Eloxx Pharmaceuticals, Inc. (NASDAQ: ELOX), a leader in ribosomal
RNA-targeted genetic therapies for rare diseases, today announced
positive topline results from the monotherapy arms of its Phase 2
clinical trial of ELX-02 in Class 1 cystic fibrosis (CF) patients
with at least one G542X nonsense allele mutation. ELX-02 was well
tolerated and achieved a statistically significant 5.4mmol/L
reduction in sweat chloride in patients at the1.5mg/kg/day dose.
The intra-patient dose escalation stage of the trial has
successfully identified 1.5 mg/kg/day as the dose for further
development. Based on the statistically significant monotherapy
results observed at the 1.5mg/kg/day dose, planning for the
advancement of ELX-02 into Phase 3 clinical development has
started. The U.S. Food and Drug Administration (FDA) has granted
Fast Track designation for ELX-02. In addition, ELX-02 has also
been granted Orphan Drug Designation for the treatment of CF
patients with nonsense mutations by the FDA and orphan medicinal
product designation by the European Medicines Agency.
“We are highly encouraged with the topline results from the
monotherapy arms of our Phase 2 trial, and believe that ELX-02, if
approved, has potential to transform the lives of Class 1 CF
patients with nonsense mutations, who do not have any available
therapies,” said Sumit Aggarwal, President and Chief Executive
Officer of Eloxx.
Topline Results of ELX-02 Phase 2 Monotherapy Trial in
Class 1 Nonsense CF Patients
The Phase 2 clinical trial of ELX-02 was designed to evaluate
safety and assess biological activity in G542X nonsense mutation
Class 1 CF patients as monotherapy and in combination with
ivacaftor. Topline results for the intra-patient dose escalation
monotherapy arms are summarized below:
- ELX-02 was generally well tolerated in the trial, with no
treatment-related serious adverse events noted.
- The study met a key secondary endpoint by showing a
statistically significant reduction in mean sweat chloride
of 5.4 mmol/L (p value=0.0218, n=12 patients) after one
week of therapy for ELX-02 dosed at 1.5mg/kg/day.
- Short term reductions in sweat chloride have been shown to
correlate with biologic activity of the CFTR protein and translate
to lung function improvement over the long term.
- A potential dose response trend was also seen in mean sweat
chloride reduction, with a stronger dose response trend in the
subset of patients (post-hoc) that completed the 1.5mg/kg/day
dosing.
- The reduction in mean sweat chloride in Class 1 CF patients
with nonsense mutations who received 1.5mg/kg/day in the trial is
similar to the activity in Class 1 CF patient organoids treated
with ELX-02 in preclinical experiments.
- As expected, no change was observed in forced expiratory volume
(FEV1) due to short treatment duration.
- While the trial was not designed as a longer-term efficacy
study and did not compare ELX-02 to any other agent, results from
prior Phase 2 trials with FDA-approved agents for CF can serve as a
contextual reference for the level of sweat chloride reduction
observed and its potential clinical relevance.
- Results of a Phase 2 study with lumacaftor and
lumacaftor/ivacaftor combination (Orkambi), an FDA-approved
combination CF agent, demonstrated 4.1mmol/L to 5.1 mmol/L
reductions in sweat chloride over two- and three-week study
durations in Class 2 CF patients with HomF50del mutations.
- Results of a phase 2 study with tezacoftor/ivacaftor
combination (Symdeko), an FDA-approved combination CF agent,
demonstrated a 1.8mmol/L to 5.2 mmol/L reduction in sweat chloride
over 28 days in Class 2 CF patients with HomF50del mutations.
- Treatment with both these agents resulted in improved lung
function as measured by forced expiratory volume FEV1 with longer
treatment duration in subsequent Phase 3 trials with Orkambi and
Symdeko.
“These significant results for sweat chloride, a surrogate for
CFTR protein function in patients, are very exciting. I look
forward to working with Eloxx on future development of ELX-02,”
said Prof. Eitan Kerem, Head of The Division of Pediatrics Hadassah
Medical Center.
Planned Next Steps for ELX-02 CF Program
ELX-02 in combination with other CF therapies.
First patient dosing has occurred in the expansion arm of the
Phase 2 trial, which includes a combination of ELX-02 and Kalydeco
(ivacaftor), a CFTR protein potentiator. In preclinical studies,
Class 1 CF patient organoids had a 2- to 3-fold higher swelling
response with a combination of ELX-02 and Kalydeco than with ELX-02
as a monotherapy. Topline results are expected by the end of the
first half of 2022.
“With dosing of the first patient, we have now advanced ELX-02
into the Phase 2 combination study and have begun preparations for
Phase 3 clinical development,” said Vijay Modur MD, PhD, Head of
Research & Development of Eloxx.
Inhaled delivery of ELX-02
Eloxx has also begun evaluation of inhaled (nebulizer-based)
delivery of the current subcutaneous formulation of ELX-02. Eloxx
believes that inhaled delivery has the potential to further improve
the activity of ELX-02 as a single agent and in combination with
other drugs given potential for increased drug exposure in the lung
versus plasma. Prior animal studies have shown a 19-fold increase
in ELX-02 exposure at a similar dose when administered as an
inhalation agent versus subcutaneously. We expect to submit an
Investigational New Drug application the second half of 2022.
About Class 1 CF
CF patients with a Class 1 nonsense mutation remain highly
underserved with no approved disease modifying therapies. An
estimated 10-12% of CF patients are Class 1 patients with one or
both alleles harboring nonsense mutations, leading to less than
full length CFTR proteins on the cell membrane in these
patients.
Conference Call and Webcast
Eloxx’s management will host a conference call and webcast today
at 8:30 a.m. ET. A live webcast of the conference call can be
accessed through the “Investors” tab on the Eloxx website, and a
replay will be available online after the call. For those planning
to ask a question, the dial-in number for the conference call is
(866) 913-8546 for domestic participants and (210) 874-7715 for
international participants, with Conference ID # 2393967. Please
dial in at least 15 minutes in advance to ensure a timely
connection to the call.
About Eloxx Pharmaceuticals
Eloxx Pharmaceuticals, Inc. is engaged in the science of
ribosome modulation, leveraging its innovative TURBO-ZM™ chemistry
technology platform in an effort to develop novel Ribosome
Modulating Agents (RMAs) and its library of Eukaryotic Ribosome
Selective Glycosides (ERSGs). Eloxx’s lead investigational product
candidate, ELX-02, is a small molecule drug candidate designed to
restore production of full-length functional proteins. ELX-02 is in
clinical development, focusing on cystic fibrosis (US Trial
NCT04135495, EU/IL Trial NCT04126473). Eloxx also has preclinical
programs focused on select rare diseases, including inherited
diseases, cancer caused by nonsense mutations, kidney diseases,
including autosomal dominant polycystic kidney disease, as well as
rare ocular genetic disorders.
For more information, please visit www.eloxxpharma.com.
Forward-looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995. All statements other than statements of present and
historical facts contained in this press release, including without
limitation, statements regarding our expected cash burn and future
financial results, the expected timing of trials and results from
clinical studies of our product candidates and the potential of our
product candidate to treat nonsense mutations are forward-looking
statements. Forward-looking statements can be identified by the
words “aim,” “may,” “will,” “would,” “should,” “expect,” “explore,”
“plan,” “anticipate,” “could,” “intend,” “target,” “project,”
“contemplate,” “believe,” “estimate,” “predict,” “potential,”
“seeks,” or “continue” or the negative of these terms similar
expressions, although not all forward-looking statements contain
these words.
Forward-looking statements are based on management's current
plans, estimates, assumptions and projections based on information
currently available to us. Forward-looking statements are subject
to known and unknown risks, uncertainties and assumptions, and
actual results or outcomes may differ materially from those
expressed or implied in the forward-looking statements due to
various important factors, including, but not limited to: our
ability to progress any product candidates in preclinical or
clinical trials; the uncertainty of clinical trial results and the
fact that positive results from preclinical studies are not always
indicative of positive clinical results; the scope, rate and
progress of our preclinical studies and clinical trials and other
research and development activities; the competition for patient
enrollment from drug candidates in development; the impact of the
global COVID-19 pandemic on our clinical trials, operations,
vendors, suppliers, and employees; our ability to obtain the
capital necessary to fund our operations; the cost of filing,
prosecuting, defending and enforcing any patent claims and other
intellectual property rights; our ability to obtain financial in
the future through product licensing, public or private equity or
debt financing or otherwise; general business conditions,
regulatory environment, competition and market for our products;
and business ability and judgment of personnel, and the
availability of qualified personnel and other important factors
discussed under the caption “Risk Factors” in our Quarterly Report
on Form 10-Q for the quarter ended September 30, 2021, as any such
factors may be updated from time to time in our other filings with
the SEC, accessible on the SEC’s website at www.sec.gov and the
“Financials & Filings” page of our website at
https://investors.eloxxpharma.com/financial-information/sec-filings.
All forward-looking statements speak only as of the date of this
press release and, except as required by applicable law, we have no
obligation to update or revise any forward-looking statements
contained herein, whether as a result of any new information,
future events, changed circumstances or otherwise.
Contact
InvestorsJohn
Woolfordjohn.woolford@westwicke.com443.213.0506
MediaLaureen Cassidylaureen@outcomescg.com
SOURCE: Eloxx Pharmaceuticals, Inc.
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