Preliminary Clinical Data with Cold/Hot Dosing
Regimen Demonstrate Potential to Improve Therapeutic Index and
Safety Profile
Company Prioritizing Cold/Hot Dosing Regimen
in Phase 1 Trial; Cohort 2 in this Arm is Currently
Enrolling
Data to be Presented at the Society of Nuclear
Medicine and Molecular Imaging (SNMMI) Annual Meeting
Fusion to Host Conference Call Tomorrow,
Tuesday, June 27th at
4:00 p.m. ET/3:00 p.m. CT
HAMILTON, ON and BOSTON, June 26,
2023 /CNW/ -- Fusion Pharmaceuticals Inc.
(Nasdaq: FUSN), a clinical-stage oncology company focused on
developing next-generation radiopharmaceuticals as precision
medicines, today announced the presentation of interim data from
the dose escalation portion of the Phase 1 trial of
[225Ac]-FPI-1434 (FPI-1434) in patients with solid
tumors expressing IGF-1R. The data will be presented by
Neeta Pandit-Taskar, M.D., of
Memorial Sloan Kettering Cancer Center, tomorrow at the Society of
Nuclear Medicine and Molecular Imaging (SNMMI) Annual Meeting and
will include molecular imaging, safety and pharmacokinetics (PK)
from two dosing regimens: one with FPI-1434 alone ("hot only"), and
another in which a small dose of cold antibody (naked IGF-1R
antibody without the isotope) is administered prior to each dose of
FPI-1434 ("cold/hot"). The poster presentation is available via the
SNMMI Annual Meeting mobile application.
"Antibody drug conjugates (ADCs) have shown tremendous success
recently, driven in part by the benefits of using more potent
payloads. We believe that the high potency of alpha emitters in
place of conventional chemical toxins represents the evolution of
the ADC field and is a significant and underexploited opportunity.
While much is known about optimal dosing levels and paradigms for
small molecule radiopharmaceuticals against well-known targets like
PSMA, there is comparatively less experience for antibody-based
alpha therapies in solid tumors. Consequently, in the Phase 1 study
of FPI-1434, we undertook a stepwise dose exploration, in patients
with various cancer types expressing IGF-1R, that included three
stages: (i) hot only regimen in a single ascending dose escalation;
(ii) hot only regimen in a multiple ascending dose escalation; and
(iii) cold/hot regimen in a multiple ascending dose escalation.
Learnings from this multi-part study have taken us a step further
towards unlocking the potential of antibody-based TATs as
next-generation ADCs," said Chief Executive Officer John Valliant, Ph.D.
Dr. Valliant continued, "We are pleased to report data and key
learnings from our first antibody targeted alpha therapy (TAT)
program which showed pre-administration of cold antibody prior to
administering radiolabeled FPI-1434 has the potential to
significantly enhance the therapeutic index by driving more active
drug to tumor sites with an improved safety profile compared to
hot-only dosing. In addition, with pre-administration of cold
antibody, only a fraction of the injected amount of radiation is
needed to achieve comparable exposures to hot-only cohorts. Results
show the pharmacokinetic profile of 15 kBq/kg in the cold/hot
regimen is comparable to 40 kBq/kg hot only, with a safety profile
that made it possible to deliver up to five cycles thus far. With
encouraging safety, dosimetry, and PK results, as well as stable
disease observed in two heavily pretreated patients despite a low
dose, we are continuing evaluation of the cold/hot regimen at a
higher dose level in Cohort 2. We expect to share those results
around the end of 2023."
The Phase 1, multi-center, open-label clinical trial is designed
to investigate the safety, tolerability and pharmacokinetics of
FPI-1434 in patients with solid tumors expressing IGF-1R. The trial
is also designed to establish the maximum tolerated dose for
FPI-1434 and the recommended Phase 2 dose. As part of the precision
medicine approach, prior to receiving the therapeutic injection of
FPI-1434, patients are administered an indium-111 imaging analogue,
[111In]-FPI-1547 (FPI-1547). The images collected are
used to confirm the presence of tumor uptake and ensure that
estimated radiation doses to organs and tissues are below
protocol-specified safety limits.
Based on results from an imaging sub-study evaluating
pre-administration of cold antibody prior to each dose of FPI-1547
that demonstrated a favorable gain in tumor lesion uptake versus
normal tissue, the Company amended the Phase 1 trial protocol to
evaluate both the hot only and cold/hot dosing regimens.
Cold/Hot Dosing Regimen
In the cold/hot arm, three
patients were dosed in Cohort 1 at a dose of 15 kBq/kg following
pre-administration of cold antibody. In Cohort 1, cold/hot dosing
was observed to be safe with no treatment-related serious adverse
events (SAEs) or dose limiting toxicities (DLTs). Absorbed dose to
critical organs (kidney, liver and lungs) in this dosing regimen
were less than 7% of defined limits, supporting continued dose
escalation.
Pre-administration of cold antibody demonstrated improved tumor
uptake while also reducing hematological toxicity observed in the
hot only dosing arm. When normalized to 15 kBq/kg, the average
lesion absorbed dose and dose/volume in the cold/hot arm were
nearly double the level compared to hot only. Further, 15 kBq/kg in
the cold/hot dosing arm shows comparable systemic exposure to
approximately 40 kBq/kg of a hot only dose, but shows an improved
hematological safety profile as measured by changes in platelet
count.
Two heavily pre-treated patients from the cold/hot dosing arm
received three and five cycles of treatment, with both achieving
durable stable disease as their best response. The dose level from
Cohort 1, while sufficient to demonstrate marked differences in
tumor uptake and achieve stable disease, was expected to be
sub-optimal with respect to efficacy.
Fusion is currently enrolling Cohort 2 in the cold/hot dosing
regimen at 25 kBq/kg and expects to report data from this cohort
around year-end 2023.
Hot Only Dosing Regimen
In the hot only multiple
ascending arm, six patients were dosed across two cohorts.
Dose-dependent decrease in blood counts, particularly
thrombocytopenia, was identified as the most common type of adverse
event related to FPI-1434, with Grade 4 thrombocytopenia observed
at 75 kBq/kg and 55 kBq/kg. The Company has discontinued dosing in
the hot only dosing arm and no longer plans to use this method of
FPI-1434 administration.
"Given the known expression of IGF-1R on multiple cancers,
Fusion believes in the opportunity for FPI-1434 to treat a broad
array of cancer types," said Chief Medical Officer Dmitri Bobilev, M.D. "We believe that
thrombocytopenia observed at higher dose levels in the hot only
part of the trial, may result at least in part from direct effect
of FPI-1434 on IGF-1R-expressing megakaryocytes and from
Fc-mediated binding in normal tissues. The ability to use
pre-administration of cold antibody to block the IGF-1R receptors
on normal cells and non-target specific binding and deliver higher
doses of radioactivity to tumor cells is highly encouraging. We
look forward to sharing results from the second cohort."
Following the conclusion of the SNMMI Annual Meeting, the
presentation can be found at
https://fusionpharma.com/fusion-scientific-presentations/.
Fusion Conference Call Information
Fusion will host a
live conference call and webcast tomorrow beginning at 4:00 p.m. ET/3:00 p.m.
CT to discuss the data presentation. To access the live
call, please dial 1-877-870-4263 (U.S.), 1-855-669-9657
(Canada) or 1-412-317-0790
(international) and reference Fusion Pharmaceuticals. A webcast of
the conference call will be available under "Events and
Presentations" in the Investors & Media section of Fusion's
website at https://ir.fusionpharma.com/overview. The archived
webcast will be available on Fusion's website shortly after the
conclusion of the call and will be available for 90 days following
the event.
About FPI-1434
FPI-1434 is a radioimmunoconjugate
designed to target and deliver alpha emitting medical isotopes to
cancer cells expressing IGF-1R, a receptor that is overexpressed on
many tumor types. FPI-1434 utilizes Fusion's Fast-Clear linker to
connect a human monoclonal antibody that targets IGF-1R with
actinium-225, a powerful alpha-emitting isotope with desirable
half-life and decay chain properties.
About Fusion
Fusion Pharmaceuticals is a
clinical-stage oncology company focused on developing
next-generation radiopharmaceuticals as precision medicines. Fusion
connects alpha particle emitting isotopes to various targeting
molecules to selectively deliver the alpha emitting payloads to
tumors. Fusion's clinical portfolio includes: FPI-2265 targeting
prostate specific membrane antigen (PSMA) for metastatic castration
resistant prostate cancer currently in a Phase 2 trial with data
from 20-30 patients anticipated in the first quarter of 2024;
FPI-1434 targeting insulin-like growth factor 1 receptor currently
in a Phase 1 trial; and FPI-2059, a small molecule targeting
neurotensin receptor 1 (NTSR1), currently in a Phase 1 trial. In
addition to a robust proprietary pipeline, Fusion has a
collaboration with AstraZeneca to jointly develop novel targeted
alpha therapies (TATs) and combination programs between Fusion's
TATs and AstraZeneca's DNA Damage Response Inhibitors (DDRis) and
immuno-oncology agents. The Company recently received IND clearance
for FPI-2068, the first novel TAT under the collaboration, which
targets EGFR-cMET. Fusion has also entered into a collaboration
with Merck to evaluate FPI-1434 in combination with Merck's
KEYTRUDA® (pembrolizumab) in patients with solid tumors
expressing IGF-1R. To support Fusion's growing pipeline of TATs,
the Company has signed strategic actinium supply agreements with
TRIUMF, Niowave, Inc. and BWXT Medical.
Forward-Looking Statements
This press release contains
"forward-looking statements" for purposes of the safe harbor
provisions of The Private Securities Litigation Reform Act of 1995,
including but not limited to the statements regarding Fusion
Pharmaceuticals Inc.'s (the "Company") future business. For this
purpose, any statements contained herein that are not statements of
historical fact may be deemed forward-looking statements. Without
limiting the foregoing, the words "expect," "plans," "anticipates,"
"intends," "will," and similar expressions are also intended to
identify forward-looking statements, as are expressed or implied
statements with respect to the Company's potential drug candidates,
including any expressed or implied statements regarding the
successful development of its product candidates. Actual results
may differ materially from those indicated by such forward-looking
statements as a result of risks and uncertainties, including but
not limited to the following: there can be no guarantees that the
Company will advance any clinical product candidate or other
component of its potential pipeline to the clinic, to the
regulatory process or to commercialization; management's
expectations could be affected by unexpected patient recruitment
delays, regulatory actions or delays, or changes in the competitive
landscape; uncertainties relating to, or unsuccessful results of,
clinical trials, including additional data relating to the ongoing
clinical trials evaluating its product candidates; and competition
in general. Such forward-looking statements involve known and
unknown risks, uncertainties and other factors that may cause
actual results to be materially different from any future results,
performance or achievements expressed or implied by such
statements. These and other risks which may impact management's
expectations are described in greater detail under the heading
"Risk Factors" in the Company's quarterly report on Form 10-Q for
the year ended March 31, 2023, as
filed with the SEC and in any subsequent periodic or current report
that the Company files with the SEC. All forward-looking statements
reflect the Company's estimates only as of the date of this release
(unless another date is indicated) and should not be relied upon as
reflecting the Company's views, expectations or beliefs at any date
subsequent to the date of this release. While Fusion may elect to
update these forward-looking statements at some point in the
future, it specifically disclaims any obligation to do so, even if
the Company's estimates change.
Investors and others should note that Fusion communicates with
its investors and the public using the Fusion website,
www.fusionpharma.com, including, but not limited to, company
disclosures, investor presentations, SEC filings, and press
releases. The information that Fusion posts on this website could
be deemed to be material information. As a result, Fusion
encourages investors, media and others interested to review the
information that Fusion posts there on a regular basis.
Contact:
Amanda Cray
Senior Director of Investor Relations & Corporate
Communications
(617) 967-0207
cray@fusionpharma.com
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