The first three blogs I'll bring here were my first publications at Seeking Alpha. This was published April 10th, 2008.
about stocks: ALKS / GNBT / MNKD / NKTR / PFE
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.
This Is Generex Biotechnology Pipeline Review
Antigen Express
Antigen Express is the fully owned life science subsidiary of Generex Biotechnology. Antigen Express is a platform and product-based company developing proprietary vaccine formulations for large, unmet medical needs. Their focus is on stimulating critical members of the immune response, known as T helper cells. The technology allows for antigen-specific stimulation or suppression of a T-helper response to virtually any antigen of known pathogenic potential. Antigen Express is building a deep pipeline of therapeutics aimed at a variety of major diseases, including cancer, infectious diseases and autoimmune-based syndromes.
Early efficacy analysis of the AE37 vaccine in a Phase II study
Click the logo to see the results for AE37 that were presented at the 2012 ASCO Breast Cancer Symposium
Peptide Vaccine Stimulates Immune Response in Patients With Breast Cancer
Click the logo to read about the results for AE37 that were presented at AACR 2012
Antigen Express President Dr Eric von Hofe
The President of Antigen Express is Dr Eric von Hofe, who has been impressive with advancing Antigen Express' pipeline and entering into smart collaborations. Dr. von Hofe joined Antigen Express in November of 2003. Prior to this time he held two positions at Millennium Pharmaceuticals; first as Program Director for Target Validation, where he presided over technology development efforts for Aventis and Cereon, and second as Director of Programs and Operations, Discovery Research. He received his Ph.D. from the University of Southern California and was a postdoctoral fellow at the University Hospital of Zurich and Harvard. From 1989 to 1992 he was Assistant Professor of Pharmacology at the University of Massachusetts Medical School. Click on the image of Dr von Hofe to read the abstract for his latest peer review article regarding cancer vaccines.
The AE37 Ii-Key synthetic peptide vaccine
Click on image to enlarge. Harvard scientists, who founded and lead Antigen Express, have pioneered and patented technology that modify MHC class II epitope peptides with a fragment of the MHC class II-associated invariant chain. Antigen Express recently reported interim results from a Phase II trial of the AE37 HER2/neu Ii-Key modified peptide vaccine for patients treated for breast cancer who are at high risk of relapse. While there was a 7% relapse rate in the control arm, there were no relapses in the Ii-Key peptide arm (AE37) when analyzed at the 13-month time point. A review article co-authored by Dr. Eric von Hofe, Ph.D., President of Antigen Express, entitled "A New Era in Anticancer Peptide Vaccines", will appear in an early 2010 edition of the journal Cancer, the International Interdisciplinary Journal published by the American Cancer Society. An advantage of using the type of active immunotherapy offered by AE37, as opposed to passive immunotherapy such as treatment with Herceptin, is that activated immune cells can detect and destroy cancer cells expressing much lower levels of HER-2/neu than is needed for recognition by Herceptin.
San Antonio Breast Cancer Symposium December 2009
Positive AE37 Phase II Interim results were reported at the San Antonio Breast Cancer Symposium in December 2009. Click the SABCS logo to view the poster presentation for AE37's Interim Phase II results, while the abstract text will be provided below.
Antigen Express' Ii-Key Peptide Vaccine Platform Technology
Click on the image for Antigen Express' pipeline to enlarge. AE37 is a novel peptide vaccine that is the product of a proprietary technology platform established at Antigen Express designed to increase the antigen-specific stimulation of CD4+ T helper cells. AE37 is capable of eliciting HER2/neu-specific immune responses, even without the use of an adjuvant. AE37 is the first peptide-based cancer vaccine to show potency in the absence of an immunoadjuvant.
Mary Crowely Cancer Research Center is Fully Funding the AE37 Combo Vaccine Study
Click on the Mary Crowley logo, provided above, to see the clinical trial listing for the AE37 Combo Vaccine
About Me
- Rich Steffens
- Rich Steffens has grown up in New Jersey, is a successful businessman, and studies social media trends amongst life science and biotech companies. His family is deeply influenced by the ill effects of diabetes. I am not qualified to offer investment or medical advice, and make no claims that I am an expert in these areas. I seek to share and learn.
The Future of Insulin Treatment
Dr Gerald Bernstein, Generex VP and former Pres of the ADA, was featured in an online video at the Doctor's Channel in a segment titled "Diabetes & Endocrinology Oral Insulin Delivery with Oral-Lyn". With many new insulin based drugs on the horizon, Dr Bernstein explains both the history of insulin treatment and what he believes to be the best future option- Oral-lyn. Click on the image of the current new insulin based drugs in development to view the video.
Oral-lyn's time profile; insulin only when a diabetic needs it, bringing less risk of hypoglycemia
This image, which you can click to enlarge, illustrates that with its very fast onset and offset of action, Oral-lyn buccal insulin spray may offer less risk of postprandial hypoglycemia as compared to conventional injected insulin therapy. Hypoglycemia is a life-threatening risk, and along with injections is the most important obstacle towards achieving good metabolic control. With each spray of the RapidMist device one unit of meal time Oral-lyn buccal insulin is said to be rapidly delivered into the bloodstream. The amount of sprays given is determined by the amount of insulin each unique diabetic requires to cover a meal. The company informs that the insulin only remains in the bloodstream during the time period the diabetic needs it, promising a safer and simpler approach.
The extended action of injectables may lead to hypoglycemia; the insulin often lingers too long
In this graph, which you can click to enlarge, we can see the long tail of both meal time analogues and regular insulin. Analogue prandial insulin is dosed approx 15 minutes before a meal, peaks in an hour, and with a duration of effect of 4 hours. Regular insulin is dosed 30 minutes before a meal, peaks in 2 hours and lingers up to 6 hours in the bloodstream. This slow acting tail activity often causes low blood sugar levels to occur after the glucose spike provided by the meal starts to decline. Generex states that Oral-lyn is taken right before the first bite of the meal, immediately begins to be absorbed in the inner lining of the mouth, peaks in 30 minutes, and blood sugar levels cleanly return to baseline within two hours. Generex finds there is no tail of activity with Oral-lyn as there is with all other forms of injectable insulin, so they believe the risk of postprandial hypoglycemia is greatly minimized. If blood levels are back at baseline after the meal, there is no reason to gorge on post meal snacks to offset any lingering insulin, which helps avoid unhealthy weight gain. The unique time action profile for Oral-lyn, if proven in the Phase III study, may provide greater flexibility in usage, as well as the ability to take small dose sprays before a snack when that tasty treat simply can not be resisted. Another main advantage for Oral-lyn may be its ability to mimic the first-phase insulin response seen in a healthy person. This first-phase insulin release is one of the first functions that people with diabetes lose. In healthy people our bodies release insulin within 10 minutes after eating.
Oral-lyn Buccal Insulin X-RAY imagery proves no deposition into the lungs
Unlike Mannkind's Afrezza, in which a powder insulin formulation is inhaled into and absorbed by the lungs, Oral-lyn is delivered as a fine spray to the buccal cavity by the RapidMist delivery system. Generex states the result is rapid insulin absorption through the buccal mucosal lining of the mouth without pulmonary (lung) exposure. The lungs, like all other vital organs in the body, are already a target of diabetes leading to lower lung function over time. The lungs are meant to process gasses, and not proteins. I think that Generex, via Oral-lyn buccal insulin, avoids potential pulmonary complications in a simpler and safer approach. Click on the provided X-Ray image to learn more.
Prandial insulin dosing is now as simple as a spray
Oral-lyn is available in a US FDA approved Treatment IND as well as in Phase III trials as a 1 UNIT per spray dose. For Oral-lyn, the delivery devise appears built to provide fine tuning post meal dosing. It appears as simple as taking another quick spray. In my opinion, as the safety concerns swirl around prospects for inhalable insulin, the Oral-lyn buccal insulin Treatment IND sounds like a great marketing advantage, since more and more diabetics and physicians will learn of buccal insulin as Generex works towards full approval.
Generex Oral-lyn Buccal Insulin
"Patients who are needle averse face a serious barrier to their recommended treatment," warns Generex "Generex Oral-lyn promises a pain-free alternative to injectable insulin, which is good news especially for older patients and children who find needles uncomfortable." Click on the image provided above to learn more about aversion to injections and diabetes.
Dr Gerald Bernstein, VP Medical Affairs Generex, former President of American Diabetes Association
Click on the photo of Dr Bernstein to view his interview on FOX Health. Dr Bernstein recently commented further on the unique safety profile for Oral-lyn: "It’s extremely safe by all the studies that have been done so far, including two years in animal tests. We haven’t seen allergic reaction. The lining of the mouth hasn’t shown any abnormalities. The buccal mucosa is an extra-tough and resilient tissue, it’s beaten up all the time. People bite themselves or burn themselves. Whatever doesn’t get absorbed is going to go to the stomach. Now the insulin molecule is unprotected and therefore it will be denatured by the acid and then broken down. There are no side effects." Dr Bernstein is an attending physician at Beth Israel Medical Center, and physician emeritus at Lenox Hill Hospital and Montefiore Medical Center, all in New York. He was formerly Director of the Beth Israel Health Care Systems Diabetes Management Program. Dr. Bernstein was president of the American Diabetes Association in 1998-99 and was for many years a member of the ADA's Board of Directors and its Executive Committee. He received the ADA's Banting Medal for Service in 1999. Dr. Bernstein presently serves on several ADA committees and on the Board of Directors of the American Diabetes Association Research Foundation.
Buccal Absorbtion
RapidMist Buccal Drug Delivery Device
