- Encouraging preliminary anti-tumor activity
observed in heavily pre-treated population -
- At ≥ 90 mg QD, 6 out of 11 (54.5%) patients
with FGFR3+ mUC achieved a confirmed partial response (PR), with
100% disease control rate and sustained duration of activity
-
- Positive safety results across all QD
doses, with infrequent FGFR2/FGFR1-associated toxicities
-
- Conference call scheduled for October 25th, 2024, at 8AM
EDT -
CARLSBAD, Calif., Oct. 24,
2024 /PRNewswire/ -- Tyra Biosciences, Inc. (Nasdaq:
TYRA), a clinical-stage biotechnology company focused on developing
next-generation precision medicines that target large opportunities
in Fibroblast Growth Factor Receptor (FGFR) biology, announced
today clinical proof-of-concept data for TYRA-300 in patients with
metastatic urothelial (mUC) cancer from its ongoing SURF301 Phase
1/2 study. These data will be presented in a late-breaking
oral presentation at the 36th EORTC-NCI-AACR (ENA)
Symposium on Molecular Targets and Cancer Therapeutics, being held
October 23-25, 2024 in
Barcelona, Spain. TYRA-300
is a potential first-in-class, investigational, oral,
FGFR3-selective inhibitor designed to avoid the toxicities
associated with inhibition of FGFR1, FGFR2 and FGFR4, while being
agnostic for the FGFR3 gatekeeper mutations.
"FGFR3 alterations are known to drive tumor biology in a subset
of urothelial cancer. While pan-FGFR inhibitors have
demonstrated benefit and are approved for use in FGFR3 altered
urothelial cancer, they are associated with multiple intolerable
on-target toxicities that limit their clinical utility. There
remains an unmet need to deliver improved precision medicine for
urothelial cancer patients, that allow patients to not only live
longer, but live better," said Ben
Tran, M.D., Associate Professor, Peter McCallum Cancer
Centre, Melbourne,
Australia. "The initial results from TYRA-300 are very
encouraging. I believe TYRA-300 has the potential to be a
next generation targeted therapy, with high selectivity for FGFR3.
These early data provide support that TYRA-300 can deliver improved
anti-tumor activity and tolerability for our FGFR3 altered
urothelial cancer patients. TYRA-300 has real potential to
improve outcomes, and I look forward to its continued development
in all FGFR3 altered cancers."
Summary of Interim Clinical Results
As of August 15, 2024, the data
cutoff date, 41 patients were enrolled in the Phase 1 portion of
the SURF301 Phase 1/2 study. Eligible participants were adults with
advanced malignancies with or without FGFR3 alterations, including
those with prior treatment with erdafitinib. The enrolled
patient population was heavily pre-treated, with 44% of patients
receiving ≥ 3 lines of therapy prior to receiving TYRA-300, and 76%
of FGFR3+ mUC patients receiving ≥ 3 lines of therapy.
Treatment with TYRA-300 was evaluated across six dose levels,
ranging from 10 mg-120 mg once daily (QD).
- Preliminary PK/PD analysis in 41 patients as of the data cutoff
date: TYRA-300 plasma concentrations indicate adequate target
coverage at ≥ 90 mg QD, with further pharmacokinetic
characterization ongoing.
- In patients with FGFR3+ mUC who received doses ≥ 90
mg QD, anti-tumor activity was observed in all patients:
- 6 out of 11 (54.5%) patients at ≥ 90 mg QD achieved a PR, 3 of
which are still ongoing.
- 5 out of 10 (50%) patients at 90 mg QD achieved a PR.
- 1 out of 1 (100%) patient at 120 mg QD achieved a PR.
- A 100% disease control rate (DCR) was achieved for all patients
at ≥ 90 mg QD (PR + stable disease).
- TYRA-300 has demonstrated favorable interim safety results as
of the data cutoff date:
- Preliminary data from SURF301 suggest TYRA-300 to be generally
well-tolerated, with infrequent FGFR2- and FGFR1-associated
toxicities.
- In doses from 10 mg up to 120 mg QD, there were 4 (10%) serious
adverse events related to TYRA-300, 1 dose-limiting toxicity (DLT)
of grade (Gr) 3 diarrhea at 90 mg QD, and 1 treatment-related
adverse event (TRAE) leading to discontinuation of treatment (Gr3
ALT, 90 mg QD).
- There were no ≥ Gr4 TRAEs.
- The 120 mg QD dose was the highest dose evaluated with no
DLTs reported.
"The preliminary data are what we were expecting to see with
TYRA-300, being generally well-tolerated with
fewer toxicities, and anti-tumor activity in FGRF3+ mUC
patients," said Doug Warner, M.D.,
Chief Medical Officer of TYRA. "The emerging profile of
TYRA-300 supports further development in metastatic urothelial
cancer, where an attractive opportunity exists for a more tolerable
option in second line."
Dr. Warner continued, "We are grateful for the support of our
study participants, their families and our global collaborators on
SURF301. We remain focused on progressing TYRA-300 through
dose optimization in SURF301 and toward patients in need."
"Our team set out to solve an ambitious chemistry problem that
had stumped the field of precision oncology - to create an
efficacious FGFR3-selective inhibitor with a favorable tolerability
profile to address the limitations of pan-FGFR inhibitors. We
believe that today's interim results provide clinical support for
addressing this difficult problem, and the data are in line with
our expectations," said Todd Harris,
CEO of TYRA. "These data give us confidence to advance TYRA-300
through Part B in SURF301 and explore larger opportunities with
Phase 2 studies in metastatic urothelial cancer, non-muscle
invasive bladder cancer and achondroplasia."
ENA 2024 presentation details:
Title: "Preliminary safety and anti-tumor activity of
TYRA-300, a highly selective FGFR3 inhibitor, in participants with
advanced solid tumors with activating FGFR3 mutations/fusions
(SURF301)"
Session: Late Breaking Abstracts and Proffered Papers: Novel
discoveries in drug development
Date: Friday, October 25, 2024
Time: 15:36 - 15:48 hrs CEST
Abstract #: 500LBA
Conference Call Information
TYRA is hosting a conference call and webcast on October 25, 2024, at 8am
ET to review the interim clinical proof-of-concept results
demonstrated with TYRA-300 in mUC. Participants may access a
live webcast of the call and the associated slide presentation on
the "For Investors" page of the TYRA website
at https://ir.tyra.bio. To participate via telephone, please
register in advance at this link. Upon registration,
all telephone participants will receive a confirmation email
detailing how to join the conference call, including the dial-in
number along with a unique passcode and registrant ID that can be
used to access the call. A replay of the conference call and
webcast will be archived on the Company's website for at least 30
days.
About TYRA-300 and the SURF301 Study
TYRA-300 is TYRA's lead precision medicine program stemming from
its in-house SNÅP platform. TYRA-300 is an investigational, oral,
FGFR3-selective inhibitor currently in development for the
treatment of cancer and skeletal dysplasias, including
achondroplasia and hypochondroplasia. In oncology, TYRA-300 is
being evaluated in a multi-center, open label Phase 1/2 clinical
study, SURF301 (Study in Untreated
and Resistant FGFR3+ Advanced Solid Tumors)
(NCT05544552). The study is designed to determine the optimal
and the recommended Phase 2 dose (RP2D) of TYRA-300, as well as to
evaluate the preliminary anti-tumor activity of TYRA-300.
Part A of the study included patients with all solid tumors
who are FGFR3 +/-, and explored doses of TYRA-300 ranging from 10mg
-120mg once-daily (QD). Part A of SURF301 is complete.
The Company continues to advance TYRA-300 through dose expansion in
Part B, which includes patients with solid tumors who are
FGFR3+, to evaluate potentially therapeutic doses in
preparation for potential future Phase 2 studies in metastatic
urothelial carcinoma (mUC) and non-muscle invasive bladder cancer
(NMIBC).
In skeletal dysplasias, TYRA-300 has demonstrated positive
preclinical results in achondroplasia and hypochondroplasia.
In July 2023 and January 2024, the FDA granted
Orphan Drug Designation (ODD) and Rare Pediatric Designation (RPD)
to TYRA-300, respectively, for the treatment of achondroplasia.
About Tyra Biosciences
Tyra Biosciences, Inc. (Nasdaq: TYRA) is a clinical-stage
biotechnology company focused on developing next-generation
precision medicines that target large opportunities in FGFR
biology. The Company's in-house precision medicine platform, SNÅP,
enables rapid and precise drug design through iterative molecular
SNÅPshots that help predict genetic alterations most likely to
cause acquired resistance to existing therapies. TYRA's expertise
in FGFR biology has created a differentiated pipeline with three
clinical-stage programs in targeted oncology and genetically
defined conditions. The Company's lead precision medicine
stemming from SNÅP, TYRA-300, is a potential first-in-class
selective FGFR3 inhibitor that is designed to avoid the toxicities
associated with inhibition of FGFR1, FGFR2 and FGFR4, while being
agnostic for the FGFR3 gatekeeper mutations. TYRA-300 is in
development for the treatment of cancer in the SURF301 Phase 1/2
study and for skeletal dysplasias, including achondroplasia and
hypochondroplasia. TYRA is also developing TYRA-200, an
investigational, FGFR1/2/3 inhibitor, in the SURF201 study for
metastatic intrahepatic cholangiocarcinoma, and TYRA-430, an
investigational FGFR4/3-biased inhibitor for
FGF19+/FGFR4-driven cancers. TYRA is based in
Carlsbad, CA.
For more information about our science, pipeline and people,
please visit www.tyra.bio and engage with us on
LinkedIn.
Forward-Looking Statements
TYRA cautions you that statements contained in this press
release regarding matters that are not historical facts are
forward-looking statements. The forward-looking statements are
based on our current beliefs and expectations and include, but are
not limited to: the potential to develop next-generation precision
medicines and for TYRA-300 to be first-in-class, and the potential
safety and therapeutic benefits of TYRA-300; the continued
evaluation of TYRA-300 through Part B dose escalation in SURF301;
the expected timing and phase of clinical development of TYRA-300;
and the potential for SNÅP to develop therapies in targeted
oncology and genetically defined conditions. 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: interim results of a clinical trial are not necessarily
indicative of final results and one or more of the clinical
outcomes may materially change as patient enrollment continues,
following more comprehensive reviews of the data, as follow-up on
the outcome of any particular patient continues and as more patient
or final data becomes available, including the risk that
unconfirmed responses may not ultimately result in confirmed
responses to treatment after follow-up evaluations; the potential
for proof-of-concept results to fail to result in successful
subsequent development of TYRA-300; we are early in our development
efforts, have only recently begun testing TYRA-300 and TYRA-200 for
oncology in clinical trials and the approach we are taking to
discover and develop drugs based on our SNÅP platform is novel and
unproven and it may never lead to product candidates that are
successful in clinical development or approved products of
commercial value; potential delays in the commencement, enrollment,
data readouts and completion of preclinical studies and clinical
trials; results from preclinical studies or early clinical trials
not necessarily being predictive of future results; our dependence
on third parties in connection with manufacturing, research and
preclinical testing; acceptance by the FDA of INDs or of similar
regulatory submissions by comparable foreign regulatory authorities
for the conduct of clinical trials of TYRA-300 in pediatric
achondroplasia and hypochondroplasia; an accelerated development or
approval pathway may not be available for TYRA-300 or other product
candidates and any such pathway may not lead to a faster
development process; later developments with the FDA may be
inconsistent with the minutes from our prior meetings, including
with respect to the proposed design of our planned Phase 2 study of
TYRA-300 in ACH; unexpected adverse side effects or inadequate
efficacy of our product candidates that may limit their
development, regulatory approval, and/or commercialization; the
potential for our programs and prospects to be negatively impacted
by developments relating to our competitors, including the results
of studies or regulatory determinations relating to our
competitors; unfavorable results from preclinical studies; we may
not realize the benefits associated with ODD, including that orphan
drug exclusivity may not effectively protect a product from
competition and that such exclusivity may not be maintained, or
from the RPD Designation, including receipt of a Priority Review
Voucher or any value therefrom; regulatory developments in the
United States and foreign countries; our ability to obtain and
maintain intellectual property protection for our product
candidates and proprietary technologies; and other risks described
in our prior filings with the Securities and Exchange
Commission (SEC), including under the heading "Risk Factors"
in our annual report on Form 10-K 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 we undertake 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.
Contact:
Amy Conrad
aconrad@tyra.bio
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