Neurotrope Publishes on Phase 2 Study of Bryostatin-1 in Alzheimer’s

Neurotrope Inc. (NASDAQ:NTRP), a clinical-stage biopharmaceutical company developing novel therapies for neurodegenerative diseases, including Alzheimer’s disease (AD), today announced that data from its Phase 2, multidose, exploratory trial evaluating Bryostatin-1 as a treatment of cognitive deficits in moderate to severe Alzheimer’s disease were published online in the Journal of Alzheimer’s Disease. The double-blind, placebo-controlled, Phase 2 trial, which was completed in May 2017, randomized patients 1:1:1 into 20 μg Bryostatin-1, 40 μg Bryostatin-1, and placebo arms. This peer-reviewed article provides what we believe is the first comprehensive data presentation of the Phase 2 trial of a drug with a new mechanistic approach for advanced AD.

“Neurotrope’s Phase 2 trial of Bryostatin for advanced Alzheimer’s patients has shown promising positive signals of improvement,” said Dr. Marwan Sabbagh, MD, Director of the Cleveland Clinic Lou Ruvo Center for Brain Health. “This drug’s observed sustained reversal of cognitive deterioration is consistent with the restorative, synaptogenic findings that Dr. Alkon and his teams have described during the years of pre-clinical research that preceded this potentially breakthrough clinical approach for treating neurodegeneration.”

“Therapeutic strategies for AD have focused on immunotherapy, and enhancement or blockade of neurotransmitters at synaptic junctions, approaches which may offer some symptomatic efficacy but have not demonstrated the ability to reverse the relentless progression of AD,” stated Dr. Martin R. Farlow, MD, Professor Emeritus in the Department of Neurology at Indiana University and co-director of the Alzheimer’s Disease Center at Indiana University. “Preclinically, Bryostatin-1 has demonstrated the ability to restore synaptic loss, prevent neuronal apoptosis, reduce A Beta oligomers, lower hyperphosphorylated tau and reduce oxidative stress.  These Phase 2 results show the early promise of translating this preclinical work, supported by years of research at the NIH and Blanchette Rockefeller Neurosciences Institute, into clinical outcomes.  I look forward to seeing them expanded upon in further ongoing studies.”

The study was designed to assess the safety and efficacy of Bryostatin-1 as a treatment of cognitive deficits in patients with moderate to severe AD (n=147).  Patients enrolled in the study were allowed to continue on background therapy, including cholinergic and/or anti-glutamatergic treatment.  These therapies are known to yield symptomatic efficacy, but their effect has not been shown to treat underlying disease progression.  The primary efficacy analysis for this Bryostatin-1 trial was change in Severe Impairment Battery (SIB) scores. For patients in the 20 µg Bryostatin-1 dose group (n=49, with 38 completers), SIB scores were greater than baseline, indicating persistence of improvement in cognitive function. A pre-specified ANCOVA for baseline memantine interaction with Bryostatin-1 and positive post-hoc trend analyses were statistically significant.

The magnitude of improvement was greater in a pre-specified exploratory analysis of patients not on memantine therapy (n=16).  Analyses of patients in this group showed evidence of sustained SIB improvement over baseline compared to placebo patients not on memantine (> 6.30 points, 8.4 points when compared to all placebo). Individual patient SIB scores over time revealed that 15 out of 16 patients (94%) in the 20 μg Bryostatin-1, non-memantine group showed improvement in SIB at 2 – 4 weeks post-dosing. For placebo patients and for patients on baseline memantine, there were no consistent increases in SIB measures over time. In addition, the safety profile was similar for patients treated with 20 μg Bryostatin-1 and placebo.

https://www.biospace.com/article/releases/neurotrope-announces-publication-of-phase-2-study-of-bryostatin-1-in-moderate-to-severe-alzheimer-s-disease-in-the-journal-of-alzheimer-s-disease/

WellCare Issues 2019 Annual Guidance

Company Reaffirms 2018 Annual Guidance

TAMPA, Fla., Dec. 17, 2018 /PRNewswire/ — WellCare Health Plans, Inc. (NYSE: WCG) (“WellCare”) today issued full-year 2019 guidance and reaffirmed its full-year 2018 guidance. For the full-year 2019, the company expects its adjusted earnings per diluted share (EPS) to be in the range of $13.15 to $13.40. For the full-year 2018, WellCare continues to expect its adjusted EPS to be in a range of $10.90 to $11.00.

Refer to the Appendix included in this news release for specific 2019 and 2018 guidance metrics, related footnotes and basis of presentation. In addition to the information in this release, a presentation describing the highlights of WellCare’s full-year 2019 guidance can be accessed via the following link: http://ir.wellcare.com/presentations.

Full-Year 2019 Guidance Highlights

• GAAP¹ total revenue is expected to increase to a range of $25.8 billion to $26.7 billionprimarily as a result of the acquisition of Meridian in 2018 and organic growth in all three business segments.

• The GAAP and adjusted Medicaid Health Plans medical benefits ratios (MBR) are expected to be in a range of 88.8% to 89.3% and 89.5% to 90.0%, respectively, primarily reflecting new business mix as a result of the company’s expanded Medicaid contract in Florida and the acquisition of Meridian in 2018. Additionally, the GAAP Medicaid Health Plans MBR reflects the absence of Medicaid ACA industry fee reimbursement in 2019.

• The Medicare Health Plans MBR is expected to be in a range of 85.0% to 85.8%, primarily as a result of the ACA industry fee moratorium in 2019, partially offset by continued operational execution.

• The Medicare PDP MBR is expected to be in a range of 82.5% to 83.5%, primarily due to bid positioning.

• The adjusted selling, general and administrative (SG&A)² expense ratio is expected to decrease to a range of 7.65% to 7.80%, primarily as a result of operational leverage and the company’s acquisition of Meridian in 2018.

¹Generally Accepted Accounting Principles (“GAAP”)
²Refer to Guidance Footnotes and Basis of Presentation for reconciliation of adjusted item to GAAP

About WellCare Health Plans, Inc.

Headquartered in Tampa, Fla., WellCare Health Plans, Inc. (NYSE: WCG) focuses primarily on providing government-sponsored managed care services to families, children, seniors and individuals with complex medical needs primarily through Medicaid, Medicare Advantage and Medicare Prescription Drug Plans, as well as individuals in the Health Insurance Marketplace. WellCare serves approximately 5.5 million members nationwide as of September 30, 2018. For more information about WellCare, please visit the company’s website at www.wellcare.com.

Appendix: Full-Year 2019 and 2018 Guidance Metrics

Guidance Metric	2019 Guidance as of December 17, 2018	2018 Guidance As of October 30, 2018
Revenue:
GAAP Medicaid Health Plans	$17.1B to $17.6B	$12.7B to $12.9B
Adjusted Medicaid Health Plans(1)	$17.0B to $17.5B	$12.3B to $12.45B
Medicare Health Plans	$7.2B to $7.5B	$6.25B to $6.35B
Medicare PDP	$1.0B to $1.1B	$825M to $875M
Medicaid ACA industry fee reimbursement	–	$280M to $285M
Products and services	$300M to $325M	$120M to $125M
Investment and other income(2)	$125M to $135M	$101M to $105M
GAAP total revenue	$25.8B to $26.7B	$20.0B to $20.3B
Adjusted total revenue(1)	$25.6B to $26.6B	$19.6B to $19.9B
Segment MBR:
GAAP Medicaid Health Plans	88.8% to 89.3%	85.6% to 85.9%
Adjusted Medicaid Health Plans(1)	89.5% to 90.0%	88.4% to 88.8%
Medicare Health Plans	85.0% to 85.8%	84.1% to 84.7%
Medicare PDP	82.5% to 83.5%	75.0% to 76.5%
Costs of products and services	$290M to $315M	$117M to $121M
Adjusted SG&A ratio(3)(4)	7.65% to 7.80%	8.35% to 8.45%
ACA industry fee expense	–	$342M to $346M
GAAP depreciation and amortization (D&A) expense	$280M to $287M	$178M to $182M
Adjusted D&A expense(5)	$130M to $137M	$102M to $106M
Interest expense	$120M to $124M	$87M to $89M
Adjusted effective income tax rate(4)(6)	23.5% to 24.5%	34.0% to 35.0%
Diluted shares outstanding	50.7M to 51.0M	–
Adjusted EPS(4)(7)	$13.15 to $13.40	$10.90 to $11.00

⁽¹⁾  Excludes an estimated $125.0 million to $130.0 million and $130.0 million to $135.0 millionin Medicaid premium taxes for 2018 and 2019, respectively.  Excludes an estimated $280.0 million to $285.0 million in ACA industry fee reimbursement for 2018. There is no ACA industry fee reimbursement due to a one-year federal moratorium of the ACA industry fee in 2019.
⁽²⁾ Investment & other income primarily includes investment income.
⁽³⁾ SG&A expense (GAAP) less investigation costs and transaction and integration costs divided by total revenue (GAAP) less Medicaid premium taxes revenue and ACA industry fee reimbursement in 2018. SG&A expense (GAAP) less transaction and integration costs divided by total revenue (GAAP) less Medicaid premium taxes revenue in 2019.
⁽⁴⁾ WellCare is not able to estimate amounts and the timing of expense associated with acquisition-related transaction and integration costs expected to be incurred as well as 2018 investigation costs and, therefore, cannot reconcile these metrics to total projected GAAP metrics.
⁽⁵⁾  Excludes an estimated $145.0 million to $155.0 million in acquisition-related amortization expenses in 2019. Excludes an estimated $75.0 million to $77.0 million in acquisition-related amortization expenses in 2018.
⁽⁶⁾  Excludes the estimated income tax effect associated with the 2018 investigation costs, acquisition-related amortization expenses, and transaction and integration costs.
⁽⁷⁾  The company estimates adjusted earnings per diluted share guidance by adjusting net income for the estimated net-of-tax effect of acquisition-related amortization expense, transaction and integration costs and 2018 investigation costs.

https://www.biospace.com/article/releases/wellcare-issues-2019-annual-guidance/

Hamilton County Ohio Sees Drop In Opioid Overdose-Related Deaths

Hamilton County Public Health announced today data showing that Hamilton County, Ohio, has seen a significant reduction in the overdose-related emergency department visits, EMS runs and overdose-related deaths, the vast majority of which are opioid related. An epicenter of the national opioid overdose epidemic, Hamilton County has been working hard to increase education, awareness, and treatment resources as part of their overall community activation plan.

In particular, Hamilton County Public Health has been leading the nation’s largest effort to distribute take-home naloxone, the life-saving antidote to opioid overdose.  Supported in part by a large charitable donation from Emergent BioSolutions, and in partnership with multiple community-based organizations and all major regional health systems known as the Narcan Distribution Collaborative (NDC), Hamilton County was able to distribute nearly 25,000 doses of NARCAN^® (Naloxone HCL) Nasal Spray 4mg in approximately one year’s time.

This program contributed to an increase of 674% in take-home naloxone; this is likely to have contributed recent changes in community statistics.  The NDC program launched October 1, 2017. Compared with the 8 months prior to the NDC, the subsequent 8 months had significantly fewer overdose-related incidents in Hamilton County:

• 42 percent reduction of emergency department visits,
• 37 percent reduction of EMS runs,
• 31 percent reduction of opioid overdose deaths.

The NDC also frequently provides Narcan to individuals from surrounding counties.  Across multiple Ohio counties in Greater Cincinnati that received NARCAN^® from the NDC, opioid overdose deaths fell by 28 percent, following the start of the NDC.

“The opioid epidemic is a national problem, and our county is severely affected,” said Tim Ingram, Health Commissioner of Hamilton County Public Health. “Based on these initial results, we are optimistic that we are making progress in our fight against the epidemic. We are committed to continuing to work to reduce potential harm from opioids in our community.”

The NDC has been working to expand NARCAN^® Nasal Spray to as many points of population access as possible.  One important distribution method was a syringe exchange mobile unit, managed by Hamilton County Public Health.  Dozens of other locations included community health fairs, hospital emergency departments, substance use disorder treatment centers, the Hamilton County Justice Center, social service agencies, and many more.

A more comprehensive evaluation of the program is ongoing, led by Shawn Ryan, MD, MBA, ABEM, ABAM, President and Chief Medical Officer of Brightview Health, and investigators of the University of Cincinnati.

“NARCAN^® is able to reverse the effects of an opioid overdose if administered in time,” said Dr. Ryan. “These data suggest that increased access to NARCAN^®, in combination with increased awareness and immediate access to treatment for opioid use disorder, can significantly reduce the negative impact opioid overdoses can have on a community.”

“We are quite pleased with the initial results of the NDC effort,” said Dr. Michael Lyons, MD, MPH, Associate Professor of Emergency Medicine and Director of the Early Intervention Program at the University of Cincinnati.  “As a result of the success of the program so far, our health department has received an additional 12,000 doses of NARCAN^® from Emergent BioSolutions. We look forward to continuing to activate our local community against the opioid epidemic.”

https://www.biospace.com/article/releases/hamilton-county-ohio-public-health-officials-announce-decrease-in-opioid-overdose-related-deaths/

Seer Launches to Develop Protein-Based Liquid Biopsies

Yet another company has launched to develop liquid biopsies. Founded and headed by Omid Farokhzad, formerly a professor at Brigham and Women’s Hospital, Seer is based in San Francisco.

Liquid biopsies are tests performed on blood to look for cancer cells or DNA from a tumor circulating in the blood. They are also used to detect other diseases. The key difference between a liquid biopsy and a traditional clinical blood test is the focus on identifying cells or DNA from whatever illness is being tested for. Traditional lab tests do this as well, but typically not by trying to identify and sort so much information.

There are quite a number of companies working in the area, including Guardant Health, Karius, Freenome, Apostle, and GRAIL Bio.

So far, Seer has raised $36 million combined in a Series A round led by Maverick Ventures and a Series B round led by Invus, with participation from other investors.

How Seer hopes to differentiate itself from the competitors is the focus on proteins, compared to the more typical focus on free-floating DNA. The proteomics technology originated in Farokhzad’s laboratory, which he tells Xconomy, “uses nanotechnology-based ‘biosensors’ to measure and profile the proteome in patient samples, and machine learning algorithms to crunch the data and find disease biomarkers.”

Currently Seer has about 20 employees and has already begun clinical studies in cancer diagnostics and neurological disorders.

Farokhzad has a mixed history with biotech startups. He was the founder and director of BIND Therapeutics, which declared bankruptcy in 2016 and sold its assets to Pfizer. In 2011 he founded Blend Therapeutics, which eventually became Tarveda Therapeutics. He remains on the company’s Scientific Advisory Board. In 2008 he founded Selecta Biosciences. Earlier this year Selecta halted a Phase I trial of SEL-403 in solid tumors after a patient death, although another drug, SEL-212, is in the clinic for severe gout.

But Farokhzad has gone all-in on Seer, leaving his position at Brigham and Women’s Hospital and moving from Boston to San Francisco. He indicates he wants to really have his fingerprints on the company.

Farokhzad suggests Seer will have clinical readouts in 2019 and 2020, and will plan to have a product to market in 2021. He also believes he will double the number of staffers in the next year.

Seer would seem to be in a catch-up position behind other companies, such as Grail. In June, Grail released new data from its Circulating Cell-free Genome Atlas (CCGA) study. The data released was from blood samples from 127 patients with lung cancer. Detection rates had a sensitivity at 98 percent specificity and ranged from 38 to 51 percent in patients with early-stage lung cancer and 87 to 79 percent in late-stage lung cancers. And in May, Grail raised $300 million in an oversubscribed Series C financing. Since early 2016, Grail has raised more than $1.5 billion.

Johns Hopkins University is also investigating a liquid biopsy that uses genomic and proteomic biomarker data, and in a Science article published in January, identified 70 to 98 percent of cancers in more than 1,000 previously diagnosed patients. That test, Cancer-SEEK, is now being evaluated in 10,000 women with no history of cancer with the Geisinger health system in Pennsylvania.

If Farokhzad is daunted by this competition, he’s not admitting it. “Genomic information can only be part of the solution,” he said, emphasizing that the Grail results aren’t good enough, especially for early-stage disease, Xconomy reports.

https://www.biospace.com/article/seer-launches-to-develop-protein-based-liquid-biopsies/

Bristol, Eisai, H3 Collaborate Using RNA Splicing Platform

Bristol-Myers Squibb Company (NYSE: BMY), Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, “Eisai”) and its U.S.-based precision medicine research & development subsidiary H3 Biomedicine, Inc. (Massachusetts, “H3”) today announced a multi-year research collaboration focused on evaluating whether novel therapeutics leveraging H3’s RNA splicing platform can provide a more powerful response against cancer.

The new collaboration will explore modulating RNA splicing to develop potential first-in-class therapies that would direct the immune system to target cancer cells and help more patients experience the benefits of immunotherapy.

Under the terms of the multi-year agreement, H3 and Bristol-Myers Squibb will jointly conduct the research focused on developing immune therapies using H3’s RNA splicing platform. Bristol-Myers Squibb will be responsible for development and commercialization of selected compounds, and H3 is eligible to receive an upfront payment, development, regulatory and sales milestones as well as certain royalties according to sales revenue after launch. Eisai retains an option to co-develop and co-commercialize certain compounds that emerge from the collaborative research effort.

“We are excited to enter into this collaboration with Bristol-Myers Squibb, as we share a mutual commitment to discover and develop innovations that will help improve outcomes for patients,” said Lihua Yu, Ph.D., President and Chief Data Sciences Officer at H3. “We have already advanced the first application of our RNA splicing platform into the clinic and look forward to building on that track record with research on this potential new immuno-oncology application together with Bristol-Myers Squibb, a leader in immuno-oncology. We believe this collaboration will help us better understand whether our RNA splicing platform can help enhance the immune system’s ability to more effectively fight cancer.”

“Bristol-Myers Squibb is looking forward to collaborating with H3 to advance the science and research around RNA splicing,” said Percy Carter, Head of Discovery Chemistry and Molecular Technologies, Bristol-Myers Squibb. “H3 has deep expertise in defining the role of changes in RNA homeostasis that contribute to cancer. This collaboration will allow both companies to gain a deeper understanding about alterations in RNA splicing and an opportunity to discover new medicines that can potentially improve outcomes for patients.”

“Since its inception, H3 has discovered potential new therapeutic options that leverage breakthroughs from cancer genomics and biotechnologies. We’re very proud of this new research collaboration with Bristol-Myers Squibb, as it represents another critical milestone for H3 and an opportunity for patients,” said Terushige Iike, President, Oncology Business Group at Eisai and Chief Executive Officer at H3.

https://www.marketscreener.com/BRISTOL-MYERS-SQUIBB-COMP-11877/news/Bristol-Myers-Squibb-and-H3-Biomedicine-Announce-Research-Collaboration-to-Advance-Novel-Therapeut-27762658/

Shanghai Henlius up for Hong Kong IPO

Biosimilars company Shanghai Henlius Biotech Inc. (Shanghai, China) proposed on Friday to list on the Hong Kong stock exchange.

Shanghai Henlius’ lead compound is HLX01, a biosimilar of cancer and autoimmune drug MabThera rituximab from Roche (SIX:ROG; OTCQX:RHHBY). China’sNational Medical Products Administration (NMPA) is reviewing an NDA for the drug under Priority Review to treat non-Hodgkin lymphoma; Henlius expects a decision this year or early next.

According to its prospectus, the company’s pipeline includes over 25 biologics as well as immuno-oncology combination therapies.

Shanghai Henlius’ management team includes co-founders Scott Liu, who is president and CEO, and CSO Weidong Jiang. Prior to Henlius, Liu was director of the biologics QC department at Bristol-Myers Squibb Co. (NYSE:BMY) and the director of QAL/QC at Amgen Inc. (NASDAQ:AMGN). Jiang was an associate director at Catalyst Biosciences Inc. (NASDAQ:CBIO).

Shanghai Henlius’ substantial shareholders include Fosun International Ltd. (HKSE:656) and its Chairman Guangchang Guo as well as Fosun Pharmaceutical.

Underwriters for the offering include CICC, BofA Merrill Lynch, CMB International, Fosun Hani and Citi.

In September, Shanghai Fosun Pharmaceutical Group Co. Ltd. (Shanghai:600196; HKSE:2196) said its board approved a resolution to list Shanghai Henlius, a JV between Fosun and Henlius Biopharmaceuticals Co. Ltd. (Shanghai, China), in Hong Kong.

https://www.marketscreener.com/BRISTOL-MYERS-SQUIBB-COMP-11877/news/Shanghai-Henlius-up-for-Hong-Kong-IPO-27762990/

Vernalis Achieves Success Milestone in Collaboration with Asahi Kasei Pharma

Vernalis Research, a Ligand Company, announced the achievement of a £1 million success milestone in its drug discovery collaboration with Asahi Kasei Pharma (AKP).

This collaboration with AKP was initiated in October 2013 and utilises Vernalis’ fragment and structure-based drug discovery platform against an undisclosed target for rheumatoid arthritis and other autoimmune diseases. This is the third milestone achieved under the collaboration recognising the significant progress made to date. Additional financial terms of this collaboration have not been disclosed.

Mike Wood, Ph.D. Research Director of Vernalis Research, commented, “We are delighted with the success we have achieved in our close collaboration with the scientists at Asahi Kasei Pharma. This collaboration is another excellent endorsement of our world-leading fragment and structure-based drug discovery platform, and we look forward to the potential for continued success in our collaboration with AKP.”

https://www.marketscreener.com/LIGAND-PHARMACEUTICALS-IN-17306/news/Vernalis-Research-a-Ligand-Company-Achieves-Success-Milestone-in-Collaboration-with-Asahi-Kasei-27763799/