Categorynews

Imbrium Therapeutics Announces U.S. FDA Orphan Drug Designation for Tinostamustine for the Treatment of T-cell Prolymphocytic Leukemia

March 28, 2019 Off By BusinessWire

STAMFORD, Conn.–(BUSINESS WIRE)–Imbrium Therapeutics L.P., a clinical-stage biopharmaceutical company
and operating subsidiary of Purdue Pharma L.P., in conjunction with
Mundipharma EDO GmbH, today announced that the U.S. Food and Drug
Administration (FDA) has granted orphan drug designation (ODD) to its
investigational drug tinostamustine, a potentially first-in-class
alkylating deacetylase inhibiting molecule being studied in early phase
clinical trials, for the treatment of T-cell prolymphocytic leukemia
(T-PLL).

T-PLL is an extremely rare and aggressive T-cell leukemia that is
characterized by out of control growth of mature T-cells. There are very
limited effective treatment options for T-PLL. The disease typically
progresses rapidly and does not respond well to standard multi-agent
chemotherapy.

“This orphan drug designation represents an important step not just for
Imbrium and the development of tinostamustine, but also for the patients
suffering from T-PLL who do not currently have sufficient treatment
options,” said Richard Fanelli, PhD, head of Regulatory Affairs, Imbrium
Therapeutics.

The FDA grants ODD status to medicines intended for the treatment,
diagnosis or prevention of rare diseases or disorders that affect fewer
than 200,000 people in the United States. Orphan drug designation is
intended to facilitate drug development for rare diseases and may
provide certain incentives to drug developers.^1,2 T-PLL is an
extremely rare and typically aggressive blood cancer. It is so rare that
healthcare professionals may only see one case of T-PLL every five to 10
years.³ Due to its rarity, T-PLL can be misdiagnosed,
resulting in poor patient outcomes with a median survival of around one
year.^3,4 There is no guarantee that tinostamustine, an
investigational agent, will successfully complete clinical development
or gain FDA approval.

Craig Landau, MD, president and CEO, Purdue Pharma L.P. added, “This
marks the second orphan drug designation we have received from the U.S.
FDA in just the last two months and demonstrates our commitment to
rapidly advancing our pipeline of oncology chemotherapeutics for rare
and difficult to treat cancers.”

In addition to T-PLL, Imbrium Therapeutics has initiated the early phase
clinical development of tinostamustine in a range of rare and
difficult-to-treat blood cancers and advanced solid tumors.

About T-cell prolymphocytic leukemia
T-cell prolymphocytic
leukemia (T-PLL) affects approximately 2 percent of all patients with
mature lymphocytic leukemias.⁵ It is characterized by the out
of control growth of mature T-cells (T-lymphocytes). T-cells are a type
of white blood cell that protects the body from infections.⁶The
majority of patients present with hepatosplenomegaly and generalized
lymphadenopathy, with skin infiltration, anemia and thrombocytopenia
often seen.⁵ T-PLL affects older adults with a median age at
diagnosis of 61 years, and it is more common in men than in women.⁶

T-PLL typically has rapid progression and does not respond well to
standard multi-agent chemotherapy.

About tinostamustine
Tinostamustine (EDO-S101), is a novel
multi-action therapy in Phase 2 clinical development for a range of rare
and difficult-to-treat blood cancers and advanced solid tumors.

Preclinical studies have shown that tinostamustine has the potential to
improve access to the DNA strands within cancer cells, break them, and
counteract damage repair.^7,8,9,10 The preclinical data also
suggest that these complementary and simultaneous modes of action have
the potential to overcome resistance toward some other cancer treatments.^7,8,9,10

Tinostamustine is currently being studied in multiple myeloma, Hodgkin
lymphoma, peripheral T-cell lymphoma, cutaneous T-cell lymphoma, T-cell
prolymphocytic leukemia, soft tissue sarcoma, small cell lung cancer,
triple-negative breast cancer, ovarian cancer, endometrial cancer and
MGMT-unmethylated glioblastoma.

About Imbrium Therapeutics
Imbrium is a clinical-stage
biopharmaceutical company dedicated to advancing medical science through
the development of important new pharmacologic and biologic
therapeutics. We are pursuing oncology chemotherapeutics, treatments for
disorders of the central nervous system, and non-opioid approaches to
the management of pain. As an operating subsidiary of Purdue Pharma
L.P., Imbrium strives to develop and bring to market new medicines that
serve the unmet needs of patients, physicians and health systems
worldwide. We have built a robust and diversified pipeline of
investigational drug candidates, and we actively collaborate with
industry and academic partners to identify and advance future impactful
medicines. For more information, please visit: www.imbriumthera.com.

About Mundipharma EDO
Mundipharma EDO is part of the
Mundipharma global network of privately-owned independent associated
companies, which operate in over 120 countries worldwide. We develop
treatments for patients around the world with rare or
relapsed/refractory cancer, investigating smart approaches to new cancer
treatments from concept through to clinical development and regulatory
approval.

We operate a lean, agile research and development model, empowering the
team to form conclusions and make quick decisions with the aim of
getting new therapies to patients as rapidly as possible. For more
information please visit: www.edoncology.com.

¹ U.S. Food & Drug Administration. Designating an Orphan
Product: Drugs and Biological Products. Last updated Jul 2018. Accessed
Mar 25, 2019. Retrieved from https://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/HowtoapplyforOrphanProductDesignation/default.htm.
²
U.S. Government Publishing Office. Electronic Code of Federal
Regulations. 316.21: Verification of orphan-drug status. Accessed Mar
25, 2019. Retrieved from https://www.ecfr.gov/cgi-bin/retrieveECFR?gp=&SID=718f6fcbc20f2755bd1f5a980eb5eecd&mc=true&n=sp21.5.316.c&r=SUBPART&ty=HTML#se21.5.316_120.
³
Dearden C. How I treat prolymphocytic leukemia. Blood. 2012;
120(3):538–551. Accessed Mar 25, 2019. Retrieved from http://www.bloodjournal.org/content/bloodjournal/120/3/538.full.pdf.
⁴
National Institutes of Health. National Cancer Institute SEER Database:
T-cell prolymphocytic leukemia. Accessed Mar 25, 2019. Retrieved from https://seer.cancer.gov/seertools/hemelymph/51f6cf58e3e27c3994bd53f3/.
⁵
Swerdlow SH, et al. WHO Classification of Tumours of Haematopoietic
and Lymphoid Tissues (Revised 4th Edition). IARC: Lyon, 2017.
⁶
Leukemia and Lymphoma Society. T-cell Prolymphocytic Leukemia (T-PLL).
Accessed Mar 25, 2019. Retrieved from https://www.lls.org/leukemia/t-cell-prolymphocytic-leukemia-t-pll.
⁷
Loìpez-Iglesias AA, et al. The Alkylating Histone Deacetylase Inhibitor
Fusion Molecule Edo-S101 Displays Full Bi-Functional Properties in
Preclinical Models of Hematological Malignancies. Blood. 2014;
124:2100.
⁸ Loìpez-Iglesias AA, et al. Preclinical
Antimyleoma Activity of EDO-S101. Clinical Lymphoma, Myeloma &
Leukemia. 2015; 15(Suppl 3):PO-238.
⁹ De Filippi R,
et al. The First-in-Class Alkylating Histone-Deacetylase Inhibitor
(HDACi) Fusion Molecule Edo-S101 Exerts Potent Preclinical Activity
Against Tumor Cells of Hodgkin Lymphoma (HL) Including
Bendamustine-Resistant Clones. Blood. 2015; 126:2481.
¹⁰
Yan S et. al. Synergistic inhibition of tumor growth and overcoming
chemo-resistance by simultaneously targeting key components in DNA
damage/repair, epigenetic, and putative cancer stem cell signaling
pathways using novel dual-functional DNA-alkylating/HDAC inhibitor and
tumor suppressor gene nanoparticles in lung cancer. Cancer Res
2012;72(8 Suppl):Abstract nr 2741. Accessed Mar 25, 2019. Retrieved from http://cancerres.aacrjournals.org/content/72/8_Supplement/2741.