Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage
biopharmaceutical company focused on discovering and developing a
pipeline of antibody-drug conjugates (ADCs) targeting cancers in
areas of high unmet medical need, today presented preclinical
data from XMT-1660, a B7-H4-targeted Dolasynthen antibody-drug
conjugate (ADC), and XMT-2056, an Immunosynthen-based STING-agonist
ADC at the Virtual 2021 American Association for Cancer
Research Annual Meeting being held from April 10-15th.
“The ability of Immunosynthen-based ADCs to
activate the innate immune system via STING in tumor cells in
addition to tumor-resident immune cells in a targeted manner could
offer a significant therapeutic advantage over ADCs that modulate
other immune activating pathways. These data demonstrate that
XMT-2056 is highly differentiated from other innate immune
activating approaches and has the anti-tumor activity and
tolerability to support continued development of this novel
STING-agonist ADC candidate,” said Timothy B. Lowinger, Ph.D.,
Chief Science and Technology Officer of Mersana Therapeutics.
“Additionally, we presented data showing that XMT-1660 outperformed
other B7-H4 ADCs in vivo. The inversely correlated expression of
B7-H4 and PD-L1 in breast tumors suggests an opportunity for a
B7-H4 Dolasynthen ADC to address patients poorly served by
checkpoint inhibitors. We expect to complete IND-enabling studies
and advance both XMT-1660 and XMT-2056 into the clinic in early
2022.”
“These encouraging data for both the Dolasynthen
and Immunosynthen platforms demonstrate the scientific prowess of
the Mersana research team and our commitment to discover and
develop life-changing antibody-drug conjugates for patients
fighting cancer,” said Anna Protopapas, President and Chief
Executive Officer of Mersana Therapeutics.
Details of the posters are as follows:
Poster Title: XMT-1660, a
B7-H4-targeted Dolasynthen antibody-drug conjugate for the
treatment of breast cancerPoster Number:
907Session Category: Experimental and Molecular
TherapeuticsSession Title: Antibody
Technologies
These data show that B7-H4 is a promising target
for a Dolasynthen ADC due to its expression and function. B7-H4 is
expressed across multiple different tumor types with high unmet
medical need, including breast, endometrial and ovarian. XMT-1660
demonstrated robust in vivo activity against multiple
triple-negative breast cancer models, as well as an ER+/HER2-
breast cancer model, all of which express B7-H4.
- In the MX-1 triple-negative breast
model, XMT-1660 showed complete, durable regressions of tumors at a
DolaLock payload dose of 0.15 mg/kg. In contrast, the DAR-2 and
DAR-12 ADCs required twice the payload dose for comparable
efficacy. XMT-1660 also showed superior efficacy at matched payload
doses in the TNBC patient-derived xenograft model HBCx-24, and in
the ER+/HER2- breast cancer PDX model HBCx-19 versus
comparators.
- Pharmacokinetics of XMT-1660 as
well as the Dolasynthen DAR-2 and Dolaflexin DAR-12 comparator ADCs
were evaluated in tumor-bearing mice and all were shown to be
highly stable in vivo. Pharmacokinetics and tolerability of
XMT-1660 and the Dolasynthen DAR-2 ADC were evaluated in non-human
primates at equivalent payload doses. The PK and tolerability
profiles were comparable and both ADCs exhibited high stability.
These results, together with the superior efficacy of XMT-1660,
support the selection of XMT-1660 for further development and for
clinical study for the treatment of B7-H4-expressing tumors, such
as breast, endometrial and ovarian.
Poster Title: XMT-2056, a
well-tolerated, Immunosynthen-based STING-agonist antibody-drug
conjugate which induces anti-tumor immune activityPoster
Number: 1738Session Category:
ImmunologySession Title: Immunomodulatory Agents
and Interventions
These data suggest that XMT-2056, an
Immunosynthen STING-agonist ADC, can overcome the limitations of
the current therapeutic approaches, enabling tumor-targeted
delivery of a STING agonist with improved efficacy and tolerability
over a free IV STING agonist. Anti-tumor activity of Immunosynthen
STING-agonist ADCs involves targeted activation of the STING
pathway in both tumor-resident immune cells and tumor cells,
delivering a one-two punch with the potential to increase
the therapeutic index.
- In vitro studies show that XMT-2056
has potent STING activity with >100-fold improvement in activity
in comparison to the free STING-agonist payload.
- XMT-2056 shows excellent in vivo
efficacy even after a single IV dose, while having minimal effect
on systemic cytokines. A single, low dose administration of
XMT-2056 led to sustained tumor regressions in mice in comparison
to the IV STING agonist which showed modest activity even at a dose
approximately 100 times higher than that of the ADC. In contrast,
when comparing the effect on systemic cytokine levels, the IV STING
agonist had significantly higher levels compared to the
STING-agonist ADC, which supports the hypothesis that a
STING-agonist ADC can target STING activation to the tumor
microenvironment, leading to improved anti-tumor activity and a
significantly greater therapeutic index.
- In vitro and in vivo studies
demonstrate that STING agonist ADCs are able to activate the STING
pathway in both tumor-resident immune cells and tumor cells,
offering a potential advantage over other innate immune activating
pathways.
- To evaluate the safety profile,
XMT-2056 was administered intravenously to non-human primates (NHP)
in single and repeat-dose studies at multiple dose levels. XMT-2056
shows favorable pharmacokinetics in NHPs and is well tolerated at a
dose level >10-fold higher than required for sustained tumor
regression in mice models. Together these data support the clinical
development of XMT-2056.
Poster Title: Tumor
cell-intrinsic STING pathway activation leads to robust induction
of Type III Interferons and contributes to the anti-tumor activity
elicited by STING agonismPoster Number:
1773Session Category: ImmunologySession
Title: Innate Immunity to Tumors
STING pathway agonism induces anti-tumor
immunity by upregulating a Type I interferon response within the
tumor microenvironment. While systemically or intra-tumorally
administered free STING agonists are currently being evaluated in
the clinic, these data suggest that a STING-agonist ADC, in which
the STING agonist is conjugated to an antibody directed to a tumor
antigen, can overcome the limitations of the current therapeutic
approaches.
- In vitro studies show that while
most cancer cell lines do not respond to STING agonism in standard
monoculture conditions, Immunosynthen STING-agonist ADCs do
activate STING in the same cancer cells in the presence of immune
cell-conditioned media, suggesting that the tumor cell-intrinsic
STING pathway can be activated in the presence of cues from immune
cells.
- Nanostring analysis of human tumor xenografts reveal tumor cell
specific induction of type III interferons (IFNs) by tumor
cell-targeting Immunosynthen STING-agonist ADCs. In vitro studies
confirmed the Type III interferon induction at the mRNA and
cytokine level. Type III interferon production was markedly reduced
in STING knock out cancer cell and immune cell co-cultures,
suggesting that the tumor intrinsic STING activation is required
for a robust Type III interferon induction in response to STING
agonism. In addition, these data show that blocking Type III IFNs
with neutralizing antibodies in cancer cell:immune cell co-cultures
inhibits the production of key cytokines and cancer cell killing
induced by STING-agonist ADC treatment, pointing to a potentially
important role for Type III IFNs in anti-tumor immune responses
downstream of STING pathway activation in tumor cells.
- Together these data demonstrate
that tumor cell intrinsic STING activation leads to a robust type
III interferon induction, which contributes to the anti-tumor
activity of tumor cell-targeted STING-agonist ADCs. This study
supports the further development of Immunosynthen STING-agonist ADC
candidates.
About Mersana
TherapeuticsMersana Therapeutics is a clinical-stage
biopharmaceutical company using its differentiated and proprietary
ADC platforms to rapidly develop novel ADCs with optimal efficacy,
safety and tolerability to meaningfully improve the lives of people
fighting cancer. Mersana’s lead product candidate, upifitamab
rilsodotin (UpRi), is a Dolaflexin ADC targeting NaPi2b and is
being studied in UPLIFT, a single-arm registration strategy, in
patients with platinum-resistant ovarian cancer as well as the
expansion portion of a Phase 1 proof-of-concept clinical study in
patients with NSCLC adenocarcinoma. XMT-1592, Mersana’s second ADC
product candidate targeting NaPi2b-expressing tumors, was created
using Mersana’s customizable and homogeneous Dolasynthen platform
and is in the dose escalation portion of a Phase 1 proof-of-concept
clinical study. The Company’s early-stage programs include
XMT-1660, a Dolasynthen ADC targeting B7-H4, as well as XMT-2056, a
STING-agonist ADC developed using the Company’s Immunosynthen
platform. In addition, multiple partners are using Mersana’s
Dolaflexin platform to advance their ADC pipelines.
Forward-Looking StatementsThis
press release contains “forward-looking” statements within the
meaning of federal securities laws. These forward-looking
statements are not statements of historical facts and are based on
management’s beliefs and assumptions and on information currently
available to management. Forward-looking statements include
information concerning the Company’s business strategy and the
design, progression and timing of its clinical trials, the ability
of the single-arm UPLIFT cohort to enable registration, and
expectations regarding future clinical trial results based on data
achieved to date, and the sufficiency of the Company’s cash on
hand. Forward-looking statements generally can be identified by
terms such as “aims,” “anticipates,” “believes,” “contemplates,”
“continues,” “could,” “estimates,” “expects,” “goal,” “intends,”
“may,” “on track,” “opportunity,” “plans,” “poised for,”
“possible,” “potential,” “predicts,” “projects,” “promises to be,”
“seeks,” “should,” “target,” “will,” “would” or similar expressions
and the negatives of those terms. Forward-looking statements
represent management’s beliefs and assumptions only as of the date
of this press release. The Company’s operations involve risks and
uncertainties, many of which are outside its control, and any one
of which, or combination of which, could materially affect its
results of operations and whether the forward-looking statements
ultimately prove to be correct. Factors that may materially affect
the Company’s results of operations and whether these
forward-looking statements prove to be correct include, among other
things, that preclinical testing or early clinical results may not
be predictive of the results or success of ongoing or later
preclinical or clinical studies, that the identification,
development and testing of the Company’s product candidates and new
platforms will take longer and/or cost more than planned, and that
our clinical studies may not be initiated or completed on schedule,
if at all, as well as those listed in the Company’s Annual Report
on Form 10-K filed on February 26, 2021, with the Securities and
Exchange Commission (“SEC”), and subsequent SEC filings. In
addition, while we expect that the COVID-19 pandemic might
adversely affect the Company’s preclinical and clinical development
efforts, business operations and financial results, the extent of
the impact on the Company’s operations and the value of and market
for the Company’s common stock will depend on future developments
that are highly uncertain and cannot be predicted with confidence
at this time, such as the ultimate duration of the pandemic, travel
restrictions, quarantines, physical distancing and business closure
requirements in the U.S. and in other countries, and the
effectiveness of actions taken globally to contain and treat the
disease. Except as required by law, the Company assumes no
obligation to update these forward-looking statements publicly, or
to update the reasons actual results could differ materially from
those anticipated in the forward-looking statements, even if new
information becomes available in the future.
Contact:
Investor & Media
ContactSarah Carmody, 617-844-8577scarmody@mersana.com
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