Milk Hypersensitivity

DBV reported cash reserves of $46.4m as of 30 September, down by $92.2m it had at the end of last year. Image credit: UncleFredDesign / Shutterstock. DBV Technologies , which specialises in developing treatments for food allergies, has said that it will not have sufficient cash reserves to fund operations for “at least the next 12 months”. Noted as part of its third quarter (Q3) earnings report, the company cited operating losses and negative cash flows since the company’s inception as the reason for the low cash reserves. The French biotech’s lead candidate, peanut allergy treatment Viaskin Peanut, has till date failed to secure US regulatory approval. DBV noted that it intends to “seek additional capital as it continues research and development (R&D) efforts and prepares for the launch of Viaskin Peanut if approved.” While cautioning its investors that the company could not guarantee that it could secure financing at favourable terms, if at all. Adding DBV may need to scale back operations, by delaying or reducing its R&D operations, or may relinquish the rights to its pipeline candidates, if it fails to secure financing. DBV’s stock dropped by more than 8.17% in trading today (7 November) on the Euronext market. The company reported cash reserves of $46.4m as of 30 September, down by $92.2m from the cash on hand it had at the end of last year (31 December 2023). DBV noted that the funds were primarily directed towards clinical trial activity for Viaskin Peanut. In April 2023, the US Food and Drug Administration (FDA) stated that although DBV’s peanut allergy patch successfully met the primary endpoints in the Phase III EPITOPE trial (NCT03211247) in toddlers (aged one to three years), an additional safety study is required for approval. The Viaskin patch’s approval process has been a tumultuous one. In 2017, the allergy path failed to meet its primary endpoint in the Phase III PEPITES clinical trial (NCT02636699) in children aged 4-11 years. The company’s second attempt at Phase III VITESSE trial (NCT05741476) in a more narrowed age group of 4-7 years suffered a setback when the FDA placed a partial clinical hold on the study in September 2022. The hold has since been lifted and the company expects to share topline data from the study in Q4 2025. Following the back and forth with the FDA, DBV plans to pursue Viaskin Peanut’s approval in toddlers in the US and children aged one to seven years in Europe. LAst month, the company noted that as part of the accelerated approval pathway, the FDA requires additional safety data. DBV plans to start an additional safety study , COMFORT Toddlers, evaluating Viaskin Peanut in approximately 250 toddlers in Q2 2025. The company also plans to start a COMFORT Children, a safety study in four-to-seven-year-olds in Q2 2025. The trial is expected to enrol 250 participants. Another candidate in DBV’s pipeline is a milk allergy treatment, DBV135 (Viaskin milk patch). The company evaluated the patch in children aged two to 17 years in a Phase I/II MILES trial (NCT02223182). DBV is also investigating DVB135 as a treatment for an allergic inflammatory condition, eosinophilic esophagitis. DBV has also stated its intention to expand beyond food allergy therapies into vaccines and treatments for autoimmune and inflammatory disorders. However, these programmes are in the preclinical stage.

Researchers have discovered a link between gut bacteria and the success of milk-allergy oral immunotherapy. The study found that Bifidobacterium -- a genus of beneficial bacteria in the gut -- was associated with a higher chance of successful treatment. The finding may help in the development of more effective oral immunotherapies, perhaps by combining them with probiotic supplements. Researchers led by Hiroshi Ohno at the RIKEN Center for Integrative Medical Sciences in Japan have discovered a link between gut bacteria and the success of milk-allergy oral immunotherapy. Published in the scientific journal Allergology International, the study found that Bifidobacterium -- a genus of beneficial bacteria in the gut -- was associated with a higher chance of successful treatment. The finding may help in the development of more effective oral immunotherapies, perhaps by combining them with probiotic supplements. Many children have allergic reactions to cow's milk, specifically to certain milk proteins. Although most grow out of it, for some it becomes a life-long challenge to avoid all foods that include milk, especially when the allergic reactions are severe and include anaphylactic shock. Researchers have found that milk allergy is improved by oral immunotherapy, a treatment in which patients purposely drink small amounts of milk. Unfortunately, while allergic reactions are controlled during treatment, in most cases, tolerance disappears soon after the treatment ends. Gut bacteria are thought to help reduce allergic reactions to some foods, but little is known about the link between these bacteria and oral immunotherapy for milk allergy. Therefore, the RIKEN IMS team examined 32 children with cow's milk allergy who received oral immunotherapy, with the first month being conducted in a hospital. "Oral immunotherapy is not without risk," explains Ohno. "We closely monitored the children in the hospital, and in fact 4 children had such severe reactions to the milk that we could not allow them to continue the treatment." The remaining 28 children then completed an additional 12 months of treatment at home. Next, they avoided milk for two weeks, and were then tested on a double-blind, placebo-controlled food challenge to see if they could still tolerate milk without any allergic reactions. During the food challenge, children were initially given a tiny amount of placebo or milk -- only 0.01 ml -- which was gradually increased every 20 minutes until they had an allergic reaction or until they could drink the final 30 ml without a reaction. The researchers focused their analyses on immunological and bacterial changes during the treatment and the relationship between gut bacteria and successful treatment -- which was defined as showing milk tolerance that lasted beyond the treatment period by passing the food challenge. They found that during treatment, immunological markers for cow's milk allergy improved, and bacteria in the gut changed. Nevertheless, after two weeks of avoiding milk, only 7 of the 28 children passed the food challenge, even though they had been able to drink milk safely at the end of the treatment. To understand why the treatment worked for these seven children but not the others, the team looked for the clinical factors and types of gut bacteria that were related to successful treatment. Of the clinical factors, unsuccessful treatment was more likely in children who were being treated for eczema or asthma and in children who initially had higher levels of milk-protein antibodies. Among the gut bacteria, the presence of Bifidobacterium, a genus of beneficial bacteria in the Bifidobacteriaceae family was related to a higher chance of successful treatment. In fact, only children who passed the final food challenge showed an increasing trend in these bacteria over the course of treatment. When considering ways to improve oral immunotherapy, this is good news because while the first two factors are difficult to change, the types of bacteria in one's gut are not set in stone. "With this study, we have identified gut environmental factors that help establish immune tolerance against cow's milk allergy via oral immunotherapy," says Ohno. "The next step is to examine the mechanisms underlying this phenomenon and to develop ways to improve the effectiveness of oral immunotherapy, such as the addition of probiotic supplements."

DBV Technologies hopes to complete enrollment in two supplemental safety trials of a peanut allergy therapy this year. DBV Technologies, a French biotech working on a treatment for food allergies, says it's running out of cash. The disclosure came via a going concern note in the company’s fourth-quarter and full-year 2023 earnings report on Friday, with DBV saying it doesn’t have enough money to keep the lights on for a full 12 months. DBV says it has until the very end of the year based on the $141.4 million in cash reported as of the end of December 2023.  To persevere, the biotech will look to raise more money via debt and equity offerings. DBV’s cash reserves fell by nearly $68 million in 2023, with most of the money going toward R&D.   Much of the biotech’s focus centers on lead peanut allergy treatment DBV712, with two phase 3 safety trials ongoing in kids. The goal is to complete enrollment in two supplemental six-month safety trials this year, despite experiencing delays that were attributed to new clinical trial rules in Europe.  “We expect good momentum regarding Vitesse recruitment in the next several months and last subject screened by Q3 2024,” DBV CEO Daniel Tassé said in a release. The late-stage development work makes DBV’s current cash crunch all the more perilous, given how close the company potentially is to the market.  In addition to wrapping up enrollment in the two COMFORT trials, DBV expects to have three-year data from an efficacy trial in toddlers 1-3 years old. A sibling trial for kids 4-7 years old is slated to screen its last patient by the third quarter of 2024. That study, named VITESSE, was previously on an FDA partial hold while the company and regulators worked on an updated trial protocol.  Should DBV strengthen its balance sheet, there are two additional phase 2 trials waiting in the wings for runner-up med DBV135, which is in development for milk allergies and eosinophilic esophagitis.