Anti-drug antibodies noted in the phase Ib portion of the PREVAIL study in lupus drew queries for Oldwick, N.J.-based Provention Bio Inc. during a conference call related to earnings, but analysts seemed more interested in the company’s later-stage push in type 1 diabetes (T1D).

Shares of Provention (NASDAQ:PRVB) closed at $7.16, down $1.85, or 20.5%, after the firm disclosed top-line results from PREVAIL (PRV-3279 EVAluation In Lupus), testing PRV-3279 in 16 healthy volunteers. A humanized diabody targeting the B-cell surface proteins CD32B and CD79B, the compound is meant to intercept the pathophysiology of systemic lupus erythematosus and other B cell-mediated autoimmune diseases and to prevent or reduce the immunogenicity of biotherapeutics, including gene therapy products.

PRV-3279 proved well-tolerated in PREVAIL, with no serious adverse events. Pharmacokinetic parameters turned out dose-proportional, and high levels of B-cell engagement resulted in durable pharmacodynamic responses, Provention said. As expected by researchers, the candidate did not deplete B cells and yielded dose-proportional, extensive and sustained binding to circulating B lymphocytes, plus an extended pharmacodynamic effect was shown by the drop in circulating immunoglobulin M levels.

Alethia Young, of Cantor Fitzgerald, however, wanted to know more about the anti-drug antibodies that showed up at both dose levels tested. Chief Scientific Officer Francisco Leon said the finding was expected and “known from the prior phase I trials” done by Rockville, Md.-based Macrogenics Inc., “like with any biotherapeutic.” In May 2018, Provention licensed PRV-3279 (formerly MGD-010) from Macrogenics in a deal that gave Macrogenics a warrant to purchase a minority equity interest in Provention, as well as milestone payments if goals are met, plus royalties. The agreement also included PRV-031 (teplizumab) for early onset T1D, a pediatric orphan indication.

Leon stressed that, with PRV-3279, the immunogenicity “was not affecting exposure, was not affecting safety, and was not affecting the ability of the drug to inhibit the B cells. What comes next is digesting these data, discussing [them] with our key opinion leaders, and finalizing the design of the lupus phase IIa protocol.” Thomas Smith, of SVB Leerink, pursued Young’s line of questioning, asking whether more work with regard to dosing might lie ahead. Leon said Provention “chose the doses [for the phase Ib] based on the dose-escalation work done by Macrogenics in the first-in-human studies.” He said the firm has “already identified a dose level that is both well-tolerated and highly efficacious, so we do not anticipate requiring any additional dose-finding work in the phase IIa trial.”

Talk turned to teplizumab, a humanized, anti-CD3 monoclonal antibody. Provention expects to complete submission of a BLA in the fourth quarter of 2020. CEO Ashleigh Palmer said the company will not try commercializing the drug in Europe and is “actively seeking partnerships” there. Chief Commercial Officer Jason Hoitt noted that Provention is “18 months or so away” from a possible launch of teplizumab in the U.S. and therefore “nowhere near finalizing the price. Initial work is now underway around building the health-economic story. I think the addition of Jessica Blumstein to the team brings a wealth of experience in doing just that.” Blumstein was brought aboard as vice president of market access and distribution. In the biotech sector for 18 years, she most recently served as head of global commercial development and general U.S. manager at Enzyvant Therapeutics Inc., and before that was senior director of global market access at Sarepta Therapeutics Inc. for more than two years.

Hoitt said Provention will “start to engage payers as early as next quarter,” and “the formal pricing research will come later this year.” Regarding the size of the sales force, he said nothing is set in stone yet; the company plans to let the data drive such decisions. “We want to approach this in as lean a way as we possibly can to maximize the opportunity,” he said, and guessed “ballpark numbers” of between 35 and 50 sales reps.

In December 2019, Provention disclosed that Johnson & Johnson had decided not to take up an option to buy back the rights to the CSF1R inhibitor PRV-6527, which Provention had been developing for Crohn’s disease. That wasn’t much of a surprise, since in October phase IIa top-line data showed that the drug did not differentiate from placebo. J&J unit Janssen Pharmaceuticals said it would support and expand the field of the license agreement between Provention and Janssen, originally established in inflammatory bowel disease in April 2017. “In our view, Janssen's decision, though minor and in line with our expectations, constitutes a potentially important step, as it should make out-licensing of PRV-6527 easier,” Wainwright analyst Raghuram Selvaraju wrote in a Dec. 30 report that reiterated his buy rating and 12-month price target of $20. Like others, he placed most of the stock’s value on teplizumab. “While manufacturing-related gating items may only permit completion of the BLA filing in the fourth quarter of 2020, we believe the breakthrough therapy designation that has already been accorded to teplizumab could confer priority review,” he wrote, leading to launch in the second half of 2021.

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