Acrivon Therapeutics Presents Data at AACR Annual Meeting Highlighting the Capabilities of Acrivon Predictive Precision Proteomics (AP3) for the Discovery of ACR-2316, a Novel, Selective WEE1/PKMYT1 Inhibitor, and the Identification of Actionable Resistanc
10 Abril 2024 - 7:00AM
Acrivon Therapeutics, Inc. (“Acrivon” or “Acrivon Therapeutics”)
(Nasdaq: ACRV), a clinical stage biopharmaceutical company
developing precision oncology medicines that it matches to patients
whose tumors are predicted to be sensitive to each specific
medicine by utilizing its proprietary proteomics-based patient
responder identification platform, Acrivon Predictive Precision
Proteomics (AP3), today announced data from two posters that the
company presented at the American Association for Cancer Research
(AACR) Annual Meeting.
“Our data at AACR illustrate several of the
broad capabilities of our AP3 platform and the power of employing
this precision proteomics-based approach in both drug discovery and
drug development,” said Peter Blume-Jensen, M.D., Ph.D., chief
executive officer, president, and founder of Acrivon Therapeutics.
“Uniquely enabled by AP3, we designed a selective and potent dual
inhibitor of both WEE1 and PKMYT1, ACR-2316, designed for potent
single agent activity. We presented preclinical data showing its
superior activity versus benchmark WEE1 and PKMYT1 single-agent
inhibitors in multiple cancer models and look forward to advancing
this compound into the clinic. Additionally at AACR, we presented
data on the underlying mechanisms that drive resistance to
treatment with ACR-368, which were discovered through AP3
profiling, and which led to the identification of ULDG as a way to
sensitize resistant ovarian cancer cells to ACR-368. These
actionable insights highlight Acrivon’s differentiated approach to
drug development.”
In a poster titled “ACR-2316: A potentially first-in-class,
potent, selective WEE1/PKMYT1 inhibitor rationally designed for
superior single agent activity through synergistic disruption of
cell cycle checkpoints,” preclinical data showing that ACR-2316 is
a potent dual WEE1/PKMYT1 inhibitor with superior anticancer
activity were presented. ACR-2316 was highly potent across multiple
human tumor cell lines and patient-derived ex vivo tumor models. In
proliferation assays across a panel of 19 cancer cell lines,
ACR-2316 demonstrated greater potency in all cell lines tested
compared to adavosertib and lunresertib (mean IC50 = 70, 252 and
364 nM, respectively). In the 12 ovarian cancer patient-derived
xenograft models tested, superior ex vivo anticancer activity of
ACR-2316 was observed compared to azenosertib and lunresertib (mean
IC50 = 9, 248 and 1620 nM, respectively). The complete responses
observed with ACR-2316 in human tumor xenograft mouse models were
associated with strong WEE1 and balanced PKMYT1 inhibition activity
in tumors.
In the second poster titled “Acrivon predictive precision
proteomics (AP3) uncovers mechanism of resistance to ACR-368, a
clinical-stage CHK1/2 inhibitor, and identifies rational
combination treatment,” preclinical studies using five ovarian
cancer cell lines that were generated to be durably resistant to
ACR-368 were reported. These cell lines were profiled using AP3
mass spectrometry, and comprehensive pathway reconstitution, and
kinase activity analysis was performed to identify drug resistance
mechanisms to ACR-368 to uncover actionable vulnerabilities. As a
result, ULDG was identified as a rational sensitization treatment,
and in in vivo CDX and PDX models of ovarian cancer, data confirmed
that ULDG sensitizes cancer cells to ACR-368. This corresponded
with the subsequent upregulation of ACR-368 OncoSignature
biomarkers, indicating that the OncoSignature assay can predict
which ULDG sensitized tumors would be responsive to treatment with
ACR-368.
About Acrivon Therapeutics Acrivon is a
clinical stage biopharmaceutical company developing precision
oncology medicines that it matches to patients whose tumors are
predicted to be sensitive to each specific medicine by utilizing
Acrivon’s proprietary proteomics-based patient responder
identification platform, Acrivon Predictive Precision Proteomics,
or AP3. The AP3 platform is engineered to measure compound-specific
effects on the entire tumor cell protein signaling network and
drug-induced resistance mechanisms in an unbiased manner. These
distinctive capabilities enable AP3’s direct application for drug
design optimization for monotherapy activity, the identification of
rational drug combinations, and the creation of drug-specific
proprietary OncoSignature companion diagnostics that are used to
identify the patients most likely to benefit from Acrivon’s drug
candidates. Acrivon is currently advancing its lead candidate,
ACR-368, a selective small molecule inhibitor targeting CHK1 and
CHK2 in a potentially registrational Phase 2 trial across multiple
tumor types. The company has received Fast Track designation from
the Food and Drug Administration, or FDA, for the investigation of
ACR-368 as monotherapy based on OncoSignature-predicted sensitivity
in patients with platinum-resistant ovarian or endometrial cancer.
Acrivon’s ACR-368 OncoSignature test, which has not yet obtained
regulatory approval, has been extensively evaluated in preclinical
studies, including in two separate, blinded, prospectively-designed
studies on pretreatment tumor biopsies collected from past
third-party Phase 2 trials in patients with ovarian cancer treated
with ACR-368. The FDA has granted Breakthrough Device designation
for the ACR-368 OncoSignature assay for the identification of
ovarian cancer patients who may benefit from ACR-368 treatment. In
addition to ACR-368, Acrivon is also leveraging its proprietary AP3
precision medicine platform for developing its
co-crystallography-driven, internally-discovered preclinical stage
pipeline programs. These include ACR-2316, a potent, selective
WEE1/PKMYT1 inhibitor designed for superior single-agent activity
as demonstrated in preclinical studies against benchmark
inhibitors, and a cell cycle program with an undisclosed
target.
Forward-Looking Statements This press release
includes certain disclosures that contain “forward-looking
statements” within the meaning of the Private Securities Litigation
Reform Act of 1995 about us and our industry that involve
substantial risks and uncertainties. All statements other than
statements of historical facts contained in this press release,
including statements regarding our future results of operations or
financial condition, business strategy and plans and objectives of
management for future operations, are forward-looking statements.
In some cases, you can identify forward-looking statements because
they contain words such as “anticipate,” “believe,” “contemplate,”
“continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,”
“potential,” “predict,” “project,” “should,” “target,” “will,” or
“would” or the negative of these words or other similar terms or
expressions. Forward-looking statements are based on Acrivon’s
current expectations and are subject to inherent uncertainties,
risks and assumptions that are difficult to predict. Factors that
could cause actual results to differ include, but are not limited
to, risks and uncertainties that are described more fully in the
section titled “Risk Factors” in our reports filed with the
Securities and Exchange Commission. Forward-looking statements
contained in this press release are made as of this date, and
Acrivon undertakes no duty to update such information except as
required under applicable law.
Investor and Media Contacts: Adam D. Levy,
Ph.D., M.B.A.alevy@acrivon.com
Alexandra Santos asantos@wheelhouselsa.com
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