On July 7, 2020 MAIA Biotechnology, Inc., a targeted therapy, immuno-oncology company focused on development of first-in-class drugs, reported that encouraging preclinical results supporting newly-identified immunogenic effects of the company’s lead product candidate, investigational THIO (6-thio-dG), the only telomere-by-telomerase targeting agent in development for the treatment of cancer, has been published in Cancer Cell, a renowned peer-reviewed scientific journal covering major advances in cancer research (Press release, MAIA Biotechnology, JUL 7, 2020, View Source [SID1234561728]). The manuscript entitled: "Telomere Stress Potentiates STING-Dependent Anti-tumor Immunity," Mender et al., is now featured online and will also be published in the September 2020 edition of Cancer Cell, Volume 38, pages 1-12.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Telomerase is the enzyme responsible for the maintenance of telomeres. While inactive in most normal cells, telomerase is activated in the majority of cancer cells, making it an attractive target for cancer therapy. Preclinical data have demonstrated that THIO kills cancer cells by targeting and uncapping telomeres thereby inducing DNA damage. The latest preclinical data showed this is complemented by an immunogenic effect, which may allow for more durable outcomes when used sequentially with immunotherapy. THIO’s activity was shown to be cancer-specific in tumor types with active telomerase. Since up to 35 million patients have telomerase-positive cancers, MAIA Biotech believes these results suggest that THIO holds significant potential to treat large patient populations across many types of cancers.

In these preclinical studies published in Cancer Cell, investigators demonstrated that THIO leads to tumor regression through induction of innate and adaptive host immune system responses. THIO was shown to be directly incorporated into telomeres by telomerase, where it rapidly induced telomeric DNA damage responses, which is selective to telomerase-positive TERT(+) cancer cells without affecting normal telomerase-silent cells. The findings also indicated that THIO induces DNA-mediated innate sensing and activation of immune responses in a host cGAS/STING-dependent manner, leading to improved anti-tumor efficacy. Low doses of THIO, followed by anti-PD-L1 therapy, completely eliminated advanced tumors in preclinical models and produced cancer cell specific immune memory where the immune system continued to be active against the cancer cells after extended periods of time with no additional treatment. These results are significant as they demonstrate how the THIO-produced telomere stress increases innate sensing and adaptive anti-tumor immunity, which provides a strong rationale for sequentially combining telomere-targeted therapy with immunotherapy.

"We believe THIO has the potential to transform the immuno-oncology landscape and change the cancer treatment paradigm, and these most recent findings provide a strong rationale for combining telomere-targeted therapy with immunotherapy," stated Vlad Vitoc, MD, MAIA’s Chief Executive Officer and President. "We believe the publication of these unprecedented immunogenic effects of THIO in Cancer Cell provides additional validation for this innovative program. We are highly encouraged by these promising findings of tumor elimination, cancer specific immune responses, and stimulation of immune memory, which build upon prior positive preclinical results. These findings provide further support for the company’s plans to advance THIO into Phase 1 clinical studies in 2021."

About THIO

THIO (6-thio-dG) is a small molecule in preclinical development and is the only telomere-by-telomerase targeting agent currently in development. THIO is designed to selectively kill cancer cells by modifying telomeric DNA structure and function utilizing telomerase. Telomerase is present in >85% of human cancers and contributes significantly to proliferation and immortality of cancer cells. THIO is recognized by telomerase and incorporated into telomeres selectively in cancer cells. Once incorporated, it compromises the telomere structure and function, leading to ‘uncapping’ of the chromosome ends and thus resulting in rapid tumor cell death. In preclinical studies, this rapid cancer cell death occurred without impacting normal cells. THIO is investigational and has not been approved for any use anywhere in the world.

About Cancer Cell

Cancer Cell provides a high-profile forum to promote major advances in cancer research and oncology. The primary criterion for considering manuscripts is whether the studies provide major advances into answering important questions relevant to naturally occurring cancers. Cancer Cell is also interested in publishing clinical investigations, in particular those that lead to establishing new paradigms in the treatment, diagnosis, or prevention of cancers; those that provide important insights into cancer biology beyond what has been revealed by preclinical studies; and those that are mechanism-based proof-of-principle clinical studies. For more information, please visit www.cell.com/cancer-cell or follow the journal on Twitter: @Cancer_Cell.

On July 7, 2020 Astex Pharmaceuticals, Inc.; Taiho Oncology, Inc.; and Otsuka Pharmaceutical Co., Ltd. reported that the U.S. Food and Drug Administration (FDA) and Health Canada have approved INQOVI (decitabine and cedazuridine) tablets (Press release, Astex Pharmaceuticals, JUL 7, 2020, View Source [SID1234561727]). The three companies are all part of the Otsuka group of companies.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

INQOVI is the first and only orally administered hypomethylating agent for the treatment for adults with intermediate and high-risk myelodysplastic syndromes (MDS) including chronic myelomonocytic leukemia (CMML),1 two blood malignancies.

Approval was based on data from the ASCERTAIN phase 3 study and supporting phase 1 and 2 clinical studies. The ASCERTAIN phase 3 study evaluated the five-day, decitabine exposure equivalence between oral INQOVI and intravenous decitabine. The safety and efficacy of INQOVI was also assessed in the clinical studies.

The review and approval of INQOVI was conducted under the ORBIS initiative from the FDA Oncology Center of Excellence (OCE) with simultaneous submission and regulatory review in the U.S., Canada, and Australia. The FDA also reviewed the NDA under Priority Review status. INQOVI is not currently approved in Australia. INQOVI was formerly named ASTX727, its experimental compound code.

"Intravenous or subcutaneous administered hypomethylating agents have been the cornerstone for the treatment of patients with MDS and CMML since the mid-2000s," said Guillermo Garcia-Manero, MD, Professor and Chief of Section of Myelodysplastic Syndromes, Department of Leukemia at The University of Texas MD Anderson Cancer Center, Houston, Texas, and Principal Investigator of the ASCERTAIN clinical study. "The FDA’s approval of INQOVI builds on the proven therapeutic utility of hypomethylating agents in these diseases and offers a new orally administered option that offers patients an alternative to five consecutive days of IV infusions every month during a treatment period that can extend to several months."

"Until now, patients with intermediate and high-risk MDS and CMML have not had an approved, orally administered hypomethylating agent option for treatment of their disease," said Mohammad Azab, MD, president and chief medical officer of Astex Pharmaceuticals, Inc. "The INQOVI clinical program was designed to deliver an oral alternative to IV decitabine based on comparative decitabine exposure data in the clinical trials, and to assess INQOVI’s safety and efficacy profile. As part of the ORBIS project initiative of FDA and Health Canada we were able to share and address information requests simultaneously with both agencies resulting in a more efficient review and completion of assessment in a timely manner. The outcome is expedited availability of this important oral alternative to patients in both countries," added Dr. Azab. "We greatly appreciate the FDA’s priority review and Health Canada’s review of the INQOVI NDA / NDS under Project ORBIS and the approval of a new therapeutic option for patients with these diseases."

INQOVI is an orally administered, fixed-dose combination of the approved anti-cancer DNA hypomethylating agent, decitabine, together with cedazuridine,2 an inhibitor of cytidine deaminase.3 By inhibiting cytidine deaminase in the gut and the liver, INQOVI is designed to allow for oral delivery of decitabine over five days in a given cycle to achieve comparable systemic exposure to IV decitabine (geometric mean ratio of the 5-day cumulative decitabine area-under-the-curve following 5 consecutive once daily doses of INQOVI compared to that of intravenous decitabine was 99% (90% CI: 93, 106).1 The phase 1 and phase 2 clinical study results have been published in Lancet Haematology4 and Blood,5 respectively. The phase 3 ASCERTAIN study data was presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting in Orlando, Florida, in December 2019 by Dr. Garcia-Manero.6

Astex’s parent company, Otsuka Pharmaceutical Co., Ltd., and Taiho Pharmaceutical Co., Ltd. previously announced that, subject to regulatory approvals, commercialization of oral INQOVI in the U.S. and Canada will be conducted by Taiho Oncology, Inc. and Taiho Pharma Canada, Inc. respectively.

"Our partnership with Astex is a demonstration of the commitment that Taiho Oncology has to bringing new therapeutic options to patients with cancer," said Tim Whitten, president and chief executive officer of Taiho Oncology, Inc. "The approval of INQOVI makes the possibility of at-home hypomethylating agent treatment of intermediate and high-risk MDS and CMML a reality, enabling patients to take their medication from the convenience and comfort of their home. This is especially significant during the COVID-19 pandemic, allowing patients to potentially reduce the number of office visits needed for current IV treatment administration. We look forward to working with all healthcare professionals to help deliver the first new oral HMA treatment alternative for patients with intermediate and high-risk MDS and CMML in nearly fifteen years."

About INQOVI (See View Source)

INQOVI is indicated for treatment of adult patients with myelodysplastic syndromes (MDS), including previously treated and untreated, de novo and secondary MDS with the following French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, and chronic myelomonocytic leukemia [CMML]) and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.1

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Myelosuppression: Fatal and serious myelosuppression can occur with INQOVI. Based on laboratory values, new or worsening thrombocytopenia occurred in 82% of patients, with Grade 3 or 4 occurring in 76%. Neutropenia occurred in 73% of patients, with Grade 3 or 4 occurring in 71%. Anemia occurred in 71% of patients, with Grade 3 or 4 occurring in 55%. Febrile neutropenia occurred in 33% of patients, with Grade 3 or 4 occurring in 32%.

Fatal and serious infectious complications can occur with INQOVI. Pneumonia occurred in 21% of patients, with Grade 3 or 4 occurring in 15%. Sepsis occurred in 14% of patients, with Grade 3 or 4 occurring in 11%. Fatal pneumonia occurred in 1% of patients, fatal sepsis in 1%, and fatal septic shock in 1%.

Obtain complete blood cell counts prior to initiation of INQOVI, prior to each cycle, and as clinically indicated to monitor response and toxicity. Administer growth factors, and anti‑infective therapies for treatment or prophylaxis as appropriate. Delay the next cycle and resume at the same or reduced dose as recommended.

Embryo-Fetal Toxicity: INQOVI can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise patients to use effective contraception during treatment with INQOVI and for 6 months (females) or 3 months (males) after last dose.

ADVERSE REACTIONS

Serious adverse reactions in > 5% of patients included febrile neutropenia (30%), pneumonia (14%), and sepsis (13%). Fatal adverse reactions included sepsis (1%), septic shock (1%), pneumonia (1%), respiratory failure (1%), and one case each of cerebral hemorrhage and sudden death.

The most common adverse reactions (≥ 20%) were fatigue, constipation, hemorrhage, myalgia, mucositis, arthralgia, nausea, dyspnea, diarrhea, rash, dizziness, febrile neutropenia, edema, headache, cough, decreased appetite, upper respiratory tract infection, pneumonia, and transaminase increased. The most common Grade 3 or 4 laboratory abnormalities (>50%) were leukocytes decreased, platelet count decreased, neutrophil count decreased, and hemoglobin decreased.

USE IN SPECIFIC POPULATIONS

Lactation: Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with INQOVI and for at least 2 weeks after the last dose.

Renal Impairment: No dosage modification of INQOVI is recommended for patients with mild or moderate renal impairment (creatinine clearance [CLcr] of 30 to 89 mL/min based on Cockcroft-Gault). Due to the potential for increased adverse reactions, monitor patients with moderate renal impairment (CLcr 30 to 59 mL/min) frequently for adverse reactions. INQOVI has not been studied in patients with severe renal impairment (CLcr 15 to 29 mL/min) or end-stage renal disease (ESRD: CLcr <15 mL/min).

About Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML)

Myelodysplastic syndromes are a heterogeneous group of hematopoietic stem cell disorders characterized by dysplastic changes in myeloid, erythroid, and megakaryocytic progenitor cells, and associated with cytopenias affecting one or more of the three lineages. U.S. incidence of MDS is estimated to be 10,000 cases per year, although the condition is thought to be under-diagnosed.7,8 The prevalence has been estimated to be from 60,000 to 170,000 in the U.S.9 MDS may evolve into acute myeloid leukemia (AML) in one-third of patients.10 The prognosis for MDS patients is poor; patients die from complications associated with cytopenias (infections and bleeding) or from transformation to AML.

CMML is a clonal hematopoietic malignancy characterized by accumulation of abnormal monocytes in the bone marrow and in blood. The incidence of CMML in the U.S. is approximately 1,100 new cases per year,11 and CMML may transform into AML in 15% to 30% of patients.12 The hypomethylating agents decitabine and azacitidine are effective treatment modalities and are FDA-approved for the treatment of intermediate and high-risk MDS and CMML. These agents are administered by IV infusion, or by large-volume subcutaneous injections.

On July 7, 2020 Boehringer Ingelheim and Numab Therapeutics (Numab) reported that they have entered into a research collaboration and worldwide licensing agreement (Press release, Boehringer Ingelheim, JUL 7, 2020, View Source [SID1234561726]). It will start with two projects aiming at novel therapies for difficult-to-treat lung and gastrointestinal (GI) cancers and patients with geographic atrophy (GA), a progressive, irreversible retinal disease that occurs in patients with age-related macular degeneration (AMD) for which there is no current treatment. The collaboration brings together Boehringer Ingelheim’s leading expertise in the research and development of life changing breakthrough therapies with Numab’s multi-specific antibody platform.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Lung and GI cancers and retinal diseases are key focus areas of Boehringer Ingelheim’s research and development program. In oncology the company has built a broad and diverse pipeline, combining cancer immunology and cancer cell directed approaches. The novel T-cell engager to be developed with Numab adds to Boehringer Ingelheim’s growing cancer immunology portfolio and supports the strategy to take cancer on by targeting ‘cold’ tumors with synergistic combination approaches. In retinal diseases Boehringer Ingelheim is pursuing a holistic approach leveraging existing expertise in oncology, inflammation, neurodegeneration, fibrosis and cardiometabolic diseases. The new GA program with Numab further broadens the company’s comprehensive portfolio of next generation retinal therapy approaches in various stages of development up to Phase 2 in macular degeneration and diabetic retinal diseases.

"We are thrilled to work with the excellent team at Numab to advance our portfolio assets. Numab’s technology platform fits well with our internal antibody discovery and engineering capabilities and will enhance our efforts to deliver transformative antibody-based therapeutics to patients," said Paige Mahaney, SVP and US Discovery Research Site Head at Boehringer Ingelheim.

"We are looking forward to working with Boehringer Ingelheim, a global leader in pharmaceutical R&D with profound expertise across a broad spectrum of therapeutic areas, further validating our technology platform. This addition to our growing roster of partnerships represents another key milestone in our business development efforts," commented Dr. Oliver Middendorp, Chief Business Officer of Numab Therapeutics. "The upfront payment and near-term milestones attached to this alliance will further strengthen Numab’s ability to accelerate the development of key proprietary assets."

Under the terms of the alliance, the partners will work together to discover one novel multi-specific antibody drug candidate in each area. Boehringer Ingelheim receives from Numab an exclusive worldwide license to develop and commercialize the resulting candidates in exchange for upfront and milestone payments, as well as tiered royalties on net sales of all products resulting from the alliance.

With today’s announcement, Numab has been able to secure seven ongoing relationships with leading pharmaceutical companies including 3SBio / Sunshine Guojian, Boehringer Ingelheim, Eisai Co., Ltd., CStone Pharmaceuticals, Ono Pharmaceutical Co., Ltd., Kaken Pharmaceutical Co., Ltd., and Tillotts Pharma AG.

On July 7, 2020 Novocure (NASDAQ: NVCR) reported that the last patient has been enrolled in the HEPANOVA trial, a phase 2 pilot trial testing Tumor Treating Fields in combination with sorafenib in patients with advanced liver cancer (Press release, NovoCure, JUL 7, 2020, View Source [SID1234561725]). The final data collection date is six months after the last patient in.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Tumor Treating Fields therapy has demonstrated efficacy in in vitro and in vivo models of hepatocellular carcinoma," said Asaf Danziger, Novocure’s Chief Executive Officer. "We believe that Tumor Treating Fields’ mechanism of action is broadly applicable to solid tumor cancers. We look forward to seeing results from the HEPANOVA trial and further exploring the potential of Tumor Treating Fields as a treatment for advanced liver cancer."

The open-label trial includes 25 patients with advanced hepatocellular carcinoma that are not eligible for surgical resection or local treatments. HEPANOVA’s primary endpoint is overall response rate. Second endpoints include in-field control rate, progression free survival rate at 12 months, overall survival rate at 1 year and distant metastases free survival rate at 1 year. The sample size was based on the ability to detect an overall response rate of 20 percent in patients treated with Tumor Treating Fields compared to the 4.5 percent overall response rate calculated from historical controls.

Tumor Treating Fields have demonstrated efficacy in in vitro and in vivo models of hepatocellular carcinoma and can be delivered to the abdominal region. In preclinical studies, Tumor Treating Fields delivered at 150 kHz reduced both HepG2 and Huh-7D12 cell counts (53 percent to 64 percent) and clonogenic potential (~70 percent). The combined treatment of Tumor Treating Fields and sorafenib led to a significant reduction in the number of HepG2 and Huh-7D12 cells (p<0.001) versus each treatment alone.1 Tumor Treating Fields delivered at 150 kHz plus sorafenib led to reduced viability and clonogenicity, as well as increased apoptosis and autophagy in vitro and to a significant reduction in tumor volume in vivo.2

Treatment with Tumor Treating Fields is not approved for liver cancer. The safety and effectiveness of treatment with Tumor Treating Fields for liver cancer has not been established.

About Liver Cancer

Liver cancer is a leading cause of cancer deaths worldwide and is the fifth leading cause of cancer deaths annually in the U.S. The incidence of liver cancer is approximately 38,000 new cases annually in the U.S., approximately 82,500 new cases annually in Europe, and approximately 35,500 new cases annually in Japan. The five-year survival rate with existing standards of care is less than 18 percent.

Hepatocellular carcinoma is the most widespread type of cancer that originates from the liver. Advanced liver cancer has spread either to the lymph nodes or to other organs, and because these cancers are widespread, they cannot be treated with surgery. The current common standard treatment for patients with advanced disease and those who progress on loco-regional therapy is systemic therapy with sorafenib.

About Tumor Treating Fields

Tumor Treating Fields is a cancer therapy that uses electric fields tuned to specific frequencies to disrupt cell division, inhibiting tumor growth and potentially causing cancer cells to die. Tumor Treating Fields does not stimulate or heat tissue and targets dividing cancer cells of a specific size. Tumor Treating Fields causes minimal damage to healthy cells. Mild to moderate skin irritation is the most common side effect reported. Tumor Treating Fields is approved in certain countries for the treatment of adults with glioblastoma and in the U.S. for mesothelioma, two of the most difficult cancer types to treat. The therapy shows promise in multiple solid tumor types – including some of the most aggressive forms of cancer.

Use of Tumor Treating Fields for the treatment of liver cancer is investigational only.

On July 7, 2020 Onconova Therapeutics, Inc. (NASDAQ: ONTX), a Phase 3-stage biopharmaceutical company focused on discovering and developing novel products to treat cancer, with an initial focus on myelodysplastic syndromes (MDS), reported the e-publication of results from a Phase 1 company-sponsored study of oral rigosertib in combination with standard dose azacitidine in the treatment of patients diagnosed with either higher-risk myelodysplastic syndrome (HR-MDS) or acute myeloid leukemia (AML) in the international hematological malignancy journal Leukemia Research (Press release, Onconova, JUL 7, 2020, View Source [SID1234561724]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"A key strategy emerging in the treatment of MDS is the identification of safe and effective combinations, particularly those involving oral agents. The results from this Phase 1 study represent Onconova’s first efforts to explore oral rigosertib in combination with azacitidine to address the unmet medical need in patients with MDS and AML. We anticipate meeting with the FDA, in conjunction with the pivotal data readout from the INSPIRE Trial, for alignment with the agency on a registration trial for the combination of oral rigosertib plus azacitidine in HMA-naïve HR-MDS," said Steven M. Fruchtman, M.D., President and CEO of Onconova.

"These results coupled with preliminary data from the phase II studies, support further clinical development of this novel combination with a manageable safety profile and efficacy in patients with MDS both those HMA naïve and after HMA failure," said study principal investigator Lewis R. Silverman, M.D., Director, Translational Research Center for the Myelodysplastic Syndrome, Associate Professor, Medicine, Hematology, and Medical Oncology, The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai. "The oral administration of rigosertib is not just more convenient for patients, but may improve treatment compliance, leading to improved clinical outcomes."

This publication reports the results of an open-label, dose-escalating Phase 1 study with the combination oral of rigosertib and standard dose azacitidine administered sequentially to patients diagnosed with HR-MDS following HMA-failure, or relapsed/refractory AML. The study objectives were to assess safety and determine the recommended Phase 2 dose (RP2D) for future studies. The study evaluated three dose cohorts of oral rigosertib with no dose-limiting toxicities reported. In addition, the oral rigosertib/azacitidine combination demonstrated an overall response rate of 7/9 (78%) in patients with HR-MDS and 2/7 (29%) in patients with AML. The Phase 2 part of the study is ongoing. Additional details are available on www.clinicaltrials.gov (NCT01926587).

"We believe this combination could eventually prove very beneficial for patients with higher-risk MDS. In addition to its oral formulation and thus ease of administration, rigosertib is potentially an attractive partner for a variety of combination approaches due to its novel mechanism of action as a RAS mimetic that differentiates it from other MDS therapies," said Richard C. Woodman, M.D., Chief Medical Officer of Onconova.

About Rigosertib

Rigosertib, Onconova’s lead candidate, is a proprietary Phase 3 small molecule. A key publication in a preclinical model reported rigosertib’s ability to block cellular signaling by targeting RAS effector pathways (Divakar, S.K., et al., 2016: "A Small Molecule RAS-Mimetic Disrupts RAS Association with Effector Proteins to Block Signaling." Cell 165, 643). Onconova is currently in the clinical development stage with oral and IV rigosertib, including clinical trials studying single agent IV rigosertib in second-line higher-risk MDS patients (pivotal Phase 3 INSPIRE trial) and oral rigosertib plus azacitidine in HMA naive and refractory higher-risk MDS patients (Phase 2). Patents covering oral and injectable rigosertib have been issued in the US and are expected to provide coverage until at least 2037.