It seems like Vera Therapeutics, Inc. are working on a lead candidate called atacicept, which targets IgAN and Persistent Proteinuria, and they recently presented some positive phase 2b data.

Now, atacicept might sound a bit complicated if you’re not familiar with the technical details, but what’s important to note is that it’s a legacy molecule that has been around for a couple of decades. Initially developed by a small U.S. company, it was later taken up by Merck Serano for further development in various indications. Unfortunately, it didn’t show promising results back then and was seemingly abandoned.

According to a review article from 2020, atacicept failed to demonstrate effectiveness in multiple sclerosis, optic neuritis, rheumatoid arthritis, and systemic lupus erythematosus. It did show increased infection rates in patients with systemic lupus erythematosus, but not in the other diseases it was tested on.

Despite this historical background, Vera Therapeutics saw potential in atacicept and acquired the license to develop it. The advantage of working with such molecules is that they’re well-studied and there are no surprises. However, the downside is that if there was something truly valuable about them, it’s likely someone would have discovered it in the past two decades. So, the general consensus is that it might not be a worthwhile endeavor.

Interestingly, Vera Therapeutics presented data last month from a phase 2b trial called ORIGIN, focusing on IgAN and Persistent Proteinuria. The trial showed positive results, meeting the primary and key secondary endpoints. Patients experienced reductions in proteinuria and stabilization of eGFR (estimated glomerular filtration rate) up to week 36. These results are particularly relevant because a 30% reduction in UPCR is considered clinically meaningful for improving renal function in IgAN patients.

One significant takeaway from the trial is the safety profile of atacicept. The highest dose, 150 mg, had a safety profile equivalent to placebo, and the lower doses were actually safer than placebo. There were no higher infection rates or interruptions due to low IgG (hypogammaglobulinemia).

Now, Vera Therapeutics is enrolling patients for a confirmatory phase 3 study. They expect to release top-line data in the first half of 2025, submit a BLA (Biologics License Application) in the same year, and potentially launch the treatment in 2026.

Aside from IgAN, Vera is also conducting a phase 3 study of atacicept in Lupus Nephritis, based on previous phase 2 studies conducted by other sponsors. They believe that atacicept, with its dual inhibition of BLyS and APRIL, may be more potent than blocking BLyS alone, providing an advantage over other therapies.

It’s worth mentioning that Vera has another molecule called MAU868, which is currently in a phase 2 trial for the treatment of allograft-threatening BKV infection in kidney transplant recipients. So they have multiple irons in the fire!

Looking at their financials, Vera Therapeutics has a market cap of $710 million and a cash reserve of $197 million. They spent $25 million on R&D and $6 million on general administration in the previous quarter. At their current spending rate, they have enough cash for about six more quarters, or well into 2025. However, the company believes their cash will last them into 2026 or beyond the top-line data of their lead asset/indication combination.

Vera Therapeutics is primarily owned by institutional investors and private equity/

venture capital firms, with little retail presence. Interestingly, insiders within the company have been buying stock in recent months, which can be seen as a positive sign.

Of course, there are risks involved. Vera Therapeutics is considered a microcap company, which comes with its own set of associated risks like relatively low trading volume. In terms of company-specific risks, the short exclusivity period for approved biologics and the fact that atacicept is an old molecule with limited intellectual property protection are notable concerns. Additionally, the previous trial data doesn’t align with the positive results presented by Vera, which raises doubts about the outcome of the confirmatory phase 3 trial.

All in all, despite the positive phase 2b data, I personally remain cautious about Vera Therapeutics, Inc. due to the mentioned risk factors. I prefer to stay on the sidelines and observe how things progress.