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Moleculin Announces Positive Trial Data with 100% Safe Delivery of p-STAT3 Inhibitor and Efficacy in Majority of Patients

On November 19, 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 it now has preliminary data from its clinical trial of WP1220 for the treatment of cutaneous T-cell lymphoma ("CTCL"), which was published in Blood in conjunction with the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition to be held December 7-10, 2019 (Press release, Moleculin, NOV 19, 2019, View Source [SID1234551470]).

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"For years, p-STAT3 (the activated form of STAT3) has been considered an ‘undruggable’ target because of the difficulty of reaching and affecting this cell-signaling protein," commented Walter Klemp, Moleculin’s Chairman and CEO. "Some consider it to be a master regulator of cancer-related gene transcription, so we believe the ability to show a therapeutic effect from a p-STAT3 inhibitor could be considered a significant breakthrough in cancer research."

Results: There were 6 patients screened, and 5 patients enrolled between March and July 2019. Three are evaluable for both safety and efficacy after completing 3 months of treatment, with 2 ongoing and evaluable for safety. The only AE reported potentially related to study drug in one of the five patients was a mild contact dermatitis not requiring treatment. CAILS scores on index lesions were significantly decreased in the first 3 patients, who were stages IA, IB, and IIB, respectively, at entry. A composite score was obtained for all treated lesions for each patient, and percent changes were calculated from baseline to Day 84. There was a median reduction of 70.8% (range 62.1%-76.2%) for the 3 patients. Improvement was noted as early as 7 days after initiation of treatment, and maintenance of improvement was also shown at follow up (1 month after discontinuation, as per protocol). The fourth patient has also shown an initial reduction in the composite CAILS score after 56 days (26.7%), and is continuing on treatment. Evaluations of the biopsy samples for histopathology and status of p-STAT3 in treated lesions are in progress.

Conclusions: WP1220, an inhibitor of p-STAT3, has shown demonstrable safety and significant efficacy after at least 3 months of topical treatment in 3 patients with progressive MF, with a continuing trend towards improvement in additional patients currently in treatment. This is the first demonstration that inhibition of the STAT3 activation pathway with topical therapy has impacted the course of this disease. The trial is continuing, and updated and more comprehensive data from this study as well as assessment of STAT3 phosphorylation in treated lesions will be reported.

Dr. Sandra Silberman, Chief Medical Officer for New Projects at Moleculin, added: "this is the first topical delivery of a p-STAT3 inhibitor that we know of for CTCL, where there is a significant unmet need for improved treatment of the lesions associated with this potentially deadly skin cancer. But, we believe the significance

of this data goes well beyond CTCL, as it speaks to the targeting of p-STAT3 as a general strategy. We are excited to share these preliminary results in association with ASH (Free ASH Whitepaper), especially because we believe showing activity here could have exciting implications for the future of STAT3 inhibitors in general. Although this is a relatively small pilot study, we believe the results justify an expansion to a larger patient population in a Phase 2 clinical trial."

Merck Announces First-Quarter 2020 Dividend

On November 19, 2019 Merck (NYSE: MRK), known as MSD outside the United States and Canada, reported that the Board of Directors has declared a quarterly dividend of $0.61 per share of the company’s common stock for the first quarter of 2020 (Press release, Merck & Co, NOV 19, 2019, View Source [SID1234551469]). Payment will be made on Jan. 8, 2020 to shareholders of record at the close of business on Dec. 16, 2019.

Genmab Announces European Marketing Authorization for DARZALEX® (Daratumumab) in Combination with Lenalidomide and Dexamethasone in Frontline Multiple Myeloma

On November 19, 2019 Genmab A/S (Nasdaq: GMAB) reported that the European Commission (EC) has granted marketing authorization for DARZALEX (daratumumab) in combination with lenalidomide and dexamethasone (Rd) as treatment for adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT) (Press release, Genmab, NOV 19, 2019, View Source [SID1234551468]). The EC approval follows a positive opinion issued for DARZALEX by the CHMP of the European Medicines Agency (EMA) in October 2019. In August 2012, Genmab granted Janssen Biotech, Inc. (Janssen) an exclusive worldwide license to develop, manufacture and commercialize daratumumab.

"We are pleased that with this approval, patients in the European Union newly diagnosed with multiple myeloma who are not candidates for transplant will now have two potential options for treatment with DARZALEX containing regimens. We look forward to seeing the combination therapy of DARZALEX with lenalidomide and dexamethasone launched in Europe," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

The approval was based on data from the Phase III MAIA (MMY3008) study of daratumumab in combination with Rd as treatment for patients with newly diagnosed multiple myeloma, who are not candidates for high dose chemotherapy and ASCT. Data from this study was published in The New England Journal of Medicine and was presented as a Late-Breaking Abstract at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2018.

About the MAIA (MMY3008) study
The Phase III study (NCT02252172) is a randomized, open-label, multicenter study that includes 737 newly diagnosed patients with multiple myeloma who are not candidates for high dose chemotherapy and ASCT. Patients were randomized to receive either treatment with daratumumab in combination with lenalidomide (an immunomodulatory drug) and dexamethasone (a corticosteroid) or treatment with lenalidomide and dexamethasone alone. In the daratumumab treatment arm, patients received 16 milligrams per kilogram (mg/kg) weekly for the first 8 weeks (Cycles 1 and 2), every other week for 16 weeks (Cycles 3 to 6) and then every 4 weeks (Cycle 7 and beyond) until progression of disease or unacceptable toxicity. Lenalidomide is administered at 25 mg orally on days 1 through 21 of each 28-day cycle, and dexamethasone is administered at 40 mg once a week for both treatment arms. Participants in both treatment arms will continue Rd until disease progression or unacceptable toxicity. The primary endpoint of the study is progression free survival.

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 Approximately 16,830 new patients were expected to be diagnosed with multiple myeloma and approximately 10,480 people were expected to die from the disease in the Western Europe in 2018.2 Globally, it was estimated that 160,000 people were diagnosed and 106,000 died from the disease in 2018.3 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.4

About DARZALEX(daratumumab)
DARZALEX (daratumumab) intravenous infusion is indicated for the treatment of adult patients in the United States: in combination with bortezomib, thalidomide and dexamethasone as treatment for patients newly diagnosed with multiple myeloma who are eligible for autologous stem cell transplant; in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; 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.5 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (U.S. FDA) approval to treat multiple myeloma. DARZALEX intravenous infusion is indicated for the treatment of adult patients in Europe: in combination with lenalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; 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 therapy6. 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 intravenous infusion is approved for the treatment of adult patients: in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone for the treatment of relapsed or refractory multiple myeloma; 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. DARZALEX is the first human CD38 monoclonal antibody to reach the market in the United States, Europe and Japan. 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).5,6,7,8,9,10

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 refractory and frontline multiple myeloma settings. Additional studies are ongoing or planned to assess the potential of daratumumab in other malignant and pre-malignant diseases in which CD38 is expressed, such as amyloidosis, NKT-cell lymphoma and B-cell and T-cell ALL. Daratumumab has received two Breakthrough Therapy Designations from the U.S. FDA for certain indications of multiple myeloma, including as a monotherapy for heavily pretreated multiple myeloma and in combination with certain other therapies for second-line treatment of multiple myeloma.

Lilly Confirms Date and Conference Call for 2020 Financial Guidance Announcement

On November 19, 2019 Eli Lilly and Company (NYSE: LLY) will reported its financial guidance for 2020 on Tuesday, December 17, 2019 (Press release, Eli Lilly, NOV 19, 2019, View Source [SID1234551467]). Lilly will also conduct a conference call on that day with the investment community and media to further detail the company’s financial guidance.

The conference call will begin at 9 a.m. Eastern time. Investors, media and the general public can access a live webcast of the conference call through a link that will be posted on Lilly’s website at View Source A replay will also be available on the website following the conference call.

Diffusion Pharmaceuticals Presents Early Findings Showing Increased Survival in Lead-in Portion of Phase 3 Glioblastoma Study with TSC plus Standard of Care

On November 19, 2019 Diffusion Pharmaceuticals Inc. (Nasdaq: DFFN), a cutting-edge biotechnology company developing new treatments for life-threatening medical conditions by improving the body’s ability to bring oxygen to the areas where it is needed most, reported increased survival in inoperable glioblastoma patients enrolled in the 19-patient, open-label, dose-escalation lead-in portion of its Phase 3 study with Trans Sodium Crocetinate (TSC) plus standard of care (SOC) (Press release, Diffusion Pharmaceuticals, NOV 19, 2019, View Source [SID1234551466]). John Gainer, Ph.D., the Company’s chief scientific officer, will present details of these findings at the inaugural Glioblastoma Drug Development Summit being held in Boston December 10-11, and sponsored by Hanson Wade. Dr. Gainer’s slide presentation will be posted to the Company’s website at www.diffusionpharma.com immediately prior to the conference.

In an earlier Phase 2 study testing TSC in newly diagnosed glioblastoma multiforme (GBM) brain cancer patients, an almost fourfold increase in 2-year survival was seen versus historical controls in inoperable patients. The current Phase 3 INTACT (INvestigating Tsc Against Cancerous Tumors) study – an open-label, randomized, controlled trial – is designed to examine this finding in a fully powered safety and efficacy registration study, which, if successful, could be the basis for US FDA approval.

In the INTACT trial, subjects are randomized at baseline to SOC for first-line treatment of GBM plus TSC, or to SOC alone. The SOC for GBM is temozolomide plus radiation therapy for 6 weeks, followed by 28 days of rest, then by 6 cycles of post-radiation temozolomide treatment. In a modification to the Phase 2 dosing regimen, patients in the INTACT trial will also receive high-dose TSC during the post-radiation chemotherapy phase.

A 19-patient, open-label, dose-escalation lead-in portion to the INTACT trial was recently completed, sending a positive safety signal across all patients receiving TSC. In addition, six of the seven patients who received the high dose TSC treatment are still alive, with a median survival at the present time of 14.3 months. This is compared with 9.2 months for the historical standard of patients with inoperable GBM. Since six of the TSC-treated patients are still alive, median survival time is actually increasing with the passage of time, suggesting the INTACT trial may confirm or better the efficacy findings seen in the Phase 2 study.

Patients’ abilities to perform their daily activities as measured by Karnofsky performance scores increased from the baseline following completion of high dose treatment with TSC. Investigators have also reported instances of inoperable GBM patients treated with the higher dose TSC regimen leaving hospice or returning to work after treatment in the open-label portion of the study.

"We are encouraged by these early findings showing that patients enrolled in the lead-in portion of the INTACT trial have experienced increased survival with our new protocol," said Dr. Gainer. "Although final conclusions will depend on the completion of the randomized portion of the trial, we believe that TSC helps to eradicate the low oxygen status of cancerous tumors, and it appears this may also result in a survival benefit compared with the current standard therapy."

The Company previously announced it is seeking a partner to continue development of TSC in the GBM indication and has begun patient enrollment in its Phase 2 on-ambulance trial with TSC for the treatment of stroke.

About Hanson Wade

Hanson Wade’s goal is to accelerate progress within organizations and across industries. Its primary method for achieving this is by creating exclusive business conferences that gather together the world’s smartest thinkers and doers. The inaugural Glioblastoma Drug Development Summit is designed with two critical and ambitious objectives: to help overcome the major biological challenges limiting effective Glioblastoma treatment; and to evaluate novel therapies and innovative trial design to prevent more tragic Phase 2 failures.