I’ve recently had a series of conversations with the president and CEO of one of Breakthrough Technology Alert’s portfolio holdings. The company is involved in discovery stage biopharmaceutical therapies – some truly amazing new advances – and the things that their CEO told me were no less impressive.

The reason for my recent focus on the firm is the company’s announced collaboration with Philips Electronics. Specifically, the two companies are investigating the use of medical ultrasound technology to improve the delivery and potency of our stock’s proprietary self-delivering RNA.

If you’re not familiar with the implications of self-delivering RNA, let me fill you in…

At the risk of being repetitious, I’ll tell you that RNA interference is an established biological fact. Our bodies use this mechanism routinely to turn genes on and off. These genes, in turn, produce messenger proteins that cause and prevent virtually all diseases. We know, therefore, that the science of RNAi has the potential to treat a wide variety of serious diseases.

The problem, however, is that the interfering sequences that provoke RNA interference are very fragile. They are, therefore, difficult to deliver efficiently to their target organs. The race to solve this delivery problem defines, therefore, the challenge of RNA interference.

This is where Philips Electronics comes in. Ultrasound has been used for years to assist in drug delivery. Focused sound, at precise frequencies, can alter tissues to promote the delivery and effectiveness of a variety of drugs. Philips, in fact, is the leader of the European “SonoDrugs” project. Other participants are leading pharmaceuticals and research universities.

The CEO of my favorite RNA play graciously arranged for me a conference with some of the top scientists involved in this new research. It involved his own vice president of technology development, as well as two leading scientists in the Netherlands. On the Dutch side were Steve Link, director of communications of Philips Corporate Technologies/Philips Research, and Dr. Oliver Steinbach, senior director of Philips Research Department Bio-Molecular Engineering.

Fundamentally, as I understand it, the mechanisms of actions involved in Philips’ drug delivery platform are extravasation and sonoporation, which I will explain briefly. Using these phenomena, tissues and cell walls can be disrupted to promote drug delivery through the use of precise frequencies and focused ultrasound.

The team of researchers explained the two-step process. First, ultrasound facilitates extravasation, the movement of molecules through cell walls. This is a natural process used in a variety of metabolic functions, including oxygen delivery. The size of the opening through which extravasation occurs varies. Livers, for example, have large openings. The blood-brain barrier, however, is extremely “tight” and presents a particular delivery problem for many kinds of drugs.

The Philips technology employs an approved, commercially available diagnostic contrasting agent, microbubbles. Microbubbles are routinely used for imaging purposes, providing contrast for therapists monitoring the location of injected substances. These microbubbles are co-injected with the RNAi sequences into the target region.

When the drug-containing microbubbles are in place, temporary extravasation is created with the right frequency of ultrasound. This bursts the microbubbles, improving the delivery of the drug in precise locations. Even the blood-brain barrier can be penetrated noninvasively using this new technology.

Following extravasation using microbubbles, sonoporation is induced to increase the permeability of cell membranes. This is a procedure already in use by molecular biologists to get large molecules, such as DNA, into cells. RNAi sequences are thus better able to reach their target — the RNAi mechanism itself. A doubling of efficacy is not an unreasonable expectation.

Philips has previously demonstrated, using in vivo studies, that this technology works using small interfering RNA. The collaborators have publicly discussed using this strategy to treat cardiovascular disease and cancers. It could be applied, in principle, to any organ.

Research will be conducted at Philips’ Life Tech research facilities at the High Tech Campus in Eindhoven, Netherlands, and at our pick’s own research facilities stateside. Results are expected by next year or earlier.

As amazing as the technological implications of these advances may be, the profit potential is even bigger. Naturally, I can’t give the name of my RNA pick to all 400,000 Penny Sleuth readers – it wouldn’t be fair to my own subscribers. But I can give you the opportunity to join their ranks…

With my RNA pick still in buying range, now’s as good a time as any to enter the market. Click here to learn more about Breakthrough Technology Alert…

Sincerely,
Patrick Cox
Penny Sleuth

June 14, 2010

Exploding Bubbles Deliver RNAi Profits was originally featured in the Penny Sleuth.

For those of you who are not familiar with RNA interference, here’s what it is and how it works: DNA is, in a sense, the operating system software for our cells. As such, DNA does not directly interact with genes. It’s too important to risk corruption through unnecessary exposure. Instead, DNA operates by sending out chemical instructions. These instructions are in the form of complex RNA molecules. They are similar to double-stranded DNA, but are usually single stranded.

Basically, these extraordinarily complex RNA molecules control gene activity or expression. This is important because nearly all diseases are either caused or cured by the proteins produced by genes. You can, therefore, think of the ability to increase or decrease the production of these proteins as an on/off switch for diseases.

The remarkably young science of RNA interference is based on the accidental discovery that it is possible to flip these switches. The remote control, so to speak, for these switches consists of portions of RNA molecules. Because these portions are recognized as invaders by the body, they provoke the rejection of larger disease causing RNA molecules. The other side of the coin is “RNA activation.” This is the process that increases gene expression.

The birthday of the science, according to many, was in 1998. That was when an academic paper by Craig Mello and Andrew Fire was published. Based on RNA interference in a nematode worm, it won them the Nobel Prize in physiology or medicine in 2006.

RNAi companies, unlike stem cell firms, have grown very rapidly. Many have already been gobbled up and their value diluted in big pharma umbrella companies. This is not, by the way, because RNAi is further along. Nor is it because RNAi has more potential than regenerative medicine.

It is because RNAi was spared the legal and ethical concerns that stem cell companies had to deal with. Now the legal situation has been clarified and embryonic stem cells have been replaced for therapeutic uses by iPS and parthenogenetic cells. As a result, we can expect important stem cell companies to make similar deals.

Regardless, many RNAi companies already have significant capitalization and big pharma partnerships. Even at that stage of their development, however, they still have profound transformational potential. For example, I would have added RNAi pioneer Sirna Therapeutics to our portfolio. Sirna, however, was acquired in 2006 by Merck & Co. Inc. in a deal worth $1.1 billion.

That deal, the largest in the RNAi space so far, was followed by others:

Anglo-Swedish pharm firm AstraZeneca Intl. made a $400 million deal with a European RNAi firm Silence Therapeutics.

Alnylam formed a $1 billion partnership with Swiss giant Roche.

The high-water mark for RNAi stockholders, however, is still the Sirna Therapeutics acquisition by Merck in October 2006.

As I’ve written before, RNA interfering molecules work. There is no question that they flip the switches they’re supposed to flip. The challenge, however, is getting them to their target genes before they are recognized and destroyed by the body’s immune system. Various companies are homing in on specific delivery solutions now. There are, however, many different solutions to the delivery problem. Each gene switch has its own special considerations and there is no “one size fits all” solution.

For transformational profits,
Patrick Cox

March 31, 2009

RNAi’s Huge Buyout Deals: Who Will Benefit? was originally featured in the Penny Sleuth.

Mencken had a genius for stating overlooked truths. One, which I’ll paraphrase, is that we all know that the media get it wrong when they’re covering our areas of expertise. Then, defying logic, we believe the media when it covers something outside our fields. There are exceptions, of course, but his observation is too often true.

This is the case, by the way, not only for the newspapers and networks. Even the more respected scientific journals are making huge mistakes. If you subscribe to Nature, you may have seen the recent article titled “Virus-free pluripotency for human cells.” The authors write, “For the first time, specialized human cells have been transformed into a state similar to that seen in embryonic stem cells, without using viruses.”

If you’ve been reading Breakthrough Technology Alert for any length of time, you know this is not true. In fact, there was one doctor who accomplished this virus-free transformation several years ago…

I suppose I should actually be happy when journalists get it wrong. It means that my readers are among the very few people outside of the scientists doing the research who know what’s really going on.

Incidentally, my colleague Chris Mayer once took a group of us to the bar, not far from Agora Financial headquarters, where Mencken often drank. Let me give you one more quote from the Sage of Baltimore. He wrote, “The whole aim of practical politics is to keep the populace alarmed (and hence clamorous to be led to safety).”

The new administration is now saying the economy is “fundamentally sound.” Since it mocked Sen. McCain for saying the same thing before the election, we are being asked to believe that the stimulus bill has fixed the problem.

Unfortunately, this is not true. I agree that the economy is sound in the sense that it will overcome the damage done by the political classes. Most stocks, though, continue to suffer. The evaporation of investment capital is even more of a problem. Some startups and small-caps that would have succeeded wildly will not survive.

That’s why I’ve always diversified into transformational stocks. If you had bought into the leading six or seven computer companies at the start of the computer revolution, more than half would have failed, but the winners would have made you rich.

It’s important to remember that there are several sectors now that will be bigger than computers. Stem cells is one of them, but so are RNAi and nanotechnology. Don’t be alarmed. Don’t mistake temporary problems for long-term trends.

The people who are getting their cues from the mainstream media have bid up stem cell companies, including the wrong ones. For that reason, I’m going back to RNA interference in the next issue. This industry is making miraculous progress toward controlling the genetic switches that cause most diseases.

Sincerely,
Patrick Cox

March 19, 2009

How Transformational Biotech Will Make You Richer Than Early Computer Investors was originally featured in the Penny Sleuth.