Full Press Release Details
Applied Therapeutics Announces Full
Data and Scientific Presentations from the Pivotal Phase 2 ACTION-Galactosemia Trial
AT-007 demonstrated rapid and
sustained reduction in toxic galactitol levels with no accompanying increase in galactose
Positive trend on MRI outcomes,
including indirect measures of edema, neuronal health and brain galactitol levels in AT-007-treated patients
40 mg/kg dose of AT-007 was
well-tolerated with no drug-related adverse events reported in healthy volunteers; evaluation of 40 mg/kg dose in Galactosemia
patients remains ongoing
NEW YORK, April 21, 2020 - Applied Therapeutics,
Inc. (Nasdaq: APLT), a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates against validated
molecular targets in indications of high unmet medical need, today announced new data and scientific presentations from the pivotal
Phase 2 ACTION-Galactosemia trial. The full study data, originally planned to be presented at the Society for Inherited Metabolic
Disorders conference this week, will be available on the company's website.
The double-blind placebo-controlled ACTION-Galactosemia
trial evaluated safety and pharmacokinetics of AT-007, a Central Nervous System (CNS) penetrant Aldose Reductase Inhibitor (ARI)
in healthy volunteers, as well as safety, pharmacokinetics, and efficacy biomarkers in adult Galactosemia patients. The key biomarker
outcome of the study was reduction in galactitol, an aberrant toxic metabolite of galactose, formed by Aldose Reductase in Galactosemia
patients. Accumulation of galactitol causes long-term complications ranging from CNS dysfunction to cataracts.
"We are pleased to share the full
results of ACTION-Galactosemia," said Riccardo Perfetti, MD, PhD, Chief Medical Officer of Applied Therapeutics. "Patients
with this devastating disease experience life-long accumulation of galactitol in the CNS and in other tissues, and our data demonstrates
rapid and sustained reduction in this toxic metabolite."
"We remain steadfast in our commitment
to bring this treatment to patients as quickly as possible, and understand the urgency to potentially prevent worsening of disease
in adults and onset of disease-related complications in children," said Shoshana Shendelman, PhD, Founder and CEO of Applied
Therapeutics. "We look forward to initiating a pediatric study in Q2 and remain on track to submit an NDA later this year."
Galactitol Reduction
As previously announced, once-daily 20mg/kg
AT-007 reduced galactitol levels by approximately 50% in Galactosemia patients. Reduction in galactitol levels was rapid (within
6 days of consecutive AT-007 treatment) and sustained throughout the treatment period of 27 days. Reduction in galactitol from
baseline was statistically significant at the 20mg/kg vs placebo (p<0.01). The lower dose tested, 5mg/kg, demonstrated a similar
trend in reducing galactitol levels approximately 20% from baseline (p=NS from placebo).
Other Galactose Metabolites
Reduction in galactitol was not accompanied
by any increase in galactose. This data confirms that reduction of the toxic metabolite galactitol through Aldose Reductase inhibition
does not result in derangement of other metabolites in the galactose pathway as previously demonstrated in animal models of Galactosemia.
Patients treated with AT-007 (once-daily
over 27 days) demonstrated a positive trend in MRI outcomes, specifically on measures of edema and overall neuronal health. AT-007
treated patients demonstrated improvement in ventricular volume, a measure of edema, which has been shown to occur in the brain
of Galactosemia patients due to osmotic dysregulation caused by galactitol. Patients treated with AT-007 also demonstrated improvements
in N-acetyl-aspartate, a marker of neuronal health. Galactitol was visible on MRI in the brain of all patients at baseline, and
a positive trend toward decreased brain galactitol levels in AT-007 treated patients was observed by quantitative MR Spectroscopy
As no drug-related adverse
events were seen at the once-daily 20mg/kg dose, a once-daily 40mg/kg dose was subsequently studied in healthy volunteers and
is ongoing in Galactosemia patients. The 40mg/kg dose was safe and well tolerated. Evaluation of once-daily 40mg/kg AT-007 in
Galactosemia patients remains ongoing and this data will be shared when available.
No drug-related adverse events were reported
at any dose of AT-007 in ACTION-Galactosemia. This robust safety data includes all 80 healthy volunteers and 8 adult Galactosemia
patients who received active drug during the core study.
A 90-day safety extension study for ACTION-Galactosemia
is ongoing. The extension study is open to patients from the core study and to new adult Galactosemia patients. A pediatric study
with a safety and biomarker design similar to ACTION-Galactosemia is planned to commence in Q2 of this year. Both the extension
study and the pediatric study are designed to incorporate primarily home health visits in order to limit travel and risk of exposure
to COVID-19. More information on the pediatric study will be shared in coming weeks.
About Applied Therapeutics
Applied Therapeutics is a clinical-stage
biopharmaceutical company developing a pipeline of novel drug candidates against validated molecular targets in indications of
high unmet medical need. The Company's lead drug candidate, AT-007, is a novel central nervous system penetrant aldose reductase
inhibitor (ARI) for the treatment of Galactosemia, a rare pediatric metabolic disease. The Company initiated a Phase 1/2 clinical
trial in June 2019 and read out positive top-line biomarker data in adult Galactosemia patients in January of 2020. The Company
is also developing AT-001, a novel potent ARI that is being developed for the treatment of Diabetic Cardiomyopathy, or DbCM, a
fatal fibrosis of the heart. The Company initiated a Phase 3 registrational study in DbCM in September 2019. The preclinical pipeline
also includes AT-003, an ARI designed to cross through the back of the eye when dosed orally, for the treatment of diabetic retinopathy,
expected to advance into a Phase 1 study in 2020, as well as novel dual PI3k inhibitors in preclinical development for orphan oncology
Forward-Looking Statements
This press release contains
"forward-looking statements" that involve substantial risks and uncertainties for purposes of the safe harbor
provided by the Private Securities Litigation Reform Act of 1995. Any statements, other than statements of historical fact,
included in this press release regarding strategy, future operations, prospects, plans and objectives of management,
including words such as "may," "will," "expect," "anticipate,"
"plan," "intend," and similar expressions (as well as other words or expressions referencing future
events, conditions or circumstances) are forward-looking statements. These include, without limitation, statements regarding
(i) our plan to move quickly towards regulatory filing following our pivotal Phase 2 ACTION-Galactosemia study, while
preparing for Galactosemia commercial launch and growing our organization, (ii) the design, scope and results of our clinical
trials, (iii) the timing of the initiation and completion of our clinical trials, (iv) the likelihood that data from our
clinical trials will support future development of our product candidates, and (v) the likelihood of obtaining regulatory
approval of our product candidates and qualifying for any special designations, such as orphan drug designation.
Forward-looking statements in this release involve substantial risks and uncertainties that could cause actual results to
differ materially from those expressed or implied by the forward-looking statements, and we, therefore cannot assure you that
our plans, intentions, expectations or strategies will be attained or achieved. Such risks and uncertainties include, without
limitation, (i) our plans to develop and commercialize our product candidates, (ii) the initiation, timing, progress and
results of our current and future preclinical studies and clinical trials and our research and development programs, (iii)
our ability to take advantage of expedited regulatory pathways for any of our product candidates, (iv) our estimates
regarding expenses, future revenue, capital requirements and needs for additional financing, (v) our ability to successfully
acquire or license additional product candidates on reasonable terms, (vi) our ability to maintain and establish
collaborations or obtain additional funding, (vii) our ability to obtain regulatory approval of our current and future
product candidates, (viii) our expectations regarding the potential market size and the rate and degree of market acceptance
of such product candidates, (ix) our ability to fund our working capital requirements and expectations regarding the
sufficiency of our capital resources, (x) the implementation of our business model and strategic plans for our business and
product candidates, (xi) our intellectual property position and the duration of our patent rights, (xii) developments or
disputes concerning our intellectual property or other proprietary rights, (xiii) our expectations regarding government and
third-party payor coverage and reimbursement, (xiv) our ability to compete in the markets we serve, (xv) the impact of
government laws and regulations and liabilities thereunder, (xvi) developments relating to our competitors and our industry,
(xvii) the impact of the COVID-19 pandemic on the timing and progress of our ongoing clinical trials and our business in
general and (xviii) other factors that may impact our financial results. In light of the significant uncertainties in these
forward-looking statements, you should not rely upon forward-looking statements as predictions of future events. Although we
believe that we have a reasonable basis for each forward-looking statement contained in this press release, we cannot
guarantee that the future results, levels of activity, performance or events and circumstances reflected in the
forward-looking statements will be achieved or occur at all. Factors that may cause actual results to differ from those