History & IP

Predecessor Molecules

The predecessor molecules to BOLD-100, IT-139 / NKP-1339 / KP1339 and KP1019, were originally discovered at the Institute of Inorganic Chemistry at the University of Vienna by Dr. Bernhard Keppler and his team, who continues to collaborate with Bold Therapeutics. Dr. Keppler is currently Dean of the Faculty of Chemistry and Head of the Department of Inorganic Chemistry at the University of Vienna.

BOLD-100 (2016 – present)

(sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)]) with cesium as an intermediate salt form

BOLD-100 Molecule Diagram BOLD-100 was previously owned by Intezyne Technologies, a biopharmaceutical company focused on platform drug delivery technologies based in Tampa, Florida. Bold Therapeutics was established by Gaston Capital, the largest investor in Intezyne Technologies, specifically to develop BOLD-100.

Unlike IT-139 / NKP-1339 / KP1339, BOLD-100 can be manufactured predictably and at commercial scale, with a clean and well-defined impurity profile. This stemmed from research and development leading to the cesium salt intermediate synthesis route that eliminated the need for multiple aqueous extraction steps which contributed to impurities and lack of scalability.

Intellectual Property
Reference Number
Grant / Expiration Date
Description

US Patent 11,040,993
PCT/US2018/031436
22JUN21 -> 2038

US Patent 10,611,787
07APR20 -> 2038

WO 2018/204930 08NOV18 -> TBD

BOLD-100 composition-of-matter (drug substance)
BOLD-100 composition-of-matter (drug product)
BOLD-100 method-of-manufacturing

AU2018263965
EP3618827
JP2020518676
CN111372939
WO/2018/204930
RU2019138773
CA3062369
KR1020197036075

US Patent 10,821,095
03NOV20 -> 2037

BOLD-100 method-of-use (GRP78 mechanism-of-action)
BOLD-100 method-of-use (resistant cancers)

Notes: Additional patent applications have been filed and are expected to be filed in the near-future as additional clinical data becomes available.

IT-139 / NKP-1339 / KP1339 (~2008 - 2016)

sodium trans-[tetrachlorobis(1H-indazole)ruthenate(III)]

IT-139 Molecule Diagram In IT-139 / NKP-1339 / KP1339, KP1019’s indazole salt is replaced by a sodium salt to improve solubility and clinical application.

Intezyne Technologies acquired NKP-1339 (then renamed to IT-139) as part of its acquisition of Niiki Pharmaceuticals in June 2013. While IT-139 / NKP-1339 had intriguing anti-cancer activity, it could not be manufactured predictably or at commercial scale. More specifically, the need for multiple aqueous extraction steps during drug substance synthesis severely limited batch size, purity, and overall yield of the process.

Between 2013 and 2016, Intezyne Technologies studied the chemistry of IT-139 / NKP-1339 and explored various alternative chemical synthesis routes. A surprising discovery in 2016 resulted in elucidation of the synthesis route that eventually produced BOLD-100. Concurrently, preclinical studies first identified the importance of GRP78 in the compound’s anti-resistance mechanism-of-action.

Niiki Pharma acquired KP1339 (then renamed to NKP-1339) from Momentous Ventures in 2008, who had previously licensed the asset from the University of Vienna. Niiki Pharma began the initial clinical development of the asset, including the aforementioned monotherapy Phase 1 clinical trial. However, Niiki Pharma had not yet identified the mechanism-of-action and consequently struggled with how best to develop the asset. At the time of the monotherapy study, NKP-1339 / KP1339 was thought to be a replacement for cisplatin – and the compound’s combinational potential was not yet recognized. In addition, the clinical development program at Nikki Pharma extended significantly beyond projections due to a long monotherapy dose-escalation process involving 20 dose levels and the need to investigate a dosing schedule.

Intellectual Property
Reference Number Grant / Expiration Date Description
US7,338,946
US7,589,084
US7,485,659
04MAR08 -> 2022
15SEP09 -> 2022
03FEB09 -> 2022
KP1339 composition-of-matter
US8,362,266 29JAN13 -> 2030 KP1339 method-of-manufacturing
US9,283,208
EU2709623
CA2,835,885
15MAR16 -> 2031
20AUG19 -> 2031
25AUG20 -> 2032
IT-139 method-of-use (treatment of cancer)
SK10-1783190
JP6034288
25SEP16 -> 2031
04NOV16 -> 2031
IT-139 method-of-use (combination therapy)
EU2560638
CN102939086B
JP5865896
11MAR15 -> 2031
18MAR15 -> 2031
08JAN16 -> 2031
IT-139 method-of-use (gastric cancer)
EU2509599
AU2010328023
CA2821034
SK10-1824934
13AUG14 -> 2030
14JUL16 -> 2030
05DEC17 -> 2030
29JAN18 -> 2030
IT-139 method-of-use (pancreatic cancer)
Notes: These method-of-use patents also cover the use of BOLD-100.

KP1019 (1989 – 2008)

indazolium trans-[tetrachlorobis(1H-indazol)ruthenate(III)]

KP-1019 Molecule Diagram KP1019, indazolium trans-[tetrachlorobis(1H-indazol)-ruthenate(III)], was discovered by Dr. Bernhard Keppler in 1989 during a rare metals screen of a variety of compounds looking for platinum alternatives for chemotherapy. This ruthenium-based asset was found to have medical advantages compared to traditional metal-based drugs, including a better safety profile in humans. The drug then was licensed and owned by Momentous Ventures.