Viridian Therapeutics, Inc., a biopharmaceutical company, focuses on discovering, developing, and commercializing potential best-in-class medicines for serious and rare diseases.
The company targets disease areas where marketed therapies often leave room for improvements in efficacy, safety, and/or dosing convenience.
The company’s business model is designed to identify and evaluate product opportunities in disease areas where trial data establishes proof-of-concept for a drug target in the cl...
Viridian Therapeutics, Inc., a biopharmaceutical company, focuses on discovering, developing, and commercializing potential best-in-class medicines for serious and rare diseases.
The company targets disease areas where marketed therapies often leave room for improvements in efficacy, safety, and/or dosing convenience.
The company’s business model is designed to identify and evaluate product opportunities in disease areas where trial data establishes proof-of-concept for a drug target in the clinic, but the competitive evolution of the product life cycle management, and the number of entrants appears incomplete. The company intends to prioritize indications where a fast-follower and a potentially differentiated drug candidate, or overall product profile, could create significant medical benefit for patients. It is engineering product candidates to address unmet medical needs for patients and further advance drug innovation.
The company focuses on advancing therapeutic proteins that it either in-licenses or discovers internally, incorporating proprietary therapeutic protein and antibody discovery and optimization platforms to advance clinical candidates with unique characteristics. The company has built relevant expertise in protein and antibody discovery and engineering, biologics manufacturing, nonclinical and clinical development, and commercialization for thyroid eye disease (‘TED’), development of anti-neonatal Fc receptor (‘FcRn’) therapies, and nonclinical and clinical development for indications in rare and autoimmune diseases.
The company’s approach to rapidly discovering and developing novel therapeutics relies on its scientific expertise in evaluating pre-existing clinical proof-of-concept data for the drug targets it is pursuing, and opportunities to improve upon existing investigational and/or approved therapies. This approach informs how it designs, selects, and develops its product candidates, including in critical areas, such as pharmacokinetics, pharmacodynamics, clinical trial design, trial endpoints, and the selection and recruitment of patients.
The company is developing therapies for the treatment of TED, a serious and debilitating rare autoimmune disease that causes inflammation within the orbit of the eye, which can cause bulging of the eyes, redness and swelling, double vision, pain, and potential blindness. TED significantly impacts quality of life, imposing a high burden on activities of daily living and mental health for patients suffering from the disease. TED is a progressive disease consisting of an initial active phase (‘active TED’), followed by a transition to a secondary chronic phase (‘chronic TED’). The only medicine approved by the FDA for TED is Tepezza (teprotumumab), which is an intravenously administered monoclonal antibody that targets insulin-like growth factor 1 receptor (‘IGF-1R’). Tepezza is marketed in the United States (‘U.S.’) by Horizon Therapeutics plc (‘Horizon’), which was acquired by Amgen Inc. (‘Amgen’) in October 2023. In 2024, Amgen gained approval for Tepezza in Japan, and submitted a Marketing Authorization Application (‘MAA’) to the European Medicines Agency (‘EMA’).
The company is developing two product candidates, veligrotug for intravenous (‘IV’) and VRDN-003 for subcutaneous (‘SC’) administration, to treat patients who suffer from TED. The company’s most advanced program, veligrotug, is a differentiated humanized monoclonal antibody targeting IGF-1R, intravenously administered for the treatment of TED. In previously presented in vitro nonclinical data, the company showed that veligrotug is a potentially differentiated full antagonist of IGF-1R, compared to teprotumumab’s incomplete antagonism of IGF-1R. VRDN-003 has the same binding domain as veligrotug, and was engineered to have a longer half-life. VRDN-003 is designed to be a low-volume, infrequently-dosed subcutaneous IGF-1R for TED, which the company plans to launch commercially with an auto-injector to enable at-home patient self-administration.
The company conducted phase 1/2 clinical trials of veligrotug in patients with active or chronic TED. In the active TED portion of the phase 1/2 clinical trials, data reported from all three dose cohorts of veligrotug (n=21) showed significant and rapid improvement in both the signs and symptoms of TED after two infusions of veligrotug compared to placebo.
The company is conducting a global pivotal program for veligrotug, including evaluating its efficacy and safety in two global well-controlled phase 3 clinical trials, THRIVE and THRIVE-2, for the treatment of active and chronic TED, respectively. THRIVE and THRIVE-2 are each designed to compare a five-dose IV treatment arm of veligrotug at 10 mg/kg, dosed three weeks apart, to placebo. This five-dose veligrotug regimen features fewer infusions and a shorter time per infusion compared to teprotumumab, the currently marketed IGF-1R inhibitor. On September 10, 2024, the company announced topline data from the THRIVE study, which enrolled 113 patients, randomized to veligrotug (n=75) and placebo (n=38). THRIVE achieved all primary and secondary endpoints with a high level of statistical significance (p < 0.0001) and was generally well-tolerated, with no treatment-related serious adverse events (‘SAEs’). Veligrotug additionally showed a rapid onset of treatment effect, with the majority (53%) of veligrotug-treated patients achieving a proptosis response as early as three weeks. On December 16, 2024, the company announced topline data from the THRIVE-2 study, which enrolled 188 patients, randomized to veligrotug (n=125) and placebo (n=63). THRIVE-2 achieved all primary and secondary endpoints with statistical significance and was generally well-tolerated. Veligrotug continued to demonstrate a rapid onset of treatment effect, with a statistically significant proptosis response as early as three weeks, and a statistically significant reduction and resolution of diplopia as early as six weeks. THRIVE-2 is the first global phase 3 study in patients with chronic TED to demonstrate a statistically significant and clinically meaningful diplopia responder rate and rate of diplopia complete resolution. To meet the 300 patient standard safety database requirements for the veligrotug biologics license application (‘BLA’), the company is conducting its STRIVE clinical trial (safety database inclusive of patients from the THRIVE and THRIVE-2 trials). STRIVE is a global study of veligrotug in TED patients that utilizes broad inclusion criteria (e.g., any severity or duration of disease) and is randomized 3:1 (10 mg/kg IV with an active control of 3 mg/kg IV). In January 2025, the company completed enrollment in STRIVE with a total of 231 patients, exceeding the enrollment target of 212 due to patient demand. The company has also completed enrollment of the open label extension study for non-responding patients in THRIVE and THRIVE-2. The company anticipates submitting a BLA for veligrotug in the second half of 2025, and an MAA to the EMA in the first half of 2026.
In addition to the company’s intravenous veligrotug program, VRDN-003 is its subcutaneous product candidate currently in pivotal development in TED, which the company selected in December 2023 following positive data in a phase 1 clinical trial in healthy volunteers.
The VRDN-003 phase 1 clinical study showed VRDN-003 to have a prolonged half-life of 40 to 50 days, which is four to five times that of veligrotug. Because of the healthy volunteer data, and the similarities between the veligrotug and VRDN-003 antibodies, the company expects VRDN-003 to have similar clinical responses at the exposure levels of veligrotug that led to robust clinical activity in its clinical trials to date in TED. Further, pharmacokinetic modeling of VRDN-003 based on the healthy volunteer data predicted that exposure levels of VRDN-003 could be achieved that are equivalent to exposure levels of veligrotug that produced clinically meaningful results with multiple dosing regimens of VRDN-003, i.e., subcutaneous injection every two, four, or eight weeks.
The company is conducting a global pivotal program for VRDN-003, including evaluating its efficacy and safety in two global well-controlled phase 3 clinical trials, REVEAL-1 and REVEAL-2, for the treatment of active and chronic TED, respectively. In addition, to enable BLA submission for VRDN-003, the company has initiated a safety study to meet the 300 patient standard safety database requirement (to also include patients from the REVEAL-1 and REVEAL-2 trials), and plans to initiate an auto-injector study in 2025 to enable launching VRDN-003 in an auto-injector device.
Development of FcRn Inhibitors
In addition to developing therapies for TED, the company is also developing a portfolio of engineered FcRn inhibitors, including VRDN-006 and VRDN-008. FcRn inhibitors have the potential to treat a broad array of autoimmune diseases, representing a possible significant commercial market opportunity. The company’s multi-pronged engineering approach has resulted in a portfolio of FcRn-targeting molecules that leverage the clinically and commercially validated mechanism of FcRn inhibition, while potentially addressing the limitations of current agents, such as incomplete immunoglobulin G (‘IgG’) suppression, safety, and inconvenience of dosing.
VRDN-006 is a highly selective Fc fragment that inhibits FcRn and is designed to be a convenient subcutaneous and self-administered option for patients. In non-human primate (‘NHP’) studies, VRDN-006 demonstrated specificity for blocking FcRn-IgG interactions while not showing decreases in albumin or increases in low-density lipoprotein (‘LDL’) levels, which are known potential side effects associated with certain full-length anti-FcRn monoclonal antibodies. In the company’s head-to-head NHP studies, VRDN-006 demonstrated comparable potency and IgG reductions to efgartigimod, which is the current standard of care in FcRn inhibition, as well as a similar safety profile. The company submitted an IND for VRDN-006 in December 2024, which cleared in January 2025, and expects proof-of-concept IgG reduction data in healthy volunteers in the third quarter of 2025.
VRDN-008 is a half-life extended bispecific FcRn inhibitor comprising an Fc fragment and an albumin-binding domain designed to prolong IgG suppression and provide a potentially best-in-class subcutaneous option for patients. In a single, high-dose, head-to-head study in NHPs, VRDN-008 demonstrated three times the half-life of efgartigimod. Additionally, VRDN-008 showed a deeper and more sustained IgG reduction with peak IgG reductions that were 20% deeper than efgartigimod, while not showing decreases in albumin or increases in LDL levels. NHP studies are ongoing to generate additional data for VRDN-008. Once completed, the company plans to use the totality of VRDN-008’s NHP data to build a robust pharmacokinetic and pharmacodynamic model to predict potential human dosing regimens for VRDN-008. The company anticipates submitting an IND for VRDN-008 by the end of 2025.
Strategy
Key elements of the company’s business strategy are to evaluate opportunities to identify, engineer, and develop potential best-in-class therapeutic proteins and antibodies that optimize patient care; the company’s clinical development and commercial focus on thyroid eye disease (TED), which seeks marketing approval for veligrotug, rapidly develop subcutaneous VRDN-003 as its next generation, potential best-in-class IGF-1R antibody, be a trusted partner in the care of TED patients, and prepare for commercialization of veligrotug and VRDN-003 for the treatment of patients with TED; advance the company’s portfolio of FcRn inhibitors with the potential to treat a broad array of autoimmune disorders, which generate VRDN-006 proof-of-concept IgG reduction data in healthy volunteers, and advance VRDN-008 to the clinic; and leverage the company’s therapeutic protein, antibody, and multi-disciplinary search expertise to continue discovering and developing novel, best-in-class product candidates.
Product Candidates
Veligrotug, a potential best-in-class intravenously administered IGF-1R antibody
Veligrotug is a monoclonal antibody that binds to and acts as a full antagonist of the IGF-1R signaling pathway. This mechanism of action is clinically and commercially validated by the only FDA product approved for the treatment of TED, Tepezza. Based on the company’s ongoing THRIVE and THRIVE-2 phase 3 clinical trials, its goal is for veligrotug to be second to market in this class of medicine, with the opportunity to offer a differentiated IV product.
The company has an exclusive license to the worldwide rights to develop and commercialize veligrotug for all non-oncology indications that do not use radiopharmaceuticals, including the treatment of patients with TED, from ImmunoGen, Inc. (‘ImmunoGen’). The antibody sequence that the company is developing as veligrotug in TED had previously been developed in oncology as AVE-1642 and studied in over 100 patients. However, development in oncology was stopped in 2009 due to its failure to meet the primary efficacy endpoints in multiple myeloma. The company sublicensed the right to develop, manufacture, and commercialize certain IGF-1R directed antibody products for non-oncology indications in the greater area of China to Zenas BioPharma (Cayman) Limited (now Zenas BioPharma, Inc., their successor in interest, ‘Zenas BioPharma’). In January 2025, Zenas BioPharma sublicensed their rights to Zai Lab (Hong Kong) Limited (‘Zai Lab’).
Clinical Trials for veligrotug
Phase 1/2 Trial of veligrotug in Patients with Active TED
In the second half of 2022 and early 2023, the company announced data from its phase 1/2 clinical trial evaluating the safety and efficacy of veligrotug in patients with active TED. The proof-of-concept portion of this double-blind, placebo-controlled phase 1/2 trial evaluated two infusions of veligrotug administered intravenously, three weeks apart, with efficacy measured six weeks after the first dose. Veligrotug was evaluated at doses of 3, 10, and 20 mg/kg, with each cohort designed to include six patients randomized to drug, and two patients randomized to placebo.
Phase 1/2 Trial of veligrotug in Patients with Chronic TED
In July 2023, the company announced data from its phase 1/2 clinical trial evaluating the safety and efficacy of veligrotug in patients with chronic TED. The proof-of-concept portion of this double-blind, placebo-controlled phase 1/2 trial evaluated two infusions of veligrotug administered intravenously, three weeks apart, with efficacy measured six weeks after the first dose. Veligrotug was evaluated at doses of 3 and 10 mg/kg, with each cohort designed to include six patients randomized to drug, and two patients randomized to placebo. The company previously announced positive results from both cohorts, and veligrotug demonstrated a favorable safety profile that was generally consistent with the previously reported results in patients with active TED with veligrotug.
Phase 3 Trial (THRIVE) of veligrotug in Patients with Active TED
THRIVE is a global double-masked, placebo-controlled phase 3 clinical trial evaluating the safety and efficacy of veligrotug in patients with active TED. THRIVE evaluated five infusions of veligrotug at 10 mg/kg, dosed three weeks apart. Patients were randomized two to drug and one to placebo.
In September 2024, the company announced positive topline data from THRIVE. THRIVE met the primary and all secondary endpoints at fifteen weeks after five infusions of veligrotug, showing highly statistically significant (p < 0.0001) improvements on all of the measured signs and symptoms of TED. Veligrotug additionally showed a rapid onset of treatment effect, with the majority (53%) of veligrotug-treated patients achieving a proptosis response as early as three weeks. THRIVE enrolled 113 patients, randomized to veligrotug (n=75) and placebo (n=38).
Phase 3 Trial (THRIVE-2) of veligrotug in Patients with Chronic TED
THRIVE-2 is a global double-masked, placebo-controlled phase 3 clinical trial evaluating the safety and efficacy of veligrotug in patients with chronic TED. THRIVE-2 evaluated five infusions of veligrotug at 10 mg/kg, dosed three weeks apart. Patients were randomized two to drug and one to placebo.
In December 2024, the company announced positive topline data from THRIVE-2. THRIVE-2 met the primary and all secondary endpoints at fifteen weeks after five infusions of veligrotug, showing statistically significant responses on all of the measured signs and symptoms of TED. Veligrotug continued to demonstrate a rapid onset of treatment effect, with a statistically significant proptosis response as early as three weeks, and statistically significant diplopia reduction and resolution as early as six weeks. THRIVE-2 is the first global phase 3 study in patients with chronic TED to demonstrate a statistically significant and clinically meaningful diplopia responder rate and rate of diplopia complete resolution. THRIVE-2 enrolled 188 patients, randomized to veligrotug (n=125) and placebo (n=63). The mean time since onset of TED in patients treated with veligrotug was 69.8 months.
VRDN-003, a potential best-in-class subcutaneously administered IGF-1R antibody
VRDN-003 is a monoclonal antibody that acts as a full antagonist of IGF-1R. VRDN-003 utilizes the same binding domain as veligrotug and is engineered to extend its half-life, and therefore potentially enabling less frequent and more convenient dosing. VRDN-003 is designed to maintain the clinical response of veligrotug IV while significantly increasing patient convenience.
The company is conducting a global pivotal program for VRDN-003, including evaluating its efficacy and safety in two global well-controlled phase 3 pivotal clinical trials, REVEAL-1 and REVEAL-2, for the treatment of active and chronic TED, respectively. The company selected VRDN-003 for pivotal development in TED following positive data in a phase 1 clinical trial in healthy volunteers. This study showed VRDN-003 to have a prolonged half-life of 40 to 50 days, which is four to five times that of its parent molecule, veligrotug. Because of the similarities of veligrotug and VRDN-003, the company expects VRDN-003 to have similar clinical responses at the exposure levels of veligrotug that led to robust clinical activity in its phase 2 clinical study in TED. Further, pharmacokinetic modeling of VRDN-003 predicted that exposure levels of VRDN-003 could be achieved that are equivalent to exposure levels of veligrotug that produced clinically meaningful results with multiple dosing regimens of VRDN-003, i.e., subcutaneous injection every two, four, or eight weeks. Patient enrollment and dosing continue in both REVEAL-1 and REVEAL-2. Both studies will evaluate subcutaneous VRDN-003 administered every four weeks or every eight weeks, and will assess outcomes versus placebo.
Phase 1 Trial of VRDN-003 in Healthy Volunteers
Study Design: VRDN-003 was dosed in four single dose cohorts of healthy volunteers at a concentration of 150 mg/ml receiving 5 mg/kg IV (n=4), 300 mg SC (n=6), 15 mg/kg IV (n=4), 600 mg SC (n=6), and a fifth cohort of two doses of VRDN-003 (n=4).
Summary of Results:
Extended Half-Life: VRDN-003 pharmacokinetics data showed an extended half-life of 40 to 50 days, which is a 4-to-5-fold increase over the half-life of veligrotug (which showed a half-life of 10 to 12 days).
Prolonged Pharmacodynamics (‘PD’): Following a single subcutaneous dose of VRDN-003, IGF-1 serum levels increased approximately 4-fold at peak. This was consistent with the increases in IGF-1 levels that have been shown in the clinic following a single dose of veligrotug SC and IV. IGF-1 is a PD biomarker for IGF-1R target engagement.
Well-Tolerated: VRDN-003 was well tolerated in all subjects with no SAEs. All treatment-related, treatment-emergent adverse events were grade 1 (mild). In the reported dataset, no antidrug antibodies (‘ADAs’) were detected.
Dosing Flexibility for Pivotal Development: VRDN-003 modeling demonstrated dosing flexibility for the program’s anticipated global pivotal development. The modeling showed that dosing VRDN-003 every eight weeks, every four weeks, and every two weeks achieved a range of exposure levels that were seen for veligrotug after intravenous doses of 3 mg/kg, 10 mg/kg, and 20 mg/kg, respectively.
FcRn Inhibitor Portfolio: VRDN-006 and VRDN-008
In October 2023, consistent with the company’s vision to develop the next generation of best-in-class products for severe autoimmune and rare diseases, the company unveiled VRDN-006 and VRDN-008 from its portfolio of engineered FcRn inhibitors. FcRn inhibitors have the potential to treat a broad array of autoimmune diseases, representing a possible significant commercial market opportunity. The company’s multi-pronged engineering approach has resulted in a portfolio of FcRn-targeting molecules that leverage the clinically and commercially validated mechanism of FcRn inhibition in myasthenia gravis and chronic inflammatory demyelinating polyneuropathy (‘CIDP’), while potentially addressing the limitations of current agents, such as incomplete IgG suppression and safety. VRDN-006 and VRDN-008 are both designed to be convenient, self-administered, subcutaneous products.
VRDN-006
VRDN-006 is a highly-selective Fc fragment. In the company’s NHP studies, VRDN-006 demonstrated specificity for blocking FcRn-IgG interactions while not showing decreases in albumin or increases in low-density lipoprotein (‘LDL’) levels, which are known potential side effects associated with certain full-length monoclonal anti-FcRn antibodies. With efgartigimod, Argenx has proven that an Fc fragment can achieve clinical efficacy while sparing an effect on albumin or LDL, and shows better tolerability than full-length antibodies against FcRn. VRDN-006 is the only other known Fc fragment currently in development.
VRDN-006 received IND clearance from the FDA in January 2025, and the company expects proof-of-concept IgG reduction data in healthy volunteers in the third quarter of 2025.
VRDN-008
VRDN-008 is a half-life extended bispecific FcRn inhibitor comprising an Fc fragment and an albumin-binding domain designed to prolong IgG suppression and provide a potentially best-in-class subcutaneous option for patients. In a single, high-dose, head-to-head study in NHPs, VRDN-008 demonstrated three times the half-life of efgartigimod, and a deeper and more sustained IgG reduction with peak IgG reductions that were 20% deeper than efgartigimod.
NHP studies are ongoing to generate additional data for VRDN-008. Once completed, the company plans to use the totality of VRDN-008’s NHP data to build a robust pharmacokinetic and pharmacodynamic model to enable the prediction of potential human dosing regimens for VRDN-008.
Intellectual Property
As of January 15, 2025, the company’s in-licensed and owned patent portfolio consists of approximately one U.S. issued patent, approximately seventeen U.S. pending patent applications, no patents issued in jurisdictions outside of the United States, one allowed patent in China, and approximately seventy-eight patent applications pending in jurisdictions outside of the United States (including approximately seven pending Patent Cooperation Treaty (PCT) applications) that, in many cases, are counterparts to the foregoing U.S. patents and patent applications. The company’s patent issued as of January 15, 2025, is expected to expire no earlier than 2041.
License Agreements
License Agreement with Zenas BioPharma
In October 2020, the company (‘Private Viridian’) entered a license agreement with Zenas BioPharma to license technology comprising certain materials, patent rights, and know-how to Zenas BioPharma. On October 27, 2020, in connection with the closing of the Private Viridian acquisition, the company became party to the license agreement with Zenas BioPharma. Since February 2021, the company has entered into several letter agreements with Zenas BioPharma in which it agreed to provide assistance to Zenas BioPharma with certain development activities, including manufacturing.
License Agreement with ImmunoGen, Inc.
On October 12, 2020, Private Viridian entered into a license agreement with ImmunoGen (the ‘ImmunoGen License Agreement’), under which the company obtained rights to an exclusive, sublicensable, worldwide license to certain patents and other intellectual property rights to develop, manufacture, and commercialize certain products for non-oncology and non-radiopharmaceutical indications.
Antibody and Discovery Option Agreement and License Agreement with Paragon Therapeutics, Inc.
In January 2022, the company entered into an antibody and discovery option agreement (the ‘Paragon Research Agreement’) with Paragon Therapeutics, Inc. (‘Paragon’), under which the company and Paragon will cooperate to develop one or more therapeutic proteins or antibodies.
Government Regulation
Prior to beginning the first clinical trial with a product candidate, the company must submit an Investigational New Drug Application (‘IND’) to the U.S. Food and Drug Administration (‘FDA’).
The uncertainty regarding the interplay between different regulatory frameworks, such as the EU Clinical Trials Regulation No.536/2014 (‘CTR’), and the E.U. General Data Protection Regulation (the ‘GDPR’), further adds to the complexity that the company faces with regard to data protection regulation.
Sales and Marketing
The company has not yet defined its sales, marketing, or product distribution strategy for its product candidates because its product candidates are still in development. The company’s commercial strategy may include the use of strategic partners, distributors, a contract sales force, or the establishment of the company’s own commercial and specialty sales force. The company plans to further evaluate these alternatives as it continues to advance into later stages of development for each one of its product candidates.
History
The company was founded in 2010. The company was incorporated as a Delaware corporation in 2014. The company was formerly known as Miragen Therapeutics, Inc. and changed its name to Viridian Therapeutics, Inc. in January 2021.
