Boston Positioning To Become Retail Cannabis Hub Of The East Coast

The West Coast is no stranger to cannabis shops, and the cannabis-oriented industrial space that supports them, but now it is the East Coast’s turn.

The sale of recreational marijuana becomes legal under Massachusetts law on July 1, and retail shops will begin popping up soon afterward. Dank Depot, Flickr “We think it’s hugely consequential — Massachusetts becomes an anchor market on the East Coast,” John Kagia, an analyst at cannabis research firm New Frontier Data, told Bloomberg.

Voters in the commonwealth approved Question 4 in 2016, which legalized the recreational use and sale of cannabis, pending the establishment of a regulatory framework and the issuing of retail licenses, which have been in the works since then.

According to New Frontier Data, cannabis sales in the Bay State are projected to rise from $52M in 2016 — when the only sales were medical marijuana — to $1.07B in 2020, with the vast majority being recreational sales.

The opening of retail shops might be a little slow at first in Massachusetts, as the Cannabis Control Commission awards licenses. There has been a crush of interest in getting licenses.

As of this week, none had been issued, but according to Boston.com, the agency plans to vote soon on issuing the first retail license to Cultivate, a medical marijuana dispensary that opened recently in Leicester.

Vermont, Maine and the District of Columbia have also legalized marijuana, but unlike Massachusetts, do not have a system of regulation in place under which retail shops could be set up.

Marijuana is still unlawful under federal law, but despite U.S. Attorney General Jeff Sessions’ avowed stance against legalization at any level, he has made little progress in putting the cannabis genie back in the bottle, the Wall Street Journal reports.

Even so, the federal prohibition makes it harder for marijuana retailers and growers to do business even in legal states, especially when it comes to gaining access to financing. But there is momentum to change that, with various bills proposed in Congress.

Last month, Sen. Cory Gardner, (R-Colo.) joined Sen. Elizabeth Warren (D-Mass.) in introducing a bill that would bar federal interference in state marijuana policy — and President Donald Trump told the press he would likely support it.

https://bit.ly/2KHW46i

Lilly med provides fast migraine relief without cardiovascular side effects

Lasmiditan, a new type of drug for acute treatment of migraine, provided prompt relief of pain and other bothersome symptoms as soon as an hour after administration, researchers reported here.

About 20% of patients treated with the highest dose of lasmiditan in one of two phase III trials reported being free of headache pain at 1 hour post-treatment, rising to nearly 40% at 2 hours.

The results were presented at the American Headache Society annual meeting.

Lasmiditan could potentially represent the first major innovation for the treatment of acute migraine in two decades. The drug is a serotonin agonist selective for the 5-HT_1F receptor. Triptans activate that receptor, but they are also active at other 5-HT receptor subtypes that are believed to be responsible for these agents’ unwanted cardiovascular effects.

In the current study with lasmiditan, cardiovascular effects were nearly absent.

These phase III results follow the recent approval of the first of another new class of migraine drugs, the calcitonin gene-related peptide (CGRP) inhibitors. Other research presented at the meeting showed that lasmiditan inhibits the release of CGRP from central and peripheral trigeminal nerve terminals in the mouse brain to the same degree as sumatriptan.

“This is an incredibly exciting time to be in the headache field. So much is happening. This is a golden age for people with migraines,” AHS scientific program committee chair Peter Goadsby, MD, PhD, told reporters during an advance media briefing ahead of the meeting.

Sheena Aurora, MD, of lasmiditan’s developer Eli Lilly, presented results from a pair of randomized phase III studies of lasmiditan.

SAMURAI and SPARTAN were randomized, double-blind trials comparing lasmiditan versus placebo for the treatment of acute migraine. Together, the studies included 4,439 participants. More than 80% were women, most were white, and the mean age was approximately 42 years. They had an average of about five migraines per month, one-third experienced aura, and they had moderate migraine-related disability (MIDAS score of 11 or higher). About 20% used prophylactic medications to reduce migraine frequency.

About 80% of patients had at least one risk factor for cardiovascular disease, including family history, smoking, hypertension, hyperlipidemia, and type 2 diabetes. SAMURAI, but not SPARTAN, excluded people with known coronary artery disease, arrhythmias, or uncontrolled hypertension.

In both studies, participants were randomly assigned to receive lasmiditan or placebo within 4 hours after the onset of migraine. Both studies evaluated oral doses of 100 mg and 200 mg, and SPARTAN also included a 50-mg dose. Patients could receive a randomized second dose, if needed, 2 to 24 hours after the first.

In both studies, patients experienced headache pain relief in as little as one hour, with better response rates seen at the higher doses, Aurora reported.

In SAMURAI, about 15% of people taking the 200-mg dose were pain-free at 1 hour after lasmiditan administration, rising to 32.2% at 2 hours in a modified intention-to-treat analysis. The same proportion in SPARTAN taking the highest dose were pain-free at 1 hour, rising to nearly 30% at 1.5 hours and 38.8% at 2 hours. Response rates in the placebo group at 2 hours were 15.3% and 21.3% in the two studies. Participants taking the 50-mg dose did not see a significant advantage over placebo until 2 hours post-administration.

The researchers also looked at relief of the most bothersome symptom as defined by the patient, most often photophobia. In both studies, about 25% of participants taking the highest dose reported being free of this symptom at 1 hour after administration, rising to 40.7% in SAMURAI and 48.7% in SPARTAN at 2 hours. Corresponding 2-hour rates in the placebo arms were 29.5% and 33.5%. Significant separation from the placebo was seen as early as half an hour in the high-dose lasmiditan arm.

Overall, SAMURAI participants reported about 60% headache pain relief and SPARTAN participants reported nearly 65% relief at 2 hours after the first dose of lasmiditan at either 100 mg or 200 mg. Placebo recipients reported about 40% pain relief in both studies.

Treatment with lasmiditan was generally safe and well tolerated. About 40% of patients receiving the 200-mg dose and 36% of those taking 100 mg experienced treatment-emergent adverse events, all mild to moderate. The most common side effects in the 200-mg arm were dizziness (16.3%-18.0%), paresthesia (6.6%-7.9%), somnolence (5.4%-6.5%), fatigue (3.1%-4.8%), and nausea (2.6%-5.3%). Less than 1% experienced cardiovascular adverse events.

An open-label trial called GLADIATOR is now underway to assess the longer-term safety and efficacy of lasmiditan, Aurora said.

Presentation session moderator Andrew Charles, MD, of the David Geffen School of Medicine at UCLA, told MedPage Today, “As a whole, we’re seeing dramatic new approaches from multiple sources. My overall impression is that these are extraordinary times, with new approaches based on new delivery methods and modification of old approaches, but also new molecules.”

The research was funded by Eli Lilly and multiple authors were company employees.

Goadsby reported relationships with numerous companies active in migraine drug development and marketing. Charles reported no relevant disclosures.

• Primary Source

  American Headache Society

  Source Reference: Wietecha L, et al “Phase 3 studies (SAMURAI, SPARTAN) of lasmiditan compared to placebo for acute treatment of migraine” AHS 2018; Abstract IOR-02.

• Secondary Source

  American Headache Society

  Source Reference: Maassen van den Brink A, et al “Lasmiditan inhibits CGRP release in the mouse trigeminovascular system” AHS 2018; Abstract OR-03.

https://bit.ly/2KzkvDb

Many top FDA execs eligible to retire soon

The FDA is looking to strengthen its workforce using new authorities granted under the 21st Century Cures Act, according to a report sent to Congress earlier this month. And they’ll need all the help they can get.

After digging in and reducing the number of open jobs in the past year, FDA leaders say that 40% of senior execs will be eligible to retire next year — leaving the agency susceptible to a major top-level transition period at a time the hunt for top talent has never been more intense.

The Cures Act granted FDA the authority to streamline the hiring process for certain scientific, technical and professional positions, and allows the agency to provide higher salaries to ensure the agency can compete with industry and academia.

“This authority will allow us to better build and maintain the highly talented workforce needed to meet the challenges of today’s rapid advances in science, medicine, and technology,” FDA Commissioner Scott Gottlieb writes in the opening of the report.

According to Gottlieb, FDA has been using the human resources authorities granted under Cures since February 2018 but has “only begun to tap its potential.”

In the years leading up to Cures enactment, FDA struggled to fill hundreds of vacancies in its review divisions, often citing a drawn out hiring process and low salaries compared to industry as major hurdles in attracting new talent, especially in emerging scientific and technical areas.

However, within the last two years the number of vacancies at the Center for Drug Evaluation and Research has come down from more than 900 in May 2016 to 650 in July 2017.

Since Cures‘ passage in 2016, FDA says it has been working towards implementing its new hiring and HR authorities.

According to the agency, some of those efforts include creating a staffing team to identify candidates for “hard-to-fill” scientific positions, developing processes to reduce time to hire to less than 80 days and designing a new alternative pay structure for 38 occupations that is more competitive than under the agency’s earlier authorities.

FDA says it is still working on completing new policies and procedures around hiring but says that it made its first two hires using Cures authorities in early 2018 and expects to fill additional positions in the coming months.

Aside from salary levels and lengthy hiring times, FDA says that its swelling size has contributed to the challenge of filling open positions. In the last decade, FDA says its staff has more than doubled from 8,000 employees to approximately 17,000 today.

“The need to rapidly recruit highly skilled and experienced staff has been a challenge for the agency,” FDA writes.

Another major challenge FDA faces in maintaining its workforce is the sheer number of staff who will become eligible to retire in the coming years.

According to the report, staff turnover is currently around five percent each year, consistent with other federal agencies, but may soon spike as a growing number of staff become eligible for retirement.

As of 2017, FDA says that 13.3% of its staff are eligible to retire, and by 2019 the agency says that more than 40% of senior leadership will be eligible to retire.

In anticipation of the coming departures, FDA says it is working to develop succession planning strategies, though specific strategies have yet to be determined.

https://bit.ly/2NhGNb2

Nuvectra asked for more data by FDA on bladder condition med

Nuvectra Corporation (NVTR), a neurostimulation medical device company, today provided an update on its U.S. Food and Drug Administration (FDA) pre-market approval (PMA) application and its TÜV SÜD application for CE Mark in Europe for Virtis^TM, the Company’s Sacral Neuromodulation (SNM) System for the treatment of chronic urinary retention and the symptoms of overactive bladder.

As part of its review of the Virtis PMA original application and the amendment submitted in April 2018, the FDA recently requested that the Company provide supplemental information related to any modifications or changes to the Virtis device, labeling and manufacturing, as well as clarifications of data related to MRI.  The Company has been in active communications with the FDA and intends to promptly file comprehensive responses to address the FDA’s requests. The FDA will then have up to 180 days to review the Company’s responses.  The Company plans to work proactively with the FDA to complete the review process as soon as possible.

Also, TÜV SÜD recently informed the Company that clinical study data will be required before it can recommend approval of CE Mark for the Virtis system.  The Company is continuing its discussions with TÜV SÜD regarding its application to clarify the breadth of clinical data that may be requested.

Scott Drees, Chief Executive Officer, commented, “Our primary focus is gaining FDA approval of the Virtis system in order to both provide therapy to patients and to address the significant market opportunity for SNM in the U.S. We remain encouraged by our recent interactions with the FDA and believe that our responses will adequately address the FDA’s requests.  We are pleased that our facility and pre-PMA audit have been completed without findings. We will continue to work cooperatively with the FDA to conclude the review of our application expeditiously and look forward to entering the U.S. SNM market as soon as possible following FDA approval.”

Mr. Drees continued, “We will revisit our corporate strategy to enter the SNM market in Europe and will engage with TÜV SÜD to determine a reasonable clinical pathway to CE Mark approval.”

https://yhoo.it/2KGvzLv

Athenex Details Pipeline Plans, $100M Investment

• Collaboration with Xiangxue Pharmaceutical Expands Portfolio in to TCR-T Immunotherapy
• In-Licensing of a Biologic Product from Avalon BioMedical Management

Athenex, Inc. (ATNX), a global biopharmaceutical company dedicated to the discovery, development and commercialization of novel therapies for the treatment of cancer and related conditions, today announced that it has entered into the following agreements:

• Establishment of a joint venture with Xiangxue Life Sciences, a wholly-owned subsidiary of Guangzhou Xiangxue Pharmaceutical Co., Ltd. (Xiangxue Pharmaceutical), for the research, development and commercialization of T-cell receptor-engineered T cells (TCR-T), a cancer immunotherapy technology, based on the novel approach on high-affinity TCR developed by Xiangxue Life Sciences;
• In-licensing of worldwide rights to a pegylated genetically modified human arginase from Avalon PolyTom (HK) Limited (PolyTom), a subsidiary of Avalon Biomedical Management Limited; and
• A strategic investment of US$100 million from Perceptive Advisors, an institution dedicated to supporting the most promising technologies in healthcare.

Xiangxue Life Sciences is a wholly-owned subsidiary of Xiangxue Pharmaceutical, a long term partner of Athenex for the development of KX-02 for glioblastoma multiforme in China. Xiangxue Life Sciences is a Chinese biopharmaceutical company focused on TCR-based therapies for cancer and has developed a new generation TCR-T, named HATac, which consists of the expression of high binding affinity soluble T-cell receptors on the engineered T-cells to target HLA-antigenic peptide complex on certain types of cancer cells. Early clinical studies in China demonstrated a good safety profile in patients.

Axis Therapeutics Limited, a new joint venture to be established and owned initially as 55% by Athenex and 45% by Xiangxue Life Sciences, has in-licensed the worldwide (excluding mainland China) rights of all the intellectual properties and know-how of the TCR-T immunotherapy technology from Xiangxue Life Sciences, subject to certain closing conditions and approvals.  Pursuant to the terms of the license agreement and shareholders agreement, Athenex will issue US$5 million worth of Athenex common stock to Xiangxue Life Sciences as an upfront payment and Athenex will contribute US$30 million in cash to the joint venture. Axis Therapeutics will also pay various clinical and regulatory milestones of up to US$110 million to Xiangxue Life Sciences. Xiangxue Life Sciences will retain the mainland China rights to the technology and there will be royalties on net income payable to Axis Therapeutics upon successful commercialization in mainland China. Additional new TCR-T technologies developed by Axis will also be partnered with Xiangxue Pharmaceutical in the future for the mainland China rights.

Athenex has strategically in-licensed a pegylated genetically modified human arginase, or Pegtomarginase, which was initially developed by the Hong Kong Polytechnic University and subsequently licensed to PolyTom. Through extensive research, a single isomer of pegylated genetically modified human arginase with a favorable pharmacokinetic and potency profile was identified and preclinical work demonstrated that the molecule represents a promising clinical candidate. The anti-cancer mechanism of this biologic product lies in that some cancers do not express either ornithine transcarbamylase (OTC) and/or argininosuccinate synthetase (ASS), two enzymes critical for the synthesis of arginine in the urea cycle pathway. As cancer cells will not be able to synthesize arginine, they will have to depend on external supply of arginine for tumor survival and growth. This treatment approach shows specificity as the depletion of circulating arginine will starve such OTC-/ASS- deficient cancer cells, while normal cells can synthesize arginine intracellularly through urea cycle for their survival.

Perceptive Advisors, an investment manager with a deep history in supporting biotechnology companies, will provide a combination of equity and debt financing to support Athenex’s operations and continued development, including pipeline expansion initiatives. Perceptive Advisors will invest US$100 million in Athenex, comprised of US$50 million in equity and US$50 million in debt.

Dr. Johnson Lau, Chairman and CEO of Athenex, commented, “Given our confidence in our two Phase III programs in Oraxol for metastatic breast cancer and KX-01 ointment for actinic keratosis, we are delighted to have this opportunity to further expand our product pipeline. The additions of TCR-T based cancer immunotherapy in collaboration with our long term business partner, Xiangxue Pharmaceutical and its subsidiary Xiangxue Life Sciences, and of an anti-cancer biologic will further complement and enhance our Oncology Innovation Platform. We are particularly excited about the potential synergies that can be created between the new therapies and our existing pipeline. We have developed a business strategy to fully explore the potential of all these platforms. We are also grateful to have Perceptive Advisors as our financial partner.”

https://yhoo.it/2MJ45FM

BioLife preannounces revenue up >100%

– BioLife Solutions, Inc. (BLFS) (“BioLife”), the leading developer, manufacturer and marketer of proprietary clinical grade cell and tissue hypothermic storage and cryopreservation freeze media, today reported preliminary revenue for the three months ended June 30, 2018 and increased its revenue guidance for 2018.

Second quarter 2018 preliminary revenue from sales of BioLife’s biopreservation media products reached a record $5.2 million.  This represents a 103% increase from the second quarter of 2017 and a 36% increase from the first quarter of 2018.

BioLife CEO Mike Rice commented, “Strong product demand during the second quarter from our cell and gene therapy customers in the regenerative medicine market segment resulted in more than 100% revenue growth over the prior-year period. Given our performance for the first half of 2018, increased adoption of our products in cell therapy clinical trials, and our outlook on product demand for the remainder of the year, we are significantly increasing our revenue guidance for the full year 2018.”

Management estimates that BioLife’s proprietary biopreservation media products have been used in nearly 300 customer clinical applications, including dozens of CAR T-cell and other T cell immunotherapies targeting blood cancers and solid tumors as well as other cell types targeting debilitating diseases and disorders.

Roderick de Greef, Chief Financial Officer, remarked, “Based primarily on additional warrant exercises during the period, we ended the second quarter with more than $14 million in cash, up from $7 million at March 31, 2018.”

Management is raising its revenue guidance for the full year 2018 as follows:

• Biopreservation media revenue is now expected to be in a range of $18.5 million to $20 million, representing growth of approximately 68% to 82% over 2017. This is an increase from the Company’s prior revenue guidance issued in April 2018 of a range of $14.5 million to $15.5 million.

Management is affirming the remainder of its financial guidance for 2018 as follows:

• Gross margin is expected to be between 63% and 65%, up from 61% for 2017.
• Operating expenses are expected to range from $9.0 million to $9.5 million, compared with $7.8 million for 2017.
• Full year GAAP operating profit with proportional increases in adjusted EBITDA and cash flow from operations.

https://yhoo.it/2lP5fnJ

Neurotrope Has Additional Phase 2 Data at Alzheimer’s Association Conference

Neurotrope Inc. (NASDAQ: NTRP) a clinical-stage biopharmaceutical company developing novel therapies for neurodegenerative diseases, including Alzheimer’s disease (AD), is announcing the acceptance of a presentation at the Alzheimer’s Association International Conference 2018 (AAIC) being held in Chicago, from July 22-26, 2018.

    Title Significant Cognitive Improvement with Bryostatin
          for Advanced Alzheimer's

          Patients in the Absence of Memantine (Poster
          presentation Abstract #27295)

    Developing Topics Session: P4-199:

    Date/Time                  Wednesday, July 25, 2018: 9:30 AM-
                                4:15 PM

    Location Hall              F1 - McCormick Place

“The primary mechanisms of action (MOAs) of bryostatin, Neurotrope’s lead compound to treat Alzheimer’s disease (AD) neurodegeneration, are synaptogenesis and anti-apoptosis: the generation of new, mature synaptic connections and the prevention of neuronal death. This has been demonstrated in pre-clinical models because our target PKC epsilon activates synaptic growth factors like BDNF, NGF and IGF-1. Our most recent comprehensive data analyses, to be reported at AAIC 2018, have demonstrated that advanced AD patients show improvement (> 6.0 points vs. placebo and baseline) in the Severe Impairment Battery (SIB) even 30 days after all drug dosing has been completed in patients not on memantine. The data indicate that PKC’s synaptogenesis efficacy cannot occur when the NMDA receptor is blocked. Data from many other laboratories over the years implicating NMDA in memory processing could now take on new meaning from Neurotrope’s clinical results with bryostatin – in the absence of memantine. We are excited to be presenting this new data at this prestigious international forum” stated Dr. Daniel Alkon, President and Chief Scientific Officer of Neurotrope.

https://bit.ly/2KFP9KU