Saturday, 14 December 2013

2013 Biotech & Pharma IPO Review – Most Popular Therapeutic trends, Trending Clinical Stages and post-IPO Winners & Losers

2013 was generally a good year for the markets (and underwriters!). The S&P 500 is up 26% on this time last year, with the NASDAQ composite running slightly higher at 30% - but not even close to the stellar 56% performance of the Biotech Index (fig 1). In fact, few events in other industries could compete with the Great Biotech IPO Fever of 2013, when the IPO conveyor belt went full overdrive, churning out an average of four biotechs a month into the public domain.


Figure 1. Performance of the NASDAQ composite Index, the S&P500 and the NASDAQ Biotech Index, Dec 11, 2012 – Dec 11, 2013
An awesome $3.5 billion was raised in 46 NASDAQ biotech IPOs this year (not even including the monster $1 billion IPO of the global CRO Quintiles, or companies which have gone public on other exchanges) – second only to the historic year 2000, when altogether 63 biopharmaceutical players floated, raising nearly $6 billion. Table 1 has a list of this year’s 46 biopharmaceutical IPOs – the last one of which, TetraLogic, began trading just 20 hours ago (on Dec. 12th).

Judging by the performance of the biotech IPO class of ’13, the markets didn’t seem to mind the craze at all. In contrast with last year, when the opening share price median was 20% below anticipated target range, the vast majority of ’13’s IPOs opened above IPO offer price (despite several necessary revisions), and as of December 11 are performing at an average of +46% on IPO price, and at +32% (mean) and +3% (median) since their share price on the first day of trading.

Table 1. Biopharmaceutical IPOs on the NASDAQ in 2013




For some companies, dreams of public markets did not materialize this year. Some companies have postponed going public as the markets no longer seem favorable this year, whilst others have withdrawn IPO filings altogether. Table 2 has queued, postponed and withdrawn IPOs.

Table 2. Queued, postponed and withdrawn IPOs
(CLICK HERE for PDF Text version of this table)

Stage of Development

PhII and PhIII products constituted an equally shared majority of this year’s IPOs’ products (fig. 1), as one of the Phase III products already failed in clinical trials (Prosensa’s disapersen). 9 of the leads in 2013 were already marketed products, and one somewhere in between—the yet-unapproved Omthera’s (now AstraZeneca) Epanova is anticipating an FDA verdict on May 5th.

There were no pre-clinical lead players in the 2013 IPO frenzy, unlike the two – Verastem and Regulus—seen in 2012. However, the non-negligible portion of 5 Phase I leads appears to show that going public for earlier-stage companies is certainly trending, although not excelling – see below.   

Figure 1. Development stages of lead products of companies which had an IPO in 2013

Best performing clinical stage

As one would expect, market interest is very visibly deterred by perceived clinical development risk. Development stage is directly proportional to the performance of the company’s stock post-IPO, and 2013 was no exception (Fig. 2). Companies with leads in PhI have performed at an average of just +5% since opening day, whilst marketed products in contrast performed at t 87% - thanks to some major stars like Insys and GW Pharmaceuticals.

Figure 2. Average performance of 2013 IPO Companies’ lead products by stage of development

Therapeutic Area

The most popular therapeutic area of leads whose companies went public in 2013 was, by a large margin, cancer – no surprises there (fig. 3). The popularity of this therapeutic area resonates in other 2013 pharma activities, such as Mergers and Acquisitions and Drug Approvals. With a higher chance of success, CNS would have long been the therapeutic area of choice, but pharma and biotech are seemingly shying away as chances to trial success are now extremely low (with the exception of pain).

A novel therapeutic area in this year’s IPO landscape was pet therapeutics (which will probably be gaining popularity in the near future). Meanwhile, ophthalmology is a quickly expanding therapeutic field, mainly aimed at eye disorders in the growing elderly population.

So far, hematology, CNS and pet medicine players are the best performers of this year’s IPO cycle. The worst performers are orphan and genetic diseases, with a -44% average since first trade. 

Emerging trend in biomarkers & other diagnostic tools

Novel diagnostic tools took second place in this year’s therapeutic area popularity rankings, comprising 11% of 2013 IPO leads. Biomarkers and novel indicators of hard-to-detect disease, or disease which needs to be detected in its early stages, such as Alzheimer’s, are a quickly emerging trend – not just for diagnostic purposes in hospital settings, but as useful tools which would help companies better define concrete endpoints in clinical trials.

Many failed CNS drugs of recent years, for instance, have failed to demonstrate efficacy based on endpoints which many have deemed far too ambiguous (cognitive improvement based on verbal memory/performance tests, etc).  In fact, it is likely that the massive potential of CNS will only explored again when better metabolic and/or genomic markers are present – firstly, to signal the presence of disease decades before it manifests, and secondly, to eradicate the destructive ambiguity of questionnaire-type clinical trial design. 

Figure 3. 2013 Biopharma IPOs by therapeutic area of lead product

Rising Stars

Some of the brightest stars in this year’s IPO group were perhaps unexpected, particularly because two of them – Alcobra Pharma and GW Phrarmaceuticals are foreigners, hailing from Israel and the UK, respectively.

Rather suspiciously, the markets were particularly interested in the “weed experts” Insys Therapeutics (INSY) and GW Pharmaceuticals (GWPH), which specialize in opioid and cannabinoid marijuana-derived therapeutics for cancer pain and nausea management. Unlike the majority of IPOs this year, both companies already had products on the market prior to IPO. Insys has had everyone talking with a 564% surge in just 5 months, from an opening price of $8.50 on May 2nd all the way up to $53.64 in October. GW Pharmceuticals is up 264% since its debut in May, having hit a peak performance of 338% in November. Two more opioid developers are due to join GW and Insys soon: Cara Therapeutics and the Danish Egalet have both filed for IPOs in Nov/Dec.

Update: On Dec 13th Insys Therapeutics received a subpoena from the Office of Inspector General of the Department of Health and Human Services in connection with an investigation of potential violations involving Health and Human Services programs. Insys stock plunged by 22% intra-day. 





Another rising star is Aratana Therapeutics (PETX) – one of the first ever developers of specialty medicines for pets (primarily cats and dogs). Aratana’s $6 IPO share price was below its expected $11-13 range, as the company’s unfamiliar business model may have caught some investors off guard. Having conveyed the massive, untapped and much-too-long ignored potential of the pet market, the PETX share price has now been steadily climbing, currently up 129% since it started trading. Despite the fact that pet owners spent $53 billion in 2012 on their animal companions (according to Aratana’s website), pet drugs are still mostly dose-adjusted drugs prescribed for humans. Aratana’s business model is centered around licensing drugs proved effective in animals and humans, and commercializing them through the FDA's Center for Veterinary Medicine (CVM). The cost of licensing Aratana pays is low in comparison to potential returns, and CVM regulatory pathways are obviously less stringent than pathways regulating human drugs. Aratana is currently advancing three pet drugs through their pipeline, and it shares soared on October 14 when the company announced its intention to acquire Vet Therapeutics, Inc. 



Entanta Pharma (ENTA) is another starlet worth watching – the company is now at +111% on its first-trading-day price as its Hepatitis C drug ABT-450, co-developed with AbbVie, and is getting encouragingly close to the market following some great results of its Phase III Sapphire-II trial. ABT-450 is part of an antiviral  cocktail shown effective in treating an amazing 96% of the most common genotype 1 HepC sufferers who have not responded to older treatments. Enanta’s drug is seen as one of the most threatening contenders to the throne of new, safer and more effective HepC medications – a throne currently being conquered by Gilead with Sovaldi, approved just last Friday (December 6th). Like Sovaldi, ABT-450 received a Breakthrough Therapy Designation (BTD) from the FDA, which shortens development and paperwork times. ABT-450 is thus looking at a New Drug Application (NDA) in Q2 2014, and a Prescription Drug User Fee Act (PDUFA) date of 3-4 months later.



Alcobra Pharma (ADHD), based in Israel, is the newest entrant to the Attention Deficit Hyperactivity Disorder (ADHD) scene, dominated by drugs like Ritalin, Concerta, Vyvanse and Strattera. Alcobra’s lead compound, MG01CI, is an extended-release version of metadoxine – a hepatoprotective drug which has been on the market for nearly 30 years for the treatment of acute alcohol intoxication, alcoholism and alcoholism-related fatty liver.  Although MG01Cl is not a novel compound, it has a crucial advantage over its “black box warning competitors” in that it is not a neurostimulant based on methylphenidate or amphetamines. In addition, having been tried and tested for 30 years now, metadoxine has a significantly better side effect profile than other ADHD meds – an important factor for a medication intended to be taken daily for many years.

An encouraging sign of buyout potential for Alcobra is the fact that New River Pharmaceuticals, the original developer of Vyvanse - now an $800-million-a-year modified version of Adderall, was bought by Shire in 2006 for $2.6 billion. New River was a company roughly comparable to Alcobra, and was acquired when Vyvanse was in Phase III clinical trials. Shire and New River were already in collaboration on the drug since Phase II.

Update: On Dec. 18, 2013 U.S. Food & Drug Administration has granted "Orphan Drug" designation to Alcobra's metadoxine for the treatment of Fragile X Syndrome.




Falling comets


The Dutch Prosensa (RNA), developing disapersen for the treatment of Duchenne’s muscular dystrophy in collaboration with GlaxoSmithKline, announced that the drug did not meet its primary endpoints in Phase III clinical trials, just two months after the company began trading. Prosensa’s share price tumbled on the news, and is currently hovering at -78% on first trading price. Several investors are holding on, as Prosensa has two more drugs in the pipeline, which are, however, based on the same RNA Exon-skipping idea as disapersen. 

Sunday, 8 December 2013

2013 Pharma M&A Review: Earlier-Stage Pipelines, Lower Premiums, and Cancer

2013 will go down in history as the year of biotech IPO frenzy, but some may also know it as the year dealmaking bounced back to fertile levels. In 2012, $109 billion was spent on biopharma and medical device M&A, with only one deal exceeding the $10 billion mark, in contrast with four in 2011. In 2013, three $10+ billion megadeals have been struck, which include Amgen’s $10.4B takeover of Onyx and Thermo Fisher’s $13.6 billion takeover of Life Technologies.

Overall, pharma, biotech and medical device M&A deals have continued to outpace the global market, according to Dealogic. Whilst the global M&A scene performed only 9.3% on last year, pharma deals are up 38%. The average deal volume is 15% up on last year, with the total standing at over $141 billion. So far, there have been 225 biopharma, diagnostics and medical device deals, 14 of which exceeded the 500million+ mark in 2013.

The most voluminous mega-deals of the year were in medical device and diagnostic sectors, as pharmaceutical players have opted for less pricey earlier-stage acquisitions. In terms of numbers, however, biotech has certainly outshined the rest, accounting for 76% of all Pharma, Medical and Biotech (PMB) sectors, according to a recent report by Mergermarket.

Unlocked Pharma Cash


Post-patent-cliff in-house R&D closures are unlocking substantial deal-ready cash for Big Pharma. After several years of pawning, re-organizing and sorting out previous acquisitions the giants entered 2013 with cash, strategy and malnourished pipelines, braced for more inorganic growth. Whilst mega-M&A activity of recent years has been filled with power play and consolidation activities, 2013 was more about pipeline acquisitions and occasional foreign market entries. 
Below (table 1) is a list of the year’s most prominent acquisitions:

Table 1. Top 2013 Biopharma deals
Sum
Premium
Acquirer
Acquisition
Pipeline interests
10,400
89%
Amgen
Onyx
Liver, kidney, breast, colorectal, thyroid cancers
8,600
10.5%
Perrigo
Elan
Alzheimer’s, bipolar, Down syndrome, Multiple Sclerosis, Crohn’s disease
8,500
34%
Actavis
Warner Chilcott
Seven pipeline products in women’s health and Urology
4,200
27%
Shire
Viropharma
Five investigational antiviral products
4,200
36%
Salix
Santarus
Four investigational gastrointestinal products
1,600
20%
Endo Health
Paladin Labs
Gastroenterology and growth in Canadian and emerging markets
958
60%
Allergan
MAP Pharma
Migraine specialty
886
27%
Otsuka
Astex
Seven oncology products
704
15%
Cubist Pharmaceuticals
Trius Therapeutics
Antibiotic-resistant gram-positive antibacterials
700
private
NovoNordisk
Xellia
Novel drug delivery platforms
650 (+350 milestones)
private
Johnson & Johnson
Aragon Pharmaceuticals
Phase II prostate cancer lead, milestone subject to FDA approval
560 (+590 milestones)
private
AstraZeneca
Pearl Therapeutics
Chronic respiratory diseases
551
15%
Cubist Pharmaceuticals
Optimer
Antibiotics
443
88%
AstraZeneca
Omthera Pharmaceuticals
Cardiovascular: fish oil – derived medicines
418
28%
Valeant
Obagi Medical Products
Specialty skin health products
340
private
Elan
AOP Orphan
Orphan diseases
324
private
GlaxoSmithKline
Okairos
Genetic vaccines
250
private
Takeda
InviraGen
Vaccines
250
private
Actelion
Ceptaris
Lymphoma drug mechlorethamine gel, deal subject to FDA approval, which was granted in August
225 (+275 milestones)
private
Medimmune (AstraZeneca)
Amplimmune
Cancer and autoimmune diseases
207.4
private
Ipsen
Syntaxin
Targeted Secretion Inhibitor (TSI) in development for treatments of cancer, neurological, endocrine and inflammatory disorders
200 (+240 milestones)
private
Medimmune (AstraZeneca)
Spirogen
DNA sequence targeted agents for cancer
200 (+470 milestones)
private
Clovis Oncology
EOS (Ethical Oncology Science)
Oncology
200
N/A
BTG
Targeted Therapies business of Nordion
TheraSphere targeted technology for cancer treatment
165
private
Teva
Microdose Therapeutx
Seven respiratory, constipation, COPD and auto-immune pipeline products
160
private
Shire
SARcode
Ophthalmology
150
private
Watson
S.A. Uteron
Women’s health
140 (+334 milestones)
private
The Medicines Company
Rempex Pharmaceuticals
Gram-negative antibiotic resistant anti-bacterials
135
private
MEDA
Acton
Respiratory disorders

Development Stage


2010 and 2011 M&A landscapes were characterized by late- and marketing-stage pipelines, in line with pharma’s pressing need to compensate for immediate patent cliff losses. In 2012, earlier-stage shifts became apparent with 42% of acquired products in Phase II clinical trials. In 2013, Phase III products marked a nearly 10-fold comeback, whilst the number of market-stage acquisitions remained virtually unchanged from last year (Fig. 1). Early-phase and pre-clinical leads remained a popular acquisition choice in 2013. Roughly two thirds of early-stage deals included some form of approval-dependent milestones.

Figure 1: Development stage of acquired products in 2013 and 2012 


Therapeutic landscape


Oncology remained the most popular acquisition area in 2013, growing in popularity nearly 35% on last year, in line with increasing global incidence (fig. 2). However, CNS disorders, which still appear to be the most lucrative therapeutic area in terms of numbers and unmet need, accounted only for 7% of acquisitions in 2013 (down 10% from 2012), following a series of loud and painful CNS trial failures in recent years. Rather than embarking on high-risk CNS trials, pharma players have this year opted for new therapeutic entrants, such as novel drug delivery systems, women’s health, and orphan specialists. In comparison with 2012, when cardiovascular leads accounted of 12% of all acquisitions, 2013 saw virtually no activity in this area, with the exception of AstraZeneca’s acquisition of the fish oil specialist Omthera.

Another strong comeback was made by the infectious diseases niche, growing nearly 3-fold in 2013. For the most part, drugs in this area are targeting the unmet need for effective treatments against antibiotic resistant bacteria, particularly gram-negative bacteria. Vaccines and anti-viral agents remain highly coveted.

Ophthalmic acquisitions have made a surprising comeback in recent years, due to increasing incidence of eye disorders in the world’s ageing populations. They have accounted for 4% of all acquisitions in 2012 and 2013.

Figure 2:  Therapeutic area of acquired products in 2013 and 2012 


Financials


Of the top 28 biopharma deals shown in Table 1, 12 of the acquisitions were public companies, 15 were private and one was a divested unit. In terms of premiums paid by public companies, the average premium figure for 2013 was 37% - significantly lower than the 52% average of 2012, pushed up by the Bristol-Myers – Inhibidex 163% acquisition - the highest premium paid in five years. 2013’s highest premium was 89% in the year’s most expensive Amgen-Onyx deal, followed closely by the 88% AstraZeneca – Omthera acquisition deal. It will be interesting to watch happens to the premiums of the graduating IPO class of 2013.

Wednesday, 4 December 2013

Order your FREE print copy of Israel's Reign in the Golden Age of Neuroscience!

Bioassociate's "Israel's Reign in the Golden Age of Neuroscience", written in conjunction with Israel Brain Technologies, proved to be a great hit amongst brain enthusiasts. A digital copy can be downloaded here.

Due to popular demand, we are now offering the copies in print, free of charge - just pay for shipping.

Order your copy below (via Paypal), and check out the intro to the report here.

Shipping Options


Contact Bioassociate for more info. 

Tuesday, 5 November 2013

Five Israeli Brain Techs to Watch

For reasons which remain a subject of vigorous debate, an 8-million-strong country only 65 years of age has been enthusiastically climbing the world’s scientific, technological and intellectual ladders. Despite the divergent opinion of Israel which exists today, few can deny that, notwithstanding the circumstances and the sizeable hindrances, many expectations have been exceeded here.

As tech-frontrunning has been one of Israel's fortes, the country did not disappoint when the world began waking up to the past decade's Brain Tech Revolution. In fact, Israel’s President Shimon Peres was one of the first global leaders to see the immense potential of neurotechnology and to lay foundations for Israel’s now burgeoning Israel Brain Technologies initiative, officially founded in 2011. Many figures and organizations quickly followed suit, in what has now become a global gold rush to fill the emerging power vacuum on the throne of world brain leaders.

Whilst many countries are still working to put their "neuro-infrastructures" in place, Israel can already boast a few prominent brain tech start-ups, some of which already have products on the market. Below is a list of our five favorites. Obama likes them too!

Brain Techs to Watch

The selection criteria for our favorite brain start-up list did not include the requirement for the word “brain” in the company name, we swear. 

Considering Israel’s strength in medical devices, and also in line with the global neurological therapeutic landscape which is seemingly swerving away from neuropharmaceuticals, only one of the technologies is a therapeutic, whilst the rest are neurodevices or neurodiagnostic tools. 

BRAINSWAY (BRIN: TASE) | www.Brainsway.com

Therapeutic neurostimulation has been hot off the conveyor belt last year. Jerusalem-based Brainsway is a developer of a Transcranial Magnetic Stimulation (TMS) device which, in essence, is a fancy name for a deep brain tissue massager. Brainsway’s key technology—Deep TMS System—exploits scientific knowledge about areas of the brain responsible for depression and other neurological disorders, the likes of which are Alzheimers and schizophrenia, and Brainsway’s breakthrough ability to penetrate deep into brain tissues with magnetic fields. The FDA has recently approved Brainsway’s TMS system for the treatment of depression patients who have not responded well to other treatments, and the company is working on expanding their therapeutic targets towards autism, obesity, bipolar disorder and Parkinson’s disease in the near future. 

Technology specifics

TMS technology was invented during the 1980s as a diagnostic tool. It operates by sending an electric current through a coil, whereby an intense magnetic field is generated. When encompassing the brain, the field penetrates the cranium and stimulates nerve cells in a particular area of the brain. During the 1990s, Israeli scientists began speculating as to the potential psychiatric applications of TMS after accounts emerged of patients reporting mood improvement following exposure to TMS. Researchers from Beer Sheva, Haifa and Tel HaShomer pioneered studies relating to TMS and treatment of depression, mania and posttraumatic stress disorder.

Early TMS devices were limited by the extent to which they could penetrate beyond the cerebral cortex (which was at most 1.5cm). Elevating the intensity of the magnetic field increased the depth of penetration but brought with it a higher risk of negative side effects, such as pain.

H-coil technology



The deepTMS technology was conceived by Avraham Zangen, a Bar-Ilan University alumnus, and Yiftach Roth. Attempting to achieve more substantial penetration of brain tissues with TMS, Zangen thought of a way to reach areas deep in the brain by activating the magnetic field at several points and having them target the same area of the brain. At the same time that the field being directed at the targeted area would undergo an effect similar to constructive interference on account of emanating from more than one point, the areas not being targeted could be made to experience a reduced-intensity field on account of the opposite effect, similar to destructive interference. The emanating technology was termed the H-coil, and was capable of safely penetrating an unprecedented 8 centimeters into the brain, which opened up the possibility of treating such deep-brain disorders as depression, schizophrenia, Parkinson's disease, and addiction. The H-coil was patented in 2002, and the procedure whereby the H-coil was applied to TMS became known as Deep TMS.

Brainsway

Brainsway was founded in 2003 by its current CEO Uzi Sofer and Avner Hagai, together with David Zacut. Brainsway conducted its first clinical Deep TMS trials at Tel Aviv University in 2005. It subsequently obtained European Union CE mark approval to treat major depressive disorder (2008), manic depression (2009), schizophrenia (2010), and posttraumatic stress disorder (2011). In January 2013, Brainsway won approval from the FDA and from Health Canada to market its Deep TMS device in the United States and in Canada as a treatment for depression in cases where patients failed to make a recovery following drug treatment.

In June 2013 Brainsway announced the company has found a U.S. partner to distribute its Deep TMS technology, and is also due to begin marketing dTMS in Japan. The company is now again seeking listing on the Nasdaq exchange, following an initial failed attempt when it did not obtain the value it was anticipating. In 2007 Brainsway completed an IPO on the Tel Aviv Stock Exchange. Leading up to, and following FDA approval of deepTMS, Brainsway’s stock price has been on a considerable climb. 


In September 2013 Brainsway obtained FDA approval of IDE for Multi-Center Smoking Cessation Study.

BRAINSGATE (private)| www.brainsgate.com 

Established in 2000, BrainsGate is a medical device company committed to developing innovative therapies for patients suffering from CNS diseases. BrainsGate's platform technology involves electrical stimulation of the Spheno-Palatine Ganglion (SPG), a nervous center known to increase cerebral blood flow. BrainsGate’s SPG stimulation technology ISS (Ischemic Stroke System) has been shown to be effective in improving the outcome of patients suffering from ischemic stroke, in a 24 hour window after onset of symptoms. Currently available treatments have a maximum 4.5 window efficacy. Long-term SPG stimulation has also been found efficacious for the treatment of vascular dementia.

The SPG stimulation technology utilizes a miniature electrode implanted at the roof of the mouth in a minimally invasive, local anesthesia procedure comparable to dental treatment. 

Upon activation, the system augments cerebral blood flow. Treatment can be either acute (over a short period of time, hours or days) or chronic (over an extended period, months to years). In addition, the stimulation regimen selected determines the biological effect: a mild stimulation profile leads to gentle augmentation of cerebral perfusion aiding in the management of ischemic stroke or dementia, while a different, more intense regimen enhances the bioavailability of drugs in the CNS by increasing the permeability of the Blood Brain Barrier (BBB).

Following very promising results in a pilot clinical study, BriansGate has launched ImpACT-24: a randomized, double-blind, sham-controlled study to assess the safety and efficacy of SPG stimulation in a 24 hour window from symptom onset. ImpACT-24 is a multi-national trial with centers in America, Europe and Asia, and is currently enrolling patients. 

BrainsGate's investors include Johnson & Johnson, Boston Scientific, Elron Electronics Industries, Pitango Venture Capital, Alice Ventures, Agate Medical Investments, Infinity Ventures and Cipio Partners. BrainsGate is headquartered in Caesarea, Israel.

INTERVIEW WITH BRAINSGATE CFO NOAM LEVY
BrainsGate’s CFO Noam Levy holds an MBA from Stanford University and a B.Sc. in Aeronautical Engineering from the Technion-Israel Institute of Technology. Prior to joining BrainsGate Noam co-founded and served as CEO of Paycard Ltd., an Internet payment service company. Before that Noam served as CFO of Itamar Medical Ltd., a medical device company.

Speaking enthusiastically about BrainsGate’s recent clinical trials, Mr. Levy says that in ischemic stroke virtually no existing therapy is effective in a 24-hour window, which makes ISS a one-of-a-kind, breakthrough therapy. Therapies which do exist are clot busters, and are effective up to a maximum of 4.5 hours after stroke. 24-hour therapies on the market or in clinical development carry substantial risks or inconveniences, such as the need to surgically remove blood clots from the brain, to implant tubes in the aorta or to shave and irradiate patients’ heads. The simplicity and safety of ISS are unmatched in the current stroke market. 

He says the patient recruitment for the SPG device’s impACT-24 clinical trials is 60% complete, and expects the trials to be finished within two years, if all goes according to plan. He added that stroke clinical studies are known in the industry as the “graveyard” for drug development, particularly due to the difficulty of designing the trials, and due to the ambiguous FDA trial assessment criteria. But in 2012 BrainsGate was proud to announce that, after 1.5 years of correspondence with the FDA, the company has been able to revolutionize the way in which stroke studies were conducted by convincing the agency to change its standard patient assessment scale to a much more accurate and optimal one. This is certainly great news for the company and future market entrants. 

A lucrative side to SPG stimulation is its ability to temporarily open the blood-brain barrier, which could be an extremely useful tool for CNS drug delivery of large molecules. BrainsGate chose not to explore this market, Mr. Levy explains, because clearly no drug which would complement the system exists. If the company followed this development path, it would be offset by another decade trying to develop a drug which would work with the device. Instead, BrainsGate chose to develop one therapy at a time, although that does not mean that in the future the company won’t be tackling the many other indications which SPG stimulation could address. He indicated that preliminary studies have demonstrated the SPG device’s efficacy in dementia. 

Mr. Levy says that President Peres’s B.R.A.I.N. initiative will complement the already-blossoming Israeli neurotech arena, but minor creases in Israel’s regulatory system at the Ministry of Health should be ironed out to help the industry, particularly the difficulty in gaining clinical trial and market approval.


BRAINSTORM CELL THERAPEUTICS (BCLI) | www.brainstorm-cell.com
BrainStorm Cell Therapeutics Inc. (BCLI) is a biotechnology company engaged in the development of first-of-its-kind adult stem cell therapies derived from autologous bone marrow cells for the treatment of highly debilitating neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS, also known as Lou Gehrig's disease), Multiple Sclerosis (MS) and Parkinson’s Disease (PD).

NurOwn™

In recent months BrainStorm has featured strongly on the international media front with announcements of highly positive preliminary results of the company’s NurOwn technology, currently in Phase IIa dose-escalating clinical trials in Israel. So promising is the technology that initial signs of efficacy were demonstrated during a Phase I safety trial, before efficacy was even assessed. Thus multiple breaths are being held in anticipation of what miracles the dose-escalating trial has yet to unravel. 

NurOwn is thus termed because it utilizes the patient’s own stem cells, which can be differentiated into specialized, neuron-supporting cells. These specialized cells secrete neurotrophic, or nerve-growth, factors for protection of existing motor neurons, promotion of motor neuron growth, and re-establishment of nerve-muscle interaction. The hope is that injection of these cells in ALS patients will significantly slow down, halt or potentially even reverse disease progression.



A FEW WORDS WITH BRAINSTORM CEO ALON NATANSON:
Mr. Natanson joined BrainStorm in February 2013. Previously, as Director of Marketing and Finance in Teva Pharmaceuticals’ (NYSE:TEVA) Copaxone division, he played a key role in the commercialization of patented therapeutics for multiple sclerosis, establishing the division and executing its international strategy and product launch. He holds a BA in Economy and an MBA from the Hebrew University. 

NurOwn is currently in Phase II clinical trials for the treatment of ALS with very promising results. If everything goes according to plan, when do you anticipate the product launch?

Clinical validation and regulatory approval of a drug or stem cell treatment is not a short process. We intend to launch another Phase II in the US towards the end of this year, which we expect will run for up to 1 ½ years. In addition, we plan to conduct a repeat-dose trial, which we hope will transition into a Phase III. In short, we anticipate product launch in 2015-2016.

Everyone wants to know: will NurOwn cure Stephen Hawking? (Is it theoretically possible?)

Our clinical goal is to slow down or halt the disease progression. If we succeed in patients with advanced disease, their potential ability to regain function of their various systems is an unknown.

ELMINDA (private) | www.elminda.com 

“Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM (Diagnostic and Statistical Manual of Mental Disorders) diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure. In the rest of medicine, this would be equivalent to creating diagnostic systems based on the nature of chest pain or the quality of fever. Indeed, symptom-based diagnosis, once common in other areas of medicine, has been largely replaced in the past half century as we have understood that symptoms alone rarely indicate the best choice of treatment.”

                                                                 --Thomas Insel, National Institute of Mental Health (NIMH)

ElMindA is a neurodiagnostic company with a potential to take the ambiguous guesswork out the way brain disorders are diagnosed. Founded in 2006 by Prof. Amir Geva of BGU’s Department of Electrical and Computer Engineering, the company’s lead technology, BNA (Brain Network Activation), is a non-invasive brain scanner technology which combines EEG readings with patented signal processing and analytical algorithms. The purpose of BNA is to read the activity of multiple neuronal areas simultaneously, to recognize patterns with the help of sophisticated analytical software, and to process this information into a diagnostic output which is meaningful for the physician, all in 15-30 minutes. Rather than observing the electrical activity of distinct brain areas, the technology aims to create a picture of the neural network which is active at any particular time. 

The idea is that certain neurological disorders will have “signature” patterns of activation and communication in these neural activity networks, and can thus be diagnosed. Another way in which the technology can be used is to compare neural network maps before and after drug administration, or during post-injury recovery. On several occasions ElMindA has now been able to demonstrate that administration of certain drugs yields distinctly altered activity networks. 

ElmindA was one of the six Israeli technologies chosen to be showcased to President Obama during his latest visit to Israel (it was his favorite)

BNA is not yet available as a diagnostic tool (although ElmindA is working on it), but pharmaceutical companies are eager to get their hands on the technology. There is a clear unmet niche in measuring drug effects on cognitive processes in CNS clinical trials—a tool which could help companies save hundreds of millions of dollars if they can foresee clinical trial failure. ElMindA recently entered into research collaboration with Purdue Pharma LP, which will focus on gathering data on brain changes during clinical trials of novel pain medications, and on improving understanding of pain pathways in the brain. 


NEURONIX (private) | www.neuronixmedical.com

Neuronix, founded in 2008, is working on introducing new methods for modifying the course of treatment for Neuro-degenerative Diseases and in particular Alzheimer Disease (AD). 

Neuronix’s neuroAD technology is currently undergoing advanced clinical trials in major medical centers across the globe, including the Beth Israel Deaconess Medical Center (BIDMC), Boston MA—the teaching hospital of Harvard Medical School. The neuroAD system for the treatment of mild to moderate Alzheimer’s Disease is based on the company’s core Non Invasive Cortical Enhancer (NICE™) technology, CE-cleared for this indication. This patent-pending technology uses magnetic stimulation of affected brain regions concurrently interlaced with Cognitive Training and directed at specific brain regions affected by Alzheimer’s disease. The stimulation induces LTP (Long-Term Potentiation), which is associated with learning and memory processes, and results in a measurable cognitive improvement after just a few weeks of treatment.

In clinical trials, neuroAD technology has shown measurable cognitive improvement after just a few weeks. The results, published in peer-reviewed journal, showed marked reversal of disease progression with patients improving to a state comparable to two years before treatment initiation. Trials also indicated that improvement is maintained for at least six months post treatment.


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