Familial Mediterranean Fever

Aristea Team/Courtesy Photo Due to safety concerns, Aristea Therapeutics announced Friday it is discontinuing the development of its Phase II lead program RIST4721. As a result, the San Diego-based biotech is also dissolving its business. After careful and extensive consideration and “exploring a range of strategic alternatives,” Aristea’s board decided that ending the company and its operations was a sound business decision, said James Mackay, Ph.D., president and CEO, Aristea, in a statement. Aristea launched in December 2018 as an AstraZeneca spin-out. The company dove into the biopharma space with $15 million in Series A backing to rehome molecules to develop novel treatments against severe inflammatory conditions. “Our aim here is to take molecules that have been discarded by big pharma for a variety of reasons, or from other biotechs who have taken them through preclinical development but are not equipped to take them into clinical,” Mackay told BioSpace in a January 2022 interview. Novo Holdings, the private limited liability company under the Novo Nordisk group, backed the startup. Aristea gained exclusive global rights to RIST4721, its lead asset, from AstraZeneca. The candidate is an antagonist of the CXCR2 protein and was set to enter Phase II assessments in palmoplantar pustulosis when the company launched. The company completed enrollment into this study in October 2019. Palmoplantar pustulosis is a recurrent inflammatory disorder characterized by flares of neutrophil-filled pustules on the palms and feet, causing pain, itching and burning sensations at these sites. RIST4721 intended to treat this condition by suppressing CXCR2, which is chiefly responsible for recruiting neutrophils at the site of inflammation. In July 2021, RIST4721’s potential attracted $63 million in Series B financing, which helped Aristea further advance the candidate through the clinic, build its leadership team and form new strategic partnerships. The Series B was again led by Novo Holdings, with new investors Arena Pharmaceuticals and Tekla Capital Management joining. Concurrent with the funding round, Aristea entered into a strategic collaboration with Arena Pharmaceuticals, a Pfizer unit, giving the latter the exclusive option to acquire Aristea and all its CXCR2 programs post-Phase II in exchange for $60 million upfront and $10 million in equity investments. However, in Friday’s announcement, Aristea revealed that safety concerns had snuffed out RIST4721’s promise. In an email to BioSpace, a company representative said they did not have additional information to provide regarding the safety concerns. By the time Aristea folded, RIST4721 was also being trialed for hidradenitis suppurativa, familial Mediterranean fever and Behcet’s disease. The company also developed RIST5122 and RIST8309, both CXCR2 antagonists, for undisclosed indications.

February alone has seen Magenta Therapeutics and Vyant Bio announce they are closing down. Confronted with safety findings, Aristea Therapeutics is not only canning work on its mid-stage inflammatory program but has decided to dissolve the business entirely. Things seemed to be going well for Aristea as recently as last November, with the biotech taking on board a crop of clinical experts as it looked to expand its pipeline. The company’s lead asset, a CXCR2 antagonist dubbed RIST4721, was undergoing phase 2 trials for four neutrophil-mediated diseases: a rare inflammatory disorder called palmoplantar pustulosis (PPP), a painful skin condition called hidradenitis suppurativa, a genetic disorder called familial Mediterranean fever and Behcet's disease, which causes inflammation of the blood vessels. But safety findings from the phase 2 trials have blown up those plans, the company revealed in a bombshell announcement this morning. Aristea didn’t go into details of the specific safety signals or which trials they had been observed in. Whatever they were, the findings were significant enough that the San Diego-based biotech “has discontinued the RIST4721 development program in order to protect patient safety.” With that decision goes any hopes of keeping the business up and running. "Although the decision to discontinue the RIST4721 development program is disappointing for the Aristea Therapeutics team and patients in need of new treatment options, we believe it is absolutely the right decision to protect patient safety, which must always be paramount in drug development," CEO James Mackay, Ph.D., said in the release. "The board's decision to dissolve Aristea Therapeutics was reached after exploring a range of strategic alternatives and is a sound business decision."  The news may be felt all the way up at Pfizer’s headquarters. The Big Pharma had acquired the option to take over the biotech after it bought Arena Pharmaceuticals at the tail end of December 2021. That deal came six months after Arena had stumped up funding for Aristea as part of a collaboration to push RIST4721 through the clinic. Once the therapy completed the phase 2 trial in PPP, Arena—and later Pfizer—had the option to buy Aristea outright. At the time, analysts also saw potential in RIST4721 as a PPP treatment. There are no treatments specifically for the condition—which causes blisterlike sores to form on the palms of the hands and soles of the feet. Patients use topical steroids, moisturizers or ultraviolet light therapy to ease symptoms. Aristea’s drug was designed to tackle PPP at the source by dialing down CXCR2, a receptor that plays a role in recruiting neutrophils, or white blood cells, to areas of inflammation. Aristea is only the latest in a string of biotech closures in the opening weeks of this year, a reflection of the tough climate that the industry still faces. February alone has already seen Magenta Therapeutics wind down in the wake of a patient death as well as Vyant Bio announce that it's reached the end of the road.

AstraZeneca spinout Aristea Therapeutics is shutting down after terminating multiple Phase II studies of its inflammatory drug, citing undisclosed safety issues. With the culling of multiple mid-stage tests of the investigational drug RIST4721, “to protect patient safety,” Aristea said Friday its board considered “a range of strategic alternatives” and decided to turn off the lights on the 12-employee San Diego biotech. The company declined to comment on the safety findings or make an executive available for an interview. Aristea joins a cohort of folded biotechs , like Arch Oncology and Goldfinch Bio , which have ended operations for a variety of reasons . President and CEO James Mackay had taken a neglected AstraZeneca CXCR2 antagonist and revived it as the central focus of a new biotech that raised $138 million from the likes of Novo Holdings, Fidelity, Tekla Capital and others. Also at play was a potential exit to Pfizer via the Big Pharma’s Arena unit, which had the exclusive option to buy the biotech once wrapping up a Phase IIb study of the drug in palmoplantar pustulosis, a rare chronic inflammatory skin disease. But that study and others — including in hidradenitis suppurativa , Behçet’s disease and familial Mediterranean fever — are ending. In the Friday morning press release, Mackay called the move a “sound business decision.” At the time of leadership hires last fall, Mackay said Aristea would expand the pipeline with more “immunology/inflammation assets.” The company also had two other CXCR2 antagonists in preclinical stages for undisclosed indications. The goal was to inhibit the activity of CXCR2, a cytokine receptor that helps attract neutrophils to inflammation sites. The white blood cell plays a role in tissue damage in autoimmune and inflammatory diseases.