Date: 2017-07-20
Type of information: Termination of an agreement
Compound: inhibitors of Lysine Specific Demethylase-1 (LSD1; KDM1A) including ORY-1001 (RG6016)
Company: Roche (Switzerland) Oryzon Genomics (Spain)
Therapeutic area: Cancer - Oncology
Type agreement: research - development - licensing
Action mechanism: enzyme inhibitor/LSD1 inhibitor. LSD1 is also called an “eraser”, for it removes signals in the histone, provoking changes in the reading context of the chromosome and turning off genes. Aberrant “erasing” activity may lead to disease. In mixed lineage leukaemia (e.g., AML, ALL) LSD1 has been identified as playing a pivotal role. Drugs inhibiting LSD1 produced changes in gene expression leading to differentiation of leukemic blasts cells into normal differentiated cells, reducing proliferation and reducing viability of leukemic stem cells. ORY-1001 is a highly selective and potent LSD1 inhibitor which can be orally administered to patients. ORY-1001 affects AML stem cells, a sub-population of cancer cells that has been proposed to be responsible for frequent relapses of the disease. ORY-1001 also significantly reduces tumour cell load and increases survival time in mouse models of Acute Lymphoblastic Leukaemia. LSD1 has been also related with other malignancies such as solid tumours and other haematological diseases.
Disease: acute myeloid leukaemia
Details:
- • On April 7, 2014, Roche and Oryzon Genomics have announced they have entered into a worldwide collaboration to research, develop and commercialize inhibitors of Lysine Specific Demethylase-1 (LSD1; KDM1A), an epigenetic modulator that regulates gene expression. The lead molecule, ORY-1001, was granted orphan drug status by EMA in August 2013 and is currently in phase I/IIA for acute myeloid leukaemia (AML) in the UK and in Spain. Roche will have sole responsibility for developing and commercializing ORY-1001 and/or its backup compounds.
- The agreement includes the licensing of two patent families that Oryzon has created in its pioneering research in LSD1, and includes options for other Oryzon programs to be incorporated in future. The agreement also includes an initial two-year collaborative research program between Oryzon and Roche’s New York-based Translational Clinical Research Center (TCRC), Roche’s hub for research and early development activities in North America, to better understand the potential of LSD1 inhibitors in oncology and haematology.
Financial terms:
- Under the terms of the agreement, Oryzon will receive an upfront payment and near-term milestones totalling $21 million, plus potential development, commercial and sales milestone payments across haematology, cancer and non-malignant indications that could exceed $500 million, together with tiered royalties on sales which range up to mid-double digits.
Latest news:
- • On July 20, 2017, Oryzon Genomics announced that Roche informed the company that due to a portfolio prioritization, it has decided to discontinue its involvement in the clinical development of ORY-1001 (RG6016) for the treatment of patients with acute myeloid leukemia (AML) and solid tumors pursuant to the license agreement between Oryzon and Roche dated April 1 st, 2014. As a consequence of such decision, the rights that Oryzon had licensed to Roche with respect to ORY-
1001 will revert to Oryzon when the termination of the license agreement becomes effective. Also pursuant to the terms of the license agreement, Roche is committed to finalize the ongoing Phase I in small cell lung cancer (SCLC) following the clinical development plan, which is expected to occur in the
following months.
- • On January 9, 2017, Oryzon Genomics announced that the first patient has been treated in the phase 1 study of RG6016, a LSD1 inhibitor, in small cell lung cancer (SCLC). This clinical trial is executed by Roche. Roche has started a dose finding and expansion study of RG6016 administered orally in participants with relapsed, extensive-stage disease small cell lung cancer (ED SCLC). The study initially will be conducted in several European countries and Canada.
- • On May 18, 2016, Oryzon Genomics announced that the 2-year R&D collaboration with Roche concerning
ORY-1001, licensed to Roche in 2014, has been extended until March 2017. ORY-1001 (RG6016) is currently in Phase 1/2a in acute leukemia patients. The license agreement by which the development and commercial rights to ORY-1001 were granted to Roche, included a 2-year collaborative research program between Oryzon and Roche to further explore the potential of ORY-1001 in oncology and haematology. The program has delivered additional insight into the drug’s mechanism of action, provided support for its use in indications beyond acute leukemia and has expanded the toolbox for future and current clinical trials. Oryzon will continue to support the development of ORY-1001 through an extension of the collaborative research program that will run until March 2017 with the main goal to finalize the transfer of the newly generated technology and knowledge.
- • On November 10, 2015, Oryzon Genomics announced the dosing of the first patient in the extension cohort (Part 2) of its ORY-1001 Phase I clinical trial.
- • On September 7, 2015, Oryzon Genomics announced that it has finalized the multiple ascending dose (MAD) stage of its Phase I clinical trial to evaluate the safety, tolerability and pharmacokinetics of ORY-1001 in patients with relapsed or refractory acute leukemia. Through the establishment of a Recommended Dose of ORY-1001, Oryzon has achieved this development milestone included in the License Agreement with Roche signed in April 2014 and will receive a payment of $ 4 million.
Is general: Yes
