Monte Rosa Therapeutics, Inc. (Nasdaq: GLUE), a clinical-stage
biotechnology company developing novel molecular glue degrader
(MGD)-based medicines, today announced the company will present
preclinical data at the European Alliance of Associations for
Rheumatology (EULAR) 2024 Congress, being held June 12-15 in
Vienna, Austria. The data demonstrated that in a collagen-induced
arthritis (CIA) murine model, oral dosing of MRT-6160 inhibited
disease progression as compared to vehicle and anti-TNF,
concomitant with reduced serum pro-inflammatory cytokines and
anti-collagen II autoantibodies. In vitro, MRT-6160-mediated
degradation of human VAV1 dose-dependently reduced T-cell receptor
(TCR)- and B-cell receptor (BCR)-mediated activation,
proliferation, and function in T- and B-cells, including cytokine
and IgG secretion. VAV1 is a key signaling protein downstream of
both the T-and B-cell receptors, and its degradation has potential
to treat multiple T-cell, T/B-cell, and Th17-mediated autoimmune
and inflammatory diseases.
“We believe these preclinical data support our
hypothesis that targeting VAV1 has strong therapeutic potential for
rheumatoid arthritis,” said Sharon Townson, Ph.D., Chief Scientific
Officer of Monte Rosa Therapeutics. “The data being presented at
EULAR showed that oral dosing of MRT-6160 led to decreased TCR- and
BCR-mediated immune activation and reduced levels of clinically
relevant pro-inflammatory cytokines and autoantibodies, as well as
statistically significant reductions in clinical scores of disease
activity, in the CIA murine model. Today’s data combined with data
from other autoimmune disease models and our GLP toxicology data
reinforce our belief in the therapeutic potential of VAV1 across
multiple autoimmune and inflammatory diseases. We look forward to
initiating our Phase 1 single ascending dose/multiple ascending
dose (SAD/MAD) study of MRT-6160 this summer and sharing initial
clinical data from that study in Q1 2025.”
The poster, entitled “MRT-6160, a VAV1-Directed
Molecular Glue Degrader, Reduces Joint Inflammation and
Autoantibody Production in a Collagen-Induced Arthritis Autoimmune
Disease Model” (Poster Number 1200), will be presented today by
Adam Cartwright, Ph.D., Senior Scientist II at Monte Rosa
Therapeutics, at 14:45 CET / 8:45 a.m. ET.
Summary of findings:
- In a CIA murine model,
MRT-6160-mediated mouse VAV1 (mVAV1) degradation was associated
with significantly reduced clinical scores and inhibition of
disease progression in mice, with observable impact on signs of
arthritis compared to control and anti-TNF-treated mice.
- Analysis of murine serum samples
from the CIA model showed that degradation of mVAV1 was associated
with significantly reduced production of key pro-inflammatory
cytokines, including IL-1β, IL-6, TNF, and IL-17A, and autoantibody
production, including anti-collagen II IgG1.
- Primary human T- and B-cells
treated with MRT-6160 in vitro resulted in dose-dependent
attenuation of TCR- and BCR-mediated activation (CD69 expression)
and effector function in T- and B-cells, including cytokine and IgG
secretion.
About VAV1 and MRT-6160VAV1, a
Rho-family guanine nucleotide exchange factor, is a key signaling
protein downstream of both the T-and B-cell receptors. VAV1
expression is restricted to blood and immune cells, including T and
B cells. Preclinical studies have shown that targeted degradation
of VAV1 protein via an MGD modulates both T- and B-cell
receptor-mediated activity. This modulation is evident both in
vitro and in vivo, demonstrated by a significant decrease in
cytokine secretion, proteins vital for maintaining autoimmune
diseases. Moreover, VAV1-directed MGDs have shown promising
activity in preclinical models of autoimmune diseases and thus have
the potential to provide therapeutic benefits in multiple systemic
and neurological autoimmune indications, such as inflammatory bowel
disease, rheumatoid arthritis, multiple sclerosis, and
dermatological disorders.
MRT-6160 is a potent, highly selective, and
orally bioavailable degrader of VAV1, which has shown deep
degradation of its target with no detectable effects on other
proteins. Preclinical studies demonstrate MRT-6160 inhibits disease
progression in in vivo autoimmunity models.
About Monte RosaMonte Rosa
Therapeutics is a clinical-stage biotechnology company developing
highly selective molecular glue degrader (MGD) medicines for
patients living with serious diseases in the areas of oncology,
autoimmune and inflammatory diseases, and more. MGDs are small
molecule protein degraders that have the potential to treat many
diseases that other modalities, including other degraders, cannot.
Monte Rosa’s QuEEN™ (Quantitative and Engineered Elimination of
Neosubstrates) discovery engine combines AI-guided chemistry,
diverse chemical libraries, structural biology and proteomics to
identify degradable protein targets and rationally design MGDs with
unprecedented selectivity. The QuEEN discovery engine enables
access to a wide-ranging and differentiated target space of
well-validated biology across multiple therapeutic areas. Monte
Rosa has developed the industry’s leading pipeline of MGDs, which
spans oncology, autoimmune and inflammatory disease and beyond, and
has a strategic collaboration with Roche to discover and develop
MGDs against targets in cancer and neurological diseases previously
considered impossible to drug. For more information, visit
www.monterosatx.com.
Forward-Looking StatementsThis
communication includes express and implied “forward-looking
statements,” including forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995.
Forward-looking statements include all statements that are not
historical facts and in some cases, can be identified by terms such
as “may,” “might,” “will,” “could,” “would,” “should,” “expect,”
“intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,”
“predict,” “potential,” “continue,” “ongoing,” or the negative of
these terms, or other comparable terminology intended to identify
statements about the future. Forward-looking statements contained
herein include, but are not limited to, statements about the
advancement and timeline of our preclinical and clinical programs,
including the ongoing development of MRT-6160, and the planned
submission of an IND to the FDA for MRT-6160 in the second quarter
of 2024, our expectations of timing for initiation of a Phase 1
SAD/MAD study mid-2024 and the timing for our disclosure of Phase 1
clinical data of MRT-6160 in the first quarter of 2025, as well as
our expectation to present additional preclinical data in models of
autoimmune and inflammatory diseases at the upcoming medical
meetings and our expectation to initiate POC studies for MRT-6160
in autoimmune/inflammatory diseases including ulcerative colitis
and rheumatoid arthritis, with additional potential POC studies,
dermatology, rheumatology, and neurology indications in mid-2025,
our expectations of success for our programs, among others. By
their nature, these statements are subject to numerous risks and
uncertainties, including those risks and uncertainties set forth in
our most recent Annual Report on Form 10-K for the year ended
December 31, 2023, filed with the U.S. Securities and Exchange
Commission on March 14, 2024, and any subsequent filings, that
could cause actual results, performance or achievement to differ
materially and adversely from those anticipated or implied in the
statements. You should not rely upon forward-looking statements as
predictions of future events. Although our management believes that
the expectations reflected in our statements are reasonable, we
cannot guarantee that the future results, performance, or events
and circumstances described in the forward-looking statements will
be achieved or occur. Recipients are cautioned not to place undue
reliance on these forward-looking statements, which speak only as
of the date such statements are made and should not be construed as
statements of fact. We undertake no obligation to publicly update
any forward-looking statements, whether as a result of new
information, any future presentations, or otherwise, except as
required by applicable law. Certain information contained in these
materials and any statements made orally during any presentation of
these materials that relate to the materials or are based on
studies, publications, surveys and other data obtained from
third-party sources and our own internal estimates and research.
While we believe these third-party studies, publications, surveys
and other data to be reliable as of the date of these materials, we
have not independently verified, and make no representations as to
the adequacy, fairness, accuracy or completeness of, any
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independent source has evaluated the reasonableness or accuracy of
our internal estimates or research and no reliance should be made
on any information or statements made in these materials relating
to or based on such internal estimates and research.
Investors Andrew
Funderburkir@monterosatx.com
Media Cory Tromblee, Scient
PRmedia@monterosatx.com
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