Protego Biopharma has completed a $130 million oversubscribed Series B financing that it said will help it advance its lead candidate, the amyloid light-chain (AL) amyloidosis treatment PROT-001, into a pivotal clinical trial expected to start in the second half of 2026.
PROT-001 is an oral small molecule kinetic stabilizer of lambda light chains (λLCs). PROT-001 reflects Protego’s approach of developing small-molecule pharmacological chaperones that directly bind to and modulate target protein stability. These chaperones get their name by acting as cellular “guides,” ensuring proteins fold correctly.
The approach aims to restore healthy-state structure and function by modulating cellular stress and secretory pathways to restore proteostasis. By stabilizing immunoglobulin light chains and preventing amyloid buildup, Protego reasons, PROT-001 can address disease at its root cause rather than simply managing symptoms.
It’s an approach successfully applied by Vyndamxax® (tafamidis) and its lower-dose version Vyndaqel® (tafamidis meglumine), which Pfizer plans to stop selling in the United States as of December 31. Both are once-daily capsule transthyretin stabilizers indicated to treat the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults.
Protego reasons that its approach could treat a wide variety of protein misfolding disorders. The company said it is exploring addressing monogenic protein misfolding diseases that cause myopathy, stroke, renal disease, retinal diseases, channelopathies, and various degenerative diseases.
“We really see 001 as not its own class, but its own effective therapy where there’s not true competition against us,” Brent Warner, Protego’s president and CEO, told GEN. “Most of the other approaches are to eradicate and remove the clonal plasma cells that are producing this toxic light chain. But what we know is, even with the daratumumab data, while some patients can get to a heme response and a cardiac response, that’s not true for all.”
The reason, Warner explained, is the residual amount of clonal plasma cells pumping out the misfolded light chain.
Tandem treatment
Protego envisions PROT-001 working in tandem with the current standard of care. It consists of daratumumab, the adult multiple myeloma intravenous drug marketed as monotherapy and in numerous combinations by Johnson & Johnson (J&J)’s Janssen Biotech as Darzalex®; and CyBorD (cyclophosphamide-bortezomib-dexamethasone), a chemotherapy combo also indicated for multiple myeloma.
“With PROT-001 working upstream, we expect to put 001 alongside the standard of care cocktail by having daratumumab and CyBorD eradicate as many of the plasma cells as it can, while we capture and re-stabilize that misfolded light chain,” Warner added. “We should see a drastic improvement in morbidity and mortality in these subjects.”
That standard of care cocktail, known as Dara-CyBorD, is the only treatment approved to date by the FDA for AL amyloidosis. In a retrospective analysis published August 18 in the journal Blood, researchers at the Mayo Clinic reported that their institution’s use of autologous stem cell transplant (ASCT) showed a 71% average annual reduction in the 15 years since the introduction of the immunomodulatory drug-sparing regimen CyBorD, which was supplanted as standard of care after the FDA granted accelerated approval to Dara-CyBorD in 2021 for adults newly diagnosed with AL amyloidosis.
“Dara-CyBorD is an effective regimen that can achieve a rapid and deep hematological response, deep organ responses, and provides an OS benefit in AL amyloidosis when compared with CyBorD,” a team of researchers based at Mayo Clinic’s Rochester, MN, campus concluded in a study published in Blood Neoplasia.
The FDA granted full approval last month to Dara-CyBorD, using the subcutaneous form of daratumumab, Darzalex Faspro® (daratumumab and hyaluronidase-fihj), along with CyBorD. The FDA based its full approval on data from the Phase III open-label ANDROMEDA trial (NCT03201965) in 388 patients with newly diagnosed AL amyloidosis with measurable disease and at least one affected organ.
ASH presentations
In targeting AL amyloidosis, Protego is one of numerous companies aiming to develop newer, patient-friendlier treatments for the disorder. Two of those companies are presenting positive Phase I/II data for their AL amyloidosis candidates at the 67th American Society of Hematology (ASH) Annual meeting, to be held in Orlando, FL.
One is Attralus, which will report data from its Phase I/II clinical program (NCT05521022 and NCT05951049) showing that its recombinant immunoglobulin 1 (IgG1) monoclonal antibody fusion protein AT-02 can improve renal function in AL amyloidosis patients with renal disease.
In November, Attralus reported seeing a mean increase in eGFR of ~16 mL/min over 40 weeks above baseline in 5 of 6 patients (83%) who received AT-02 2500 mg once every two weeks (q2w), while 4 of 6 patients (67%) experienced a >10 mL/min/1.73 m2 increase in estimated glomerular filtration rate (eGFR).
The mean eGFR decreased from baseline, however, by 5.1 mL/min/1.73 m2 in the AT-02 2500 mg every four weeks (q4w) group of three evaluable patients. Mean baseline eGFR was 73 mL/min/1.73 m2 in the 2500 q4w cohort and 57 mL/min/1.73 m2 2500 q2w cohort.
“These initial data support the potential for AT-02, a novel pan-amyloid depleting Ig fusion protein, to improve renal function in AL patients with renal disease who have achieved hematologic response,” the Attralus researchers concluded in an abstract.
Also presenting data at ASH is Immix Biopharma, which in November announced positive data from its Phase I/II NEXICART-2 trial (NCT06097832) assessing its NXC-201 in relapsed/refractory AL amyloidosis. The study, conducted by Immix’s Nexcella subsidiary, showed 95% of patients (19/20) normalized pathological disease markers (involved free light chain [FLC] or M-spike) after treatment with NXC-201, all within 14 days, with a median of 7 days, all with a reduction of the difference between involved and uninvolved FLC to <1 mg/dL. Fourteen of 16 patients tested were minimal residual disease (MRD) negative in bone marrow at day 25.
“Our data suggests that the novel anti-BCMA CAR-T NXC-201 may become a valuable treatment option for RR AL pts,” Immix researchers concluded in their abstract. The researchers are set to present their data at the ASH Annual Meeting.
Clinical landscape
Kristen Hsu, executive director of research with the Amyloidosis Research Consortium, last month highlighted in a video the clinical trial landscape for NXC-201 and six other AL amyloidosis drug candidates being developed. Of the seven non-Protego candidates Hsu discussed, NXC-201 and three others are being studied in relapsed/refractory AL amyloidosis:
- Linvoseltamab—Regeneron Pharmaceuticals is recruiting patients for the Phase I/II LINKER-AL2 trial (NCT06292780) assessing linvoseltamab, a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager now marketed to treat adults with multiple myeloma under the brand name Lynozyfic™ (linvoseltamab-gcpt).
- Etantamig (ABBV-383)—AbbVie is recruiting patients for a Phase I/II trial (NCT06158854) evaluating etantamig, a BCMA x CD3 bispecific T-cell engager (BiTE).
- AZD0120/GC012F—AstraZeneca is recruiting patients for the Phase I/II ALACRITY trial (NCT07081646) assessing AZD0120, a chimeric antigen receptor T cell (CAR T) therapy targeting CD19 and BCMA, while AZ’s Gracell Biotechnologies subsidiary (acquired for up to $1.2 billion in 2024) is recruiting patients for a Phase Ib open-label, nonrandomized trial (NCT07250269) designed to determine a recommended dose for Phase II study.
Johnson & Johnson’s teclistamab, a bispecific BCMA-directed CD3 T-cell engager now marketed to treat multiple myeloma as Tecvayli® (teclistamab-cqyv)—is the subject of four Phase II trials all recruiting patients: A combination study with daratumumab (NCT07110844); a study in previously treated immunoglobulin AL Amyloidosis sponsored by Peking Union Medical College Hospital (NCT06935162); a similar study sponsored by European Myeloma Network (NCT06649695); and a study in patients with newly diagnosed Mayo stage IIIB immunoglobulin AL amyloidosis, also by Peking Union Medical College Hospital (NCT07079423).
Teclistamab is also being evaluated in an observational study in systemic AL amyloidosis from Peking University People’s Hospital (NCT06699394); while AL amyloidosis is one of three conditions under study in the Norwegian Immunotherapy in Multiple Myeloma Study, along with plasma cell leukemia (NCT06855121).
Another J&J AL amyloidosis candidate, ramantamig (JNJ-79635322), is a trispecific antibody targeting BCMA and G-protein-coupled receptor class 5 member D (GPRC5D). Ramantamig is under study in a Phase I trial (NCT05652335) in patients with previously treated AL amyloidosis or relapsed or refractory multiple myeloma.
PROT-001 anchors Protego’s pipeline of first-in-class small molecule therapeutics that reprogram protein folding to address systemic amyloid diseases and other protein misfolding disorders.
Other pharmacological chaperones being developed by Protego include PROT-002, which is being developed to target lambda and kappa light-chain amyloidosis, and several programs designed to treat myelofibrosis and pseudoachondroplasia.
“Next step up”
“The way that the team and I have envisioned 002, it’s not meant to be a replacement for 001, but it’s meant to be the next step up,” Warner said. “The toxicity is greater in lambda than it is kappa patients. So by 002 capturing both lambda and kappa, this molecule will be providing a nice, life cycle management plan for the disease area.”
Also in Protego’s pipeline are a pair of programs that use small molecules to activate the unfolded protein response (UPR). The targeted activation is intended to enhance the cell’s capacity to fold proteins, addressing underlying pathologies associated with misfolded proteins. One program is being developed to treat an unspecified liver disorder; the other carries an oncology indication.
The Series B round comes four years to the month that the company closed on a $51 million Series A round.
“When I take a step back and think about what separated us, maybe from some of the rest of the pack, we were very fortunate to have participation from both our current investors and our new ones,” Warner said. “I think it came down to three buckets: scientific leadership, rare disease expertise, and then a first-in-class novel approach.”
“Rare diseases are challenging. Patients are scarce, heterogeneity is something that always needs to be sorted out, and the regulatory environment is ever-changing,” Warner observed. “But what we’ve built, both from a company standpoint with associates, along with our scientific advisory board members and our board members, we’ve assembled a decent and significant amount of rare disease expertise, that really helps us to accelerate our thinking in this disease forward.”
Warner joined Protego as CEO in April 2024 after previously serving as president, gene therapy at Poseida Therapeutics, a CAR T cell therapy developer that was acquired by Roche in an up-to-$1.5 billion deal completed in January. Before Poseida, Warner was vice president, gene therapy and rare disease with Novartis.
Did that help Protego attract Novartis’ venture arm among investors for the Series B?
“Mike Petrassi [PhD, Protego’s chief scientific officer] also used to work at Novartis, so we like to think that it did,” Warner quipped, then quickly added: “But I truly believe it was the novelty of our approach and just the scientific ingenuity here that really catapulted this round to move forward.”
“Mike had such a significant influence and impact on our fundraising and really brought a lot of credibility to what we’re trying to do,” Warner added.
Novartis Venture Fund joined Forbion in leading the Series B round, which attracted new investors that included Omega Funds, Droia Ventures, YK Bioventures, and Digitalis Ventures. They were joined by existing investors that included Scripps Research, MPM BioImpact, Lightspeed Venture Partners, and Vida Ventures.
“Inflection points”
“That financing now allows us to get to the clinical inflection points that we deem are necessary. So, yeah, we’re very pleased with how the round ended out,” Warner said.
Chris Weyrer, MD, PhD, a principal at Vida Ventures, is also Protego’s acting chief business officer. Protego said Weyrer was actively engaged in the latest financing along with Ed Hurwitz, the company’s executive chairman, as well as the founder and managing director of Precision Bioventures, an investment advisory firm focused on founding and seed-financing biotech companies.
Hurwitz co-founded Protego in 2017 along with Scripps Research investigator Jeffrey W. Kelly, PhD, the H. Lutcher Brown Professor of Chemistry; and Richard Labaudinière, PhD, Warner’s predecessor as Protego CEO.
As president and CEO of FoldRx Pharmaceuticals from 2004–2011, Labaudinière oversaw the development of tafamidis, which only eight years later became the first FDA-approved treatment for cardiomyopathy of wild-type or hereditary ATTR-CM in adults. “His understanding of protein misfolding diseases, to me, is unmatched by any other lab around the world,” Warner said.
Kelly’s research laid the groundwork for FoldRx, which was acquired by Pfizer in 2010 for an undisclosed price. The deal expanded the buyer’s presence in rare and orphan diseases as well as CNS diseases—especially those caused by protein misfolding.
Pfizer won European Commission approval for tafamidis in 2011 to treat transthyretin amyloidosis with polyneuropathy. Pfizer sought FDA approval in the same indication, but its new drug application (NDA) was rejected two years later after the agency concluded the company failed to present substantial evidence of efficacy on a clinical endpoint, though an advisory committee found tafamidis showed effectiveness on a surrogate endpoint.
The FDA requested that Pfizer complete a second study to establish efficacy, but instead, Pfizer pivoted to a related indication, winning FDA approval for tafamidis in 2019 for wild-type or hereditary transthyretin-mediated amyloidosis cardiomyopathy (ATTR-CM).
Pfizer’s two tafamidis-based drugs, Vyndamxax and Vyndaqel, generated $4.692 billion in the first nine months of 2025, up 20% from $3.907 billion in Q1–Q3 2024. Those figures include $1.591 billion that was racked up in the third quarter, up 10% year over year from $1.447 billion.
“For us, light chain represents an evolution of the original tafamidis idea,” Warner said. “Light chain amyloidosis is amyloidosis, so you can expand and believe that there are some proxies and learnings that we can employ from tafamidis over to the light chain program.”