Biotech Buzz Post No. 23 - XON

Intrexon (Nasdaq: XON) is taking the new field of synthetic biology into the commercial stage. Wow, it’s already a US$2bn company!          

Intrexon (Nasdaq: XON) – Betting on the future of synthetic biology

“What I cannot build, I cannot understand” – Richard Feynman, American physicist and Nobel laureate (1918-1988).

When we look back in time we may regard Thursday 20 May 2010 as a major landmark in the evolution of the global economy. That was the day when the J. Craig Venter Institute (JCVI), of San Diego and Rockville, Md, announced that it had created the world’s first self-replicating synthetic bacterial cell. The same Craig Venter who had won the race to sequence the human genome in 2000, and subsequently sailed his yacht around the world discovering thousands of new species of ocean-dwelling microbes, was now publishing his greatest-ever biological feat. Venter’s team at the JCVI, which included the Nobel laureate Ham Smith, had used powerful computers to design a bacterial cell, assembled the components of that cell in a petrie dish, and got the cell to replicate as though it was E. Coli (click here for the Science paper).  If you’re reading this in the year 2050, ask yourself from the perspective of forty years ago how amazing this development was. Up until 2010 the only thing us biotech folks had really been able to do was take an existing bacterium and tinker with it using the tools of genetic engineering to make a few therapeutically useful proteins.  The JCVI team had now made the big leap forward and built an entire bacterium from scratch, having shown two years previous to this that you could create an entire synthetic bacterial genome (click here). Self-replicating synthetic bacterial cells are a big deal because when you can design entire organisms, you can theoretically design them to make all sorts of things we need in daily life, like fuel, food and clean water. In short, the arrival of synthetic biology wasn’t just a medical breakthrough, it was an economic breakthrough.

As with any scientific field that has this kind of potential, Venter and friends haven’t been the only ones doing synthetic biology. Another serious player has been Intrexon (Nasdaq: XON), a biotech company from Germantown, Md which did its IPO this year, raising US$184m. Clearly between 2010 and 2013 the word had gotten around regarding Venter’s giant leap because when Intrexon, which went out at US$16 per share, started listed life on 8 August the stock finished the day at US$24.73. At the current US$21.51 Intrexon is capitalised at just over US$2bn. That may be considered a little high for a company that can’t really say what its first product is going to be, but it does point to rising awareness of the ‘bioindustrial revolution’ coming over the horizon. It also reflects the halo effect of previous biomedical success. Intrexon’s major shareholder and CEO is Randal Kirk, the world’s 613^th richest person according to this year’s Forbes billionaire’s list. His previous companies have been New River Pharmaceutical (developer of the ADHD drug Vyvanse, sold to Shire for $2.6 billion in 2007) and Clinical Data (developer the antidepressant Viibryd, sold to Forest Laboratories for $1.2 billion in 2011). Kirk was worth US$2.4bn when Forbes published its latest list. Intrexon made him, on paper, another US$1.5bn richer two months ago.

What Randal Kirk has put together in Intrexon is a suite of technologies to do synthetic biology at commercial scale. With Intrexon’s UltraVector platform, you can use sophisticated bioinformatics-based tools to design multiple synthetic genomes and put them inside cells. You can then pick out the cells you particularly like for further development using Intrexon’s LEAP (Laser-Enabled Analysis and Processing) technology. Probably the most interesting piece of Intrexon know-how is a transcriptional regulation system called the RheoSwitch, so called because, like a rheostat, the elements of this system allow the genome designer to not only induce protein expression, but also to control the level and timing of expression. It’s this sort of control that can make the difference between success or failure in terms of the useful products a cell can be engineered to produce.

Intrexon is commercialising its various technologies through ‘exclusive channel collaborations’, or ECCs, with companies looking to use synthetic biology in new product development. There are a lot of these collaborations in place and more are being added all the time. Elanco, the animal health division of Eli Lilly, is a collaborator, as is Rentokil, the pest control business owned by the major British business services company Rentokil Initial.  However most of Intrexon’s collaborations are with companies considerably lower in profile. The Boston-based Ziopharm Oncology (Nasdaq: ZIOP), which is using Intrexon technology in cancer drug candidates, may be capped at US$302m. However Fibrocell Science (NYSE MKT: FCSC) of Exton, Pa., which wants to use Intrexon’s technology to treat a rare blistering disorder called ‘recessive dystrophic epidermolysis bullosa’, is only worth US$106m. Oragenics (NYSE MKT: OGEN), working on new antibiotics in Tampa, Fl, sits at US$72m. And AquaBounty Technologies (AIM: ABTX), creator of a new strain of salmon that grows twice as fast as conventional salmon, can only manage £32m (ie US$52m – the company is from Maynard, Ma. but the stock only trades in London).  Moreover none of the products being worked on is anywhere near the market.

Don’t get me wrong. Intrexon’s technology still has the potential for positive outcomes. Ziopharm is using it to deliver interleukin-12 (IL-12) directly to tumours. We’ve known for years that this cytokine is deadly to cancer, but is too toxic to be delivered systemically at therapeutic doses (click here). Ziopharm sidesteps this problem by putting the gene for IL-12 inside an adenovirus and placing the gene under the control of an Intrexon-sourced Rheoswitch. After the adenoviral vector has been delivered, the patient takes a pill which turns the Rheoswitch on, causing a whole bunch of IL-12 to suddenly express inside cancer cells. Pre-clinical data and Phase I clinical data on this cancer immunotherapy have been encouraging and the product, called Ad-RTS-IL-12, is now in Phase II in melanoma and breast cancer. Interestingly, Australia’s Mesoblast (ASX: MSB) is now working with Ziopharm on a similar approach under a collaboration announced yesterday. The thinking is that Mesoblast’s mesenchymal cells could also be used to dump Rheoswitch-controlled payloads at the site of tumours. Apparently the pre-clinical work here has gone well - in which case, chalk up yet another capability for Mesoblast’s increasingly versatile suite of mesenchymal-lineage cells.

But to return to Intrexon. Favourable early data for collaborators is one thing. A US$2bn market capitalisation for a concept play is another. I would argue that investors are currently pricing Intrexon’s technologies at ~US$2bn in part because of the perception that they are helping to solve pressing major global problems like peak oil rather than just inventing a new drug or two. Here’s how Intrexon puts it in its S-1 filing with the SEC from earlier this year:  ‘At present rates of global industrialization and population growth, food and energy supplies and environmental and healthcare resources are becoming more scarce and/or costly. We believe it is not a viable option for mankind to continue on this path — new solutions will be necessary to preserve and globally expand a high quality of life. We believe that synthetic biology is a solution.’ In my opinion, when you talk big like that and are valued accordingly you need to be in a truly high profile collaborations such as the one between Exxon and the Venter-funded Synthetic Genomics. For a couple of years after 2009 those two companies worked together on using synthetic biology to make algae fuel at commercial scale. It didn’t work out, but it sure sounded exciting at the time given what oil prices had done up until 2008. I expect that if Intrexon came up with a similar collaboration in the energy area the market reaction would be highly favourable.

That’s the trouble with breakthroughs like those Craig Venter achieved in 2010.  It’s a reasonable bet that synthetic biology can transform our lives and work, and that Intrexon can play a part in this bioindustrial revolution over time. However like all great breakthroughs, the transformation will probably take decades rather than months or years. Will investors buying the first notable synthetic biology play on Nasdaq be able to wait that long?

Stuart Roberts, Australian biotechnology analyst, with global focus

Nisi Dominus Frustra

+61 (0)447 247 909

sroberts2164@gmail.com

Twitter @Biotech_buzz

About Stuart Roberts. I started as an equities analyst at the Sydney-based Southern Cross Equities in April 2001, focused on the Life Sciences sector from February 2002. Southern Cross Equities was acquired by Bell Financial Group (ASX: BFG) in 2008 and I continued at Bell Potter Securities until June 2013. I joined Baillieu Holst in October 2013. Over the last twelve years I have built a reputation as one of Australia's leading biotech analysts. Before joining Southern Cross Equities I wrote for The Intelligent Investor, probably the most readable investment publication in Australia. I have a Masters Degree in Finance from Finsia. My hobbies are jazz, cinema, US politics and reading patent applications filed by biotechnology and medical device companies.

Previous Australian Biotechnology Buzz posts:

Acorda Therapeutics (Nasdaq: ACOR), 10 October 2013.

Advanced Cell Technology (OTCBB: ACTC), 4 September 2013

Alcobra Pharma (Nasdaq: ADHD), 17 September 2013

Amicus Therapeutics (Nasdaq: FOLD), 22 September 2013

Aradigm (OTCBB: ARDM), 8 September 2013

BioSpecifics Technologies (Nasdaq: BSTC), 26 September 2013

Celldex Therapeutics (Nasdaq: CLDX), 9 November 2013

Cellular Dyamics (Nasdaq: ICEL), 3 September 2013
Exelixis (Nasdaq: EXEL), 17 October 2013

ImmunoCellular Therapeutics (NYSE MKT: IMUC), 27 August 2013

Immunomedics (Nasdaq: IMMU), 21 August 2013

Inovio Pharmaceuticals (NYSE MKT: INO), 24 August 2013
Intrexon (Nasdaq: XON), 24 August 2013

Merrimack Pharmcaceuticals (Nasdaq: MACK), 26 August 2013

Novavax (Nasdaq: NVAX), 3 October 2013

Oncolytics Biotech (Nasdaq: ONCY),  22 August 2013

Pharmacyclics (Nasdaq: PCYC), 2 September 2013

Regulus Therapeutics (Nasdaq: RGLS), 23 August 2013

SIGA Technologies (Nasdaq: SIGA) - 30 September 2013

Sunshine Heart (Nasdaq: SSH), 28 August 2013

Synta Pharmaceuticals (Nasdaq: SNTA), 1 September 2013

TrovaGene (Nasdaq: TROV), 15 September 2013

Verastem (Nasdaq: VSTM), 5 September 2013

Disclaimer. This is commentary, not investment research. If you buy the stock of any biotech company in Australia, the US or wherever you need to do your own homework, and I mean, do your own homework. I'm not responsible if you lose money.

Biotech Buzz Post No. 22 - EXEL

Exelixis (Nasdaq: EXEL) gained FDA approval in November 2012 for its first drug, a receptor tyrosine kinase inhibitor called Cometriq.      

Exelixis (Nasdaq: EXEL) – A report from the frontline

“Diseases desperate grown by desperate appliance are relieved, or not at all.” -  Hamlet, Act IV, Scene 3.


This week has been a great week to be me. On Monday, I joined my new firm of Baillieu Holst, ending the enforced ‘gardening leave’ that was imposed on me by Bell Potter Securities when I left them in June (which, by the way, was unpaid for three months – go figure). Then on Thursday I met a patient with an interesting story to tell about a newly approved drug from an emerging US company. Let me tell you about my new job doing equities research at Baillieu Holst and then I’ll tell you about the patient who’s doing well with the new drug.

Baillieu Holst is an Australian stockbroking firm with a long history and a great reputation down here. The firm is now seriously building its institutional business and I believe that under the current leadership we can grow to be the No 1 majority Australian-owned firm in our capital market. I’ve joined Baillieu Holst with a mandate to build its Life Sciences coverage, and I confidently predict that in the not-too-distant future we will become the No 1 house for healthcare and biotechnology transactions in Australia, given the high level of expertise that’s already here, combined with my own knowledge base from covering the sector for the last twelve years.

One of the things I find gratifying about going to work for Baillieu Holst is the fact that there’s a lot of heritage in this firm. Edward Lloyd Baillieu (1867-1939), known as 'Prince', and his brother Richard Percy Clive Baillieu (1874-1941), known as Joe, started E.L. & C Baillieu in 1889, so we’ve seen a fair few market cycles over the last 124 years. It’s fair to say that the Baillieu family, led by Prince and Joe’s elder brother William Lawrence Baillieu (1859-1936), were the leading players in the building of the Australian economy from the 1890s through to the 1930s. Their legacy, through the Collins House group of companies they were associated with, lives on today in names like the ANZ Bank, Rio Tinto, Amcor and Pacific Brands. I’ll tell you more about the Baillieus and how they helped make Australia rich in a future Blog entry. I like to think that if Willie, Prince and Joe were around today they’d be founding and investing in Australian biotech and medical device companies, because that’s where a fair bit of new wealth is going to be created here in Australia as the 21st Century progresses.

Now let me tell you about the patient that I met on Thursday.  Meeting a patient is a big deal for us biotech analysts because we spend so much time looking at abstract stuff like p values, response rates and composite endpoints, but rarely get to meet the real people who sit behind that data – real people who can experience anxiety about their illness, face bewildering treatment choices, and have a whole bunch of other muck to deal with, but still bravely show up at the infusion room to be the human guinea pigs we need to move this whole biotech thing forward. My new friend told me in our first conversation that he had prostate cancer. Before I could tell him that treatment outcomes for that cancer were fairly good these days – the 15 year survival rate is 93% - he added that it was metastatic. That’s not so good. If longevity is your game don’t get diagnosed with metastatic Castration-Resistant Prostate Cancer (CRPC). The castration-resistant part means you’ve already cut off the supply of testosterone feeding the tumour (chemically with LHRH agonists or surgically) and the tumour is still growing.  The metastatic part means the tumour has spread to other organs, most notably the bones. That generally means you’ve got a little over a year left (click here), with perhaps another drug like taxotere buying you some time. This didn’t seem to bother my friend, who had failed on taxotere but seemed to have calmly accepted the whole prostate cancer curveball. Maybe it was because he was a stockbroker by profession and still working – in this industry natural-born optimists are more likely to succeed. However my friend had another thing going his way. Have you heard, he said, of cabozantinib? He was in a clinical trial. No, I hadn’t, I replied. We googled it. It was from Exelixis (Nasdaq: EXEL), the drug developer from South San Francisco, Ca.  Wow, I said, this company is capitalised on Nasdaq at US$999m. I might buy some, said my friend, who also told me during this conversation that there’d been a reduction in his tumour size at about the third months after he’d enrolled, and he hadn’t experienced any adverse events other than perhaps some mild neuropathy, which is something you already get with taxotere.  I told him I’d take a look ahead of this Blog post.

Now I think I know why my new friend seems to be doing well, other things being equal. Cabozantinib is Cometriq, a small molecule which gained FDA approval in November 2012 for the treatment of metastatic medullary thyroid cancer. It was Exelixis’s first drug after 13 years as a public company. As with all these cancer drugs the first indication is just the beginning. ‘Medullary’ thyroid cancer is a subtype of thyroid cancer that got its name because, when pathologists first saw this kind of tumour, they were reminded of the grey-coloured soft tissue in the medulla, or brainstem.  It's a rare condition. Medullary thyroid cancer only goes metastatic in around 500-700 patients a year in America. For these patients at Phase III Cometriq improved Progression-Free Survival (PFS) to 11 months versus only 4 for placebo. However the big money for Exelixis will come from where the drug goes next. Cometriq is now in two Phase IIIs in metastatic CRPC, one of which has my friend as a trial subject. The drug started Phase III in metastatic Renal Cell Carcinoma in May 2013, and a Phase III trial in advanced Hepatocellular Carcinoma started in September.

The big news for Exelixis in 2014 will be top-line results from the metastatic CRPC trials, called COMET-1 and COMET-2. The Phase II data, from 171 men, suggests that this drug seems to work. You know it’s good when the trial report, as published in the Journal of Clinical Oncology, tells us that randomisation of patients to either treatment or control ‘was halted early based on the observed activity of cabozantinib’. Where men did get placebo, before this decision was taken, the median PFS was just under six weeks. For the men who got Cometriq, median PFS was 23.9 weeks (p<0.001). The investigators also found a reduction of soft tissue and bone lesions, and, importantly, lower levels of pain. When cancer metastasises to the bones it really, really hurts, to the point where you need narcotics like oxycodone to kill the pain. At Phase II Cometriq was able to cut narcotic use in half, which is great news given how controversial opioid use in medicine has become over the last decade or so. Exelixis was so excited about the effect of its drug on bone pain that it wrote a pain palliation endpoint into the COMET-2 trial.

Cometriq is able to work its anti-tumour magic because it’s an inhibitor of multiple receptor tyrosine kinases. I’ve written in the past about a particularly successful tyrosine kinase inhibitor called Gleevec, the Novartis drug for the treatment of Chronic Myeloid Leukaemia (click here for that post) which did US$4.7bn in sales last year. Since Gleevec was FDA approved in 2001, various other tyrosine kinase inhibitors have come on the market such as Sutent and Inlyta from Pfizer, Tarceva from Roche, and Tykerb from GSK. The attraction of tyrosine kinases is that they are commonly found in those cellular signalling pathways that go wrong in cancer. Kinases are simply enzymes that attach a phosphate group to a particular target molecule, the target for tyrosine kinases being the amino acid tyrosine (others act on serine and threonine). When this attachment takes place it changes the target molecule, which induces that target to act on other downstream molecules until the phosphate-based signal has made its way to the nucleus of the cell. Receptor tyrosine kinases sit on the cell surface where signals come in from the outside. If something goes wrong in one of those signalling gateways, cells can end up processing a continual and uncontrolled stream of messages to grow and divide, resulting in cancer. Block that gateway with a tyrosine kinase inhibitor and you shut off the faulty signals. There’s dozens of  known tyrosine kinasess, and Cometriq seems to work well as a cancer drug because it can block more than one, with activity against RET, MET and VEGFR2.

Cometriq isn’t the only arrow in Exelexis’s quiver – it has spent the last 13 years building up a strong pipeline of small molecules, most of which hit rogue elements in the bad signalling pathways. XL518, partnered with Roche’s Genentech division, targets a serine/threonine kinase called MEK, part of the RAS/RAF/MEK/ERK pathway.  That drug just generated some great objective responses in a Phase Ib trial in metastatic melanoma where there’s a particular kind of mutation called BRAFV600. Meanwhile GSK is in Phase II with Foretinib, an Exelixis-sourced VEGFR2 and MET inhibitor and Sanofi has gone to Phase II with a couple of drugs that act on the PI3K pathway.  However all eyes with be on Cometriq ahead of the COMET data given the widespread prevalence of prostate cancer – about 240,000 cases a year in the US, with one in six of us guys in line to get it one day – and the potential to be one of the first cancer drugs that can cut the level of pain associated with the disease. Hopefully my friend is in one of the COMET treatment groups and it gives him a chance to see that top-line data come out – and maybe to see Baillieu Holst turn in to the new biotech powerhouse in Australia.

Stuart Roberts, Australian biotechnology analyst, with global focus

Nisi Dominus Frustra

+61 (0)447 247 909

sroberts2164@gmail.com, sroberts@baillieuholst.com.au

Twitter @Biotech_buzz

About Stuart Roberts. I started as an equities analyst at the Sydney-based Southern Cross Equities in April 2001, focused on the Life Sciences sector from February 2002. Southern Cross Equities was acquired by Bell Financial Group (ASX: BFG) in 2008 and I continued at Bell Potter Securities until June 2013. I joined Baillieu Holst in October 2013. Over the last twelve years I have built a reputation as one of Australia's leading biotech analysts. Before joining Southern Cross Equities I wrote for The Intelligent Investor, probably the most readable investment publication in Australia. I have a Masters Degree in Finance from Finsia. My hobbies are jazz, cinema, US politics and reading patent applications filed by biotechnology and medical device companies.

Previous Australian Biotechnology Buzz posts:

Acorda Therapeutics (Nasdaq: ACOR), 10 October 2013.

Advanced Cell Technology (OTCBB: ACTC), 4 September 2013

Alcobra Pharma (Nasdaq: ADHD), 17 September 2013

Amicus Therapeutics (Nasdaq: FOLD), 22 September 2013

Aradigm (OTCBB: ARDM), 8 September 2013

BioSpecifics Technologies (Nasdaq: BSTC), 26 September 2013

Celldex Therapeutics (Nasdaq: CLDX), 9 November 2013

Cellular Dyamics (Nasdaq: ICEL), 3 September 2013
Exelixis (Nasdaq: EXEL), 17 October 2013

ImmunoCellular Therapeutics (NYSE MKT: IMUC), 27 August 2013

Immunomedics (Nasdaq: IMMU), 21 August 2013

Inovio Pharmaceuticals (NYSE MKT: INO), 24 August 2013

Merrimack Pharmcaceuticals (Nasdaq: MACK), 26 August 2013

Novavax (Nasdaq: NVAX), 3 October 2013

Oncolytics Biotech (Nasdaq: ONCY),  22 August 2013

Pharmacyclics (Nasdaq: PCYC), 2 September 2013

Regulus Therapeutics (Nasdaq: RGLS), 23 August 2013

SIGA Technologies (Nasdaq: SIGA) - 30 September 2013

Sunshine Heart (Nasdaq: SSH), 28 August 2013

Synta Pharmaceuticals (Nasdaq: SNTA), 1 September 2013

TrovaGene (Nasdaq: TROV), 15 September 2013

Verastem (Nasdaq: VSTM), 5 September 2013

Disclaimer. This is commentary, not investment research. If you buy the stock of any biotech company in Australia, the US or wherever you need to do your own homework, and I mean, do your own homework. I'm not responsible if you lose money.

Biotech Buzz Post No. 21 - ACOR

Acorda Therapeutics (Nasdaq: ACOR) got US$266m in net revenue from the MS drug Ampyra in 2012. Its pipeline continues to be adventurous.       

Acorda Therapeutics (Nasdaq: ACOR) – Giant steps for a new CNS company

“No man is worth his salt who is not ready at all times to risk his well-being, to risk his body, to risk his life, in a great cause.” - Theodore Roosevelt (1858-1919), 26th US President and, in my opinion, one of the great ones.


One of the thinkers that has greatly impressed me over the years is Jim Collins, author of the classic management texts Built to Last and Good to Great. Collins has spent over two decades studying the reasons why some companies become truly great while others remain just average. One quality Collins identifies in companies making the journey from Good to Great is that they have ‘Big Hairy Audacious Goals’ towards which they are striving. For example, Sam Walton (1918-1992) opened his first ever dime store in Newport, Ar. with a goal of making the store ‘the best, most profitable in Arkansas within five years’. It was that kind of attitude which set Wal-Mart on the path to greatness it subsequently pursued, and made Sam a truly rich man. With this Blog post I would like to nominate Acorda Therapeutics (Nasdaq: ACOR), from the Westchester County suburb of Ardsley, NY, as a candidate for ‘Good to Great’ status because the Big Hairy Audacious Goal of this US$1.4bn company is to become a ‘a leading neurology company with a portfolio of innovative products’. The reason that this worthy aim is so big, hairy and audacious is that in recent years Big Pharma has been seen to be exiting out of neuroscience research. For example, GSK was in the news in early 2010 cutting back on its neuroscience effort (click here), while Novartis (click here) and AstraZeneca (click here) had similar stories told about them in late 2011 and early 2012. Why? Because coming up with new drugs for things like stroke recovery, spinal cord injury and cerebral palsy was considered just too hard. Acorda, by contrast, hasn’t been concerned about how tough the CNS field has traditionally been. What it sees is the enormous upside in terms of patient benefits and, ultimately, financial benefits for shareholders.

Acorda can have this confidence in part because it has already brought its first successful neurology product to market. In January 2010 it gained FDA approval for Ampyra, a drug that improves walking in patients with Multiple Sclerosis (MS). Ampyra is a voltage-dependent potassium channel blocker (click here for the paper which evaluates the mechanism of action). In Multiple Sclerosis the patient’s immune system starts attacking the myelin sheath that surrounds nerve fibres in the brain and spinal cord. This makes it difficult for nerve impulses to be transmitted and results in a wide range of neurological impairments. Part of the problem is that the voltage-gated potassium channels on nerve cells are exposed when the myelin is stripped away. Too much charged potassium flows into the cells, so they can’t properly conduct nerve impulses through their axons and into the next nerve cell. Blocking the potassium channels with Ampyra significantly improves conduction, allowing more nervous impulses to travel down to the legs so patients can walk better. Ampyra was great news for the MS community because it worked in all four types of MS, including the ‘secondary progressives’ for whom treatment options are limited. In the registration trials patients walking speed went up by an average 25%. Around half of all MS patients will have difficulty walking within 15 years of diagnosis, and perhaps 20-30% will start having difficulty within the first two years. If, like me, you’re a fan of the television series The West Wing you’ll recall that Martin Sheen plays a US President who has relapsing/remitting MS from the time he takes office. By the later seasons of the show the writers had the President getting around with a cane. If you want to see what Ampyra can partly rectify, check out Episode 133 from the final season, where there’s a ‘flash forward’ showing a visibly frail ex-President visiting his new library (click here).

The obvious patient benefits of Ampyra in a not-insubstantial market – there are 400,000 MS patients in the US alone – has made the drug a success for Acorda. Net Ampyra revenue in calendar 2012 for Acorda was US$266.1m, and in the June 2013 quarter it was US$77.8m, up 17% on the previous corresponding period. Biogen Idec has ex-US rights under a 2009 partnering deal and markets the product as Fampyra. Both companies have a lot of growth left in the MS market – only ~70,000 US patients had taken the drug by the end of 2012 – and after that the vast market for stroke recovery awaits, with clinical evidence now at hand that Ampyra can improve walking in people with post-stroke deficits. Ampyra is distributed in the US via a 90-person sales force calling on around 7,000 doctors, meaning that Acorda has the makings of a potential new specialty pharma company. What I like about this company is that it’s not playing it safe in terms of the next major drug it will put in the briefcases of those sales people. It’s swinging for the bleachers again.

Take, for a good example, the neuregulin GGF2. The neuregulins are class of growth factors similar to epidermal growth factor that promote recovery after neurological injury (GGF stands for glial growth factor). They’re also known to improve heart function, where is where Acorda is trying it out GGF2 first. Preclinically there’s evidence that GGF2 is involved in repairing cardiac muscle, and in a Phase I trial in heart failure patients GGF2 was able to raise Ejection Fraction (the percentage of the heart’s volume that moves with each pump) from ~29% to 40% in the 28 days mark. Acorda has just initiated a second Phase I for GGF2. This is the kind of drug that Big Pharma doesn’t tend to look at today, even though 2% of the US population has heart failure. It’s not that they don’t see the market opportunity. It’s just that their cardiology franchises ran out of steam in the 1990s and left all the action to the device guys with their pacemakers, defibrillators and LVADs. Acorda has no such hangup.

AC105 for spinal cord injury represents another adventurous project from Acorda. Spinal cord injury is something that happens 12,000 times year in America, but at the moment there’s nothing much the doctors can do for you. AC105, a new magnesium formulation, could change all that. We’ve known for a while now that magnesium gets depleted from the site of nerve damage, contributing to tissue injury and lesion development. AC105 would put the magnesium back in a way that regular magnesium salts can’t. Preclinically AC105 has been shown to be neuroprotective and improve locomotor function in animal models, so long as the animals got the drug within a few hours of injury. Uncle Sam has liked what he has seen so far - Acorda took this drug into Phase II in September 2013 with the help of a US$2.67m grant from the US Department of Defense. The DoD wants this drug, or anything like it, because 1% of its combat casualties in Iraq and Afghanistan have involved spinal cord injuries (click here).

Probably the most exciting thing Acorda has in the pipeline right now is rHIgM22, a remyelinating antibody. That’s right – there’s a monoclonal antibody in clinical development that, by targeting myelin and oligodendrocytes (the myelin producing cells), seems to promote new myelin growth and effectively reverse some of the damage in MS and related disorders (click here). This antibody, discovered at the Mayo Clinic, entered Phase I under Acorda’s aegis in April 2013. If this thing works it’ll be the biggest breakthrough in MS since Teva’s Copaxone gave the world the first non-immunosuppressive mechanism of action for an MS drug.

So how come Acorda has been allowed to get away with all this risk taking? That’s what you can do if you don’t have a Big Pharma background. Acorda’s CEO, Dr Ron Cohen, ran a tissue engineering start-up before founding Acorda. Ron and his colleagues now face a challenge. I reckon the market is looking at Acorda the way people would have looked at Amgen back in the early 1990s. The argument would be ‘okay, they got lucky with their first drug, but can they do it again?’ GGF2, AC105 and rHIgM22 are at too early a stage to give a definitive ‘yes’ answer to that question. But you can’t fault Acorda for being adventurous, and it is adventurousness that ultimately yields the big bucks in this game. Worthy of some homework.

Stuart Roberts, Australian Life Sciences consultant, with global focus

Nisi Dominus Frustra

+61 (0)447 247 909

sroberts2164@gmail.com

Twitter @Biotech_buzz

About Stuart Roberts. I started as an equities analyst at the Sydney-based Southern Cross Equities in April 2001, focused on the Life Sciences sector from February 2002. Southern Cross Equities was acquired by Bell Financial Group (ASX: BFG) in 2008 and I continued at Bell Potter Securities until June 2013. Over the twelve years to 2013 I built a reputation as one of Australia's leading biotech analysts. I am currently consulting to the Australian biotech industry. Before joining Southern Cross Equities I wrote for The Intelligent Investor, probably the most readable investment publication in Australia. I have a Masters Degree in Finance from Finsia. My hobbies are jazz, cinema, US politics and reading patent applications filed by biotechnology and medical device companies.

Previous Australian Biotechnology Buzz posts:

Acorda Therapeutics (Nasdaq: ACOR), 10 October 2013.

Advanced Cell Technology (OTCBB: ACTC), 4 September 2013

Alcobra Pharma (Nasdaq: ADHD), 17 September 2013

Amicus Therapeutics (Nasdaq: FOLD), 22 September 2013

Aradigm (OTCBB: ARDM), 8 September 2013

BioSpecifics Technologies (Nasdaq: BSTC), 26 September 2013

Celldex Therapeutics (Nasdaq: CLDX), 9 November 2013

Cellular Dyamics (Nasdaq: ICEL), 3 September 2013

ImmunoCellular Therapeutics (NYSE MKT: IMUC), 27 August 2013

Immunomedics (Nasdaq: IMMU), 21 August 2013

Inovio Pharmaceuticals (NYSE MKT: INO), 24 August 2013

Merrimack Pharmcaceuticals (Nasdaq: MACK), 26 August 2013

Novavax (Nasdaq: NVAX), 3 October 2013

Oncolytics Biotech (Nasdaq: ONCY),  22 August 2013

Pharmacyclics (Nasdaq: PCYC), 2 September 2013

Regulus Therapeutics (Nasdaq: RGLS), 23 August 2013

SIGA Technologies (Nasdaq: SIGA) - 30 September 2013

Sunshine Heart (Nasdaq: SSH), 28 August 2013

Synta Pharmaceuticals (Nasdaq: SNTA), 1 September 2013

TrovaGene (Nasdaq: TROV), 15 September 2013

Verastem (Nasdaq: VSTM), 5 September 2013

Disclaimer. This is commentary, not investment research. If you buy the stock of any biotech company in Australia, the US or wherever you need to do your own homework, and I mean, do your own homework. I'm not responsible if you lose money.

Biotech Buzz Post No. 20 - CLDX

Celldex Therapeutics (Nasdaq: CLDX) is in Phase III with a cancer vaccine which can double median overall survival for glioblastoma patients.

Celldex Therapeutics (Nasdaq: CLDX) – Too late for Ted, but a big breakthrough for the rest of us

“We cannot have a fair prosperity in isolation from a fair society. So I will continue to stand for a national health insurance.” – Senator Ted Kennedy (1932-2009), 1980 Democratic National Convention.

We’ve all got to go sometime, but if you had a choice you wouldn’t be taken out by the disease that claimed Ted Kennedy four years ago. The legendary Senator, who never lived to see America get the universal healthcare he championed for decades, was diagnosed in May 2008 with glioblastoma multiforme (GBM). The ‘glioblastoma’ part tells you that this was a brain tumour - it’s a cancer of the glial cells, the cells that provide support and protection for neurons. The ‘multiforme’ part refers to the fact that every GBM tumour looks different under the microscope. That’s one reason you don’t want to get GBM – the presence of many different kinds of cells in a tumour has traditionally made successful treatment a difficult proposition. Another reason you don’t want to get GBM is what the patient has to go through. Kennedy would have experienced all the usual headaches and extreme nausea, as well as the problems with memory, balance, speech and vision, before he died fifteen months later at the age of 77. Fifteen months was about the median survival time for GBM, where only 4% of patients can expect to be alive at the five year mark (click here), even though there are treatment options available - surgery followed by radiotherapy, and a couple of drugs (Temodar, from Merck, and Avastin, from Roche) that provide a modest survival benefit. Thankfully GBM is rare - Kennedy was one of only around 6,000 to 9,000 Americans who would have been diagnosed in 2008. However for those of us destined to get it, I have some good news – survival is set to stretch out markedly in the next few years. Celldex Therapeutics (Nasdaq: CLDX), from Needham in Ted Kennedy’s home state of Massachusetts, is now in Phase III with Rindopepimut (CDX-110), a cancer vaccine that in Phase II engineered median overall survival in GBM patients of more than 24 months.

Celldex’s glioblastoma breakthrough represents a fairly simple vaccine concept. You take a surface marker that is expressed only in cancer cells and not in normal tissue, and attach that protein to something that the immune system is likely to recognise. Just to make certain the immune system does what it is supposed to – wake up and smell the antigenic coffee - you administer an adjuvant as well. In Celldex’s case the marker is epidermal growth factor receptor variant III, or EGFRvIII, which is expressed in around a third of all GBM tumours. The immunostimulating protein is KLH, or Keyhole Limpet Hemocyanin, a respiratory glycoprotein obtained from Megathura crenulata, the giant keyhole limpet, which people have studied for its immunomodulatory properties since the 1960s (click here). The adjuvant is GM-CSF, the white blood cell stimulator routinely given to cancer patients to reboot their immune system after chemotherapy. Put these three together and you consistently get the immune response you want. In GBM patients whose tumour was EGFRvIII-positive, three trials of Rindopepimut showed median overall survival of 24-25 months from diagnosis. That wasn’t good enough for Pfizer, which pulled out of a three year partnership over Rindopepimut in late 2010. It was good enough, however, for Celldex’s backers to fund a pivotal study of Rindopepimut called ACT IV, which initiated in December 2011. ACT IV is a randomised, double-blind, controlled study that will treat newly-diagnosed EGFRvIII-positive GBM patients after surgical resection. Celldex expects to finish recruiting to ACT IV this year and be reading out data around the end of 2015. The company is also in Phase II with ReACT, which is studying Rindopepimut in combination with Avastin in recurrent EGFRvIII-positive GBM. The market is pretty optimistic about Rindopepimut’s prospects in both indications, with Celldex now capitalised at over US$2bn.

It helps that Celldex is also working on two other disease treatment approaches that the market has learned to like due to other success stories. CDX-011 (glembatumumab vedotin) is one of those antibody drug conjugates (ADCs) that have made Seattle Genetics (Nasdaq: SGEN) a US$4.8bn company. Celldex’s ADC has registered great Phase II data in triple-negative breast cancer where patients overexpress a marker called glycoprotein NMB. Meanwhile CDX-1135, a soluble receptor which inhibits a part of the complement system, just entered a Phase I/II pilot study in Dense Deposit Disease. That’s an ultra-rare progressive kidney disorder cause by dysregulation of the complement pathway. To some observers CDX-1135 sounds like the making of another Alexion (Nasdaq: ALXN), whose Soliris product, a complement inhibitor, has kept Alexion’s market capitalisation above US$20bn as we speak.

So there’s multiple arms to the exciting Celldex story. The naysayers will likely object that ImmunoCellular Therapeutics (NYSE MKT: IMUC), which I wrote about in my 27 August post  has much better data on GBM than Celldex - it recorded 38.4 months of median overall survival in a Phase I GBM trial with its ICT-107 cancer vaccine (click here), but today you can buy the company for only US$136m. ImmunoCellular is, however, further behind in the journey – ICT-107 is still in Phase II. More importantly, ICT-107 is an autologous therapy. I described what ImmunoCellular’s vaccines involve on 27 August: ‘As with Dendreon, ImmunoCellular’s approach to cancer immunotherapy is to take from the patient white blood cells responsible for processing and orchestrating an immune response to antigens, exposing those cells to cancer antigens, and then giving back to the patient a large enough numbers of such cells so that his immune system finally recognises the tumour that has hitherto eluded it.’ There’s the problem. You get 38 months survival but you have the massive expense of processing individual batches of cells, something that has hindered Dendreon (Nasdaq: DEND) over the last couple of years with Provenge. Rindopepimut is off-the-shelf and therefore notionally much more cost effective. There’s no reason why both products can’t gain approval and go on to vastly change the treatment landscape for GBM – and get paid for under the Obamacare Ted Kennedy spent his Senatorial career working for. But at the moment the market is saying that Rindopepimut is the easier option.

The market didn’t always like Rindopepimut. I just went back and looked at an October 2009 report I wrote on another cancer vaccine Prima Biomed (ASX: PRR, Nasdaq: PBMD). Celldex was only US$216m back then. Which shows you how the wheel can turn once the favourable data starts to accumulate. Like Ted Kennedy on universal healthcare, with biotech stocks one has to keep the faith.

Stuart Roberts, Australian Life Sciences consultant, with global focus

Nisi Dominus Frustra

+61 (0)447 247 909

sroberts2164@gmail.com

Twitter @Biotech_buzz

About Stuart Roberts. I started as an equities analyst at the Sydney-based Southern Cross Equities in April 2001, focused on the Life Sciences sector from February 2002. Southern Cross Equities was acquired by Bell Financial Group (ASX: BFG) in 2008 and I continued at Bell Potter Securities until June 2013. Over the twelve years to 2013 I built a reputation as one of Australia's leading biotech analysts. I am currently consulting to the Australian biotech industry. Before joining Southern Cross Equities I wrote for The Intelligent Investor, probably the most readable investment publication in Australia. I have a Masters Degree in Finance from Finsia. My hobbies are jazz, cinema, US politics and reading patent applications filed by biotechnology and medical device companies.

Previous Australian Biotechnology Buzz posts:

Advanced Cell Technology (OTCBB: ACTC), 4 September 2013

Alcobra Pharma (Nasdaq: ADHD), 17 September 2013

Amicus Therapeutics (Nasdaq: FOLD), 22 September 2013

Aradigm (OTCBB: ARDM), 8 September 2013

BioSpecifics Technologies (Nasdaq: BSTC), 26 September 2013
Celldex Therapeutics (Nasdaq: CLDX), 9 November 2013

Cellular Dyamics (Nasdaq: ICEL), 3 September 2013

ImmunoCellular Therapeutics (NYSE MKT: IMUC), 27 August 2013

Immunomedics (Nasdaq: IMMU), 21 August 2013

Inovio Pharmaceuticals (NYSE MKT: INO), 24 August 2013

Merrimack Pharmcaceuticals (Nasdaq: MACK), 26 August 2013

Novavax (Nasdaq: NVAX), 3 October 2013

Oncolytics Biotech (Nasdaq: ONCY),  22 August 2013

Pharmacyclics (Nasdaq: PCYC), 2 September 2013

Regulus Therapeutics (Nasdaq: RGLS), 23 August 2013

SIGA Technologies (Nasdaq: SIGA) - 30 September 2013

Sunshine Heart (Nasdaq: SSH), 28 August 2013

Synta Pharmaceuticals (Nasdaq: SNTA), 1 September 2013

TrovaGene (Nasdaq: TROV), 15 September 2013

Verastem (Nasdaq: VSTM), 5 September 2013

Disclaimer. This is commentary, not investment research. If you buy the stock of any biotech company in Australia, the US or wherever you need to do your own homework, and I mean, do your own homework. I'm not responsible if you lose money.

Biotech Buzz Post No. 19 - NVAX

Novavax (Nasdaq: NVAX) has made some progress in developing VLP-based influenza vaccines. Uncle Sam is funding Phase II clinical development.

Novavax (Nasdaq: NVAX) – Taking the stress out of future influenza pandemics

“The chickens of America stand ready to do their duty” – US agriculture secretary Earl Butz (1909-2008), telling President Gerry Ford in 1976 not to worry about influenza vaccine supply ahead of a potential swine flu epidemic.


Seven years ago Merck & Co. gained FDA approval for a remarkable Australian invention called Gardasil. I suspect not many Americans know that this vaccine against Human Papilloma Virus (HPV), the causative agent in cervical cancer, first originated in the laboratory of Professor Ian Frazer at the University of Queensland (click here to read an article that'll make you think it's as American as apple pie). CSL Ltd (ASX: CSL), the Australian plasma products major and now the world’s 27th largest pharma company, was the original UQ commercialisation partner, having funded Frazer’s work for several years before they licensed the product and swiftly on-licensed it to Merck in 1995. This was an Australian invention so it had to be good, and by 2001 it was clear to the Merck folks that they had an effective vaccine on their hands, with ample virus-neutralising antibodies in all test subjects. Indeed, the product was so good it subsequently made it into an episode of The West Wing (Episode 104, first screened in 2004 and featuring the President’s daughter as a scientist working on HPV). Merck’s vaccine went on to gain FDA approval in June 2006. Last year the company realised US$1.6bn in net sales from Gardasil, making it the company’s seventh biggest seller. More importantly, thanks to Frazer’s work, cervical cancer is now on its way to being just one of those diseases we used to get ‘in the olden days’, like diphtheria or polio.

Ian Frazer was able to make this big step forward in cancer prevention because of Virus-Like Particles, another Australian invention, albeit an indirect one. Back in the mid-to-late 1960s the American researcher Barry Blumberg (1925-2011), while studying the genetics of haemophilia, had found that the serum of a haemophilia patient was reacting to the ‘Australia antigen’, so called because it came from the serum of an Australian Aboriginal. As he and others sought to figure out why this happened, Blumberg won himself half of the 1976 Nobel Prize in Medicine. It turned out that the Australia antigen was actually HBsAg, a protein that sat on the surface of the Hepatitis B Virus, to which the haemophilia patient had antibodies. Blumberg’s work had given us the basis for the Hepatitis B vaccine we’ve had since the early 1980s, which is simply the recombinant HBsAg protein rather than the whole Hepatitis B Virus killed or attenuated. This vaccine introduced would-be vaccine makers to the idea of using sub-viral particles as vaccines. The DNA that codes for HBsAg creates a protein which self-assembles into an empty sphere. The shape of the HBsAG is such that the immune system sits up and takes notice when it sees it, but you don’t have any viral DNA still hanging around inside the spheres like you would with a regular killed or attenuated vaccines, or, for that matter, a DNA vaccine like Inovio’s. It’s a Virus-Like Particle (VLP) rather than a virus. Such vaccines are very safe to use as well as easy to manufacture and, as Frazer and Merck have shown, if you get the right antigen they work like a dream.

The success of Gardasil suggests that it’s worth watching Novavax (Nasdaq: NVAX), from Rockville, Md. Novavax knows how to get broadly immunogenic VLPs from all sorts of pathogens, and has a large proprietary suite of them, many quite advanced in terms of earlier VLP approaches that only included a single protein or lipid. The company is going after influenza for its first VLP vaccine, and I would argue that VLPs could be a substantial improvement over the way we handle influenza today, which is - let’s face it – far from optimal.

Ignore for a moment the fact that Google does a better job of identifying influenza epidemics than the health authorities funded by the taxpayer (click here for that story). The really annoying thing about influenza is that when those authorities have decided which strains are the ones to worry about for the coming winter, the vaccine makers are still doing their quadrivalent vaccine thing (two influenza A strains and two B strains – it used to be trivalent with just one influenza B strain) in eggs. If you just got here in a time machine from the mid-1970s, you heard it right. In 2013, four decades after we figured out how to do genetic engineering, we still get most of our influenza vaccine starting material from the humble chicken egg. Growing influenza in eggs was an Australian invention from 1936, when Sir Mac Burnet (1899-1985), whose work on immunological tolerance won the 1960 Nobel Prize for Medicine, was a world leader in virology working out of Melbourne. Today, when you can grow virus in mammalian cells, egg-based production doesn’t make sense. For one thing, it takes four to six months lead time to get those egg-based factories to turn out vaccines. For another, you’ve often got to alter the virus strain in order for it to grow efficiently in the egg. You don’t have to go back very far in time to see the shortcomings of this system. In 2004 you’ll recall that Americans were forced to rely on herd immunity because a Novartis plant was out of action. And in 2009, when the H1N1 pandemic strain started killing people, we got the vaccine too late to deal with it effectively. Which made people wonder what we’d do next time a real badass 1919-style pandemic roared out of Asia.

Now, don’t get me wrong. Governments have been egged on by the experts for years about this issue, and in 2006 Uncle Sam showed he wasn’t chicken about cell-based manufacturing when he handed out contracts worth more than US$1bn to develop such vaccines. The first fruits of this investment were harvested late last year when Novartis gained FDA approval for Flucelvax, the first seasonal influenza vaccine made in mammalian cells. So eggs are on the way out, which is bad news for companies like CSL. But the cell-based producers had better watch their back as well because Novavax may have all the advantages of cell-based manufacture – such as the ability to use wild-type hemagglutinin instead of hemagglutinin altered to fit the egg production system – and offer a few extra benefits on top of this.

For one thing, cell-based vaccine manufacturing still makes influenza virus that has to be inactivated or attenuated, whereas Novavax’s VLPs don’t have anything with the potential to come alive again. For another, Novavax can move faster and cheaper whenever vaccine is needed. It makes its influenza VLPs under GMP using a recombinant baculovirus and insect culture system (just like Dendreon uses with Provenge) and, significantly, the bioreactor systems involved are single use. You make your vaccine and then you throw away the material you made it in. It all makes for a quick but not dirty system of making vaccines that, so Novavax claims, can qualify a vaccine facility with low capital costs ‘six to nine months faster than a fixed-pipe bioreactor facility used in cell-based manufacturing’.

The proof of the pudding for this kind of system will be when there’s another pandemic like 2009. Back then Novavax’s white coats took H1N1 as soon as the CDC made its sequence available for analysis. 11 weeks later they were making a H1N1 vaccine under GMP that was good enough to license in terms of its immunogenicity. This admirable celerity in vaccine production has helped ensure that the flow of funds from BARDA – the US government’s Biomedical Advanced Research and Development Authority – to develop VLP-based vaccines continues. In 2013 Novavax has shown that it still has the right stuff on ultra-rapid vaccine development. In February a serious H7N9 bird flu emerged in China that killed 44 people in 135 known cases. Novavax started work on a vaccine in early April. By 10 May they were making clinical trial material and by 8 July they were in Phase I.

Now, followers of Novavax shouldn’t get too excited about Novavax’s theoretical ability to deal with pandemics. The company is still some way away from having a regular influenza vaccine ready for approval. In July 2012 it announced that a quadrivalent seasonal influenza VLP vaccine candidate had proved seroprotective against all four strains in a clinical trial, but only brought about adequate seroconversion in three. In other words, this vaccine would likely have protected people from influenza infection, but in the case of one strain the test subjects didn’t quite make enough antibodies for the FDA's people to sleep easily at night. Novavax went back to the drawing board on its manufacturing process and expects to return to the clinic for another Phase II early this year. It will also start a clinical trial for a pandemic H5N1 vaccine in the first half of next year after favourable Phase I data came out in October 2012.

Influenza isn’t the only thing on Novavax’s agenda. It’s also got a vaccine against Respiratory Syncytial Virus (RSV) which is based on a micelle formed by RSV’s F protein. Micelles, you’ll recall from chemistry class, are molecules that can arrange themselves in a spherical form in aqueous solutions because they’re bipolar – hydrophilic at one end, hydrophobic at the other. The common theme with Novavax’s VLPs is that a micelle is, like a VLP, the kind of three-dimensional protein the immune system will take notice of. The difference between RSV and influenza is the damage a good vaccine can do to drug sales. RSV made Synagis a blockbuster, and, with Novavax having generated favourable data so far, the business development folks at AstraZeneca will have to be on their toes if they want to keep this franchise.

Let me leave you with a thought on Novavax and influenza. Unlike the cervical cancer story post Gardasil, influenza isn’t going away any time soon – the influenza antigens shift around too frequently to make that possible. We may, however, be on our way to cutting the death rate from influenza to just about nothing through ease of vaccine manufacture that could tie in with more rapid identification of new strains. Another infectious scourge dealt with, another billion-dollar company created, and perhaps a few older vaccine companies forced out of business would be three happy outcomes of all this. Worth doing some homework.

Stuart Roberts, Australian Life Sciences consultant, with global focus

Nisi Dominus Frustra

+61 (0)447 247 909

sroberts2164@gmail.com

Twitter @Biotech_buzz

About Stuart Roberts. I started as an equities analyst at the Sydney-based Southern Cross Equities in April 2001, focused on the Life Sciences sector from February 2002. Southern Cross Equities was acquired by Bell Financial Group (ASX: BFG) in 2008 and I continued at Bell Potter Securities until June 2013. Over the twelve years to 2013 I built a reputation as one of Australia's leading biotech analysts. I am currently consulting to the Australian biotech industry. Before joining Southern Cross Equities I wrote for The Intelligent Investor, probably the most readable investment publication in Australia. I have a Masters Degree in Finance from Finsia. My hobbies are jazz, cinema, US politics and reading patent applications filed by biotechnology and medical device companies.

Previous Australian Biotechnology Buzz posts:

Advanced Cell Technology (OTCBB: ACTC), 4 September 2013

Alcobra Pharma (Nasdaq: ADHD), 17 September 2013

Amicus Therapeutics (Nasdaq: FOLD), 22 September 2013

Aradigm (OTCBB: ARDM), 8 September 2013

BioSpecifics Technologies (Nasdaq: BSTC), 26 September 2013

Cellular Dyamics (Nasdaq: ICEL), 3 September 2013

ImmunoCellular Therapeutics (NYSE MKT: IMUC), 27 August 2013

Immunomedics (Nasdaq: IMMU), 21 August 2013

Inovio Pharmaceuticals (NYSE MKT: INO), 24 August 2013

Merrimack Pharmcaceuticals (Nasdaq: MACK), 26 August 2013
Novavax (Nasdaq: NVAX), 3 October 2013

Oncolytics Biotech (Nasdaq: ONCY),  22 August 2013

Pharmacyclics (Nasdaq: PCYC), 2 September 2013

Regulus Therapeutics (Nasdaq: RGLS), 23 August 2013
SIGA Technologies (Nasdaq: SIGA) - 30 September 2013

Sunshine Heart (Nasdaq: SSH), 28 August 2013

Synta Pharmaceuticals (Nasdaq: SNTA), 1 September 2013

TrovaGene (Nasdaq: TROV), 15 September 2013

Verastem (Nasdaq: VSTM), 5 September 2013

Disclaimer. This is commentary, not investment research. If you buy the stock of any biotech company in Australia, the US or wherever you need to do your own homework, and I mean, do your own homework. I'm not responsible if you lose money.