6 of 7 (86%) patients on 300 mg of FT-4202 for
14 days achieved a hemoglobin increase > 1 g/dL from
baseline
Hemolytic markers support the hypothesis that
FT-4202 improves red blood cell survival and reduces turnover
A favorable tolerability profile was observed
after once-daily dosing of FT-4202 for 14 days and a 7-day follow
up period in patients with SCD
Initiated 600 mg MAD2 cohort and 12-week open
label extension study
Forma Therapeutics Holdings, Inc. (Nasdaq: FMTX), a
clinical-stage biopharmaceutical company focused on rare
hematologic diseases and cancers, today announced that clinical
proof-of-concept in patients with sickle cell disease (SCD) has
been observed in the ongoing randomized, placebo-controlled,
multi-center Phase 1 trial of FT-4202. FT-4202 is a novel,
investigational, selective red blood cell (RBC) pyruvate kinase-R
(PKR) activator in development as a potential disease-modifying
therapy for SCD. In a cohort of nine patients, six of seven
patients (86%) who received FT-4202 achieved a hemoglobin increase
of greater than 1 g/dL from baseline with once-daily dosing at 300
mg for 14 days. The data, being presented today at the 62nd
American Society of Hematology (ASH) Annual Meeting, also
demonstrate improvements in hemolytic parameters showing that
activation of PKR by FT-4202 decreases reticulocyte counts and
sickle RBC hemolysis in patients with SCD.
“These results are remarkable for a Phase 1 study, and they’re
encouraging for sickle cell patients,” said Marilyn J. Telen, M.D.,
director of the Duke Comprehensive Sickle Cell Center, Professor of
Medicine, Duke University School of Medicine, and one of the study
investigators. “The absence of serious treatment-related adverse
events, together with increased hemoglobin and reduced markers of
hemolysis among the group receiving FT-4202, indicate a potential
impact on overall red blood cell health and support further
studies.”
“We are pleased to present our clinical proof-of-concept data
and continue to see potential for FT-4202 to improve the lives of
people living with sickle cell disease,” said Patrick Kelly, M.D.,
chief medical officer of Forma. “As we prepare to initiate Forma’s
pivotal Phase 2/3 trial, we plan to evaluate whether the combined
ability of FT-4202 to increase hemoglobin levels in red blood cells
and bring about improved red blood cell health will meaningfully
reduce the frequent painful vaso-occlusive crises these patients
endure.”
Presentation Overview
FT-4202, an Allosteric Activator of Pyruvate Kinase-R,
Demonstrates Proof of Mechanism and Proof of Concept after a Single
Dose and after Multiple Daily Doses in a Phase 1 Study of Patients
with Sickle Cell Disease
The data will be presented in an oral presentation by R. Clark
Brown, M.D., Ph.D., Pediatric Hematologist/Oncologist, Medical
Director of Sickle Cell at Scottish Rite, Aflac Cancer and Blood
Disorders Center of Children’s Healthcare of Atlanta, and Associate
Professor of Pediatrics, Emory University School of Medicine.
The results announced today are based on nine patients with SCD
(FT-4202 n=7; placebo n=2) randomly assigned to receive a single
oral dose of 300 mg daily of FT-4202 or placebo for 14 days. The
data show that, from baseline, in patients receiving FT-4202:
- 6 of 7 achieved a > 1 g/dL increase in hemoglobin (Hb);
median 1.2 g/dL increase (range 0, 2.3 g/dL);
- 2,3-DPG levels were reduced, thus increasing oxygen affinity
and decreasing sickle hemoglobin polymerization;
- Adenosine triphosphate (ATP) levels were increased resulting in
improved RBC function and reduced hemolysis;
- 7 of 7 achieved a reduction in reticulocytes; median 60%
decrease (range -39%, -81%);
- 6 of 7 achieved a reduction in lactate dehydrogenase (LDH);
median 36% decrease (range +18%, -57%); and
- 7 of 7 achieved a reduction in bilirubin; median 35% decrease
(range -7%, -63%).
The tolerability data presented today are based on nine patients
enrolled at the time of submission of the presentation to ASH.
Since then, findings from these nine patients have been unblinded.
Among the seven patients receiving FT-4202, the tolerability
analysis indicates:
- Eighteen adverse events (AEs) were reported;
- Two Grade 1 AEs considered possibly related to study treatment
were reported by one patient each and included headache and
nausea;
- No treatment-related serious AEs were reported.
Non-treatment-related AEs were consistent with sickle cell
disease-related events commonly experienced in this patient
population.
The ongoing Phase 1 study is evaluating the safety,
tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a
single ascending dose and multiple ascending doses of FT-4202,
first in healthy volunteers and now in patients with sickle cell
disease. Based on the safety results and tolerability profile
observed in the initial multiple dose cohort of patients, a second
multiple dose cohort is being enrolled in which patients are
randomly assigned to receive a single daily 600 mg oral dose of
FT-4202 or placebo for 14 days. Patients who complete this second
14-day dose cohort can then enroll into a 12-week, open label
cohort receiving a single daily 400 mg oral dose of FT-4202. For
more information, please visit
clinicaltrials.gov/NCT03815695.
The data presented today, along with the results from the single
700 mg dose arm of the study presented in June 2020 at the European
Hematology Association (EHA) Annual Congress, support initiation of
a randomized, placebo-controlled, double-blind, global multicenter
Phase 2/3 registrational study to evaluate the safety and efficacy
of FT-4202 in adults and adolescents with SCD in the first quarter
of 2021.
Investor Event
Forma Therapeutics will conduct a webcast today, Dec. 7, at 6
p.m. Eastern Standard Time (EST) to further discuss the results
from the ongoing study and to provide additional details of the
company’s development plans for FT-4202. A live webcast will be
available in the “News & Investors” section of Forma’s website:
https://ir.formatherapeutics.com/.
About Sickle Cell Disease
Sickle cell disease (SCD) is one of the most common single-gene
disorders and is estimated to affect approximately 100,000 people
in the United States, as well as approximately 30,000 in France,
Germany, Italy, Spain and the United Kingdom. The National
Institutes of Health (NIH) reports that prevalence is estimated at
more than 20 million individuals globally. From 2010 to 2050, the
annual number of newborns with SCD is expected to rise globally by
approximately one-third.1 Despite recent advances in treatment,
most patients with SCD still suffer from pain crises, lifelong
disability, significant morbidity and reduced quality of life.
About FT-4202
FT-4202 is a novel investigational selective red blood cell
(RBC) pyruvate kinase-R (PKR) activator designed to be a
disease-modifying therapy for the treatment of sickle cell disease
(SCD). Employing a multimodal approach, FT-4202 is designed to work
upstream by activating the RBCs’ natural PKR activity to decrease
2,3-DPG levels, which leads hemoglobin to hold on to oxygen
molecules longer to reduce RBC sickling. The downstream activity of
FT-4202 is designed to increase ATP levels, the fuel that provides
energy to cells, to improve RBC health and survival. Together,
these effects are anticipated to increase hemoglobin levels and
decrease painful vaso-occlusive crises. In preclinical safety
studies, FT-4202 did not inhibit aromatase activity or affect
steroidogenesis, important biological processes responsible for
sexual development. FT-4202 has been granted Fast Track, Rare
Pediatric Disease and Orphan Drug designations from the U.S. Food
and Drug Administration (FDA), and Orphan Drug Designation from the
European Commission based on a positive opinion from the Committee
for Orphan Medicinal Products of the European Medicines Agency for
the treatment of patients with SCD.
About Forma Therapeutics
Forma Therapeutics is a clinical-stage biopharmaceutical company
focused on the research, development and commercialization of novel
therapeutics to transform the lives of patients with rare
hematologic diseases and cancers. Our R&D engine combines deep
biology insight, chemistry expertise and clinical development
capabilities to create drug candidates with differentiated
mechanisms of action focused on indications with high unmet need.
Our work has generated a broad proprietary portfolio of programs
with the potential to provide profound patient benefit. For more
information, please visit www.FormaTherapeutics.com or follow us on
Twitter @FORMAInc and LinkedIn.
Forward-looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995, as amended, including, without limitation, express or implied
statements regarding our beliefs and expectations regarding: our
ability to complete our ongoing Phase 1 clinical trial for FT-4202,
including its timing and success, our expectations of the
therapeutic benefits related to FT-4202, , whether positive interim
results from a clinical study are predictive of the results of
ongoing or future clinical studies, our expectations around our
future regulatory filings and our growth as a company. The words
“may,” “will,” “could,” “would,” “should,” “expect,” “plan,”
“anticipate,” “intend,” “believe,” “estimate,” “predict,”
“project,” “potential,” “continue,” “target” and similar
expressions are intended to identify forward-looking statements,
although not all forward-looking statements contain these
identifying words.
Any forward-looking statements in this press release are based
on management’s current expectations and beliefs and are subject to
a number of risks, uncertainties and important factors that may
cause actual events or results to differ materially from those
expressed or implied by any forward-looking statements contained in
this press release, including, without limitation, those risks and
uncertainties related to the advancement of our clinical programs
and other risks identified in our SEC filings, including those
risks discussed under the heading “Risk Factors” in our Quarterly
Report on Form 10-Q for the quarter ended September 30, 2020, as
well as other risks detailed in our subsequent filings with the
SEC. We caution you not to place undue reliance on any
forward-looking statements, which speak only as of the date they
are made. We disclaim any obligation to publicly update or revise
any such statements to reflect any change in expectations or in
events, conditions or circumstances on which any such statements
may be based, or that may affect the likelihood that actual results
will differ from those set forth in the forward-looking statements.
Any forward-looking statements contained in this press release
represent our views only as of the date hereof and should not be
relied upon as representing its views as of any subsequent date. We
explicitly disclaim any obligation to update any forward-looking
statements.
_______________________ 1Piel, F. B., Hay, S. I., Gupta, S.,
Weatherall, D. J., & Williams, T. N. (2013). Global burden of
sickle cell anaemia in children under five, 2010-2015: Modelling
based on demographics, excess mortality, and interventions. PLOS
Medicine, 10(7). Retrieved from link.
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version on businesswire.com: https://www.businesswire.com/news/home/20201207005857/en/
Media Contact: Megan McGrath, +1 781-591-3488 MacDougall
mmcgrath@macbiocom.com Investor Contacts: Mario Corso, +1
781-366-5726 Forma Therapeutics mcorso@formatherapeutics.com
Stephanie Ascher, +1 212-362-1200 Stern Investor Relations
stephanie.ascher@sternir.com
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