Replies to post #60138 on Biotech Values

[xrymd]

Bio Specialist: Did you ever work with with Lindsay Rosenwald or Blinder (in the 80s)? I fell over laughing reading about iodine for fibrocystic breast disease. There must be a penny stock bio tech board for you to monitor. LOL.

[Preciouslife1]

BioSpecialist, if your small Biotron can come up with
results in phase 2/3, like they are claiming now
with the HIV and HCV phase 1 data, showing no/little
toxicity as well as the potential to hit HIV where it
lives, hides, resides, and mutates, in the body, then
maybe this little company has a chance. The HCV drug
was well tolerated and effective in triple combo with
Ribavirin and interferon, whose toxicities and side
effect profiles are very well known on this board.

+++"BIT225 represents a novel, first in class approach to the treatment of HIV. BIT225 specifically targets HIV in reservoir
cells and represents an opportunity to attack HIV at its source in the body. Current HIV therapies have little or no effect on HIV in the underlying reservoir of infected cells where the virus hides from the immune system.
In addition, BIT225 represents a first-in-class drug for treatment of HCV, targeting the p7 protein of HCV.
" Existing drugs for HCV have limited effectiveness and toxicity issues, leaving a significant need for new therapies. The worldwide market is currently almost US$3.0 billion, but it is estimated that this market will expand to over US$10.0 billion as safe, effective therapies enter the market.
During this half year period, independent research in the USA demonstrated that Biotron's lead antiviral drug, BIT225,
significantly enhances the activity of existing HCV therapies in an in vitro model system. The results of this research,
performed by Southern Research Institute, Maryland, USA, are significant as they indicate that BIT225 has the potential
to be used in combination therapy to achieve a higher level of antiviral activity against HCV than is currently possible,
while improving the potency of each of the drugs in the combination.
The results demonstrated that BIT225 was highly synergistic in a triple combination with two of the most commonly used
HCV therapies - ribavirin and interferon. The addition of BIT225 to ribavirin and interferon, increased the level of
inhibition of viral replication from 70% with the two other drugs to 100% when BIT225 was added to the mix. The
potency of BIT225 was increased tenfold in this triple combination, compared to its activity on its own."

That being said, this compound will have to prove her
mettle through the rigors of phase 2/3 clinical trials, toxicity levels, morbidity and mortality potholes, and
the lag time behind current drugs in clinical trials.
I hope the best for you and for this platform as the current
SOC in the HCV space is archaic and the HIV drugs while being
very effective, do not eradicate the virus, but rather subdues
it due to the mutating and hiding effects of the HIV virus
within the human genome. Great luck to you with this small
company and to any potential victories showing great
efficacy and ethicacy.

PL1

[Preciouslife1]

Biospecialist and board, did you ever read this article
about eradicating the HIV virus from 2004?

HIV's crystal key

http://www.nj.com/news/ledger/index.ssf?/news/ledger/stories/1212hiv2.html

The AIDS virus is a quick-change artist that copies itself at lighting speed. But a team of scientists at Rutgers believes it can outsmart the killer.Sunday, December 12, 2004
BY KITTA MacPHERSON/Star-Ledger Staff
To change the world, Eddy Arnold has always tried to think small.

For nearly 20 years, the Rutgers University chemist has obsessively dismantled the AIDS virus to untangle its deadly submicroscopic machinery.

And it is there, in the complex world of the minuscule, he believes he finally has found a magic bullet that stops AIDS in its tracks.

Arnold and his coterie of researchers have developed what they regard as three revolutionary AIDS drugs, each part of a family they call DAPY (which rhymes with happy).

The drugs, they believe, can destroy HIV, the deadly virus that causes AIDS.

To do this, the drugs do as HIV does when it devours immune systems: They change shape. Put another way, DAPYs are a master key that can fit any strand of the virus, regardless of how it tries to disguise itself.

As Arnold says: "We're onto something very, very special."

Understanding and controlling this flexibility in a treatment is crucial because HIV's biggest challenge to science and medicine has been its ability to consistently mutate, outrunning any drug or vaccine custom-designed to quash it. And unlike other treatments that focus on blocking HIV from entering healthy cells or from containing contaminated ones, DAPYs literally douse a lit firecracker by interfering with any of the 20,000 steps HIV takes to copy itself at warp speed.

At the core of this discovery is reverse transcriptase -- the villain in this story and a submicroscopic protein not normally found in healthy human cells. The team believes RT is the ideal protein to disable because it offers so many opportunities to be blocked.
The most promising of the three DAPY drugs in the family is a new supercompound known as R278474.

Because DAPYs can be delivered in just one pill instead of the present drug cocktail taken by millions of AIDS patients, Arnold and others believe, they are another step toward the goal of creating a cheaper, more effective way to stay ahead of the epidemic.

So far, tests conducted internally at New Brunswick-based Johnson & Johnson indicate the drug is a snap to synthesize, is easily absorbed with minimal side effects and shows promise as a once- daily, low-dose oral treatment.
For researchers on the front line, R278474 and its cousins may be that magic bullet.
"This could be it," said Stephen Smith, a physician/scientist who directs the department of infectious disease at St. Michael's Medical Center in Newark. "We're all looking for the next class of drugs."

Smith manages dozens of clinical trials testing AIDS treatments and said the idea underlying the new RT inhibitors makes sense.

"Reverse transcriptase is very important in the biology of AIDS," Smith said. "If you can really inhibit reverse transcriptase, you can stop AIDS."

This is the story of how a team of AIDS researchers remained true to their instincts about reverse transcriptase during nearly 20 years of painstaking research -- even when the rest of the scientific world was spinning in another direction.

THE CHALLENGE

It will take an extraordinary remedy to beat AIDS for good. After being held in check for 17 years -- first by workhorse medications such as AZT, introduced in 1987, and then by drug cocktails, available since 1996 -- the disease now is becoming resistant to long- held treatments.
Worldwide, AIDS has killed 20 million people since appearing in the United States in 1981. And 40 million now live with the disease, according to United Nations statistics.

In New Jersey, more than 32,000 people suffer from AIDS, ranking the state fifth in the country. In the developing world, where many cannot afford generic versions of AIDS medications, the virus kills people during their most productive years and decimates regions.

It also has been an expensive fight. Government funding for research, prevention and assistance was more than $14.7 billion in 2002.

Eddy Arnold thinks he can solve some of these problems.

Known to faculty and students on Rutgers University's Busch Campus in Piscataway as a sweet- natured scientist, Arnold, 47, studies the structure of biological molecules -- the proteins that are the beating heart of HIV.

He does this through X-ray crystallography, an increasingly popular technique used in chemistry and biology to determine the structure of molecules -- the smallest particles of an element or compound that can exist and still retain all the same characteristics.

Arnold, whom you might find in a shirt and bolo tie one day and a rock'n'roll band's T-shirt the next, always has enjoyed complex puzzles. Growing up in Pittsburgh, at age 3 he was completing 500-piece jigsaw puzzles. By 10, he was up to 2,000-piece sets.

Even now, when Arnold sits in his book-lined office, deep in the cavernous Center for Advanced Biotechnology and Medicine, he can close his eyes and see thousands of atoms that make up RT.

Reverse transcriptase is composed of two coiled chains of amino acids, the same building blocks found in egg whites, milk, blood and meat. The protein is minuscule; if laid lengthwise on a ruler, you could fit about 2.5 million RTs within one inch.
Though easily mistaken for a tangled piece of confetti, RT is a highly complex machine. Composed of chains containing combinations of 20 amino acids, it is folded in unpredictable ways. Scientists believe there are patterns in these ribbons, but no one has deciphered them.
RT inhibitors interfere with an enzyme that HIV needs to copy itself. If the enzyme fails to function, HIV cannot insert itself into a human host cell and will die.

Compared with HIV's other proteins, protease and integrase, RT is monstrous and complex, a lethal Rube Goldberg device seeking conquests at warp speed. People like Arnold see it as the puzzle to beat all puzzles.

BUILDING THE TEAM

Arnold established his lab at Rutgers in 1987 with his biologist wife, Gail Ferstandig, and set off building what is now a 30-member research team that partners with Janssen Pharmaceutica and Tibotec-Virco NV, both subsidiaries of Johnson & Johnson.

Arnold's first big move was forming a partnership, also in 1987, with Stephen Hughes, a leading virologist and AIDS researcher at the National Cancer Institute in Frederick, Md.

In 1990, the collaboration added Paul Janssen, a legendary drug pioneer and one of the few scientists who believed in Arnold's early work. Janssen, according to Arnold, had a dream to devise a drug that could be distributed cheaply in the developing world.

That dream and Arnold's team ultimately produced R278474 or ripilvirine, Janssen's favorite anti- AIDS compound and the newest DAPY. The compounds are so named because they have diarylpyrimidine at their core. The other two compounds -- dapivirine or TMC-120, and etravirine or TMC- 125 -- have gone through early phases of clinical trials.
Making it through those experiments, something most drugs don't accomplish, shows the compounds hold great promise to win federal approval.

Details of R278474 will be published early next year in an issue of the Journal of Medicinal Chemistry to be dedicated to "Dr. Paul," as the Belgian physician-scientist was known to colleagues. (On Nov. 11, Arnold's team pre-published details in the electronic edition of the Journal of Medicinal Chemistry. The article represents the pinnacle of their work.)

R278474 never would have existed without Janssen's work 14 years earlier.

In 1990, he published a paper in the science journal Nature describing a new drug that blocked HIV's key protein, reverse transcriptase. Problem was, the compounds caused resistant strains to pop up too quickly, infecting cells with offspring that had tiny mistakes in their genetic code. That meant drugs designed to target a specifically formed virus could fail to recognize and treat mutant strains.

Unable to see this relationship between the drug and the killer virus under a microscope, Janssen needed a scientist to make a crystal that would combine reverse transcriptase with his experimental compound. He was told there were only three people who could do it.

Arnold was one of them.

Together -- along with Hughes and other determined colleagues -- they embarked on a journey under the banner of modern molecular biology, a discipline defined by DNA co-discoverer Francis Crick as "the attempt to understand any biological problem at the level of atoms and molecules."

For the next decade, they talked weekly, sometimes daily. First, they would need to understand RT. Then, they could start working on the mysteries of RT inhibitors. Hughes provided RT; Janssen, the inhibitors, and Arnold eventually brought it all together with his crystals.


CRYSTAL GAZING

Crystallography, which involves rendering materials into well-ordered crystals and then fathoming their atomic structures, may be as much art as science.
The Picasso that Arnold's lab was chasing was the crystal structure of reverse transcriptase.

"It took us from 1987 until mid- 1991 to get RT crystals that were useful for getting a detailed structure," Arnold said. "But it took until mid- to late 1992 to solve the detailed structure from these crystals. It was very technically challenging."

Compounding the tension was a team of researchers at the lab of eminent scientist Thomas Steitz at Yale University, also on the case.
In May 1992, Arnold and his team published a paper showing what amounted to a rough map of the reverse transcriptase molecule.
But the following month, the Steitz team published a paper with greater details, revealing the overall structure of the molecule. The scientific community hailed the paper as a breakthrough.

Undeterred, Arnold's lab came back in June 1993 with a tour de force. The paper showed not just RT, but the molecule bound with double-stranded DNA -- in essence, a snapshot of the protein in action as it co-opts a healthy cell.

"At the time, it filled in a lot of gaps in terms of details of what is where in RT -- where drug-resistant mutations are located," Arnold said.

The paper made the 35-year-old Arnold a star and earned him permanent tenure at Rutgers. It also helped him win funding from the National Institutes of Health and pharmaceutical companies. More funding meant more staff.
He was also given more space in his building.

It didn't make him rich, though, and he will not receive royalties or any other fees if the DAPYs are commercially successful.

He doesn't like to discuss specifics, but his salary is consistent with that of other top professors at Rutgers -- meaning he earns well into the six figures, but far short of the university's football and basketball coaches.

After the 1993 paper, the Arnold team produced many variant structures of the reverse transcriptase molecule, or new looks at the virus' mutating dances.
It was work that led to the RT inhibitors.

But Arnold's team didn't know that at the time. "We were just feeling our way through the science, picking the best, most interesting topics," he said.

"Arnold was an up-and-coming scientist without tenure," said Stefan Sarafianos, a molecular biologist who joined the Arnold lab in 1995. "This was an absolutely crazy thing to do. This was a high-risk project and he was competing with the super-duper labs of the world like Steitz's.

"It was a folly. But it turned out all right for him."
For a while, anyway.


IN AND OUT

In 1996 Arnold suddenly found his research out of step.

The introduction of protease inhibitors, another important class of commercially available AIDS drugs, lowered the profile of RT inhibitors, which attacked the virus during its development.

Protease inhibitors affected the virus in a late stage of its reproductive cycle, meaning the new drugs zapped the virus and already-infected immune cells, slowing the lethal spread from virtual virus factories.

When combined with other drugs in the so-called AIDS cocktails, protease inhibitors are highly effective in extending lives. Its efficacy produced the flawed perception that the disease finally had been beaten. It also nearly killed funding for research on new versions of older drugs.
"When I first heard the results of the protease inhibitors, I thought, 'Boy, this is really going to change the treatment paradigm,'" said Norbert Bischofberger of Gilead Sciences, who had been championing RT inhibitor research since 1989. "Eclipsed would be a good word for what we felt."
After protease inhibitors were featured at an international AIDS meeting in July 1996 in Vancouver, Wall Street's enthusiasm for other research flagged.

"Analysts and investors would say to me, 'We're done. Right?'" Bischofberger said.
But science had tamed the tiger only in places where patients could afford medications.
Bischofberger urged Gilead, his firm, to press ahead.

"In science, this is a long-term effort. Projects can take 10 to 12 years," he said. "You can't pay attention to where the wind is blowing at one particular moment. If you believe in something, you just have to keep moving toward your goal."

Arnold's team hung on, too.

They knew what they had to do: thwart reverse transcriptase. And they knew they needed a magical crystal, of sorts, to light their way.

THE BREAKTHROUGH

A crystallographer, with just the right mix of chutzpah, luck and intelligence, can believe he has a shot at understanding any living thing.

Even if a molecule is too tiny to see with a microscope, a crystallographer can figure out its shape and composition -- what scientists call its structure.

About 2 a.m. one spring night in 2000, Rutgers University physicist- turned-crystallographer Kalyan Das was sitting before a computer monitor in the basement of his Edison townhouse.
He stared at an image of a DAPY drug -- TMC-120 -- that had been shown in lab studies by scientists at Tibotec Virco. There was a hitch, though: The people who made the compound did not yet understand exactly how it worked.
How is it, Das wondered, that the compound could fit so neatly into the cleft of so many versions of the viral protein, effectively blocking its copying action?
To do this, the molecule he was viewing had to wiggle.
Just then, he thought back to his childhood, to the winding caves near a Hindu temple his family attended in India. He remembered how he had to twist and turn to make it back toward the light.

Das then reasoned that the atoms at the extreme end of the compound exhibited "torsional flexibility," like the movement of a gate swinging on hinges attached to a post.
The molecule, he ventured, also had to jiggle, or rock lightly. In short, the compound seemed to be flexible.

Das was excited.

A drug that could wiggle and jiggle -- acting like a master key -- would be groundbreaking.

The Rutgers group had kicked around the idea of molecular nimbleness for a couple of years and several earlier compounds had shown some degree of bending. But nothing had acted like this. Now it would be the team's job to use crystallography to figure out exactly how the DAPYs worked.

The battleground would be a tiny room at the Cornell High Energy Synchrotron Source in Ithaca, N.Y., a favorite destination for the Rutgers crystallographers for more than a decade.

CHESS is one of the world's leading centers for X-ray research in biology and materials science, a 23-year-old facility in Wilson Laboratory under a football field on the vast campus.

The facility's workhorse is the synchrotron, a massive, ring- shaped machine that actually is the size of the field under which it sits. It accelerates subatomic particles almost to the speed of light, producing synchrotron radiation -- a form of light researchers shine on molecules, atoms, crystals and other forms of new materials to understand their structure and behavior.

The radiation gives researchers unparalleled power and precision to probe the fundamentals of matter. The light is a million times brighter than sunlight and a billion times greater than the radiation from a typical lab X-ray.

The emerging beams are just a few thousandths of a millimeter across and are emitted in extremely short pulses, typically 10 to 100 picoseconds (trillionths of a second) in length. The beams barely scrape the precious crystals.

Colleagues often told Das he had a velvet touch with the synchrotron. When others brought dozens of crystals and left without relevant data, Das brought one or two and always got results. That is, until he ran into DAPY.

For more than a year, Das blasted through hundreds of crystals at CHESS and other synchrotrons.
Still, he could not obtain useful data.

"We had the crystals and they didn't diffract," said Das, meaning samples failed to yield patterns revealing chemical structure. "That was surprising and frustrating. I knew I was doing everything right."

In October 2002, the Rutgers lab crystal maker, Art Clark, gave Das one crystal for a trip to CHESS. The sample, merely a speck of RT with the TMC-125 inhibitor, was as clear and glittery as a diamond when viewed through a microscope, but otherwise unimpressive. With this crystal, however, Clark had extracted some surrounding liquid.
Within a minute of placing the crystal on the beam, Das knew he not only had data, but suspected he also had finally found the key to the puzzle.

Having gone to the Cornell facility by himself, he was alone when the moment came. It was after midnight, but he called Eddy Arnold at home anyway -- afraid to be too ecstatic.
"So much had gone wrong in the past, I had trouble believing my own data," he said.

After a few hours of sleep, Das tried to calm himself during the four-hour drive back to Piscataway where he went straight to the lab -- and to Arnold.

"It's good," he said, handing Arnold the images that had been eluding the team for so long.

ONE MORE HURDLE

In the fall of 2003, after a year of fine-tuning, testing and writing, editors at both Science and Nature rejected Das' paper on the work, saying it was focused on drug development and not of sufficient general interest. The team took it hard, especially since, as Arnold put it, the work may be "the best thing we've ever done."

With nearly two decades invested, they had little choice but to forge ahead and run experiments to understand what made the DAPY drugs work so well. They also studied the mechanism of resistance in RT -- how it occurs, step by step, on a molecular level.

Finally, Das published the results of the team's work on the DAPY crystal in May 2004 in the Journal of Medicinal Chemistry. By summer, molecular flexibility was the talk of a meeting at the National Institutes of Health. It remains a popular theme among researchers.

Meanwhile, TMC-120 and TMC- 125 -- the older cousins to the Super DAPY -- have shown great promise in Phase I and Phase II trials the past two years.

Smith, the AIDS expert at St. Michael's Medical Center, said clinical trials testing safety and effectiveness of TMC-125 are moving apace. He already is enrolling patients for Phase III, the all-important stage where the federal government assesses patients before approving or rejecting a drug.

Any company embarking on such a multimillion-dollar endeavor is committed to bringing the drug to market, Smith said. Johnson & Johnson officials confirm TMC-120 and TMC-125 are of major interest to them. But they won't discuss R278474.

In the end, one or more of the DAPY compounds could represent J&J's first foray into the multibillion-dollar market for AIDS drugs. If TMC-125 moves successfully through its third phase, which would last about two years, it could be approved by the FDA in 2007.

For Arnold -- who lives in Belle Mead with his wife, Gail, and their daughters, Lizzie, 14, and Emmie, 10, and their pet hedgehog, Thistle -- a successful drug will mean he has helped win an important battle.

"We may eventually win the war against HIV/AIDS. That would be an extremely rewarding and satisfying outcome," he said. "But even to have contributed to helping the health and well-being of the many people infected by HIV will be very satisfying if that were to happen."

Until then, the clock continues ticking as Arnold and his team work on their latest project, an AIDS vaccine -- one of the most difficult-to-achieve scientific goals in history.

"Only the impossible is worth doing," Arnold said.

[DewDiligence]

The claims in your post are not even close to being believable, IMO. Sounds like yet another scam stock.

[Kadaicher1]

HIV & HCV first-in-class drug. Biotron has taken 7 years to get to the stage of clinical trials, so it is probably not a scam.
It has been trading a several hours on the ASX at 16c with zero transactions. I guess that can only happen in a market like the ASX, where shorting is not permitted on small companies. I would like to buy some, but the problem is you are trapped if the trial goes wrong.
That analyst review on the sight gives a 500% upside.
There is another short review of the SP in this website, along with most other Aus biotechs.
http://www.valutech.com.au/pages/Biotech2008B.html

[BioSpecialist]

re HIV & HCV first-in-class drug..Undiscovered Stock

Biotron Limited (Bit.ax)
Marketcap: 17 million US$

HIV trial start Phase 1b/2a in 2Q 2008 results in 3Q 2008
HCV trial start Phase 1b/2a in 2Q 2008 results in 3Q 2008

Shareholder Update 9 may 2008

Dear Shareholder

Welcome to this edition of Biotron’s newsletter, BITNews. These first few months of 2008 have seen turmoil in the stock market, and Biotron has not escaped the general downturn. The Directors believe that the current share price does not reflect the intrinsic value of the Company’s technologies.
Biotron continues with a robust drug development program which shows every promise of achieving commercial success. Since completing the Phase I clinical trial in healthy volunteers in late 2007, we have been compiling the drug data packages that will support two new trials – one in HIV-positive and one in HCV-positive patients. These are highly detailed documents that are required for submission to relevant ethics and regulatory authorities. Preparation of these data packages is now complete, which is a substantial milestone for the Company
During the first quarter of this year the Company has been in extensive consultation with international and national clinical advisors who have specific expertise in the design of trials of new drugs in patients. Biotron’s lead drug, BIT225, is a new class of drug with a new mode of action. It is critical that the trials are designed correctly to ensure the required outcomes can be achieved. The data from these trials will be used to support on-going development of BIT225, and critically, will be the major item that maximises their value to a multinational pharmaceutical company. Correctly designed and implemented trials will benefit shareholders as returns to the Company from a commercial deal will be maximised.
The other key reason for ensuring the trials are correctly designed is to maximise patient recruitability. Defining inclusion and exclusion criteria for trial participants – such as stage of disease, past treatment, current co-treatment, unrelated diseases, age and gender – determine how quickly we will be able to recruit sufficient patients and complete the trial. Delaying commencement of the trials while these criteria are determined is preferable to commencing a poorly-designed trial with slow recruitment and significantly prolonged outcomes.
At time of writing, final versions of trial protocols have been prepared, and will shortly be submitted to ethics and regulatory authorities. We anticipate receiving approvals to commence these trials before mid-year.
In December 2007 Biotron initiated and completed a Share Purchase Plan (SPP) to raise additional capital for clinical development of its antiviral programs. The issue of 14,700,000 shares to raise $2.5 million was underwritten by Martin Place Securities Pty Limited. The Directors would like to thank all those shareholders who supported the Company by participating in this recent capital raising.

Extended Safety Doses for BIT225
Biotron recently completed an additional higher dosage of BIT225 in healthy volunteers. This was done as an extension to the Phase I trial that was completed late last year. The higher dose was given as no dose-limiting toxicities were noted during dosing at the lower levels. This higher dose of 600mg BIT225 was well tolerated and results have further strengthened the data package that will support the proposed trials in HIV+ and HCV+ patients.
Presentation of Phase I Study to International Experts
In December 2007 Biotron presented the results of the Phase I clinical trial of BIT225 to an international audience of clinicians, researchers, scientists and pharmaceutical company representatives from around the world assembled at the HCV DART 2007 conference, Maui, Hawaii.
At the same meeting, Biotron presented a second paper on BIT225, with data showing that BIT225 significantly improves the activity of the current leading HCV therapies in an in vitro model system. Studies performed in the USA have shown BIT225 is highly synergistic in a triple combination with two of the most common HCV therapies in use today - ribavirin and interferon-á. The addition of BIT225 to ribavirin and interferon-á increased the level of inhibition of viral replication from 70% with the two other drugs to 100% when BIT225 was added to the mix. The potency of BIT225 was increased tenfold in this triple combination, compared to its activity on its own, with only one tenth the amount of BIT225 needed to achieve this excellent result in combination compared to on its own. The data indicate that BIT225 has the potential to be used in combination therapy to achieve a higher level of antiviral activity against HCV than is currently possible, while improving the potency of each of the drugs in the combination.
The two papers generated significant interest and discussion by the international antiviral drug community.
Further evidence of this interest was the invitation extended to Biotron to present at another international conference in March 2008. The 5th Anti-Infectives Partnering & Deal Making Summit , held in Philadelphia, PA, USA, was an infectious disease partnering and business development conference that gives global biotechnology and pharmaceutical companies an opportunity to network with high-level executives from top pharma and various biotech/ pharmaceutical companies, as well as explore potential collaborations, and discuss relevant anti-infective issues and deals that affect the industry. Biotron presented a paper on BIT225 to an audience of experts from leading organizations such as AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Global Alliance for TB Drug Development, GlaxoSmithKline, Human Genome Sciences, Merck, Novartis, Wyeth, and many more.
BIO2008, San Diego
In June Biotron will be attending the annual international biotechnology partnering conference, BIO2008 in San Diego. This conference provides an excellent opportunity to showcase Biotron’s antiviral drug programs to an international audience, and Biotron will participate in one-on-one meetings with business executives from US and European companies. This provides an opportunity to further advance discussions with potential partners.
Thank you for your continuing support

[BioSpecialist]

Hep C trial for Biotron

Biotron commences phase Ib/IIa testing of HCV treatment
Dylan Bushell-Embling 07/08/2008 15:54:52

Biotron [ASX: BIT] has started Phase Ib/IIa clinical trials of its BIT225 hepatitis C candidate.

The study will enlist 18 hep C positive patients, who will be sorted into two dosage groups and a placebo control group.

The trial is primarily a safety and tolerability study, but determining the pharmacokinetics and effectiveness of the drug are secondary objectives of the trial.

Biotron expects to conclude the trial by the end of the year.

BIT225 targets the p7 protein of HCV, and has demonstrated good antiviral activity in surrogate models of HCV infection. This trial follows on from a successful Phase I trail conducted in healthy volunteers.

Biotron began as the commercialisation arm of the John Curtin School of Medical Research at ANU.

[BioSpecialist]

Hep C Phase 1b/2a results soon

Biotron (BIT.AX)

MarketCap: 11,4 MioA$ ( 8,3 MioUS$)
Price : 0,09 A$

Your support of your Company at this time is critical to:

Completion of the Phase Ib/IIa Hepatitis C virus ('HCV') clinical trial.
Ensuring that commercialisation negotiations following the completion of the HCV clinical trial are
undertaken with the Company in a position of financial security.
The Directors encourage all eligible shareholders to support the Company and take advantage of this
opportunity to acquire Biotron shares without brokerage or other transaction costs and at a discount of
approximately 15% to the weighted average share price for the five business days preceding the date that the
SPP was announced.
Introduction
Biotron has achieved great success in its antiviral drug development program to date, culminating in its lead
investigation drug, BIT225, currently being trialed in HCV positive patients.
This human trial will provide the first evidence of the efficacy (the antiviral effectiveness) of BIT225 in HCV
positive patients. The successful completion of this human trial will represent the most significant milestone
achievement for the Company to date and is the result of many years of painstaking work.
The vast majority of potential drugs never reach this stage of development and the significance of BIT225
reaching this stage of development and the work completed to get BIT225 to this stage should not be
underestimated.
Following a successful completion of this human trial, the Company will focus its efforts on completing a
commercial deal with a pharmaceutical company to continue the development of BIT225 to a marketable drug.
Discussions with a number of pharmaceutical companies have been ongoing for some time and BIT225 is well
known in the drug development industry. The Directors are keen to ensure that completion of commercial deal
is not hurried or compromised by the Company's short term financial constraints. The success of a commercial
deal will be assisted by the support of shareholders at this critical time.

History
In late 2007, the Company completed a successful Phase I, first-in-human study of BIT225 in healthy
volunteers.
Following this success, the first half of 2008 was spent designing the Phase Ib/IIa trial of BIT225 in patients
infected with HCV – the first study of the drug in a patient population.
2
In consultation with experts in the field, the trial design was finalised, and documentation prepared for obligatory
ethics and regulatory submissions. Approval for commencement of the Phase Ib/IIa trial was given in August
2008. The trial, code-named BIT225-003, is a placebo-controlled, randomised study of the safety,
pharmacokinetics and antiviral activity of BIT225 in patients with HCV infection designed to assess the safety
and tolerability of BIT225, to assess the pharmacokinetics of BIT225 and to assess the antiviral efficacy of
BIT225 in these patients.
Eighteen patients are being randomly assigned to receive one of two dose levels of BIT225 or placebo. The
trial is being conducted at two trial sites, based in Sydney and Brisbane, to expedite the trial by maximising the
eligible patient recruitment rate.
Patient recruitment was initially slower than expected, however, modifications to the trial which have been made
with ethics and regulatory approvals have resulted in a significant improvement in patient recruitment rates. To
date, a total of 6 patients have successfully completed the trial and a further 6 patients are currently in a pre-trial
process and are expected to be dosed within the next two weeks, subject to passing the pre-trial eligibility
criteria.
Patient recruitment for the trial is expected to be completed by the end of March 2009.
Due to the design of the trial, results are not available until the end of the study. The trial is blinded, with
patients receiving one of two dose levels of BIT225 or placebo and the study will only be unblinded at the
conclusion of the trial.
While data from the patients dosed to date is incomplete and unknown to the Company, there have been no
reported serious adverse events and the trial continues. It is truly a case of 'no news is good news'.
Financial History
The Company has been strictly managed financially, having raised a total of only $19.1 million from
shareholders and only seeking shareholder support on three occasions since its initial public offering in
December 2000.
At the time of the last capital raising in late 2007, Biotron anticipated leveraging shareholder funds, as it had
done so before, by accessing matching funding for the Phase Ib/IIa trial through the Federal Government’s
Commercial Ready grant program. Regrettably and without any indication to do so, the Federal Government
cancelled the Commercial Ready grant program in the May 2008 Federal budget, right at the time that Biotron
was finalising protocols. Biotron had not anticipated having to fully fund the trial, so the cancellation of the grant
program has had a significant adverse impact on the financial position of the Company.
The cancellation of the Commercial Ready grant program caused the Company to hold the commencement of a
second Phase Ib/IIa clinical trial for the treatment of HIV and focus the Company's financial resources on the
HCV clinical trial. The HIV clinical trial, which has finalised protocols ready for submission for ethical and
regulatory approvals, could be commenced quickly with sufficient financial resources.
The Company is focused on achieving a successful outcome from the HCV trial, and has been progressing
discussions with potential pharmaceutical companies in anticipation of finalising a deal once the trial has been
completed. The trial has been designed to benefit shareholders through significantly increasing the value of
Biotron in the market and to its future pharmaceutical company partners.
It is critical that the Company be sufficiently funded to enable full analysis and review of the data, and to enable
negotiation of a partnership/licensing deal with an international pharmaceutical company at the conclusion of
the trial. To this end, the Directors believe it is prudent at this time to raise additional capital to ensure that
maximal value can be extracted from the trial for shareholder value creation. Being in a strong financial position
will put Biotron in a stronger negotiating position with potential partners. The Directors also believe it
appropriate to offer existing eligible shareholders the opportunity to participate in this exciting time of the
Company's development by way of the SPP.
Purpose of the Capital Raising
The funds raised by the SPP will be used to support the Company's ongoing operational costs, including
funding the completion of the Phase Ib/IIa HCV clinical trial and ensuring the Company is in a position to
complete negotiation of a licensing deal.