On February 8, 2018 Rexahn Pharmaceuticals, Inc. (NYSE American: RNN), a clinical stage biopharmaceutical company developing innovative, targeted therapeutics for the treatment of cancer, reported that it has entered into a collaboration and license agreement with Zhejiang Haichang Biotechnology Co., Ltd. (Haichang), to develop RX-0201 (Archexin) for the treatment of hepatocellular carcinoma (HCC), the most common form of liver cancer (Press release, Rexahn, FEB 8, 2018, View Source [SID1234523867]).

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Under the terms of the agreement, Haichang will develop a nano-liposomal formulation of RX-0201 using its proprietary QTsome technology and conduct certain pre-clinical and clinical activities through completion of a Phase IIa proof-of-concept clinical trial for the treatment of HCC. Any clinical trials conducted by Haichang will be designed to meet both U.S. and Chinese regulatory requirements. Haichang will fund all research and development activities through completion of the Phase IIa clinical trial.

The parties will share in an agreed ratio downstream licensing fees and royalties paid by third parties in connection with the further development and commercialization of the nano-liposomal formulation of RX-0201 for the treatment of HCC.

"We are delighted to enter into this collaboration to take RX-0201 forward in hepatocellular carcinoma," said Peter D. Suzdak, Ph.D., Chief Executive Officer of Rexahn. "We are impressed with Haichang’s QTsometechnology. It has the potential to target RX-0201 to the liver and to promote uptake into cancer cells to enhance efficacy. We are also very pleased to have non-dilutive funding to take the program through Phase IIa proof-of-concept studies."

"The incidence of liver cancer is growing worldwide, and especially in Asia," said Dr. Ben Zhao, Chief Executive Officer of Haichang. "There are very few treatment options for patients and unfortunately, the prognosis for patients with advanced disease is very poor. Akt-1 is an important signaling protein in liver cancer and we are excited about the potential for RX-0201. It is an ideal candidate for our liposomal technology and we look forward to advancing the development of RX-0201 in collaboration with Rexahn."

"While we continue to be encouraged by the safety and efficacy of RX-0201, the treatment landscape for metastatic renal cell carcinoma (mRCC) has significantly changed over the past two years with the approval of three new therapies by the FDA. This will limit the commercial viability of RX-0201 in mRCC. For this reason, Rexahn has decided to stop the development of RX-0201 for mRCC," said Lisa Nolan, Ph.D., Chief Business Officer for Rexahn. "The Haichang collaboration allows Rexahn to capitalize on the clinical data already generated in Phase I and Phase II clinical studies and change the focus of the RX-0201 program to hepatocellular carcinoma using non-dilutive funding to take the program through Phase IIa proof-of-concept studies while retaining the potential for future milestones/royalties for the product. This will also allow Rexahn to focus its own resources on progressing RX-3117 and Supinoxin (RX-5902) through Phase II clinical development."

In connection with the agreement with Haichang, Rexahn plans to discontinue the internally funded programs of Archexin and will cease enrollment in the current Phase IIa clinical study of Archexin in metastatic renal cell carcinoma (mRCC). Patients currently enrolled in the trial will continue to be followed

About Hepatocellular Carcinoma

Hepatocellular carcinoma (liver cancer) is the sixth most common type of cancer worldwide and the second-leading cause of cancer-related deaths. Each year approximately 780,000 new cases of liver cancer are diagnosed worldwide and over 740,000 people will die of the disease.1 The incidence of liver cancer in the U.S. has more than tripled since 1980.2 It is estimated that there will be approximately 41,000 new cases of liver and intrahepatic bile duct cancer and 29,000 deaths from these diseases in the U.S. in 2017.3 The majority of these cases are caused by Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infections. The increasing prevalence of metabolic syndrome and nonalcoholic steatohepatitis (NASH) is expected to contribute to increased rates of liver cancer in the U.S. in the foreseeable future.4 Outside the U.S., the incidence of liver cancer is approximately 40,000 in Europe and 36,000 Japan. Incidence is particularly high in China due to the prevalence of HBV and HCV infections and the incidence is estimated at 260,000 in 2017.

Treatment options are limited for patients with advanced liver cancer, which account for approximately 30% of newly diagnosed patients. Nexavar (sorafenib) is approved for first line treatment. Supportive care is the standard of care for second line treatment. Opdivo (nivolumab) has recently been approved for patients who have disease progression after treatment with Nexavar, but only 14% of patients respond to treatment. Overall, the prognosis for patients with advanced liver cancer is typically very poor.

About Zhejiang Haichang Biotechnology Co. Ltd

Zhejiang Haichang Biotechnology Co., Ltd. is a privately owned specialized biotechnology company headquartered in Hangzhou, China. The company is focused on the development and manufacture of complex intravenous pharmaceutical products including liposome and microsphere products, primarily for cancer treatment. The company has strategic collaborations with Sinopharm and and its liposomal doxorubicin product (Libaoduo) is marketed by Shanghai Fudan-Zhangjiang Bio-pharm Co., Ltd in China.

Haichang’s QTsome technology is a patented gene delivery technology that was co-developed with Professor Robert Lee at the Ohio State University. The technology is designed to enhance cellular uptake of large molecules such as oligonucleotides (antisense, siRNA and miRNA) and to target certain organs such as the liver where nanoparticles accumulate.

About RX-0201 (Archexin)

RX-0201 is an antisense oligonucleotide compound that is complementary to Akt-1 mRNA and highly selective for inhibiting its mRNA expression, which leads to reduced production of Akt-1. Akt-1 is a protein that is associated with cancer cell growth and proliferation and the development of resistance to certain anticancer agents. Akt-1 is over-expressed in multiple forms of cancer including hepatic, renal, breast, colorectal, gastric, pancreatic, prostate and melanoma. In a Phase I clinical trial in patients with advanced cancers, RX-0201 appears to be safe and well tolerated with minimal side effects. The dose-limiting adverse event in such clinical trial was Grade 3 fatigue with no significant hematological abnormalities observed.

On February 8, 2018 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that the U.S. Food and Drug Administration (FDA) has approved a new indication for ZYTIGA (abiraterone acetate) in combination with prednisone for the treatment of patients with metastatic high-risk castration-sensitive prostate cancer (CSPC) (Press release, Johnson & Johnson, FEB 8, 2018, View Source [SID1234523841]). The approval is based on Phase 3 data from the pivotal LATITUDE clinical trial, which found that in patients with metastatic high-risk CSPC, ZYTIGA in combination with prednisone reduced the risk of death by 38 percent compared to placebos.

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"LATITUDE was a large global trial which produced impressive and clinically significant results in overall survival," said Karim Fizazi, M.D., Ph.D., Principal Investigator and Head of the Medical Oncology Department at Institute Gustave Roussy, Villejuif, France. "With today’s approval, abiraterone acetate plus prednisone could become a standard of care for patients with metastatic high-risk castration-sensitive prostate cancer."

"Today’s approval marks an important step in addressing the unmet needs of patients with metastatic high-risk castration-sensitive prostate cancer by providing an option that has demonstrated improvement in overall survival," said Andree Amelsberg, M.D., Vice President of Oncology Medical Affairs at Janssen Biotech, Inc., part of the Janssen Pharmaceutical Companies of Johnson & Johnson. "This milestone is an exciting turning point for researchers and clinicians, and most importantly, for patients suffering from this disease and their families who now have an important additional therapeutic option."

LATITUDE was a multinational, multicenter, randomized, double-blind, placebo-controlled clinical trial that examined the use of ZYTIGA 1,000 mg once daily in combination with prednisone 5 mg once daily, compared to placebos (N=1,199) in patients with newly diagnosed, metastatic high-risk CSPC, who had not received prior cytotoxic chemotherapy. All the patients received a gonadotropin-releasing hormone (GnRH) analog or had prior bilateral orchiectomy. The study data were presented at the plenary session of the 2017 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, and simultaneously published in The New England Journal of Medicine.1 The study showed ZYTIGA in combination with prednisone reduced the risk of death by 38 percent compared to placebos (median OS not estimable vs. 34.7 months, respectively; hazard ratio (HR)=0.62; 95% confidence interval (CI): [0.51, 0.76], p<0.0001). Additional data demonstrated statistically significant delay in time to initiation of chemotherapy for patients in the ZYTIGA arm compared to those in the placebo arm (median time to initiation of chemotherapy not reached vs. 38.9 months, respectively; HR=0.44; 95% CI: [0.35, 0.56], p < 0.0001).

The most common adverse reactions (≥10%) that occurred more commonly (>2%) in the ZYTIGA arm from an analysis of pooled safety data were fatigue, arthralgia, hypertension, nausea, edema, hypokalemia, hot flush, diarrhea, vomiting, upper respiratory infection, cough and headache.

On November 20, 2017, the European Commission (EC) granted approval to broaden the marketing authorization for ZYTIGA in combination with prednisone or prednisolone to include newly-diagnosed high-risk metastatic hormone-sensitive prostate cancer (HSPC). Similar submissions have been made in Japan, Canada, Mexico, Switzerland, Singapore, and the Philippines, and approved in Brazil and Taiwan. If approved, these submissions will broaden the use of ZYTIGA in combination with prednisone or prednisolone to include an earlier stage of prostate cancer than its current indications.

Metastatic prostate cancer is cancer that has spread to another part of the body.2 Metastatic castration-sensitive prostate cancer (CSPC), also referred to as metastatic hormone-sensitive prostate cancer (HSPC) in literature, refers to prostate cancer that still responds to testosterone suppression therapy.2 Patients with newly-diagnosed metastatic disease and high-risk disease characteristics tend to have a poorer prognosis.3

About the LATITUDE Clinical Trial4
The Phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled LATITUDE study enrolled 1,199 patients with newly diagnosed metastatic, high-risk castration-sensitive prostate cancer (CSPC), who had not received prior cytotoxic chemotherapy. The study was conducted at 235 sites in 34 countries in Europe, Asia-Pacific, Latin America, and Canada. A total number of 597 patients were randomized to receive ZYTIGA plus prednisone, while 602 patients were randomized to receive placebos. All patients received a gonadotropin-releasing hormone (GnRH) analog or had prior bilateral orchiectomy. High-risk disease was defined as having at least two of three risk factors at baseline: a total Gleason score of ≥8, presence of ≥3 lesions on bone scan, and evidence of measurable visceral metastases. Patients with significant cardiac, adrenal, or hepatic dysfunction were excluded. The median duration of treatment with ZYTIGA and prednisone was 24 months.

About ZYTIGA

ZYTIGA (abiraterone acetate) in combination with prednisone is indicated for the treatment of patients

with metastatic castration-resistant prostate cancer (CRPC)
with metastatic high-risk castration-sensitive prostate cancer (CSPC)
Since its first approval in the U.S. in 2011, ZYTIGA has been approved in combination with prednisone or prednisolone, in 105 countries. More than 330,000 patients worldwide, including 113,000 in the U.S., have received treatment with it, and it was the number one prescribed oral medication in the U.S. for patients with metastatic CRPC in 2016.

For more information about ZYTIGA, visit www.ZYTIGA.com.

IMPORTANT SAFETY INFORMATION

Contraindications – ZYTIGA (abiraterone acetate) can cause fetal harm and potential loss of pregnancy.

Hypertension, Hypokalemia and Fluid Retention Due to Mineralocorticoid Excess – ZYTIGA may cause hypertension, hypokalemia, and fluid retention as a consequence of increased mineralocorticoid levels resulting from CYP17 inhibition [see Clinical Pharmacology (12.1)]. Monitor patients for hypertension, hypokalemia, and fluid retention at least once a month. Control hypertension and correct hypokalemia before and during treatment.

Closely monitor patients whose underlying medical conditions might be compromised by increases in blood pressure, hypokalemia or fluid retention, such as those with heart failure, recent myocardial infarction, cardiovascular disease, or ventricular arrhythmia. The safety of ZYTIGA in patients with left ventricular ejection fraction <50% or New York Heart Association (NYHA) Class III or IV heart failure (in COU-AA-301) or NYHA Class II to IV heart failure (in COU-AA-302 and LATITUDE) has not been established because these patients were excluded from these randomized clinical trials [see Clinical Studies (14)].

Adrenocortical Insufficiency (AI) – AI was reported in patients receiving ZYTIGA in combination with prednisone, after an interruption of daily steroids and/or with concurrent infection or stress. Monitor patients for symptoms and signs of AI if prednisone is stopped or withdrawn, if prednisone dose is reduced, or if the patient experiences unusual stress. Symptoms and signs of AI may be masked by adverse reactions associated with mineralocorticoid excess seen in patients treated with ZYTIGA. Perform appropriate tests, if indicated, to confirm AI. Increased dosages of corticosteroids may be used before, during, and after stressful situations.

Hepatotoxicity – In postmarketing experience, there have been ZYTIGA-associated severe hepatic toxicities, including fulminant hepatitis, acute liver failure and deaths. Measure serum transaminases alanine aminotransferase (ALT and AST) and bilirubin levels prior to starting treatment with ZYTIGA, every two weeks for the first three months of treatment, and monthly thereafter. In patients with baseline moderate hepatic impairment receiving a reduced ZYTIGA dose of 250 mg, measure ALT, AST, and bilirubin prior to the start of treatment, every week for the first month, every two weeks for the following two months of treatment and monthly thereafter. Promptly measure serum total bilirubin, AST, and ALT if clinical symptoms or signs suggestive of hepatotoxicity develop. Elevations of AST, ALT, or bilirubin from the patient’s baseline should prompt more frequent monitoring. If at any time AST or ALT rise above five times the upper limit of normal (ULN) or the bilirubin rises above three times the ULN, interrupt ZYTIGA treatment and closely monitor liver function. Re-treatment with ZYTIGA at a reduced dose level may take place only after return of liver function tests to the patient’s baseline or to AST and ALT less than or equal to 2.5X ULN and total bilirubin less than or equal to 1.5X ULN [See Dosage and Administration (2.4)].

Permanently discontinue ZYTIGA for patients who develop a concurrent elevation of ALT greater than 3X ULN and total bilirubin greater than 2X ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation.

The safety of ZYTIGA re-treatment of patients who develop AST or ALT greater than or equal to 20X ULN and/or bilirubin greater than or equal to 10X ULN is unknown.

Adverse Reactions – The most common adverse reactions (≥10%) are fatigue, arthralgia, hypertension, nausea, edema, hypokalemia, hot flush, diarrhea, vomiting, upper respiratory tract infection, cough, and headache.

The most common laboratory abnormalities (>20%) are anemia, elevated alkaline phosphatase, hypertriglyceridemia, lymphopenia, hypercholesterolemia, hyperglycemia and hypokalemia.

Drug Interactions – Based on in vitro data, ZYTIGA is a substrate of CYP3A4. In a drug interaction trial, co-administration of rifampin, a strong CYP3A4 inducer, decreased exposure of abiraterone by 55%. Avoid concomitant strong CYP3A4 inducers during ZYTIGA treatment. If a strong CYP3A4 inducer must be co-administered, increase the ZYTIGA dosing frequency only during the co-administration period [see Dosage and Administration (2.3)]. In a dedicated drug interaction trial, co-administration of ketoconazole, a strong inhibitor of CYP3A4, had no clinically meaningful effect on the pharmacokinetics of abiraterone.

ZYTIGA is an inhibitor of the hepatic drug-metabolizing enzymes CYP2D6 and CYP2C8. Avoid co-administration with CYP2D6 substrates with a narrow therapeutic index. If alternative treatments cannot be used, consider a dose reduction of the CYP2D6 substrate drug. In a CYP2C8 drug interaction trial in healthy subjects, the AUC of pioglitazone, a CYP2C8 substrate, was increased by 46% when administered with a single dose of ZYTIGA. Patients should be monitored closely for signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic index if used concomitantly with ZYTIGA.

Use in Specific Populations

Females and Males of Reproductive Potential: Advise males with female partners of reproductive potential to use effective contraception.
Do not use ZYTIGA in patients with baseline severe hepatic impairment (Child-Pugh Class C).

On February 8, 2018 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that the National Comprehensive Cancer Network (NCCN) added Vyxeos (daunorubicin and cytarabine) liposome for injection to the Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Acute Myeloid Leukemia (AML) (Press release, Jazz Pharmaceuticals, FEB 8, 2018, View Source;p=RssLanding&cat=news&id=2331464 [SID1234523839]).

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The United States Food and Drug Administration (FDA) approved Vyxeos on August 3, 2017 for the treatment of adults with two types of AML, a rapidly progressing and life-threatening blood cancer. Vyxeos is the first FDA-approved treatment specifically for adults with newly-diagnosed Therapy-Related AML (t-AML) or AML with Myelodysplasia-Related Changes (AML-MRC). Based on the data from the pivotal Phase 3 randomized trial of Vyxeos versus the standard of care, the NCCN Guidelines now include a Category 1 recommendation for use of Vyxeos for adult patients 60 years of age or greater with newly-diagnosed t-AML or AML-MRC. The Category 1 recommendation indicates that based upon high-level evidence, there is uniform NCCN consensus that Vyxeos is appropriate for these patients.

"We appreciate the decision by the NCCN to incorporate Vyxeos into the Clinical Practice Guidelines in Oncology as it supports our commitment to ensuring that patients, through their health care professionals, are able to access this important new treatment option," said Karen Smith, M.D., Ph.D., executive vice president of research and development and chief medical officer of Jazz Pharmaceuticals. "Vyxeos is the first chemotherapy advance for adults with newly-diagnosed t-AML or AML-MRC in more than 40 years."

The NCCN, a not-for-profit alliance of 27 leading U.S. cancer centers devoted to patient care, research, and education, is dedicated to improving the quality, effectiveness, and efficiency of cancer care. The intent of the NCCN Guidelines is to assist in the decision-making process of individuals involved in cancer care—including physicians, nurses, pharmacists, payers, patients and their families—with the ultimate goal of improving patient care and outcomes.

About VyxeosTM

Vyxeos (daunorubicin and cytarabine) liposome for injection 44mg/100mg is a liposome formulation of a fixed combination of daunorubicin and cytarabine for intravenous infusion.1 Vyxeos is indicated for the treatment of adults with newly-diagnosed t-AML or AML-MRC. For more information about Vyxeos in the United States, please visit View Source

Important Safety Information

Vyxeos has different dosage recommendations from other medications that contain daunorubicin and/or cytarabine. Do not substitute Vyxeos for other daunorubicin- and/or cytarabine- containing products.

Vyxeos should not be given to patients who have a history of serious allergic reaction to daunorubicin, cytarabine or any of its ingredients.

Vyxeos can cause a severe decrease in blood cells (red and white blood cells and cells that prevent bleeding, called platelets) which can result in serious infection or bleeding and possibly lead to death. Your doctor will monitor your blood counts during treatment with Vyxeos. Patients should tell the doctor about new onset fever or symptoms of infection or if they notice signs of bruising or bleeding.

Vyxeos can cause heart-related side effects. Tell your doctor about any history of heart disease, radiation to the chest, or previous chemotherapy. Inform your doctor if you develop symptoms of heart failure such as:

shortness of breath or trouble breathing
swelling or fluid retention, especially in the feet, ankles or legs
unusual tiredness
Vyxeos may cause allergic reactions including anaphylaxis. Seek immediate medical attention if you develop signs and symptoms of anaphylaxis such as:

trouble breathing
severe itching
skin rash or hives
swelling of the face, lips, mouth, or tongue
Vyxeos contains copper and may cause copper overload in patients with Wilson’s disease or other copper-processing disorders.

Vyxeos can damage the skin if it leaks out of the vein. Tell your doctor right away if you experience symptoms of burning, stinging, or blisters and skin sores at the injection site.

Vyxeos can harm your unborn baby. Inform your doctor if you are pregnant, planning to become pregnant, or nursing. Do not breastfeed while receiving Vyxeos. Females and males of reproductive potential should use effective contraception during treatment and for 6 months following the last dose of Vyxeos.

The most common side effects were bleeding events, fever, rash, swelling, nausea, sores in the mouth or throat, diarrhea, constipation, muscle pain, tiredness, stomach pain, difficulty breathing, headache, cough, decreased appetite, irregular heartbeat, pneumonia, blood infection, chills, sleep disorders, and vomiting.

Please see full Prescribing Information for Vyxeos before prescribing: View Source

About AML

Acute myeloid leukemia (AML) is a blood cancer that begins in the bone marrow, which produces most of the body’s new blood cells.2 AML cells crowd out healthy cells and move aggressively into the bloodstream to spread cancer to other parts of the body.3 AML is a relatively rare disease representing 1.3 percent of all new cancer cases.4 It is estimated that more than 21,000 people will be diagnosed with AML in the United States this year with the potential for nearly 11,000 people to die from the disease.5 The median age at diagnosis is 68 years old,4 with rising age associated with a progressively worsening prognosis.6 There is also a reduced tolerance for intensive chemotherapy as patients age.7 AML has the lowest survival rate of any other form of leukemia.4 Patients with newly diagnosed t-AML or AML-MRC may have a particularly poor prognosis.8-10 A hematopoietic stem cell transplant (HSCT) may be a curative treatment option for patients.11

On February 8, 2018 Innovation Pharmaceuticals Inc., (OTCQB:IPIX) ("the Company"), a clinical stage biopharmaceutical company, reported the closure of its Phase 2a clinical trial (see NCT03042702) of Kevetrin for the treatment of late-stage Ovarian Cancer (OC) (Press release, Innovation Pharmaceuticals, FEB 8, 2018, View Source [SID1234523838]). The Company initiated the trial for the purpose of demonstrating modulation of the key tumor-suppressor protein p53, which was achieved in analysis of the first patients at the lowest dose of Kevetrin (see December 27, 2017 press release).

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Throughout pre-clinical testing and two successful clinical trials, Kevetrin has demonstrated promising signs of efficacy as an anti-cancer agent and a favorable pharmacokinetic profile that includes a very short half-life and good bioavailability. It is believed that these characteristics make Kevetrin an ideal candidate for oral delivery (capsule or tablet), which will facilitate convenient and frequent dosing, perhaps even multiple times daily, to maximize the therapeutic benefit of the compound. With the positive observation of intra-tumor p53 modulation, the Company will now allocate resources to focus its efforts on completing development of an oral formulation, including performing bridging toxicology work.

The Company is adhering to a value-building strategy born from discussions with larger pharmaceutical companies interested in Kevetrin, one of the world’s most advanced p53 drug candidates. Securing the right development partner for Kevetrin remains an important objective.

"This study delivered multiple insights into how Kevetrin modulates the p53 protein and affects related molecular pathways," commented Arthur P. Bertolino, MD, PhD, MBA, President and Chief Medical Officer at Innovation Pharmaceuticals. "Moreover, if we successfully transition to oral dosing of Kevetrin, we believe the therapeutic effect will be maximized, providing important benefits to cancer patients in need—beyond the ultimate convenience of oral delivery. An effective orally-delivered p53-modulating drug has the potential to transform cancer care and we are proud to be at the forefront toward achieving this goal."

About Kevetrin and p53

Kevetrin is a small molecule that has demonstrated the potential of becoming a breakthrough cancer treatment by modulating p53, a protein frequently referred to as the "Guardian of the Genome" due to its critical role in controlling cell mutations. In the majority of cancers, and regardless of origin, type, and location, the p53 pathway is mutated, preventing the body from performing its natural anti-tumor functions. Conducted at Dana-Farber Cancer Institute and Beth Israel Deaconess Medical Center, a Phase 1 clinical trial (see NCT01664000) of Kevetrin in treating advanced solid tumors has been successfully completed, with patients showing good toleration and encouraging signs of potential therapeutic response (see ASCO (Free ASCO Whitepaper) 2015, ASCO (Free ASCO Whitepaper) 2013). Additional pre-clinical work supporting Kevetrin’s anti-cancer activity has recently been presented at scientific conferences (see EHA (Free EHA Whitepaper) 2017, AACR (Free AACR Whitepaper) 2017). The Company has initiated a Phase 2a trial of Kevetrin (see NCT03042702) in late stage, platinum-resistant/refractory ovarian cancer. Patients receive more frequent dosing (3 times per week) at higher levels and then receive standard of care treatment after trial conclusion. Efforts also are underway to develop Kevetrin as an oral anti-cancer agent that can be administered daily, potentially multiple times per day. The FDA has awarded Kevetrin Orphan Drug status for ovarian cancer, pancreatic cancer, and retinoblastoma, qualifying it for developmental incentives and a potential extra 7 years of market exclusivity upon drug approval. The FDA also has granted Kevetrin Rare Pediatric Disease designation for childhood retinoblastoma.

On February 8, 2018 GlycoMimetics, Inc. (NASDAQ: GLYC) reported that it has entered into an agreement with the Haemato Oncology Foundation for Adults in the Netherlands (HOVON) group to initiate clinical trial startup activities (Press release, GlycoMimetics, FEB 8, 2018, View Source [SID1234523836]). In the planned clinical trial, HOVON researchers will evaluate GlycoMimetics’ drug candidate, GMI-1271, in adults with newly diagnosed acute myeloid leukemia (AML) but who cannot tolerate intensive chemotherapy, as well as in patients with myelodysplastic syndrome (MDS) with a high risk of leukemia. The HOVON Central Office has already approved a protocol concept, and this agreement enables HOVON to commit staff to the planned trial in order to finalize the protocol, start regulatory and ethics reviews, and begin development of the database. Separately, GlycoMimetics said it plans to announce the design details for its company-sponsored Phase 3 trial in relapsed/refractory AML patients as part of its fourth-quarter and year-end 2017 earnings call scheduled for March 6, 2018.

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"HOVON is one of the most prestigious collaborative clinical groups in Europe and is focused exclusively on improving clinical outcomes in patients with hematologic malignancies. HOVON’s interest in evaluating GMI-1271 in patients with previously untreated AML and MDS who are unable to tolerate intensive chemotherapy underscores the importance of the efficacy and safety data we’ve generated to date in clinical trials with GMI-1271," noted Helen Thackray, M.D., FAAP, GlycoMimetics Senior Vice-President, Clinical Development and Chief Medical Officer. "We believe GMI-1271 has the potential for broad utility in the treatment of hematologic malignancies, and this trial expands the scope of development across the continuum of care in AML and complements our own planned Phase 3 registration trial in patients with relapsed/refractory disease."

Professor Gerwin Huls, Principal Investigator at HOVON and Professor of Haematology at University Medical Centre Groningen, said, "With Breakthrough Therapy designation awarded by the U.S. Food and Drug Administration in patients with relapsed/refractory AML, GMI-1271 is clearly a promising agent. We look forward to generating data in this ‘unfit’ AML population to see if GMI-1271 can improve patient outcomes over what is achieved with decitabine alone."

The HOVON trial will be the first to evaluate GMI-1271 together with decitabine in this underserved population of AML and MDS patients, who are not considered by their physicians to be candidates for intensive chemotherapy; these two populations represent a significant potential label expansion opportunity for GMI-1271. HOVON intends to enroll approximately 140 patients in the clinical trial, including a control arm. Key efficacy endpoints will include complete remission rate, disease-free survival, and overall survival. The trial is expected to start this year and will be conducted in five countries across Europe.

About GMI-1271

GMI-1271 is designed to block E-selectin (an adhesion molecule on cells in the bone marrow) from binding with blood cancer cells as a targeted approach to disrupting well-established mechanisms of leukemic cell resistance within the bone marrow microenvironment. In the Phase 1/2 clinical trial that has now completed enrollment, GMI-1271 was evaluated in both newly diagnosed elderly and relapsed/refractory patients with acute myeloid leukemia (AML). In both populations, patients treated with GMI-1271 together with standard chemotherapy achieved better than expected remission rates and overall survival based on historical controls, as well as lower than expected induction-related mortality rates. Importantly, treatment in this patient population was well tolerated with minimal adverse effects.