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In December 2011, FARE (through its predecessor organization FAI) acquired a 42 percent interest in ARC for $500,000. On June 15, 2012, FAI issued ARC an unsecured convertible promissory note in the amount of 750,000. The note included 3 percent simple interest accrued on the unpaid principal. The note contained a conversion feature to purchase series A preferred stock at a purchase price of 85 percent of the share price offered to investors. At December 31, 2012, the excess equity in ARC losses over FARE’s investment in ARC of $139,325 was recognized by FARE and reduced the carrying amount of the convertible promissory note as discussed in Note 1. FARE had no further obligations or commitments to provide additional support to ARC.
On February 8, 2013, FARE converted its promissory note and related accrued interest of $14,486 into 527,232 shares of series A preferred stock and purchased an additional 1,029,412 shares of series A preferred stock of ARC at $1.70 per share or $1,750,000. On February 20, 2013, FARE purchased an additional 500,000 shares of series A preferred stock of ARC at $1.70 per share or $850,000. There was an additional issuance of series A preferred stock in April 2013 to other third-party investors which resulted in a dilution of FARE’s ownership interest in ARC.
At December 31, 2013, FARE owned 2,056,644 shares of series A preferred stock and 925,926 shares of common stock of ARC representing approximately 20.42 percent of the 10,071,352 shares of series A preferred stock and approximately 21.08 percent of the 4,391,676 shares of common stock issued by ARC. FARE’s ownership of common stock and series A preferred stock represents a 20.62 percent interest in the outstanding shares of ARC.
About Aimmune Therapeutics
Aimmune Therapeutics, Inc., founded in 2011 as Allergen Research Corporation (ARC), is a clinical-stage biopharmaceutical company developing treatments for peanut and other food allergies. Aimmune Therapeutics’ characterized oral desensitization immunotherapy (CODIT™) system, an approach to oral immunotherapy (OIT), combines proprietary product candidates with gradual, controlled up-dosing protocols to obtain meaningful desensitization to food allergens. Aimmune Therapeutics recently completed a Phase 2 study of its lead product, AR101, a highly characterized, complex mixture of naturally occurring proteins and pharmaceutical-grade ingredients for the treatment of peanut allergy, one of the most common food allergies. For more information, please see [url=http://www.aimmune.com]www.aimmune.com[/url].
Thus, in addition to the unmet medical need, food allergies can impose a significant quality of life burden.
"We are very pleased by the results of this study and see it as an important step toward addressing the stress and anxiety patients and their caregivers feel around the possibility of an accidental exposure to peanut," said Stephen Dilly, M.B.B.S., Ph.D., chief executive officer of Aimmune Therapeutics.
Red Flag Raised Over Long-term Efficacy of Oral Immunotherapy
Kate JohnsonFebruary 26, 2013
SAN ANTONIO, Texas — After oral immunotherapy for milk allergy, the initial benefits sometimes wear off and reactions can return more aggressively than before, according to the first long-term follow-up of children.
"We had a high degree of optimism," senior investigator Robert Wood, MD, director of pediatric allergy and immunology at Johns Hopkins University in Baltimore, Maryland, told reporters attending a news conference. "I'm not saying we've lost that optimism, but it has certainly been tempered by looking at where these kids stand 3 to 5 years out."
The study results were presented here at American Academy of Allergy, Asthma & Immunology 2013 Annual Meeting by lead investigator Corinne Keet, MD, also from Johns Hopkins University. "These results underline the fact that oral immunotherapy for food allergy is not yet ready for clinical practice," she said. Moving forward, long-term follow-up of oral immunotherapy will be essential, she noted.
Oral immunotherapy for food allergy is not yet ready for clinical practice.
Dr. Wood told Medscape Medical News that despite initial excitement in the field, the findings are discouraging because they suggest that treatment cessation might not be an option for some patients.
"Some of them probably do require consistent lifetime exposure to stay protected," he said. "We've worried that a patient may leave a study with a false sense of security.... Some of the more dramatic failures were kids that looked like absolute successes at the end of the study."
The investigators followed 32 children from 2 previous randomized trials (J Allergy Clin Immunol. 2008;122:1154-1560 and 2012;129:448-455). After those children completed their initial oral immunotherapy for milk and passed an oral food challenge for milk protein, they were sent home with instructions to continue consumption.
A median of 4.5 years after the start of their therapy and 3 to 15 months after treatment cessation, the investigators questioned the children about their milk consumption and symptoms, and tested their blood for milk-specific immunoglobulin (Ig)E and IgG4.
They found that only 19% of children were consuming uncooked cow's milk in an unrestricted fashion; 31% had restricted their intake, but consumed at least 1 serving per day.
Table. Milk Consumption After Immunotherapy Cessation
Milk Consumption Patients (%)
Unrestricted 19
≥1 uncooked serving/d 31
<1 uncooked serving/d 28
Only minimal or baked 6
None 16
"So roughly 50% of subjects were consuming at least 1 serving per day," said Dr. Keet. However, the symptoms reported were disappointing, she noted.
"We initially thought that most subjects were doing quite well after these milk oral immunotherapy studies, but we found that 3 to 5 years after their desensitization, only 25% are consuming milk without symptoms at all," Dr. Keet said.
Table. Symptoms After Milk Consumption
Symptoms Patients (%)
None 25
Occasional 22
Frequent and predictable 38
No milk consumption 16
A total of 31% of children reported a systemic reaction to milk consumption, and 19% had used at least 1 dose of epinephrine.
"We initially thought that with continued milk consumption, subjects would have fewer and fewer symptoms, but we found that some subjects became far more reactive than they had been early in therapy," Dr. Keet explained.
This is still a potentially dangerous therapy.
Session moderator Stacie Jones, MD, told Medscape Medical News that "this is still a potentially dangerous therapy."
"It's great that we are seeing these very exciting clinical results in oral immunotherapy — particularly for egg, milk, and peanut — early on," said Dr. Jones, who is from the Arkansas Children's Hospital in Little Rock. "But the warning is that these effects may not be long lasting."
Asked why he thinks the initial benefits of oral immunotherapy can wear off, Dr. Wood said that many patients continue to avoid milk, even if they have passed an oral milk challenge test. With continued avoidance, symptoms can recur, he noted.
"Everyone left the protocol on an individually prescribed dose of milk," Dr. Wood explained. However, "kids who are allergic to food don't tend to like that food.... The main thing I've come to believe is that they self-restricted because they didn't like the side effects, so they were not as protected as we believed."
The presenters have disclosed no relevant financial relationships.
American Academy of Allergy, Asthma & Immunology (AAAAI) 2013 Annual Meeting: Abstract 467. Presented February 24, 2013.
Medscape Medical News © 2013 WebMD, LLC
In addition, it is important to recognize that the risk if OIT extends far beyond the use of epinephrine. Because adverse events were not systematically collected for these patients, we do not have any idea about the rate of less-severe reactions, the number of reactions that required treatment with other medications or that resulted in emergency department visits or even severe reactions for which epinephrine was not administered. Information also was not provided on the development of eosinophilic esophagitis, which had previously been reported by one of these practices to occur in at least 10% of their patients treated with peanut OIT.7
Because this was not a clinical trial, institutional review board and/or US Food and Drug Administration approval was not necessarily required. Although 2 sites did have institutional review board approval for OIT treatment, the other 3 only had approval for retrospective chart reviews. The investigators state that all the patients and their parents were provided detailed information, including discussions about “the unproven nature of the treatment,” and that a consent was signed by all the participants. However, we are concerned that the information provided may not have been completely unbiased, in that a brief look at the Web sites of these practices revealed statements such as OIT “is a safe and effective treatment to desensitize patients with peanut allergy,” and that it “can provide a long-term solution for patients with peanut, egg, milk, or other food allergies. At the end of this 3-6 month program, patients should be able to consume these foods with no allergic reactions.” We believe that such claims are potentially misleading and certainly not justified by the current state of research in this field, including the report of Wasserman et al4 itself. We strongly recommend that these experimental treatments still be provided only under the oversight of institutional review boards and the US Food and Drug Administration.
In addition to risk-benefit considerations, it also is important to consider cost in the development of new treatments for any condition. Because we do not know how patients included in the report by Wasserman et al4 were billed for their treatments, we are not able to provide a clear assessment in this regard. It is clear, however, that this treatment requires frequent, time-consuming office visits, and, in some cases, the costs for provision of the treatment materials. Without treatment, we would expect that most patients with peanut allergy would require only an annual office visit and a rare emergency department visit. Because costs for epinephrine or other medications are not reduced by this treatment, it would appear that the overall cost of care would increase dramatically with treatment compared with the current standard of care. It may well be that the long-term outcomes of treatment will clearly justify these costs, but this will not be known until the appropriate clinical trials have been conducted. Furthermore, we would presume that the cost for this treatment currently represents an out-of-pocket expense for most patients, although the Web site of one of the investigators does state that “most insurance policies cover this treatment.”
In the highlights of this report, the investigators conclude that “this study suggests that some allergists may be able to offer oral immunotherapy for peanut allergy.” In fact, there are a variety of unproven therapies that we could offer but that does not necessarily mean that it is the right thing to do. Furthermore, very few, if any, of other unproven treatments for food allergy carry the risk of anaphylaxis. Even more importantly, this treatment is not only unproven in the short term, it is completely unproven with regard to longer-term results. This concern was clearly evidenced in the recent study by Keet et al8 on the long-term outcomes of milk OIT, in which they found that many patients regained significant reactivity, sometimes with very severe reactions, after having an apparent short-term treatment success. In our estimation, these long-term concerns are far more worrisome than the short-term concerns related simply to the risk of reactions while on treatment. The greatest risks of OIT may not be apparent until after treatment, when the patients may be at true risk of anaphylaxis but living with a false sense of security and potentially without epinephrine. These concerns are further magnified by studies demonstrating that protection after OIT may be lost with even brief periods of avoidance.9
'Undue influence by donors' is the number-one issue in fundraising today, says Jon Dellandrea, PhD, vice president and chief development officer, University of Toronto. With donors increasingly seeking philanthropic control, fundraisers are more likely to encounter directions that push ethical boundaries. No prescribed answers exist -- it's a matter of case-by-case negotiation and judgment -- but nonprofit mission statements, tax law, and AFP codes and standards do provide guidance. Here are a few reminders, in a nutshell:
26 USC Section 501(c)(3): Exempt organizations must operate exclusively for exempt purposes; no earnings may inure to private benefit.
AFP's Statement of Ethical Principles: Charitable fundraisers have obligations to (a) honor public trust, (b) adhere to a nonprofit's standards and plans, (c) consider affected individuals, and (d) avoid the appearance of impropriety.
AFP Standards of Professional Practice 1 and 2: These standards (a) prohibit conflicts with fiduciary obligations and (b) require disclosure of real or potential conflicts of interest.
Why regulate pharmaceutical promotion?
The pharmaceutical industry provides a valuable and legitimate contribution to society. At the same time, the pharmaceutical industry is a business and its profits are heavily dependent on marketing. The greater the volume of medicines sold, the greater the return on investments. Promotion is a key factor driving sales volumes. As the examples in the introduction show, when product sales are given priority over public health, promotion can lead to over-prescribing as well as poor quality prescribing and medicine use. This, in turn, leads to an increased risk of adverse effects and higher health-care costs. Prescribers often find themselves trapped between patients' needs and health-care priorities on the one hand and promotional influences on the other. Dual allegiances and conflicts of interest can cloud judgement and cause distortions in both the delivery of health care and the conduct of research in medicine.
We've probably all read this but posting on some longitudinal observations of OIT.
[url]http://www.medscape.com/viewarticle/779896[/url]QuoteRed Flag Raised Over Long-term Efficacy of Oral Immunotherapy
Kate JohnsonFebruary 26, 2013
SAN ANTONIO, Texas — After oral immunotherapy for milk allergy, the initial benefits sometimes wear off and reactions can return more aggressively than before, according to the first long-term follow-up of children.
"We had a high degree of optimism," senior investigator Robert Wood, MD, director of pediatric allergy and immunology at Johns Hopkins University in Baltimore, Maryland, told reporters attending a news conference. "I'm not saying we've lost that optimism, but it has certainly been tempered by looking at where these kids stand 3 to 5 years out."
The study results were presented here at American Academy of Allergy, Asthma & Immunology 2013 Annual Meeting by lead investigator Corinne Keet, MD, also from Johns Hopkins University. "These results underline the fact that oral immunotherapy for food allergy is not yet ready for clinical practice," she said. Moving forward, long-term follow-up of oral immunotherapy will be essential, she noted.
Oral immunotherapy for food allergy is not yet ready for clinical practice.
Dr. Wood told Medscape Medical News that despite initial excitement in the field, the findings are discouraging because they suggest that treatment cessation might not be an option for some patients.
"Some of them probably do require consistent lifetime exposure to stay protected," he said. "We've worried that a patient may leave a study with a false sense of security.... Some of the more dramatic failures were kids that looked like absolute successes at the end of the study."
The investigators followed 32 children from 2 previous randomized trials (J Allergy Clin Immunol. 2008;122:1154-1560 and 2012;129:448-455). After those children completed their initial oral immunotherapy for milk and passed an oral food challenge for milk protein, they were sent home with instructions to continue consumption.
A median of 4.5 years after the start of their therapy and 3 to 15 months after treatment cessation, the investigators questioned the children about their milk consumption and symptoms, and tested their blood for milk-specific immunoglobulin (Ig)E and IgG4.
They found that only 19% of children were consuming uncooked cow's milk in an unrestricted fashion; 31% had restricted their intake, but consumed at least 1 serving per day.
Table. Milk Consumption After Immunotherapy Cessation
Milk Consumption Patients (%)
Unrestricted 19
≥1 uncooked serving/d 31
<1 uncooked serving/d 28
Only minimal or baked 6
None 16
"So roughly 50% of subjects were consuming at least 1 serving per day," said Dr. Keet. However, the symptoms reported were disappointing, she noted.
"We initially thought that most subjects were doing quite well after these milk oral immunotherapy studies, but we found that 3 to 5 years after their desensitization, only 25% are consuming milk without symptoms at all," Dr. Keet said.
Table. Symptoms After Milk Consumption
Symptoms Patients (%)
None 25
Occasional 22
Frequent and predictable 38
No milk consumption 16
A total of 31% of children reported a systemic reaction to milk consumption, and 19% had used at least 1 dose of epinephrine.
"We initially thought that with continued milk consumption, subjects would have fewer and fewer symptoms, but we found that some subjects became far more reactive than they had been early in therapy," Dr. Keet explained.
This is still a potentially dangerous therapy.
Session moderator Stacie Jones, MD, told Medscape Medical News that "this is still a potentially dangerous therapy."
"It's great that we are seeing these very exciting clinical results in oral immunotherapy — particularly for egg, milk, and peanut — early on," said Dr. Jones, who is from the Arkansas Children's Hospital in Little Rock. "But the warning is that these effects may not be long lasting."
Asked why he thinks the initial benefits of oral immunotherapy can wear off, Dr. Wood said that many patients continue to avoid milk, even if they have passed an oral milk challenge test. With continued avoidance, symptoms can recur, he noted.
"Everyone left the protocol on an individually prescribed dose of milk," Dr. Wood explained. However, "kids who are allergic to food don't tend to like that food.... The main thing I've come to believe is that they self-restricted because they didn't like the side effects, so they were not as protected as we believed."
The presenters have disclosed no relevant financial relationships.
American Academy of Allergy, Asthma & Immunology (AAAAI) 2013 Annual Meeting: Abstract 467. Presented February 24, 2013.
Medscape Medical News © 2013 WebMD, LLC
The private U.S.-based Aimmune Therapeutics -- formerly Allergen Research Corporation -- is also working on a pill called AR101 that will help allergy sufferers become desensitized to peanuts.
Good WaPo on translation-focused disease orgs; deserves less cynical headline wapo.st/1C3qYwU my '12 Atlantic: theatlantic.com/health/archive…
“They no longer had to solve the science problem. . . . What they needed was drugs,” he said. “If you need to solve a science problem, venture philanthropy is probably not right for you.”
The result has been two systems that operate nearly independently, yet fundamentally, should be seamlessly connected; industry is absolutely dependent on the creativity-driven research of university scientists, and these scientists in turn absolutely require industry to develop their preliminary ideas into reliable products (and could probably also benefit from the opportunity to pressure-test their results in a rigorous and systematic fashion).
And now that the FDA is getting ready to approve Aimmune, FARE says, "Note from FARE: FARE provided seed funding for Aimmune, formerly known as Allergen Research Corporation (ARC), after convening its 2011 Research Retreat. The retreat brought together leading scientists from all over the world and helped to frame key challenges with advancing oral immunotherapy through the FDA approval process, including the lack of a standardized product that could be tested in clinical trials on a broad scale. ARC sought to solve those problems, and with seed funding from FARE and other investors was able to create a standardized peanut OIT product that is being tested in Phase III clinical trials.
As an initial investor, FARE continues to hold stock in Aimmune, but we do not have any involvement with the governance or day-to-day workings of the company. This information was disclosed to the FDA."
[url]http://blog.foodallergy.org/2016/01/26/fare-urges-fda-to-help-meet-the-unmet-need-for-food-allergy-therapeutics/?tr=y&auid=16421601[/url]
So when FARE "discovers and endorses" OIT suddenly in 2018-2019, they will be simply re-creating what Dr. Burks declared in 2009 : "These initial results suggest that food specific OIT is safe and effective in attaining desensitization. Although desensitization in itself is better than complete avoidance, the induction of tolerance would be the ultimate goal."
The Burks Duke protocol of 2009 is no different than the Burks Aiummune/peanut pill of 2018, even down to being sourced from Golden Peanut Company of Alpharetta, GA and ending at a dose of 300 mg which requires strict avoidance. Oh and the fact that the peanut pill "drug" will only contain 3 of the 9 proteins that cause anaphylaxis. But it will make $1.33 billion.
So what's different between 2009 and 2019? Just that 10 years of OIT has been withheld from food allergic kids. And the $1.33 billion.
12/2009: [url]http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3650994/[/url]
8/2009: [url]http://www.jacionline.org/article/S0091-6749(09)00813-6/fulltext[/url]
Missing proteins in Aimmune: [url]http://asthmaallergieschildren.com/2015/09/10/new-peanut-therapy-gets-fast-tracked/#sthash.sGHDH1II.dpuf[/url]
And I would hope, down the road, that there would be studies as to OIT and comparison of straight-from-manufacturer peanut flour use vs. Aimmune's patented peanut flour based product.
Of course, this would take years and assume that OIT remains a viable treatment for desensitizing as to LTFA.
The jury is still out.
Pondering . . . wonder if the proteins removed from Aimmune might be culprits in exacerbating or creating EoE and that is why there would be this change too?
Ultimately, the decision to enter private practice OIT is an individual one that should be reached after extensive consultation between a patient and his/her allergist including an assessment of the involved risk. We believe the discussions around starting OIT should occur in a manner akin to the informed consent procedures in a clinical trial setting.