Ketamine is widely known as a party drug sold under the moniker Special K, as well as others. While it may provide a euphoric sensation for partiers, the drug also has properties that could be used to treat forms of depression.
A recent study showed that ketamine can possibly provide hours of relief for depression patients. According to a report published in the journal, Science, the use of ketamine on mice improved their functions. According to the report, “ketamine rescued behavior in mice that was associated with depression-like phenotypes by selectively reversing stress-induced spine loss and restoring coordinated multicellular ensemble activity in prefrontal microcircuits.” After dosing the mice with ketamine, the antidepressant effect occurred independently of effects on spine formation, the researchers said.
Depression-related behavior in the mice was associated with targeted, branch-specific elimination of postsynaptic dendritic spines and a loss of correlated multicellular ensemble activity in PFC projection neurons, the researchers said. The mice in the study were first dosed with a stress hormone that caused them to act depressed, NPR reported. This caused the animals to lose interest in many of their favorite activities, similar to what some people go through. When the mice were dosed with ketamine, the effects were reversed. The researchers said that the drug restored coordinated activity in multicellular ensembles that predicted motivated escape behavior.
The latest study on anesthetic ketamine provides a window into a greater understanding of how the drug can affect patients. Dr. Conor Liston, one of the researchers involved in the ketamine project, told NPR that part of the study was to examine the synapses in the mice brains. When the mice were induced with the stress hormone, researchers observed a loss of synapses. Then ketamine was introduced and the scientists were surprised.
“Ketamine was actually restoring many of the exact same synapses in their exact same configuration that existed before the animal was exposed to chronic stress," Liston told NPR.
The positive results from the ketamine dosing occurred within six hours of the treatment. Within just that short time frame, the mice stopped acting depressed, according to the report. After 12 hours, Liston said researchers saw a “big increase in the formation of new connections between neurons.”
The next question for the researchers will be to discover how to maintain the effect to provide a potential long-term benefit for human patients.
The study was published about a month after the U.S. Food and Drug Administration approvedJanssen’s Spravato, an esketamine-based nasal spray treatment for major depressive disorder. Spravato is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, which is also known as a glutamate receptor modulator. Janssen believes the treatment works by restoring synaptic connections in brain cells in individuals with major depressive disorder. Esketamine is related to the well-known party drug ketamine.
Janssen isn't the only company focusing on ketamine-type treatments for depression. Allergan and VistaGen also have similar products in their pipeline. Last month though, Allergan announced that its MDD treatment rapastinel would not meet endpoints in a Phase III trial.
https://www.biospace.com/article/ketamine-appears-to-repair-damaged-brain-circuits-to-relieve-depression-in-mice-study/
Friday, April 12, 2019
5 things to know about Hookipa Pharma ahead of its IPO
Hookipa Pharma Inc., a biotech that’s using arenavirus-based platforms to develop treatments targeting infectious diseases and cancers, set terms for its initial public offering shares this week, saying it will offer 6.7 million shares priced at $14 to $16 each.
At the midpoint of that range, the deal will raise about $100.5 million.
Hookipa HOOK, +0.00% has applied to trade on the Nasdaq exchange under the ticker symbol “HOOK.”
Only one of Hookipa’s six pipeline drugs is in the clinical stage of development. It’s a therapy called HB-101, meant to treat cytomegalovirus (CMV), a common virus that is generally clinically benign in healthy people but can cause serious issues in people who are immunocompromised. HB-101 uses Hookipa’s VaxWave technology, an arenavirus that can induce a strong immune response against infectious disease but does not replicate. The other five pipeline drugs, all in preclinical stages of development, target hepatitis B, human immunodeficiency virus (HIV), cancers caused by human papilloma virus (HPV) and prostate cancer. The oncologic therapies use the company’s TheraT technology, which is based on the arenavirus but is supposed to produce an even more powerful immune response.
Like many biotech prospectuses, Hookipa’s S-1 is filled with language about the speculative nature of biotech and the fact that the company has operated at a loss since its inception. “We are not profitable and have incurred losses in each period since our inception in 2011,” Hookipa wrote, noting it reported net losses of $12.7 million and $16.7 million in the years ended 2017 and 2018, respectively. The company added that it expects to continue to incur significant losses for the foreseeable future, another statement commonly found in biotech prospectuses.
Bank of America Merrill Lynch, SVB Leerink and RBC Capital Markets are joint bookrunners on the deal with Kempen acting as co-manager.
Here are five things to know about the company as it readies its IPO.
Hookipa doesn’t have sufficient personnel to properly check the company’s accounting
Hookipa disclosed in its prospectus that it does not have enough people to do proper checks and balances on its numbers.
“Prior to this offering, we have been a private company with limited accounting personnel and other resources with which to address our internal control over financial reporting,” the company wrote in its prospectus, adding that it “did not maintain a sufficient complement of resources with an appropriate level of accounting knowledge, experience, and training, which would allow for appropriate monitoring, presentation and disclosure, and internal control over financial reporting.”
“Specifically, we have not designed and implemented a sufficient level of formal accounting policies and procedures. Additionally, the limited personnel resulted in our inability to consistently establish appropriate authorities and responsibilities in pursuit of our financial reporting objectives, as demonstrated by, amongst other things, our insufficient segregation of duties in their finance and accounting functions,” Hookipa wrote.
A situation like this opens up the opportunity for accounting mistakes and, in the worst case, fraud.
There are some holes in Hookipa’s insurance coverage
Hookipa does not carry biological or hazardous waste insurance, and its property, casualty and general liability insurance policies specifically exclude coverage for damages arising from biological or hazardous waste exposure or contamination, according to the company’s prospectus.
“Accordingly, in the event of contamination or injury, we could be held liable for damages or be penalized with fines in an amount exceeding our resources, and our clinical trials or regulatory approvals could be suspended,” the company wrote.
The company does carry general liability, employment practices liability, property, umbrella, and directors’ and officers’ insurance, but noted that “operating as a public company will make it more difficult and more expensive for us to obtain director and officer liability insurance, and we may be required to accept reduced policy limits and coverage or incur substantially higher costs to obtain the same or similar coverage. As a result, it may be more difficult for us to attract and retain qualified people to serve on our board of directors, our board committees or as executive officers.”
Pharmaceutical giant Gilead is a drug development partner
In June, Gilead Sciences Inc. GILD, +0.48% obtained exclusive rights to Hookipa’s TheraT and VaxWave technologies for HBV and HIV in a deal where the drug maker agreed to fund all related research and development activities and Hookipa would be eligible to receive tiered royalties on net sales.
Under the terms of the agreement, Hookipa received $10 million from Gilead up front and will be eligible to receive milestone payments up to a total of more than $400 million.
A significant chunk of Hoopika’s research and development operations are located in Austria, and the Austrian government has helped bankroll some of Hookipa’s programs
Hoopika was originally incorporated in Austria in 2011. In February 2017, the company reorganized and became a U.S. company. Hookipa wrote in its prospectus that it has “significant” research and development operations in Austria and sources third-party manufacturing, consulting and other services in the European Union.
The company has also contracted “numerous” funding agreements, including below-market loans and grants, with an agency of the Austrian government to partially finance its research and development programs, according to the prospectus. That includes “personnel costs, material costs, third-party services, travel expenses and research and development infrastructure use,” the company said. As such, Hookipa needs to get approval for any significant changes it makes in the cost structure of any research and development programs the government funds.
Hookipa is entering a crowded space
In CMV research, Hookipa faces significant competition from companies such as Helocyte, Inc., VBI Vaccines, Inc. VBIV, +1.45% Moderna, Inc. MRNA, -1.20% SL VaxiGen, Inc., Merck & Co. MRK, -0.10% GlaxoSmithKline GSK, -0.76% and Pfizer, Inc. PFE, -0.35% all of whom have approved drugs or drugs in the pipeline for CMV management, including vaccines, in some cases.
For HPV-associated cancers, there’s competition from Gilead’s Kite Pharma, which is developing an early-stage CAR-T therapy with the National Cancer Institute, and Advaxis, Inc. ADXS, -2.14% which is working on a Phase 3 immunotherapy to treat cervical cancer. ISA Pharmaceuticals B.V. is working with Regeneron Pharmaceuticals, Inc. REGN, -0.90% to develop a combination immunotherapy consisting of ISA’s ISA101b and Regeneron’s cemiplimab, and BioNtech AG is developing a personalized cancer vaccine.
Quest Diagnostics to hold a webcast
Scientific Directors Sample & Samano discuss Quest’s Drug Testing Index data and analysis on a webcast to be held on April 16 at 11 am.
Veeva price target raised to $160 from $140 at DA Davidson
DA Davidson analyst Rishi Jaluria raised his price target on Veeva (VEEV) to $160 and kept his Buy rating after meeting with its president Matt Wallach. The analyst says the discussion indicated that the company’s “tone of business is very strong”, and that Wallach’s expected replacement Tom Schwenger can be successful in bringing the company’s first customers with over $100M in sales value. Jaluria further anticipates 2019 to be a “breakout year” for the company’s Clinical Data Management Suite as well as for its Data Workbench to be a “competitive differentiator” relative to Medidata Solutions’ (MDSO) offerings.
CymaBay announces results from Phase 2 seladelpar study at ILC
CymaBay announced results from its Phase 2 study of seladelpar in a subset of cirrhotic patients with primary biliary cholangitis, or PBC. These data are being presented at The International Liver Congress, or ILC, along with three other seladelpar clinical and preclinical presentations. Seladelpar is a potent and selective peroxisome proliferator-activated receptor delta, or PPARd, agonist currently in development for PBC and nonalcoholic steatohepatitis, or NASH. The company will be reporting the results of a subset of patients with compensated cirrhosis from an ongoing Phase 2 study designed to assess the safety and efficacy of seladelpar at a daily dose of 5 mg or 10 mg in PBC patients who had an inadequate response or an intolerance to ursodiol and a total bilirubin. Cirrhosis was diagnosed using liver biopsy, liver elastography or liver imaging. Patients initiated on 5 mg could be dose-escalated to 10 mg after 12 weeks of treatment if it was tolerated and AP threshold criterion was not met. The primary outcome was percent change from baseline in AP. Secondary outcome measures included ALT, total bilirubin, and pruritus using the visual analogue scale. At 52 weeks in patients with cirrhosis, mean relative decreases in AP were -36% and -43% in the 5/10 mg and 10 mg group, respectively. Treatment with seladelpar also demonstrated anti-inflammatory activity with a decrease in ALT comparable to what was observed in non-cirrhotic patients. Total bilirubin remained stable throughout 52 weeks. Seladelpar was well tolerated and appeared safe. Three patients with cirrhosis experienced an SAE, all unrelated to seladelpar. Total bilirubin, platelets, albumin, and INR remained stable. No liver decompensation events were observed. There was no transaminase safety signal, and seladelpar treatment was not associated with drug-induced pruritus or hepatotoxicity. A second clinical presentation demonstrates that single dose oral administration of seladelpar was well tolerated and appeared safe in subjects with varying degrees of hepatic impairment and thus provided important information on seladelpar pharmacokinetic exposure and implications for dosing in this population. Additionally, a presentation using the validated GLOBE score to model PBC clinical progression suggests that seladelpar treatment has the potential to be associated with long-term improvement in disease progression. Finally, a preclinical presentation highlights that seladelpar demonstrated substantial anti-fibrotic and anti-steatotic activity in an obese mouse model of NASH.
https://thefly.com/landingPageNews.php?id=2891907
https://thefly.com/landingPageNews.php?id=2891907
Merck KGaA to hold a conference call
Conference call to discuss the definitive acquisition of Versum Materials will be held on April 12 at 10 am.
Bruker upgraded to Buy from Hold at Deutsche Bank
Deutsche Bank analyst Dan Leonard upgraded Bruker to Buy from Hold saying the company’s growth acceleration “looks durable.”
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