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 26, 2019 Zenyaku Kogyo Co., Ltd. (Japanese-only website) and Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that Zenyaku obtained regulatory approval from the Ministry of Health, Labour and Welfare (MHLW), for an anti-CD20 monoclonal antibody, RITUXAN injection 100 mg and 500 mg [generic name: rituximab (genetical recombination)] (hereafter, "RITUXAN"), which was co-developed by the two companies for an additional indication of CD20-positive chronic lymphocytic leukemia (CLL) (Press release, Chugai, MAR 26, 2019, View Source [SID1234534622]). RITUXIAN is co-marketed by the two companies in Japan.

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RITUXAN is an anti-CD20 monoclonal antibody that specifically binds to CD20, a protein expressed on B cells other than stem and plasma cells, which attacks B cells as targets with the immune system in the body. RITUXAN is used in combination with other antineoplastic drugs for the treatment of CD20-positive CLL, the additional indication approved this time.

CLL is a disease in which small mature B lymphocytes proliferate monoclonally and proliferate in peripheral blood, bone marrow, lymph nodes and spleen, many of which progress slowly. This rare disease is mostly prevalent in elderly people, and considered as difficult to cure with current treatments while many patients often experience recurrence and progression repeatedly. The number of patients in Japan is small, reportedly about 0.3 to 100,000 people per year. The age of onset is typically over 50 years, and rarely seen in people under 30 years of age. In patients with CLL, the ratio of males to females is higher at about 1.5 or 2 to 1*.

Zenyaku and Chugai will continue to work closely together to make RITUXAN contribute to the treatment of CD20-positive CLL.

* Center for Cancer Control and Information Services. Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma
View Source (Japanese only)

On March 26, 2019 Prometic Life Sciences Inc. (TSX: PLI, OTCQX: PFSCF) ("Prometic" or the "Corporation") reported that it will report its financial results for the fourth quarter and year ended December 31, 2018 on Monday April 1, 2019 after market close (Press release, ProMetic Life Sciences, MAR 26, 2019, View Source [SID1234534638]).

Prometic will host a conference call at 11:00am (ET) on Tuesday April 2, 2019. The telephone numbers to access the conference call are 1-888-231-8191 and 647-427-7450. An audio replay of the call will be available as of Tuesday April 2, 2019 at 2:00pm (ET). The numbers to access the audio replay are 416-849-0833 and 1-855-859-2056 using the following password (3198209).

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A live audio webcast of the conference call will be available via: View Source About Prometic Life Sciences Inc.

On March 26, 2019 Arvinas, Inc. (Nasdaq: ARVN), a biopharmaceutical company creating a new class of therapies that degrade disease-causing proteins, reported financial results for the fourth quarter and full year ended December 31, 2018 and provided a corporate update (Press release, Arvinas, MAR 26, 2019, View Source [SID1234534623]).

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"Since our founding in 2013, Arvinas has been focused on leading and advancing the field of targeted protein degradation and we are proud of our progress to date. 2018 was a transition year for Arvinas with preparations for moving into the clinic with our two lead programs. The hard work and dedication of our team recently enabled us to initiate patient dosing in our first Phase 1 clinical trial of ARV-110, our oral androgen receptor (AR)-targeted PROTAC protein degrader for the treatment of men with metastatic castration-resistant prostate cancer," said John Houston, Ph.D., President and CEO of Arvinas. "We believe ARV-110 is the first in this new class of targeted protein degraders to enter human clinical trials, and we anticipate bringing ARV-471, an estrogen receptor (ER)-targeted PROTAC protein degrader for the treatment of women with locally advanced or metastatic ER+ / HER2- breast cancer, into the clinic in the third quarter of 2019."

"While our initial clinical programs will be in oncology, this is just the beginning for Arvinas. There are many protein targets for which our PROTAC technology may be advantageous, including ‘undruggable’ targets. We are moving into new and exciting therapeutic areas, developing new PROTAC protein degraders against neurodegenerative targets such as tau, which is implicated in Alzheimer’s Disease. We have engineered targeted PROTAC protein degraders that, in preclinical studies, have achieved blood-brain barrier penetration, a key step in developing drugs with the potential to treat neurodegenerative diseases," continued Dr. Houston.

Business Highlights and Recent Developments

Initiated patient dosing in the first Phase 1 clinical trial of ARV-110, which will evaluate the safety and tolerability of ARV-110 in patients with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on standard of care therapies. Arvinas believes ARV-110 is the first in a new class of targeted protein degraders to enter human clinical trials and anticipates preliminary data from the study in the second half of 2019.
Completed an initial public offering ("IPO") in October 2018, issuing an aggregate of 7,700,482 shares of common stock, including 200,482 additional shares of common stock upon the exercise in part by the underwriters of their option to purchase additional shares at a public offering price of $16.00 per share, for aggregate gross proceeds of approximately $123.2 million.
Closed a $55 million Series C financing in March 2018. The financing was led by new investor Nextech Invest, with participation from additional new investors Deerfield Management, and Hillhouse Capital. All existing investors also participated in this financing round, including Canaan Partners, 5AM Ventures, RA Capital Management, OrbiMed, and New Leaf Venture Partners.
Presented positive preclinical data, at the 2018 San Antonio Breast Cancer Symposium (SABCS) on ARV-471, a PROTAC protein degrader for the degradation of the estrogen receptor (ER), which demonstrated:

Potent ER degradation in wild-type and mutant ER-expressing cell lines
Tumor shrinkage after oral administration in an orthotopic MCF7 breast cancer xenograft model, accompanied by near-complete ER degradation
More robust tumor growth inhibition and ER degradation compared to fulvestrant, a standard of care agent
Significant tumor regressions when combined with a CDK4/6 inhibitor and overall superior anti-tumor activity when compared to the combination of fulvestrant and a CDK4/6 inhibitor
Tumor growth inhibition of tamoxifen-resistant and ER gene (ESR1) mutant tumors while also reducing tumor ER levels
No ER agonist activity
Anticipated Milestones and Expectations

Disclose preliminary data from the Phase 1 clinical trial of ARV-110 in the second half of 2019.
Initiate a Phase 1 clinical trial of ARV-471 in women with locally advanced or metastatic ER+ positive / HER2- negative breast cancer in the third quarter of 2019 and collect preliminary clinical data in 2020.
Present preclinical data from our tau program in the second half of 2019.
Financial Guidance

Based on its current operating plan, Arvinas expects its cash, cash equivalents, and marketable securities as of December 31, 2018 will be sufficient to fund its operating expenses and capital expenditure requirements into the first half of 2021.

Full Year and Fourth Quarter Financial Highlights

Cash, Cash Equivalents and Marketable Securities Position: As of December 31, 2018, cash, cash equivalents, and marketable securities were $187.8 million as compared to $39.2 million as of December 31, 2017. The increase related to net proceeds from our IPO of $114.6 million, proceeds from our Series C financing of $55.0 million, proceeds from our Pfizer collaboration of $28.0 million, and proceeds from a partially forgivable loan of $2.0 million; offset by cash used to fund operations and professional fees paid related to our IPO of $51.0 million. Cash, cash equivalents, and marketable securities increased by $98.0 million in the fourth quarter of 2018. This increase related to net proceeds from our IPO of $114.6 million, offset by cash used to fund operations, and professional fees paid related to our IPO of $16.6 million.

Research and Development Expenses: Research and development expenses were $45.2 million and $14.6 million for the year and quarter ended December 31, 2018, respectively as compared to $28.8 million and $6.7 million for the year and quarter ended December 31, 2017, respectively. The increase in research and development expenses for the year and quarter primarily related to investigational new drug application ("IND")-enabling costs associated with ARV-110 and ARV-471 in addition to increases in costs associated with our discovery operations.

General and Administrative Expenses: General and administrative expenses were $12.9 million and $5.8 million for the year and quarter ended December 31, 2018, respectively as compared to $3.5 million and $1.2 million for the year and quarter ended December 31, 2017, respectively. The increase in general and administrative expenses for the year and quarter primarily relate to increases in our infrastructure in preparation of becoming a publicly traded company.

Revenues: Revenue was $14.3 million and $3.4 million for the year and quarter ended December 31, 2018, respectively as compared to $7.6 million and $2.6 million for the year and quarter ended December 31, 2017, respectively. This increase in the year and quarter was due to an increase in license and rights to technology and research and development activities primarily related to the Pfizer collaboration agreement initiated in January 2018 and the expanded Genentech agreement that was initiated in November 2017.

Net Loss: Net loss was $41.5 million and $16.1 million for the year and quarter ended December 31, 2018, respectively as compared to $24.0 million and $4.7 million for the year and quarter ended December 31, 2017, respectively. The increase in net loss for the year and quarter ended December 31, 2018 was primarily due to the progression of ARV-110 through IND-enabling activities, clinical trial start-up costs for ARV-110, the initiation of IND-enabling activities for ARV-471, investments in our discovery programs and investments in our infrastructure in preparation for becoming a publicly traded company offset by an increase in revenue primarily related to the expanded Genentech collaboration agreement initiated in November 2017 and the Pfizer collaboration agreement initiated in January 2018.

About ARV-110
ARV-110 is an orally-bioavailable PROTAC protein degrader designed to selectively target and degrade androgen receptor (AR). ARV-110 is being developed as a potential treatment for men with metastatic castration-resistant prostate cancer (mCRPC). ARV-110 has demonstrated activity in preclinical models of AR mutation or overexpression, both common mechanisms of resistance to currently available AR-targeted therapies. Arvinas believes the differentiated pharmacology of ARV-110, including its iterative activity, has the potential to translate into improved clinical outcomes for patients.

About ARV-471
ARV-471 is targeting the estrogen receptor (ER) for the treatment of women with locally advanced or metastatic ER+ / HER2- breast cancer. A Phase 1 clinical trial for ARV-471 in women with locally advanced or metastatic ER+ positive / HER2- negative breast cancer, is expected to begin in the third quarter of 2019 and preliminary clinical data is expected in 2020.