On March 26, 2019 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors, reported positive interim safety and efficacy data from two ongoing open label, single arm Phase 1/2 studies of Annamycin. In the first study, being conducted in the US, four patients have completed treatment at 100 mg/m2 with no significant adverse events related to Annamycin, and the study will now proceed to the next higher dose of 120 mg/m2 (Press release, Moleculin, MAR 26, 2019, https://www.prnewswire.com/news-releases/moleculin-announces-positive-interim-results-in-first-cohort-of-phase-12-clinical-studies-of-annamycin-in-acute-myeloid-leukemia-in-the-us-and-in-poland-300818195.html [SID1234534636]). The second trial, taking place in Poland, started at a 120 mg/m2 dose of Annamycin and has treated three patients. The first patient treated in that trial received a single course of Annamycin and his bone marrow blasts have reduced from 60% to 11%. Our principal investigator considers this response sufficient for the patient to proceed to consolidation therapy, with the goal of receiving a potentially curative bone marrow transplant. To date in Poland, one patient experienced grade 2 mucositis (which resolved to grade 1 within 2 days) and no other adverse events related to Annamycin have been reported. Trial results for the other two patients treated in Poland will not be known until the second quarter of this year.

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"We are very pleased to have completed the treatment of patients in cohort 1 of the US trial and move to the next higher dose," commented Walter Klemp, Moleculin’s Chairman and CEO. "In Poland, we are pleased to have such a positive response at the starting dose level in this trial. Of course the response of a single patient doesn’t necessarily predict the outcome of the trial, but this is a great way to begin and it’s consistent with our expectations for Annamycin."

Mr. Klemp continued: "One of the advantages we believe Annamycin will offer is a lack of cardiotoxicity. We have seen no evidence of cardiotoxicity in any of the patients treated thus far. We intend to advance the clinical study of Annamycin with the goal of ultimately demonstrating the drug’s safety and effectiveness to support regulatory approval in the US and European Union."

Dr. Robert Shepard, Moleculin’s Chief Medical Officer for Annamycin added: "A prior clinical trial for Annamycin in acute leukemia demonstrated activity at its Maximum Tolerable Dose of 150 mg/m2, so we are pleased for the US trial to move to the next higher dose in cohort 2 of 120 mg/m2. In Poland, we consider reducing bone marrow blasts for Patient 1 down to 11% with a single course of Annamycin to be very encouraging. Of course, significant additional study is necessary to definitively demonstrate causality."

"We have begun a second course of Annamycin as a consolidation phase for Patient 1," commented Dr. Lidia Gil, Principal Investigator in the Polish Annamycin clinical trial. "Considering that this patient was refractory to standard of care induction therapy, I am very pleased to see that Annamycin appears to be showing activity. While this is considered a ‘Partial Response,’ I believe it’s enough of a reduction to serve as a ‘bridge to transplant’ for this patient. Importantly, with the first course of Annamycin, no toxicities have been observed that would limit continued dosing with Annamycin."

Study Design

The Company is studying Annamycin in both the US and Poland in open label, single arm clinical trials to assess the safety and efficacy of Annamycin for the treatment of adults with relapsed or refractory acute myeloid leukemia. Both the US and Polish trials have the same study design, providing for a Phase 1 intended to establish a "Recommended Phase 2 Dose," ("RP2D") with cohorts of 3 patients each where the first cohort starts at a low beginning dose and each successive cohort receives the next higher dose level until "dose limiting toxicities" prevent further increases. In the case of cohort 1 in the US, one patient did not complete the evaluation protocol, so a fourth patient was added to complete that cohort.

A key difference in the US is that the starting dose was 100 mg/m2, whereas, in Poland, the starting dose was 120 mg/m2. Having completed the first cohort in the US, the Company is seeking patients for the second cohort at a dose level of 120 mg/m2. Once 3 patients have completed the safety evaluation period of the first cohort in Poland, the second cohort will begin there at a dose level of 150 mg/m2. Once the Company establishes an RP2D, the intent is for each trial to advance to a Phase 2 arm planned to assess the safety and efficacy of Annamycin in 21 additional patients.

The US trial also differs from the Polish trial in that the FDA would like to review safety data relating to cardiotoxicity from patients treated prior to advancing beyond 120 mg/m2. The Company believes that the additional patient safety data gained from the Polish trial may also assist in the FDA’s review of cardiac safety.

On March 26, 2019 Genmab A/S (Nasdaq Copenhagen: GEN) reported that its licensing partner, Janssen Biotech, Inc., has submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (U.S. FDA) for the use of daratumumab (DARZALEX) in combination with bortezomib, thalidomide and dexamethasone (VTD) as treatment for newly diagnosed patients with multiple myeloma who are candidates for autologous stem cell transplant (ASCT) (Press release, Genmab, MAR 26, 2019, View Source [SID1234534637]). In August 2012, Genmab granted Janssen an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

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"This application is an important step in potentially providing a new group of multiple myeloma patients access to DARZALEX. We look forward to the U.S. FDA’s feedback regarding this proposed front line indication," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The submission is based on data from the Phase III CASSIOPEIA study of daratumumab in combination with VTD as frontline treatment for patients with multiple myeloma who are candidates for ASCT. The study is sponsored by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen R&D, LLC. The topline results of the data were announced in October 2018 and Janssen expects to publish detailed data from the study during 2019.

About the CASSIOPEIA (MMY3006) study
This Phase III study is a randomized, open-label, multicenter study, run by the French Intergroupe Francophone du Myelome (IFM) in collaboration with the Dutch-Belgian Cooperative Trial Group for Hematology Oncology (HOVON) and Janssen R&D, LLC, including 1,085 newly diagnosed subjects with previously untreated symptomatic multiple myeloma who are eligible for high dose chemotherapy and stem cell transplant. In the first part of the study, patients were randomized to receive induction and consolidation treatment with daratumumab combined with bortezomib, thalidomide (an immunomodulatory agent) and dexamethasone (a corticosteroid) or bortezomib, thalidomide and dexamethasone alone. The primary endpoint is the proportion of patients that achieve a stringent Complete Response (sCR). In the second part of the study, patients that achieved a response will undergo a second randomization to either receive maintenance treatment of daratumumab 16 mg/kg every 8 weeks for up to 2 years versus no further treatment (observation). The primary endpoint of this part of the study is progression free survival (PFS).

About multiple myeloma
Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excess proliferation of plasma cells.1 Multiple myeloma is the third most common blood cancer in the U.S., after leukemia and lymphoma.2 Approximately 26,000 new patients were expected to be diagnosed with multiple myeloma and approximately 13,650 people were expected to die from the disease in the U.S. in 2018.3 Globally, it was estimated that 160,000 people were diagnosed and 106,000 died from the disease in 2018.4 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms which can include bone problems, low blood counts, calcium elevation, kidney problems or infections.5

About DARZALEX(daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy; in combination with pomalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor (PI); and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a PI and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.6 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe in combination with bortezomib, melphalan and prednisone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; for use in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; and as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a PI and an immunomodulatory agent and who have demonstrated disease progression on the last therapy. The option to split the first infusion of DARZALEX over two consecutive days has been approved in both Europe and the U.S. In Japan, DARZALEX is approved in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for treatment of adults with relapsed or refractory multiple myeloma. DARZALEX is the first human CD38 monoclonal antibody to reach the market. For more information, visit www.DARZALEX.com.

Daratumumab is a human IgG1k monoclonal antibody (mAb) that binds with high affinity to the CD38 molecule, which is highly expressed on the surface of multiple myeloma cells. Daratumumab triggers a person’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death, via apoptosis (programmed cell death).6,7,8,9,10

Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. A comprehensive clinical development program for daratumumab is ongoing, including multiple Phase III studies in smoldering, relapsed and frontline multiple myeloma settings and in amyloidosis. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases, such as NKT-cell lymphoma B and T-ALL. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA, for multiple myeloma, as both a monotherapy and in combination with other therapies.

On March 25, 2019 Propanc Biopharma, Inc. (OTCQB: PPCB) ("Propanc"), a biopharmaceutical company developing new cancer treatments for patients suffering from recurring and metastatic cancer, reported that it has initiated development of a bio-analytical assay intended to quantify the active ingredients of the company’s lead product candidate, PRP, in preparation for human trials, planned for later this year (Press release, Propanc, MAR 25, 2019, View Source [SID1234534581]). The work will be conducted by a specialist Contract Research Organization with extensive knowledge in the development of functional assays for different bio-therapeutics. PRP is a solution of two proenzymes, trypsinogen and chymotrypsinogen, administered by I.V. injection.

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"We are keen to undertake this important work, as the quantification of PRP in human serum will provide invaluable information that links the biodistribution of the two proenzymes, as it exerts its potent anti-cancer and anti-tumor effects, to the efficacy and safety of our therapy on patients at different dosing levels," said Dr. Julian Kenyon, Propanc’s Chief Scientific Officer. "Initially we will carry out a feasibility study to quantify the two proenzymes trypsinogen and chymotrypsinogen, but in addition, the enzymes which become activated at the tumor site, trypsin and chymotrypsin. It is the activated enzymes which exert their effects on the cancer cells, by turning off important protein markers responsible for tumorigenicity and malignancy, so that the cancer cells die naturally. Measuring all four analytes will provide an important link to the action of PRP and its effects on cancer patients."

Development of the bio-analytical assay will be an important step towards the clinical development of PRP, as Propanc considers the possible sites to conduct a First-In-Human study in advanced cancer patients, possibly in Europe, specifically the UK, or at a prominent cancer hospital in Australia, with significant experience in early stage clinical development. Attractive R&D tax incentive benefits could be gained by undertaking the trial in Australia, as well as utilizing world-class facilities dedicated to treating and caring for people with cancer. Propanc will investigate selected clinical trial sites more thoroughly as it commences preparation of a clinical trial application for PRP.

On March 25, 2019 VBL Therapeutics (Nasdaq: VBLT), reported that the Company will present data on its Phase 3 drug candidate VB-111, at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, to be held March 29 – April 3, 2019 at Georgia World Congress Center in Atlanta, Georgia (Press release, VBL Therapeutics, MAR 25, 2019, View Source [SID1234534604]). VB-111 is a first-in-class, targeted anti-cancer gene-therapy biologic with broad potential to treat a wide range of solid tumors. In addition, the company will provide a corporate overview at the H.C. Wainwright Global Life Sciences Conference to be held April 7 – 9, 2019 at the Grosvenor House, a JW Marriott Hotel in London, UK.

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The AACR (Free AACR Whitepaper) Annual Meeting – Presentation Details:
Title: Ofranergene Obadenovec (VB-111), an anti-cancer gene therapy, induces immunologic responses in solid tumors transforming ‘cold’ tumors to ‘hot’ tumors
Session Category: Immunology
Session Title: Immunomodulators and Response to Therapy
Date: Wednesday Apr 3, 2019
Time: 8:00 AM – 12:00 PM Eastern Time
Session Location: Exhibit Hall B, Poster Section 24
Poster Board Number: 2
Abstract Number: 4979

HCW Global Life Sciences Conference – Presentation Details:

Date:Monday, April 8
Time: 15:40 – 16:00 BST

On March 25, 2019 Race Oncology reported that it has announced the US Food and Drug Administration has received its Investigational New Drug (IND) application for the company’s cancer drug Bisantrene (Press release, Race Oncology, MAR 25, 2019, View Source [SID1234534583]).

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The IND application is a major milestone in the approval process for the company’s Acute Myeloid Leukaemia (AML) drug in the United States. The application is a precursor to Race Oncology’s intended 250-patient clinical trial of Bisantrene for the treatment of adult AML.

"The filing of the IND definitely brands Bisantrene as a Phase III asset," said Race Oncology CEO Peter Molloy.

Because Bisantrene is entering the clinical and regulatory process at Phase III, the IND comprises the entire history of Bisantrene’s preclinical and clinical development, along with Phase III quality manufacturing and other data.

"Race Oncology is well advanced in our push to get FDA approval of Bisantrene in the United States. Our team has been focused on this milestone for the past six months," said Race Oncology CEO Peter Molloy.

The FDA will now take 30 days to review the application, which consists of new chemistry and manufacturing data developed by Race Oncology, as well as the entire history of the pre-clinical and clinical development of Bisantrene over three decades.

Bisantrene is a chemotherapy drug that was the subject of more than forty phase two clinical studies during the 1980s and 1990s. Race has rescued the drug after it was lost in a series of big pharma mergers.

In addition to underpinning the adult AML approval of Bisantrene, the IND will be the core regulatory document and springboard for Race’s planned trial in paediatric AML.

Race has received a Rare Paediatric Disease designation for Bisantrene from the FDA, and upon a successful paediatric trial, could receive a valuable and saleable ‘Priority Review Voucher’ (PRV).

The Company is now in advanced discussions around the funding and conduct of the paediatric trial.

"The IND is the culmination of nearly three years of manufacturing and development work at Race Oncology, and it now provides the launch pad for a number of value creating programs," said Mr Molloy.

"I regard this IND as our most important achievement to date," added Mr Molloy.