Biotech Buzz Post No. 11 - ACTC

Advanced Cell (ACTC.OB) has gained good, albeit early, results from its trials of stem cells in AMD and Stargardt’s Macular Dystrophy.

Advanced Cell ( ACTC.OB) – Proof that you can lead your field and still trade over-the-counter

"What wilt thou that I shall do unto thee? And he said, Lord, that I may receive my sight" - Luke 18:41.

Back in March the people who organise the World Stem Cells & Regenerative Medicine Congress, a firm called Terapinn, published its list of the Top 50 most influential people in stem cells today. Unsurprisingly, No. 1 on the list was the Japanese Nobel laureate Shinya Yamanaka, the discoverer of induced pluripotent stem cells (iPS cells) whom I wrote about yesterday in my Blog post on Cellular Dynamics. No 2. was James Thomson, whose lab isolated the first human embryonic stem cells and who later founded Cellular Dynamics. And No. 3 was the Professor Chris Mason of University College London, noted for the many commercial and academic collaborations in regenerative medicine that his lab is involved with. Australia’s Alan Trounson, who runs the California Institute of Regenerative Medicine, was No. 7, while his fellow Australian Silviu Itescu, CEO of Mesoblast (ASX: MSB), was No. 29. What particularly interested me, though, was No. 4 on the list – Robert Lanza, Chief Scientific Officer of Advanced Cell Technology. Here, I thought, is an interesting opportunity. Currently Mesoblast has a market capitalisation of ~ US$1.56bn while Advanced Cell is just 10% of that, at A$157m, but the intellectual insiders pay more attention to the ideas of the smaller company. It doesn’t mean Mesoblast stock has to come down – I’ve felt for a while ago that a boom was coming for the whole regenerative medicine sector - but it may mean that Advanced Cell has to move up as the field becomes more prominent from an investor perspective and Advanced Cell starts to get a move on in terms of its clinical work.

Let me tell you about Robert Lanza and then we’ll look at Advanced Cell. I first noticed Robert Lanza when I read his 2000 book Xeno: The Promise of Transplanting Animal Organs into Humans, co-authored with David Cooper shortly after Lanza left a now-defunct company called BioHybrid Technologies, where he’d worked on an artificial pancreas among other things. Lanza’s book convinced me that the era of xenotransplantation was more or less here. He’s been with Advanced Cell since 1999. I’ve never met Lanza but it seems to me that he brings four much-needed things to the stem cell field. Firstly, good communication skills. Secondly, multidisciplinary intellectual firepower – you can tell that he’s got a huge mind by the title of his 2010 book (with Bob Berman) - Biocentrism: How Life and Consciousness are the Keys to Understanding the True Nature of the Universe. Thirdly, the willingness to, as we say in Australia, ‘have a go’ (let’s face it – an artificial pancreas was a tough ask). Fourthly, and most importantly, the ability to use available technology to get around problems in the stem cell field.

Now for Lanza’s company. Advanced Cell is from Marlborough, Ma., a town around 40-50 minutes’ drive west of Boston and the place where the success story writer Horatio Alger (1832-1899) went to school. The comparison is apt because Advanced Cell may turn out to be a rags to riches story if Lanza et. al. have done their homework.

The rags part has to do with Advanced Cell’s past, when they were a pioneer in embryonic stem cells being built up by the Geron (Nasdaq: GERN) founder Michael West. If you want some background on the Advanced Cell of that time check out Stephen Hall’s 2003 book Merchants of Immortality: Chasing the Dream of Human Life Extension. Basically Hall and others were down on Advanced Cell not just because of the ethics of embryonic stem cell research but also for the hype the company supposedly engaged in. They were criticised, for example, when they announced in November 2001 that they had cloned the first human embryo. Actually only three of their eight eggs began dividing, and only one was able to make it to six cells before stopping (click here for the Scientific American article). Moreover no stem cells were harvested. People called the announcement over-promotion. The Advanced Cell team had, however, managed to transfer the nucleus of an adult cell into an egg cell which had had its own nucleus removed, something that was new.

Now fast forward a few years to the potential riches part of the Horatio Alger story. In 2005 Lanza and his colleagues used the ‘single cell biopsy’ method routinely used by IVF clinics to remove a single cell called a ‘blastomere’ from a human 4-8 cell pre-embryo. Single cell biopsy lets IVF doctors check for genetic abnormalities in an embryo but not harm that embryo. For Lanza et. al. the technique provided the starting cell for a powerful new human embryonic stem cell line called NED-07, without any embryo destruction. A major ethical issue for the stem cell field had been overcome, and when this breakthrough was announced in a letter to Nature in August 2006 (click here) you could hear the champagne corks popping all across America from those right-to-lifers who didn’t like embryonic stem cell research (and whose consciences allowed them to drink). Now you know why Robert Lanza made it to No 4 on that list I described above.

Like any good biotech company Advanced Cell is not putting all its technology eggs in one basket. It has also worked on iPS cells and is now developing a platelet replacement programme using its iPS technology, but that’s still pre-clinical. The real action for Advanced Cell at the moment is in embryonic stem cells and eye disease, where it gaining evidence from the clinic on the therapeutic power of its cells. Advanced Cell has focused in the first instance on eye disease because there’s been a lot of work done in this organ by scientists looking at embryonic stem cells (the eye makes a great model system). More importantly, the markets are huge thanks to the 25-30 million people in Europe and North America with Age-related Macular Degeneration (AMD) and the large sales being enjoyed by Roche’s Lucentis and Regeneron’s Eyelea.

Advanced Cell’s clinical story started in mid-2011. Having gathered good pre-clinical evidence that their cells can repair damaged retinal pigment epithelium (RPE) and thereby treat macular degeneration (click here for the 2009 paper) trials were started in both dry AMD as well as a rare juvenile onset form of macular degeneration called Stargardt’s Macular Dystrophy. Another indication, for myopic macular degeneration, had its IND cleared in February 2013. The first results for dry AMD and Stargardt’s, as published in The Lancet in January 2012 (click here), were encouraging. The implanted cells were engrafting in the RPE layer of the first two patients's eyes, and repairing the damage to such a degree that patients that visual acuity was apparently improving. Subsequent patients also experienced this. In case you think that’s hype, let me quote from Advanced Cell’s 2012 10-k: “Visual acuity was improved to varying degrees in several of these very late stage patients – a result that was not anticipated in the original design of these studies due to the then inclusion criteria permitting participation by only very late stage patients that had been rendered blind by these diseases”. I love it when a biotech company gets good results that it didn’t anticipate. Advanced Cell’s trials are now recruiting sighted patients under protocol amendments so that visual acuity improvements can be better measured. In May 2013 the company reported that one patient had gone from 20/400 to 20/40 following treatment. Talk about a company with vision…

Looking ahead there are other big opportunities on the horizon. Consider Mesoblast’s bailiwick, Mesenchymal Stem Cells (MSCs). The great thing about these cells are their anti-inflammatory properties, which is something about which Mesoblast has gathered great clinical and pre-clinical evidence. The MSC space may be one that Advanced Cell can ultimately get into. The company has used both its embryonic stem cells and its iPS cells to create MSCs they reckon are more potent in terms of suppressing autoimmune response than an equivalent dose of bone marrow-derived MSCs. It will be very interesting to see where this work can lead.

So why, I hear you asking, if Advanced Cell is doing such great work, and has people like Robert Lanza working for it, not to mention the über-inventive MIT genius Robert Langer on the board (Fierce Biotech have named him No. 11 on its list of the 25 most influential people in biopharma today) is the stock still traded on the OTCBB? I think that relatively low-rent market address is symptomatic of the way regenerative medicine has been up until recently – investors being unwilling to put a premium on the sector until the clinical data and partnering interest from established pharma companies started to kick in. Well, that’s changing thanks to Mesoblast, which has both the data and the first partner as well as a market cap above a billion dollars. Makes you wonder if other companies aren’t set to play catch up.

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
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
Oncolytics Biotech (Nasdaq: ONCY),  22 August 2013
Pharmacyclics (Nasdaq: PCYC), 2 September 2013
Regulus Therapeutics (Nasdaq: RGLS), 23 August 2013
Sunshine Heart (Nasdaq: SSH), 28 August 2013
Synta Pharmaceuticals (Nasdaq: SNTA), 1 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.