Protara Therapeutics, Inc. (Nasdaq: TARA), a clinical-stage
company developing transformative therapies for the treatment of
cancer and rare diseases, today announced positive data from
three-month evaluable carcinoma in situ (CIS) patients treated
across its ongoing clinical program of TARA-002, the Company’s
investigational cell-based therapy, in high-risk Non-Muscle
Invasive Bladder Cancer (NMIBC), including Bacillus Calmette-Guérin
(BCG)-Unresponsive, BCG-Experienced and BCG-Naïve patient
populations.
“These promising three-month results support the
continued development of TARA-002 for patients with NMIBC for whom
there are currently limited treatment options,” said Timothy Lyon,
M.D., Associate Professor of Urology and the Urology Residency
Program Director at Mayo Clinic in Florida, and TARA-002 study
investigator. “Given our understanding that up to half of patients
treated with intravesical immune therapies that do not initially
respond can be salvaged with repeat induction, there is reason to
believe that the promising three-month response rates shared today
could be further improved through reinduction with TARA-002. This
encouraging anti-tumor activity coupled with a favorable safety
profile and mode of administration that is both convenient and
familiar to urologists indicates that, if confirmed in future
studies, TARA-002 could potentially play a meaningful role in NMIBC
treatment in the future.”
Enrollment continues in the Company’s ADVANCED-2
Phase 2 clinical trial of TARA-002 in patients with high-grade
NMIBC with BCG-Unresponsive CIS and BCG-Naïve CIS. The ADVANCED-2
trial design incorporates both reinduction and maintenance
dosing. The Company expects to share preliminary
results from a pre-planned risk-benefit analysis of the ADVANCED-2
trial in ten patients, who are six-month evaluable in the second
half of 2024.
“We are highly encouraged by these early results
observed in these three-month evaluable patients across our
ADVANCED-1 and ADVANCED-2 clinical trials, which clearly
demonstrate TARA-002’s activity in both BCG-Unresponsive and
BCG-Naïve patients. We look forward to sharing data from
post-reinduction, six-month evaluable patients in our ADVANCED-2
trial in the second half of 2024,” said Jesse Shefferman, Chief
Executive Officer of Protara Therapeutics.
Overview of Three-Month Evaluable
Data
Data reported today highlight the potential of
TARA-002 in patients with NMIBC. Data were derived from three-month
evaluable NMIBC patients with CIS pooled across the Company’s
ADVANCED-1 Phase 1a, Phase 1b-expansion and ADVANCED-2 Phase 2
trials of TARA-002 in patients with high-risk NMIBC, including
BCG-Unresponsive, BCG-Experienced and BCG-Naïve patients. The
overall three-month complete response (CR) rate prior to
reinduction for 16 evaluable patients treated across the three
trials with varying BCG status was 38% (6/16), with a CR rate of
63% (5/8) in CIS-only patients and 13% (1/8) in patients with CIS
+Ta/T1. The Company believes that reinduction and planned
enhancements to dosing and administration will lead to an increased
CR rate at six months in patients who did not achieve a CR at three
months, as reinduction with other immune agents in NMIBC patients
with CIS has demonstrated a 30%-50% salvage rate. The Company plans
to explore additional dosing cohorts, which may prove effective in
patients who might benefit.
|
Three Month Evaluable Patients |
|
# Patients |
# of CRs |
CR % |
|
|
|
|
BCG-Unresponsive/ Experienced |
CIS-only |
6 |
3 |
50% |
|
CIS +Ta/T1 |
1 |
- |
-% |
|
|
7 |
3 |
43% |
|
BCG-Naïve |
|
|
|
CIS-only |
2 |
2 |
100% |
|
CIS +Ta/T1 |
7 |
1 |
14% |
|
|
9 |
3 |
33% |
|
|
16 |
6 |
38% |
|
|
|
|
|
By Stage
of Disease at Baseline |
|
CIS-only |
8 |
5 |
63% |
|
CIS +Ta/T1 |
8 |
1 |
13% |
|
|
16 |
6 |
38% |
|
|
|
|
|
By Study |
|
|
|
Phase 1a |
3 |
1 |
33% |
|
Phase 1b-EXP |
8 |
3 |
38% |
|
Phase 2 Naïve |
5 |
2 |
40% |
|
|
16 |
6 |
38% |
|
|
|
|
|
|
The majority of reported adverse events were
Grades 1 and 2 across all dose levels, and treatment emergent
adverse events (TEAEs), as assessed by study investigators, were in
line with typical responses to bacterial immunopotentiation, and
included fatigue, headache, fever, and chills. The most common
urinary symptoms were urinary urgency, urinary frequency, urinary
tract pain/burning, incomplete emptying, and bladder spasm. Most
bladder irritations resolved soon after administration or in a few
hours to a few days.
“TARA-002 is a broad spectrum immunopotentiator
with a similar mechanism of action as the standard of care, BCG.
Because TARA-002 is an inactivated bacteria, there are no special
dosing and administration protocol requirements, which makes it
ideal for administration in the community urology practice
setting,” said Gautam Jayram, MD., Director, Advanced Therapeutics
Center, Urology Associates PC in Nashville and TARA-002 study
investigator. “I am encouraged by the early three-month data in a
challenging disease state and look forward to continued
participation in the TARA-002 clinical program.”
NMIBC Clinical Program
The ADVANCED-1 expansion trial is evaluating
intravesical TARA-002 at the 40KE1 dose in up to 12 NMIBC patients
with CIS and CIS +Ta/T1, including BCG-Unresponsive, BCG-Naïve, and
BCG-Experienced patient populations. The primary endpoint is safety
and complete response (CR) rate at the preliminary three-month
assessment timepoint.
The Phase 2 open-label ADVANCED-2 trial is
assessing intravesical TARA-002 in at least 102 NMIBC patients with
CIS (± Ta/T1) who are BCG-Unresponsive (n=75-100) and BCG-Naïve
(n=27). The BCG-Unresponsive cohort has been designed to be
registrational aligned with the FDA’s 2018 BCG-Unresponsive
Non-muscle Invasive Bladder Cancer: Developing Drugs and Biologics
for Treatment Guidance for Industry. Trial subjects receive an
induction course of six weekly intravesical instillations, followed
by either reinduction (if eligible) or maintenance for up to 24
months.
Two additional exploratory cohorts will be added
to the ADVANCED-2 trial assessing higher dosing at an 80KE dose
(Cohort C) and systemic priming prior to initiation of intravesical
administration (Cohort D). In addition, the Company intends to
initiate a proof-of-concept study of TARA-002 in combination with
pembrolizumab in NMIBC patients with CIS to assess the potential
synergistic effects of the combination regimen.
About TARA-002
TARA-002 is an investigational cell therapy in
development for the treatment of NMIBC and of lymphatic
malformations (LMs), for which it has been granted Rare Pediatric
Disease Designation by the U.S. Food and Drug Administration.
TARA-002 was developed from the same master cell bank of
genetically distinct group A Streptococcus pyogenes as OK-432, a
broad immunopotentiator marketed as Picibanil® in Japan and
approved in Taiwan by Chugai Pharmaceutical Co., Ltd. Protara has
successfully shown manufacturing comparability between TARA-002 and
OK-432.
When TARA-002 is administered, it is
hypothesized that innate and adaptive immune cells within the cyst
or tumor are activated and produce a pro-inflammatory response with
release of cytokines such as tumor necrosis factor (TNF)-alpha,
interferon (IFN)-gamma, IL-1b, IL-6, IL-12, granulocyte-macrophage
colony-stimulating factor (GM-CSF) and natural killer cells.
TARA-002 also directly kills tumor cells and triggers a host immune
response by inducing immunogenic cell death, which further enhances
the antitumor immune response.
About Non-Muscle Invasive Bladder Cancer
(NMIBC)
Bladder cancer is the 6th most common cancer in
the United States, with NMIBC representing approximately 80% of
bladder cancer diagnoses. Approximately 65,000 patients are
diagnosed with NMIBC in the United States each year. NMIBC is
cancer found in the tissue that lines the inner surface of the
bladder that has not spread into the bladder muscle.
About Protara Therapeutics,
Inc.
Protara is a clinical-stage biotechnology
company committed to advancing transformative therapies for people
with cancer and rare diseases. Protara’s portfolio includes its
lead candidate, TARA-002, an investigational cell-based therapy in
development for the treatment of non-muscle invasive bladder cancer
(NMIBC) and lymphatic malformations (LMs). The Company is
evaluating TARA-002 in an ongoing Phase 2 trial in NMIBC patients
with carcinoma in situ (CIS) who are unresponsive or naïve to
treatment with Bacillus Calmette-Guérin (BCG), as well as a Phase 2
trial in pediatric patients with LMs. Additionally, Protara is
developing IV Choline Chloride, an investigational phospholipid
substrate replacement for patients on parenteral nutrition who are
otherwise unable to meet their choline needs via oral or enteral
routes. For more information, visit www.protaratx.com.
References
1. Klinische Einheit, or KE, is a German term indicating a
specified weight of dried cells in a vial.
Forward-Looking Statements
Statements contained in this press release
regarding matters that are not historical facts are "forward
looking statements" within the meaning of the Private Securities
Litigation Reform Act of 1995. Protara may, in some cases, use
terms such as “predicts,” “believes,” “potential,” “proposed,”
“continue,” “designed,” “estimates,” “anticipates,” “expects,”
“plans,” “intends,” “may,” “could,” “might,” “will,” “should” or
other words or expressions referencing future events, conditions or
circumstances that convey uncertainty of future events or outcomes
to identify these forward-looking statements. Such forward-looking
statements include but are not limited to, statements regarding
Protara’s intentions, beliefs, projections, outlook, analyses or
current expectations concerning, among other things: Protara’s
business strategy, including its development plans for its product
candidates and plans regarding the timing or outcome of existing or
future clinical trials; statements related to expectations
regarding interactions with the FDA; Protara’s financial position;
statements regarding the anticipated safety or efficacy of
Protara’s product candidates; and Protara’s outlook for the
remainder of the year. Because such statements are subject to risks
and uncertainties, actual results may differ materially from those
expressed or implied by such forward-looking statements. Factors
that contribute to the uncertain nature of the forward-looking
statements include: risks that Protara’s financial guidance may not
be as expected, as well as risks and uncertainties associated with:
Protara’s development programs, including the initiation and
completion of non-clinical studies and clinical trials and the
timing of required filings with the FDA and other regulatory
agencies; general market conditions; changes in the competitive
landscape; changes in Protara’s strategic and commercial plans;
Protara’s ability to obtain sufficient financing to fund its
strategic plans and commercialization efforts; having to use cash
in ways or on timing other than expected; the impact of market
volatility on cash reserves; failure to attract and retain
management and key personnel; the impact of general U.S. and
foreign, economic, industry, market, regulatory, political or
public health conditions; and the risks and uncertainties
associated with Protara’s business and financial condition in
general, including the risks and uncertainties described more fully
under the caption “Risk Factors” and elsewhere in Protara's filings
and reports with the United States Securities and Exchange
Commission. All forward-looking statements contained in this press
release speak only as of the date on which they were made and are
based on management's assumptions and estimates as of such date.
Protara undertakes no obligation to update any forward-looking
statements, whether as a result of the receipt of new information,
the occurrence of future events or otherwise, except as required by
law.
Company Contact:
Justine O'MalleyProtara
TherapeuticsJustine.OMalley@protaratx.com646-817-2836
Protara Therapeutics (NASDAQ:TARA)
Gráfico Histórico do Ativo
De Abr 2024 até Mai 2024
Protara Therapeutics (NASDAQ:TARA)
Gráfico Histórico do Ativo
De Mai 2023 até Mai 2024