Startup Protego Bio secures $130 million in funding for critical test of first-in-class drug to treat rare plasma disease
Light-chain amyloidosis is not cancer, but anticancer drugs are the standard treatment for this rare disease. Patient demand for new treatment options spurs research and development efforts by biotech and Big Pharma companies. Protego Biopharma aims to launch a potential first-in-class drug that differentiates itself from the disease by targeting the proteins that drive it before they cause most of the damage.
The San Diego-based startup doesn't have Phase 1 data yet, but what it does have is the confidence of a consortium of investors that has pledged a new $130 million to support plans to advance the drug into pivotal clinical trials. Novartis Venture Fund and Forbion led the investment in Protego, which announced a Series B round of financing on Monday.
Light chain amyloidosis, or AL amyloidosis, begins in the bone marrow, where abnormal plasma cells produce misfolded proteins called light chains. Because of this misfolding, the body is unable to recognize these proteins and clear them properly. As a result, the protein forms amyloid clumps around organs. The heart is the organ most affected by AL amyloidosis; heart failure is the most common cause of death from the disease.
“[Misfolded proteins] “The core problem with light chain amyloidosis is that too many of these bad light chains, even in small amounts, can be very toxic to organs,” said Protego CEO Brent Warner.
AL amyloidosis originates in plasma cells, similar to multiple myeloma, a cancer of plasma cells. That's why multiple myeloma drugs are the standard treatment for the disease. Warner said Protego is not intended to replace the current combination of plasma cell-targeting drugs used to treat AL amyloidosis. But the startup is bringing a novel approach with its small molecule PROT-001.
Warner said there are two key challenges in drugging misfolded light chains with small molecules. First, these proteins do not have natural binding sites for drugs. Second, the genetic mutations that cause misfolding are different for each patient.
Werner said Protego's scientific founders discovered a mysterious binding site, a hidden pocket where molecules can bind, making the protein druggable. The company designed PROT-001, bound it to the mysterious site, and explained the sequence that causes the disease in most patients. Binding to the light chain stabilizes it, Warner said, returning the protein to a state that the body recognizes and eliminates naturally. Over time, protein buildup on the heart and other organs should also be cleared. In addition, the drug's effect of immediately binding to light chains produced by plasma cells should prevent further aggregation.
Late-stage clinical studies of AL amyloidosis have not been very successful. Takeda Pharmaceutical's ixazomib (brand name Ninlaro) is an oral proteasome inhibitor approved for multiple myeloma but failed a Phase 3 trial in Al amyloidosis in 2019. Last year, Prothena's birtimab and AstraZeneca's anselamimab each failed in Phase 3 trials for the disease.
The Prothena and AstraZeneca drugs are antibodies designed to bind to amyloid that has accumulated on organs, reducing the buildup of this protein. Warner said Protego believes its small molecule can achieve better clinical trial results because the drug works upstream of amyloid aggregation and the damage it has already caused.
“Apoptosis (cell death) may already occur in many cells,” he explains. “So you can remove some of the aggregates, but you're not removing the toxic light chains that are still floating around and can continue to damage cells.”
Protego's approach to protein stabilization is similar to that of tafamidis, a drug marketed by Pfizer under the brand names Vyndaqel and Vyndamax to treat the rare disease transthyretin amyloidosis (ATTR). Like AL amyloidosis, ATTR is caused by misfolded proteins, causing amyloid to accumulate on organs, especially the heart. Tafamidis comes from startup FoldRx Pharmaceuticals, which Pfizer acquired in 2010. Pfizer guided Vyndaqel and Vyndamax to FDA approval, and the drugs are currently top sellers as treatments for ATTR cardiomyopathy, although the field has expanded over the past year with new FDA-approved treatments.
Protego was co-founded in 2017 by Scripps Research chemistry professor Jeffery Kelly. Kelly is an expert in protein folding and previously co-founded FoldRx based on his research at Scripps. Protego builds on tafamidis, and the startup's team includes many former FoldRx employees, Warner said. Protego raised $51 million in Series A funding in 2023 but has disclosed little since then. Warner most recently served as president of Poseida Therapeutics' gene therapy business and was named CEO of Protego last year. He said the company was keeping a low profile until it secured financing and was ready to move forward with its lead project.
A placebo-controlled Phase 1 study is underway in Australia evaluating PROT-001 in more than 100 healthy volunteers. While the primary goal is to assess the safety of the molecule, secondary endpoints include measuring how the drug is distributed and its concentration in the body and confirming that it binds to its target. This confirmation will come from Protego's proprietary AmyLite assay. A key test for once-daily or twice-daily dosing will depend on the half-life of the molecule, which was also measured in the phase 1 study. Data from the Phase 1 study are expected early next year. Protego plans to begin Phase 2/3 clinical trials in late 2026.
Joining Protego as major investors in Series B are new financial backers Omega Funds, Droia Ventures, YK Bioventures and Digitalis Ventures. Early investors Vida Ventures, MPM BioImpact, Lightspeed Venture Partners and Scripps Research also participated in the latest financing.
Photography: Protego Biopharma
