Christophe Bancel, Founder and CEO

Since developing and validating SETALUM, a versatile vascular sealant in 2013, closely-held, Paris-based Gecko Biomedical is now poised to seek FDA approval for SETALUM, validate new programs, and open a state-of-the-art manufacturing facility in Northern France.

 “As a company, we are at a tipping point,” Christophe Bancel, founder and CEO, says in an interview with BioTuesdays.

“Our platform is ready for acceleration in very diverse directions. We launched as a vascular sealant company, but we are expanding as a tissue reconstruction company with a fully industrialized polymer platform that can be used in a variety of medical device applications, and produced en masse,” he adds.

Mr. Bancel explains that Gecko’s technology is based on world-class research and intellectual property from the laboratories of Professor Robert Langer, MIT, and Professor Jeffrey M. Karp, Brigham and Women’s Hospital, who co-founded Gecko in 2013 along with himself, and Bernard Gilly of iBionext Network.

A broad and exclusive IP position

Polymers are materials made of long, repeating chains of molecules, and have unique properties depending on the type of molecule being bonded, and how they are bonded.

“In our case, our platform is composed of fully synthetic, light activated polymers that can be ‘printed’ on living tissue inside and outside the body,” he points out.

Regarding competition in the marketplace, Mr. Bancel says unlike other sealants that are watery, dilute when mixed with blood and become polymerized as soon as they are mixed, “our polymers are of a honey-like consistency so they have excellent tissue adhesion capabilities with the added benefit of being adjustable, making it easier for surgeons to apply.”

Once in place, they polymerize into a solid yet flexible state when the surgeon decides. In addition, they are bioresorbable and fully hydrophobic so they don’t become diluted in wet environments, he adds.

The polymers are activated using Gecko’s proprietary blue light activation pen for on demand curing. Once printed, the polymers are biodegradable, biocompatible and elastic, complying with the dynamics of the tissues on which they have been printed.

“We chose the vascular sealant space to launch our first product entry because we knew we would be successful within a short amount of time, but our polymers can be leveraged in so many different ways that support the extension for applications with different tissue types, such as cardiovascular, bone, nerve, ophthalmological and urological,” Mr. Bancel says.

Gecko’s vision is to create an ecosystem around its versatile technology platform that will drive innovation

SETALUM, an add-on to sutures during vascular surgery, received CE Mark in June 2017, paving the way for further development of other indications such as using it as an adhesive, a barrier, a filler, and as a frame or scaffolding by combining it with 3D printing technology, Mr. Bancel says.

Gecko is currently undergoing the FDA premarket approval process for SETALUM and anticipates filing an investigational device exemption by the end of 2018, with clinical trials beginning in 2019 in the U.S.

“Our polymers are made up of three monomers and you can play with the ratio so different proportions can lead to distinct properties,” Mr. Bancel says. “The versatile design allows for each use case to leverage the right formulation, distinct delivery device, and specific activation technology to solve individual, unmet medical needs,” he adds.

In order to meet the demand of the expansion and industrialization of Gecko’s polymers platform, Mr. Bancel says the company is currently in the process of running validation tests and protocols on a globally unique, state-of-the-art manufacturing site in Roncq, France, to be certified by the end of 2018, and that will facilitate the production of any version of the polymer.

He describes the facility as 100% green powered space that features four clean rooms and an analytical laboratory.

“Cutting-edge processes will be performed at the site to produce all our liquid polymers in individual, sterile conditions, ready for use by surgeons,” Mr. Bancel reveals. “We also intend to speed up a second phase in our strategy through the industrial and clinical development of our polymers as a biomedical resin, as well as by optimizing state-of-the-art 3D printing techniques,” he adds.

Looking forward, Mr. Bancel describes the rapid expansion of Gecko’s portfolio of products using a standardized process that he calls the Innovation Hub to bring innovative solutions for patients.

In fact, it’s a sophisticated business model that allows Gecko to swiftly transition from an idea, to proof of concept, to full device specifications in order to begin first-in-man trials in less than two years from the start of the process, he explains. The Innovation Hub not only supports product development that takes place internally but it also supports potential product development that may occur from strategic partnership.

“As a result, Gecko becomes an open R&D ecosystem on a proprietary technology that designs for third parties from small start-ups to larger medtechs,” Mr. Bancel contends.

“We have a fully proprietary platform, but we want to open it up to the innovators of the world – from surgeons to large medical device companies, to produce innovative solutions, co-design products, and ultimately provide a better quality of life for patients worldwide,” he adds.

Mr. Bancel says the design of their technology platform is reflective of the vision the team has had for the technology since the inception of Gecko Biomedical. “Our focus is tissue reconstruction and our primary tool is our polymers.”

Since Gecko received regulatory validation in the form of CE Mark last year, they have proceeded to expand their portfolio with greater speed, putting the Innovation Hub into full swing.

“We are very optimistic about the vast potential of our product development with extended novel applications in other fields of tissue reconstruction such as guided tissue repair, and in the field of localized drug delivery,” he adds.

George Adam, CEO

FDA approval last week of Ventripoint Diagnostics’ (TSXV:VPT) VMS+ medical device with a four-chamber heart analysis system Is expected to change the paradigm of diagnosing and managing heart patients through a five-minute procedure that can be read in a cardiologist’s office in 10 minutes.

“VMS+ is the first simple echocardiography system to be approved by the FDA for the 3D volumetric analysis of all four chambers of the heart using 2D ultrasound,” CEO, Dr. George Adams, says in an interview with BioTuesdays. 

“We can now offer VMS+ to American physicians so they can accurately and easily evaluate and monitor hearts in children and adults during a routine cardiology appointment,” he adds. 

Dr. Adams explains that measurements of heart function, expressed as ejection fraction or the volumes of any of the four chambers of the heart, are increasingly recognized as critically important in monitoring the heart and predicting outcomes of patients.

“This applies to patients with heart failure, abnormal heart rhythms, congenital heart disease, pulmonary hypertension and hypertension,” he points out. “With the VMS+, it is now possible to obtain this valuable information quickly, easily and cost effectively.”

Ventripoint’s first generation VMS system is the only 2D echocardiography approach certified equivalent to MRI for right ventricle analysis. It has been approved by the FDA, Health Canada, and has CE Mark in Europe for all patients.

“There is no fundamental difference in how our VMS and VMS+ work other than VMS measures changes in the right ventricle only, while VMS+ measures all four chambers of the heart,” he adds.

The company’s right ventricle VMS device currently has an installed base of more than 20 major hospitals in North America, Europe and China, some of which have participated in Ventripoint’s clinical trials.

Dr. Adams says the company’s marketing plan will involve targeting key opinion leaders in the cardiovascular sector as well as centers of excellence such as the Mayo Clinic, MD Anderson Cancer Center, Cleveland Clinic and major hospitals in regional clusters, including Chicago, New York, Houston and California. “We’re hoping to announce a couple of orders before the end of the month.”

Key opinion leaders have validated the VMS technology in numerous peer-reviewed articles, including in the Journal of the American Society of Echocardiography.

Among other things, researchers have concluded that VMS gives accurate results even with complex and unpredictable shape variations in adult congenital heard disease patients with right ventricle-to-pulmonary conduits.

In addition, VMS has been shown to have excellent reproducibility even with complete retesting by different examiners in patients with pulmonary hypertension and is superior to conventional 2D echo analysis.

According to Dr. Adams, cardiologists need volumetric information on all four chambers of the heart because the left atrium is involved in heart attacks and blood pressure control; the left ventricle in chronic heart failure; the right atrium in electrophysiology and pacemakers; and the right ventricle in pediatric conditions, pulmonary hypertension and cancer therapeutics.

“Cardiologists now will have a convenient, easy-to-use method of determining whether patients need more therapy, less therapy or no therapy at all,” he contends. “They will be able to sort patients that need a simple medicine or a more complex medicine and whether patients need dual therapy or triple therapy. Cardiologists are not going to order a MRI every time they want to change your medication because there aren’t enough MRI machines and the cost would drown the system.”

New VMS-PLUS model being developed for 4-Chamber analysis (RA, RV, LA, LV)

The VMS+ system received Health Canada approval in 2017 and CE Mark at the beginning of 2018. Ventripoint also has established a joint venture in China to manufacture and distribute VMS+, following regulatory approval in China expected by mid-2018.

Dr. Adams points out that the number of people with hypertension is increasing, and an estimated 44% of the 64 million U.S. adults with hypertension did not have this condition controlled in 2014. “As a result, there is an enormous potential for improving population health by expanding treatment and improving outcomes.”

Controlling hypertension could prevent some 56,000 cardiovascular events and 13,000 deaths a year and also would result in significant cost savings for the healthcare system, he adds.

“For example, accurate and reliable repeat measurements of left atrium volume would inform the cardiologist which patients need to have their therapy changed to obtain greater stability of blood pressure,” he contends.

Even during pregnancy, Dr. Adams says it is difficult to determine how the mother’s heart is coping with the 40% increased load in the third trimester. “Normal volumetric index curves would enable cardiologists to determine if the heart is unusually large to determine whether a high-risk pregnancy has developed.”

The economic benefit of VMS technology also extends to cancer patients because most chemotherapies impact the heart. According to a study published in 2016 in the peer-reviewed journal, Echo Research and Practice, right heart function deteriorates in breast cancer patients undergoing anthracycline-based chemotherapy.

“We’re hoping to further study how our device can determine the impact of these adverse effects on right and left heart function,” he adds. 
Ventripoint also is studying how VMS can read cardiac ultrasounds without the use of contrast media infusions. Currently, 30% to 40% of cardiac ultrasounds are unreadable and blurry, which requires the use of contrast media to get readable outcomes, Dr. Adams points out.

But upping the use of contrast media infusions is expensive, dangerous and time consuming, and requires an IV technologist to attend the ultrasound. “In the 10% of cases, even when contrast media is used, study is still unreadable, VMS should be able to analyze the study and get results,” he adds.

Laurent Levy, CEO

France’s Nanobiotix (Euronext:NANO) is hoping to change the paradigm for cancer treatment with a single nanomedicine applicable across oncology for millions of patients.

“What differentiates us is that we do not use biology or chemistry, but rather physics to destroy cancer cells, and activate the immune system.” CEO, Laurent Levy, says in an interview with BioTuesdays.

“We have a broad ongoing clinical development program underway in seven cancer indications in the EU, U.S. and Asia and hope to receive our first EU market approval in soft tissue sarcoma later this year,” he adds.

Mr. Levy says Nanobiotix targets radiation therapy - one of the largest oncology markets with minimal competition. “We are developing solutions designed to solve the issue of improving the energy dose from radiation within the tumor but without increasing damages in healthy surrounding tissue.”

He explains that the company’s lead therapy, NBTXR3, has been designed to maximize x-ray absorption within the tumor. “We have nanosized it to 50 nanometers to enter the cell, to strongly absorb x-rays and to be non-toxic,” he contends. “Our IP covers 11 patent families, with protection until at least 2029.”

50 nanometer HfO2* particles were chosen because they have the best ratio for X-ray absorption and non-toxicity

According to Mr. Levy, NBTXR3 plus radiotherapy demonstrates a universal physical mechanism of action both locally, for primary tumor destruction, and to generate immunogenic cell death potentially to harness immune generating systemic activity.

“NBTXR3 has a physical mode of action that could work across all solid tumors to enhance the efficacy of radiotherapy alone with standard of care or in combination with immunoncology, chemotherapy and PARP inhibitors,” he adds. “Only one administration of NBTXR3 is required before the first radiotherapy session.”

As a single agent, Nanobiotix is developing NBTXR3 for the treatment of soft tissue sarcoma, head and neck cancer alone and in combination with chemotherapy, liver metastasis, hepatocellular cancers and prostate cancer. And, in combination with checkpoint inhibitors, the company is pursuing recurrent head and neck cancer and lung metastasis.

NBTXR3 has a physical mode of action: Increase dose absorption & deposition in the tumor

In an ongoing Phase 1/2 in elderly and frail patients with head and neck cancer, Mr. Levy says NBTXR3 presented in June 2017 at ASCO, an excellent safety profile, with no serious adverse events related to NBTXR3, which is a “huge asset in this frail population.”

In addition, 10-out-of-11 patients responded to treatment, with seven complete responses, “meaning that the tumor is completely gone and quality of life improved.” Mr. Levy also points out that all patients had prolonged response and survival at higher dose levels.

“These three pillars – overall survival, low toxicity and quality of life – represent the holy grail of oncology,” he adds. “That’s why we are going full speed ahead in this indication where we could have an opportunity to bring this to patients.”

As a result, Nanobiotix has amended the trial’s protocol to include 44 additional patients and new clinical sites in Europe to speed up recruitment. An update on data is expected in mid-2018 to confirm the potential value of NBTXR3 in head and neck cancer.

Mr. Levy says that when the company obtains further data, the plan is to approach the FDA to discuss the regulatory path forward of NBTXR3 in head and neck cancer.

In soft tissue sarcoma, Nanobiotix has completed recruitment in a pivotal trial of NBTXR3, with top-line data expected around the end of the second quarter of 2018.

“The value of NBTXR3 is to go forward in head and neck cancer but our strategy is to get approval initially in soft tissue sarcoma,” Mr. Levy points out. “We can’t assume that we will get the amount of clinical benefits and reimbursement in soft tissue sarcoma that we could get in head and neck cancer because of the nature of the population we are treating. So we plan use the head and neck data to seek reimbursement first before expanding it to soft tissue sarcoma in later stage.”

The company’s European Phase 2/3 soft tissue sarcoma study of the extremity and trunk wall has completed enrollment of more than 156 patients in 12 countries, with topline data scheduled for release at the end of the second quarter of 2018. Top line data will be focusing on the endpoints, which are complete path response rate, and operability, which is critical for those patients and related to better survival. Full data will be presented in medical conference later.

“We do not plan, for now, to pursue this indication in the U.S., where our focus will be head and neck and prostate cancer, and combining NBTXR3 with immunoncology,” Mr. Levy says.

To test its theory of combining NBTXR3 with immunoncology, Nanobiotix sampled 40 of the 156 patients in the Phase 2/3 soft tissue sarcoma trial. The comparative study measured 20 patients treated with NBTXR3 plus radiotherapy against 20 patients with radiotherapy alone to determine whether there was an increase in CD8 cells, which represents a marker for the immune system’s cytotoxic T-cells.

“What we found was an increase number of patients with CD8 infiltration, compared with radiation therapy alone. Also, a significant up regulation of Immune checkpoint inhibitor and adaptive immune response-related genes has been observed, which could indicate the potential of NBRXR3 to increase the response rate in patients and the quality of response of multiple checkpoint inhibitors,” Mr. Levy contends.

Of the four checkpoint inhibitors approved for use in head and neck cancer and non-small cell lung cancer - Opdivo, Keytruda, Tecentriq and Imfinzi –around 20% to 25% of patients respond to treatment, he points out. Nevertheless, the four drugs are expected to generate $15-billion in revenue by 2024 in the two indications.

The immune system uses checkpoints on certain immune cells that need to be activated to start an immune response. Cancer cells, however, find ways to use these checkpoints to avoid being attacked by the immune system. Checkpoint inhibitor drugs that target these checkpoints have become an important element in the immunotherapy arsenal.

In the next few months, Nanobiotix plans to dose the first patients in Phase 1/2 trial in patients with advanced head and neck cancer and non-small cell lung cancer that do not respond to checkpoint inhibitors. The goal of the dose escalation and dose expansion study is to transform non-respondent patients into responders, with NBTXR3 activated by radiotherapy and checkpoint inhibitors.

For example, Mr. Levy suggests that for every 10 cancer patients, around two will respond to checkpoint inhibitors. “If two of the remaining eight patients respond to our treatment, we will have doubled the current rate of response to checkpoint inhibitors. If we can achieve better response and survival, our product can have an important impact, if not the main impact, in the checkpoint market in these two indications.”

A leading pipeline of nanomedicines in oncology

Rocky Ganske, CEO

In addition to several large ongoing investigator-sponsored studies in Europe and Canada using its autoRIC device for automated remote ischemic conditioning (RIC), closely-held CellAegis Devices expects its own U.S. pivotal trial for the treatment of elective percutaneous coronary intervention (ePCI) to complete enrolment before the end of 2018.

“RIC has broad clinical evidence dating back to 1986, demonstrating protection in heart, kidney, and brain. This includes heart attacks, elective stenting, stroke and imaging procedures to prevent contrast-induced kidney injury,” CEO, Rocky Ganske, says in an interview with BioTuesdays. 

“With our innovative automated device, we are making this protective therapy easily accessible to healthcare providers,” he adds. 

According to Mr. Ganske, the benefits of RIC have been reported in more than 7,000 peer-reviewed articles on local ischemic pre-conditioning and more than 650 scientific papers in limb occlusion RIC. In addition to proven protection of the heart and kidneys, RIC can contribute to significant cost savings for healthcare systems, he adds. 

The autoRIC® Device System

The company’s non-invasive autoRIC device has regulatory approval in Europe and Canada, and is currently limited to investigational use in the U.S.

Mr. Ganske explains that autoRIC uses four, five-minute cycles of limb occlusion and reperfusion to protect the heart against ischemia-reperfusion injury and reduce the amount of damage sustained by the heart. The kidneys also receive protection at the same time.

“By inducing a controlled ischemic event and harnessing several of the body’s adaptive responses, which can condition the body against ischemia, tissues are not injured and function is improved,” he adds. “An anti-inflammatory effect also contributes to preventing endothelial dysfunction and platelet activation.”

Mr. Ganske says the autoRIC solution ensures easy, safe, reliable and accurate delivery of RIC with a fully automated, single-button start. The disposable single-use cuff also reduces the risk of infections.

The company’s technology is covered by more than 100 patents worldwide and more than 40 pending patents. 

The autoRIC device can be applied in the back of an ambulance by paramedics or in hospitals during a heart attack, “which we call per-conditioning” and for chronic rehabilitation in home care recovery after a cardiovascular event, “which we call chronic-conditioning.”

Remote Ischemic Conditioning: Pre, Per and Chronic

According to published peer-reviewed studies, RIC can provide significant benefits in patient outcomes. For example, RIC can contribute to a 43% improvement in clinical outcomes of heart attacks, a 42% reduction in kidney damage, a 32% reduction in heart damage from ePCI and a 20% cost savings in heart attack treatment and care in Europe.

Mr. Ganske says recruitment has been completed in two investigator-sponsored trials to further assess the efficacy of RIC in reducing clinical events in patients presenting with ST-segment-elevation myocardial infarction (STEMI). Both trials utilized CellAegis’ autoRIC device to deliver RIC therapy and are designed to support expanded adoption of CellAegis’ technology in Europe.

Both trials are investigating the difference between RIC and standard-of-care treatment in reducing cardiac death and hospitalization for heart failure in STEMI patients.

autoRIC®: EU, US and Canadian Trials – Clinical Strategy Overview

One study, CONDI 2, sponsored by Aarhus University Hospital in Denmark has enrolled 2,600 STEMI patients in ambulances in Denmark, Serbia, and Spain. The second study, ERIC-PPCI, has enrolled 2,700 STEMI patients across 20 National Health Service hospitals in the UK. It was sponsored by the London School of Hygiene and Tropical Medicine. Trial results from both studies are expected in the second half of 2019.

Last month, CellAegis entered into a definitive agreement with Cardiologic to market and distribute autoRIC in the UK and Ireland. “This marks our first distribution agreement for autoRIC outside of Canada and is a significant step forward for our international commercialization strategy,” Mr. Ganske says. The company is currently considering a distribution partner for Germany.

In addition, the William Osler Health System in Ontario is currently sponsoring the 1,800-patient FIRST field implementation study, with enrollment scheduled for completion in August. Patients experiencing a heart attack are treated with the autoRIC device either in the ambulance by Peel or Halton emergency medical services or in the emergency department or catherization lab of Brampton Civic Hospital or Trillium Healthcare Partners. 

The benefit of the autoRIC device treatment will be assessed by comparing clinical outcomes, including hospital readmissions and future heart attacks, of treated patients with those of untreated heart attack patients. “Following the completion of this study, we anticipate that autoRIC treatment will be added to standard treatment for heart attacks in the Region of Halton-Peel, followed by wider Ontario and Canadian adoption,” Mr. Ganske adds.

In January, CellAegis enrolled the first patients in its SHIELD pivotal trial in the U.S., a 500-patient single-blind clinical trial designed to evaluate the safety and effectiveness of the autoRIC device to attenuate myocardial injury, as measured by a validated cardiac biomarker, troponin 1, in patients undergoing ePCI.

Patients scheduled either for an ePCI procedure, or a diagnostic catheterization procedure that may be followed with stenting, will be enrolled in the study across 15 research sites in the U.S. and Canada. The company expects to complete enrollment in the third quarter of 2018.

The primary efficacy outcome of the U.S. trial is to show a statistically significant reduction in the prevalence of ischemia-reperfusion injury to the myocardium in patients using the autoRIC device, compared with patients using a placebo device. Patients will exit the study after completion of their 30-day post-procedure follow-up. The company hopes to file for FDA approval by the end of 2018.

“There are approximately one million ePCI procedures performed annually in the U.S. in patients with ischemic heart disease, many of whom have procedural related troponin elevations, which have been shown to result in poorer clinical outcomes,” Mr. Ganske points out.

Multiple Indications: autoRIC® Platform Therapy

“We are in a unique position of having our device used by investigators in multiple cardiovascular studies, where we are paid for the use of the device and consumables, and also obtain access to study data for regulatory purposes,” he adds. “This leverages more than $25-million of third-party capital.”

He estimates that the autoRIC cuff market potential in North America and Europe, covering STEMI, ePCI and angiography to prevent contrast-induced kidney injury, is approximately $400-million at launch. Additional future indications, such as stroke and heart failure, would expand the market significantly above $5-billion annually.

Eric Bjerkholt, CFO

On the heels of positive data from its PALISADE pivotal trial, Aimmune Therapeutics (NASDAQ:AIMT) plans to submit a biologics license application with the FDA by the end of 2018 for its peanut allergy therapy, AR101.

“We set the efficacy bar high in our clinical testing with the goal of achieving meaningful levels of allergy protection,” CFO, Eric Bjerkholt, says in an interview with BioTuesdays. “We hope to receive FDA approval by the third quarter of 2019 and launch by the end of 2019.”

That approval could be the first for any food allergy treatment, an accomplishment that would be shared with food allergy advocates, who helped establish the company earlier this decade to pursue a promising approach studied in academic research. 

Mr. Bjerkholt explains that research suggests that patients with food allergies can be desensitized to exposure to food allergens by ingesting controlled, increasing amounts of the allergen over a period of time, an approach known as oral immunotherapy (OIT).

Personalized Up-Dosing for Dependable Protection

Building on OIT research, Aimmune’s CODIT platform, or Characterized Oral Desensitization ImmunoTherapy, has been designed as a standardized approach using characterized pharmaceutical products to treat food allergies, starting with peanut allergy, where gradually increasing doses of AR101 would desensitize patients to peanut over a period of about six months. Afterward, patients would continue to take maintenance doses of AR101, as the level of desensitization will continue to improve with time.

AR101 has a characterized protein profile found in peanuts, analyzed to ensure consistent major allergen content. The amount of active ingredient in each AR101 capsule is controlled to ensure minimal variability of allergen content across doses of a given strength. 

“CODIT is very much a platform technology that can be applied to other allergies, with a six-month up-dosing phase followed by ongoing maintenance,” Mr. Bjerkholt points out.

The company is developing two other biologics for egg and walnut allergies, with plans to begin Phase 2 testing in 2019. “Our goal is file an IND for the egg therapeutic, AR201, by the end of 2018 and for a walnut IND for AR301 approximately six months later,” he adds.

Expanding CODIT™ to Other Major Food Allergies

In February, Aimmune reported that its PALISADE Phase 3 study met the primary efficacy endpoint, as 67.2% of AR101 patients aged four-to17 tolerated at least a 600-mg dose of peanut protein in the exit food challenge, compared with 4% of placebo patients. The 600-mg dose has the protein equivalent of approximately two peanut kernels. Before treatment, patients had been able to tolerate, at maximum, the equivalent of approximately one tenth of a single peanut kernel.

The trial enrolled 498 peanut-allergic patients aged four-to-17 at more than 60 clinical sites in North America and eight countries in the EU.

In addition, the lower bound of the 95% confidence interval of the difference between treatment arms at the primary endpoint was 53%, greatly exceeding the pre-specified threshold of 15%.

PALISADE Met Primary and Key Secondary Efficacy Endpoints for Ages 4-17

Compared with placebo, in the exit food challenge, the AR101 treatment group developed fewer moderate and severe symptoms; required more peanut exposure for the onset of symptoms; was more likely to complete the challenge; and needed less epinephrine.

In the U.S., AR101 has FDA fast track designation and FDA breakthrough therapy designation for peanut-allergic patients aged four-to-17.

Mr. Bjerkholt also points out that Aimmune has three active late-stage AR101 studies underway. They include an open-label follow-on trial to PALISADE, ARC004, crossing PALISADE placebo patients over to active treatment and rolling AR101 patients over to extended maintenance. Aimmune plans a data cut from this trial in the third quarter of 2018.

Aimmune also expects data from the RAMSES trial, taking place in the U.S. and Canada and designed to illuminate real-world patient and allergist experiences with AR101, in the second half of 2018, followed by data from the ARTEMIS trial, a dedicated European study of AR101, in early 2019. 

The company plans to file a marketing authorization application with the European Medicines Agency in the first half of 2019.

Numerous Value-Creating Milestones Anticipated

According to Mr. Bjerkholt, the prevalence of peanut allergy is some six million individuals in the U.S. and Europe, of which about half are in the four-to-17 age group, almost equally divided between the U.S. and Europe. “We have first mover advantage in this potentially life-threatening indication and our goal is to build a trusted brand.”

He says Aimmune’s Florida manufacturing plant has the commercial capacity to meet global demand and also produce enough AR101 to treat about 200,000 new patients a year.

There are about 5,000 allergists in the U.S. A survey by the American Academy of Allergy, Asthma and Immunology in 2015 found that 75% of allergists would prescribe an FDA-approved oral immunotherapy, with the remainder needing more information. “For kids and teens, we think this is a good solution,” Mr. Bjerkholt suggests.

He also points out that AR101 in-office dosing would be similar to allergy shots. And payer market research suggests strong access for this life-threatening pediatric indication, he adds.

Aimmune plans to build a sales force to promote AR101 to allergy group practices. “We think we can accomplish our sales and marketing objectives with a team of 80-to-100 sales people,” Mr. Bjerkholt figures. The company plans to hire a VP of sales this year and build out the sales team closer to launch.

“The therapeutic goals of AR101 align with what parents want, specifically a meaningful level of protection for their kids against an accidental exposure to peanut, with no or muted reactions,” Mr. Bjerkholt contends. “Parents want to know that if their kids go through the therapy, they are protected.”

As part of its goal on advancing the field of food allergies, Aimmune has collaborations with Golden Peanut and Tree Nuts, Nestlé Health Science, and Regeneron and its strategic alliance collaborator, Sanofi.

Nestlé Health Science has injected $175-million into Aimmune for a 15% stake under a two-year collaboration that ends in November 2018. The accord is focused on expansion of Aimmune’s pipeline and Aimmune retains full commercial rights to all CODIT pipeline assets, including AR101.

Mr. Bjerkholt says the innovation accord with Regeneron involves Phase 2 testing, sponsored by Regeneron, of AR101 with adjunctive use of dupilumab in 2018. “The plan is to explore sustained unresponsiveness in peanut allergy or a potential functional cure,” he adds.