eFFECTOR Therapeutics, Inc. (NASDAQ: EFTR), a leader in the
development of selective translation regulator inhibitors (“STRIs”)
for the treatment of cancer, today reported positive interim
results of the company’s ongoing Phase 1/2 clinical trial of eIF4A
inhibitor zotatifin in patients with solid tumors that showed
treatment was generally well tolerated, resulted in suppression of
multiple oncogenic drivers and demonstrated initial signals of
clinical activity.
The interim data was presented today at the 2022 ASCO Annual
Meeting in a poster, entitled “First-in-human phase 1/2 dose
escalation and expansion study evaluating first-in-class eIF4A
inhibitor zotatifin in patients with solid tumors,” by Funda
Meric-Bernstam, M.D., chair of Investigational Cancer Therapeutics,
and The Nellie B. Connally Chair in Breast Cancer at The University
of Texas MD Anderson Cancer Center.
As of the cutoff date of March 4, 2022, interim results showed
that zotatifin was generally well tolerated. Treatment emergent
adverse events (TEAEs) related to zotatifin were mostly mild,
readily managed and reversible, and included fatigue, anemia,
diarrhea, vomiting and nausea. In the 25 patients who received the
recommended Phase 2 dose, none exhibited zotatifin-related Grade 3,
4 or 5 TEAEs.
In Part 2 of the trial, early signals of clinical activity were
observed in two patients with breast cancer. One patient with
amplified Cyclin D1 and an ESR1 mutation, who had progressed on
prior treatment with fulvestrant, experienced a confirmed partial
response when zotatifin was combined with fulvestrant. A second
partial response, which was awaiting confirmatory scan at the time
of data analysis, was observed with the combination of zotatifin,
fulvestrant and abemaciclib in a patient with PIK3CA mutations.
Both patients were heavily pretreated for metastatic disease,
having failed multiple lines of therapy prior to trial
enrollment.
“The low emergence of adverse events with this entirely new
class of medicines is a very important point to highlight,” said
Dr. Meric-Bernstam. “Coupled with the initial signals of activity,
these early results are encouraging for further development of
zotatifin, especially in ER+ breast cancer.”
In a pharmacodynamic analysis measuring protein expression,
modulation of protein translation by zotatifin was highly
selective, with less than 1% of protein expression altered.
Patients treated with zotatifin demonstrated reductions in the
expression of key oncogenic drivers, including Cyclin E1 and Bcl-2.
The most dramatic reductions in expression of these two proteins
were seen in patients who showed the highest levels of expression
prior to treatment with zotatifin.
“We are very encouraged by these interim data analyses as they
provide evidence that zotatifin has the potential to suppress a
network of cancer driving proteins and still remain generally well
tolerated. Most cancers require suppression at multiple points in a
complex network of cancer drivers to effectively manage disease. We
saw encouraging results for down regulation of a number of
oncogenic drivers, which not only provides clinical proof of
mechanism, but also paves the way for how to combine zotatifin with
other medicines,” said Steve Worland, Ph.D., president and chief
executive officer of eFFECTOR. “Notably, based on the evidence, we
have advanced to Stage 2 of a Simon 2-stage trial design in the
cohort of patients treated with zotatifin and fulvestrant after
progressing on a CDK4/6 inhibitor and endocrine therapy and plan to
open a new cohort in patients with ER+ breast with Cyclin D1
amplification. We look forward to generating more data in this
cohort as the resulting dataset in a defined patient population
could support a potential path to registration. We anticipate
reporting topline data from our current expansion cohorts by the
end of 2022, as well as initial overall response rate data from the
Cyclin D1 amplified ER+ breast cancer cohort in the first half of
2023.”
Based on zotatifin’s mechanism and results observed to date, the
company has expanded the cohort evaluating zotatifin in combination
with fulvestrant in ER+ breast cancer patients to 18 patients. A
new cohort evaluating zotatifin in combination with fulvestrant in
ER+ breast cancer patients with Cyclin D1 amplification is being
planned.
Conference CalleFFECTOR management will host a
conference call with commentary from key opinion leaders to provide
additional details of the interim study results and discuss
upcoming milestones. Call details are as follows:
Date: June 5, 2022Time: 7:00 p.m. ET | 6 p.m. CT | 4:00 p.m.
PTConference ID: 7267595Dial-in: Toll-Free Dial-In Number: (855)
493-1511; International Dial-In Number: (409) 497-0884
The webcast can be accessed on the “Events and Presentations”
page of the “Investors” section of the Company’s website. The
webcast will be archived and available for replay on the Company’s
website for 30 days following the call. Please log on approximately
5 to 10 minutes prior to the scheduled start time to download and
install any audio software if needed. For more information, please
visit investors.effector.com.
About the Phase 1/2 Trial The open label study
had enrolled a total of 54 patients with advanced solid tumors as
of the cut off date of March 4, 2022 – 37 in the Phase 1 dose
escalation portion and 17 in the Phase 2 expansion portion of the
trial. The primary objectives of part one of the trial are to
evaluate the safety and tolerability of zotatifin as a monotherapy
in patients with defined, advanced solid tumors, determine the
recommended Phase 2 dose for zotatifin as a monotherapy and to
evaluate the PK profile. In part 2, the primary objective is to
evaluate the preliminary antitumor activity of zotatifin as a
monotherapy and as combination therapy in patients with defined,
advanced solid tumors.
About Zotatifin (eFT226)Zotatifin is a potent
and sequence-selective small molecule inhibitor of eIF4A that is
designed to supress expression of a network of cancer driving
proteins, including Cyclins D and E, CDKs 2, 4 and 6 and select
RTKs as well as KRAS. We are currently investigating zotatifin in
ongoing clinical trials for solid tumors and as a potential
host-directed antiviral therapy in patients with mild to moderate
COVID-19 in collaboration with the University of California, San
Francisco.
About eFFECTOR TherapeuticseFFECTOR is a
clinical-stage biopharmaceutical company pioneering the development
of a new class of oncology drugs referred to as STRIs. eFFECTOR’s
STRI product candidates target the eIF4F complex and its activating
kinase, mitogen-activated protein kinase interacting kinase (MNK).
The eIF4F complex is a central node where two of the most
frequently mutated signaling pathways in cancer, the PI3K-AKT and
RAS-MEK pathways, converge to activate the translation of select
mRNA into proteins that are frequent culprits in key
disease-driving processes. Each of eFFECTOR’s product candidates is
designed to act on a single protein that drives the expression of a
network of functionally related proteins, including oncoproteins
and immunosuppressive proteins in T cells, that together control
tumor growth, survival and immune evasion. eFFECTOR’s lead product
candidate, tomivosertib, is a MNK inhibitor currently being
evaluated in KICKSTART, a randomized, double-blind,
placebo-controlled Phase 2b trial of tomivosertib in combination
with pembrolizumab in patients with metastatic non-small cell lung
cancer (NSCLC). Zotatifin, eFFECTOR’s inhibitor of eIF4A, is
currently being evaluated in Phase 2a expansion cohorts in certain
biomarker-positive solid tumors, including ER+ breast cancer and
KRAS-mutant NSCLC. eFFECTOR has a global collaboration with Pfizer
to develop inhibitors of a third target, eIF4E. In addition to the
company’s oncology focus, zotatifin is being evaluated as a
potential host-directed anti-viral therapy in patients with mild to
moderate COVID-19 in collaboration with the University of
California, San Francisco, under a $5 million grant sponsored by
the Defense Advanced Research Projects Agency.
Forward-Looking StatementseFFECTOR 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 future
clinical development of our product candidates, including
expectations on enrollment and the timing of reporting data from
ongoing clinical trials; the planned expanded development of
zotatifin and the timing thereof; and the potential therapeutic
benefits of our product candidates. 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 and more patient
data become available; potential delays in the commencement,
enrollment and completion of clinical trials; additional
disruptions to our operations from the COVID-19 pandemic, including
clinical trial and manufacturing delays; our dependence on third
parties in connection with product manufacturing, research and
preclinical and clinical testing; the results of preclinical
studies and early clinical trials are not necessarily predictive of
future results; the success of our clinical trials and preclinical
studies for our product candidates is uncertain; we may use our
capital resources sooner than expected and they may be insufficient
to allow clinical trial readouts; regulatory developments in the
United States and foreign countries; unexpected adverse side
effects or inadequate efficacy of our product candidates that may
limit their development, regulatory approval and/or
commercialization, or may result in recalls or product liability
claims; our ability to obtain and maintain intellectual property
protection for our product candidates; any future impacts to our
business resulting from the conflict between Russia and Ukraine and
other risks described in our prior filings with the Securities and
Exchange Commission. 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.
Contacts:Investors:Stephanie
CarringtonICR
Westwicke646-277-1282Stephanie.Carrington@westwicke.com
Media:Heidi Chokeir, Ph.D.Canale
Communications619-203-5391heidi.chokeir@canalecomm.com
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