- VRDN-003 clinical data exceeded expectations
with extended half-life of 40-50 days, 4-5x longer than VRDN-001,
supporting a potential best-in-class, low-volume, less frequent,
self-administered subcutaneous therapy for thyroid eye disease
(TED) -
- Data support VRDN-003 dosing as infrequently
as once every eight weeks and is expected to reach exposure levels
associated with robust clinical response in earlier trials of
VRDN-001 in TED patients -
- Pivotal clinical development of subcutaneous
VRDN-003 in TED patients expected to initiate mid-2024 pending
alignment with regulatory authorities -
- Viridian to host investor conference call and
webcast today at 8:00am ET -
Viridian Therapeutics, Inc. (NASDAQ: VRDN), a biotechnology
company focused on discovering and developing potential
best-in-class medicines for serious and rare diseases, today
announced the selection of VRDN-003 as its lead subcutaneous (SC)
program for thyroid eye disease (TED) based on positive data from a
Phase 1 clinical study in healthy volunteers. The data showed that
VRDN-003 has an extended half-life of 40-50 days, about 4-5 times
longer than VRDN-001 and based upon comparisons of publicly
disclosed data, significantly longer than other first generation
anti-insulin-like growth factor-1 receptor (IGF-1R) antibodies.
VRDN-003 was well tolerated and exhibited sustained
pharmacodynamics supporting its development as a potential
best-in-class, more convenient, less frequent, low-volume,
self-administered, subcutaneous IGF-1R therapy for patients with
TED.
“The VRDN-003 data exceeded our expectations as a potential
best-in-class treatment option for patients affected by TED and
support advancing dosing regimens as infrequently as once every
eight weeks, which we believe could be transformative for TED
patients who currently only have access to intravenous (IV) IGF-1R
therapy,” said Steve Mahoney, President and CEO of Viridian
Therapeutics. “The data reinforce our confidence in VRDN-003’s
rapid development as a low-volume, self-administered, subcutaneous
product. Given VRDN-003’s comparable pharmacology with VRDN-001,
which has already generated compelling clinical data in TED
patients, we are excited about the clinical potential of this
program for patients and our ability to rapidly move toward pivotal
development.”
VRDN-003 Results
VRDN-003 is a monoclonal antibody that acts as a full antagonist
of IGF-1R, a clinically and commercially validated target for TED.
VRDN-003 utilizes the same binding domain as VRDN-001 and is
engineered with three amino acid changes to the Fc region designed
to extend the half-life of the parent antibody, and therefore
potentially enabling less frequent and more convenient dosing.
VRDN-003 is designed to maintain the clinical response of VRDN-001
IV while significantly increasing patient convenience.
- 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) and 600 mg SC (n=6). A fifth cohort of two
doses of VRDN-003 (n=4) is ongoing.
- Summary of Results:
- Extended Half Life: VRDN-003
pharmacokinetics data showed an extended half-life of 40-50 days,
which is a 4-to-5-fold increase over the half-life of VRDN-001
(which showed a half-life of 10-12 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 VRDN-001 SC and IV. IGF-1 is a PD
biomarker for IGF-1R target engagement. IGF-1R inhibition by an
anti-IGF-1R antibody demonstrated an increase in serum levels of
its natural ligand IGF-1.
- Well Tolerated: VRDN-003 was well
tolerated in all subjects with no serious adverse events. 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 demonstrates dosing
flexibility for the program’s anticipated global pivotal
development.
- Q8W (dosing once every 8 weeks): Modeled dose schedule is
predicted to achieve Cmin and Cavg exposures seen for 3 mg/kg
VRDN-001 IV.
- Q4W (dosing once every 4 weeks): Modeled dose schedule is
predicted to achieve Cmin exposures seen for 10 mg/kg VRDN-001 IV
and exceed the Cavg exposures seen for 3 mg/kg by a factor of
2.
- Q2W (dosing once every 2 weeks): Modeled dose schedule is
predicted to exceed Cmin exposures seen for 20 mg/kg VRDN-001 IV
and the Cavg exposures seen for 10 mg/kg VRDN-001 IV.
“The shared binding domain and pharmacology of VRDN-003 with
VRDN-001 allow us to leverage the clinical activity of VRDN-001 IV
at different exposure levels to confidently select doses for
VRDN-003 that we expect to demonstrate an impactful clinical
response,” said Tom Ciulla, Viridian’s Chief Development Officer.
“We are enthusiastic about delivering a product with highly
attractive, low-volume subcutaneous dosing schedules that we firmly
believe will be preferred by patients.”
Based on the data being reported today, VRDN-003 has been
selected as Viridian’s go-forward candidate for subcutaneous
development. We expect to initiate the VRDN-003 pivotal program in
mid-2024, pending alignment with regulatory authorities. Based on
these positive results and the expected development timeline for
VRDN-003, both VRDN-001 SC and VRDN-002 SC development have been
deprioritized.
VRDN-001 SC and VRDN-002 Results
VRDN-001 SC is a subcutaneous formulation of the same antibody
being evaluated as an IV product candidate in the company’s ongoing
Phase 3 THRIVE and THRIVE-2 clinical trials. The Phase 1 healthy
volunteer study included a cohort of the SC formulation of VRDN-001
at a concentration of 150 mg/ml dosed in two single dose cohorts of
healthy volunteers either receiving 3.5 mg/kg IV (n=8) or 300mg SC
(n=8). SC data showed an expected half-life of 10-12 days. Q1W
dosing of VRDN-001 SC was modeled to achieve or exceed exposures
shown for 10 mg/kg VRDN-001 IV and would be expected to achieve
comparable clinical response to VRDN-001 10 mg/kg IV. VRDN-001 SC
also showed an increase in IGF-1 levels similar to VRDN-001 IV and
VRDN-003 SC. VRDN-001 SC was well tolerated in all subjects with no
serious adverse events. All treatment-related, treatment-emergent
adverse events were grade 1 (mild) and grade 2 (moderate).
VRDN-002 is a different and novel monoclonal antibody targeting
IGF-1R as compared to VRDN-001 or VRDN-003. Similar to VRDN-003,
VRDN-002 was engineered to have an extended half-life to allow for
less frequent dosing. VRDN-002 SC was dosed at a concentration of
150 mg/ml in two single dose cohorts of healthy volunteers, either
receiving 3.5 mg/kg IV (n=8) or 300 mg SC (n=8). Healthy volunteer
data for VRDN-002 showed an extended half-life of 43 days as
previously disclosed. VRDN-002 also showed a prolonged
pharmacodynamic effect and increased IGF-1 levels, but the
magnitude of increase was not as great as with VRDN-003 or
VRDN-001. VRDN-002 was well tolerated in all subjects with no
serious adverse events. All treatment-related, treatment-emergent
adverse events were grade 1 (mild). No ADAs were detected.
Next Steps for the Development of VRDN-003 in TED
Based on the results reported today, the company expects to
initiate global pivotal clinical trials of VRDN-003 in mid-2024
with planned trials in both active and chronic TED patients pending
alignment with regulatory authorities.
“We view the VRDN-003 data as a crucial step forward for TED
patients,” said Mr. Mahoney. “Based on the data, we expect that
VRDN-003 could be a leader in the large TED commercial market that
may be poised for expanded growth with a more convenient, less
frequent, at-home, self-administered, subcutaneous product. We plan
to move forward rapidly and will provide additional details about
our trial design and development plans in the first half of
2024.”
Conference call and webcast information
The Company will host a conference call today at 8:00 a.m. ET to
discuss the data for Viridian’s lead selection for the IGF-1R
subcutaneous program. The dial-in number for the conference call is
1-888-330-3622 for domestic participants and 1-646-960-0662 for
international participants. The conference ID is 3961606.
A live webcast of the conference call can be accessed through
the “Events” page in the Investors section of the Viridian
Therapeutics website. Following the live webcast, an archived
version of the call will also be available on the website.
About Viridian’s Thyroid Eye Disease Pipeline (VRDN-001 and
VRDN-003)
Viridian’s lead product candidate, VRDN-001, is a differentiated
monoclonal antibody targeting insulin-like growth factor-1 receptor
(IGF-1R), a clinically and commercially validated target for the
treatment of thyroid eye disease (TED). In preclinical studies,
VRDN-001 was shown to be a full antagonist of IGF-1R, with more
complete receptor blockade than other anti-IGF-1R antibodies,
including the only currently approved TED therapy. Data from the
Phase 2 portion of the trial established clinical proof-of-concept
for VRDN-001 in patients with active and chronic TED. VRDN-001 was
generally well tolerated in the trial.
The THRIVE and THRIVE-2 Phase 3 clinical trials in patients with
active and chronic TED are ongoing.
Viridian’s goal is to advance VRDN-001 as a best-in-class IV
therapy followed by VRDN-003 as a first- and best-in-class SC
therapy for the treatment of TED. The company has selected VRDN-003
as its lead SC program for TED based on positive data from its
Phase 1 clinical study in healthy volunteers and expects to
initiate global pivotal development of VRDN-003 with planned trials
in both active and chronic TED patients pending alignment with
regulatory authorities.
About TED
TED is a serious and debilitating rare autoimmune disease that
causes inflammation within the orbit of the eye that can cause
double vision, pain, and potential blindness. TED is a progressive
disease consisting of an initial active phase, followed by a
transition to a secondary chronic phase. More than 50,000 and
200,000 people are estimated to suffer from active and chronic TED,
respectively, in the United States and Europe.
About Viridian Therapeutics
Viridian is a biopharmaceutical company focused on engineering
and developing potential best-in-class medicines for patients with
serious and rare diseases. Viridian’s expertise in antibody
discovery and engineering enables it to develop differentiated
therapeutic candidates for previously validated drug targets in
commercially established disease areas.
Viridian is advancing multiple candidates in the clinic for the
treatment of patients with TED. The company is conducting two
global Phase 3 clinical trials (THRIVE and THRIVE-2) to evaluate
the safety and efficacy of VRDN-001 in patients with active and
chronic TED. Viridian’s goal is to advance VRDN-001 as a
best-in-class IV therapy followed by VRDN-003 as a first- and
best-in-class SC therapy for the treatment of TED. In addition to
its TED portfolio, Viridian is advancing a novel portfolio of
neonatal Fc receptor (FcRn) inhibitors, VRDN-006 and VRDN-008,
which has the potential to be developed in multiple autoimmune
diseases. Viridian is also developing additional preclinical assets
in autoimmune and rare diseases.
Viridian is based in Waltham, Massachusetts. For more
information, please visit www.viridiantherapeutics.com. Follow
Viridian on LinkedIn and X.
Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. These statements may be identified by the use of words such
as, but not limited to, “anticipate,” “believe,” “continue,”
“could,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,”
“potential,” “predict,” “project,” “should,” “target,” “will,” or
“would” or other similar terms or expressions that concern our
expectations, plans and intentions. Forward-looking statements are
neither historical facts nor assurances of future performance.
Instead, they are based on our current beliefs, expectations, and
assumptions. Forward-looking statements include, without
limitation, statements regarding: the therapeutic potential and
utility, efficacy and clinical benefits of VRDN-003 for Thyroid Eye
Disease (TED); the expected exposure levels of VRDN-003; the safety
profile of VRDN-003; the potential dosing frequency for VRDN-003;
trial designs, clinical development plans and timing for VRDN-003,
including the global pivotal clinical trials of VRDN-003 in active
and chronic TED patients; the expected attractiveness of VRDN-003
and convenience for patients; and anticipated work with regulatory
authorities. New risks and uncertainties may emerge from time to
time, and it is not possible to predict all risks and
uncertainties. No representations or warranties (expressed or
implied) are made about the accuracy of any such forward-looking
statements. Such forward-looking statements are subject to a number
of material risks and uncertainties including but not limited to:
the potential efficacy and safety of VRDN-001, VRDN-002, and
VRDN-003 for the treatment of TED; the potential for VRDN-006 and
VRDN-008; the relationship between the results from the positive
data from completed or ongoing clinical trials and the results of
ongoing or future clinical trials; the timing, progress and plans
for our ongoing or future research, pre-clinical and clinical
development programs; trial protocols for ongoing clinical trials;
expectations regarding the timing for IND filings; expectations
regarding the timing for enrollment and data; uncertainty and
potential delays related to clinical drug development; the duration
and impact of regulatory delays in our clinical programs; the
timing of and our ability to obtain and maintain regulatory
approvals for our therapeutic candidates; manufacturing risks;
competition from other therapies or products; estimates of market
size; other matters that could affect the sufficiency of existing
cash, cash equivalents and short-term investments to fund
operations; our financial position and its projected cash runway;
our future operating results and financial performance; the
clinical utility of our therapeutic candidates and our intellectual
property position; the timing of pre-clinical and clinical trial
activities and reporting results from same, including those risks
set forth under the caption “Risk Factors” in our Quarterly Report
on Form 10-Q filed with the Securities and Exchange Commission
(SEC) on November 13, 2023 and other subsequent disclosure
documents filed with the SEC. Any forward-looking statement speaks
only as of the date on which it was made. Neither the Company, nor
its affiliates, advisors, or representatives, undertake any
obligation to publicly update or revise any forward-looking
statement, whether as a result of new information, future events or
otherwise, except as required by law. These forward-looking
statements should not be relied upon as representing the Company’s
views as of any date subsequent to the date hereof.
View source
version on businesswire.com: https://www.businesswire.com/news/home/20231218302697/en/
Louisa Stone, 617-272-4604 Manager, Investor Relations
IR@viridiantherapeutics.com
Viridian Therapeutics (NASDAQ:VRDN)
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