On March 7, 2019 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage oncology therapeutics company, using a precision medicine approach to develop drugs that target cell division (mitosis) for the treatment of leukemias, lymphomas and solid tumor cancers, reported company highlights and financial results for the first quarter ended March 31, 2019 (Press release, Trovagene, MAY 7, 2019, View Source [SID1234535858]). The company is issuing this press release in lieu of conducting a conference call.

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"We are pleased with our accomplishments year-to-date, and our onvansertib clinical development programs continue to advance as planned," said Dr. Thomas Adams, Chief Executive Officer and Chairman of Trovagene. "We began the year with presentation of data from our Phase 2 trial in metastatic Castration-Resistant Prostate Cancer (mCRPC) at the Genitourinary Cancers Symposium (ASCO-GU) and followed this with a presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) demonstrating activity of onvansertib in prostate cancer patients showing initial resistance to anti-androgen therapy. We also achieved a critical milestone in our ongoing Phase 1b/2 trial in Acute Myeloid Leukemia (AML), with a complete response (2 CR’s and 1 CRi) to treatment achieved in 3 of 6 (50%) of evaluable patients at the highest doses of onvansertib (27mg/m2 and 40mg/m2) evaluated in combination with standard-of-care chemotherapy, decitabine."

Dr. Adams added, "We achieved a number of key milestones in the first quarter of 2019, including: Successful completion of the first four dose levels, without any dose-limiting toxicities, in the Phase 1b segment of our AML trial; receipt of a "Study May Proceed" notification from the FDA for our Phase 1b/2 trial in metastatic Colorectal Cancer (mCRC) in January and subsequent agreement with PoC Capital to fund this trial."

The Company has advanced its business to-date in 2019, with the following activities and milestone achievements:

Announced Data Demonstrating Significant Synergy of Onvansertib in Combination with Venetoclax in Cell Model of Venetoclax Resistant AML
On April 23, 2019, Trovagene announced preclinical data that provides support for clinical evaluation of onvansertib in combination with venetoclax (Venclexta – AbbVie) in patients with difficult-to-treat relapsed or refractory acute myeloid leukemia (AML). Preclinical data showed that the combination demonstrated synergy (the combined effect of the two drugs is greater than the sum of their individual effects) with a significant decrease in tumor cell viability.

Announced Update to Phase 1b/2 AML Trial Data Presented at AACR (Free AACR Whitepaper) – Additional Patients Achieve Complete Response at Two Highest Dose Levels of Onvansertib
On April 5, 2019, Trovagene announced updates to the Phase1b/2 AML trial data presented at the AACR (Free AACR Whitepaper) conference on April 1, 2019. Complete response (2 CR’s and 1 CRi) to treatment with onvansertib in combination with decitabine was achieved in 3 of 6 (50%) of evaluable patients at the highest doses (27mg/m2 and 40mg/m2). The first complete response was achieved at the highest dose of onvansertib (40mg/m2) in combination with low-dose cytarabine (LDAC). Overall, approximately 90% clinical benefit has been achieved to-date in the trial and there have been no dose limiting toxicities observed. Dose escalation is continuing with enrollment in the onvansertib 60mg/m2 cohort.

Announced Early Data from Phase 2 Trial Indicates Activity of Onvansertib in Prostate Cancer Patients Showing Initial Resistance to Anti-Androgen Therapy
On April 2, 2019, Trovagene announced early data from its ongoing Phase 2 study evaluating onvansertib in combination with Zytiga in patients with mCRPC. Early prostate specific antigen ("PSA") response was observed when onvansertib is added to abiraterone (Zytiga) in 2 of 6 patients to-date; the first patient achieved the primary efficacy endpoint of disease stabilization. The PSA trajectory in the patient achieving the primary efficacy endpoint indicates alteration of the natural history of early signs of resistance to Zytiga. Patients with observed responses to-date harbor the highly aggressive androgen receptor variant (AR-V7) which is known to be resistant to treatment with Zytiga.

Announced Phase 1b/2 Dose Escalation Trial of Onvansertib in Relapsed/Refractory AML Demonstrates Safety, Tolerability and Relative Durability with Complete Responses at Highest Dose Levels
On April 1, 2019, Trovagene announced the presentation of new data from its ongoing Phase 1b/2 study evaluating onvansertib in combination with standard-of-care chemotherapy in AML. The greatest anti-leukemic activity has been observed in the onvansertib + decitabine arm, with complete response in 2 (1 CR and 1 CRi) of 4 (50%) of evaluable patients from the two highest dose levels. There have been no dose-limiting toxicities observed to-date and two-thirds of patients have completed ≥2 cycles of treatment, with 2 patients currently on treatment for more than 11 and 5 months, respectively. There has been a significant association observed between biomarker-positive patients and response to onvansertib treatment.

Announced Presentation Update on Phase 2 Study of Onvansertib in Combination with Zytiga in Patients with mCRPC at ASCO (Free ASCO Whitepaper)-GU
On February 14, 2019, Trovagene announced the presentation of a poster reviewing its ongoing Phase 2 study evaluating onvansertib in combination with Zytiga (abiraterone acetate)/prednisone in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC) at the Genitourinary Cancers Symposium (ASCO-GU) in San Francisco, CA. The data featured demonstrates the safety and tolerability of onvansertib in combination with Zytiga which was confirmed in the safety lead-in portion of the trial that was completed prior to opening the trial to full enrollment. In addition, a second arm is planned with the goal of maximizing clinical activity by reducing the dosing schedule from the current 21-day cycle to a 14-day cycle.

Announced that Trovagene and PoC Capital Entered into an Agreement to Fund Clinical Development of Onvansertib in Metastatic Colorectal Cancer (mCRC)
On January 29, 2019, Trovagene announced an agreement with PoC Capital to fund its Phase 1b/2 trial of onvansertib in combination with FOLFIRI and Avastin in patients with mCRC with a KRAS mutation. Trovagene submitted an Investigational New Drug (IND) application and protocol to the FDA on December 19, 2018, and received a "study may proceed" notification from the FDA, 28-days later, on January 16, 2019. The trial is being conducted at two prestigious cancer centers in the U.S.; USC Norris Comprehensive Cancer Center and The Mayo Clinic.

Announced New Patent Issued for Combination of Onvansertib and Anti-Androgen Drugs to Treat Non-Metastatic and Metastatic Prostate Cancer
On January 23, 2019, Trovagene announced the issuance of a new patent (10,155,006), entitled Combination Therapies and Methods of Use Thereof for Treating Cancer, by the U.S. Patent and Trademark Office (USPTO). This patent broadens previously issued patent (9,566,280), by expanding the use of onvansertib to encompass combination therapies with any anti-androgen and androgen antagonist drug, such as Zytiga, Xtandi and Erleada for the treatment of metastatic and non-metastatic castrate-resistant prostate cancer. The issuance of this patent further strengthens Trovagene’s existing intellectual property portfolio obtained with the licensing of exclusive global development and commercialization rights to onvansertib from Nerviano Medical Sciences in March, 2017.

First Quarter 2019 Financial Results

Total operating expenses were approximately $4.1 million for the three months ended March 31, 2019, a decrease of $0.7 million from $4.8 million for the same period in 2018. The decrease in operating expenses is attributed to a reduction of $1.0 million in SG&A and $0.4 million for cost of revenues related to the disposition of the CLIA lab, and partially offset by an increase of $0.8 million in R&D costs.

Net cash used in operating activities in the first quarter of 2019 was approximately $3.4 million, compared to $2.9 million in the same period in 2018. The year-over-year increase of $0.5 million can be attributed primarily to funding used to advance the onvansertib clinical trials.

Research and development expenses increased by approximately $0.8 million to $2.6 million for the three months ended March 31, 2019 from $1.9 million for the same period in 2018. The overall increase in research and development expenses was primarily due to the increased outside service costs for clinical studies related to the development of our drug candidate, onvansertib. We expect increases in research and development costs as we advance the onvansertib clinical development programs in AML, mCRPC and mCRC.

Selling, general and administrative expenses decreased by approximately $1.0 million to $1.5 million for the three months ended March 31, 2019 from $2.5 million for the same period in 2018. The significant components of the decrease were primarily due to the reduction in salaries and staff costs and stock-based compensation.

The weighted average diluted shares of common stock outstanding used to calculate per share results for the three months ended March 31, 2019 was 4.1 million.

As of March 31, 2019, Trovagene had approximately $11.3 million of cash and cash equivalents

On May 7, 2019 DURECT Corporation (Nasdaq: DRRX) reported financial results for the three months ended March 31, 2019 and provided a corporate update, including preliminary data from the ongoing DUR-928 Phase 2a alcoholic hepatitis (AH) trial (Press release, DURECT, MAY 7, 2019, https://www.prnewswire.com/news-releases/durect-corporation-announces-first-quarter-2019-financial-results-and-update-of-programs-300845760.html [SID1234535857]).

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Total revenues were $4.1million and net loss was $7.1million for the three months ended March 31, 2019 as compared to total revenues of $3.5 million and net loss of $8.3 million for the three months ended March 31, 2018.
At March 31, 2019, cash and investments were $28.8 million, compared to cash and investments of $34.5 million at December 31, 2018. Debt at March 31, 2019, including partial accrual for the final payment of our term loan, was $20.7 million.
"Several important development milestones were achieved during the first quarter, including achieving impressive preliminary data in the ongoing AH trial and initiating dosing in the NASH and psoriasis clinical trials. We also made progress toward filing a response to the POSIMIR CRL and strengthened our board with the addition of two new members who bring valuable experience and perspective." stated James E. Brown, D.V.M., President and CEO of DURECT. "Thanks to the progress made during the quarter, we have four potential major catalysts ahead of us this year: additional AH data, readouts from the NASH and psoriasis DUR-928 clincal trials, and a potential approval for POSIMIR if our filing strategy is successful."

Update on Selected Programs and Transactions:

Epigenetic Regulator Program. DUR-928, the lead product candidate in the Company’s Epigenetic Regulator Program, is an endogenous, first-in-class small molecule, which may have broad applicability in chronic liver diseases such as NASH, in acute organ injuries such as AH and acute kidney injury (AKI), and in inflammatory skin disorders such as psoriasis and atopic dermatitis.

Clinical Trials

Alcoholic Hepatitis (AH)

Preliminary Data
Ten patients have completed dosing with DUR-928 to date in the ongoing Phase 2a open label, dose-escalation, multi-center U.S. trial. Eight patients (4 moderate and 4 severe) have been treated with DUR-98 at the 30 mg dose, and two patients (1 moderate and 1 severe) at the 90 mg dose.
Lille scores are used in clinical practice to help determine the prognosis for AH patients after 7 days of treatment. Patients with a Lille score below 0.45 have an 85% 6-month survival rate vs. those with Lille scores of above 0.45, who have a 25% 6-month survival rate (Louvet A et al. Hepatology 2007; 45: 1348-54). In another study looking at 28-day survival rates in severe AH patients, a Lille score of ≤0.16 is associated with a 91% 28-day survival rate; a Lille score of 0.16-0.56, 79% 28-day survival rate and a Lille score of ≥0.56 is associated with a 53% 28-day survival rate. (Mathurin, et. al., Gut 2011;60:255-260). The lower the Lille score, the better the prognosis is for the AH patient. Of the 10 AH patients dosed to date with DUR-928, one patient did not return for the day 7 visit, so Lille scores could only be calculated for 9 of 10 patients. In the 9 patients with Lille scores treated with DUR-928, the median Lille score is 0.04, with a range of 0.01 to 0.19.
Model of End-Stage Liver Disease (MELD) score is another common scoring system used to assess the severity and prognosis of AH patients. Patients with initial MELD scores of 11-19 are classified as having moderate AH and patients with initial MELD scores of 20-30 are classified as having severe AH. As with Lille scores, the lower the MELD score, the better the prognosis for the AH patient. Compared to baseline (prior to treatment) (n=10), the median reduction in MELD was 4% at Day 7 (n=9) and 21% at Day 28 (n=8).
Bilirubin is formed by the breakdown of red blood cells in the body. The level of total bilirubin in the blood is an indication of how well the liver is functioning. Compared to baseline (n=10), the median reduction in total bilirubin was 16% at Day 7 (n=9) and 41% at Day 28 (n=8).
A more detailed description of the preliminary data from the DUR-928 AH study is provided in a separate press release today and will be presented during the KOL and earnings call tomorrow at 8:30 a.m. ET.
About the trial
DURECT is conducting a Phase 2a clinical trial with intravenously administered DUR-928 in patients with AH. This is an open label, dose escalation (30, 90 and 150 mg), multi-center U.S. study, that includes patients with moderate and severe AH (as determined by initial MELD score). Dose escalation may occur following review of safety and pharmacokinetic (PK) results of the prior dose level by a Dose Escalation Committee (DEC). The target number of patients for the study is 4 per dose group. The objectives of this study include assessment of safety, PK and pharmacodynamic (PD) signals, including liver chemistry, and biomarkers.
After completing the low-dose 30 mg cohort (n=4) in moderate AH patients, the DEC approved commencement of the 90 mg cohort in moderate AH patients while simultaneously commencing recruitment of severe AH patients with the 30 mg dose.
Enrollment of severe AH patients has been more rapid than that of moderate patients. Upon completion the 30 mg cohort (n=4) in severe AH patients, the DEC approved advancement to the 90 mg dosing in severe AH patients. We are now enrolling both moderate and severe AH patients for the 90 mg cohorts.
Additional information on the trial design, including eligibility criteria and site locations, can be found at www.clinicaltrials.gov using the NCT Identifier NCT03432260.
In parallel with our ongoing trial, we are supporting Professor Craig McClain, MD (Chief of Research Affairs, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville) in his efforts to initiate an NIH-funded study of DUR-928 in AH patients at the University of Louisville.
AH is a syndrome of progressive inflammatory liver injury associated with long-term heavy intake of alcohol, and encompasses a spectrum that ranges from mild injury to severe, life threatening liver damage. The prevalence of AH is estimated to occur in 10-35% of heavy drinkers. According to an article in the Journal of Clinical Gastroenterology (2015 July; 49(6):506-511), there were over 320,000 hospitalizations related to alcoholic hepatitis in the U.S. in 2010, resulting in hospitalization costs of nearly $50,000 per patient. The cost of a liver transplant exceeds $800,000.
Non-Alcoholic Steatohepatitis (NASH)

In March 2019 we began enrolling patients in a Phase 1b randomized and open-label clinical study being conducted in the U.S. to evaluate safety, pharmacokinetics and signals of biological activity of DUR-928 in NASH patients with stage 1-3 fibrosis. Three doses of DUR-928 (50 mg QD, 150 mg QD and 300 mg BID) will be administered orally for 28 consecutive days with approximately 20 patients per dose group for a total of approximately 60 patients in the trial.
Key endpoints include safety and pharmacokinetics (PK), clinical chemistry and biomarkers (e.g., bilirubin, lipids, liver enzymes, CK-18s, and inflammatory cytokines) as well as liver imaging (e.g., MRI-PDFF).
We expect to announce initial data from this study in the second half of 2019.
In the Company’s previous Phase 1b NASH study, reported at the European Association for the Study of the Liver (EASL) in April 2017, exploratory biomarker analysis demonstrated that a single oral dose of DUR-928 in NASH patients, at both dose levels tested (50 mg and 200 mg), resulted in statistically significant reductions from baseline of both full-length and cleaved cytokeratin-18 (CK-18), bilirubin, hsCRP and IL-18.
Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in both children and adults. It is estimated that NAFLD affects about 20% to 30% of adults and 10% of children in the United States. NASH, a more severe and progressive form of NAFLD, is one of the most common chronic liver diseases worldwide, with an estimated prevalence of more than 10% of adults in the United States, Europe, Japan and other developed countries. No drug is currently approved for NAFLD or NASH.
Psoriasis

We are conducting a Phase 2a, randomized, double-blind, vehicle-controlled proof-of-concept clinical trial, in which DUR-928 is applied topically once-daily for four weeks in patients with mild to moderate plaque psoriasis. The trial is being conducted at multiple clinical sites in the U.S. Twenty patients are planned to be enrolled to obtain approximately 15 evaluable patients. Patients serve as their own controls, applying DUR-928 to the plaque on one arm and the vehicle to a similar plaque on the other arm. After the treatment period, patients will be followed for an additional four weeks. The primary efficacy endpoint is the change in local psoriasis scores from baseline in the DUR-928-treated plaques compared to that in the vehicle-treated plaques. Additional information on the trial design, including eligibility criteria and site locations, can be found at www.clinicaltrials.gov using the NCT Identifier 03837743.
We began enrolling patients in March of 2019 and expect to announce top line data from this study in the second half of 2019.
We previously conducted an exploratory Phase 1b trial in psoriasis patients (9 evaluable patients) in Australia. The trial was randomized, double-blinded, placebo and self-controlled, using a micro-plaque assay with intralesional injections of DUR-928. The results were encouraging and warranted advancing into the current proof-of-concept trial with topically applied DUR-928. In support of the Phase 2a study, we have completed multiple non-clinical safety studies for topically applied DUR-928.
Psoriasis is an inflammatory skin disease and an immune-mediated condition that causes the body to make new skin cells in days rather than weeks. In the United States, there are about 150,000 new cases of psoriasis every year and it affects an estimated 7.5 million Americans. According to the International Federation of Psoriasis Associations (IFPA), nearly 3% of the world’s population has some form of psoriasis or about 125 million people. Psoriasis causes itchiness and irritation and may be painful. There’s no cure for psoriasis yet, but currently approved treatment can ease symptoms. Approximately 80% of patients with psoriasis have localized disease, which can be treated with topical therapies. As such, topical agents remain the mainstay of psoriasis treatment.
POSIMIR (bupivacaine extended-release solution) Post-Operative Pain Relief Depot. POSIMIR is our investigational post-operative pain relief depot that utilizes our patented SABER technology and is designed to deliver bupivacaine to provide up to 3 days of pain relief after surgery.

After a comprehensive review of the POSIMIR program in light of the issues raised by the FDA in our communications with them, including the Complete Response Letter (CRL), we are planning to submit a full response to the CRL in the second quarter of 2019. As the submission will be a response to a CRL, we expect a 6-month FDA review period.
The effort to evaluate the program, develop a strategy for filing the response, and the actual writing of key sections of the response, has been under the direction of Dr. Lee Simon, who was formerly FDA’s Division Director of Analgesic, Anti-inflammatory and Ophthalmologic Drug Products.
We believe that the completed inguinal hernia and subacromial decompression (shoulder) clinical trials support the efficacy of POSIMIR in post-operative pain and meet the requirements to be considered as adequate and well-controlled pivotal clinical trials. Both trials demonstrated a significant decrease in pain and opioid use over the 0-72 hour period following surgery as compared to placebo.
We have completed 16 clinical trials in the POSIMIR program, involving over 1,400 patients, over 850 of whom received POSIMIR with the remainder in control groups. We believe this is a sufficiently sized safety database. We believe that, with the PERSIST safety data included, we now have sufficient data to address FDA’s issues raised in the CRL and that the data package meets the requirements for FDA approval.
POSIMIR has not been approved by the FDA for marketing in the U.S. for any indication and there can be no assurance that FDA will approve the planned submission described above.
Indivior Agreement and PERSERIS. In September 2017, we entered into a patent purchase agreement with an affiliate of Indivior PLC, whereby we assigned certain of its U.S. patent rights to Indivior. This assignment may provide further intellectual property protection for PERSERIS (risperidone) extended-release injectable suspension for the treatment of schizophrenia in adults.

Under the terms of the agreement, Indivior has paid us $12.5 million upfront and a $5 million milestone based on NDA approval of PERSERIS. We also receive quarterly earn-out payments based on a single digit percentage of U.S. net sales for certain products covered by the patent rights, including PERSERIS. The patent rights include granted patents extending into at least 2026.
According to its recent press releases, Indivior has stated that:
The PERSERIS commercial launch took place in the last week of February 2019 with a field force of 50 representatives and that modest initial net revenue for Q1 2019 was consistent with their expectations.
As of February 14, 2019, payor access was at 38% and Indivior is targeting quality of access comparable with peers.
Indivior is targeting appropriate health care providers (HCPs) with high volume Long Acting Injectables (LAI) practices.
Indivior plans to focus on key differentiating product specific attributes, including the first and only once-monthly risperidone LAI, supplemental oral risperidone or loading dose not recommended, initial peak plasma concentrations achieved in 4 to 6 hours, and just one subcutaneous injection monthly.
Indivior remained confident in its peak year net revenue goal for PERSERIS of $200 to $300 million.
U.S. sales of long acting injectables to treat schizophrenia were in excess of $3 billion in 2017.
Full prescribing information for PERSERIS, including BOXED WARNING, and Medication Guide can be found at www.perseris.com.
Methydur Sustained Release Capsules (ORADUR-methylphenidate ER Capsules). In September 2018, our licensee, Orient Pharma, informed DURECT that it had obtained marketing authorization from the Ministry of Health and Welfare in Taiwan for Methydur Sustained Release Capsules. This product is indicated for the treatment of attention deficit hyperactivity disorder (ADHD) and Orient Pharma has stated that it expects to make Methydur Sustained Release Capsules commercially available in Taiwan in 2019, while seeking a partner in China and pursuing regulatory approvals in selected other countries where it has commercialization rights and a commercial presence. DURECT retains rights to North America, Europe, Japan and all other countries not specifically licensed to Orient Pharma. DURECT is entitled to receive a royalty on sales of Methydur Sustained Release Capsules by Orient Pharma. Orient Pharma has also committed to supply a portion of the commercial requirements in territories other than the United States for Methydur Sustained Release Capsules.

Earnings Conference Call
A live audio webcast of a conference call to discuss first quarter 2019 results and provide a corporate update will be broadcast live over the internet at 8:30 a.m. Eastern Time on May 8, 2019 and is available by accessing DURECT’s homepage at www.durect.com and clicking "Investors." A replay of the call will be archived on DURECT’s website under Audio Archive in the "Investors" section.

On May 7, 2019 Takeda Pharmaceutical Company Limited [TSE: 4502 / NYSE: TAK] reported that it will present a total of five company-sponsored poster presentations, as well as an oral pipeline symposium, at the 15th International Symposium on Myelodysplastic Syndromes taking place in Copenhagen, Denmark from May 8-11, 2019 (Press release, Takeda, MAY 7, 2019, View Source [SID1234535855]). Takeda’s presentations will highlight the company’s investigations into the epidemiology, prognosis and patient reported outcomes for higher-risk myelodysplastic syndromes (HR-MDS) and the related conditions – chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) – to achieve a deep understanding of these rare cancers and the needs of this patient community.

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"We are excited to join the MDS community at this upcoming meeting where we will share key findings around Takeda’s research in HR-MDS, CMML and AML," said Hui Huang, PhD, Head, Oncology Global Outcomes Research at Takeda. "For over a decade, there has been little advancement in treatment options for people living with HR-MDS and CMML, despite poor patient outcomes. Takeda’s investment in this wide-ranging global outcomes research directly captures patient input to better understand these cancers, as well as AML, and the impact on their lives. These findings are an important aspect of our work as we strive to bring new treatment options to patients."

At this year’s International Symposium on Myelodysplastic Syndromes, Takeda will present results from a variety of innovative research studies. These results are the first global systematic review of HR-MDS and CMML on incidence and prevalence, including the risk of transformation to AML. The results will also quantify the disease burden, discuss the difficulties associated with diagnosis and underscore the significant unmet need of this patient population. Some of this research was conducted in collaboration with the MDS Foundation – an international non-profit advocacy organization whose mission is to support and educate patients and healthcare providers with innovative research into the fields of MDS, AML and related myeloid neoplasms.

Five Takeda Oncology-sponsored abstracts were accepted for poster presentation, as well as an oral pipeline symposium during MDS 2019:

Note: All times listed are in Central European Standard Time

Understanding and Measuring Fatigue In Higher-Risk Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, and Acute Myeloid Leukemia: Mixed Method Research. Abstract MDS19-0051. Wednesday, May 8, 1:00 p.m. – 9:30 p.m. (Tivoli Conference Center, Room Vandsalen).
Epidemiology of Chronic Myelomonocytic Leukemia: A Systematic Review. Abstract MDS19-0038. Wednesday, May 8, 1:00 p.m. – 9:30 p.m. (Tivoli Conference Center, Room Vandsalen).
Is Contemporary Incidence Estimation of Higher-Risk Myelodysplastic Syndrome Possible? Results From a Systematic Literature Review. Abstract MDS19-0037. Wednesday, May 8, 1:00 p.m. – 9:30 p.m. (Tivoli Conference Center, Room Vandsalen).
Identification of the Most Suitable Patient-Reported Outcomes Measure for Trials in Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, and Acute Myeloid Leukemia. Abstract MDS19-0052. Wednesday, May 8, 1:00 p.m. – 9:30 p.m. (Tivoli Conference Center, Room Vandsalen).
Characteristics of Untreated Patients with Higher-Risk Myelodysplastic Syndromes (HR-MDS) Identified in a United States (US) Electronic Medical Record (EMR) Database. Abstract MDS19-0035. Wednesday, May 8, 1:00 p.m. – 9:30 p.m. (Tivoli Conference Center, Room Vandsalen).
A Pragmatic Patient-Reported Outcome Strategy for Rare Disease Clinical Trials: Application of the EORTC Item Library. Oral Symposium Presentation. Thursday, May 9, 11:45 a.m. – 12:45 p.m. (Tivoli Congress Hall).
For more information, the MDS 2019 program is available here: View Source

About Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia and Acute Myeloid Leukemia

Myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) are rare forms of blood cancer that are caused by irregular blood cell production within the bone marrow. As a result of this irregular production, a person with MDS, CMML or AML does not have enough normal red blood cells, white blood cells and/or platelets in circulation. Symptoms for MDS, CMML and AML are often vague and related to low blood counts, and may include fatigue, shortness of breath, easy bruising or bleeding, loss of appetite, weakness, pale skin, fever and frequent or severe infections.

There are several classifications of MDS – lower risk to higher-risk – determined by blood counts, blast counts, mutations and cytogenetics. Higher-risk disease is defined as intermediate, high or very high risk on the International Prognostic Scoring System – Revised (IPSS-R), and these patients often have a poorer prognosis. In some cases, MDS and CMML can progress into AML.

On May 7, 2019 Clover Biopharmaceuticals, a biotechnology company focused on developing novel and transformative biologic therapies, reported it has received Clinical Trial Application (CTA) approval from the Chinese National Medical Products Administration (NMPA) to conduct clinical trials in China with SCB-313, an investigational fully-human TRAIL-Trimer fusion protein, for the treatment of cancer patients with intracavitary malignancies (Press release, Clover Biopharmaceuticals, MAY 7, 2019, View Source [SID1234535854]). A phase I clinical trial for malignant ascites is planned to initiate in China this year.

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"We are delighted to receive this clearance, as it further validates Clover’s innovative and proprietary Trimer-Tag© technology, in-house R&D capabilities and biomanufacturing expertise," said Dr. Peng Liang, co-founder, Chairman and President of Clover. "We are extremely excited to initiate clinical trials for SCB-313 in China. The treatment of malignant ascites remains a high unmet need globally, with no targeted or biologic antitumor therapies currently approved and available, and we hope that SCB-313 will provide a safe and efficacious option for patients in China and worldwide."

"We believe that SCB-313 has the potential to be a first-in-class and best-in-class TRAIL-based therapy based on our preclinical results to date. TRAIL has long been considered a tantalizing target for cancer therapy because it can induce apoptosis in a tumor-specific manner across many different tumor types. SCB-313, which utilizes our proprietary Trimer-Tag© technology, is able to potently and uniquely target this trimerization-dependent pathway."

On May 7, 2019 Syros Pharmaceuticals (NASDAQ: SYRS), a leader in the development of medicines that control the expression of genes, reported the online publication of a new manuscript, Discovery and Characterization of SY-1365, a Selective, Covalent Inhibitor of CDK7, in the American Association for Cancer Research (AACR) (Free AACR Whitepaper)’s (AACR) (Free AACR Whitepaper) journal, Cancer Research (Press release, Syros Pharmaceuticals, MAY 7, 2019, View Source [SID1234535853]). SY-1365, a first-in-class selective cyclin-dependent kinase 7 (CDK7) inhibitor, is currently being investigated in a Phase 1 clinical trial as a single agent and in combination with standard-of-care therapies in multiple ovarian and breast cancer patient populations that lack effective treatment options. This publication highlights the discovery, mechanism of action and promise of SY-1365 as a new targeted approach for a range of difficult-to-treat cancers.

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"SY-1365 represents a potentially transformative targeted approach for a number of cancers that have eluded treatment with existing approaches," said Eric R. Olson, Ph.D., Syros’ Chief Scientific Officer. "While CDK7 has long been a target of interest, it was historically difficult-to-drug. This new publication profiles our work in discovering SY-1365, which we believe to be the most advanced selective CDK7 inhibitor in clinical development, and the substantial anti-tumor activity seen in preclinical models that supported its advancement into the clinic. We are excited by the promise of CDK7 inhibition and the potential benefit SY-1365 may bring to patients who are in dire need of better therapies."

Syros is currently conducting a Phase 1 clinical trial assessing the safety and efficacy of SY-1365 as a single agent and in combination with standard-of-care therapies in multiple ovarian and breast cancer patient populations. The trial includes cohorts evaluating SY-1365 as a single agent in patients with relapsed ovarian clear cell cancer and in high-grade serous ovarian cancer (HGSOC) patients who have had three or more prior lines of therapy; in combination with carboplatin in HGSOC patients who have had one or more prior lines of therapy; in combination with fulvestrant in metastatic hormone receptor-positive breast cancer patients who are resistant to treatment with a CDK4/6 inhibitor; and as a single agent in patients with solid tumors of any histology accessible for biopsy. Additional details about the trial can be found using the identifier NCT03134638 at www.clinicaltrials.gov.

CDK7 plays a key role in the transcription of genes and in cell cycle regulation, and inhibiting CDK7 disrupts two important processes that cancer cells use to survive: 1) expression of cancer-promoting genes; and 2) uncontrolled cell cycle progression. SY-1365 has shown anti-tumor activity in preclinical models of a range of solid tumors and blood cancers, including cancers that have become resistant to treatment with existing therapies or where existing options have failed to provide meaningful benefit to patients. Further, data suggests that SY-1365 works to inhibit the growth of cell lines representing many different cancer types at nanomolar concentrations, decreases MCL1 protein levels, and demonstrates activity among cancer cells with low BCL-XL expression.

Building on its leadership in CDK7 inhibition, Syros is advancing SY-5609, a highly selective and potent oral CDK7 inhibitor, toward clinical development. In preclinical studies, SY-5609 has demonstrated substantial anti-tumor activity, including inducing complete regressions in cell line-derived xenograft models of breast and ovarian cancers. The company plans to complete investigational new drug application (IND)-enabling studies by the end of 2019 to support the initiation of a Phase 1 oncology trial in early 2020.