On May 6, 2019 Onxeo S.A. (Euronext Paris, NASDAQ Copenhagen: ONXEO), ("Onxeo" or "the Company"), a clinical-stage biotechnology company specializing in the development of innovative drugs targeting tumor DNA Damage Response (DDR) in oncology, in particular against rare or resistant cancers, reported a new milestone in the clinical development of AsiDNA with the treatment of the first patient in DRIIV-1b, a phase 1b clinical study of AsiDNA, a first-in-class tumor DNA repair inhibitor, in combination with carboplatin and with carboplatin plus paclitaxel, in patients with solid tumors eligible to such treatments (Press release, Onxeo, MAY 6, 2019, View Source [SID1234535758]).

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DRIIV-1b is an extension of the DRIIV-1 (DNA Repair Inhibitor administered IntraVenously) phase 1 study currently being completed, in which AsiDNA, administered intravenously (IV) demonstrated its intratumoral activity by inducing a significant increase in its activity biomarkers in the tumor cells of patients, with a favorable safety profile at various active doses.

At the active dose of 600 mg, among the three patients included in the cohort, two patients with relapsed, multi-treated metastatic colorectal cancer were controlled with medical imaging, which showed no further disease progression after the second treatment cycle, and continued their treatment with AsiDNA for three months. The 600 mg active dose was considered to be optimal for further development of AsiDNA in combination with chemotherapy.

DRIIV-1b aims at showing the safety and efficacy of a 600 mg dose of AsiDNA in combination with carboplatin, and carboplatin plus paclitaxel, in up to 18 patients with solid tumors eligible for such treatments (lung, breast, ovarian or head and neck cancers, …). The efficacy of the combinations will be evaluated every six to eight weeks by medical imaging in accordance with RECIST criteria (Response evaluation criteria in solid tumors). The study will take place in Belgium, and initial results are expected in the second half of 2019.

Dr Nuria Kotecki of the Institute Jules Bordet in Brussels commented: "The «DDR» (DNA Damage Response) approach represents a particularly interesting alternative in cancer treatment. Indeed, combining AsiDNA, a tumor DNA repair inhibitor, with agents such as carboplatin, that causes breaks in that same DNA, is a very promising approach in terms of synergistic efficacy. On the basis of the safety profile of AsiDNA observed in monotherapy, this combination can be considered as we are looking for greater efficacy without aggravating the toxicity observed with chemotherapy. We are thrilled to start this DRIIV-1b study, which should enable us to confirm the preclinical and clinical results already obtained."

This first combination trial represents a major milestone in the clinical development of AsiDNA. Thanks to its highly differentiated mechanism of action, confirmed by exhaustive preclinical studies, the combination of AsiDNA with various anti-cancer treatments appears especially relevant to increase their efficacy and avoid the occurrence of resistance from tumors.

DRIIV-1b is the first combination study of AsiDNA by IV administration, aimed at confirming such synergistic efficacy on tumors for which the medical needs remain immense. Positive results from this study will represent a proof of the interest of AsiDNA combined with chemotherapy and will open the door to further clinical development of AsiDNA IV in a phase 2 program in one or several indications.

Olivier de Beaumont, Onxeo’s Chief Medical Officer, concluded: "This study marks the start of the clinical development of AsiDNA in combination with chemotherapy. The results, expected by the end of the year, will enable us to confirm the potential of our flagship product in indications with strong medical needs. Other combination studies are also being prepared to further support the growing interest in AsiDNA and its broad clinical potential. We are very pleased to be continuing our collaboration with Dr Nuria Kotecki, a clinical investigator already involved in the DRIIV-1 study, and we thank her for her help and support in this promising research program."

On May 6, 2019 Onconova Therapeutics, Inc. (NASDAQ:ONTX), a Phase 3 stage biopharmaceutical company focused on discovering and developing novel small molecule drug candidates to treat cancer, with a primary focus on Myelodysplastic Syndromes (MDS), reported that five posters related to the Company’s lead product candidate, rigosertib, were accepted for presentation at the 15th International Symposium on Myelodysplastic Syndromes taking place May 8-11, 2019 at the Tivoli Hotel & Congress Center in Copenhagen, Denmark (Press release, Onconova, MAY 6, 2019, View Source [SID1234535757]).

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Dr. Ric Woodman, CMO of Onconova, will be attending the Symposium and available to meet with interested parties.

DETAILS OF THE POSTERS:

1) PHASE II STUDY OF ORAL RIGOSERTIB COMBINED WITH AZACITIDINE IN PATIENTS WITH HIGHER-RISK MYELODYSPLASTIC SYNDROMES (MDS)
Abstract: MDS19-0216
May 8 – May 11, Room Vandsalen
Presenter: Lewis R. Silverman, MD
Tisch Cancer Institute, Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New York, NY

2) RIGOSERTIB /AZACITIDINE MODULATES INNATE IMMUNE SIGNALING AND HEMATOPOIETIC GENE PATHWAYS WHEN SEQUENCED IN VITRO, IN THE MYELODYSPLASTIC SYNDROME (MDS)
Abstract: MDS19-0201
May 8 – May 11, Room Vandsalen
Presenter: Lewis R. Silverman, MD
Tisch Cancer Institute, Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New York, NY

3) EMERGENCE OF PTPN11 MUTATIONS IS ASSOCIATED WITH CLINICAL RESISTANCE TO RIGOSERTIB AND AZACITIDINE IN PATIENTS WITH MYELODYSPLASTIC SYNDROME (MDS)
Abstract: MDS19-0195
May 8 – May 11, Room Vandsalen
Presenter: Lewis R. Silverman, MD
Tisch Cancer Institute, Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New York, NY

4) UTILITY OF ADAPTIVE TRIAL DESIGN IN HIGHER-RISK MYELODYSPLASTIC (HR-MDS) SYNDROMES IN A PHASE 3 TRIAL OF INTRAVENOUS RIGOSERTIB: INSPIRE TRIAL
Abstract: MDS19-0211
May 8 – May 11, Room Vandsalen
Presenter: Aref Al-Kali, MD
Mayo Clinic, Hematology, Rochester, MN

5) EX VIVO RESPONSE PROFILING OF RIGOSERTIB IDENTIFIES DISTINCT CLASSES OF RESPONDERS IN ELODYSPLASTIC SYNDROME
Abstract: MDS19-0200
Presenter: Marianne Santaguida, PhD, Director of Scientific Partnerships
Notable Labs, Foster City, CA

About Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are conditions that can occur when the blood-forming cells in the bone marrow become dysfunctional and thus produce an inadequate number of circulating blood cells. It is frequently associated with the presence of blasts or leukemic cells in the marrow. This leads to low numbers of one or more types of circulating blood cells, and to the need for blood transfusions. In MDS, some of the cells in the bone marrow are abnormal (dysplastic) and may have genetic abnormalities associated with them. Different cell types can be affected, although the most common finding in MDS is a shortage of red blood cells (anemia). Patients with higher-risk MDS may progress to the development of acute leukemia.

On March 6, 2019 La Jolla Pharmaceutical Company (Nasdaq: LJPC), a leader in the discovery, development and commercialization of innovative therapies intended to significantly improve outcomes in patients suffering from life-threatening diseases, reported financial results for the three months ended March 31, 2019 and highlighted recent corporate progress (Press release, La Jolla Pharmaceutical, MAY 6, 2019, View Source [SID1234535754]).

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For the three months ended March 31, 2019, GIAPREZA net product sales were $4.4 million, compared to $0.8 million for the same period in 2018. La Jolla launched GIAPREZA in the U.S. in March 2018. La Jolla’s net loss for the three months ended March 31, 2019 was $31.7 million, or $1.17 per share, compared to $50.5 million, or $2.22 per share, for the same period in 2018. La Jolla continues to expect full-year 2019 net sales of $24 million to $28 million.

As of March 31, 2019, La Jolla had $140.0 million in cash and cash equivalents, compared to $172.6 million as of December 31, 2018. The decrease in cash and cash equivalents was primarily the result of net cash used in operating activities. Net cash used in operating activities for the three months ended March 31, 2019 was $32.7 million, compared to $45.9 million for the same period in 2018. La Jolla had no debt as of March 31, 2019 and December 31, 2018. La Jolla continues to expect that its net cash used in operating activities in 2019 will be $89 million to $94 million.

"We are pleased to have recently been granted Breakthrough Therapy designation by the FDA for LJPC-0118, which will help us expedite bringing this treatment to patients suffering from severe malaria," said George Tidmarsh, M.D., Ph.D., La Jolla’s President and Chief Executive Officer. "We also look forward to the continued execution of a number of initiatives to support the increased adoption of GIAPREZA under the leadership of Darryl Wellinghoff, our new Chief Commercial Officer. Furthermore, we look forward to the continued progress of our clinical studies of LJPC-401; we continue to expect top-line results in the second half of 2019 for our Phase 2 study in patients with hereditary hemochromatosis and in mid-2020 for our pivotal study in patients with beta thalassemia."

About GIAPREZA

In December 2017, GIAPREZA (angiotensin II) was approved by the U.S. Food and Drug Administration (FDA) as a vasoconstrictor indicated to increase blood pressure in adults with septic or other distributive shock. GIAPREZA mimics the body’s endogenous regulatory peptide that is central to the renin-angiotensin-aldosterone system to increase blood pressure. Prescribing information for GIAPREZA is available at www.giapreza.com. GIAPREZA is marketed by La Jolla Pharmaceutical Company on behalf of La Jolla Pharma, LLC, its wholly owned subsidiary.

In June 2018, we announced that the Marketing Authorization Application (MAA) for GIAPREZA was validated by the European Medical Agency (EMA). We expect a decision on the GIAPREZA MAA by the EMA in June 2019. If approved, GIAPREZA could be available for marketing in the EU in early 2020.

IMPORTANT SAFETY INFORMATION

Contraindications

None

Warnings and Precautions

There is a potential for venous and arterial thrombotic and thromboembolic events in patients who receive GIAPREZA. Use concurrent venous thromboembolism (VTE) prophylaxis.

Adverse Reactions

The most common adverse reactions that were reported in greater than 10% of GIAPREZA-treated patients were thromboembolic events.

Drug Interactions

Angiotensin converting enzyme (ACE) inhibitors may increase response to GIAPREZA. Angiotensin II receptor blockers (ARB) may reduce response to GIAPREZA.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

For additional information, please see Full Prescribing Information.

About LJPC-0118

LJPC-0118 is La Jolla’s investigational product for the treatment of severe malaria. The active pharmaceutical ingredient in LJPC-0118 was demonstrated to be superior to quinine in reducing mortality in patients with severe falciparum malaria infection in two randomized, controlled, clinical studies. LJPC-0118 was granted Breakthrough Therapy designation by the U.S. Food and Drug Administration (FDA) in April 2019. La Jolla plans to file a New Drug Application (NDA) with the FDA in the fourth quarter of 2019 for LJPC-0118. Severe malaria is a serious and sometimes fatal disease caused by a parasite that commonly infects a certain type of mosquito, which feeds on humans. Symptoms include but are not limited to: fever, chills, sweating, hypoglycemia and shock. Severe malaria is often complicated by central nervous system infections that may lead to delirium, which may progress to coma. Infections usually occur a few weeks after being bitten. In 2017, an estimated 219 million cases of malaria occurred worldwide, with an estimated 200 million of these cases occurring in the World Health Organization (WHO) African Region, and, in 2013, the global annual incidence of severe malaria was estimated to be 2 million cases. In 2017, an estimated 435,000 people died from malaria worldwide.

About LJPC-401

LJPC-401, a clinical-stage investigational product, is La Jolla’s proprietary formulation of synthetic human hepcidin. Hepcidin, an endogenous peptide hormone, is the body’s naturally occurring regulator of iron absorption and distribution. In healthy individuals, hepcidin prevents excessive iron accumulation in vital organs, such as the liver and heart, where it can cause significant damage and even result in death. La Jolla is developing LJPC-401 for the potential treatment of iron overload, which occurs as a result of primary iron overload diseases such as hereditary hemochromatosis (HH), or secondary iron overload diseases such as beta thalassemia (BT), sickle cell disease (SCD), myelodysplastic syndrome (MDS) and polycythemia vera. The European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) has designated LJPC-401 as an orphan medicinal product for the treatment of beta thalassemia intermedia and major and SCD.

On May 6, 2019 Heat Biologics, Inc. (NASDAQ: HTBX), a biopharmaceutical company developing immunotherapies designed to activate a patient’s immune system against cancer, reported that John Prendergast, Heat Biologic’s Lead Board member, is scheduled to present at the ChinaBio 2019 conference on Thursday, May 9th, at 2:15 PM China Standard Time (CST), which is being held at Pudong Ballroom 5, 3F, Kerry Hotel in Pudong, Shanghai, China (Press release, Heat Biologics, MAY 6, 2019, View Source [SID1234535753]).

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Additional information on the conference is available at: View Source

On May 6, 2019 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the US Food and Drug Administration (FDA) has approved Kadcyla (trastuzumab emtansine) for adjuvant (after surgery) treatment of people with HER2-positive early breast cancer (eBC) who have residual invasive disease after neoadjuvant (before surgery) taxane and Herceptin (trastuzumab)-based treatment (Press release, Hoffmann-La Roche, MAY 6, 2019, View Source [SID1234535752]).

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"This approval is a significant treatment advance for HER2-positive early breast cancer. By working closely with the FDA and participating in the Real-Time Oncology Review pilot programme, we are able to make Kadcyla available for people with residual invasive disease after neoadjuvant therapy much sooner than anticipated," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "With every step forward in reducing the risk of disease recurrence, we come closer to the goal of helping each person with early breast cancer have the greatest opportunity for cure."

The goal in treating eBC is to provide people with the best chance for a cure, which may involve treatment before and after surgery as part of a comprehensive treatment approach.1,2 While we come closer to this goal with each advance, many people still have a disease recurrence in the long-term.3 Neoadjuvant treatment is given before surgery with the goal of shrinking tumours and helping to improve surgical outcomes.2 Adjuvant treatment is given after surgery and aims to eliminate any remaining cancer cells in the body to help reduce the risk of the cancer returning.2

The FDA rapidly reviewed and approved the application under the FDA’s Real-Time Oncology Review (RTOR) and Assessment Aid pilot programmes, leading to an approval in just over 12 weeks after completing the submission. Kadcyla is the first Roche medicine approved under the RTOR pilot programme, which is exploring a more efficient review process to ensure safe and effective treatments are available to patients as early as possible.4 For this indication, Kadcyla was also granted Breakthrough Therapy Designation, which is designed to expedite the development and review of medicines intended to treat serious or life-threatening diseases.5

This approval is based on results of the phase III KATHERINE study showing Kadcyla significantly reduced the risk of invasive breast cancer recurrence or death from any cause (invasive disease-free survival; iDFS) by 50% (HR=0.50, 95% CI 0.39-0.64, p<0.0001) compared to Herceptin as an adjuvant treatment in people with HER2-positive eBC who have residual invasive disease after neoadjuvant taxane and Herceptin-based treatment.6 At three years, 88.3% of people treated with Kadcyla did not have their breast cancer return compared to 77.0% treated with Herceptin, an absolute improvement of 11.3%.6 People who have residual disease after neoadjuvant treatment have a worse prognosis than those with no detectable disease.7,8

The most common Grade 3 or higher side effects (>2%) with Kadcyla in the KATHERINE study were decreased platelet count and high blood pressure. The most common side effects (>25%) with Kadcyla were fatigue; nausea; increased blood levels of liver enzymes; musculoskeletal pain; bleeding; decreased platelet count; headache; numbness, tingling or pain in the hands or feet; and joint pain.6,9

About the KATHERINE study10
KATHERINE is an international, multi-centre, two-arm, randomised, open-label, phase III study evaluating the efficacy and safety of Kadcyla versus Herceptin as an adjuvant therapy in people with HER2-positive eBC who have pathological invasive residual disease in the breast and/or axillary lymph nodes following neoadjuvant therapy that included Herceptin and taxane-based chemotherapy. The primary endpoint of the study is iDFS, which in this study is defined as the time from randomisation free from invasive breast cancer recurrence or death from any cause. Secondary endpoints include iDFS including second primary non-breast cancer, disease-free survival and overall survival.

About Kadcyla
Kadcyla is an antibody-drug conjugate (ADC) engineered to deliver potent chemotherapy directly to HER2-positive cancer cells, potentially limiting damage to healthy tissues.11,12 It combines two anti-cancer properties joined together by a stable linker: the HER2-targeting properties of trastuzumab (the active ingredient in Herceptin) and the chemotherapy agent DM1.13 Kadcyla is the only ADC approved as a single agent in 104 countries including the US and EU for the treatment of people with HER2-positive metastatic breast cancer who have previously received Herceptin and taxane chemotherapy, separately or in combination. Roche licenses technology for Kadcyla under an agreement with ImmunoGen, Inc.

About Roche’s medicines for HER2-positive breast cancer
Roche has been leading research into the HER2 pathway for over 30 years and is committed to improving the health, quality of life and survival of people with both early and advanced HER2-positive disease. HER2-positive breast cancer is a particularly aggressive form of the disease that affects approximately 15-20% of patients.14 Roche has developed three innovative medicines that have helped transform the treatment of HER2-positive breast cancer: Herceptin (trastuzumab), Perjeta (pertuzumab) and Kadcyla (trastuzumab emtansine). Eligibility for treatment with Roche’s HER2-targeted medicines is determined via a diagnostic test, which identifies people who will likely benefit from these medicines at the onset of their disease.