R.J Steffens

Oral-lyn vs. Afresa: How Generex Will Beat Mannkind

Bob, your link to the EASD abstracts is what I am speaking about in the articles. What I am concerned about is what happens to lung function after years of chronic usage of this or any inhalable insulin? Mannkind is vying for approval of Afresa and the MedTone device, and wishes to change from the MedTone to the newer Dreamboat. These abstracts are for the MedTone device and I understand decreases in FEV1 return to levels typically seen in diabetics "3 months after cessation" (discontinuing) of Afresa treatment. That bodes well in a sense because there are no structural changes within lung tissue at that point. But long term chronic usage without cessation? A diabetics lung function decreases faster than a healthy person. Diabetes is attacking even this vital organ and insulin treatment, unless new advances come along, are a lifetime burden.

Also, with the Dreamboat device delivering the insulin powder deep into the lung at a better rate than the MedTone, are the previous studies with MedTone relevant? Since Mannkind believes (and I agree they have a reputable team) a short bioequivalance study is all that the FDA may require, the answer very well may be yes. And then time will tell the true tale.

PS. The links in the SA articles about Oral-lyn lead to previously accepted ADA Scientific Session abstracts. I believe you when you say you "have no interest in learning much more about" Generex or Oral-lyn. Before you can learn more about a new drug, you may want to actually begin. To help, the reason the Phase III trial is vs. regular human injectable insulin is due to the fact that this is the main protocol required of developmental prandial insulins to gain FDA approval- with establishment of A1C non-inferiority being the main endpoint. And Generex's Oral-lyn IS a liquid formulation of human insulin. Buccal insulin is a very fast acting human insulin with a short duration of effect. One reason it is so fast has to do with the usual hexamer is broken up into monomers during the formulation process. So while this is a human insulin, it acts more like an improved version of a meal time analogue. The short acting nature of Oral-lyn, which is shorter than even Afresa, is the reason it carries less risk of hypoglycemia than anything currently on the market today.

For anyone, in contrast to Silent Bob, that wants to learn more about Oral-lyn they can view this PDF by Dr Gerald Bernstein from a few years back:

www.iptonline.com/arti...

Or listen to his latest broadcast on Health Radio when, or after, it becomes available on November 23rd:

healthradio.net/compon...

I am glad we helped Bob get over his silent problem.

Oral-lyn vs. Afresa: How Generex Will Beat Mannkind

sstrumello: "For the type 2 universe, I question that, as a large majority of insulin-using type 2's take basal insulin only, usually Lantus or Levemir. Is that going to make Oral-lyn (or Afresa) a hit with that group?"

Hi ss. A fast acting prandial insulin with a friendly and non-invasive delivery device is going to compete not only with other meal time insulins, but with the new class of type 2 oral pills. We read about safety issues concerning Avandia and Byetta every week, and what the developers of Oral-lyn will hope to see is some of those patients switching to their insulin. But as for basal control, no, that is not what Oral-lyn or any prandial insulin provides. I believe they are at the early stages of developing a buccal basal insulin, but they haven't made any formal announcements in that area.

ss: "you seem to blatantly neglects the fact that the draft guidance for the pharmaceutical and biotechnology industry issued by the FDA last year for "Diabetes Mellitus: Developing Drugs and Therapeutic Biologics for Treatment and Prevention" was, after public comments, revised to address ONLY type 2 medicines."

I didn't mention the latest FDA draft guidance in this article. But I am very aware of the guidance and wrote about it in another article concerning Oral-lyn and Afresa (TI): "In general, the FDA wants companies to exceed previous expectations considering the growing diabetes population and the increased complexity of treatments, but it will be an absolute stickler with those drugs exhibiting serious side effects."

seekingalpha.com/artic...

ss: "therefore the final guidance released was only for type 2 drugs, therefore insulin was excluded."

No, a section of the report focused on inhalable insulin. That is also a reaason we see more patients enrolled in trials for certain drugs such as Afresa, or a type 2 oral pill with safety concerns. Those safety issues are not as dramatic in studies of buccal insulin.

ss: "If a company wants to succeed in selling insulin, they absolutely MUST reach the type 1 audience, and so far, Generx is ignoring that group, just as Pfizer did with Exubera."

No, that is the group Generex is targeting. They are vying for approval of Oral-lyn in Type 1 diabetes before they make a submission for Type 2 patients. Although, through the FDA approved Treatment IND they are providing Oral-lyn to the full spectrum of diabetic patients in the US.

Oral-lyn vs. Afresa: How Generex Will Beat Mannkind

Silent Bob: "Their other studies are usually not comparing versus other insulin"'

Hi Bob. That is simply not true. If you click on the links in the article you can see a couple exmaples, and it would also not be hard to do a little dd in finding many other trials vs. injectable meal time insulin.

Silent Bob: "They did not even have the guts to take on rapid acting insulin, probably because they knew Oralyn is inferior to rapid acting insulin."

Try this Bob: "The year-long Oral-lyn study examined 26 subjects with type-1 diabetes. Members of the control study group received insulin glargine (an insulin analogue) once a day as their basal dose, and a faster-acting insulin analogue before meals. Members of the treatment group received a non-analogue long-acting insulin twice a day as their basal insulin; before meals they took Oral-lyn, a liquid formulation of regular human insulin, developed by Generex, that is absorbed through the lining of the mouth. Study results consistently and clearly illustrate the rapid onset of action and superb glycemic control of Oral-lyn as compared to the analogues. / "When Oral-lyn is absorbed through the buccal mucosa its rapid entry into the blood stream mimics and improves upon the rapid acting analogues." commented Dr. Jaime Guevara, a study author and clinician that has conducted studies for Generex's Oral-lyn."

seekingalpha.com/artic...

Silent Bob: "The author says a lot of nonsense about Afresa but I don't think I should write about that again."

I have been following and writing about these companies for a few years. I admire Mr. Mann, but in making my case I tried to present a thoughtful reasoning on why I feel adding an inhalable insulin to a diabetic patients is problematic since it has been shown that their lung function is already decreasing at a more dramatic rate than in people without the disease. I sited research that reported these findings, but I can understand why you would not want anyone to mention the subject again. When you state the Generex is a trainwreck, when in reality the are a small biotech R and D with a very promising pipeline of diabetes and vaccine candidates it sounds as if you are more concerned with the performance of a stock while I am focused on the potential of the drugs. To say that "GNBT is scamming investors" tells us more about you than it does about Generex. Best of luck in your investment.

ADA's 68th Scientific Sessions: A New Look at Insulin Therapy

"the downtrend was not accompanied by any vlome to speak of, and that is the only are that is comforting. ;)"

I'll redo that one! LOL. I was watching the Yankee game and typing.

The downtrend was not accompanied by any substantial volume, and that is an area we may draw comfort. ;)

ADA's 68th Scientific Sessions: A New Look at Insulin Therapy

I think part of the problem has to do with the overall state of the market and how that has caused some problems for baby microcap biotechs such as Generex. All of the news coming from Generex has been positive- from new Phase II data for Oral-lyn regarding a one year and 372 day study in Type 1 diabetes to the positive AE37 results that were just published with the USMCI and Walter Reed in the Journal of Clinical Oncology.

If we look at what they are doing in the clinic, which is what is important, we see they have one Phase III (Oral-lyn) and one Phase II (AE37 in breast cancer) underway for drugs targeting diabetes and cancer. Metcontrol Gum will probably be an Abbreviated Submission and their next trial looks set to begin. The wholly owned subsidiary, Antigen Express, also has two Phase I's that are dosing and three other vaccines (AE37 Combo with/and funded by Mary Crowley Medical, the melanoma vaccine with the Mayo Clinic, and the RNAi/Ii-key with Dr. Daopei Lu in Beijing) getting ready for human trials. The HIV DNA vaccine could pop up sometime in late 2008.

But financing also occured a couple of months back that may have added 30 mm shares to the outstanding total, and we will see in the 10K (Oct 2009) what the current OS total equals. That may have augmented the woes seen in the market, because there appears to be no bad news associated with the company or stock. Pending early approvals in the Middle East or Asia (China) for Oral-lyn may sneak up and lift the stock, as well as any other positive developments that the company announces.

Oral-lyn was featured on FOX News Health segment this week with Generex's Dr. Gerald Bernstein (former pres of the ADA):

www.foxnews.com/video2.../

I don't think delisting is a concern, because there is too much positive action occuring in the pipeline. They have 180 days to regain compliance and that should offer them enough room for announcing the type of news that will generate investor confidence. the downtrend was not accompanied by any vlome to speak of, and that is the only are that is comforting. ;)

ADA's 68th Scientific Sessions: A New Look at Insulin Therapy

There was a link in a posted comment there to an article about the event that I was talking about as being well written. Now I don't see it. That's funny, but I guess I'll now take the compliment to myself. LOL.

Mannkind: Overlooked Biotech With Excellent Prospects (Part VI)

Daddy One: Upon FDA approval of TI, your eleven year old daughter would have to wait until she is 18 to take this inhalable insulin product. Mannkind is not studying TI on children, and Exubera was not approved for diabetics under age 18. The prevailing thought has been that their young lungs are not well suited for insulin delivery through this vital organ. Many would include adults in this category and that one of Mannkind's marketing hurdles which they will be hard pressed to overcome. It will take many more years of Phase IV testing for this barrier to be put to rest- 'if' long term post approval safety results prove positive. Oral-lyn, the buccal insulin spray that has been mentioned, is also a 'rapid' acting insulin with a short duration of action and has been successfully studied in Type 1 juveniles in 2007.

It appears that your daughter has a good dad on her side, so she is a lucky girl.

Ahithophel Weissberger has done a nice job presenting his opinions. But I don't think the market is pricing in a discount with the thought the FDA will not approve TI. I think the market feels even after approval, TI would require a massive and costly orientation effort and sales potential that do not match the high burn rate and cummalitive losses. Commercial success is not tested in a clinic. Unfortunatly, Exubera did not pave the way for inhalable delivery systems and burned downed the bridge. The marketing and orientation campaigns could restore some of what has been lost in the public percetption, but how much would a potential partner be willing to risk?

The efforts of these companies are impressive and worthy. Watching market reaction to Mannkind's Phase III studies will certainly be interesting. Maybe A.W. is right that this was a good time to buy, and all of the concerns do not matter when you take your POP and run. I'm not sure, and eagerly wait to see what a partner would pay and if one can be found. If I am not mistaken, Mannkind has an unused $500 mm SHELF available. This could help them 'go it alone". But continued dilution is a concern of all biotechs, and especially when the biotech burns close to $70 to $100 mm per quarter.

Thanks for your efforts, A.W. For this reader, you have provided a well written and interesting series of articles in an area I am very interested. Hopefully, in time, we will discuss the many novel insulin delivery options available to diabetics in a new age of care. At some point, those needles will be seen as a very unnatural way to deliver a protein and a relic of the medicinal past. These biotechnology companies, such as Mannkind and Generex, are trying to be one of the solutions and that is a respectable business goal.

Best of luck to us all, and especially the eleven year old diabetic.

Mannkind: Overlooked Biotech With Excellent Prospects (Part IV)

PS. I hope you delve into the GLP1 product. I also wanted to use my real name and step into the light. The psuedos sometimes fall into default and cause confusion. Neither of us are psuedoname types of people. Keep up the good work.

Mannkind: Overlooked Biotech With Excellent Prospects (Part IV)

Hi Ahithophel. You have interesting thoughts and I look foward to your articles. I wrote a few about another biotech- Generex. Terms for a partnership should be more lucrative considering Mannkind has brought Technosphere into Phase III alone. They have done a great job and efficacy seems clear. The main concern to a potential partner would be the odds of success for another "inhalable" insulin and perhaps long term safety issues. All of the data Mannkind presents could show could be very positive, but diabetics and endros may shun another inhalable until time erases doubt. Not all, but a percentage. Right now this large marketing hurdles. That would bring with it a huge orientation and educational need, on top of what already would be needed for any new delivery option.

The regional deals do remind me of Generex's position. They have signed distribution deals with Shreya Life Science in India and Bioton's Sci Gen in the China region. The terms are unique- with the partner paying regulatory costs for submission of approval, marketing, educational and be responsible for sales and distribution. They also provide the insulin crystals used to make their Oral-lyn buccal spray. (Oral-lyn is not an inhalable.) For the US and other large markets, we do not know if a more typical partnership will ensue. Generex has also brought there product to Phase III and for such a tiny firm this was a great accomplishment:

Friday, June 13, 2008

Biomed Notebook
By Ryan McBride
Oral insulin back in Worcester

<In the turbulent business of developing insulin taken orally rather than by injection, a Canadian biotech with R&D operations in Worcester hopes to pick up where such drug industry giants as Pfizer Inc. and Eli Lilly & Co. left off.

Generex Biotechnology Corp., a Toronto-based firm with a 12-person lab in Massachusetts, said last week it has launched a Phase 3 clinical trial of an oral insulin spray. Once seen as a Holy Grail of drug delivery, orally administered insulin has lost some luster because New York’s Pfizer, Eli Lilly of Indianapolis, Denmark’s Novo Nordisk AS have all pulled the plug on inhaled insulin programs in the past year.

No large U.S. drug companies have formed partnerships related to the oral insulin product with Generex — as Eli Lilly did with Cambridge biotech firm Alkermes Inc. — but Generex CEO Anna Gluskin indicated that her firm wouldn’t jump into a partnership without a big payday. “They are the ones that failed,” Gluskin said of Pfizer, Lilly and Novo. “So they really have to look at paying us a lot of money.”>

www.masshightech.com/s...

I hope they ALL succeed and give diabetics the choice they deserve. That would be a welcome change from a prison sentance of needles. It will be interesting to see how this plays out for Mannkind and what kind of terms they could now procure. From the strong efforts of Mannkind to the novel system developed by Generex, a new dawn in diabetic care is near.

Mannkind: Overlooked Biotech With Excellent Prospects (Part III)

Ahit- As a supportor of Mannkind, I must say your comments regarding a competitor appear out of line. Keep in mind that this small Generex firm has it's oral insulin research led by a former ADA President. So never underestimate the rest of the field. The debators were actually informative and presented a seemingly factual and educated alternate view. Your own analysis needs to stand on a foundation of factual DD, and nothing short. Anyway, thanks for the articles and please keep it positive. The overall writings on TI have been an interesting read.

Mannkind: Overlooked Biotech With Excellent Prospects (Part III)

You say: "I agree with you that it is likely that the FDA will want Mannkind to continue longer studies after it reaches the market, but that is a far cry from the FDA suggesting that ALL patients prescribed TI should undergo pulmonary tests."

I FIRMLY disagree, and I believe you will find any inhalable insulin product that the FDA approves will come with the condition that patients undergo pulmonary testing before and during treatment. This is costly and inconvienant. The FDA now has further and newer confirmatory evidence that lung function decreases in diabetes through the progression of the desease and hightened concern as a result of the Exubera's follies. They will be careful and safety comes before your $2.95 investment.

You say: "As for Generex: My information about them was taken straight out of their 10-Ks for 2005, 2006, and 2007. It speaks there clearly about the 200-patient trial and about their licensing revenue (although I believe that the licensing revenue was not recent)."

Nowhere in Generex's 10K's do they mention a 200 patient trial. You had earlier stated that "they have yet to show significant revenue -- only $67,000 in the last nine months (as of April 31, 2008), much of which is from licensing other patents of theirs." So if this licensing of patent revenue was "not recent", why would you have stated it was contained in the 9 month period ending April 31st? I will also inform you that Generex has never licensed a patent (?) and has never earned revenue in that way. Your due diligence appears to be make believe, and if you can show me this 200 person trial or revenue from licensing patents I will take my medicine. ;) Generex does have a very extensive patent portfolio for buccal delivery of insulin, peptides, and pain relief drugs such as morophine. They also have solid IP for Antigen Express's therapuetic vaccine candidates. They do not license patents but should soon license Antigen's Ii-Key technolgy. But not yet.

You say: "The amount that Generex is losing per quarter has to be taken in context of how much cash they have, which is around $25 million, much less than Mannkind. They are going to have liquidity problems far sooner than Mannkind at their respective burn rates." In your earlier response you had stated: "They may well be headed into bankruptcy (not tomorrow, but within the next 2 years) if they can't raise more money, and I don't know that they can."

The amount of cash Generex has one hand as of the quartley report issued last week is $38,450,627. That is approx 4 quarters worth of capital and their recent financing arrangement contains warrants that when exercised brings the company an additional $50+ mm plus. Generex also has a $150,000 million shelf approved by shareholders in May 2006 that is fully intact. So why would you state they may go "bankrupt" within two years? They have never had problems raising cash, and unlike Mannkind, have a manageable and respectable BURN RATE.

Mannkind'se burn rate was $99.2 million in the first quarter of '08. In the quarterly CC, CFO Pfeffer stated this burn rate will GROW in the next couple of qrtrs before falling again. He believes they have enough cash, $269.1 million, coupled with the availabiltyof a $350 line of credit from Mr Mann, to last until the end of 2009. But with a burn rate of $99.2 million in the first quarter of '08 and an anticipated increase over the next one to two quarters would leave under $100 mm by the end of the third quarter 2008. Even with the availabilty of the $350 line of credit he mentioned that is available from Mr Mann, how does he state the company is able to fund operations through the end of 2009?

There is a greater cause for concern for Mannkind's high spending ways and not for tiny Generex's modest $7 to $9 burn per quarter. Revenue from India or another country may also help augment their cash needs. Shreya already placed an order for $2.1 mm, so next quarter Generex has 25% of the quarter paid for. And as I illustrated, they do NOT have a current cash crises. Mannkind does presently have this grave concern associated with it's cash position as noted by Grant Zeng a senior analyst covering the biotechnology industry for Zacks Equity Research in a recent report:

We have a Sell rating on Mannkind based on our general negative view on the inhaled insulin segment. MNKD relies heavily on inhaled insulin program with a very weak pipeline. Also, the company is burning cash at a too high rate and cash position is a matter of great concern. www.istockanalyst.com/...~zoneid_Home.html

You state regarding the FDA's Draft Guidance: "But the parts that I quoted (about the necessary size and length of trials) were from the general part about ALL diabetes medications. I suggest that you reread it to ascertain that for yourself... I stand by my statement that Oral-lyn has ZERO chance of being approved in the U.S. or Europe until there is a major redoing of their Phase II and Phase III trials, which would take many years."

I am very familar with the guidance and you should read it closer. The part talking about the larger sized studies deals with Type "2" diabetes and Generex does not have ANY need to redesign their Phase III study protocol which is specifically for Type "1".

I understand you want your investment to increase in value and with a strong CEO you have reason for optimism, but TI will have one heck of a marketing disadvantage with diabetics weary of inhalable insulin and Mannkind is a company burning cash at an alarming rate. Blockbuster status would be needed to ever gain profitability and that is not the case for Oral-lyn. In one year Mannkind burned more cash then Generex has since it was founded. Mr Mann would need massive sales to recoup the losses and is this addressed in the research report you are trying to sell for $35?

Perhaps that is why you dismiss a smaller competitor with erroneous statements and gloss over Mannkinds own obstacles. PS. I never stated that India's standards matched the USA's. The FDA has been under hightened scrutiny for approving drugs that later exhibit safety problems (Avandia comes to mind.) I said that the other countries approving Oral-lyn speak well of it's safety and efficacy results in over 1,500 patients to date. MANY of their trials all had A1C levels as a protocol endpoint. Oral-lyn ALWAYS does well and also has a rapid (hence the name Rapidmist) onset and an even more natural "offset" compared to TI. Generex's CEO simply didn't have a CEO willing to BURN $1 B of his (her) own money. Themn again, Generex's CEO doesn't have to, since their are NO pulmonary tests needed for Oral-lyn.

Good luck with your investment and I hope you can carefully check assertions you make if you wish to present yourself as a credible source of information.

Mannkind: Overlooked Biotech With Excellent Prospects (Part III)

Hi Ahithophel- Perhaps I was unclear. I am talking about how a Type 2 diabetic is already experiencing decreased lung function and how that could be further effected by ANY inhalable insulin:

Reduced Lung Capacity Accelerates with Diabetes
March 26, 2008
March 26, 2008 (Newswise) — People who have diabetes encounter a faster loss of lung capacity than those who do not have diabetes, a finding that may have implications for the potential use of inhaled insulin, according to a study appearing in the April issue of Diabetes Care.

Reduced Lung Capacity in People with Diabetes

The lung research, part of a larger investigation known as the Atherosclerosis Risk in Communities (ARIC) study, confirmed previous suggestions that the lung is a target organ for diabetic injury and that lung abnormalities accelerate once diabetes takes hold. Previous research by the same authors established that decreased lung capacity precedes and may predict a diagnosis of diabetes. The new study is accompanied by an editorial that concludes that diminished lung function may contribute to diabetes morbidity and mortality.

Specifically, the study found that people with type 2 diabetes experienced a more rapid decline in forced vital capacity, the measure of how well the lungs fill with air, than people who did not have diabetes. Though all people experience a decline in forced vital capacity as they age, people with diabetes appear to undergo a more rapid loss that appears before the diabetes diagnosis and accelerates after the disease sets in.

This could be because high blood sugar levels stiffen the lung tissue, or because the fat tissue in the chest and abdomen may confine the lungs more in people with diabetes, explained the researchers. They concluded the study with advice to clinicians to “pay heightened attention to pulmonary function in their patients with type 2 diabetes.”

“Think of the lung as a crime victim who unwittingly abets the perpetrator to hasten the demise of the host,” wrote Dr. Connie Hsia, of the University of Texas Southwestern Medical Center’s Department of Internal Medicine, in an editorial accompanying the study. She suggested that the loss of pulmonary function could add
to diabetic morbidity and mortality, and raised concerns about the potential use of inhaled insulin, since it may “trigger or exacerbate pulmonary dysfunction.” www.dlife.com/diabetes...

There is not sufficient data to state that Technosphere would not trigger pulmonary dysfunction after prolonged usage and investors should be aware of the issue. The decreased lung function condition has been confirmed to be found in more Type 2 patients, so the FDA would be wise in asking for further studies and perhaps this could be accomplished in larger sized Phase IV's.

You also made a lot of incorrect statements regarding Generex. When did Generex conduct a study on 200 patients and what revenue did it earn licensing patents? The awnser would be never and none. The only revenue Generex reported has been for Glucose Rapidspray, which is a new OTC item. Revenue has not been declared yet in tiny Ecuador and sales have not commenced in India. India is not as rich as the USA, but has a growing middle class and is home to 1/3rd of the world's diabetics. Approval in India illustrates both the unique safety profile of Oral-lyn and the clarity of the efficacy within the dossier. Also, Oral-lyn HAS been measured by final A1c levels in many of the smaller tests (totaling over 1,500 diabetcs) and has also acheived superior results in this area vs standard injection. Here is one example: professional.diabetes....

Generex's partner in India, Shreya, did recently place an initial purchase order for 210,000 cannisters of Oral-lyn and sales are hoped to BEGIN by August. Also, Is Generex losing money "hand over first?" Their burn rate was approx $9 mm last quarter and averaged $7 mm the few periods before. So Mannkind loses as much in 1 quarter as Generex does in 9. The numbers are striking. Mannkind has 600 employees and Generex has close to 25. Mannkind has two products in Phase I one in Phase III. Generex has Metcontrol Gum slated to begin the next study (the first Phase I was in 2006) this summer to help complete the Abbreviated Drug Submission, a prostate cancer in Phase 1 with Phase II to start in 2008, an avian flu vaccine in Phase I with the next study with Dr John Treanor set to start in 2008, a collaboration with the United States Military Cancer Institute for a peptide breast cancer vaccine that is in a large Phase II, and Oral-lyn now in Phase III. Their HIV vaccine is set to begin Phase I in 2008 with Dr Bruce Walker, a combo peptide vaccine Phase I for 2008 is to be entirely funded by a cancer clinic and an rnai vaccine is set to begin in the Fall. That's not too shabby for the little penny stock. ;)

The FDA's new draft guidance you mention is specifically for diabetes drugs that have certain safety issues- such as some oral pills and "inhalable" insulin. They have a whole section for inhalable insulin. Oral-lyn is a simple buccal spray and is not effected by, nor mentioned within, this draft guidance. So while Technosphere will not be approved (as you state) for asthma patients, I would also say it will not be approved for smokers, children or anyone with a weakened pulmonary condition. They could all use Oral-lyn. This year Health Canada granted Oral-lyn Special Access Authorization for Type 1's under a certain condition. That sure doesn't sound like a joke.

You state: "I see no reason why the FDA would arbitrarily recommend pulmonary tests for Technosphere Insulin if it shows no problems in that regard."

If TI is approved, I believe the FDA will certainly recommend pulmonary testing for "diabetics" (not for "TI") to see if TI usage exhibits problems in that regard. If they don't, they are not doing their job.

Mannkind: Overlooked Biotech With Excellent Prospects (Part III)

"This was yet another obstacle to prescribing Exubera, especially since most doctors treating diabetics (i.e. general practitioners and internists) do not have pulmonary testing equipment in their offices. On the other hand, Mannkind found no evidence of any drop in lung function whatsoever in their clinical trials with Technosphere Insulin."

Mannkind has not reported detailed Phase III results, and did not report the additional safety data at the ADA event like they stated they planned on doing. The did have ana abstract showing absorbtion occuring 8 minutes later for smokers then for non-smokers as measured by "tmax". The FDA, in my opnion, would require a diabetic to undergo pulmonary tests for technosphere (if it is ever approved). The diabetic already is losing lung function due to the progression of the desease:

"(5) Chronic use of inhaled insulin may affect long-term pulmonary function, while preexisting pulmonary dysfunction may alter the absorption and bioavailability of inhaled insulin."

www.ncbi.nlm.nih.gov/p...

Another worth mentioning is Generex's Oral-lyn Buccal spray. Since Oral-lyn also has a very rapid onset of action, and NO deposition into the lungs, it seems as if it would be the choice amongst diabetics between these two potential products. Technosphere is said to afford low titration and Oral-lyn provides 1 U sprays as part of a fine tune regimen. Technosphere has another large obstacle that Oral-lyn does not- TI needs to be marketed as a product that does not cause decreased lung function or lung cancer. Fair or not, that is a horrible position to be in. I wish them well, and hope they all are approved to give diabetics a new choice and lifestyle freedom. This is a freedom they have in India with Oral-lyn.

Best wishes.

ADA's 68th Scientific Sessions: A New Look at Insulin Therapy

Very well written and informative. I didn't see that much coverage of the event. This was a fresh perspective, and a fresh perspective also appears to be taking place in diabetic care.

MannKind Corp. Q1 2008 Earnings Call Transcript

Hakan Edstrom, President and Chief Operating Officer, started the presentation and overall did a good job. But the problem Mannkind faces is evident in his pre-written commentary where he spent a great deal of his time defending Techonosphere as a safe drug in development and commenting on Exubera's follies and safety concerns. Even after passing the mike to the other executives, safety issues were the bulk of the presentations. Matthew J. Pfeffer, new CFO, verbally tallied the latest quarterly numbers, but Peter Richardson, slated to talk about R and D, also was obliged to spend time dealing with echoes heard throughout the market regarding the prospects of any inhalable insulin.

CEO Alfred Mann also utilized the majority of his time debunking the notion that Pfizer's Exubera's announcement has anything to do with Technosphere. He later explained that he believes Lilly and Novo Nordisk withdrew their own inhalable insulin products from development not due to safety concerns, but because they have portfolio of injectable products that would have been forced to compete against their inhalable offerings. That reasoning doesn't make sense to me, because Lilly had previously raised concern that their inhalable insulin may effect lung function. So they did see a safety issue, and if inhalable insulin was a marketable new drug, they surely would want a piece of the pie, as is illustrated by the enormous amounts of research money they spent bringing their inhalable products into Phase III. If it were simply a matter of competing against a current line of profitable products, they would not have ever entered the fray.

Mr Mann stated the FDA will not view any safety data concerns regarding Exubera as having a class effect. But Leerink Swann analyst Bill Tanner, in a MannKind research note, quoted a "regulatory consultant" who believes "the bar has been substantially raised for TI's approvability as this safety concern will likely be treated as a class effect." So he fees that the Food and Drug Administration may indeed look at all inhalable insulin products as having the same potential problems. That would mean further safety resting for TI, or one heck of an expanded Phase IV that may skyrocket future costs.

When a banking investor phoned in to todays call he asked if Mannkind will be meeting with the FDA to address these issues before filing a NDA in December 2008. The answer was no? They state the safety data so far has been positive and the safety board associated with the Phase III trials told them to continue forward. As more analysts phoned in the overwhelming amount of questions swirled around safety data- including queries on any studies on smokers and data regarding cancer. Some data will be presenetd at this summers ADA event, but that data is NOT on humans. Will that help the matter?

These questions from the professionals themselves reveal the problem of perception and how that may suffocate any of Mannkind's hopes to make Technosphere the choice of enough diabetics to justify an upcoming $100 mm per qrtr burn rate. The burn rate was $99.2 million in the first quarter of '08. In the CC, CFO Pfeffer stated this burn rate will grow in the next couple of qrtrs before falling again. He believes they have enough cash, $269.1 million, coupled with the availabiltyof a $350 line of credit from Mr mann, to last until the end of 2009. But he stated Mannkind had a burn rate of $99.2 million in the first quarter of '08 and anticipates their cash burn may increase further over the next one to two quarters. That would leave under $100 mm by the end of the third quarter 2008. Even with the availabilty of the $350 line of credit he mentioned that is available from Mr Mann, how does he state the company is able to fund operations through the end of 2009? Is more financing implied, or is something awry in the reporting of financials?

Mr Mann stated the environment for partnership would be better after the trials are complete and data can be used to ensure the Pharmas they state are, or were, interested. But by then cash will be gone unless Mr Mann ponies another lump of his fortune, and I believe that itself presents a negotiating position of weakness.

Mr Mann actually stated something that reminded me of words from Generex's R and R analyst Navdeep Jaikaria. He said the withdrawal by PFE, NVO, and LLY from the inhalable race is a positive for Mannkind and leaves the field wide open for Technosphere. Of course, Jaikaria stated "if anything their loss is Generex's gain, as safety issues with inhalable insulin only pave the way for Oral-lyn Buccal therapy as the only viable alternative to injectables."

Technosphere may prove to be an effective and safe alternative to injectable insulin. But convincing diabetics and doctors to take a prescribe an inhalable insulin may be an unsurmountable task. I would never count out a man as successful and full of integrity as Mr Al Mann, but I think I agree with Mr Jaikaria on this one.