Khaled Mahmoud

Report on Peanut Allergy Table of contents: i. ii. iii. iv. v. vi. Introduction Epidemiology of Peanut allergy in USA Diagnosis Treatment Cost of treatment Recent advances in immunotherapy and vaccine development for peanut allergy vii. Companies in the Peanut Allergy Space viii. Regulatory ix. References Introduction Peanut allergy is one of the most common food allergies. Peanuts are not the same as tree nuts (almonds, cashews, walnuts, etc.), which grow on trees. Peanuts grow underground and are part of a different plant family, the legumes. Other examples of legumes include beans, peas, lentils, and soybeans. Being allergic to peanuts does not mean you have a greater chance of being allergic to another legume. Epidemiology of Peanut allergy in USA Childhood food allergy in the United States places a considerable economic burden on families and society. National surveys in the USA suggest that 1.1% of Americans -3 million people- are allergic to peanuts, tree nuts, or both. Similarly, data from a US National Health and Nutritional Examination Survey -) indicated that 8.6% of the Americans have skin-prick test evidence of sensitivity to peanut. In newer study in the USA, the rate of peanut allergy increased from 0.4% in 1997 to 0.8% in 2002 in young children. 1 Each year, millions of Americans have allergic reactions to their food- mainly peanut allergyresulting in 30,000 emergency room visits, 2,000 hospitalizations, and 150 deaths.2 Current estimates state that food allergies affect up to 15 million people in the United States.3Peanut allergy is the leading cause of death by anaphylaxis. In the United States, food allergies cost $24.8 billion annually.4 Diagnosis Peanut allergy is a typical IgE-mediated immune disease. Clinical symptoms develop within seconds, and up to 2 h after ingestion of even a few milligrams of peanut protein ( one peanut has about 300 mg of protein). Once recognized, It is vital to consult your physician who will refer you to a specialized allergist for following up. In general, the peanut must be eaten before lifethreatening symptoms will occur. That means the allergy is not often triggered by skin or air contact with the peanut protein=n. The mean age of diagnosis in children is 14 months, with symptoms occurring after the first known peanut ingestion in 75% of those children eating peanuts for the first time.5,6 Diagnosis based on medical history indicating the temporal association between eating peanuts and appearance of symptoms ( generally seconds or minutes, but can be up to 2h) and evidence of peanut-specific IgE which can be established either by allergy skin-prick testing or determination in vitro ( the size of the wheal). In addition to, studies have shown that the peanut-specific IgE measured in the Immuno CAP-FEIA system are generally predictive of having peanut allergy when the level is greater than 14kU/L.7 Treatment Patients who have acute anaphylactic symptoms (in the early stages) should be aggressively treated with intramuscular epinephrine8 , administration of oral antihistamine (diphenhydramine 1mg per kg of bodyweight or chlorpheniramine). Then transportation to an emergency medical facility by emergency personnel and apply airway management and supplemental oxygen and IM epinephrine (0.01mL of 1:1000 dilution/kg every 1020 min as needed with maximum 0.5mL per dose)9. Oral, IM, or IV H1-receptor antagonist, Oral prednisolone(1-2 mg per kg body weight up to 75 mg), inhaled albuterol (1.25-2.5 mg every 20 min, as needed or continually)9. Generally, after an acute attack, patients will be given a 3-day course of oral prednisone (1mg/kg of bodyweight per day; maximum 75 mg/day) and an antihistamine. This recommendation is often followed; however, there are no studies indicating that this practice will reduce the risk of further symptoms ( 2nd phase of allergy which may occur after an acute attack so the patient should be followed up for 4 h for fear that a biphasic allergic response)9. Cost of treatment The overall economic cost of food allergy was estimated at $24.8 billion annually ($4184 per year per child). Direct medical costs were $4.3 billion annually, including clinician visits, emergency department visits, and hospitalizations. Costs borne by the family totaled $20.5 billion annually, including lost labor productivity, out-of-pocket, and opportunity costs. Lost labor productivity costs totaled $0.77 billion annually, accounting for caregiver time off work for medical visits. Out-of-pocket costs were $5.5 billion annually, with 31% stemming from the cost of special foods. Opportunity costs totaled $14.2 billion annually, relating to a caregiver needing to leave or change jobs. Caregivers reported a willingness to pay of $20.8 billion annually ($3504 per year per child) for food allergy treatment.4 For summary, Cost of peanut allergy have significant direct medical costs for the US healthcare system from office visits, rescue medications, emergency department (ED) visits, and hospitalizations.4 . 10 Figure 1 10 Figure 2 Recent advances in immunotherapy and vaccine development for peanut allergy 1) Development of a peanut vaccine: the vaccine failed to induce tolerance to the dominant peanut proteins and 50% of participants were unable to complete the dosing regimen, thus, the use of vaccine did not prove safe for peanut allergy. 11 In the study, Allertein Therapeutics, LLC developed a rectally administered vaccine consisting of three recombinant modified peanut antigens encapsulated within heat/phenol inactivated E. coli. Specifically, three recombinant modified peanut proteins (Ara h 1, Ara h 2, and Ara h 3) were modified by amino acid substitutions to disrupt common IgE binding sites. The study was conducted in two phases, with an initial cohort of 5 healthy volunteers followed by 10 peanut allergic subjects. Subjects were 18 to 50 years of age with no history of severe anaphylaxis. The healthy volunteers had to ingest peanut regularly, have no asthma history, and have negative skin prick tests (SPT, <3 mm wheal) and specific IgE (<0.35 kUA/L, ImmunoCAP, Phadia, Uppsula, Sweden) to peanut. The study was conducted under an Investigational New Drug application from the FDA, with approval from the NIAID Data Safety Monitoring Board, the investigational review boards of Mount Sinai and Johns Hopkins, and the NIH Recombinant DNA Advisory Committee.11 The healthy volunteers received four escalating doses of study product as a rectal suspension on a weekly basis to achieve the maximum study dose, containing 3,063 µg of total modified peanut protein delivered rectally as a 7 ml suspension. Each dose was administered with a 2- hour observation and subjects maintained a home diary to record any symptoms between visits, as well as weekly telephone interviews for 4 weeks after the last dose.11 The second phase of the study enrolled 10 peanut allergic subjects who were required to have a convincing clinical history of peanut allergy, with the development of symptoms (e.g., urticaria, flushing, rhinorrhea and sneezing, throat tightness or hoarseness, wheezing, vomiting) within minutes to 2 hours of ingestion. Additionally, a positive peanut skin prick test (SPT >5 mm wheal) and specific IgE (> 5 kUA/L) were required. Baseline oral food challenges were not done for ethical reasons given that this was a Phase 1 study. Asthmatic subjects could not be more than mild intermittent in severity. These subjects received weekly dose escalations for 10 weeks to the maximum study dose, which was then administered biweekly for 6 weeks. If adverse reactions occurred, only a single repeat dose or dose reduction was permitted. Dosing was not continued beyond 13 doses or 16 weeks, and the dose was not escalated beyond the 3,063 µg maximum study dose. Each dose was administered under observation and subjects were monitored for a minimum of 2 hours. Each dosing visit was followed by a telephone interview on the following day and subjects maintained a home diary between visits. After the final dose, weekly telephone calls were conducted for 4 weeks when a final study visit was completed. Telephone interviews were also conducted 1, 2, 3 and 6 months after the last visit. 11 2) Epicutaneous immunotherapy: The epicutaneous route of immunotherapy is currently under investigation in an effort to optimize allergen administration for food immunotherapy and, at the same time, minimize the frequency and severity of immunotherapy-induced side effects. Epicutaneous administration of the allergen has the advantage of avoiding highly vascularized sites, which are associated with systemic side effects. However, it is able to target professional allergen-presenting cells (such as Langerhans cells of the epidermis) that are necessary for optimal allergen presentation12. A pilot study13 testing clinical efficacy and safety of epicutaneous immunotherapy in children with cow’s milk allergy showed a tendency towards a higher threshold dose after a 3-month treatment period. Although the results were not statistically significant, the intervention was well tolerated with no observed systemic reactions. Phase I and II epicutaneous immunotherapy trials are currently underway for peanut allergy. 12 One of the largest companies interested in this approach is DBV Technologies. Their therapies are based on epicutaneous immunotherapy (EPIT®), a method inducing desensitization in allergic patients by delivering allergens through the skin. 3) Sublingual immunotherapy (SLIT): A double-blind placebo-controlled study of sublingual peanut immunotherapy enrolled 18 participants who underwent a 6-month period of dose escalation, followed by a 6-month period of maintenance therapy. Side effects mostly consisted of oropharyngeal symptoms and only 0.3% of doses required antihistamine treatment. Following a year of treatment, a double-blind placebo-controlled food challenge (DBPCFC) was used to assess the final outcome; this showed the treatment group safely ingesting 20 times more peanut protein than the placebo group (1710 mg versus 85 mg)14 A subsequent multicentre, randomized controlled trial (RCT) of peanut sublingual immunotherapy (SLIT) demonstrated a modest effect in desensitization to peanut. After 44 weeks of treatment, clinical desensitization was observed in 70% of the active versus 15% of the placebo subjects. For the active group, the median successfully consumed dose increased from 3.5 mg at baseline to 496 mg peanut flour (approximately 50% peanut protein) after a year of therapy. Unfortunately, none of the participants were able to pass a 5 g peanut challenge (the study’s primary outcome). The safety profile was very good with 59.9% of doses in the active group being symptom-free, and once oropharyngeal symptoms were excluded, the percentage rose to 94.7% of symptom-free doses.15 Although SLIT appears to have a favorable safety profile, the effect of desensitization is modest compared with other routes of administration (especially OIT). The allergen doses used in SLIT are much lower, due to practical limitations and this limits its efficacy. In order to determine whether this is a clinically useful intervention for peanut allergic patients, more research is required. 4) Oral immunotherapy (OIT): Phase I trials of peanut OIT tentatively investigated the feasibility and acceptability of this novel intervention for peanut allergy, showing some promising initial results. This small studies16,17,18 paved the way for further, phase II, randomized trials of peanut OIT. An RCT of peanut OIT was undertaken in the USA, including 19 children who completed a year of OIT (initial escalation phase, home dosing, build up visits and maintenance phase) and 9 placebo subjects. Participants were aged between 1 and 16 years. The investigators reported that 84% of the active subjects passed a final challenge of 20 peanuts, successfully ingesting 5 g of peanut protein compared with only one peanut or 280 mg of peanut protein (median value) ingested by the placebo subjects. The authors concluded that the degree of protection following successful immunotherapy was likely to prevent accidental peanut anaphylaxis. The study regimen was well tolerated with clinically relevant symptoms seen after only 1.2% of build up doses and no peanut OIT subject requiring adrenaline administration. 19 The largest phase II, randomized, controlled, crossover trial of peanut OIT was published in The Lancet, investigating the role of peanut OIT in desensitizing 99 children, aged 7–16 years, inclusive of all severities of peanut allergy. There was an initial gradual up-dosing phase with 2-weekly increments up to a top dose of 800 mg/day, followed by a maintenance period of daily doses for a total of 26 weeks of OIT. Following completion of the intervention, in the active group, 84% were desensitized to 800 mg (approximately five peanuts), whereas 24 of 39 (62%) OIT participants were successfully desensitized to 1400 mg of peanut protein (approximately 10 peanuts). Subjects who successfully completed the study protocol had a significant 25-fold increase of their peanut threshold, the treatment, therefore, allowing them to eat large quantities of peanuts, well above the levels present in contaminated snacks and meals. Quality of life was measured by a validated quality of life questionnaire. Both participants who were successfully desensitized, and their caregivers, had a significant improvement in the quality of life. Adverse effects, seen in most participants, were mild and easily treatable. The Oral itching was the most common side effect, occurring after 6.3% of all doses. Adrenaline was administered to one subject with prompt resolution of symptoms. Factors associated with successful desensitization included lower levels of peanut-specific IgE at baseline, younger age, and absence of a family history of peanut allergy.20 Overall, it is clear from the above studies that peanut OIT presents an interesting and promising novel form of intervention for children with peanut allergy, resulting in good efficacy for desensitization. The safety profile is also good for most subjects experiencing mild or moderate reactions during treatment. Because of this interesting novel approach, Aimmune Therapeutics build up their product to treat peanut allergy on Oral immunotherapy technique (OIT). The system they built is called Characterized Oral Desensitization Immunotherapy (CODIT). Briefly, All available studies on peanut oral immunotherapy have reported modest to good results regarding its efficacy in desensitization. Sublingual immunotherapy looks less effective unlike its safety profile is excellent. Additionally, No enough data available on epicutaneous immunotherapy. Concluding from that, Immunotherapy is considered a remarkable solution to peanut allergy, However, it is not yet recommended for routine clinical use.21 Companies in the Peanut Allergy Space As peanut allergy became a rising case for infants in the USA, a lot of studies were published about introducing peanut in the early life of the babies. One of them A new study published in the Journal of Allergy and Clinical Immunology found that children were five times less likely to develop a peanut allergy if their moms ate peanuts while nursing and introduced nuts before one year old. 22 The study reveals that maternal peanut consumption while breastfeeding paired with direct introduction of peanuts in the first year of life was associated with the lowest risk of peanut sensitization, compared with all other combinations of maternal and infant peanut consumption.22 Another study23 was interested in evaluating whether the early introduction of allergenic foods in the diet of breastfed infants would protect against the development of food allergy because The age at which allergenic foods should be introduced into the diet of breast-fed infants is uncertain. But The trial did not show the efficacy of early introduction of allergenic foods in an intention-to-treat analysis. Further analysis raised the question of whether the prevention of food allergy by means of early introduction of multiple allergenic foods was dose-dependent.23 More studies were published such as LEAP study24 (Learning Early About Peanut allergy) which is a randomized controlled clinical trial designed and conducted by the Immune Tolerant Network (ITN) to determine the best strategy to prevent peanut allergy in young children. The results of that study revealed that the early introduction of peanuts significantly decreased the frequency of the development of peanut allergy among children at high risk for this allergy and modulated immune responses to peanuts.24 Another study (LEAP-on)25 was published at the NEJM. In a follow-up study, They investigated whether the rate of peanut allergy remained low after 12 months of peanut avoidance among participants who had consumed peanuts during the primary trial (peanut-consumption group), as compared with those who had avoided peanuts (peanut-avoidance group). The results concluded that Among children at high risk for allergy in whom peanuts had been introduced in the first year of life and continued until 5 years of age, a 12-month period of peanut avoidance was not associated with an increase in the prevalence of peanut allergy. Longer-term effects are not known.25 Following study26 made along with 25 professional organizations, federal agencies, and patient advocacy groups, the National Institute of Allergy and Infectious Diseases (NIAID) facilitated the development of addendum guidelines to specifically address the prevention of peanut allergy. The guidelines have 3 categories : Addendum guideline Infant criteria Recommendations Earliest age of peanut introduction 1 Severe Strongly consider evaluation by sIgE 4–6 months eczema, egg measurement and/or SPT and, if allergy, or necessary, an OFC. Based on test both results, introduce peanut-containing foods. 2 Mild-to- Introduce peanut-containing foods Around 6 months Introduce peanut-containing foods Age appropriate and in moderate eczema 3 No eczema or any food accordance with family allergy preferences and cultural practices 26 Figure 3 Hello, Peanut! Based on these studies, Hello, Peanut! The System not only managed to gain attention but also to gain FDA approval 27, thus it is considered in phase 4 clinical trials. Hello, Peanut! was launched in 2016 based on NIAID study 26, LEAP study 24, LEAP-on Study25 and EAT Study 23. The Hello, Peanut! Introduction System contains packets of organic peanut and sprouted oat blends designed to be safely mixed into baby food over the course of seven days. The amount of peanut in each packet gradually increases daily. After this introductory phase, Maintenance Packets are recommended for use until the infant can eat the peanut in spread or whole form. Hello, Peanut! does not require a prescription or administration by a physician and can be fed to babies at home. It is USDA organic certified organic, non-GMO, dairy-free and Kosher (OU).28 Their products include29 : 1) HELLO, PEANUT! INTRODUCTION KIT , price = $25 2) HELLO, PEANUT! MAINTENANCE KIT , price = $20 3) HELLO, PEANUT! COMBINATION KIT , price = $40 Dosing Regimen 30 : Day 1 Day 2 Day 3-7 One Week Later Tear open packet (200mg) labeled day 1. Pour content of Day 1 packet into baby's meal. Feed your baby right away. Discard leftovers. Tear open packet labeled day 2. Pour content of Day 2 packet into baby's meal. feed your baby right away. Discard leftovers. Repeat steps as above with packets labeled Day 3 through Day 7. Use the packets labeled Maintenance as above. Continue to use Maintenance Packets (sold separately), up to three times weekly, until your baby can eat peanuts in spread or whole form. Aimmune Therapeutics Aimmune Therapeutics, Inc., incorporated on June 24, 2011, is a clinical-stage biopharmaceutical company developing a therapeutic approach, including the development of product candidates, for the treatment of peanut and other food allergies. The Company's therapeutic approach, which it refers to as Characterized Oral Desensitization Immunotherapy (CODIT), is a system designed to desensitize patients to food allergens using characterized biologic products, defined treatment protocols, and support services. The Company's lead CODIT product candidate, AR101, is an investigational biologic for the treatment of patients with peanut allergy. Analysts estimate a year’s supply of $5,500. The CODIT Approach31 CODIT approach is based on precise, incremental dosing of a characterized food allergen to achieve gradual desensitization, followed by a daily maintenance dose. The aim of CODIT is to provide an approach for predictable, reliable implementation of OIT that meets the requirements for regulatory approval. With the investigational CODIT approach, initial administration of a particular dose of food allergen would be done in an allergist’s office, and subsequent administrations would be done at home until the next up-dosing in the allergist’s office. Once desensitized, patients would take a daily maintenance dose to maintain desensitization and would continue to avoid exposure to their food allergens and carry epinephrine auto-injectors. The company completed phase 2 study. In this study,32 AR101 (the product) demonstrated an acceptable safety profile and demonstrated clinical activity as a potential immunomodulatory treatment option in peanut-allergic children over the age of 4, adolescents, and young adults. The Company has initiated Peanut Allergy Oral Immunotherapy Study of AR101 for Desensitization in Children and Adults (PALISADE), its Phase 3 registration trial of AR101 (oral intake, Capsule or powder). Thus, the company’s products are not FDA-approved. At the beginning of phase 4, the company may gain FDA approval. Oral immunotherapy dosing regimen In brief, study product dosing began with incremental escalation from 0.5 to a maximum of 6 mg in a single day, with confirmation of the ability to tolerate 3 or 6 mg over the next 1 to 2 days (Initial Escalation phase), followed by biweekly up-dosing to a final dose of 300 mg/day (Up-dosing phase) over 20 to 34 weeks. The protocol permitted adjustments to the biweekly up-dosing schedule as needed, for example, temporary dose reduction if a dose level was not tolerated.32 . . Figure 4 showing the procedure of OIT dosing. 32 Escalation phase Dose in milligrams 3.5 3 2.5 2 Escalation phase 1.5 1 0.5 0 Day 1 Day 2 - 3 Days Figure 5 Up-dosing phase 350 300 Dose in milligrams 32 250 200 Up-dosing phase- 2w 4w 6w 8w 10 w 12 w 14 w 16 w 18 w 20 w Time in weeks DBV Technologies and their product "Vaiskin" A novel pharmaceutical process They have engineered a proprietary manufacturing technology for Viaskin® patch, which is designed to comply with the most stringent pharmaceutical production standards. This novel pharmaceutical process, fully developed by DBV, uses an electrospray to spray homogeneous, thin, dry protein layers onto the Viaskin® patch. This process sprays a liquid solution of electrically charged proteins onto the patch’s backing, which is then turned into a dry solid charged particle, which remains stuck onto the patch’s backing. This fully patented technology is highly scalable and complies with cGMP requirements.33 The Viaskin® is an electrostatic patch, which may offer a convenient, self-administered, noninvasive immunotherapy to patients. Once applied on intact skin, Viaskin® forms a condensation chamber, which hydrates the skin and solubilizes the antigen allowing it to penetrate the epidermis, where it is captured by Langerhans cells. Our pre-clinical research and publications suggest this unique mechanism of action may be safe and may allow for a strong and highly tolerogenic immune response This epicutaneous immunotherapy method may allow to address food allergies, as well as unmet medical needs in other immunotherapy indications.34 Unfortunately, Viaskin failed its phase 3 clinical trial, but the company still believe that its product could gain FDA approval. Analysts estimate a year’s supply of Viaskin at about $6,500 About PEPITES The Peanut EPIT Efficacy and Safety Study (PEPITES) was a global, pivotal, double-blinded, placebo-controlled Phase III trial designed to evaluate the safety and efficacy of Viaskin Peanut 250 μg in children ages four to 11 years. PEPITES was conducted in 31 centers across North America (Canada and the United States), Germany, Ireland and Australia. The last patient visit for PEPITES occurred in August 2017. During PEPITES, patients’ response has been assessed using a double-blind, placebo-controlled food challenge (DBPCFC). Patients were randomized 2:1 to receive either Viaskin Peanut 250 μg or placebo for 12 months. The primary endpoint was based on a responder analysis after 12 months of treatment with Viaskin Peanut 250 μg. For patients with a baseline peanut protein eliciting dose (ED) equal to or less than 10 mg, a responder was defined as a patient with a peanut protein ED equal to or greater than 300 mg of peanut protein after 12 months of treatment. For patients with a baseline ED greater than 10 mg, a responder was defined as a patient with a peanut protein ED equal to or greater than 1,000 mg of peanut protein after 12 months of treatment. As a secondary efficacy endpoint, Cumulative Reactive Dose (CRD), has also been used in PEPITES to establish the total quantity of peanut protein that triggers patient reactions at month 12 of active treatment versus placebo. Serological markers were also measured at baseline, 3, 6, and 12 months in order to characterize the immunological changes in patients.35 35 Figure 7 m ont h 0m ont h 1 23 6 Before Brands™, Inc and their product SpoonfulOne Before Brands is a science-based health and wellness company dedicated to bringing innovative nutritional products directly to families. Their product development builds on a growing body of evidence in support of nutritional strategies that include potentially allergenic foods as a regular part of a healthy diet. The Company’s first product "SpoonfulOne" is the only holistic approach to food allergies, before foods become allergens. The dry food mix-in makes it easy for families to introduce and maintain the most common potential food allergens in the diets of infants and toddlers. Their patented dietary supplement is made with real ingredients including peanut, tree nuts, milk, egg, fish, shellfish, wheat, soy, and sesame, which together account for 90% of food allergies. The cornerstone in devolving SpoonfulOne product is LEAP study24 which reached storming conclusions. The study states that The early introduction of peanuts significantly decreased the frequency of the development of peanut allergy among children at high risk for this allergy and modulated immune responses to peanuts. SpoonfulOne Daily Food Mix-in ( Price )36 Monthly Subscription (30 packets per shipment) 1) 12 Months - $2.50/day ($75.00/month) 2) 6 Months - $2.80/day ($84.00/month) 3) 3 Months - $3.00/day ($90.00/month) Adeo Health Science, Inc and their product Inspired Start Adeo Health Science, Inc is a research-driven food company with the mission of creating easy to use, organic, and trusted products for families. With new evidence showing that allergenic foods can be introduced just like other solid foods, Adeo Health Science recently launched Inspired Start (www.inspired-start.com). Inspired Start is the only product that helps parents introduce 8 common food allergens to their infants as they transition to solid foods. The Company is headquartered in Boston, Massachusetts. Adeo’s approach is rooted in the findings of landmark studies that were published in the New England Journal of Medicine. The LEAP study demonstrated that regular consumption of peanuts by infants who are at high-risk for developing peanut allergy prevents the subsequent development of allergy. The EAT study showed that the early introduction of potentially allergenic foods (such as peanut, sesame, fish, and egg) into the infant diet from three months may prevent the development of food allergy and other allergic diseases (such as eczema) in childhood. The Inspired Start product emerged from these clinical findings and the clear need for a smart, scientifically-validated approach to these updated infant nutrition guidelines. Now, parents and physicians are turning to Adeo for information about the study and Inspired Start as a solution for early introduction. Inspired Start offers their product on their website and Amazon prime. Pack 1: introduces peanut, egg, tree nut, and soy (2 pouches of each) = $23. Pack 1 makes the early introduction of peanut, egg, tree nut, and soy deliciously simple. Their product is USDA Certified Organic and Non-GMO. Regarding the FDA approval, There is no reliable information regarding inspired start. AnaptysBio AnaptysBio is a clinical-stage antibody development company advancing therapeutic antibody product candidates focused on unmet medical needs in inflammation. They develop the product candidates to address emerging biological targets using their proprietary antibody discovery technology platform, which is based upon a breakthrough understanding of the natural process of antibody generation, known as somatic hypermutation, or SHM, and replicates this natural process of antibody generation in vitro. Their strategy is to advance the development and commercialization of the proprietary product candidates, and for certain programs, establish partnerships with leading biopharmaceutical companies where we retain certain development and commercialization rights in the United States. The wholly-owned product pipeline includes ANB020 and ANB019, which are being developed to treat severe inflammatory disorders with unmet medical need. They are advancing the ANB020 product candidate, an antibody that inhibits the activity of interleukin-33, for the treatment of moderate-to-severe adult atopic dermatitis, severe adult peanut allergy and severe adult eosinophilic asthma. In addition, They are developing the ANB019 product candidate, an antibody that inhibits the interleukin-36 receptor, for the treatment of rare inflammatory diseases called generalized pustular psoriasis (GPP) and palmoplantar pustular psoriasis (PPP). The company is led by a strong management team with a proven track record of successfully growing biotechnology companies with deep experience in antibody discovery and development, collaborations, operations and corporate finance ANB02037 IL-33 is a gatekeeper of atopic responses via activation of ILC2 leading to rapid Th2 cytokines release and by directly influencing pathogenic allergen-specific T cells and mast cells activation. Therefore IL-33 inhibition may provide a therapeutic benefit to atopic patients. ANB020 is a humanized IgG1 antibody specific for human IL-33. ANB020 has high affinity against IL-33 and inhibits IL-33 activity in preclinical models. ANB020 showed a good tolerability and safety profile with an equal AE representation in ANB020 and placebo dosed subjects. PK was linear at all doses tested for both IV and SC route of administration. Ex vivo PD activity was observed after single administration for over 43 days at the tested doses. In this Phase 1 healthy volunteer study, the PK and PD results were shown to be compatible with a monthly dosing regimen. The results of this phase 1 study support the advancement of ANB020 into clinical studies for patients with atopic diseases. Antera Therapeutics and their product Aralyte Antera Therapeutics is a Boston-based biomedical startup led by a former Pfizer biochemist, funded by Big Pharma alumni, and linked with Harvard’s iLab incubator, and it has the hallmarks of a sterling upstart. But its flagship product Aralyte, intended to help prevent peanut allergy, has dubious utility, medical experts warn, and could fleece parents out of hundreds or even thousands of dollars. Aralyte is based on the LEAP study24 , LEAP-ON study 25 , EAT study 23( which claims that introducing allergenic foods into the infant diet from three months may be effective in food allergy prevention when sufficient amounts of allergenic foods are consumed) and CHILD study 38 ( which claims that Early introduction of all three allergens reduced the risk of later allergy development. No reason to delay introduction beyond 4-6 months. You Should first consult the physician and begin with an escalating dose. Overall, food allergy was lower in the group introduced to allergenic foods early but the difference was not statistically significant. Early introduction of all the foods was not easy but it was safe. Among the infants who did manage to consume the recommended quantity of the allergenic foods, there was a two-thirds reduction in overall food allergy. Aralyte is a kit of individual capsules filled with liquid peanut protein designed to be fed to infants on a strict schedule to prevent an allergy from developing. Its least expensive formulation is $180 for a three-month supply. Aralyte is the first in a line of what Antera Therapeutics plans to be numerous early introduction products to prevent allergies. Because Aralyte is a liquid, it can be ingested at a younger age whereas parents need to wait until their child is older and able to eat pureed foods to safely ingest diluted peanut butter. Aralyte contains all-natural organic, distilled peanut extract and complete doses of essential vitamins like vitamin D, making it perfect for use in combination with breastfeeding or infant formula. Each liquid dose contains 4 mL of Aralyte, which is less than a single teaspoon. It contains slightly less than 1 gram of peanut protein to total 6 grams of peanut protein per week. Aralyte is not a desensitization strategy or form of oral immunotherapy. Desensitization and immunotherapy refer to treatment strategies that raise people’s tolerance to foods they are already allergic to, so that incidental exposure doesn’t result in more serious adverse effects. Antera, on the other hand, is strictly a preventive measure intended to reduce the risk of allergy development in children who are not allergic. On 16th Nov 2016, FDA sent an untitled letter to Cambridge, MA-based Antera Therapeutics because it's selling an unapproved biologic intended to prevent a peanut allergy. FDA says the company’s website makes unsubstantiated claims about its “all-natural formula that makes giving peanut protein to your child safe and easy.” Among other issues, the site highlights that the product, known as Aralyte, has been manufactured, packaged and stored “to be maximally effective in allergy prevention and with your family’s safety in mind.” “The Aralyte daily regiment was crafted to be a precise amount of exposure to the allergen, keeping your baby safe,” the website reads. “Based on these claims, it appears your product is intended to prevent a peanut allergy from developing in children and therefore appears to be a drug,” FDA said, noting the biologic has not been approved by the agency for safety or effectiveness. “Your product is not the subject of an approved biologics license application (BLA) nor is there an IND in effect for the use of this product. Based on this information, we have determined that your actions have violated the FFD&C [Federal Food, Drugs and Cosmetics] Act and PHS [Public Health Service] Act.” 39 Other competitors Sanofi has entered into licensing agreements of discovery platforms in selected food allergies, notably with Immune Design Corporation. Sanofi is a global life sciences company committed to improving access to healthcare and supporting the people we serve throughout the continuum of care. From prevention to treatment, Sanofi transforms scientific innovation into healthcare solutions, in human vaccines, rare diseases, multiple sclerosis, oncology, immunology, infectious diseases, diabetes and cardiovascular solutions and consumer healthcare. More than 110,000 people at Sanofi are dedicated to making a difference on patients’ daily life, wherever they live and enable them to enjoy a healthier life. They are trying to develop a peanut vaccine which called SAR439794 TLR4 agonist (Toll-like receptor 4 (TLR4) agonist immunomodulator). It has been in phase 1 trial yet. Immune Design is a clinical-stage immunotherapy company employing next-generation in vivo approaches to enable the body's immune system to fight disease. The company's technologies are engineered to activate the immune system's natural ability to generate and/or expand antigenspecific cytotoxic T cells, while also enhancing other immune effectors, to fight cancer and other chronic diseases. CMB305 and G100, the two-pronged focus of Immune Design's ongoing immuno-oncology clinical programs, are the product of its two synergistic discovery platforms, ZVex® and GLAASTM, the fundamental technologies of which were licensed from the California Institute of Technology and the Infectious Disease Research Institute (IDRI), respectively. Immune Design has offices in Seattle and South San Francisco. Table 1 – Difference between companies in price Table 2 – clinical trials of the companies Regulatory On 10th Nov 2016, Hello, peanut! Received untitled letter from FDA warning them that they are buying a non-approved product. Hello, peanut! Claims that their product can prevent the peanut allergy, but FDA said " Your product is not the subject of an approved biologics license application (BLA) nor is there an IND in effect for the use of this product. Based on this information, we have determined that your actions have violated the FFD&C Act and the PHS Act. We request that you notify this office, in writing, of the steps you have taken or will take to address the violations noted above and to prevent their recurrence". 39 However, on 7th Sep 2017, FDA Acknowledges Qualified Health Claim Linking Early Peanut Introduction and Reduced Risk of Developing Peanut Allergy. FDA said " This qualified health claim is supported by the same scientific evidence behind the first Addendum Guideline that recommends the introduction of peanut-containing foods to infants with severe eczema, egg allergy, or both, as early as 4 to 6 months of age to reduce the risk of peanut allergy. " 27 So, Hello, peanut! is regarded as the first corporation who could gain FDA approval to sell their product legally. References:-. Sicherer SH, Muñoz-Furlong A, Sampson HA. Prevalence of peanut and tree nut allergy in the United States determined by means of a random digit dial telephone survey: a 5-year follow-up study. J Allergy Clin Immunol. 2003;112(6):-. Berggren T, Lee CY. Nutrition and Health Info Sheet: Food Allergies. 2017. Johnston LK, Chien KB, Bryce PJ. The immunology of food allergy. J Immunol. 2014;192(6):-. Gupta R, Holdford D, Bilaver L, Dyer A, Holl JL, Meltzer D. The economic impact of childhood food allergy in the United States. JAMA Pediatr. 2013;167(11):-. 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