Prometheus Biosciences, Inc. (Nasdaq: RXDX), a clinical-stage
biotechnology company pioneering a precision medicine approach for
the discovery, development, and commercialization of novel
therapeutic and companion diagnostic products for the treatment of
immune-mediated diseases, today reported results from its
ARTEMIS-UC Phase 2 and APOLLO-CD Phase 2a studies of PRA023
demonstrating strong efficacy and favorable safety results in both
studies. Based on the totality of the data in these two studies,
Prometheus intends to advance PRA023 into Phase 3 studies for
ulcerative colitis (UC) and Crohn’s disease (CD) in 2023.
Topline Results from the ARTEMIS-UC
Phase 2 Study
Prometheus’ Phase 2 ARTEMIS-UC clinical trial was a 12-week,
double-blind, placebo-controlled, randomized study to evaluate the
efficacy and safety of PRA023 in patients with moderate-to-severely
active UC who have failed conventional or advanced therapy. PRA023
met the primary and all ranked secondary endpoints including
clinical, endoscopic, histologic, and patient-reported outcome
measures in the initial cohort (Cohort 1) of the trial. 68/68
(100%) of PRA023-treated patients completed the Cohort 1 study,
compared to 60/67 (89.6%) in the placebo group. The topline results
for the key endpoints were as follows:
- 26.5% of patients on PRA023 reached the primary endpoint of
clinical remission (per modified Mayo Score), compared to 1.5% on
placebo, for a placebo-adjusted clinical remission rate of 25.0% on
the primary endpoint (p<0.0001)
- 36.8% of patients on PRA023 reached the secondary endpoint of
endoscopic improvement (Mayo endoscopy subscore of ≤ 1), compared
to 6.0% on placebo, for a placebo-adjusted endoscopic improvement
rate of 30.8% on the secondary endpoint (p<0.0001)
- All secondary endpoints met with statistical significance
PRA023 was well tolerated in Cohort 1, with no
treatment-emergent serious adverse events (SAEs), adverse events
(AEs) leading to discontinuation, severe AEs, opportunistic
infections or infusion reactions reported in the PRA023 treatment
group. The only AE that occurred in more than two patients and at a
higher frequency in the PRA023 group compared to placebo was
COVID-19 (5/68 [7.4%] and 3/67 [4.5%], respectively).
Based upon confidence in its precision approach and speed to
market, the company conducted an interim companion diagnostic (CDx)
analysis of Cohort 1 to evaluate the effectiveness of the CDx
candidate in ARTEMIS-UC. Although from limited patient numbers,
data from the subset of patients who tested positive on the CDx in
Cohort 1 (N=32) demonstrated a placebo-adjusted clinical remission
rate of 37.5%, compared with the placebo-adjusted remission rate of
25.0% for all-comers. The expansion cohort (Cohort 2), which is
statistically powered to further assess the treatment effect of
PRA023 in CDx+ patients will continue to enroll, and the company
expects results in the second quarter of 2023.
Results from the APOLLO-CD Phase 2a
Study
Prometheus’ Phase 2a APOLLO-CD clinical trial
was a 12-week open-label study that enrolled 55 patients with
moderate-to-severely active CD with endoscopically active disease
who had failed conventional or biologic therapy. The study enrolled
a highly refractory patient population with 70.9% of patients
previously treated with at least one biologic therapy and 52.7%
treated with two or more biologic therapies. The results on the key
endpoints were as follows:
- 26.0% of patients on PRA023 achieved endoscopic response
(p=0.002 compared to 12% prespecified historical placebo rate)
- 49.1% of patients on PRA023 achieved
clinical remission (p<0.001 compared to 16% prespecified
historical placebo rate)
PRA023 was well tolerated in the APOLLO-CD study. There were no
treatment-emergent serious adverse events (SAE), adverse events
(AE) leading to discontinuation, or severe AEs assessed as related
to PRA023 by the investigator. There were no opportunistic
infections or infusion reactions reported. AEs that occurred in
more than two patients included COVID-19, urinary tract infection,
CD, anemia, nasopharyngitis and fatigue.
The predictive power of the company’s prespecified genetic
markers was validated using an alternative Crohn’s-specific CDx
algorithm which showed 45.0% (9/20) endoscopic response relative to
all-comers of 26% (13/50). While the original algorithm provided
limited benefit on some of the endpoints, the alternative algorithm
demonstrated enhanced performance across both clinical and
endoscopic outcomes. The company plans to advance this alternative
algorithm in registrational studies for CD.
In addition, a compelling reduction in markers of inflammation
and fibrosis was observed between pre-treatment and post-treatment
with PRA023, as measured by circulating cytokine levels,
immunohistochemistry and gene expression in disease tissue.
“We are beyond enthusiastic with these study results and what
they could mean for patients suffering from IBD. The performance of
PRA023 in both UC and Crohn’s patients has surpassed our
expectations,” said Mark McKenna, Chairman and CEO of Prometheus
Biosciences. “We believe PRA023 and our precision medicine approach
has the potential to change the paradigm of IBD treatment and we
look forward to discussions with regulatory agencies as we prepare
to advance into Phase 3 studies in Ulcerative Colitis and Crohn’s
Disease.”
“PRA023 has clearly demonstrated clinical proof-of-concept in CD
and remarkable efficacy for the treatment of UC,” added Allison
Luo, MD, Chief Medical Officer. “We are grateful to all of our
investigators and patients for their participation and look forward
to further evaluating PRA023 in Phase 3 studies with the goal of
bringing this promising candidate to the market.”
Next Steps
As a result of these positive data, Prometheus plans
to advance PRA023 into pivotal development in 2023, following
discussions with regulators. The full data sets from these studies
will be presented at a future medical meeting.
Webcasting Information
Prometheus management will hold a call today, December
7, at 8:30 am ET to discuss both ARTEMIS-UC and APOLLO-CD
Phase 2 results. Registration for the event as well as a live and
archived webcast of the webcast and call will be available in the
Events & Webcasts page of the Prometheus Biosciences
website.
About PRA023: Pipeline in a Product
Candidate
PRA023 is an IgG1 humanized monoclonal antibody that has been
shown to block tumor necrosis factor (TNF)-like ligand 1A (TL1A).
PRA023 binds both soluble and membrane-associated human TL1A with
high affinity and specificity and has the potential to
substantially improve outcomes for moderate-to-severe IBD patients
predisposed to increased TL1A expression. Prometheus is developing
PRA023 for the treatment of immune-mediated diseases including UC,
CD, and systemic sclerosis-associated interstitial lung disease
(SSc-ILD).
About Prometheus Biosciences
Prometheus Biosciences, Inc. is a clinical-stage biotechnology
company pioneering a precision medicine approach for the discovery,
development, and commercialization of novel therapeutic and
companion diagnostic products for the treatment of immune-mediated
diseases. The Company’s precision medicine platform,
Prometheus360™, combines proprietary machine learning-based
analytical approaches with one of the world’s largest
gastrointestinal bioinformatics databases to identify novel
therapeutic targets and develop therapeutic candidates to engage
those targets.
Forward Looking Statements
Prometheus cautions readers that statements contained in this
press release regarding matters that are not historical facts are
forward-looking statements. These statements are based on the
Company’s current beliefs and expectations. Such forward-looking
statements include, but are not limited to statements regarding:
the potential of PRA023 to improve IBD treatment and to be both a
first-in-class and best-in-class anti-TL1A mAb; the timing of
results from Cohort 2 of the ARTEMIS-UC trial; plans to advance
PRA023 into Phase 3 studies in UC and CD, including the timing
thereof, as well as plans to use an alternative CDx algorithm for
CD. The inclusion of forward-looking statements should not be
regarded as a representation by Prometheus that any of its plans
will be achieved. Actual results may differ from those set forth in
this press release due to the risks and uncertainties inherent in
our business, including, without limitation: topline results
Prometheus reports are based on preliminary analysis of key
efficacy and safety data, and such data may change following a more
comprehensive review of the data related to the clinical trial and
such topline data may not accurately reflect the complete results
of a clinical trial; Prometheus’ approach to the discovery and
development of precision medicines based on Prometheus360 is
unproven; interim results of a clinical trial such as with Cohort 1
CDx analysis do not predict final results and the clinical outcomes
may materially change as patient enrollment in Cohort 2 continues,
following more comprehensive reviews of the data, as follow-up on
the outcome of any particular patient continues and as more patient
data become available, including from from Cohort 2; potential
delays in the commencement, enrollment and completion of clinical
trials and preclinical studies; the results of clinical trials are
not necessarily predictive of future results; Prometheus’
dependence on third parties in connection with product
manufacturing, research and preclinical and clinical testing;
Prometheus’ ability to develop companion diagnostics for its
therapeutic product candidates; unexpected adverse side effects or
inadequate efficacy of its product candidates that may limit their
development, regulatory approval and/or commercialization, or may
result in recalls or product liability claims; planned future
trials of PRA023 may not support regulatory registration;
regulatory developments in the United States and foreign
countries; Prometheus’ ability to maintain undisrupted business
operations due to the COVID-19 pandemic, including delaying or
otherwise disrupting its preclinical studies, clinical trials,
manufacturing and supply chain; and other risks described in
the Company’s prior press releases and filings with
the Securities and Exchange Commission (SEC), including
under the heading “Risk Factors” in Prometheus’ most recent
quarterly report on Form 10-Q and any subsequent filings with
the SEC. You are cautioned not to place undue reliance on
these forward-looking statements, which speak only as of the date
hereof, and Prometheus undertakes no obligation to update such
statements to reflect events that occur or circumstances that exist
after the date hereof. All forward-looking statements are qualified
in their entirety by this cautionary statement, which is made under
the safe harbor provisions of the Private Securities Litigation
Reform Act of 1995.
Contacts:Noel KurdiVP Investor Relations and
Communications(646) 241-4400nkurdi@prometheusbiosciences.com
Media contact:Juniper PointAmy Conrad(858)
914-1962media@prometheusbiosciences.com
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