing in 2H 2020.
  • The VANISH Phase 3 program comprises two Phase 3 trials (approximately 350 patients each) designed to evaluate the safety and efficacy of one-day oral ibrexafungerp versus placebo for the treatment of VVC. Pending successful completion of these two trials, SCYNEXIS plans to file an initial NDA for oral ibrexafungerp for the treatment of VVC in 2H 2020.
  • SCYNEXIS plans to initiate a third Phase 3 trial (approximately 350 patients) evaluating oral ibrexafungerp versus placebo in recurrent VVC in 1H 2019, an indication with no product currently approved.
  • The Phase 3 program builds on the positive top-line data reported from the Phase 2bDOVE study in July 2018, which showed that the one-day oral ibrexafungerp dose selected for Phase 3 clinical evaluation was well-tolerated, with strong overall clinical and mycological activity and improved sustained effect compared to fluconazole, the current standard of care for VVC.
  • If approved, ibrexafungerp would provide an oral option for millions of women not currently well-served by existing VVC therapies, most notably patients failing fluconazole or relapsing after treatment, with infections caused by fluconazole-resistant Candida spp., with difficult-to-treat symptoms, with recurrent VVC (for which no product is currently approved) and of child-bearing age concerned about fluconazole’s reported embryo/fetal toxicities.

• Continued advancement of oral ibrexafungerp clinical development in hospital-based invasive fungal infections.
  • Site initiation activities continue to progress for the Phase 2 trial (SCYNERGIA) designed to evaluate the safety and efficacy of oral ibrexafungerp in combination with standard-of-care voriconazole in patients with invasive pulmonary aspergillosis. An animal model of pulmonary aspergillosis demonstrated improved outcomes and survival rates, supporting the potential superiority of ibrexafungerp in combination with azole therapy versus standard of care alone in this high-mortality indication.
  • The FURI study, evaluating oral ibrexafungerp for the treatment of patients with invasive fungal infections refractory or resistant to standard of care, is ongoing. A preliminary assessment by a Data Review Committee (DRC) of the first 20 completed patients was recently conducted, and SCYNEXIS anticipates reporting top-line findings by February 2019.
  • The CARES study, evaluating oral ibrexafungerp for the treatment of patients with Candida auris infections, is ongoing with several patients enrolled. C. auris is an emerging life-threatening and multidrug-resistant fungal pathogen, with a mortality rate of up to 60%. CARES is the first study assessing an investigational agent against this pathogen.
  • While oral ibrexafungerp is progressing as a potential valuable option to treat hospital-based invasive fungal infections, SCYNEXIS continues the development of the intravenous liposomal formulation of ibrexafungerp and will provide further updates in the future.

Corporate Update:

• SCYNEXIS is committed to identifying non-dilutive forms of cash injections. Through the Technology Business Tax Certificate Transfer (NOL) Program in the state of New Jersey, SCYNEXIS recently obtained $6.7 million of non-dilutive funds.
• Considering SCYNEXIS’s worldwide rights to ibrexafungerp and patent protection until 2035, SCYNEXIS continues to explore business development partnerships to maximize ibrexafungerp’s commercial opportunity.
• As of January 3, 2019, SCYNEXIS has cash, cash equivalents and short-term investments of approximately $51 million. SCYNEXIS expects this will be sufficient to ensure full funding of the VANISH Phase 3 VVC trials past top-line results, expected in 1H 2020.

https://www.biospace.com/article/releases/scynexis-provides-year-end-update-and-outlines-plans-for-2019/

UroGen Taps Oncology Veteran Elizabeth Barrett as Its New CEO

Novartis and Pfizer veteran Elizabeth Barrett will take over as the new president and chief executive officer of UroGen. Barrett, who most recently helmed Novartis Oncology, will take over as Ron Bentsur steps down from his role as CEO.

Barrett will make her first official appearance as CEO of UroGen at the J.P Morgan Healthcare Conference in San Francisco next week. Barrett has more than 30 years of experience in the field of oncology. During that time, she has gained considerable expertise in pharmaceutical development and commercialization of oncology products. That experience will be critical as UroGen looks to make the leap into becoming a leading commercial-stage entity in the urological setting.

Barrett takes over as the company moves forward with a goal of developing the first drug approved for low-grade upper tract urothelial cancer. In December, New York-based UroGen initiated a rolling submission to the U.S. Food and Drug Administration for a New Drug Application for UGN-101, (mitomycin gel). The company hopes to see approval of the asset this year. The company’s pipeline is built on its RTGel technology platform, a sustained release, hydrogel-based formulation.

Arie Belldegrun, the chairman of the board of directors for UroGen and the former Kite Pharma executive, touted Barrett as an executive who has proven to be “an exceptional leader with a well-established track record in oncology.” Belldegrun said she has the “vision and experience” to lead UroGen as the company moves forward with the potential commercialization of UGN-101.

Barrett joins UroGen from her brief tenure as head of Novartis Oncology. Prior to that, she served as Global President of Oncology at Pfizer Inc.

In a posting on her LinkedIn account, Barrett said she chose to leave big pharma for a smaller company for several reasons. Over the course of her career, she has seen a number of significant innovations in oncology, but she said uro-oncology has been a field that “innovation has left behind.”

“Therapeutic options to manage urologic cancers are limited, and for many patients, the only treatments are surgical, involving removal of the kidney, bladder and/or ureter. UroGen is the first to take important steps to treat these patients differently,” she wrote.

Barrett pointed to the RTGel platform as a potential solution to the unmet needs in uro-oncology. She said the “simple elegance” of the platform has the “potential to revolutionize how we treat urologic cancers and beyond.” In her post, she said she wants to be part of that revolution.

Barrett added that she has had an opportunity to be entrepreneurial in her various roles throughout her career, but with UroGen, she can take those lessons and apply them to a smaller company that is on the “cusp of transformation.”

“I cannot think of a more exciting time to join UroGen and work with its outstanding team as we begin to revolutionize uro-oncology and beyond,” she said in a statement.

As Bentsur steps away from his role with the company, he said he believes Barrett will have the experience to build on the clinical successes he oversaw and guide the company through commercialization.

https://www.biospace.com/article/urogen-taps-oncology-veteran-elizabeth-barrett-as-its-new-ceo/

Tiburio Launches With $31M, 2 Ipsen Rare Disease Compounds

New biotech Tiburio has surged onto the scene with $31 million in financing and two novel Phase II-ready assets licensed from Ipsen Pharma. The new company, spun out of orphan drug accelerator Cydan, is focused on rare endocrine diseases.

Abraham N. Ceesay has left his role as chief operating officer of scPharmaceuticals to take over as the new chief executive officer of Tiburio, which will be based in Cambridge, Mass. In an interview with BioSpace, Ceesay said he was drawn to the Tiburio because of its focus on developing therapies for unmet needs in neuroendocrine diseases.

“This was an opportunity to build a special company… that truly has a clinical stage pipeline,” Ceesay said.

The assets Tiburio secured from Ipsen are TBR-760, which is being developed for the treatment of an unmet need in non-functioning pituitary adenomas (NFPAs) and TBR-065 for treatment for rare endocrine diseases that the company has not disclosed. Both compounds are dopamine-somatostatin chimeric molecules, which inhibit NFPA cell proliferation and have the potential to shrink or halt tumor growth.

Ceesay noted that TBR-065, the second compound the company licensed, has a potentially wider scope than TBR-760. He said the company sees the compound for an unmet need in treating NFPAs, but has a “little more work to do to determine what the most appropriate target indication is for that.” Ceesay plans to initiate the first trial for TBR-760 in the second half of 2019. As the company moves forward with the two compounds, Tiburio will have two former Ipsen executives, Heather Halem and Michael Culler, the former head of endocrinology research, to help guide them through development.

NFPAs are non-metastatic tumors in the pituitary gland in the brain. Their development can result in life-altering and potentially life-threatening consequences for patients. Currently there are no approved therapies to treat these tumors and patients must undergo transsphenoidal surgery and/or radiation to remove or shrink the tumor.

Ceesay said the company was drawn to the two Ipsen compounds because of the unmet need in treating NFPAs. He said the current standard of treatment is an “aggressive and invasive neurosurgery” to remove the tumors. He said the fledgling company sees the potential to bring the first approved therapy to halt pituitary adenomas without the need for the surgery or radiation treatment.

With these therapies, as well as others that can be developed or acquired, Ceesay said there a real opportunity for innovation in the neuroendocrine space. He wants to establish Tiburio as a significant player in that arena. Ceesay said the company plans to be opportunistic about future opportunities in the space, but did not provide any details about what that could be.

As Tiburio moves forward, Ceesay said he intends to draw on his past experience from his days at Genzyme and build a strong relationship with clinical and patient advocacy groups in the neuroendocrine arena.

“In all rare diseases, the community… is critical as you think about establishing a company and developing a therapy. We are building our relationships with patient organizations to garner guidance we need along the way,” Ceesay said. “I hold those lessons tight. At the end of the day, what we do is truly about the patients.”

Tiburio launches with $31 million in a Series A financing round that will fund the companies’ lead compound, TBR-760, through human proof-of-concept for the treatment and further clinical assessment of TBR-065. The Series A was supported Cydan’s syndicate of leading life sciences investors, including New Enterprise Associates, Longitude Capital, Lundbeckfond Ventures, and Alexandria Venture Investments. As part of the licensing agreement, Ipsen will have a minority stake in Tiburio, and will also be eligible to receive development and commercial milestone payments and royalties on sales.

https://www.biospace.com/article/tiburio-launches-with-31-million-and-two-compounds-from-ipsen-targeting-rare-endocrine-diseases/

After Opioid OD, ‘Most Patients Can Leave Hospital in an Hour’

People who overdose on opioids can often be saved quickly with a dose of naloxone, but it hasn’t been clear how long someone should be kept in the hospital after being revived.

Now, new research bolsters existing criteria that say most patients can be discharged from the emergency department in as little as an hour after getting naloxone.

The criteria for release specify pulse, blood pressure and breathing within normal ranges, and that patients can walk out of the hospital under their own steam.

“The landscape of opioid use disorder has changed dramatically,” said study author Dr. Brian Clemency. He is an associate professor of emergency medicine in the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, in New York.

Naloxone used to be given intravenously by doctors, nurses and paramedics. Now, it’s available to the public (brand name Narcan) and is often given as a nasal spray, the researchers explained.

Still, how patients are released after getting naloxone is inconsistent, Clemency noted. Some are released immediately, while others are watched for six hours or more.

To figure out the best policy, Clemency and his colleagues studied patients who arrived by ambulance after receiving naloxone.

An hour after receiving naloxone, the nearly 540 patients had their vital signs evaluated. Most patients were observed for four hours before being discharged, the investigators found.

Most adverse events seen in patients whose vital signs were normal after receiving naloxone were minor and not likely to be life-threatening, the study authors said.

Based on these findings, the one-hour rule appears to be valid for patients with normal vitals after getting naloxone, according to the researchers.

“This rule is a way to predict which patients will have adverse outcomes after they overdose on opiates,” Clemency said in a university news release. “The rule is simple to follow and can be used by health care providers with varying levels of training and experience.”

The researchers said they hope their findings will lead to a standardized policy.

The report was published Dec. 28 in the journal Academic Emergency Medicine.

More information

For more on drug overdose, visit the Drug Policy Alliance.

SOURCE: University at Buffalo, news release, Dec. 28, 2018

https://consumer.healthday.com/bone-and-joint-information-4/opioids-990/after-opioid-od-most-patients-can-leave-hospital-in-an-hour-740969.html