On November 9, 2017 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a Phase 3 stage biopharmaceutical company focused on discovering and developing novel small molecule drug candidates to treat cancer, with a primary focus on Myelodysplastic Syndromes (MDS), reported a corporate update and financial results for the third quarter ended September 30, 2017 (Press release, Onconova, NOV 9, 2017, View Source [SID1234521892]).
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"We are getting closer to two key milestones for the INSPIRE pivotal trial for IV rigosertib in patients with higher-risk MDS. A pre-planned interim analysis is anticipated in the coming months, and encouraging recent enrollment progress for this global trial suggests full enrollment may be achieved in the first half of 2018," said Dr. Ramesh Kumar, President and Chief Executive Officer.
"We have also made good progress on our oral rigosertib-azacitidine combination program and plan to initiate a Special Protocol Assessment process with the Food and Drug Administration for a pivotal Phase 3 trial early next year. In addition, we are advancing our collaborative pre-clinical RASopathies drug program and look forward to two poster presentations at the 2017 American Society of Hematology (ASH) (Free ASH Whitepaper) conference."
INSPIRE Trial of IV Rigosertib in 2nd Line Higher-risk (HR) MDS
Interim Analysis (IA)
· In the quarter, the Company received guidance from the Food and Drug Administration (FDA) and European Medicines Agency (EMA) concerning the statistical analysis plan (SAP) for both the interim and final (top-line) analysis in the INSPIRE trial. Based on guidance received, Onconova finalized the SAP in preparation for the IA.
· The IA will be triggered with the 88th death event in this trial of 225 patients. Based on internal modeling, this could occur in the fourth quarter of 2017 or early 2018. The date of the IA is tied to reaching a pre-identified number of death events. Accordingly, the precise time of completing the IA, which will take place approximately a couple of weeks after reaching the number of events, cannot be accurately forecast.
· This adaptive trial design permits several options after the IA, including a futility analysis, trial expansion using pre-planned statistical criteria, or choosing one of two endpoints (survival analysis of the Intent-to-Treat population or the pre-defined Very High Risk subpopulation).
Trial Progress
· As of October 31, 2017, the INSPIRE study is active at approximately 170 sites in 22 countries across four continents. A final five sites will be opened, which is expected to occur in November.
· The INSPIRE trial has stringent selection criteria so as to identify a more homogenous MDS patient population. Accordingly, extensive eligibility verification and trial site education are integral to the Company’s plan.
· Due to efforts undertaken to increase participation, including the addition and replacement of CROs and opening sites in additional countries, the enrollment rate for the trial increased
recently. Consequently, Onconova expects full enrollment to be achieved in the first half of 2018, followed by top-line analysis after 176 death events in the second-half of 2018.
Oral Rigosertib in Combination with Azacitidine for 1st-line HR-MDS
Pivotal Phase 3 Trial Protocol
· Following input received from the FDA in an end-of-phase 2 meeting and from the EMA as part of the scientific advice process, Onconova has designed a Phase 3 protocol. The Company is awaiting the results of the ongoing Phase 1/2 Expansion Trial before engaging in further protocol development. Once the Expansion Trial is complete, which is expected to be in the fourth quarter of 2017, Onconova plans to submit the Pivotal Phase 3 protocol to the FDA in the first half of 2018 to initiate the SPA process with the FDA.
· Initiation of the Phase 3 trial, which is planned to be conducted globally, requires additional financing and/or business development transactions.
· This Expansion Trial is designed to enroll up to approximately 40 patients. More than half of the trial has been accrued in multiple sites in the USA. Based on this progress, the Company has decided to limit the trial to US sites.
· Onconova plans to present initial data from this study at a scientific conference in early 2018, highlighting the results of dose selection and optimization of the combination regimen.
Other Programs for Future Development or Partnership and Presentations
Rigosertib for Pediatric RASopathies
· On October 11, 2017, Onconova hosted a Key Opinion Leader meeting to discuss novel approaches to RASopathies. The meeting featured presentations by Bruce D. Gelb, M.D. (Mount Sinai, New York), and Elliot Stieglitz, M.D. (University of California San Francisco), who discussed new developments for pediatric patients with RASopathies, which are related genetic syndromes usually caused by mutations that alter the Ras subfamily and mitogen activated protein (MAP) kinases that control signal transduction. Onconova’s Chief Medical Officer, Steven Fruchtman, M.D., provided an update on rigosertib, which is initially planned to be studied in pediatric patients with RASopathies complicated by the development of associated cancers.
· The Company has completed and expects to sign a Cooperative Research and Development Agreement with the US National Institutes of Health (NIH) to advance rigosertib in pediatric clinical trials at the National Cancer Institute. This trial is expected to start next year and will be funded by the NIH.
Onconova Enters into Strategic Collaboration with Cellectar Biosciences
· On September 21, 2017, the Company announced it had entered into a strategic collaboration with Cellectar Biosciences to develop new phospholipid drug conjugates combining select proprietary compounds or payloads from Onconova’s early stage product pipeline with Cellectar’ s patented phospholipid ether delivery platform.
· Under the terms of the collaboration, Onconova will provide Cellectar with several compounds, including some from the family of molecules that contains Briciclib, which is an EIF4E targeting small molecule with early Phase 1 data. Cellectar will link the molecules to its phospholipid ether to create new, more precisely targeted antitumor agents.
Upcoming Presentations
Two abstracts relating to the Company’s lead product candidate, rigosertib, were accepted for poster presentation at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in Atlanta, Georgia, which takes place December 9-12, 2017. Details of the presentations are listed below.
Long-term follow up of patients in a Phase 2 clinical trial of single agent oral rigosertib in lower-risk transfusion dependent MDS
Abstract Number: 1689
Title: Rigosertib Oral in Transfusion Dependent Lower Risk Myelodysplastic Syndromes (LR-MDS): Optimization of Dose and Rate of Transfusion Independence (TI) or Transfusion Reduction (TR) in a Single-Arm Phase 2 Study
Session Name: 637. Myelodysplastic Syndromes – Clinical Studies: Poster I
Date: Saturday, December 9, 2017; 5:30 – 7:30 PM EST
Studies on the mechanism of action of rigosertib azacitidine combination therapy for MDS
Abstract Number: 4235
Title: Effects of Rigosertib (RIGO) Alone or in Combination with Azacitidine or Vorinostat on Epigenetic Reprogramming of CD34+ Cells in the Myelodysplastic Syndrome
Session Name: 636. Myelodysplastic Syndromes – Basic and Translational Studies: Poster III
Date: Monday, December 11, 2017; 6:00 – 8:00 PM EST
Third-Quarter Financial Results:
· Cash, cash equivalents, and marketable securities as of September 30, 2017 totaled $7.6 million, compared to $21.4 million as of December 31, 2016. Based on our cash burn for the first three quarters of 2017 and our current projections, we expect that our cash and cash equivalents will be sufficient to fund our ongoing trials and operations through the end of 2017.
· Total net revenue was $0.1 million for the third quarter of 2017 and $0.6 million for the nine months ended September 30, 2017, compared to $1.7 million and $5.4 million, respectively, for the comparable periods in 2016.
· Research and development expenses were $5.1 million for the third quarter of 2017 and $14.6 million for the nine months ended September 30, 2017, compared to $4.0 million and $15.4 million, respectively, for the comparable periods in 2016.
· General and administrative expenses were $1.7 million for the third quarter of 2017 and $5.6 million for the nine months ended September 30, 2017, compared to $2.0 million and $7.2 million, respectively, for the comparable periods in 2016.
The Company will host a conference call on November 9th at 9:00 a.m. Eastern Time to provide a corporate update and discuss third quarter financial results. Interested parties may access the call by dialing toll-free (855) 428-5741 from the US, or (210) 229-8823 internationally and using conference ID: 3588306.
The call will also be webcast live. Please click here to access the webcast.
A replay will be available at this link until February 23, 2018.