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I have a few points to make. Unless I'm mistaken:
* ELI-200's Phase III is just beginning.
* ELI-200 still has to have a successful Phase III. There are no guarantees; not even Nasrat's.
* The FDA works in mysterious ways. So in addition to the challenges of the trial, there are the challenges of getting the FDA to sign off and to do it in a timely fashion.
* Nasrat doesn't have a knack for accurate time estimates and nearly always underestimates. Six months will probably be 9-12 months.
* Until then ELI-200 isn't an actual product.
Yes, this kind of planning is necessary, but they could've inked this deal 6 months ago or 6 months from now ... especially since it's not much different from the left hand shaking hands with the right hand. Said differently Epic Pharma isn't a major pharma.
In the end the announcement is interesting news in a daily-work-a-day kind of way, but this is far from a watershed moment.
Kind regards,
Minding
FDA Clears NovaBay Pharmaceuticals’ New High-Tech Device, intelli-Case, for Safely Disinfecting Contact Lenses with Hydrogen Peroxide
Note: CC on the 9th may give clarity about cash needs.
Kind regards,
Minding
===========
From http://finance.yahoo.com/news/fda-clears-novabay-pharmaceuticals-high-110000028.html
Following the launch of Avenova™, intelli-Case™ is the second in a series of cutting-edge products being developed by NovaBay that target unmet needs in the eye care market and demonstrates our strong commitment to innovation.
Hydrogen peroxide is the gold standard for disinfection of contact lenses, but can irritate the eye or fail to kill bacteria if not used correctly. NovaBay’s new intelli-Case ensures the adequacy of the disinfection cycle and that the contact lenses are safe for insertion into the eyes, potentially benefiting millions of contact lens users.
Conference call scheduled for Tuesday, June 9, at 12:00 p.m. (noon) Eastern time
EMERYVILLE, Calif.--(BUSINESS WIRE)--
NovaBay® Pharmaceuticals, Inc. (NYSE MKT: NBY), a biopharmaceutical company commercializing and developing novel approaches for the global eye care market, including revolutionary non-antibiotic antimicrobial products, today announced receipt of 510(k) clearance from the U.S. Food and Drug Administration (FDA) to market its novel intelli-Case with hydrogen peroxide solutions.
This Smart News Release features multimedia. View the full release here: http://www.businesswire.com/news/home/20150604005363/en/
Click here to view a presentation on intelli-Case.
More than 24 million Americans now disinfect their contact lenses with a disinfection system to prevent potentially serious infections. But only about 2 million use the gold standard disinfection solution, hydrogen peroxide. That’s because hydrogen peroxide can be tricky to use. Too low a concentration and it doesn’t fully disinfect lenses; too high, and it can irritate the eye. Getting the concentration right is challenging because hydrogen peroxide degrades over time. Many ophthalmologists and optometrists favor the disinfection and lens material compatibility peroxide systems provide, yet side effects associated with misuse and non-compliance minimize peroxide system use.
Click here to watch a video explaining the technology behind intelli-Case.
“The intelli-Case is a highly innovative, extremely easy-to-use device for the millions of Americans who wear contact lenses and want to use the best disinfection system,” said Ron Najafi, Ph.D., NovaBay’s President and CEO. “We believe that intelli-Case can revolutionize contact lens care by making the peroxide disinfection system as simple as using multipurpose solutions. Following the launch of Avenova, intelli-Case is the second in a series of cutting-edge products being developed by NovaBay that target unmet needs in the eye care market and demonstrates our strong commitment to innovation.”
The intelli-Case monitors the neutralization of hydrogen peroxide during the disinfection cycle with sophisticated microprocessor electronics embedded in the cap of what otherwise looks like a standard peroxide lens case. The high-tech cap has three LED lights labeled UNSAFE, BUSY and READY. Lenses are placed into the case with hydrogen peroxide solution. The green light (READY) blinks when lenses are safe to insert into the eyes and continues to blink green until contact lenses are removed from the case.
“The intelli-Case can be co-packaged with a hydrogen peroxide disinfection/cleaning solution and we are actively seeking a partnership with a hydrogen peroxide manufacturer,” added Dr. Najafi. “Replacing the standard case that is typically boxed with hydrogen peroxide solutions with the intelli-Case will make for a highly differentiated product offering that we believe will be warmly welcomed by both eye care professionals and contact lens wearers.”
“Poor contact lens hygiene is a major risk factor for a range of eye complications,” explained David Stroman, Ph.D., NovaBay’s Senior Vice President for Ophthalmology. “Americans make more than a million visits each year to emergency rooms, clinics or their eye care professionals with contact lens-related issues. Patients often report irritation and/or red eye after insertion of their contact lenses, when the hydrogen peroxide solution has not been adequately neutralized. Failure to properly disinfect is a well-documented cause of contact lens-related infections. The intelli-Case is designed to ensure the adequacy of the peroxide disinfection cycle and that the contact lenses are safe for insertion into the eyes.
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7:01 am NovaBay Pharma announces receipt of 510(k) clearance from the FDA to market its novel intelli-Case with hydrogen peroxide solutions Briefing.com 2 hrs 35 mins ago
NOVABAY PHARMACEUTICALS, INC. Financials EDGAR Online Financials 12 days ago
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“The intelli-Case provides real-time information to the user through solution monitoring and blinking LED lights, indicating that their lenses can be safely placed into their eyes,” said Dr. Stroman. “The intelli-Case removes the guesswork.”
“The advantages of peroxide are well known, but compliance has remained a problem for many patients,” said Art Epstein, OD, FAAO, FABCO, FBCLA, DPNAP, a recognized authority on contact lens complications. “What I most like about intelli-Case is that it leverages high-tech, real-time analytics to foster improved patient compliance. From what I’ve seen, it can make a tremendous difference even for the compliance-challenged patients. I am really excited about this technology.”
Steven J. Lichtenstein, MD, FAAP, FACS, FAAO, a leading pediatric ophthalmologist, stated, “The responses I’m getting from patients who have tested the intelli-Case are very positive. For instance, one individual reported that intelli-Case was easy to use and loved the fact that each morning she could safely put her lenses in her eyes without worrying about them burning. Like many other contact wearers, she has experienced severe pain from residual hydrogen peroxide that can occur with other peroxide disinfecting solutions. I plan to move my contact lens patients from multipurpose solutions (MPS) to intelli-Case as soon as possible.”
Conference Call
NovaBay management will host an investment community conference call, which will feature key opinion leaders in both ophthalmology and optometry and a discussion of its commercialization strategy, as well as to answer questions. The call will be held on Tuesday, June 9, 2015, at 12:00 p.m. noon Eastern time (9:00 a.m. Pacific time). Shareholders and other interested parties may participate in the conference call by dialing 866-880-4999 from within the U.S. or 702-495-1913 from outside the U.S. and entering the conference identification number 57071355. The live call also will be available at www.novabay.com.
A replay of the call will be available beginning two hours after its completion through June 23, 2015 at 11:59 a.m. Eastern time by dialing 855-859-2056 from within the U.S. or 404-537-3406 from outside the U.S. and entering the conference identification number 57071355. The call will also be archived at www.novabay.com.
About NovaBay Pharmaceuticals, Inc.: Going Beyond Antibiotics®
NovaBay Pharmaceuticals is a biopharmaceutical company focusing commercializing and developing its non-antibiotic anti-infective products to address the unmet therapeutic needs of the global, topical anti-infective market with its two distinct product categories: the NEUTROX™ Family of Products, including AVENOVA™ for the eye care market and NEUTROPHASE® for wound care, and CELLERX® for the aesthetic dermatology market, cleared by the FDA as a 510(k) medical device; and its AGANOCIDE® compounds, led by AURICLOSENE™.
NovaBay is partnered in the U.S. and around the globe with: PBE, Inc. (USA), IHT, Inc. (USA), Galderma (France), Virbac (France), China Pioneer Pharma (China and Southeast Asia), Shin Poong Pharmaceuticals (South Korea), Biopharm (North African and Middle East), Sarmedic Ltd (Israel) and Alpha Pharma LLC (Ukraine).
NovaBay has received FDA-clearance of its intelli-Case, a highly innovative, easy-to-use device for use with hydrogen peroxide disinfection solutions with soft and Rigid Gas Permeable (RGP) contact lenses.
Forward-looking Statements
This release contains forward-looking statements and opinions regarding the commercial potential of intelli-Case, which are based upon management's current expectations, assumptions, estimates, projections and beliefs. The words “believe” and “will” are intended to identify the forward-looking statements. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results or achievements to be materially different and adverse from those expressed in or implied by the forward-looking statements. Factors that might cause or contribute to such differences include, but are not limited to, risks and uncertainties relating to the future commercialization and market acceptance of intelli-Case. Other risks relating to NovaBay and its products, including risks that could cause results to differ materially from those projected in the forward-looking statements in this press release, are detailed in NovaBay's latest Form 10-K and Form 10-Q filings with the Securities and Exchange Commission, especially under the heading "Risk Factors." The forward-looking statements in this release speak only as of this date, and NovaBay disclaims any intent or obligation to revise or update publicly any forward-looking statement except as required by law.
Stay informed on NovaBay's progress:
Download our Mobile Investor App from the Apple Store or Google Play
Like us on Facebook
Follow us on Twitter
Connect with NovaBay on LinkedIn
Join us on Google+
Visit NovaBay's Website
For NovaBay Avenova purchasing information, please contact:
Email us
Call us: 1-800-890-0329
www.Avenova.com
View source version on businesswire.com: http://www.businesswire.com/news/home/20150604005363/en/
MULTIMEDIA AVAILABLE:http://www.businesswire.com/news/home/20150604005363/en/
Contact:
NovaBay Pharmaceuticals, Inc.
Thomas J. Paulson, 510-899-8809
Chief Financial Officer
Contact Tom
or
Investor Contact
LHA
Jody Cain, 310-691-7100
Jcain@lhai.com
Update with Cesca's Ken Harris:
Perma-Fix Medical website: http://www.medical-isotope.com/
Thanks hweb2.
Kind regards,
Minding
Exactly.
Minding
Link to the news?
Thanks,
Minding
MediciNova Announces FDA Granted Orphan Drug Designation to MN-166 (ibudilast) for Krabbe Disease
Orphan-drug designation is a big deal. Very good news.
Kind regards,
Minding
==============
From http://finance.yahoo.com/news/medicinova-announces-fda-granted-orphan-120000412.html
LA JOLLA, Calif., June 3, 2015 (GLOBE NEWSWIRE) -- MediciNova, Inc., a biopharmaceutical company traded on the NASDAQ Global Market (MNOV) and the JASDAQ Market of the Tokyo Stock Exchange (Code Number:4875), today announced that the U.S. Food and Drug Administration (FDA) has granted orphan-drug designation to MN-166 (ibudilast) for treatment of Krabbe disease. MediciNova previously opened an Investigational New Drug (IND) application with the Division of Neurology Products (DNP) for MN-166 (ibudilast).
Yuichi Iwaki, MD, PhD, President and Chief Executive Officer of MediciNova, Inc., commented, "We are very pleased to receive orphan-drug designation for MN-166 for Krabbe Disease, a rare disease for which hematopoietic stem cell transplantation, the only currently available treatment option, is not without potential risk to the patient and is limited in efficacy. As we already have an open IND, we plan to finalize a protocol and submit it to FDA in order to conduct a clinical trial of MN-166 in Krabbe Disease."
About Krabbe Disease
Krabbe disease is a rare genetic degenerative disorder for which there is no cure and is generally fatal before two years of age. Krabbe disease has 4 clinical subtypes (Types 1 - 4), distinguished by age of onset. In the vast majority of cases, the symptoms of Krabbe disease begin at age 0 - 6 months (Type 1 early infantile form). Initial signs and symptoms typically include irritability (e.g., excessive crying), limb spasticity, absent reflexes, muscle weakness, feeding difficulties, episodes of fever with no sign of infection, stiff posture, and slowed or regressed neurocognitive development. As the disease progresses, muscles continue to weaken, affecting the infant's ability to move, chew, swallow, and breathe. Affected infants also experience vision loss and seizures, regress rapidly to a decerebrate condition and usually succumb to the disease before their 2nd birthday. Approximately 10% present symptoms later in life, including in adulthood (Types 2 - 4). Progressive loss of vision, difficulty walking, decline in thinking skills, loss of manual dexterity, and muscle weakness are the most common initial symptoms in this form of the disorder, however, signs and symptoms vary considerably among affected individuals. Patients with late-onset Krabbe Disease regress at a slower pace and have the potential to live significantly longer than patients diagnosed in early infancy.
About Orphan Drug Designation
Drugs that receive orphan-drug designation from FDA are entitled to seven years of marketing exclusivity if they are approved by the FDA for the same rare disease. The Orphan Drug Designation program provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the U.S., or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug.
About MN-166 (ibudilast)
MN-166 (ibudilast) has been marketed in Japan and Korea since 1989 to treat post-stroke complications and bronchial asthma. MediciNova licensed MN-166 (ibudilast) from Kyorin Pharmaceutical Co., Ltd. for potential utility in relapse-remitting multiple sclerosis (RRMS). Intellectual property was additionally established or obtained by MediciNova in progressive MS and other neurological conditions. MN-166 (ibudilast) is a first-in-class, orally bioavailable, small molecule phosphodiesterase (PDE) -4 and -10 inhibitor and a macrophage migration inhibitory factor (MIF) inhibitor that suppresses pro-inflammatory cytokines and promotes neurotrophic factors. It attenuates activated glia cells, which play a major role in certain neurological conditions. Ibudilast's anti-neuroinflammatory and neuroprotective actions have been demonstrated in preclinical and clinical study results and provide the rationale for its therapeutic utility in neurodegenerative diseases (e.g., progressive MS and amyotrophic lateral sclerosis (ALS)), substance abuse/addiction and chronic neuropathic pain.
About MediciNova
MediciNova, Inc. is a publicly-traded biopharmaceutical company founded upon acquiring and developing novel, small-molecule therapeutics for the treatment of diseases with unmet medical needs with a commercial focus on the U.S. market. MediciNova's current strategy is to focus on MN-166 (ibudilast) for neurological disorders such as progressive MS, ALS and substance dependence (e.g. methamphetamine dependence, opioid dependence) and MN-001 (tipelukast) for fibrotic diseases such as nonalcoholic steatohepatitis (NASH) and idiopathic pulmonary fibrosis (IPF). MediciNova's pipeline also includes MN-221 (bedoradrine) for the treatment of acute exacerbations of asthma and MN-029 (denibulin) for solid tumor cancers. MediciNova is engaged in strategic partnering and other potential funding discussions to support further development of its programs. For more information on MediciNova, Inc., please visit www.medicinova.com.
Statements in this press release that are not historical in nature constitute forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These forward-looking statements include, without limitation, statements regarding the future development and efficacy of MN-166, MN-221, MN-001, and MN-029. These forward-looking statements may be preceded by, followed by or otherwise include the words "believes," "expects," "anticipates," "intends," "estimates," "projects," "can," "could," "may," "will," "would," "considering," "planning" or similar expressions. These forward-looking statements involve a number of risks and uncertainties that may cause actual results or events to differ materially from those expressed or implied by such forward-looking statements. Factors that may cause actual results or events to differ materially from those expressed or implied by these forward-looking statements include, but are not limited to, risks of obtaining future partner or grant funding for development of MN-166, MN-221, MN-001, and MN-029, risks of raising sufficient capital when needed to fund MediciNova's operations and contribution to clinical development, risks and uncertainties inherent in clinical trials, including the potential cost, expected timing and risks associated with clinical trials designed to meet FDA guidance and the viability of further development considering these factors, product development and commercialization risks, the uncertainty of whether the results of clinical trials will be predictive of results in later stages of product development, the risk of delays or failure to obtain or maintain regulatory approval, risks associated with the reliance on third parties to sponsor and fund clinical trials, risks regarding intellectual property rights in product candidates and the ability to defend and enforce such intellectual property rights, the risk of failure of the third parties upon whom MediciNova relies to conduct its clinical trials and manufacture its product candidates to perform as expected, the risk of increased cost and delays due to delays in the commencement, enrollment, completion or analysis of clinical trials or significant issues regarding the adequacy of clinical trial designs or the execution of clinical trials, and the timing of expected filings with the regulatory authorities, MediciNova's collaborations with third parties, and the other risks and uncertainties described in MediciNova's filings with the Securities and Exchange Commission, including its annual report on Form 10-K for the year ended December 31, 2014 and its subsequent periodic reports on Forms 10-Q and 8-K. Undue reliance should not be placed on these forward-looking statements, which speak only as of the date hereof. MediciNova disclaims any intent or obligation to revise or update these forward-looking statements.
Contact:
Geoff O'Brien
Vice President
MediciNova, Inc.
info@medicinova.com
Nice find CRV.
Thanks,
Minding
This I presume: http://money.cnn.com/news/newsfeeds/articles/marketwire/11G043444-001.htm
Kind regards,
Minding
=============
Perma-Fix Medical Announces Important Milestone Towards Scale-Up of Non-Uranium Process to Produce Technetium-99m
Marketwired
Confirms Successful Tests at Higher Radiation Levels; New Process Eliminates Proliferation Risk and the Need for Either High or Low Enriched Uranium Targets
June 02, 2015: 07:30 AM ET
Perma-Fix Environmental Services, Inc. (NASDAQ: PESI) today announced that Perma-Fix Medical SA, a Polish subsidiary of the company, completed a successful scale-up of its process to produce Technetium-99m (Tc-99m) from Molybdenum-99 (Mo-99). The tests confirmed that the Company's proprietary resins could withstand high levels of radiation, up to 2 curies, while producing usable doses of Tc-99m. We have also demonstrated the successful tagging of some of the more popular kits used to target organs. Perma-Fix Medical plans to conduct additional demonstrations at even higher curie levels in the near future, as part of its multi-step validation of its technology.
Dr. Louis F. Centofanti, CEO of Perma-Fix Environmental Services, commented, "Achieving these results at higher radiation levels is an important milestone for the company. At the 2 curie level, we now meet the industry requirements in many emerging markets that are in need of a decentralized and stable supply chain. Moreover, we are moving forward with additional demonstrations, which we believe will reinforce the strength of our groundbreaking technology at even higher radiation levels in order to accommodate North American and European customer preferences. Given these encouraging results, we believe our process has the potential to reshape the global supply chain of Tc-99m in the United States and around the world."
"Our process is both cost effective and does not require the use of government-subsidized, weapons-grade materials, including Highly Enriched Uranium (HEU) or Low Enriched Uranium (LEU) targets, which are frequently cited as proliferation risks. Moreover, it can be performed in most standard research reactors, which should help solve concerns regarding supply shortages of Tc-99m around the world. Lastly, we believe our process eliminates many environmental concerns associated with Mo-99 production, including both HEU and LEU processes, both of which produce large quantities of high level waste containing enriched uranium."
By way of background, Tc-99m is the most widely used medical isotope in the world. It allows medical practitioners to image internal body organs and is used in 80-85% of the 25 million diagnostic nuclear medical procedures each year in the U.S. alone. Common procedures include: cardiac imaging; cancer detection bone scans; gastrointestinal issues; and imaging of the brain, kidney, spleen and infections. The radioisotope market in Europe alone is expected to reach $1.6 billion in 2017, up from $1.1 billion in 2012.
Nearly all of the world's supply of Tc-99m comes from the thermal fission of highly enriched uranium (HEU) targets in a small number of highly specialized reactors. The current process is costly and has proven an unreliable source of radioactive material leading to severe worldwide shortages. The scheduled closure of the NRU reactor in 2016 and the OSIRIS reactor in France in 2018 are expected to have a further impact on the manufacturing and supply of these isotopes. The current process also raises serious proliferation concerns related to the threat associated with international production, transportation and/or use of HEU in the production of medical isotopes.
Perma-Fix's technology has the potential to overcome these issues by using neutron capture to activate natural Molybdenum, a common metal, to produce Mo-99, which decays into Tc-99m. Unlike conventional processes, the Perma-Fix Medical process can be produced locally using standard research and commercial reactors, thereby eliminating the need for special purpose reactors. The new process encompasses the full production cycle, from reactor to final medical supply, and should be easily deployable around the world.
To overcome past issues with neutron activation of Molybdenum, Perma-Fix has developed a specialized resin that is radiation resistant and holds large quantities of Molybdenum, but at the same time releases almost 90% of the Tc-99m as it forms from the decay of Mo-99. The resin, loaded with the activated Mo-99, is placed in a Technetium generator and slowly washed with a saline based solution. The eluent solution containing Tc-99m has been shown to meet targeted USP and EUP standards for Pertechnetate.
About Perma-Fix Environmental ServicesPerma-Fix Environmental Services, Inc. is a nuclear services company and leading provider of nuclear and mixed waste management services. The Company's nuclear waste services include management and treatment of radioactive and mixed waste for hospitals, research labs and institutions, federal agencies, including the DOE, the Department of Defense ("DOD"), and the commercial nuclear industry. The Company's nuclear services group provides project management, waste management, environmental restoration, decontamination and decommissioning, new build construction, and radiological protection, safety and industrial hygiene capability to our clients. The Company operates four nuclear waste treatment facilities and provides nuclear services at DOE, DOD, and commercial facilities, nationwide. Please visit us on the World Wide Web at http://www.perma-fix.com.
About Perma-Fix MedicalPerma-Fix Medical is a subsidiary of Perma-Fix Environmental Services Inc., a NASDAQ listed company. It was formed to develop, obtain FDA and other regulatory approval and commercialize a new process to produce Technetium-99 (Tc-99m), the most widely used medical isotope in the world. The new process is expected to solve worldwide shortages of Tc-99m as it is less expensive, does not require the use of government-subsidized, weapons-grade materials and can be easily deployed around the world using standard research and commercial reactors, thereby eliminating the need for special purpose reactors. Please visit us on the World Wide Web at http://www.medical-isotope.com.
This press release contains "forward-looking statements" which are based largely on the Company's expectations and are subject to various business risks and uncertainties, certain of which are beyond the Company's control. Forward-looking statements generally are identifiable by use of the words such as "believe", "expects", "intends", "anticipate", "plans to", "estimates", "projects", and similar expressions. Forward-looking statements include, but are not limited to: Perma-Fix Medical plans to conduct additional demonstrations at even higher curie levels in the near future, as part of its multi-step validation of its technology; we are moving forward with additional demonstrations, which we believe will reinforce the strength of our groundbreaking technology at even higher radiation levels in order to accommodate North American and European customer preferences; we believe our process has the potential to reshape the global supply chain of Tc-99m in the United States and around the world; our process should help solve concerns regarding supply shortages of Tc-99m around the world; we believe our process eliminates many environmental concerns associated with Mo-99 production, including both HEU and LEU processes, both of which produce large quantities of high level waste containing enriched uranium; the scheduled closure of the NRU reactor in 2016 and the OSIRIS reactor in France in 2018 are expected to have a further impact on the manufacturing and supply of these isotopes; and Perma-Fix's technology has the potential to overcome issues by using neutron capture to activate natural Molybdenum, a common metal, to produce Mo-99, which decays into Tc-99m. These forward-looking statements are intended to qualify for the safe harbors from liability established by the Private Securities Litigation Reform Act of 1995. While the Company believes the expectations reflected in this news release are reasonable, it can give no assurance such expectations will prove to be correct. There are a variety of factors which could cause future outcomes to differ materially from those described in this release, including, without limitation, future economic conditions; industry conditions; U.S. and state governmental laws and regulations adopted from time to time; and the additional factors referred to under "Special Note Regarding Forward-Looking Statements" of our 2014 Form 10-K and Form 10-Q for the quarter ended March 31, 2015. The Company makes no commitment to disclose any revisions to forward-looking statements, or any facts, events or circumstances after the date hereof that bear upon forward-looking statements.
Please visit us on the World Wide Web at http://www.perma-fix.com.
The Titanic could've used TITN management's secret:
http://ih.advfn.com/p.php?pid=nmona&article=67050840&xref=newsalert
Minding
Thank you kindly Steve.
George
Right-O. Thanks.
And there's mention here: http://www.sec.gov/Archives/edgar/data/1412486/000141588915001830/cocppre14a_may182015.htm
Kind regards,
Minding
Link?
Minding
Seems like a reasonable conclusion.
Conflict minerals are minerals that come from countries like the Democratic Republic of Congo. This form (http://ih.advfn.com/p.php?pid=nmona&article=66981498&xref=newsalert) says ExOne made a concerted effort to insure their minerals don't come from any countries on the list. This is a vital process.
Kind regards,
Minding
Perhaps ... if word reaches ears not yet reached.
Minding
That perhaps explain the last minute pop yesterday. Does it fully resolve their cash needs going forward? It doesn't look like it does to me. Others' thoughts?
Thanks.
Minding
BrainStorm Cell Therapeutics Tackles Neurodegenerative Disease with Super Cells
Source: Peter Byrne of The Life Sciences Report
From http://www.investorideas.com/news/2015/biotech/05201.asp
May 20, 2015 (Investorideas.com stocks newswire) An Israeli biotech is hard at work on a new treatment for neurodegenerative disease that holds promise in a variety of devastating diseases and enjoys fast-track and orphan drug status in its lead indication, amyotrophic lateral sclerosis (ALS). Dr. Tony Fiorino, the U.S.-based CEO of BrainStorm Cell Therapeutics Inc., tells The Life Sciences Report how his company is winning over American investors with a revolutionary, university lab-backed cell therapy.
The Life Sciences Report: BrainStorm Cell Therapeutics Inc. (BCLI:NASDAQ) utilizes autologous stem cell therapies for neurodegenerative diseases, including ALS, multiple sclerosis (MS) and Parkinson's disease. Please describe the origin of your patented treatment.
Tony Fiorino: NurOwn is the trade name of our technology platform. It emerged from the neuroscience lab of Dani Offen and Eldad Melamed at Tel Aviv University. They were trying to differentiate mesenchymal stem cells (MSCs) into cells that could be active in the treatment of neurodegenerative diseases. They succeeded in identifying culture conditions that induced the MSCs to assume the phenotype of a neuronal support cell; in fact, they were called astrocyte-like cells in the early days of the company. We now refer to them as MSC-NTF cells, which is the shorthand for MSCs that are secreting neurotrophic factors (NTFs).
TLSR: Do NurOwn cells have unique characteristics that differentiate them from other cell-based therapeutics undergoing clinical trials in the neurology space?
TF: A lot of companies and academic institutions are working with MSCs, both autologous and allogeneic. MSCs are immunomodulatory, and that definitely plays a role in treating not only neurologic disease, but other diseases as well. While they are MSCs, NurOwn cells possess additional properties that "plain vanilla" MSCs lack. Using our proprietary processes, we can induce MSCs to express and secrete high levels of NTFs, which include brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, vascular endothelial growth factor and hepatocyte growth factor. After souping up, so to speak, cells taken from patient's bone marrow, we inject them back into the patient's system.
TLSR: You said that NurOwn "assumes" the phenotype. Does that mean mimicking a neuronal support cell, or is it actually transforming into that phenotype?
TF: The treated cells do not become astrocytes. They retain the immunophenotype of MSCs and seem to possess the immunomodulatory activities of MSCs. The characterization of these cells as MSC-NTF cells during the manufacturing process is done by assessing their secretion of growth factors. So, in effect, we have created a biological drug delivery system--an MSC that is capable of secreting high levels of NTFs that can be delivered to patients. In the clinic, we have delivered them intramuscularly and also intrathecally into the cerebrospinal fluid. A major underlying hypothesis for our cells is that delivering NTFs to neurons that are diseased or degrading can prolong the survival of the neurons.
TLSR: For how long?
TF: We do not know, because we've not yet had the opportunity to push out in the clinic--to extend treatment beyond a single dose.
TLSR: What's your best guess?
TF: We can see the cells out to 60 days after administration in animal models. In the two clinical studies that we have completed, there seems to be a durable effect going out as long as six months, but we do not know what happens after that time period. We are convinced that for progressive diseases like ALS, the treatment will require multiple doses, not just a single dose.
TLSR: Is the hypothesis that this drug will retard the development of ALS, buying the patient more time, or that it might actually be able to cure ALS?
TF: Our major aim in treating ALS--and this is true for neurodegenerative diseases in general--is to slow down disease progression. There are multiple processes going on in ALS. There is a neurodegenerative process, where neurons are dying, but there is also a degenerative process in the muscles. When muscles are no longer innervated, they begin to atrophy. Even if one could fully re-innervate all the muscles in an ALS patient, once the muscle has atrophied, there is not that much that can be done about the loss of motor units.
From a theoretical perspective, we do not view our treatment as curative. That said, we have seen functional scores and respiratory function improve transiently in some treated patients. We are very happy to report that the majority of patients who are exposed to NurOwn cells experience a slowdown in the disease progression in ALS. That is a huge win for cellular medicine, if we continue to see this in larger studies.
TLSR: How complex is your manufacturing process?
TF: The manufacture of MSCs has been going on for a while and is not complicated. For the first part of the process, which is the expansion of MSCs isolated from bone marrow, we have developed proprietary conditions. It is then straightforward to differentiate the cells in our patent-protected culture conditions. After several days, they are ready to harvest.
TLSR: Where do you manufacture the cells?
TF: We manufacture NurOwn cells in academic clean room facilities close to the clinical trial sites. In Israel, we manufacture them in a clean room at Hadassah Medical Center in Jerusalem. In the U.S., we manufacture at a stem cell facility at the Dana-Farber Cancer Institute in Boston, as well as at the Mayo Clinic. Eventually, we expect to have a centralized manufacturing facility. As we move toward trials with larger subject numbers and multiple doses, we fully anticipate that production needs will exceed what we are able to achieve in the clean rooms at Dana-Farber and the Mayo Clinic. We will then be working with a contract manufacturer.
TLSR: You completed a Phase 2 trial in ALS patients in Israel in 2014. Can you describe that trial and the results?
TF: The study in Israel enrolled 14 ALS patients relatively early in disease progression. The mean baseline ALS functional rating score (ALSFRS) for those patients was 40. Since the scale goes from 0-48, they were high functioning patients. The study design was similar to the prior Phase 1/2 study, which had involved a three-month run-in period. We followed patients on a monthly basis. We studied their lung function by measuring forced vital capacity (FVC), and we followed their overall function with the ALS functional rating score. In the last month of the run-in period, we manufactured the cells and administered them. Then we followed the patients for six additional months to see what happened.
That study confirmed the safety profile we had seen in the earlier Phase 1/2 study. The vast majority of adverse events were grade 1 or grade 2, were related to the treatment administration, and consisted of effects like low-grade fevers, headache and pain at the injection site, and were resolved within one to two days of the administration of cells. There were two deaths in the study, which were deemed by the investigators to not be treatment-related. One of the deaths was a physician-assisted suicide, which is, unfortunately, something that you see with ALS patients sometimes. The other was a cardiac arrest, which was also considered unrelated to the treatment.
TKSR: Was there a positive effect?
TF: We saw a treatment effect on both the ALSFRS and the FVC. In both cases, we found that the rate of disease progression slowed meaningfully for the six-month period after the cells were administered, as compared to the run-in period. For ALSFRS, the mean rate of disease progression as measured by the monthly ALSFRS score showed that patients were losing about 1.4 points per month during the run-in period. This dropped to 0.6 points per month for the six-month post-treatment period. That is an improvement of 57%. In terms of FVC, or lung function, the rate of decline for the run-in period was approximately 2.6 percentage points per month. This improved to a loss of just 0.9 percentage points per month for the six months following treatment, which is about a 67% improvement in the rate of disease progression.
TLSR: What's next in the clinical trial process?
TF: We are in the midst of a 48-patient, randomized, double-blind, placebo-controlled trial in the U.S. We expect to complete enrollment in that study in July and to have top-line results next year. This study is enrolling an early-stage patient population, similar to the Phase 2a study in Israel. With a 3:1 randomization, we will have 36 treated patients versus 12 on placebo. Like the prior Israeli study, this new study features a single dose administered intrathecally, as well intramuscularly into the right biceps and triceps.
Because the trial is randomized and double-blinded, we will not have any insight into the efficacy until the completed study is unblinded. But we do have periodic Data Safety and Monitoring Board (DSMB) reviews. A review in February gave us a very clean update on the study. There had been no treatment-associated serious adverse events detected, no unusual lab abnormalities and no important protocol deviations. The reviewers recommended that the trial continue. We will have an additional DSMB update later in 2015.
The FDA asked for this trial to be a safety study. But we are looking at the same kind of efficacy endpoints--secondary endpoints--that we examined in the Israeli studies.
TLSR: If the safety study proceeds successfully, are you then required to do another clinical trial for efficacy?
TF: Yes. We are expecting to run a pivotal study after the current U.S. study is complete and we've reviewed the results and met with the FDA. We also plan to run another study in Israel this year, looking at multiple doses for the first time. Subjects will receive three doses of cells, separated by two-month intervals. We should have interim results from this multidose study at the same time we have the final results from the U.S. study. If the results on the efficacy side are exceptionally strong, then we would discuss an accelerated approval with the FDA and other regulatory agencies.
TLSR: Does getting approval from the Israeli regulatory agency help your standing with the FDA?
TF: The Ministry of Health in Israel performs a similar function to the FDA in the U.S. and the European Medicines Agency in Europe. Each regulator has a unique approach. Sometimes drugs that are approved in Europe do not garner FDA approval, and vice versa. The advantage to doing some clinical development in Israel is that the results support the investigational new drug application (IND) that we filed with the FDA.
TLSR: In 2004, BrainStorm entered into a research and licensing agreement with Ramot, Tel Aviv University's technology transfer company. How did that occur?
TF: BrainStorm's technology was spun out of Tel Aviv University (TAU). Ramot is the licensing arm of TAU. Many of the big universities in Israel have an independent company to deal with technology transfer and licensing--for example, Yissum is the well-known licensing company affiliated with Hebrew University. The NurOwn technology was spun out of the university lab to be commercialized.
TLSR: Is Ramot investing in BrainStorm?
TF: Ramot does have some share ownership and warrants dating back to the early license agreements. And it will receive royalties, while not playing an operational role.
TLSR: Why did it take 10 years to reach the current stage of product development?
TF: The first half of the BrainStorm's life was spent developing a manufacturing process to produce cells for use in humans. A lot of work was also done on the preclinical side, obtaining proof of concept in various neurodegenerative diseases in different animal models--Parkinson's, Huntington's, MS, ALS, etc. The company has completed two clinical trials since 2010.
TLSR: What are the major obstacles moving forward?
TF: Like many small biotechs financing the long haul of clinical trials, BrainStorm needs to secure lines of capital. We were successful in raising money in 2014 and early 2015. We are now financed beyond the completion of the Phase 2 clinical trial in the U.S. That means that we have the resources to scale up the manufacturing process. That process is not complicated, but it does require a fair amount of technician time in the clean room, since the molecule is large.
The drug production constraint has limited the rate at which our clinical trials can enroll. The current U.S. study can only enroll five to six subjects per month with both clean rooms operating at full capacity. We are well on the way to the full 48 needed.
TLSR: In your 2014 year-end report, you disclosed that you needed to raise additional capital to continue with the business plan. Whom did you raise the new capital from?
TF: In January we netted $15 million ($15M), mostly from a warrant exchange with warrant holders from our prior financing, which was completed in June 2014. Those warrant holders exercised warrants that struck at $5.22/share, which was a premium to the price of the stock at the time. In exchange for exercising that warrant, we issued 1.5 warrants struck at $6.50/share. We raised about $13M in that transaction, by selling stock at a premium with 50% warrant coverage. It was a great deal for us.
TLSR: How is your background at Greywall Asset Management LP and EnzymeRx Inc. suited to the commercial needs of BrainStorm?
TF: I spent many years as a biotech investor and portfolio manager, investing in a wide variety of companies to support their development programs. My scientific background includes an MD and a PhD, which was in progenitor cell biology. In addition to my financial background, I have a lot of experience running a small company engaged in Phase 1 and Phase 2 studies. In 2008, I helped to finance EnzymeRx, which was a startup company. I joined it as the CEO and took our gout program from late-stage preclinical to Phase 2 before selling it.
TLSR: What is the professional composition of the rest of your team?
TF: In Israel, we have three PhDs and a half dozen technicians working with our cells at labs in Petach Tikva and in the clean room at Hadassah. We continue to collaborate very closely with Dani Offen at Tel Aviv University, who is our chief scientific adviser. Professor Dimitrios Karussis, a neurologist at Hadassah, has been a tremendous advocate for the clinical development of our cells.
TLSR: NurOwn was granted orphan drug status by the FDA in 2011, and also by the European Commission (EC). What's the importance of obtaining orphan drug designation?
TF: Orphan drug designation provides a period of market exclusivity after approval, meaning that a competitor with a similar product will not gain market approval until our orphan drug exclusivity expires. The orphan drug designation reflects upon the demographics of the disease--in this case ALS, where it is not as uncommon as we wished it would be, but it still is a disease that, in the U.S. and the European Union, numbers tens of thousands of patients, not millions of patients.
TLSR: How do you price an orphan drug in the market?
TF: Drugs are priced according to the benefits they provide relative to other treatments, if there are other treatments, as well as to the size of the patient population. The whole point of providing exclusivity and other incentives in orphan markets is to allow companies to create profitable enterprises in unattractive market areas, in which there may not be many patients. Our treatment is not a pill, so it is hard to predict what the cost of production will be, but it will be more than the cost of making 10 milligrams of Claritin. We expect to sell NurOwn at a margin that makes sense and is affordable.
TLSR: You see a potential use for NurOwn in treating Parkinson's disease, correct?
TF: Yes, absolutely. Parkinson's is not an orphan indication, but Huntington's disease is, and we looked at rodent models for both diseases. In our preclinical studies, we directly administered cells to damaged sites in the brain. Many different cell therapies have been administered intracerebrally in Parkinson's patients, but it is not clear if it can be done more than once. So, if we eventually plan to run a clinical study administering multiple doses of the cells in those diseases, we will need to figure that out before moving forward. We are exploring the clinical paths forward to treat several other diseases, however, where intrathecal or local injections would make sense.
TLSR: Can you tell us why investors should buy stock in BrainStorm at this point in the trajectory of your development?
TF: Look at our valuation relative to other companies in the regenerative medicine space. We absolutely trade at a discount to many of our peers, despite that fact that we are in the midst of a very solid Phase 2 ALS program. I believe our valuation does not fairly reflect the value and potential of our technology. We have shown, preclinically, that it is possible to treat multiple neurodegenerative diseases with these cells, so we really have a platform technology. We're not an ALS company per se. We are a neurology company, and there is a lot of potential upside.
TLSR: Why is the value not being reflected in the stock price?
TF: BrainStorm is an Israeli company. I am the first U.S. employee to join the company, as well its first non-Israeli CEO. Historically, BrainStorm has not had a strong presence in the U.S. capital markets. Since I joined the company, we have established a U.S. headquarters, and we will continue to expand the team here. We have added analyst coverage to the story, and I have presented at broker conferences. We are reaching out to both institutional and retail investors. BrainStorm is in its best-financed shape yet. We are in a financial position to move the ALS program forward, while moving additional indications into the clinic and broadening the preclinical profile. We are telling the story in many different venues, but it is, of course, a work in progress.
TLSR: Do you have debt?
TF: We have no debt!
TLSR: Thanks, Tony.
Dr. Tony Fiorino brings to BrainStorm Cell Therapeutics extensive experience in both biotechnology financing and drug development. Prior to joining BrainStorm, he was a managing director at Greywall Asset Management, a healthcare equity fund. Previously, Dr. Fiorino was founder, president and CEO of EnzymeRx Inc., where he led the acquisition of a late-stage preclinical biologic, and then development of the compound through Phase 1 and 2 clinical trials and its subsequent sale to 3SBio. Before founding EnzymeRx, Dr. Fiorino worked as a biotechnology and pharmaceuticals analyst and portfolio manager at firms including JP Morgan, Citigroup and Pequot Capital. He earned an MD and a PhD from the Albert Einstein College of Medicine, and a BS from the Massachusetts Institute of Technology.
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It's important to note that when Zacks or anyone else provides a target price it rarely has a target date. That's a post-Phase III target and Phase III will hopefully begin in 2017.
Kind regards,
Minding
With full enrollment for the PII trial of NurOwn targeted for late this year and top-line data not available until mid-2016 I see no catalyst for this stock to move anytime soon. Am I missing something?
Kind regards,
Minding
One question I haven't resolved is about their April 21 Notice of Effectiveness. But that doesn't strike me as adequate to finance another year.
Minding
What's Behind ExOne Co. and United Technologies Corporation's 3D Printing Partnership?
By Steve Heller | More Articles
May 20, 2015 | Comments (1)
Several years ago, before ExOne (NASDAQ: XONE ) was a publicly traded company, it was awarded a contract to develop a system around complex 3D-printed molds and metal castings for aviation applications on behalf of Sikorsky, a United Technologies (NYSE: UTX ) company that primarily produces helicopters for militaries around the world.
Specifically, the project was related to Sikorsky's still in development S-97 Raider helicopter, and thus far, ExOne has spent approximately $1 million in getting its processes and systems in place to handle the scope of the project. Although the inaugural project officially concluded in the fourth quarter and only generated a nominal amount of revenue for ExOne over its lifetime, Sikorsky was pleased with the results and has awarded ExOne with an additional project that this time involves the U.S. Army.
In the following video, 3D printing specialist Steve Heller interviews David Burns, ExOne's global head of sales about the nature of the initial project with Sikorsky, if the $1 million it invested was well spent, and whether it can pave the way for future business opportunities.
A full transcript follows the video.
Steve Heller: In terms of specifics here with ExCast and its projects, I know you guys have worked with Sikorsky, which is a United Technologies company. They make helicopters for the military.
What was the nature of this project? What was the problem that Sikorsky came to you with and what were you guys trying to solve?
David Burns: Sikorsky came to us specifically because they had a casting grouping for a new flight application they were looking at, and the characteristics they wanted in those castings weren't clearly going to be available without 3D printing as an element of the process.
When we began to collaborate, we realized we were working really hard on the front end, on design with them, to be sure that the design itself was going to be printable. Then of course we needed to heavily interface with the foundry to be sure that they could pour the design we created. Suddenly, there was a process chain that was beginning to form up around the entire casting itself.
At some point Sikorsky said, "It would be really helpful -- since you're already at the design phase, the 3D printing phase, and the casting phase, why don't you just take responsibility to then get it machined, x-rayed, and certified, and deliver that to us because we as Sikorsky don't necessarily want to manage that process."
I would say it was evolutionary, and of course as we reported often on our earnings calls, the process was bumpy and hard, and there was a lot of learning to be had. But I think most hard things are like that, and we do feel as if we learned an extraordinary amount.
We are well honed now. We are staffed well and organized well to execute full casting projects, and we're pleased with the progress we've made. While it may have been expensive and it may not, from a timing perspective, have been exactly what we initially hoped for, I think both sides are really pleased and we continue to do a lot of work with Sikorsky and other DOD [Department of Defense] projects.
Heller: From what I've gathered, it cost about $1 million, what came out in the last conference call, so far for Sikorsky and getting ExCast up to speed. I'm not really sure of the revenue figures, but I believe it's probably a nominal amount at this point. I think there were a lot of up-front costs for you guys.
Do you look at that as money well spent at this point, or do you think there's more money to be spent? The return on investment, do you think it's really going to pay off?
Burns: I do, Steve. Of course that's a hard question to answer. The initial project we did with Sikorsky is concluded, for all intents and purposes.
We have launched a secondary project with them which actually, from a revenue perspective, is going to have more revenue in it than the first project did. Our expected cost pattern against that [second project] will be far lower; we know that.
We have an excellent team in place now to do exactly what we're trying to do. I suppose you can look back retrospectively and say, "We wish we'd known before," but we didn't -- but we do now.
We're very encouraged by what we think is going to happen with Sikorsky next, and beyond that there's a myriad of other opportunities laying out there that, if we choose to execute them, we think are going to be really good for ExOne, and good for our customers.
Heller: It lays the foundation for opening up ExOne into more defense-related contracts, is what I'm gathering.
Burns: I think that's a fair statement, yes.
Steve Heller owns shares of ExOne. The Motley Fool recommends ExOne. The Motley Fool owns shares of ExOne. Try any of our Foolish newsletter services free for 30 days. We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors. The Motley Fool has a disclosure policy.
Agree on all of your points. Especially dilution which seems inevitable unless they get creative. I wouldn't expect Najaf (CEO) to know how to be creative given his background but perhaps the Paulson (CFO) and Wu (Business Development) will think outside the dilution box.
Minding
A speedy review was inadequate!
Just a little clarification: On the call and in response to a question they mentioned that 3D printer manufacturers are developing proprietary methods, that is for their machines. I suppose if all manufacturers were successful that would put Sigma out of business. It's hard to imagine that happening. I wonder how much success would be enough to dent Sigma's bottom line down the line.
Kind regards,
Minding
Thanks for those two; I missed IDI and didn't know about SFES.
So it's safe to assume the list of companies is accurate and complete?
Somewhere along the way I had heard the following were also Frost's. I'll have to do some digging.
IDI
PBTH
SFES
SNTI
SVON
TRXC
VAPO
Kind regards,
Minding
Ahnhhh. Thank you.
iBox?
Minding
Here's an excellent free resource: http://stockcharts.com/school/doku.php?id=chart_school
A classic book is Technical Analysis of Financial Markets by Murphy.
Kind regards,
Minding
Shellxo, chart reading comes in handy (though without guarantees as in all parts of investing) so what's your read of the chart?
Kind regards,
Minding
Point well-made Tkrtape. Expenses are certainly high. I give them a little more time than you given their available cash but the threat is present. We'll see what they have to say tomorrow.
"NovaBay management will discuss its financial results for the first quarter of 2015 and provide a business update during its Investor and Analyst Day Event, “Avenova: Going Beyond Antibiotics,” being held in New York City on May 19, 2015. Avenova: Going Beyond Antibiotics will feature key opinion leaders in ophthalmology and optometry discussing the use and benefits of Avenova for the management of chronic eyelid conditions. A live webcast of the event will be available on the Company’s website at www.novabay.com.'
http://novabay.com/investors/events
Kind regards,
Minding
The auditor issue is very concerning. If KOOL is fixing things, why did E&Y feel compelled to quit? The only explanation is that management wasn't listening to them.
Love the lab work, but not what's unfolding in the office.
Kind regards,
Minding
Agree. A slow creeping feeling of wariness is growing in me. Strong language of inevitability, the 'Nothing can stop us' quote, has been dissolving via delays into something more akin to praying something happens.
Kind regards,
Minding
Cesca Therapeutics Submits U.S. Pivotal IDE Amendment Application for Late Stage Critical Limb Ischemia (CLI)
Cesca Therapeutics Inc. (NASDAQ:KOOL)
Intraday Stock Chart
Today : Wednesday 13 May 2015
Cesca Therapeutics Inc. (Nasdaq:KOOL), an autologous cell-based regenerative medicine company, today announced it has submitted its amendment to the investigational device exemption (IDE) application to the U.S. Food and Drug Administration (FDA) for a U.S. pivotal multicenter study of the Company's SurgWerks™-CLI and VXP System (SurgWerks-CLI) for treating advanced stages of no-option lower limb critical limb ischemia. The amendment outlines the Company's responses to the FDA's deficiencies in the original pivotal application. The amendment includes considerable data specific to assessing the SurgWerks-CLI and VXP System autologous cellular output and new methods in assessing the rapid device output in the operating room. The Company also notes that it has filed additional intellectual property as a result of this new work.
"This proposed pivotal trial is an important step toward the development of an autologous cell-based treatment for no-option critical limb ischemia patients. The novel approach developed and outlined to the FDA combines the best of the consistency of manufactured cell therapies with the safety of autologous cells. Essentially, we have now taken the cell manufacturing plant with its quality department and miniaturized it to be completed in the operating room in 90-120 minutes," commented Ken Harris, Cesca's President and head of clinical development.
The CLIRST III study will be a randomized controlled trial evaluating the efficacy of the SurgWerks-CLI and VXP System in CLI patients with non-healing foot ulcers who have no further surgical options except a major amputation versus a blinded placebo control of the same population. The primary endpoint is major amputation free survival at 12 months following enrollment and there will be an interim analysis for futility or repowering (adding more subjects) if necessary. The study will be conducted at up to 60 centers in the U.S. under Dr. Richard Powell, M.D., Chief of Vascular Surgery at Dartmouth-Hitchock Medical Center and Professor of Surgery and Radiology at Dartmouth School of Medicine. Currently, the Company has nearly 40 sites in the pipeline and is using its in-house clinical research organization to properly qualify the sites to specifications of the trial.
CLI, the most severe and deadly form of peripheral arterial disease, currently affects up to 2 million people in the U.S., many of whom are in a later stage of disease progression. By 2020, the prevalence of CLI in the U.S. is forecasted to grow to as much as 3.5 million people. In the U.S., it is estimated that there are approximately 280 amputations per million people per year and that 25% of all patients who undergo amputation below the knee will fail rehabilitation and require chronic institutional care or professional assistance at home. Consequently, the median cost of managing a patient after amputation is estimated to be two-three times that of successful limb salvage. Beyond the physical disability and financial cost, there is a significant emotional toll on the patient and the patient's caregiver/family as well; psychological testing of patients with CLI shows quality of life indices similar to patients with terminal malignancy. Thus there is an absolute critical need to develop novel strategies to promote limb salvage or limb amputation delay in patients with late stage CLI with no further options for conventional revascularization. Based on this prevalence data in the U.S. as well as similar data for European and Asian regions, the annual economic cost of CLI related amputations is estimated at $25 billion. It is in this therapeutic arena that Cesca expects to make a significant difference in the lives of patients with this debilitating disease.
About Cesca Therapeutics Inc.
Cesca Therapeutics Inc. (www.Cescatherapeutics.com) is engaged in the research, development, and commercialization of autologous cell-based therapeutics for use in regenerative medicine. We are a leader in developing and manufacturing automated blood and bone marrow processing systems that enable the separation, processing and preservation of cell and tissue therapy products. These include:
SURGWERKS™ Platform with VXP System, proprietary stem cell therapy point-of-care device kits and cell processing systems for treating vascular and orthopedic indications that integrate the following indication specific systems:
Cell harvesting
Cell processing and selection
Cell diagnostics
Cell delivery
CellWerks™ Platform, a proprietary stem cell laboratory kit for processing target cells used in the treatments of oncological and hematological disorders.
AXP® AutoXpress® Platform (AXP), a proprietary family of automated devices that includes the AXP and the MXP® MarrowXpress® and companion sterile blood processing disposables for harvesting stem cells in closed systems. The AXP device is used for the processing of cord blood.
The MarrowXpress Platform (MXP), a derivative product of the AXP and its accompanying disposable bag set, isolates and concentrates stem cells from bone marrow. Self-powered and microprocessor-controlled, the MXP contains flow control optical sensors that volume-reduces blood from bone marrow to a user defined volume in 30 minutes, while retaining over 90% of the MNCs.
The Res-Q™ 60 (Res-Q), a point-of-care system designed for the preparation of cell concentrates, including stem cells, from bone marrow aspirates and whole blood for platelet rich plasma (PRP).
The BioArchive® System, an automated cryogenic device, used by cord blood stem cell banks in more than 35 countries for cryopreserving and archiving cord blood stem cell units for transplant.
Forward Looking Statement
The statements contained herein may include statements of future expectations and other forward-looking statements that are based on management's current views and assumptions and involve known and unknown risks and uncertainties that could cause actual results, performance or events to differ materially from those expressed or implied in such statements. A more complete description of risks that could cause actual events to differ from the outcomes predicted by Cesca Therapeutics' forward-looking statements is set forth under the caption "Risk Factors" in Cesca Therapeutics annual report on Form 10-K and other reports it files with the Securities and Exchange Commission from time to time, and you should consider each of those factors when evaluating the forward-looking statements.
CONTACT: Cesca Therapeutics Inc.
http://www.cescatherapeutics.com
Investor Contact: Kirin Smith, PCG Advisory Group
+ 1-646-863-6519, or ir@cescatherapeutics.com
Good post Alan. You've been right-on with all you've said. I remain a small investor and sit happily and patiently keeping this company in my sites and reading a lot of very intelligent posts about 3D here. None-the-les GE and Honeywell are among the few likely to create the kind of sales to which you refer, but the suite (and testing) is incomplete so that won't happen anytime soon.
Kind regards,
George
More eyeballs=good! Thanks Steve.
Nice to have Zack onboard.
Kind regards,
Minding
==============
MNOV: MediciNova's Deep Pipeline Is Meaningfully Undervalued
Zacks Small Cap Research By Zacks Small Cap Research
44 minutes ago
????
By Jason Napodano, CFA & David Bautz, PhD
NASDAQ:MNOV
We are initiating coverage of MediciNova, Inc. (MNOV) with a Buy rating and an $8.00 price target. MediciNova is a biopharmaceutical company focused on developing small molecule therapeutics for the treatment of serious diseases with unmet medical needs. Currently, the company is focused on the development of MN-166 (ibudilast) and MN-001 (tipelukast).
MN-166
MediciNova is developing MN-166 (ibudilast) for the treatment of primary and secondary progressive multiple sclerosis (PPMS and SPMS), amyotrophic lateral sclerosis (ALS), methamphetamine (MA) addiction, opioid dependence, and alcohol dependence. The drug is currently being tested in five separate clinical trials in the aforementioned indications.
…Background on MN-166…
MN-166 (ibudilast) is an anti-inflammatory drug that has been utilized for over 20 years in Japan to treat asthma (Rolan et al., 2009). It acts as a phophodiesterase (PDE) inhibitor (Suzumura et al., 1999) and preferentially inhibits PDE-4 (Huang et al., 2006). The drug has shown anti-inflammatory activity in both the peripheral immune system and in the CNS via attenuation of glial cells, which play a role in certain neurological conditions. In addition, delivery of a PDE-4 inhibitor was shown to lead to enhanced differentiation of oligodendrocyte progenitor cells within areas of demyelination and a consequent acceleration of remyelination. (Syed et al,, 2013).
…Neuroprotective Effects of MN-166…
Microglia are a type of glial cell that serve as macrophages in the brain and spinal cord, thus serving as the immune systems first line of defense in the central nervous system. Chronically activated microglia can worsen demyelinating diseases, such as MS. The cells release proinflammatory mediators, such as interleukin (IL)-1, IL-6, tumor necrosis factor-a (TNF-a), and reactive oxygen species. Overproduction of these mediators can lead to the destruction of myelin or oligodendrocytes, producing demyelinating lesions.
Preclinical work performed with MN-166 showed that the compound can suppress neuronal cell death induced by activated microglia (Mizuno et al., 2004). MN-166 was shown to suppress the production of TNF-a and IL-6 by microglia as well as enhance the production of the anti-inflammatory cytokine IL-10 and neurotrophic factors such as NGF, GDNF, and NT-4. This data is in agreement with an earlier study of MN-166 in a chronic cerebral hypoperfusion model that showed it could inhibit the activation of microglia cells and prevent the formation of white matter lesions (Wakita et al., 2003). This inhibitory effect was shown to be dose dependent and involve the suppression of TNF-a production.
Indication I: Multiple Sclerosis
Multiple sclerosis (MS) is a chronic autoimmune, inflammatory disease that affects axons in the central nervous system (CNS). Axons are long, slender projections of nerve cells (neurons) that conduct electrical impulses that transmit information to different neurons, muscles, and glands. Axons are typically insulated with a protective sheath called myelin, which facilitates the proper conductance of nerve signals. When the myelin sheath is damaged there is interference in the communication between the brain, spinal cord, and other areas of the body. This process may also lead to the deterioration of the nerve cells themselves, a condition that is not reversible.
The pattern and course of the disease is characterized by the following:
- Primary progressive (PPMS): PPMS is characterized by disease progression from the onset with occasional plateaus and temporary minor improvements. It makes up approximately 10 percent of cases at onset. There are no currently approved medications for treating primary progressive MS.
- Relapsing remitting (RRMS): RRMS is characterized by clearly defined relapses with full recovery. This type of MS accounts for approximately 85 to 90 percent of MS cases at onset.
- Secondary progressive (SPMS): SPMS is characterized by an initial relapsing-remittance phase followed by progression with or without occasional relapses, minor remissions, and plateaus. Studies suggest that approximately 50% of patients with RRMS will go on to develop SPMS.
- Progressive relapsing (PRMS): PRMS is characterized by progressive disease from the onset with clear acute relapses, with or without full recovery.
…Current Treatment Options for MS…
The goal of MS therapy is to shorten the duration of acute exacerbations, decrease their frequency, and provide symptomatic relief. There are no curative therapies currently available; however, there are twelve FDA-approved therapeutic agents that can reduce disease severity and progression in patients with relapsing forms of MS. The only drug that has FDA approval for progressive MS is mitoxantrone, but it is rarely used due to its potential to cause cardiotoxicity.
- Beta interferons: Avonex® (Biogen), Plegridy® (Biogen), Rebif® (Pfizer), Betaseron® (Bayer), and Extavia® (Novartis). Beta interferons are naturally occurring cytokines secreted by immune cells that act by inhibiting viral replication via a variety of immunomodulating and antiviral activities.
- Glatiramer Acetate (Copaxone®, Teva): This is a synthesized copolymer polypeptide mixture consisting of L-glutamic acid, L-lysine, L-alanine, and L-tyrosine.
- Mitoxantrone (Novantrone®, Merck-Serono): This is a potent inhibitor of topoisomerase II, an enzyme responsible for repairing damaged DNA. Previously used to treat certain cancers, mitoxantrone suppresses the activity of T cells, B cells, and macrophages that are thought to lead the attack on the myelin sheath.
- Natalizumab (Tysabri®, Biogen): Natalizumab is a humanized monoclonal antibody that binds to specific receptors on the surface of leukocytes and inhibits adhesion to their counter-receptors.
- Fingolimod (Gilenya®, Novartis): Fingolimod is a sphingosine-1-phosphate receptor modulator that blocks migration of lymphocytes from lymph nodes, thereby reducing the number of lymphocytes in the blood.
- Alemtuzumab (Lemtrada®, Sanofi): Alemtuzumab is a monoclonal antibody that targets the CD52 receptor on mature lymphocytes.
- Teriflunomide (Aubagio®, Sanofi): Teriflunomide inhibits de novo pyrimidine synthesis and inhibits rapidly dividing cells, including T cells, which are thought to drive the disease process in MS.
- Dimethyl fumarate (Tecfidera®, Biogen): DMF (formerly known as BG-12) is an orally administered immune modulator that was approved in March 2013 by the FDA.
…MN-166 Phase 2a MS Study…
MN-166 was previously tested in a randomized, double blind, placebo controlled Phase 2a clinical trial to evaluate its safety and effectiveness in MS patients. The study consisted of a total of 297 patients with RRMS or SPMS with continued relapses. Key inclusion criteria consisted of an Expanded Disability Status Scale (EDSS) score of
In the Phase 2a trial, the patients were randomly assigned to receive 10 mg MN-166, 20 mg MN-166, or placebo three times a day (30 mg or 60 mg MN-166 total per day). Patients were treated for 12 months and then offered extended treatment on active medication for an additional 12 months. Those who received placebo during the first 12 months were randomly assigned to receive either 30 mg or 60 mg MN-166 per day in the extension period. The primary outcome of the study was the cumulative number of newly active lesions seen on bimonthly MRI scans over the first 12 months of treatment. Secondary outcomes included the time to first exacerbation, number of relapses, and annualized relapse rate over 12 months, and the cumulative volume of Gd-enhancing lesions over 12 months.
The results showed that there was no difference in the number of newly active lesions or in the cumulative volume of Gd-enhancing lesions between treatment arms. Thus, MN-166 did not appear to have an effect on overt inflammation leading to a suppression of disease activity. However, MN-166 may exert a neuroprotective effect. A preplanned evaluation of brain atrophy showed a statistically significant dose-dependent decrease in atrophy progression in the 60-mg MN-166 group (mean -0.79) compared to placebo (mean -1.20, P = 0.04) after only one year of treatment. Brain volume and atrophy measures correlate with measures of disability (Popescu et al., 2013) and cognitive function (Yaldizli et al., 2014). Changes in brain volume in MS patients is due to the neurodegenerative effect of the disease, thus abrogating brain volume loss may be a means of improving clinical and patient-centered outcomes such as disability progression. An editorial regarding this study was published in the Journal Neurology by Dr. Robert Fox, a neurologist at the Mellon Center for Multiple Sclerosis at the Cleveland Clinic and the principal investigator of the company's Phase 2b trial of MN-166. The editorial discussed how MN-166 has the potential to be neuroprotective and that neuroprotection is the "holy grail" in the treatment of progressive MS.
…MN-166 Phase 2b MS Study…
Based on the results of the Phase 2a study, investigators from NeuroNEXT, an NIH funded clinical trial network that conducts studies of treatments for neurological diseases, have initiated the SPRINT-MS trial; a Phase 2b trial evaluating MN-166 in PPMS and SPMS patients titled "A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability and Activity of Ibudilast (MN-166) in Subjects with Progressive Multiple Sclerosis" (NCT01982942).
The study is planning to enroll 250 individuals from 21 to 65 years of age and consists of a screening phase of up to 30 days followed by a treatment phase of 96 weeks and a follow up visit one month after the week 96 visit. Patients will receive either MN-166 (100 mg/day) or placebo twice a day (e.g., MN-166 50 mg or placebo taken once in the morning and once at night). As of April 6, 2015, a total of 228 subjects have been enrolled into the trial. We estimate the final results of the trial will be available by mid 2017.
The primary outcome of the study is the rate of change in brain atrophy over 96 weeks as measured by brain parenchymal fraction (BPF) using MRI. There is a very high degree of variability in skull/brain sizes that leads to a large spread in "normal" values. The BPF was developed to decrease the range of "normal" values and is calculated by dividing the brain parenchymal volume (BPV) by the total intracranial volume (ICV) (Rudick et al., 1999).
The following studies describe brain atrophy rates for SPMS patients and allow us to estimate what would reasonably be expected to occur in the placebo group of the SPRINT-MS trial:
- Study #1: The average rate of brain atrophy (calculated using BPF) in a group of 14 progressive MS patients was found to be -0.62% over a one year time period in a study that took sequential brain MRIs (Guttman et al., 2000).
- Study #2: A recent study involving 140 patients (70 active/70 placebo) showed that simvastatin treatment decreased the rate of brain atrophy in SPMS patients compared to those taking placebo (-0.29% vs. -0.58% per year) (Chataway et al., 2014).
- Study #3: Another study of 56 subjects with SPMS found whole brain volume change of -0.59% per year (Furby et al., 2010).
- Study #4: A recent review article showed the average atrophy rate in MS patients to be approximately 0.5% - 1.3% per year, compared to 0.1% - 0.4% in healthy individuals (Radu et al., 2013).
Based on the aforementioned, we would predict a brain atrophy rate calculated using BPF for the control group in the SPRINT-MS study to be -0.6% per year. The reason for the higher rate of brain atrophy seen in the control group in the Phase 2a trial could be based on the majority of patients (92%) having RRMS or the difference in calculating brain volume loss.
We have conducted a power analysis that shows an effect size of 0.38 is necessary for the trial to be 80% powered with an alpha = 0.05 and a total of 250 subjects evenly split between MN-166 and placebo. We estimate this would correspond to an atrophy rate of approximately -0.4% per year in the MN-166 treated group if the rate in the control group is -0.6% per year. Interestingly, the percent difference in rate of brain atrophy seen in the Phase 2a study was approximately -39%. If this same difference were to be seen in the Phase 2b study, given a rate of atrophy in the control group of -0.6%, the treated group would see a rate of decline of -0.366%, which we believe would be a statistically significant effect. Furthermore, the ongoing study is testing a higher dose of MN-166 than the earlier study (100 mg per day vs. 60 mg per day) and the treatment period is longer (96 weeks vs. 52 weeks), both of which increase the likelihood that the ongoing study will achieve the primary endpoint of reducing brain volume loss.
…Market Opportunity in Progressive MS…
MS affects approximately 400,000 people in the U.S. (Tullman, 2013) and 700,000 people in the EU (European MS Platform). As mentioned earlier, approximately 10% of MS patients have the primary progressive form while approximately 85-90% are initially diagnosed with the relapse-remitting form . Approximately 50% of those diagnosed with RRMS will go on to develop SPMS, although they still may suffer from relapses.
At the present time there are no approved medications for treating PPMS. Although they are not approved for SPMS (except for mitoxantrone), all of the medications approved to treat RRMS may be used off label in patients who have progressed to SPMS. For example, if a RRMS patient is taking a beta interferon they are likely to stay on treatment even after they have progressed to SPMS, at least until it is determined that the medication is no longer working. At that time, the patient may transition to Merck-KGa's Novantrone® (mitoxantrone), the only FDA approved medication specifically for the treatment of SPMS. However, as per the label, the cumulative lifetime dose is limited to 2-3 years of treatment. In practice, very few patients actually take this medication due to its potential for cardiotoxicity.
In the following figure we have compiled a list of the top selling MS medications and their total sales for 2014. Each of these medications is approved for treating RRMS, and given the fact that half of RRMS patients go on to develop SPMS, there is an enormous market opportunity for an effective SPMS drug to become a blockbuster medication.
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Indication II: Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease whereby the nerve cells in the brain and spinal cord that control muscle movement degenerate. This rapid degeneration of the motor neurons eventually leads to death, typically in three to five years after patients are first diagnosed. As the motor neurons cease to function properly, they can no longer send signals to the muscle fibers, and thus voluntary muscle action is progressively affected. Eventually, patients in later stages of the disease may become completely paralyzed which includes losing the ability to control their breathing. In the U.S., approximately 30,000 people are currently living with ALS.
As the disease progresses all patients will eventually experience increased difficulty swallowing and speaking, with most patients not able to walk or use their arms or hands. The rate at which this occurs varies from patient to patient and is measured utilizing a scoring system called the "ALS Functional Rating Scale Revised" (ALSFRS-R) (Cedarbaum et al., 1999). This scoring system consists of a series of 12 questions on basic tasks (speech, salivation, swallowing, handwriting, cutting food, dressing and hygiene, turning in bed, walking, climbing stairs, dyspnea, orthopnea, and respiratory insufficiency) that are rated on a five-point scale where 0 = can't do and 4 = normal ability. The individual items are summed to produce a score of between 0 = death and 48 = best.
There is only one drug approved by FDA for treatment of ALS patients. Sanofi's Riluzole® (rilutek) is has been shown to improve survival, but only for two to three months. The compound works by preferentially blocking tetrodotoxin (TTX)-sensitive sodium channels that are associated with damaged neurons (Song et al., 1997). This prevents influx of calcium ions and indirectly prevents stimulation of glutamate receptors. Together with direct glutamate receptor blockade, the effect of the neurotransmitter glutamate on motor neurons is greatly reduced. Rilutek does not reverse damage already done to motor neurons, and people taking it must be monitored for liver damage (approximately 10% incidence). Sales of Riluzole® peaked at around $50 million per year. It is now available as a generic.
The remaining treatments for ALS are designed to relieve symptoms and improve quality of life. This supportive care includes a multidisciplinary approach that may include medications to reduce fatigue, control spasticity, reduce excess saliva and phlegm, limit sleep disturbances, reduce depression, and limit constipation. However, none of these treatments reduces disease progression or addresses the underlying cause of the disease.
…MN-166 Phase 2 ALS Study…
In September 2014, MediciNova initiated a Phase 2 study of MN-166 in patients with ALS (NCT02238626). This is a single center, randomized, double blind, placebo controlled six-month study to evaluate the safety, tolerability, and clinical responsiveness of MN-166 (60 mg/day) when administered as an adjunct to riluzole (100 mg/day) in 60 subjects with ALS. Patients in the study will be randomized 2:1 to receive either MN-166 or placebo. The study will consist of a three month screening phase, a six-month double blind treatment phase, and an open label six-month phase and is taking place at the Carolinas Healthcare System in Charlotte, NC. The primary endpoint of the study is the safety and tolerability of MN-166 when administered with riluzole in ALS patients. A number of secondary endpoints are being evaluated including change in ALSFRS-R, respiratory function, muscle strength, and non-invasive ventilation.
On April 21, 2015, MediciNova announced positive interim safety data from the study that showed no difference in safety or tolerability between MN-166 and placebo in the first 21 subjects enrolled in the study following three months of treatment. Importantly, the independent safety medical monitor recommended that the study continue as planned. In February 2015 the company announced that they had enrolled 30 of the 60 patients for the trial. Based on the rate of enrollment thus far, we estimate that the trial will complete enrollment during the second half of 2015, with final results from the 6-month core period of the trial being available in the first half of 2016.
…Market Opportunity in ALS…
ALS is diagnosed in approximately 5,600 people in the U.S. every year and there are an estimated 30,000 patients who are currently living with the disease. With the cost to care for a patient with advanced stage disease estimated to be as high as $200,000, this represents a direct cost of more than $6 billion each year to the healthcare system.
As mentioned previously, there are very limited treatment options for patients with ALS. Riluzole is the only FDA approved medication shown to slow the progress of ALS. It acts by reducing nerve damage and may extend the time before a patient needs a ventilator and could prolong a patient's life by several months. Prior to loss of patent exclusivity, Rilutek® cost approximately $12,000 per year and had sales peak in 2012 of $50 million. This suggests that around 4,200 ALS patients were taking Rilutek® in 2012, or around 15% of the entire U.S. ALS population. Both baclofen and diazepam are used to control muscle spasms, stiffness, or tightening that interfere with daily activities. Trihexyphenidyl and amitriptyline are used to treat patients who have excess saliva and secretions as well as emotional changes. None of the aforementioned drugs alters the course of the diseases.
ALS is a highly complex disease that has multiple pathways of degeneration. Previous ALS drug development efforts have typically focused on one specific mechanism of action, and those have largely been met with failure. MediciNova is attempting to exploit the neuroprotective actions of MN-166 as well as the compounds ability to induce production of neurotrophic factors, which are specialized proteins that promote neuron growth, differentiation, and survival. Given the limited treatment options and high costs associated with patient care, we believe an effective ALS treatment would command a premium price, possibly as high as $100,000 per patient per year. Assuming conservatively that only one third of ALS patients took the drug (10,000 patients), this would generate sales of $1.0 billion per year.
Indication III: Addiction
MN-166 is currently being evaluated in a number of studies having to do with drug dependence, including methamphetamine addiction, opioid dependence, and alcohol addiction. The FDA has granted Fast Track designation for MN-166 for the treatment of methamphetamine dependence. A common mechanism amongst drug addictions appears to be the over-activation of glial cells, thus inhibition of glial cells by MN-166 may be a means to decrease the amount of pro-inflammatory cytokines that are produced by the cells in response to activation by different drugs.
Methamphetamine addiction: Methamphetamine is a highly addictive stimulant that affects the central nervous system. The SAMHSA 2013 National Survey on Drug Use and Health revealed approximately 595,000 current MA users age 12 and older in the U.S.
A Phase 1b trial examining the safety and preliminary efficacy of MN-166 in non-treatment seeking, MA-dependent users was completed in 2012. Results showed that in the presence of methamphetamine, there were no significant changes in blood pressure or heart rate in study subjects treated with 40 or 100 mg/day of MN-166. The cardiovascular safety interaction results were a primary objective of the study. In addition, there was a significant improvement in measures of sustained attention in subjects completing a treatment sequence ending with a one-week course of MN-166 dosed at 100 mg/day compared with those treated with placebo.
These results lead to the initiation of a Phase 2 trial of MN-166 that is being funded by the National Institute on Drug Abuse (NIDA), a part of the National Institutes of Health (NIH) with MediciNova responsible for providing drug supply and regulatory support (NCT01860807). The trial will enroll 140 treatment-seeking methamphetamine addicts that will be evenly randomized to receive either MN-166 (100 mg/day) or placebo. The primary outcome of the study is methamphetamine abstinence during the final two weeks of treatment, an outcome that is favored by regulatory authorities for addiction medication assessment. Since methamphetamine abuse is often associated with HIV infection, half of the study participants will be HIV positive and the study will assess whether MN-166 also improves HIV outcomes (e.g., medication adherence, CD4 count, and risk behaviors). The trial was initiated in July 2013 and is expected to take approximately four years to complete.
Opioid withdrawal and dependency: The SAMHSA 2013 National Survey on Drug Use and Health reported approximately 1.9 million people over the age of 12 have nonmedical pain reliever dependence or abuse and approximately 517,000 people age 12 and older have heroin dependence or abuse in the U.S.
A Phase 1b/2a double blind, randomized, placebo controlled study was conducted at Columbia University in 2010 to investigate whether MN-166 could reduce opioid withdrawal symptoms. The study was funded by NIDA. Thirty non-treatment seeking heroin addicts were tested on an in-patient basis over three weeks. MN-166 reduced each of the withdrawal symptoms that are components of the SOWS (Subjective Opiate Withdrawal Scale) and showed a statistically significantly reduction in two of the withdrawal symptoms (perspiring and hot flashes).
In 2012, MediciNova announced the initiation of a NIDA-funded Phase 2a trial at Columbia University to test MN-166 in patients with prescription opioid dependency (NCT01740414). The trial plans to enroll 24 healthy prescription opioid abusers (OxyContin, Vicodin, Percocet) or heroin abusers. The study will be conducted on an in-patient basis over six weeks.
In August 2014, the company announced positive interim results from an interim analysis performed after the first seven patients had completed the study. MN-166 demonstrated a beneficial effect on the subjective, analgesic, and reinforcing effects of oxycodone and significantly decreased the craving for heroin, cocaine, and tobacco (P
Alcohol addiction: The SAMHSA 2013 National Survey on Drug Use and Health reported approximately 17.3 million people in the U.S. with alcohol dependence or abuse. There are three FDA approved medicines to treat alcohol dependence including Antabuse®, Vivitrol®, and Campral®. However, there is still a pressing need for a safe and effective treatment for alcohol addiction as the FDA approved compounds have limited efficacy (Witkiewitz et al., 2012).
In August 2013, MediciNova announced that the National Institute on Alcohol Abuse and Alcoholism (NIAAA) would fund a randomized, double blind, placebo controlled Phase 2 clinical trial of MN-166 in 24 non-treatment seeking individuals with either alcohol abuse or dependence (NCT02025998). The trial will randomly assign participants to seven days of MN-166 or placebo treatment during which time the participants will take the study medication, complete an IV alcohol challenge, and take part in laboratory tests of alcohol craving as well as mood surveys and standard safety tests. The primary outcomes for the study include safety, tolerability, and preliminary efficacy as indicated by whether MN-166 reduces alcohol craving under controlled conditions. The outcomes of this trial will inform the feasibility of a Phase 2b, regulatory-track, outpatient trial in alcohol dependence.
…Market Opportunity in Addiction Treatment…
Treatment of addiction represents a sizeable opportunity for MediciNova. For MA addiction, there are no treatments available and there are close to 600,000 MA addicts in the U.S. MA addicts are currently treated with behavioral therapies that typically combine family education, individual counseling, 12-Step support, drug testing, and encouragement for non-drug-related activities. Motivational Incentives for Enhanced Drug Abuse Recovery (MIEDAR), an incentive based program that promotes cocaine and methamphetamine abstinence, has demonstrated efficacy through NIDA's National Drug Abuse Clinical Trials Network.
There are approximately 1.9 million current opioid medicine addicts and an additional 517,000 heroin addicts in the U.S. Current treatment options for opioid addiction include generic methadone, Subutex® (buprenorphine), and Suboxone® (buprenorphine + the opioid antagonist naloxone). Subutex® had U.S. sales of approximately $108 million in 2014 while Suboxone® had sales of $1.1 billion.
In the U.S., there are approximately 17.3 million people addicted to alcohol. There are three FDA approved medications for the treatment of alcohol dependence; Antabuse® (disulfiram), Vivitrol® (naltrexone), and Campral® (acamprosate). Only 20% of eligible patients receive medications to help combat their addiction. In 2014, sales of Vivitrol® totaled $94.2 million, while sales of Antabuse® and Campral® were not disclosed.
MN-001
Tipelukast (MN-001) is a novel, orally available small molecule compound that works through several mechanisms to produce anti-fibrotic and anti-inflammatory effects in preclinical models. The compound is a leukotriene (LT) receptor antagonist, a PDE inhibitor (mainly 3 and 4), and also inhibits 5-lipoxygenase (5-LO). The 5-LO/LT pathway is though to be a pathogenic factor in fibrosis development (Zeldin et al., 2002).
MediciNova is developing MN-001 as treatment for nonalcoholic steatohepatitis (NASH) and pulmonary fibrosis (PF). Previously, the company had tested MN-001 as a treatment for asthma and completed a Phase 2 study with positive results. The compound has been tested in over 600 subjects and was considered generally safe and well tolerated.
Indication I: NASH
Nonalcoholic steatohepatitis is inflammation and damage in the liver brought on by a buildup of fat. The disease is an often "silent" liver disease as most people with NASH feel well and are not aware that they have a liver problem. Nevertheless, NASH can be severe and can lead to cirrhosis, in which the liver is permanently damaged and scarred and no longer works properly.
NASH is the most severe form of nonalcoholic fatty liver disease (NAFLD), a type of fatty liver where there is deposition of fat (steatosis) in the liver brought on by something other than alcohol consumption and is often due to obesity. Approximately 10 to 20 percent of individuals in the U.S. have fat in their liver but no indication of inflammation, while NASH affects two to five percent of people in the U.S (NIDDK).
People with NASH usually have few or no symptoms. Patients generally feel well in the early stages and only begin to have symptoms - such as fatigue, weight loss, and weakness - once the disease is more advanced or cirrhosis develops. The progression of NASH can take years or even decades, can stop on its own and even get better without therapy, or it can slowly worsen and cause fibrosis, or scarring, of the liver. As fibrosis worsens, cirrhosis develops; the liver becomes seriously scarred, hardened, and unable to function normally. Not every person with NASH develops cirrhosis, but once serious scarring or cirrhosis is present there are few treatments that can halt the progression. Liver transplantation is the only treatment for advanced cirrhosis with liver failure, and transplantation is increasingly performed in people with NASH. NASH ranks as one of the major causes of cirrhosis in America, behind hepatitis C and alcoholic liver disease.
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Elevated liver enzymes, such as alanine aminotransferase (ALT) or aspartate aminotransferase (AST), are the first sign that a person may have NASH. If further evaluation shows no apparent reason for liver disease (such as medications, viral hepatitis, or excessive use of alcohol) and x-rays or imaging studies of the liver show fat, NASH is suspected. The only means of proving a diagnosis of NASH and separating it from simple fatty liver is a liver biopsy. NASH is diagnosed when examination of liver tissue shows fat along with inflammation and damage to liver cells. If the tissue shows fat without inflammation and damage, simple fatty liver or NAFLD is diagnosed. An important piece of information learned from the biopsy is whether scar tissue has developed in the liver. Currently, no blood tests or scans can reliably provide this information.
While NASH has become more common since it was first diagnosed over 30 years ago (Ludwig et al., 1980), its exact cause is still uncertain. Since it is associated with fat accumulation in the liver, it is not surprising that many patients with NASH have elevated blood cholesterol and triglycerides. However, some patients with NASH are not overweight, do not have diabetes, and have normal blood cholesterol and triglyceride levels. Thus, while they are contributory factors, NASH is not simply a consequence of obesity or elevated blood lipid levels.
…Current Treatment Options for NASH…
There are currently no treatment options available for those that develop NASH. Physicians typically advise NASH patients to lose weight (if they are overweight or obese), get more exercise, eat healthy, and avoid alcohol and unnecessary medications. While these are simply standard recommendations for maintaining a healthy lifestyle they can make a difference in patients with NASH. Losing weight typically leads to improved liver tests and may possibly reverse the disease, but usually only to a certain extent.
Experimental approaches currently under development include the use of antioxidants, such as Vitamin E, selenium, and betaine. There is usually an increased oxidative stress in the livers of NASH patients, thus these medications may work to lower the amount of oxidative species. Another experimental approach under development is the use of antidiabetic medications, even for those NASH patients who are not diabetic. Many NASH patients are insulin resistant, thus medicines such as metformin, rosiglitazone, or pioglitazone may increase patients sensitivity to insulin and reduce liver injury by better enabling a patient to control blood glucose and lipid levels. Additional therapies under development include experimental medications obeticholic acid (Intercept Pharmaceuticals), RP103 (Raptor Pharmaceuticals), GR-MD-02 (Galectin Therapeutics), and LJPC-1010 (La Jolla Pharmaceuticals).
…Pre-clinical Data Supports MN-001 for the Treatment of NASH…
Two separate studies in mouse models of NASH have shown MN-001 to have both anti-NASH and anti-fibrotic activity.
- Study #1: MN-001 was administered orally once daily (10, 30, or 100 mg/kg) for three weeks in the STAM™ (NASH-HCC) mouse model of NASH. The model is created by a combination of chemical and dietary interventions in a standard laboratory mouse strain.
Treatment with MN-001 resulted in a dose-dependent reduction in liver fibrosis as demonstrated by a reduction in liver hydroxyproline content (P
- Study #2: In a second study, the same STAM™ (NASH-HCC) mouse model of NASH was utilized, however the mice were at a more advanced stage of NASH. MN-001 was administered orally once daily (10, 30, or 100 mg/kg) beginning at eight weeks of age for four weeks.
Once again, treatment with MN-001 resulted in a statistically significant decrease in NAS score (P Barry-Hamilton et al., 2010). Importantly, treatment with MN-001 had no effect on body weight or general condition of the mice compared to placebo.
Indication II: Pulmonary Fibrosis
Pulmonary fibrosis is a respiratory disease that occurs when lung tissue becomes damaged and scarred. As the disease progresses patients gradually become more short of breath. The disease can be caused by a number of factors, however in most cases there is no known cause. When a specific cause can't be found, it is referred to as idiopathic pulmonary fibrosis (IPF). A diagnosis of PF carries a grim prognosis, as most patients diagnosed with the disease typically die within three to five years of diagnosis (Frankel et al., 2009).
Most cases of PF will come on gradually, with patients typically first experiencing symptoms at least six months prior to a diagnosis. Symptoms of the disease include dyspnea (shortness of breath), a dry cough, fatigue, weight loss, and aching muscles and joints. Risk factors for developing PF include age (most cases are diagnosed in older adults), smoking, working in mining, farming, or construction, and certain cancer treatments.
PF appears to be a relatively rare disease; however, no large-scale studies of the incidence or prevalence are currently available. According to the Coalition for Pulmonary Fibrosis, IPF affects approximately 128,000 individuals in the U.S., with about 48,000 new cases diagnosed annually. Approximately two-thirds of people diagnosed with PF are above the age of 60 at the time of diagnosis (Raghu et al., 2006).
…Current Treatment Options for PF…
There is no cure for PF, thus currently used medications are aimed at preventing additional lung scarring, relieving symptoms, and helping patients stay active and healthy. Patients with PF typically present with a number of comorbid conditions, including chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, gastroesophageal reflux disease (GERD), and coronary artery disease (CAD). GERD is particularly prevalent amongst patients with PF and a retrospective analysis showed that of 204 patients, 34% reported symptoms of GERD, 45% had a history of GERD, and 47% reported use of medications for GERD.
In addition, the use of GERD medications was associated with longer survival time (Lee et al., 2011). Additional medications that have been utilized to treat PF include prednisone, cyclophosphamide, azathioprine, and mycophenolate mofetil. Oxygen therapy is typically prescribed when lung function begins to deteriorate and blood oxygen levels fall too low. Lastly, lung transplant may be recommended if a patient is younger than 65, has no other medical problems, and are not responding to other medications.
There are currently two agents that are FDA-approved for the treatment of PF: pirfenidone (Esbriet®) and nintedanib (Ofev®), both of which were approved in October 2014.
…Clinical Development Pathway for MN-001…
MediciNova currently has an investigational new drug (IND) application open with the FDA to initiate a Phase 2 trial of MN-001 in both NASH and IPF. In October 2014, the company announced they had received feedback in regards to the study protocol for the Phase 2 trial of MN-001 in NASH. That same month, the company announced that the FDA granted Orphan Drug designation to MN-001 for the treatment of IPF. Orphan drug designation carries a number of incentives for the company, including increased feedback from the FDA regarding clinical trial design, seven years of market exclusivity following approval for the treatment of IPF, tax credits, and a waiver of PDUFA fees. In February 2015, MediciNova announced that FDA has approved the protocol for a Phase 2 study in moderate to severe IPF. The company is currently in discussions with investigators to initiate trials in NASH and IPF.
Valuation and Recommendation
There are a number of companies developing treatments for MS, ALS, addiction, NASH, and IPF. The following table lists some of these companies, the compounds under development, and the valuations currently assigned to them.
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While it is very difficult to make an "apples to apples" comparison, as most of these companies have additional compounds under development, one company that may serve as a useful proxy is AB Science, which is developing masitinib for both progressive MS and ALS and has a current market cap of approximately $580 million. AB Science is also developing masitinib for multiple oncology indications, thus the entire market cap of the company cannot be attributed to the MS and ALS indications. However, we believe that MediciNova's $95 million market cap is low in comparison, particularly given that the company is also developing MN-001 for NASH and IPF, two indications that appear to command premium valuations based on the market caps of Intercept Pharmaceuticals and FibroGen, Inc.
…Our Valuation Methodology…
For MN-166, the vast majority of its value lies in the potential for treating progressive MS. An interim analysis for the MS trial is set to occur after half of the 250 patients targeted for enrollment in the study have received 96 weeks of treatment. The trial hit 125 enrollees in Aug. 2014, thus we anticipate an interim analysis in the second half of 2016 with the full data available in the first half of 2017. Positive interim and/or full data is very likely to lead to a partnership deal before the initiation of a Phase 3 study, which we estimate would begin in 2018, leading to an NDA filing in 2021 and approval in 2022.
A recent article in the journal Neurology shows that pricing for MS medications has increased at a very high rate since the first treatments were approved in the early 1990's (Hartung et al., 2015). As the following figure shows, yearly MS drug prices now range between $45,000 and $65,000, even for those drugs that were approved more than twenty years ago. This means that a successful MS drug is likely to command at least $50,000 per year, which we are using for valuation purposes.
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For MS, we estimate that MN-166 will have peak worldwide sales of approximately $5 billion. This may seem like an unrealistically high number, however we feel it is justified based on the pricing of MS drugs, the fact there is only one treatment for progressive MS that is not widely used, and a patient population of approximately 210,000 in the U.S. In addition, seven different MS drugs had greater than $1 billion in sales in 2014. We apply a 20% discount rate and a 33% probability of success to arrive at a probability adjusted net present value for MN-166 in MS of $115.5 million.
Results from the company's Phase 2 study of MN-166 in ALS should be available in the first half of 2016. Positive results could lead to the initiation of a Phase 3 trial in 2017, an NDA filing in 2019 and approval in 2020. Given the limited treatment options and small patient population (we estimate a target population of 18,000 in the U.S.), we believe a successful ALS drug could command $100,000 per year. Thus, we model peak worldwide sales of approximately $2.5 billion for MN-166 in ALS. Due to the fact that only one drug has ever been approved to treat ALS we model a 10% probability of success and apply a 20% discount rate. This gives a probability adjusted net present value for MN-166 in ALS of $35.8 million.
The addiction indications are not as large of an opportunity as for MS and ALS, however early results from those studies have been quite encouraging and there are few if any treatment options currently available. Treatments for addiction are capable of being blockbuster medications, as exemplified by Suboxone®, a treatment for opioid addiction, which had sales of $1.1 billion in 2014.The timelines for the addiction indications are not known at this point, thus instead of a detailed financial model, we assign a current valuation based on potential peak sales of approximately $750 million for the three indications with a discount rate of 20% and a 25% probability of success. This gives a net present value for MN-166 in addiction of $31.6 million.
The company should begin Phase 2 studies of MN-001 in both NASH and IPF in 2015. We model for a Phase 3 study in each indication in 2017 and an NDA filing and approval in 2020 and 2021, respectively. We estimate peak worldwide sales for MN-001 in NASH and IPF of $3 billion and $2 billion, respectively, and apply a 20% discount rate and a 20% probability of success. This gives a probability adjusted net present value for MN-001 in NASH and IPF of $70.8 million and $44.4 million, respectively.
Summing up the valuations for each indication, the cash on the books, and an expected $40 million in capital requirements gives a net present value for the company of approximately $270 million. Dividing this by the company's current fully diluted share count gives a target price of $8 per share, and we are assigning a 'Buy' rating to the stock.
Going by the recent PR, it looks that way JC. That would be sweet.
Thanks.
Minding
Two questions:
Unless one stays on top of this board daily, the number of messages becomes astronomical. I follow too many stocks to read them all. So I'd like to ask two questions that perhaps have been discussed but given iHub's search limitations I remain unclear about the answers:
Since Q1 has come and gone, is there a new target date for DEFORM's release?
On the CC there was no attempt to estimate when the ANALYTICS component would be released. My understanding is that, while they are working on the software, they can't put it into serious testing until they have data from DEFORM. Therefore they can't estimate a delivery date. Is that essentially correct?
My thanks to all.
Kind regards,
Minding