Biotech Buzz Post No. 7 - SSH

“Had I been present at the creation, I would have given some useful hints for the better ordering of the universe” - King Alfonso X of Castile (1221-1284)

Sunshine Heart (Nasdaq: SHC) – The Aussie success story from the frozen plains of Minnesota

Around three years ago I made my first ever visit to the United States. I’ve got to tell you – as an Aussie who has had a lifelong love affair with America to the point where I’ve read about thirty biographies of the country’s Presidents and can tell you the capital of Montana without thinking about it (it’s Helena) -  this was a big deal. My eyes were bugging out of my head the whole week because I was seeing things like Central Park in New York or Bunker Hill in Boston and having to remind myself that I was actually there and not just dreaming about it. The other good thing about going to America is that you meet lots of Americans, and one of the people that impressed me most on this October 2010 trip was Dave Rosa.

Dave is the CEO of the medical device company Sunshine Heart (Nasdaq: SSH), from Eden Prairie, Mn., a place that CNN Money ranked as America’s 3rd best small city in 2012. Before I tell you about Dave and his company let me give you a tip about the Twin Cities, that is, Minneapolis and St Paul, Mn. This Aussie thought he knew America, but for some reason had it in his head that the Twin Cities were kind of wedged up tightly against each other on opposite sides of the Mississippi like Albury and Wodonga on the Murray River here in Australia. No way. Sure, they sit next to each other, but Minneapolis and St Paul are both sprawling megalopolises with downtown areas 14 km apart. So if you want to spend the day in the Twin Cities and not just go to the Mall of America, be prepared to spend a lot of time inside a cab. I was staying, the night I got to Minnesota, at the Hilton in St Paul. Eden Prairie, so I learned the next day, was 40 km away. My next tip relates to the cab itself. A lot of the cabs in the Twin Cities are driven by migrants from Somalia, so it pays to know a little about that country in order to make small talk, as I had to do on the 42 km drive from Eden Prairie to Fridley, where Medtronic (NYSE: MDT) have that magnificent palace of theirs. Which brings me to my third tip - you get better service if you tell them you’re going to Medtronic. In fact, they’re happy to wait for you while you go in for your meeting, particularly if you tell them your next stop is MSP, that is, Minneapolis-St Paul International Airport. My guess is that was another 40 km as well.

The great thing about investing in a medical device company from Minnesota is just that – it’s Minnesota, which I reckon must have the best work ethic and entrepreneurial spirit of any state outside of Utah because it has, so I learned that balmy October day (it doesn’t freeze up there until Thanksgiving, and thank heavens because I had left my overcoat back in New Jersey), a remarkable number of Fortune 500 companies – in 2012 there were 19, which is 3.2% of the total for a state with only 1.7% of the US population. Moreover the Twin Cities have turned in recent decades into a centre of excellence for medical devices thanks to Medtronic (NYSE: MDT, No 164 on the Fortune 500) and St Jude Medical (NYSE: STJ, No 437) so if you’re a start-up company looking to develop a new device you can generally find the people and the capital to get started if the business plan makes sense.

Which brings me to Sunshine Heart. I knew I was on to something good when Dave Rosa took my call at home about 10 PM and said he was happy to make time to see me early the next day since I had come all the way from Sydney. I told you these people work hard (not that they don’t have fun in Minnesota - Dr Steve Oesterle of Medtronic assured me that the first place a decent play goes after Broadway is Minneapolis). Listening to Dave the next day out in Eden Prairie I had my instincts confirmed, and not just because he looks remarkably like one of my favourite actors, Robert De Niro. What impressed me was that finally this poor company I had followed was moving ahead - after about six years of going nowhere fast.

You see, Sunshine had actually been an ASX-listed company. It had been started in Melbourne by a Kiwi heart surgeon named Will Peters to develop a heart assist device called the C-Pulse. The idea behind C-Pulse was aortic counterpulsation – you wrap a cuff around the ascending aorta and wire it up to the heart so that it can inflate and deflate in response to the heart’s electrical impulses, with the inflation happening between the beats of the heart. Peters et. al had good evidence that this kind of counterpulsation could take the load off a failing heart, so long as the squeeze was more like a gentle thumbprint that wouldn’t wear out the aortic tissue over time. Peters got backing from a couple of VC houses here in Australia and in 2004 the stock went public on our Exchange, but with a US CEO based in California. It seemed to me at the time a very straightforward exercise to get the C-Pulse on the market. The device was not blood-contacting and therefore wouldn’t come with the kind of clot risks that LVADS had, and you wouldn’t kill the patient if you switch it off for whatever reason. In short, there was nothing complicated about C-Pulse that I could see and no shortage of NYHA Class III heart failure patients – the kind that haven’t reached Death’s Door (NYHA Class III) yet but are shambling down the corridor in that direction – to recruit into a pilot trial. Indeed, America probably has 1.5 million right now, and Europe another 3 or 4 million. And that was the competitive advantage. HeartWare (Nasdaq: HTWR) and, before them, Thoratec (Nasdaq: THOR) had given us magnificent patient outcomes in Class IV with LVADs, but all those Class III patients were still being managed by drugs, ICDs and CRT-Ds. This was a cost-effective Next Big Thing for those patients.

So what went wrong? In a word, it took forever for clinical work on C-Pulse to yield anything of use. An initial first-in-man study implanted a few patients and was able to prove that you could take heart failure patients down by one class with the C-Pulse, but the actual pilot trial didn’t get started until 2009. When my new friend David Rosa joined the company in October of that year they had only recruited four patients out of 20, a full five years after this stock started trading on the ASX. Basically Sunshine had been allowed to go public without the C-Pulse system having been optimised – the first-in-man study had seen the battery and device driver being hauled around in a suitcase-sized box. And the system they were trialling in the pilot wasn’t fantastic either – it could actually be worn on the body but was large and noisy and weighed 3.6 kilos. Enter Dave Rosa. He’d been VP of Global Marketing for cardiac surgery and cardiology for St. Jude Medical so he knew a thing or two about cardiologists and how they work. A few phone calls later and key sites were busy recruiting by the time I met Dave. Later on back in Sydney I met one of the folks doing the implanting - Sanjeev Aggarwal, MD of the Mid America Heart Institute in Kansas City (the place that gave us that remarkable 1999 study on the effects of remote, intercessory prayer on patient outcomes) and he was a big fan of C-Pulse. So it was fair to say that Sunshine was where it should have been in 2005. Indeed, they were even moving ahead on the fully implantable version of C-Pulse they should have at the beginning.

Which brings us to the 20-patient pilot, which had fully recruited by 2011 and did what I had expected it to do all along. Six months out from baseline the 20 patients had seen an average NYSA class drop of 1.1. They had improved their six minute walk by 24 metres. And their quality of life as measured by the ‘MLWHF score’ (the Minnesota Living with Heart Failure questionnaire) had improved threefold. At twelve months the gains on NYHA Class and MLWHF score had been maintained, and the six minute walk had doubled again. One patient did so well he went, as I understand it, all the way from Class IV back to Class I. So it’s fair to say that this thing worked like a dream. However when I wrote up the story in late 2011 Sunshine stock was only capped on ASX at A$56m.

There was, however, an easy solution to this problem. List on Nasdaq (which it did in February last year) and then raise the capital in the US where they genuinely get how good a 1-class reduction in NYHA Class can be in terms of cost-effectiveness in the management of heart failure. After that you can get moving towards the US pivotal. Sunshine raised US$21m at US$7.00 per share in August last year. It delisted off ASX in May 2013, which was kind of sad because I felt like I was losing an old friend. But it’s great for Sunshine, whose stock is now above US$11, helped by the fact that last November the FDA gave the company unconditional approval to initiate a pivotal. That 388-patient trial, called COUNTER HF, is now enrolling and is expected to fully recruit by 2015. This trial is randomising 1:1 between C-Pulse and ‘Optimal Medical Therapy’. If all goes well C-Pulse may be approved in the US market by 2017. The device is already approved in Europe, having gained its CE Mark in July 2012, and Sunshine is now running the OPTIONS HF post-market EU study in order to get the data required for reimbursement over there.

So how much would you expect to pay for Sunshine now? Its market capitalisation at yesterday’s close on Nasdaq is US$146m, around triple what it was when I was formally covering it. There’s an easy lesson here for US investors – if you want to get some good drug or medical device programmes, come down to Australia and if your timing is right you can probably get whatever you’re after for a song. For an American starting up a company, the moral of the story is that you can come Down Under for a few years to incubate your venture with some Aussie public risk capital and then take it back to the US for the genuine Big Money. However if I have my way that somewhat unhappy situation will change. We may like Americans, but we don’t like being short-changed by our friends across the Pacific, and now that the mining boom is over I reckon we’re about to get a whole lot more sophisticated on pricing our valuable Life Science assets.

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 analyst at the Sydney-based stockbroking firm Southern Cross Equities in April 2001, focused on the Life Sciences sector from February 2002. Southern Cross Equities was acquired by Bell Financial Group 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:
ImmunoCellular Therapeutics (NYSE MKT: IMUC), 27 August 013
Immunomedics (Nasdaq: IMMU), 21 August 2013
Inovio Pharmaceuticals (NYSE MKT: INO), 24 August 2013
Merrimack Pharmcaceuticals (Nasdaq: MACK), 26 August 2013
Oncolytics Biotech (Nasdaq: ONCY),  22 August 2013
Regulus Therapeutics (Nasdaq: RGLS), 23 August 2013
Sunshine Heart (Nasdaq: SSH), 28 August 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. 6 - IMUC

Imagination is more important than knowledge. For knowledge is limited to all we now know and understand, while imagination embraces the entire world, and all there ever will be to know and understand” – Albert Einstein (1879-1955)

ImmunoCellular Therapeutics (NYSE MKT: IMUC) – Cancer Immunotherapy Version 2.0

Last week when I blogged about Oncolytics Biotech (Nasdaq: ONCY) I described the emerging field of virotherapy for cancer as ‘immunotherapy on the cheap’. It’s immunotherapy because when you attack cancer with viruses specific for cancer cell targets, the lysing of the cells tends to promote a beneficial immune response to the cancer. And it’s ‘on the cheap’ because you don’t have to spend a fortune manipulating each individual patient’s white blood cells. That kind of treatment has been pioneered by the Seattle-based Dendreon (Nasdaq: DEND), which in 2010 gained FDA approval for the first ever cancer immunotherapy, a product called Provenge, indicated for metastatic prostate cancer. Dendreon had a lot of folks excited until the company ran into reimbursement issues – the ~US$93,000 price-tag is considered cost-effective but the process of getting paid in the US had led to reluctance to use the therapy on the part of physicians. The stock has been trending back for a while now, even though in 2012 Dendreon enjoyed US$325m in sales. Mind you, Dendreon is still a big name by Australian standards – the current market capitalisation is US$437m.

Dendreon has another issue to deal with rather than just market pushback, namely, competitor products coming across the horizon. It’s the same in drug development as in any other industry. When you invent and commercialise what looks like a world-beating product, you then need to get moving on a Second Generation that’s a whole lot better and less expensive per unit of utility than the First Generation, or someone else will do it for you. In Dendreon’s case, that someone else is southern California's ImmunoCellular Therapeutics (NYSE MKT: IMUC), from the affluent LA neighbourhood of Calabasas.

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. The difference between the two companies is in the type of cells and the type of antigens. For Dendreon’s Provenge a single antigen, called prostatic acid phosphatase, is fed to various ‘antigen presenting cells’ (APCs) that, as the name suggests, pass the antigen on to other immune system cells that then act against the cells carrying the antigen. For ImmunoCellular, multiple antigens are fed only to a more specialised class of APCs called the ‘dendritic cells’ (DCs). The result, argues ImmunoCellular, is a much more effective cancer vaccine available at lower cost. ImmunoCellular has chosen DCs that are robust enough to be stored in liquid nitrogen so that there’s no time pressure on administration to the patient. Also, the company has optimised its manufacturing process so that up to 90% of the material that is administered is actual DCs, meaning that the patient only needs to undergo one apheresis procedure to harvest the requisite cells. The comparable figures for Dendreon are 25% active cells in the final mix and three apheresis procedures. Throw in only an 18 hour window before Dendreon’s APCs are toast and ImmunoCellular appears to win this game hands down. Then there’s the price. ImmunoCellular reckons the manufacturing cost and the margins for its product will be not unlike those for monoclonal antibodies, something Dendreon can only dream of.

One thing that makes ImmunoCellular worth paying particular attention to is the cancer stem cell angle. Cancer stem cells are another one of those big trends in cancer therapy that are going to make strides this decade because we now know how to identify, thanks to cell surface markers, many of those notorious rebuilders of tumours after conventional chemo has done its worst. ImmunoCellular’s vaccines make heavy use of antigens specific for cancer stem cells. So, for example, its ICT-121 vaccine targets the cancer stem cell marker CD133, which overexpresses in many cancers including ovarian, breast and pancreatic. I have yet to see much commentary on ImmunoCellular as a cancer stem cell play, but I think the first late stage success for one of its vaccines may prompt may prompt people to join the dots given the recent excitement over Verastam (Nasdaq VSTM), Oncomed (Nasdaq OMED) et. al. and the fact that you can currently buying ImmunoCellular for only US$156m on the NYSE MKT.

That late stage data may not be long in coming. ImmunoCellular’s lead product is ICT-107, a cancer vaccine targeting six antigens and now in a 124-patient randomised, placebo-controlled, double-blind Phase IIb study in patients newly diagnosed with an aggressive brain cancer called glioblastoma. An interim analysis completed in early June after 32 deaths concluded that this trial should go forward, which suggests that things are working as planned. Phase I pointed to some good data ahead. Ordinarily with glioblastoma, which hits 10,000 Americans a year, you live around 15 months from the time of diagnosis. ImmunoCellular’s patients from Phase I enjoyed median overall survival of 38 months. Final data from ImmunoCellular’s Phase IIb, to be reported after 64 deaths, is expected to read out later in 2013. Last month ImmunoCellular’s second product, the aforementioned ICT-121, went to Phase I in recurrent glioblastoma, while a Phase IIa is planned for ICT-140 in recurrent ovarian cancer, where the IND cleared in January.

The curious reader may ask why, if I like virotherapy so much, that I also like this kind of immunotherapy as well. The answer is that we still don’t know much about the kind of anti-cancer immune response that virotherapy would prompt – that’s still being worked out – although we can infer there is one. By contrast we know a lot more about how this kind of cancer vaccine works. And we know that it does work – in its second pivotal Provenge extended the median overall survival of metastatic castrate-resistant prostate cancer patients by around four months, while we’ve seen the strong survival numbers for ICT-107 in glioblastoma. Could be worth checking out in detail. And while you’re at it, take a look an ASX listed company called Prima Biomed (ASX: PRR, Nasdaq: PBMD) currently capitalised at A$106m. Like Dendreon, Prima's CVac product only uses one antigen (MUC1), but, conjugated to a sugar called mannan, that may be enough to get a decent outcome in ovarian cancer, where it’s in Phase III. Also worth doing some homework on.

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 analyst at the Sydney-based stockbroking firm Southern Cross Equities in April 2001, focused on the Life Sciences sector from February 2002. Southern Cross Equities was acquired by Bell Financial Group 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:
ImmunoCellular Therapeutics (NYSE MKT: IMUC), 27 August 013
Immunomedics (Nasdaq: IMMU), 21 August 2013
Inovio Pharmaceuticals (NYSE MKT: INO), 24 August 2013
Merrimack Pharmcaceuticals (Nasdaq: MACK), 26 August 2013
Oncolytics Biotech (Nasdaq: ONCY),  22 August 2013
Regulus Therapeutics (Nasdaq: RGLS), 23 August 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. 5 - MACK

"When you hit a wrong note it's the next note that makes it good or bad"  -  Miles Davis (1926-1991), American jazz musician.

Merrimack Pharmaceuticals (Nasdaq: MACK) – The map is not the territory

The other day in this Blog I suggested that one of the big developments in cancer therapy going forward will centre on intracellular signalling pathways gone wrong. There are three reasons why this field is significant today and can only get bigger in the future. Firstly, signal pathways represents an enormous treasure trove of new cancer targets we’ve only begun to explore. Secondly, get a drug that works to block an aberrant pathway and the patient outcomes can be fantastic –Novartis’s Gleevec so successfully blocks the Bcr-Abl tyrosine kinase in Chronic Myeloid Leukaemia that patients can stay alive and perfectly healthy for a long period of time so long as they take their pills every day. Thirdly, the commercial outcomes can be great as well. Gleevec enjoyed US$4.7bn in global sales in 2012, and Amgen just agreed to pay US$10bn to acquire Onyx Pharmaceuticals (Nasdaq ONXX), a California specialty pharma company whose entire business from Nexavar on has more on less been built on drugs that target signal pathways.

When Gleevec gained FDA approval in 2001 the event has hailed as an important step forward for cancer therapy because for the first time there was a pill on the market that had turned a particular cancer from a death sentence into a manageable chronic disease. If you want to get inspired about the power of a drug company to create that kind of breakthrough product, I recommend the book that Novartis’s then CEO Daniel Vasella published in 2003 entitled Magic Cancer Bullet – How a Tiny Orange Pill may Rewrite Medical History. Once you’ve read it I hope you’ll feel, like me, that Vasella earned every cent of the US$78m he got paid when he stepped down as Novartis Chairman earlier this year. Gleevec is, in my view, a very good glimpse of the future of cancer therapy, and I expect to live to see most cancers make the transition that was started with Gleevec. I’m not saying it will happen ‘in the next ten years’, as most breathless commentators like to intone when they get optimistic about winning the War on Cancer. I’m giving medicine half a century to do it – I’m only in my early 40s now so I may just make it into the 2060s (God willing), if I eat my vegetables and keep exercising and Australia can still afford healthcare by then. Two things make me optimistic that signal pathways may provide the main answer to defeating cancer in the long run. Firstly, there aren’t many pathways to drug – the legendary Johns Hopkins cancer researcher Bert Vogelstein and his colleagues have done a lot of work to show that in cancer there are only around twelve (see a recent Science paper for more). Secondly, science is now getting pretty good at following these signal pathways, as MerrimackPharmaceuticals (Nasdaq: MACK), which did its IPO last year, has shown.

Merrimack (which is presumably named after the river in Massachusetts since the company’s headquarters lies on that biotech hothouse of Kendall Square in Cambridge, Ma.), is pioneering the commercial potential of Network Biology. Traditionally biologists have looked at things in isolation – how this particular protein or that particular molecule looks and behaves. Network Biology, which has only emerged as a field in its own right over the last fifteen years or so, has provided valuable conceptual and mathematical tools to show how everything interacts with everything else to create a whole that can be surprisingly different from just being the sum of its parts. This makes the field just perfect for looking at signal pathways in cancer. Merrimack’s founders have used the tools of Network Biology to create new maps of various signal pathways. What they’ve found is that the proteins within a pathway that you think would be important maybe aren’t so important. Consider the ErbB pathway. You’d think that EGFR, otherwise known as ErbB1, would be important in this pathway since it seems to be overexpressed in cancer and that’s why we have Tarceva, a US$1.3bn drug for Roche, to target it. Same story with ErbB2, otherwise known as HER2, where is why we got that legendary antibody Herceptin. Sure, ErbB1 and ErbB2 are important, says Merrimack. But the company’s models, which look more at duration and degree of signalling than at mere overexpression of a molecule in a pathway, told the researchers to take a look at the hitherto unimportant ErbB3 molecule. The result was MM-121, an antibody to ErbB3 which Sanofi liked so much it licensed it in 2009 for US$60m upfront and US$470 million in milestones as well as tiered double-digit royalties. Wow! This was a year after the Global Financial Crisis and MM-121 wasn’t even out of Phase I. The drug is now in mid-stage development for breast, ovarian and lung cancers. Mind you, Merrimack is responsible for development of MM-121 through Phase II proof of concept. Merrimack currently has six oncology therapeutics in clinical development, including MM-111, a bi-specific antibody that targets both ErbB3 and ErbB2, and MM-141, a tetravalent antibody that targets both ErbB3 and the IGF-1 receptor.

In 2013 US biotech stocks are on fire and the market has been betting that concepts like Merrimack’s in Network Biology are going to work out in the long run. Merrimack is currently capitalised at US$371m on Nasdaq. However this may turn out to be a somewhat rocky road. In April of this year Merrimack announced that one 50-patient cohort of lung cancer patients in a Phase II study of MM-121 had failed to hit a primary endpoint of 40% Progression-Free Survival (PFS) at four months. However that wasn’t really anything to worry about because Merrimack was also using the study to evaluate tissue samples from patient biopsies, the aim being to pick biomarkers that would predict treatment success. The right companion diagnostic will obviously lower the risk of clinical failure going forward. That, however, was cold comfort for the stockholders in the near term. Merrimack is now below US$4 as against the US$7 with which it went out in March 2012 when it raised US$100m.

Merrimack, however, like all good biotechs, has multiple arrows in its quiver. One other competency the company has developed beyond Network Biology is nanoliposomal formulation of oncology drugs for better localised delivery. The lead product here, called MM-398, is nanoliposomal irinotecan. MM-398 is in Phase III in metastatic pancreatic cancer where patients had failed gemcitabine. This study completes enrolment in the third quarter of 2013 and the Phase II data looked good, with median overall survival of 5.2 months. MM-398 may not be the Next Big Thing in the cancer signalling space, but if it makes it onto the market with a pancreatic cancer indication the payoff is likely to be lucrative given the poor patient outcomes at the moment for that cancer, with current five year survival down at a measly 6%. So Merrimack may still be worth paying attention to until MM-121 hits its strides. Then again, as with just about every US biotech, there’s an Australian comparable that’s a whole lot cheaper. Alchemia (ASX: ACL) delivers irinotecan using hyaluronic acid (HA) for better targeting. Because HA gets into cancer cells via CD44, we can confidently say that Alchemia’s product is knocking out cancer stem cells. And the product, called HA-Irinotecan, is in Phase III in metastatic colorectal cancer for second line therapy off the back of a doubling in PFS at Phase II. How much would you expect to pay for all this? At the moment you can get it for A$136m.

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 analyst at the Sydney-based stockbroking firm Southern Cross Equities in April 2001, focused on the Life Sciences sector from February 2002. Southern Cross Equities was acquired by Bell Financial Group 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:
Immunomedics (Nasdaq: IMMU), 21 August 2013
Inovio Pharmaceuticals (NYSE MKT: INO), 24 August 2013
Merrimack Pharmcaceuticals (Nasdaq: MACK), 26 August 2013
Oncolytics Biotech (Nasdaq: ONCY),  22 August 2013
Regulus Therapeutics (Nasdaq: RGLS), 23 August 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. 4 - INO

The ones who are crazy enough to think that they can change the world, are the ones who do - Steve Jobs (1955-2010), founder of Apple, the man who gave us Pixar, and the greatest tech entrepreneur since Edison.

Inovio Pharmaceuticals (NYSE MKT: INO) – Why we may just have a decent DNA vaccine one of these days

One of my favourite lines from the movies comes from Oliver Stone’s 1987 classic Wall Street, where the old broker is lecturing his younger colleagues on the virtue of patience.  At first you think that the older guy, played by Hal Holbrook, is hopelessly out of date when he complains that ‘the worst thing we ever did was let Nixon get us off the gold standard’. Then he reveals a more modern streak when he advises the young guys to look at the stock of an emerging pharmaceutical company whose first drug is now approved. One of the younger brokers responds somewhat dismissively that ‘it’ll take five years for that company to come around’. To which the Holbrook character reminds his listeners that ‘good things, like Hilton and IBM, sometimes take time’.

In this post I’d like to look at a very good thing that is taking a while to come around but seems to be getting closer – DNA vaccines. Science has known for at least twenty years that a string of plain old DNA, where that DNA codes for a vaccine antigen, can induce a powerful immune response to the antigen so long as you can get the DNA inside enough cells in the body. With genetic engineering having turned the mass-production of DNA constructs into low-cost child’s play, DNA vaccines would be a huge step forward for prophylaxis because you could do away with all the dangers associated with live or killed pathogens and all the inefficiencies that come with harvesting vaccine material out of eggs or cells. And of course, with therapeutic vaccines for cancer and a range of other diseases, the sky is the limit. The reason we don’t have an approved DNA vaccine yet is, I believe, two-fold. Firstly, there’s been some difficulty figuring out the appropriate delivery mechanism. Secondly, it’s taken a while to understand how to get the best antigens. However one thing you can count on in biotech is persistence (hey, look at me – I’ve been a voice crying in the wilderness for this industry in Australia since 2002), and now a company from the salubrious Philadelphia exurb of Blue Bell, Pa. called Inovio Pharmaceuticals (NYSE MKT: INO) seems to have solved many of the problems.

Inovio’s basic approach to DNA vaccines, using technology called ‘SynCon’, involves the use of bioinformatics to pick good antigens, and the delivery of plasmids carrying the chosen DNA sequences via electroporation. Twenty years ago we just didn’t have enough genomic data in order to be able to adequately compare DNA from various viral strains and pick, with the help of powerful software, consensus DNA most likely to cover all strains. Once you tweak such consensus DNA so that expression inside cells is high enough, you’ve potentially got what the DNA vaccines pioneers have been looking for all these years. But of course you then have to deliver it. Traditionally only tiny amounts of ‘naked’ DNA have been taken up by cells. DNA wrapped up in lipids or harmless viruses, or DNA attached to some membrane-penetrating particle and fired in using ‘gene guns’, has been better. However best of all would be if the cell membrane would just open up and let the naked DNA in. That’s what Inovio can do with electroporation – apply a harmless electric current to the delivery area which temporarily ‘permeabilises’ cell membranes.

The data has been looking good for Inovio on this approach, albeit early stage. In patients with a precancerous condition called cervical dysplasia, for example, a DNA vaccine against the E6 and E7 proteins of HPV has generated a strong immune response to dysplasic cells in Phase I. Same story with a vaccine targeting, in Phase II, the WT1 gene involved in Chronic Myeloid Leukaemia. Then there’s the development that may herald the start of the revolution we’ve been awaiting for in influenza – the universal vaccine that would displace the standard seasonal vaccines we get today by protecting against all types of a particular influenza. In April 2013 Inovio reported Phase I data showing that its H1N1 universal influenza vaccine was generating antibodies comparable to the current FDA-approved seasonal vaccine, while in July an H7N9 universal vaccine protected all the vaccinated animals in a challenge study. This was important because H7N9, which emerged in China in March of this year, is a scary bird flu that, like H5N1 before it, has been killing people as well as chickens.

Inovio is currently pushing ahead with a busy programme of DNA vaccines. As well as the lead programme against cervical dysplasia and the work in HCV and influenza we mentioned above, there are Phase I and preclinical programs targeting prostate, breast, and lung cancers as well as HIV and malaria. The last mentioned effort is particularly interesting because malaria has evaded all efforts to vaccinate it over the centuries due to each part of the malaria life cycle presenting different antigens. With DNA vaccines these could theoretically be targeted simultaneously. Inovios’s vaccine has worked well preclinically and goes to the clinic next year. One great part about the utility of Inovio’s vaccines is that Uncle Sam is interested – Homeland Security has been looking to the use of DNA vaccines against bioterrorism. As we all know, when it’s a National Security issue, funding for a programme becomes a whole lot easier.

Inovio is now capitalised at a healthy US$315m, and that‘s after the stock spiked and then eased back in July and in spite of the setback which the DNA vaccine field received earlier this month. On 12 August the San Diego-based DNA vaccine pioneer Vical (Nasdaq: VICL) reported that its Allovectin vaccine had failed to meet its primary endpoint in a Phase III trial in metastatic melanoma. What went wrong with Vical? Probably a misunderstanding about how well advanced melanoma patients respond to dacarbazine, which is the standard of care drug and was placebo for the Allovectin trial. It happens –a clinical trial gets designed based on science which is going out of date. This was a problem Neuren (ASX: NEU) had several years ago with its neuroprotection compound when it went to Phase III in heart bypass patients (who were understood to suffer cognitive decline after their surgery but actually don’t) rather than in Traumatic Brain Injury where they probably should have gone. In Vical’s case that company doesn’t think the DNA vaccine game is over and is now focused on going to the clinic with a vaccine against Herpes Simplex Virus type 2 (the cause of genital herpes) before the end of this year. Meanwhile the major Japanese drug company Astellas is in Phase III with a Vical-sourced DNA vaccine against cytomegalovirus in solid organ transplant patients.

In my view the DNA vaccine field has made enough progress to render it fairly resilient when challenges like the recent Vical failure come along. I’ve been arguing for a while now that one of these days a DNA vaccine will make it all the way, and when that happens the rising tide will lift all boats in the field. UQ’s Professor Ian Frazer, the creator of Gardasil, must think so too because he’s working on some DNA vaccines potentially useful in HSV2 and HPV that were created using bioinformatics tools not unlike Inovio’s. If you go to the web site for Frazer’s collaborator Allied Healthcare (ASX: AHZ) you can find some research there that lays out the case for a bright DNA vaccine future in some detail. Take a lot of time to do your own homework. Remember, good things, like Hilton, IBM and Amgen, sometimes take time.

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 analyst at the Sydney-based stockbroking firm Southern Cross Equities in April 2001, focused on the Life Sciences sector from February 2002. Southern Cross Equities was acquired by Bell Financial Group 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:
Immunomedics (Nasdaq: IMMU), 21 August 2013
Inovio Pharmaceuticals (NYSE MKT: INO), 24 August 2013
Oncolytics Biotech (Nasdaq: ONCY),  22 August 2013
Regulus Therapeutics (Nasdaq: RGLS), 23 August 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. 3 - RGLS

The world is getting better, but it’s not getting better fast enough, and it’s not getting better for everyone - Bill Gates, Microsoft founder and philanthropist (1955 -    )

Regulus Therapeutics (Nasdaq: RGLS) - The little king of RNA

I learned yesterday that Bell Potter had managed to hire my replacement as senior healthcare analyst. John Hester used to be with John Bowie-Wilson’s Linwar Securities and more recently had been with a boutique called Select Equities after the ANZ bank shut Linwar down last year. For various reasons I had been hoping that my old employer wouldn’t find anyone up to the job. I now bring to mind the famous quote from Charles De Gaulle “The graveyards are full of indispensable men”.

Let’s talk about a field of the Life Sciences that is very much alive and likely to prove indispensable to modern medicine sometime down the track – RNA therapeutics. RNA, as just about everyone knows, is the material used to translate the DNA from the nucleus of our cells into the proteins that make up just about everything in our bodies. Modulate the RNA that creates too much or too little of a particular protein, or the wrong kind of protein, and you theoretically have a way to treat hitherto incurable diseases. The devil, of course, is in the detail. Exactly what gene or genes do you need to interfere with? What kind of nucleic acid, peptide, or small molecule do you do it with? And how do you get your therapeutic into the cells where it can do its work? So far none of these questions appear to have been answered to anyone’s satisfaction. However the fact that a lot of progress has been made can be attested to the San Diego-based Regulus Therapeutics (Nasdaq: RGLS), which was able to go public last year in an US$81m raise.

The first thing to like about Regulus is its name. As star gazers will know, Regulus is the brightest star in the constellation Leo, and its name means 'the little king'. Regulus’s beat is microRNA, the short strands of RNA which regulate what messenger RNA takes to the ribosomes to turn into proteins. MicroRNA, when it associates with a set of proteins called ‘RISC’ (short for RNA-induced silencing complex), is able to target specific messenger RNA and stop it from converting to protein. Regulus was created in 2007 when two other pioneers of the RNA therapeutics space - Alnylam and Isis – pooled the intellectual property they didn’t need in order to go after microRNA while they focused on their core technologies (siRNA in the case of Alnylam, antisense in the case of Isis). MicroRNA could be a whole lot bigger a field than siRNA or antisense because with MicroRNA whole networks of disease-causing genes can be targeted. Indeed, there’s evidence that microRNA works through RNAi to regulate perhaps a third of the whole genome.

Regulus, after it has identified a microRNA target of interest, designs anti-microRNA oligonucleotides, called ‘anti-miRs’, whose chemistry has been modified for better stability, among other things. The company has some powerful friends. With Sanofi it is going after liver cancer and kidney fibrosis. With GSK it’s targeting Hepatitis C, where it could develop a much more differentiated offering than those currently in the works from Gilead et. al. And with AstraZeneca it is exploring anti-miRs that could be useful in atherosclerosis. For its own account it has a glioblastoma candidate in the works. Add it all up and these deals are worth US$1.7bn in milestones, of which ~US$100m gets paid even before a patient gets dosed and US$350m kicks in during clinical development. Regulus has only just gotten around to picking candidates this year and doesn’t expect to file INDs until next year.

How much would you expect to get in on the ground floor of microRNA drug development? Regulus is currently capitalised at a generous US$343m, the stock having performed well since last year’s arrival on Nasdaq. Part of the attraction is the Hepatitis C programme, where the race is definitely on to find therapies that deliver above and beyond what the current generation of small molecule antivirals has to offer. It’s worth noting in this regard that Regulus’s CEO Kleanthis Xanthopoulos was a founder of Anadys, which Roche bought in 2011 in order to go after Hep C. Also attractive for investors is the Regulus board, whose all-star cast includes, most notably, Caltech’s David Baltimore, the guy who discovered retroviruses in the 1960s and who won the Nobel Prize for Medicine for this in 1975 (and in whose lab Doug Hilton, the current WEHI director, worked for a while).

So Regulus basically has rock star appeal. But as we've done several times this week and will continue to do  in this blog, it's worth stopping and thinking about whom the market is missing in all this excitement. Come down to Sydney and Benitec (ASX: BLT) can show you how double-stranded RNAi (ddRNAi) is a unique RNA therapeutic approach with promise in a range of disease indications including Hepatitis C. Benitec is currently in the process of filing an IND for its TT‐034 gene silencing therapeutic ahead of a Phase II trial in Hep C, and that product, which can shut down  three separate highly conserved regions on the virus genome simultaneously, has been designed as a 'one shot cure' for HCV infection. The Benitech folks are not rock stars - yet - but Kevin Buchi, the man who built Cephalon before it went to Teva, is a director, which tells you it's something worth looking into, particularly since it's only capped at A$24m.

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 analyst at the Sydney-based stockbroking firm Southern Cross Equities in April 2001, focused on the Life Sciences sector from February 2002. Southern Cross Equities was acquired by Bell Financial Group 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:
Immunomedics (Nasdaq: IMMU), 21 August 2013
Oncolytics Biotech (Nasdaq: ONCY),  22 August 2013
Regulus Therapeutics (Nasdaq: RGLS), 23 August 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. 2 - ONCY

Life happens too fast for you ever to think about it. If you could just persuade people of this, but they insist on amassing information - Kurt Vonnegut (1922-2007), American writer.

Oncolytics Biotech (Nasdaq: ONCY) - Where viruses are good for you

Greetings from Sydney, Australia. A few months back I got chicken pox, having somehow managed to miss the disease as a child. The literature suggests about 10% of the adult population is in the same boat I was. If you're an adult and you haven't had chicken pox get yourself vaccinated today if you know what's good for you. Having chicken pox wasn't fun but at least I got to stay home from work for a week (I was still at Bell Potter at the time) and read a couple of books. One of them was Henry Adams' autobiography, The Education of Henry Adams, a classic published in 1919 which contains among other things the the real origin of the theory we now know as 'Moore's Law' (more on this in a later post). The other was The Emperor of All Maladies: A Biography of Cancer by Siddharta Mukherjee, which won the Pulitzer Prize in 2011. It's a 'biography' of cancer in the sense that it follows the life of cancer as we have known it since antiquity and how efforts to defeat it have developed over time. For anyone involved in Life Sciences The Emperor of All Maladies is a must-read because you'll appreciate how close science is to turning cancer into a manageable disease rather than a death sentence. The book got me thinking about where the cutting edge in cancer research is today. I reckon the four main hot spots, in order of importance, are:

1) Immunotherapy - Products that get the immune system to recognise and attack cancer;
2) Signalling pathways - Drugs that tackle the aberrant pathways within cells;
3) Antibodies - Cancer antibodies have been around for a while but there's still a heap of work to be done in getting the right kind of specificity as well as cancer-killing ability;
4) Diagnostics - When we can do whole body scans and catch tiny tumours at home using our smart phones then we'll truly be in a position to get the kind of early diagnosis cancer patients really need;

There are hundreds of biotech companies working on new cancer treatments, and I reckon the above screen is a great way to select for further study those companies more likely to succeed. I rate immunotherapy as the most important area to look at because most of the time our immune systems do an outstanding job keeping us free of cancer, so if we can give it a hand when it drops the ball, it may be more likely to do a lot of the heavy lifting for us in terms of treating disease. Which is why Oncolytics Biotech, from the Canadian city of Calgary ( (TSX: ONC and Nasdaq: ONCY), and currently capped at US$236m, is one to take a look at.

Oncoytics is one of the pioneers of oncolytic virotherapy, an approach to cancer treatment in which the patient is infected with viruses specific for cancer cells, and those viruses proceed to bust up all the cancer cells they can find. I call it 'immunotherapy on the cheap' because viruses are inexpensive and easy to mass produce under GMP, and, in the act of destroying cancer cells, they may just present to the immune system the cancer antigens from those cells that had hitherto been overlooked. It could be that oncolytic viral infections are the reason whya  few patients over the years have enjoyed sudden and unexplained remissions of their cancer, and I would be willing to speculate that the anti-cancer effect of an oncolytic virus are long lasting because of the restoration of the immunovigilance which had been lost. One could even make the case that bee keepers historically had significantly lower mortality from lung cancer because they had much more vigilant immune systems after all that stinging (click here for the 1979 study)

Oncolytics' particular oncolytic virus, called Reolysin, is a proprietary formulation of human reovirus. This double-stranded RNA virus is a particularly good one to use in cancer therapy because, to get into cells, reoviruses exploits what scientists can now recognise as versions of the Ras signalling pathways, a major or minor cause of perhaps two thirds of all cancers. Oncolytics has had Reolysin in around 30 clinical trials up until now, and so far the news has been good. Back in May the company announced that a Phase II study in metastatic melanoma had seen 3 out of 14 patients experience a partial response to Reolysin treatment, with an additional seven patients showing stable disease. Oncolytics had been looking for only 3 out of 18 partial responses, so this was encouraging. Oncolytics is now in Phase III in head and neck cancers.

That the smart money is starting to bet on oncolytic viruses is indicated by Amgen's January 2011 acquisition of BioVex, a privately held company from Woburn, Ma. Amgen paid US$425 million cash for BioVex in order to get an oncolytic virus based on a herpes virus called OncoVex. Amgen promised another US$575 million in milestones. The product was then in Phase III for metastatic melanoma as well as head and neck cancer. Data from the melanoma Phase III reported in March 2013 (click here) validated Amgen's billion-dollar confidence, with 16% of OncoVex-treated patients experiencing a  durable response compared with 2% of the controls, who got plain old GM-CSF.

Oncolytics Biotech and Amgen aren't the only ones doing oncolytic virotherapy. A privately held company from San Francisco called Jennerex is also a player, as is Sydney-based Viralytics (ASX: VLA). The last-mentioned outfit reckons it has a contender for leadership in the space. Its oncolytic virus, called Cavatak, is now in an open-label Phase II in metastatic melanoma under an IND. Cavatak is a coxsackievirus (named after Coxsackie, NY, where the first case of coxsackievirus infection was noted in the 1940s), which makes it a lot smaller than Oncolytics' reovirus and therefore potentially more able to penetrate cancer tissue. It may also have an advantage over Reolysin in terms of neutralising antibodies generated by the patient. Half of all children by the age of twelve having been exposed to a reovirus and just about everyone has by adulthood. By contrast most of the population do not have antibodies to a coxsackievirus. Where Oncolytics has the advantage over Viralytics is in the reams of clinical data already generated. However, should the Viralytics study register enough responses in the current Phase II, this story could become something special. It's only capitalised at A$27m at the moment so it may be worth checking out.

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 analyst at the Sydney-based stockbroking firm Southern Cross Equities in April 2001, focused on the Life Sciences sector from February 2002. Southern Cross Equities was acquired by Bell Financial Group 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:
Immunomedics (Nasdaq: IMMU), 21 August 2013
Oncolytics Biotech (Nasdaq: ONCY),  22 August 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. 1 - IMMU

We live in a society exquisitely dependent on science and technology, in which hardly anyone knows anything about science and technology - Carl Sagan (1934-1996), American astronomer

Immunomedics - the Next Big Thing in ADCs

Greetings from Sydney, Australia. Australian Biotechnology Buzz is a new Blog where I'd like to explore the people, companies and issues that make up the Life Sciences landscape. My interest is global, but I am particularly interested in what's going on in Australia. I've been an interested observer of biotech since 2002, first with Southern Cross Equities, where I was an equity analyst covering the sector, then at Bell Potter Securities, which bought Southern Cross Equities in 2008 and completed its earn-out of the business in 2011. I left Bell Potter in June 2013 and started this blog so I could keep actively following this industry that I love.

In today's inaugural entry I'm looking at Immunomedics, Nasdaq code IMMU, an antibody company from the Garden State bedroom community of Morris Plains. I've been fascinated by antibodies for years, ever since that fateful day in February 2002 when Southern Cross Equities asked me to write up Peptech (creator of one of the first anti-TNF antibodies) and thereby turned me into a biotech junkie. That was over a decade ago, and antibodies have come a long way since then. The two big antibody developments in recent years have been bi-specific antibodies that can hit more than one target at once, and antibody-drug conjugates (ADCs) that can use the exquisite specificity of antibodies to deliver drugs directly to targets of interest. The big winner in that space has been Seattle Genetics (Nasdaq: SGEN), now capped at more than US$5bn. Immunomedics, however, at a mere US$43 0m, wants to be a contender as well, with the company announcing on 12 August that  it was moving into Phase II with some ADC cancer programmes focused on solid tumours.

It's been a good year for Immunomedics. The stock was around US$2.50 back in May and now it's around US$5.00. The excitement relates mainly to an antibody called epratuzumab, which targets CD22 on B cells. The Belgian drug major UCB has taken epratuzumab to Phase III for lupus, a drug market set for strong growth thanks mainly to GSK's Benlysta, which in 2011 became the first new lupus drug in fifty years. Meanwhile for its own account Immunomedics showed on 14 August that epratuzumab combined with Roche's spectacularly success Rituxan antibody could being about solid progression-free survival numbers for follicular lymphoma in Phase II clinical work. Throw in other studies that Immunomedics has performed, both clinical and pre-clinical,  and it looks like epratuzumab has the kind of versatility we've seen with Rituxan, which had estimated global sales in 2012 of US$6.9bn.

So Wall Street already has a reason to watch this stock carefully for an old-fashioned unconjugated cancer antibody story. However the fact that the company's ADC technology is progressing suggests that this story has further to go in turns of attracting investor attention.

Is there an Australian angle to this story? If you go to the web site for the ASX-listed cancer antibody developer Patrys you can find some research there suggesting that the cancer antibody field has plenty of room for other companies to create serious shareholder value. Worth doing some homework on.

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 analyst at the Sydney-based stockbroking firm Southern Cross Equities in April 2001, focused on the Life Sciences sector from February 2002. Southern Cross Equities was acquired by Bell Financial Group 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.

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.