Generex Biotechnology: Oral-lyn Buccal Insulin Takes Center Stage

Insulin was discovered in Toronto in 1921 and arrived on the market in 1922. Since that time there have been episodic attempts to escape the inevitability of injection.

The race for developing a successful needle-less insulin delivery system has taken some recent nasty turns as the inhalable efforts of large pharma companies have all come to an end. The latest news that Pfizer (PFE) is adding a new warning label to Exubera regarding instances of lung cancer in clinical trials may prove to be the final nail in the coffin for hopes of any inhalable insulin winning the hearts and minds of needle suffering diabetics.

The news caused a devastating effect on shares of Mannkind (MNKD) as analysts cried "SELL" and investors obeyed the call. In essence, it appears Mannkind's "Technosphere Inhalable Insulin" somehow was seen as failing a Pfizer/ Nektar (NKTR) "Exubera" Phase III trial. Call it "guilt by association", or even call it unfair, but it will be impossible for Mannkind to win those hearts and minds of diabetics when they are afraid of serious damage to their lungs.

And with the FDA issuing a hardened approach towards approving diabetes drugs that may present any adverse health effect, consider the odds of Technosphere ever gaining FDA approval to now be seriously in doubt. However, diabetics' hopes for freedom from needles may not be over.

Generex Biotechnology (GNBT) is developing a needle-less insulin delivery system that does not enter the lungs and is delivered to the inner cheek wall as a metered dose buccal insulin spray. Ironically, this small microcap biotech, incorporated in Delaware, originally partnered early in the decade with Eli Lilly (LLY) for development of Oral-lyn buccal insulin spray. But Eli Lilly was already financially committed to a developmental agreement with Alkermes (ALKS) for the development of their Air Inhalable Insulin. In two years of nothing, Lilly never conducted a single trial for Oral-lyn buccal spray.

The biotech rumor mills were running rampant that Eli Lilly simply stalled Generex's development of Oral-lyn Buccal. In 2003, Generex and Lilly mutually agreed to end the agreement and Lilly left tiny Generex for dead. But Generex did not die. The management team, led by founders CEO Anna Gluskin and COO Rose Perri, hung strong and continued Oral-lyn buccal spray's development with a new found independent spirit and successfully raised enough financing to survive.

Oral-lyn buccal spray was back in the clinic in 2004 and 2005 and, as Generex fought its way back from potential bankruptcy, positive results for safety and efficacy began to filter through. In 2005, Oral-lyn buccal spray was approved for commercial marketing and sales in Ecuador, which was the location of many of the Phase I and Phase II clinical trials. In the latest Phase II trial for Oral-lyn buccal spray, the investigators concluded that Oral-lyn illustrated a “superior effect” vs. Eli Lilly’s HumalinR as measured by the patients A1C levels (6.1) after 99 days.

In 2006, Generex completed a positive Pre-NDS with Health Canada. In November of 2007, Oral-lyn buccal spray was approved for marketing and sale in India- which is home to 1/3 of the world's diabetics. In April 2008, Generex announced the initiation of the North American sites (USA and Canada) for their worldwide Phase III trial of Oral-lyn buccal spray in Type 1 patients. The company has announced that this six month study will be modeled after the Phase II study where "superior effect" was illustrated, and that all of the major regulatory bodies, including Health Canada and the FDA, have approved the Phase III study protocol. Generex is hoping for Canadian approval of Oral-lyn buccal spray within 18 months and shortly after in the USA.

Can this small biotech accomplish what large pharma could not? Perhaps the difference is in the Oral-lyn formulation and device, termed Rapidmist, which is a small handheld metered spray whose doses measure exactly 1 unit. The onset of action is quicker than what was reported for Exubera. Also, Oral-lyn requires no refrigeration. That is another positive unique feature, for a diabetic can simply keep the small spray device (the size of an asthma inhaler) in their front pants pocket or purse and spray doses as needed before and after a meal or snack. I guess since Generex's market cap is below $200,000,000, large investors have yet to pay attention.

However, if sales of Oral-lyn in India, home to 40 million diabetics, are healthy, then Generex will certainly be a biotech that jumps to the spotlight. After all, safety and efficacy must be crystal clear for Oral-lyn buccal spray since it is winning some early regulatory approvals before the first patients have been dosed in the Phase III. Dr. Gerald Bernstein, former President of the American Diabetes Association, is a member of Generex's executive management team and is named in the company's press releases as the expert traveling the globe raising awareness of Oral-lyn at endroclonogical events.

Non-compliance is a serious issue complicating the conditions caused by diabetes and it is fair to say that I am rooting for the little team to help bring this growing epidemic under control. After all, with all the safety issues involving not only inhalable insulin, but the new class of Type 2 oral pills (i.e. Avandia), a simple 1 unit buccal insulin spray may prove to be the winning solution to the puzzle of needle-less delivery.

Finding a successful needle-less option has been called the 'Holy Grail of diabetes research' and this small biotech may actually have developed the next paradigm of diabetic care. As the current spotlight shines on the questionable safety problems of inhalable insulin, investors may be wise in paying attention to Generex and their Oral-lyn buccal spray. The positive safety profile and positive Phase II efficacy results are encouraging to GNBT shareholders in a time when the diabetic epidemic is growing and its needle-less competitors are all falling.

Generex recently completed new financing that brings their cash holding to just above $40 million. Generex's burn rate has been approximately $7 million per quarter and it would be wise to note that this burn rate should move higher with the manufacturing needed for the Indian market and the continuation of the worldwide Phase III trial. Shreya Life Sciences, the 4th largest insulin distributer in India, is Generex's marketing and distribution partner for the region. Last month, Shreya placed a purchase order for 210,000 units of Oral-lyn to be used in the marketing launch. Generex's marketing and distribution partner in the China region is Scigen Ltd of Singapore. The principle shareholder of SciGen is Bioton SA, an insulin crystal manufacturer in Poland.

Perhaps in 2008 we are bearing witness to the first safe and effective achievement of this elusive goal. Generex Biotechnology, whose headquarters are based in Toronto, may be the first to redesign and improve one of the world's most vital drugs. Biotech investing is ripe with risks coupled with the prospects for large rewards. All investors need to carefully weigh the potential and realities facing any biotech and especially a microcap. Due diligence is always a necessary ingredient to wise investing. Carefully investigate my opinions and then form your own.

Disclosure: Author has a long position in GNBT

Comments

[StateOfConfusion]

I have been a long term invester in Generex. Any biotech investor needs a lot of patients to hang in. This is a superior product from a great micro cap company and its delivery system can be used for other drugs as well. Other companies like Generex are NNVC and NNBP. All have great potential for the long term.

[paul collins]

Great article very informative some other facts



Analyst has $6 Target stock is $1.25

Generex Biotechnology "market outperform"
01/16/08 - Rodman & Renshaw
NEW YORK, January 16 (newratings.com) - Analysts at Rodman & Renshaw reiterate their "market outperform" rating on Generex Biotechnology Corp (GNBT). The target price is set to $6.

In a research note published this morning, the analysts mention that the execution of the company’s low-risk Oral-lyn pre-commercialization activities and the preparations for the late-stage Phase III clinical trial are on track. Generex Biotechnology is a leading player in the alternative drug delivery market, the analysts add.



www.newratings.com/en/...


Flaherty Special Situation #2
Volume 1 Issue 2
April 2008
~~~~~~~~~~~~~~~~~~~~~~...

in this issue
Bob Flaherty Rides Again! Generex Biotechnology Corporation (NASDAQ:GNBT) is his next winner.

What exciting special situation have we found for you this issue? Take a look at Generex Biotechnology, whose stock was recently $1.04 versus a 12 month high of $2.14 and an all time high of over $22. Rodman and Renshaw forecasts a 12 month stock price of $6 and after that we think further gains are possible. GNBT is successful pioneering to introduce global needle-free delivery of insulin where many famous giants and lots of others have failed. You may even know of a person who is a diabetic who could improve the quality of their life if instead of using needles all the time they could switch to Generex Biotechnology's oral insulin spray after it is approved in the U.S. as it already is in Eucador and India.Think of how many of the 194 million diabetics in the world who would benefit if they coulld change the way that they take in insulin.

archive.constantcontac...

[garyc]

I think this article has really put the emphasis on what the GNBT team has been developing and that it would be extremely helpful for the Diabetic Patient. If the news and opinions such as this article could find a place in the mainstream news, I think you would see the stock price react positively. All other indicators for a large increase at the ticker are there, they just need to be more in the news about what they are doing. The rest will come!

[Diversify]

Oral-lyn is a real manufactured product now selling in a real country. The insulin delivered is standard insulin, the innovation is buccal absorption. Given the recent failure of lung-delivered freeze-dried insulin, it appears Generex is poised to accomplish what the major drug companies couldn't do. Good luck to Generex and I hope diabetics, especially children, soon have a needle-less way to deliver insulin safely at meal-time.

[razormd]

...I've been censored twice now!...wow, the truth must be hurting someone!...in case you missed it:

Anyone wanting the FACTS about GNBT should check my posts on Yahoo's GNBT message board...some of the things I've posted:

Apr-08: "GEN084-OL???...H... cracks me up that the specific locations of all these clinical sites evidently is top secret!...goodness knows, they're scattered among cities from one end of the world to the other...but apparently no one is allowed to know the names of the hospitals, clinicians, etc that are actually involved!!!...goodness... a poor diabetic interested in participating to do?!!!...GNBT doesn't even list a phone number to call on their website!!...and isn't it interesting that "GEN084-OL" doesn't show up on any clinical trials databases?...gee, I sure hope Anna isn't committing fraud...I'd sure hate to see her have to go to prison!..."

1-Apr-08: HAW!!...one week GNBT announcesan "order" from India and a week it announces a "death spiral" convertible managed by that lone GNBT cheerleader: Rodman & Renshaw!!!...ain't it sweet!...Anna makes money...R&R make money...shareholders get -- uhhhh...well, you know...HAW, HAW, HAW!!! "


15-Mar-08: "Re: 25,000,000 yard sale.. who needs your approval?" ...this was in regards to notification of a future stock offering: "the best part is: "...for a price of not less than 70% of the market price at the time of such issuance..."...da... I'd buy some if I could get it for 30% off!!...HAW, HAW, HAW!!!"

15-Mar-08 "HAW!...I see Bernstein grabbed... 15-Mar-08 05:16 pm ...a quick 50,000 share at 94 cents a share before bolting for the door:

yahoo.brand.edgar-onli...

biz.yahoo.com/e/080314...

...Amanatides left too?...HAW!...rats starting to abandon a sinking ship!...HAW, HAW, HAW!!

12-Mar-08: "HAW!!!...sweet 10Q!...wait a minute..aren't revenues supposed to be going UP????...I mean, after all, oralyn is selling like hotcakes in Ecuador and the Middle East, right??...and that koolaid spray they make is just flying off the shelves, right???...and old "Kaboom" is pumping people up everywhere, right???...but revenues DROPPED from 46,000 a year ago to 19,000??...well, at least those expenses keep going up!...wait a minute -- that's BAD, isn't it?...but, hey, I found one bright spot!!...the near exponential rate at which the number of shares outstanding keeps increasing means the loss per share doesn't look nearly as bad as it would have a few years ago!!!...HAW, HAW, HAW!!!"

11-Mar-08: "Re: GNBT Announces Phase III Started - When?...HAW!!!...don't get your hopes up!!...GNBT originally said they were starting phase III EIGHT YEARS AGO!...last year they said they would actually recuiting patients beginning in November, 2007...yet there is NO evidence they have recruited even one patient...they haven't even announced anywhere that prospective patients could go to sign up!...face it -- the company is a SCAM!...just another biotech playing smoke and mirrors in order to keep money flowing into management's pockets."

...make NO mistake -- this company is basically nothing but a hoax designed and managed toward ONE end -- selling worthless stock to naieve investors...AVOID!!!

[razormdthe2nd]

Never hurts to take a close look at the distributors:

11-Aug-07: "Re: HAW, HAW!!!..."Leosons Overseas Corporation"!...I get it!...you mean the one with NO affiliates:

www.leosonsco.com/affi...

...the one with NO news:

www.leosonsco.com/news...

...is that the ONE?...HAW, HAW!!...and what's that you say:

"Our clients are located throughout the middle east far east Europe and in such countries as Bahrain, Qatar, Saudi Arabia, Kuwait, Yemen, Lebanon, United Arab Emitrates, Jordan, Egypt, Cyprus, Malta, Romania, and Croatia."

...wow, I'm impressed!...all those customers to serve and Leosons only has SEVEN employees?:

www.manta.com/comsite5...

...all those customers and Leosons has only 1.3 million dollars in annual sales?:

www.manta.com/comsite5...

...HAW, HAW!!!...of course, I guess the demand for hemmorrhoid anesthetic ointments isn't all that great, huh?:

www.leosonsco.com/prod...

...HAW, HAW!!!...1.3 million -- that's rich!!...no wonder you didn't pay an upfront license fee -- probably couldn't afford it!!!...HAW!...sure hope all those "costs associated with the procurement of governmental approvals for the sale of the product, including any clinical and regulator costs" aren't too high!!!...HAW!...maybe you can recoup some from "rapidspray" sales!...oops, maybe not:

www.leosonsco.com/getP...

...HAW, HAW, HAW!!!...Anna Rocks!!!...HAW, HAW, HAW!!!"

[razormdthe2nd]

But let's not forget pertinent details:

14-Aug-07: "Now let me get this staight...each cannister of oralyn contains 400U of insulin...and 1 puff = 10U of insulin...but 10U actually only equals 0.7 units of injected insulin...so each canister actually only equals 28U of injected insulin...now let me think about this a minute...uhhhh, a type 1 diabetes patient typically requires an insulin dosage of about 1.0 unit per kg per day...so a 70 kg person needs about 70 units and that's typically divided 50% NPH and 50% R...so a patient would need 35U per day of humulin R...but each canister has only the equivalent of 28U of humulin R?????...so a typical patient will use a canister or more a day??????????...HAW, HAW, HAW!!!...sure hope those canisters are recyclable!!...HAW, HAW!!...and let's see, humulin R runs about many bucks per hundred units -- wonder what insurance companies would say about a patient flushing all that perfectly good insulin down the toilet every day?...HAW, HAW!!!...Anna rocks!!!...HAW, HAW, HAW!!!!"

[razormdthe2nd]

And don't forget GNBT's generous board of directors:

AUG-23-07: "HAW!!!,,,it must be...sweet being Rose and Anna!!...from the 8-K:

"The Board of Directors also awarded retroactive salary increases to the above-named executive officers of the Company as follows..."

...375,000 FREE shares PLUS retroactive pay raises!!...HAW!...I can just hear Anna and Rose singing in the shower: "ROLL'EM OVER, ROLL'EM OVER!!...SCREW'EM AGAIN, SCREW'EM AGAIN!!"...HAW, HAW, HAW!!!"

...and to think Anna was a real estate agent before becoming CEO of GNBT!...ain't life grand?!

[razormdthe2nd]

Want to read another of my "razormd" GNBT posts from Yahoo:

Jul-24-07: ""The nutritional label on the product (available as a PDF on their web site) says the product has 188mg of carbs (or .188g) per serving (5 sprays). A typical glucose tablet has 4g... that's about 21x more carbs in a single glucose tablet than in 5 sprays of RapidSpray. Considering you typically use at least 15g of carbs to treat hypoglycemia, you would need around 80 sprays to get 15g of carbs into your system! When you take into account the amount of sprays you need, the calorie count isn't very much different from glucose tablets.

Read the label carefully, and be very careful using this!

Posted at 2:46PM on Feb 23rd 2007 by Ismael"

...BUT he got his math a little wrong, I think...it takes 80 SERVINGS to get 15 grams of glucose from "rapidspray"... 5 sprays PER SERVING it would take about FOUR HUNDRED SPRAYS to get 15 gms of glucose!!!...HAW, HAW!!!...I can just imagine some poor diabetic with sweat pouring off him pumping away frantically before he passes out!!...on the other hand he could have just chewed 4 glucose tabs costing about 50 CENTS and saved money and a trip to the hospital...the quote is from:

thediabetesblog.com/20....../ "

[transplant]

Speaking as a kidney and pancreas transplant patient, I am delighted to hear that Generex is still pursuing Oral-lyn. Since cancer is a huge risk for me due to the immuno drugs I take, I would stay far away from Pfizer's formulation. Generex seems to offer some hope that as my pancreas becomes less efficient (as is happening to me now) and I need insulin once again, there is still a chance for needle-free delivery. Thanks to Nr. Steffens for this informative article!!

[transplant]

As both a kidney and pancreas transplant patient, I was delighted to hear that Generex is still moving forward with its Oral-lyn. I am at higher risk for cancer due to the immuno drugs I take everyday, so I would be adverse to ever trying Pfizer's formulation. Generex seens to offer me hope that as my pancreas becomes less efficient (as is happening to me now) and I require insulin once again, there may still be a needle-free alternative on the way. I'm sure I speak for many diabetics when I say to Generex, "Keep going!" Thanks to Mr. Steffens for such an informative article!!

[timurileng]

Haw! Haw! to the negative thinkers. I thank Mr. Steffens for making us aware of the possibilities that are appearing on the scene. Let's hope that tiny Generex will not give up but will emerge victorious.
Benjamin Disraeli was right when he said, "'Tis easier to be critical than correct."

[Thanh Nguyen]

Anyone known why The pharmarcist & Family Doctor don't
event know about The Oral-Lyn treatment for Diabetes without injection?