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DiaMedica Therapeutics Announces 2018 Financial Results and Provides Corporate Update

On March 19, 2019 DiaMedica Therapeutics Inc. (Nasdaq: DMAC), a clinical-stage biopharmaceutical company focused on developing novel treatments for kidney diseases and neurological disorders, reported its financial results for the year ended December 31, 2018 (Press release, DiaMedica, MAR 19, 2019, View Source [SID1234534492]).

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Business Highlights

"In the past year, DiaMedica has achieved important development goals for our two lead programs, DM199 for chronic kidney disease and acute ischemic stroke. We expect to build upon this success in 2019 as we work toward advancing our pipeline of clinical programs, which hold the potential to have significant impact on patients suffering from chronic kidney disease and acute ischemic stroke," stated Rick Pauls, DiaMedica’s President and CEO. "After our successful Nasdaq IPO in December, we have sufficient capital to obtain Phase II read-outs in our two lead programs. We are well positioned to execute on our clinical development plans to achieve meaningful milestones in the next year, and we look forward to sharing our progress."

U.S. IPO, Nasdaq Uplisting and U.S. Reporting Company

On December 6, 2018, DiaMedica completed an initial public offering ("IPO") of its common shares in the United States and uplisted to the Nasdaq Capital Market, raising $16.4 million in gross proceeds and $14.7 million in net proceeds. This was an important milestone for DiaMedica that expanded its investor base, adding several U.S. institutional investors, and strengthened its balance sheet. The IPO also provided the capital to complete Phase II clinical trials for DM199 in patients suffering acute ischemic strokes ("AIS") and chronic kidney disease ("CKD").

License of DM199 with Ahon Pharma, subsidiary of Fosun Pharma.

In September 2018, DiaMedica signed a license and collaboration agreement with Fosun Pharma’s Ahon Pharma subsidiary for acute ischemic stroke in China. Fosun is one of the largest Chinese pharmaceutical firms with an extensive hospital sales force. The agreement provides exclusive rights to clinically develop and commercialize DM199 solely for acute ischemic stroke in China, Taiwan, Hong Kong and Macau. Under the terms of the agreement, DiaMedica may receive approximately $32 million in milestone payments, plus sales-based royalties of up to approximately 10%. In addition, DiaMedica has retained full control over the manufacturing of DM199. Ahon Pharma is currently preparing an application for an investigational new drug application to the China National Medical Products Administration. In China, a form of the KLK1 protein extracted from human urine, known as u-KLK1 or Kailikang, has been approved and is considered a standard of care for AIS patients.

Clinical Developments

DM199 for the Treatment of Chronic Kidney Disease

Enrolling Patients in Phase Ib Clinical Study in Patients with CKD

In December 2018, the United States Food & Drug Administration ("FDA") accepted DiaMedica’s investigational new drug ("IND") application to study DM199 in patients with CKD. In February 2019, the Company began enrolling patients in its Phase Ib clinical study, which is being conducted at 3 sites in the U.S. and all sites are actively enrolling patients. The open label clinical trial is evaluating three dose levels of DM199, administered in a single subcutaneous ("SC") dose, in 32 patients with moderate or severe CKD. Primary endpoints include safety, tolerability, pharmacokinetics, change in KLK1 levels, albumin to creatine ratios and kidney biomarkers measured over a 12-day period. This study is intended to assist in identifying dose levels for use in subsequent Phase II trials. The Company expects a readout on the results of the CKD study in mid-2019.

Released Chronic Kidney Disease White Paper

Today, DiaMedica also released a white paper that further details the potential of KLK1/DM199 to treat patients with chronic kidney disease. The paper can be accessed at www.diamedica.com/product-candidates/chronic-kidney-disease.

DiaMedica is currently planning a randomized Phase II study in patients with rare forms of chronic kidney disease to be initiated in the second half of 2019. The Company will have updates on the rare forms to be targeted in this study and other details to follow.

DM199 for the Treatment of Acute Ischemic Stroke

DM199 Acute Ischemic Stroke Phase II "REMEDY" Trial Update.

In 2018, the Company initiated treatment of patients in its Phase II randomized, double-blind, placebo-controlled multi-center evaluation to assess the safety, tolerability and markers of DM199 in acute ischemic stroke patients, the REMEDY trial. With the success of its IPO, DiaMedica raised its target enrollment in the REMEDY trial from 60 to approximately 100 patients to provide additional data to support the design of a robust and efficient Phase III study. In this trial, the study drug (DM199 or placebo) is administered as an intravenous ("IV") infusion within 24 hours of stroke symptom onset, followed by SC injections later that day and once every 3 days for 21 days (8 SC doses). Multiple plasma-based biomarkers (e.g. C-reactive protein), the Modified Rankin Scale, National Institutes of Health Stroke Scale and the Barthel Index will be assessed at multiple points throughout the study, including 90 days post-stroke. This study will also include multiple tests to investigate DM199’s therapeutic potential. With the increase in the enrollment target, the Company expects to complete this trial in the fourth quarter of 2019 or first quarter of 2020.

AIS Review Paper Supporting the Use of DM199 for AIS Published in Peer-Reviewed Journal

On January 22, 2019, DiaMedica announced that a manuscript titled "Human Tissue Kallikrein in the Treatment of Acute Ischemic Stroke" was published in the peer-reviewed medical journal "Therapeutic Advances in Neurological Disorders (TAND)." The paper reviews the scientific literature covering the biochemical role of KLK1 and presents the mechanistic rationale for using KLK1 as an additional pharmacological treatment for AIS. In addition to the biochemical mechanism of KLK1, the paper highlights supporting results from human genetics and preclinical animal models of brain ischemia. It also reviews published clinical results for treatment of AIS by a form of KLK1 that is isolated from human urine. This form has been approved for post-infarct treatment of AIS in China and data has been published on clinical trials involving over 4,000 patients. The paper offers a series of testable therapeutic hypotheses for demonstrating the long-term beneficial effect of KLK1 treatment in AIS patients and the reasons for this action.

Financial Results

License revenue for 2018 was comprised of the initial $500,000 license payment DiaMedica received in connection with the license and collaboration agreement with Ahon Pharma.

Research and development expenses were $4.5 million for the year ended December 31, 2018 compared to $3.2 million for the year ended December 31, 2017, an increase of $1.3 million. The increase was primarily due to the additional preclinical testing and related costs required to support an application for an investigational new drug application in the United States, higher study costs for the REMEDY Phase II stroke study as compared with the DM199 bridging study which was substantially completed in 2017, and increased personnel and non-cash stock-based compensation costs.

General and administrative expenses were $2.7 million for the year ended December 31, 2018 compared to $1.3 million for the year ended December 31, 2017. General and administrative costs increased due to one-time costs incurred associated with the Company’s planned IPO in the United States, primarily the Nasdaq listing process and related legal and accounting fees. Higher salaries, fees and short-term benefits due to the addition of staff and higher share-based compensation also contributed to the increase during 2018.

Other income, net, was $1.1 million for the year ended December 31, 2018 compared to $259,000 for 2017. The increase resulted primarily from the recognition of the research and development incentive from the Australia Government paid for qualifying research work performed by DiaMedica Australia. This increase was partially offset by increased foreign currency transaction losses.

Balance Sheet and Cash Flow

Total cash resources were $16.8 million as of December 31, 2018, compared to $1.4 million as of December 31, 2017. Total current assets were $18.0 million and $1.5 million as of December 31, 2018 and December 31, 2017, respectively. These increases resulted primarily from net proceeds of $20.6 million received from the sale of common shares and warrants during 2018, partially offset by the use of cash to fund operations in the current year,

Current liabilities increased to $1.3 million as of December 31, 2018, compared to $1.0 million as of December 31, 2017. The increase in current liabilities resulted primarily from the increase in costs accrued related to clinical trials.

Net cash used in operating activities was $5.7 million for the year ended December 31, 2018, up from $3.9 million for the year ended December 31, 2017. The net cash used in each of these periods primarily reflects the net loss for these periods, and was partially offset by non-cash charges for stock-based compensation and the net effects of changes in operating assets and liabilities.

Conference Call Information

DiaMedica management will host a conference call to discuss these results on Wednesday March 20, 2019, at 8:00 a.m. Central Time:

Date:

Wednesday, March 20, 2019

Time:

8:00 AM CT

Web access:

View Source

Dial In:

(866) 962-3583 (domestic)

(630) 652-5857 (international)

Conference ID:

6773627

Listeners should log on to the website or dial in 15 minutes prior to the call. The webcast will remain available for play back on our website, under investor events and presentations, following the earnings call and for 12 months thereafter. A telephonic replay of the conference call will be available until March 28, 2019, by dialing 1(855) 859-2056 (US Toll Free Dial In), (404) 537-3406 (international), replay passcode 6773627.

About DM199

DM199 is a recombinant (synthetic) form of the human serine protease, KLK1. The KLK1 protein plays an important role in the regulation of diverse physiological processes including blood flow, inflammation, fibrosis, oxidative stress and neurogenesis via a molecular mechanism that increases production of nitric oxide and prostacyclin. KLK1 deficiency may play a role in multiple vascular and fibrotic diseases such as chronic kidney disease, retinopathy, stroke, vascular dementia, and resistant hypertension where current treatment options are limited or ineffective. DiaMedica is the first company to have developed a recombinant form of the KLK1 protein. The KLK1 protein, produced from porcine pancreas and human urine, has been used to treat patients in Japan, China and Korea for decades. DM199 is currently being studied in patients with acute ischemic stroke and patients with chronic kidney disease.

Context to Participate in Upcoming Investor Conferences in April

On March 19, 2019 Context Therapeutics, a clinical-stage biotechnology company focused on hormone driven cancers, reported it will present at the following upcoming investor conferences (Press release, Context Therapeutics, MAR 19, 2019, View Source [SID1234534482]).

Needham and Company 18th Annual Health Care Conference in New York City on Tuesday, April 9, 2019 at 2:30 p.m. ET.

Data from GARNET study indicates robust activity of dostarlimab in patients with advanced or recurrent endometrial cancer

On March 19, 2019 TESARO, an oncology-focused business acquired by GlaxoSmithKline plc (LSE/NYSE: GSK), reported the presentation of data from the Phase 1/2 GARNET study evaluating dostarlimab in women with recurrent or advanced endometrial cancer who progressed on or after a platinum-based regimen (Press release, GlaxoSmithKline, MAR 19, 2019, View Source [SID1234534481]). These data were presented at the 2019 Society for Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer in Honolulu, Hawaii. The preliminary results demonstrate clinically meaningful and durable response rates of dostarlimab (anti-PD-1 antibody, formerly TSR-042), in this patient population, regardless of microsatellite instability status. In addition, the safety findings indicate that dostarlimab is well tolerated with a safety profile consistent with what is expected of anti-PD-1 therapy.

Further data from the GARNET study will be analysed using the RECIST 1.1 criteria to support regulatory filing for dostarlimab in endometrial cancer at the end of 2019.

Mary Lynne Hedley, Ph.D., President and Chief Operating Officer of TESARO, said, "Currently, treatment options for women with advanced or recurrent endometrial cancer are limited, with only one FDA-approved agent for a subset of these patients. We intend to use these and other data from the GARNET study to seek regulatory approval of dostarlimab to potentially address the critical unmet treatment needs of women whose disease has progressed. The data presented today evaluating dostarlimab in women with recurrent/advanced endometrial cancer, combined with earlier data in patients with non-small cell lung cancer, reinforces the potential of dostarlimab in treating patients with a variety of solid tumours."

Endometrial cancer (EC) is the most common gynaecologic malignancy in the U.S. There are limited treatment options for women whose disease progresses on or after first-line therapy. EC can be classified as microsatellite stable (MSS/75%) or microsatellite instability-high (MSI-H/25%). Currently, there is only one approved therapy in the recurrent EC setting for the subset of patients with MSI-H tumours, and no approved treatments for patients with MSS EC who have recurred after platinum-based chemotherapy.

Key Study Findings
A total of 125 patients were analysed including 41 MSI-H (33%), and 79 MSS (63%) patients, as well as 5 with an unknown MSI-status (4%). Dostarlimab was dosed at 500 mg once every 3 weeks for 4 doses, followed by 1000 mg once every 6 weeks until disease progression.

Determination of MSI status was made based upon a central test using next generation sequencing (NGS). Treatment with dostarlimab monotherapy resulted in a clinically meaningful response rate in recurrent or advanced EC who progressed on or after a platinum-based regimen, regardless of MSI status. Overall response rates by irRECIST in the full population, MSI-H population, and MSS population were 30%, 49%, and 20%, respectively. Disease control rate in the full population, MSI-H population, and MSS population was 53%, 63% and 47%, respectively.

At the time of data cutoff, treatment was still ongoing in 84% of responders, with 89% of the responders (33 of 37) having been on treatment for more than six months and 49% of responders (18 of 37) having been on treatment for more than one year. Durability of response was similar between the MSI-H and MSS cohorts. The median duration of response (DOR) has not yet been reached. All responses were assessed using irRECIST criteria.

The data show that 88 out of 125 (70.4%) patients had at least 1 treatment-emergent adverse event (TEAE). The most commonly reported TEAEs related to dostarlimab were fatigue (14.4%), diarrhea (12.8%), and nausea (12.0%). In general, adverse events were low grade, with only 13.6% of patients experiencing grade 3 or higher adverse events. No deaths occurred due to a treatment-related adverse event. In total, 5.6% of all patients experienced a grade 3 or higher immune related, treatment-related adverse event.

About GARNET
The ongoing Phase 1/2 GARNET trial is evaluating dostarlimab as monotherapy in patients with advanced solid tumours. GARNET included a weight-based dose escalation study (Part 1) and a fixed-dose safety study (Part 2A), both of which have been completed. Results of these studies were used to determine the recommended Phase 2 dose (RP2D; 500 mg Q3W for the first 4 cycles then 1000 mg Q6W). Part 2B of the study includes four expansion cohorts: MSI-H endometrial cancer, MSI-H non-endometrial cancer, MSS endometrial cancer, and non-small cell lung cancer (NSCLC). Data from the NSCLC cohort have been previously presented at Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in 2018.

About dostarlimab
Dostarlimab (TSR-042) is an investigational humanized anti-programmed death (PD)-1 monoclonal antibody that binds with high affinity to the PD-1 receptor and effectively blocks its interaction with the ligands PD-L1 and PD-L2. If approved, dostarlimab would be the first anti PD-1 therapy administered as monotherapy every 3 weeks for 4 doses then every 6 weeks thereafter. Dostarlimab was developed as part of a collaboration between TESARO and AnaptysBio, Inc. This collaboration was initiated in March of 2014, and is focused on the development of monospecific antibody drugs targeting PD-1, TIM-3 (TSR-022), and LAG-3 (TSR-033), in addition to a bi-specific antibody drug candidate targeting PD-1/LAG-3 (TSR-075).

Dostarlimab is not currently approved for use anywhere in the world.

Actinium Reports Fourth Quarter and Year-End 2018 Financial Results and Provides Corporate Highlights

On March 19, 2019 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) reported its financial results for the fourth quarter and year ended December 31, 2018 as well as provided corporate and operational updates on clinical trials, research and development, recent hires, and intellectual property (Press release, Actinium Pharmaceuticals, MAR 19, 2019, View Source [SID1234534474]).

Company Highlights:

Presented interim Phase 3 SIERRA trial data at the 2018 ASH (Free ASH Whitepaper) and 2019 TCT Meetings. The SIERRA trial (Study of Iomab-B in Elderly Relapsed or Refractory AML) is a 150-patient pivotal Phase 3 multi-center randomized trial that will compare outcomes of patients who receive Iomab-B and a BMT or Bone Marrow Transplant to those patients receiving physician’s choice of salvage chemotherapy, defined as conventional care, as no standard of care exists for this patient population. Key highlights from the SIERRA Trial presented at ASH (Free ASH Whitepaper) and the TCT Meetings include:
All patients receiving a therapeutic dose of Iomab-B engrafted despite active disease with high blast count (median 30%, or median 45% for crossover patients)
15 of 19 (79%) patients in the control arm failed to achieve a complete response
67% (10/15) of patients eligible for crossover successfully transplanted after Iomab-B treatment
All patients receiving Iomab-B and a BMT (28/28) achieved Donor Chimerism prior to day 100
94% of patients initially randomized to receive Iomab-B and a BMT (17/18) achieved Full Donor Chimerism > 95% prior to day 100 with 1 patient achieving 65% donor chimerism
90% of patients who crossed-over to receive Iomab-B and a BMT (9/10), after salvage chemotherapy in the control arm failed to produce a CR or Complete Response, also achieved Full Donor Chimerism > 95% prior to day 100 with 1 patient achieving 86% donor chimerism
The SIERRA trial is currently enrolling patients at 18 sites in the U.S and Canada including many of the leading BMT sites based on volume. Patients with active, relapsed or refractory AML have dismal prognoses and are typically not offered potentially curative transplant as an option, largely because salvage treatments have a limited ability to produce a complete remission, which is necessary prior to conventional BMT if conventional BMT is to be successful. However, with Iomab-B targeted conditioning, a complete remission prior to starting the Iomab-B conditioning is not necessary for a successful transplant. Iomab-B is an ARC or Antibody Radiation-Conjugate that targets CD45, an antigen expressed on leukemia, lymphoma and immune cells, and delivers Iodine-131 that kills targeted cells via linear energy transfer. Key highlights from the SIERRA Trial presented at ASH (Free ASH Whitepaper) and the TCT Meetings include:

Initiated Actimab-A venetoclax combination trial. This novel Phase 1/2 trial will study Actimab-A in combination with venetoclax for patients with relapsed or refractory AML or Acute Myeloid Leukemia. Venetoclax is a BCL-2 or B-Cell Lymphoma 2 inhibitor, BCL-2 is one of several proteins encoded by the BCL2 gene family, which regulates apoptosis or programmed cell death. Venetoclax is jointly developed and marketed by AbbVie and Genentech and is approved for patients with CLL or Chronic Lymphocytic Leukemia, and SLL or Small Lymphocytic Leukemia and AML with an HMA or hypomethylating agent.
Response rates of relapsed or refractory patients with AML to venetoclax as a single agent have been reported to be 19%. In a recent webinar, Actinium highlighted that one study observed that of 21 relapsed or refractory AML patients that responded to venetoclax and an HMA, 13 (62%) stopped venetoclax treatment with disease progression being the most common reason for discontinuation. The study also observed that no patients with secondary AML responded to treatment with venetoclax and patients with FLT3 mutations had lower response rates.

MCL-1 is another protein encoded by the BCL2 gene family that is also overexpressed in cancers, including relapsed or refractory AML, that prevents apoptosis and promotes resistance to venetoclax, which does not bind to MCL-1. It has been observed that MCL-1 levels can be depleted with radiation, but only external radiation was used in these studies. Actinium is studying the use of targeted internalized radiation from Actimab-A to deplete MCL-1 levels thereby removing the AML cells’ resistance mechanism and rendering them more susceptible to venetoclax. Actimab-A is an ARC that delivers internalized radiation from the alpha-particle emitting isotope Ac-225 or Actinium-225 via the CD33 targeting monoclonal antibody lintuzumab

Actinium is conducting this combination study with the goal of offering a therapy to patients that do not respond or stop responding to venetoclax. In addition to the potential to deplete MCL-1 levels, Actimab-A’s radiation mechanism of action is agnostic to cytogenetic mutations and has shown to produce responses in patients with secondary AML. Actinium is also planning a Phase 1/2 trial that will study Actimab-A in combination with venetoclax and a hypomethylating agent. This triplet trial will also enroll patients with relapsed or refractory AML and is expected to initiate in the first half of 2019.

Advanced to second patient cohort in Actimab-A CLAG-M trial. Actinium is also studying Actimab-A in combination with the salvage chemotherapy regimen CLAG-M (cladribine, cytarabine, filgrastim, and mitoxantrone) in patients with relapsed or refractory AML. Chemotherapy and radiation are routinely used in combination together with a majority of patients receiving external beam radiation. However, patients with AML are not treated with external radiation as the diffuse nature of the disease prohibits therapeutic levels of radiation from being used due to safety and toxicity concerns. Ac-225 is a potent isotope capable of causing lethal double stranded breaks in cell DNA but its energy is limited to a few cell diameters. CD33 is an antigen expressed on the surface of a vast majority of AML cells. This trial is evaluating the effect targeted internalized radiation via Actimab-A will have in combination with CLAG-M on safety and tolerability, response rates, rates of BMT, PFS or progression-free survival, and OS or overall survival.
In the first dose cohort, patients received 0.25 uCi/kg of Actimab-A. This combination trial is designed as a 3+3 dose escalation study. No DLT’s or dose limiting toxicities were reported in the first patient cohort. As a result, and per the study protocol, the Institutional Review Board (IRB) at MCW authorized the initiation of the second dosing cohort, in which patients are receiving 0.50 uCi/kg of Actimab-A. Assuming no DLTs are observed in the second cohort, three patients will be treated and the study will progress to the third and final cohort that will study Actimab-A at a dose of 0.75 uCi/kg.

Advanced to second module of collaborative research program with Astellas Pharma, Inc. (Astellas). The Company’s previously announced research collaboration with Astellas is using its AWE or Antibody Warhead Enabling technology platform to conjugate and label select Astellas targeting agents with the potent Ac-225 payload. In January 2019, Actinium announced that it completed the first module of the collaboration and the second module had been initiated. Since launching its AWE Program in November 2017, Actinium has achieved the following milestones:
Appointed Dr. Dale Ludwig, a leading antibody therapeutics and antibody conjugate expert, as Chief Scientific Officer
Presented positive data at ASH (Free ASH Whitepaper) 2017 demonstrating the superior in vitro cell killing properties of Ac-225 labeled daratumumab or Darzalex, Johnson & Johnson’s blockbuster CD38 targeting therapy for multiple myeloma
Presented additional positive data from in vivo animal studies at AACR (Free AACR Whitepaper) 2018 demonstrating enhanced tumor control and survival with Ac-225 labeled daratumumab
Significantly strengthened senior leadership team in core areas. Appointed Cynthia Pussinen as Executive Vice President of Technical Operations and Supply Chain. Ms. Pussinen brings 25 years of highly relevant experience to Actinium gained at Pfizer and Ipsen Biosciences, Inc. Most recently, she was Head of Strategic Portfolio Management, Worldwide Research & Development. In this role she led efforts to maximize the value of Pfizer’s pre-Proof of Concept portfolio across 6 research units, including driving pipeline decision making, portfolio prioritization and clinical portfolio investment efforts across the R&D organization. Previously, President and General Manager of Ipsen Biosciences, Inc. where she led the operational and strategic directions of this subsidiary company, including maintaining an annual operating budget of more than $100 million, and managing two sites with more than 220 employees.
Appointed Qing Ling, PhD, DABR to newly created position of Vice President, Head of Radiation Sciences. This newly created position will drive innovation in line with Actinium’s strategic vision related to its AWE technology platform. Dr. Liang will collaborate closely with clinical trial sites and their staffs, regulators and other key stakeholders to help advance and optimize Actinium’s clinical ARC programs to deliver the best possible outcomes for patients. Dr. Liang is a Medical Physicist certified by the American Board of Radiology and prior to Actinium was Medical Physicist and Assistant Professor at Fox Chase Cancer Center at Temple University (Philadelphia, PA). Prior to that, she had worked at Mercy Health System (Janesville, WI), Turville Bay MRI & Radiation Oncology (Madison, WI), University of Wisconsin Hospital (Madison, WI), and UW Accredited Dosimetry Calibration Laboratory (Madison, WI).

Appointed Mamata Gokhale, PhD, RAC as Vice President, Global Head of Regulatory Affairs. Dr. Gokhale brings over 20 years of regulatory affairs experience to Actinium that began at the FDA as a reviewer before transitioning to industry where she worked at biotechnology and pharma companies including Amgen, Watson Pharma, Neumedicines Inc. and global Contract Research Organizations including Voisin Consulting Life Sciences and Paraxel International. At Amgen Dr. Gokhale successfully contributed to approvals and expansion of Prolia , Xgeva , Vectibix and Sensipar . Dr. Gokhale’s regulatory experience includes developing regulatory strategies for small molecules, monoclonal antibodies, cell and gene therapies, leading and managing regulatory interactions, requesting orphan drug, breakthrough therapy and fast track designations and pediatric vouchers, resolution of clinical hold issues, developing target product profiles, core data sheets and conducting labeling negotiations.

Significantly expanded patent portfolio. Through rejuvenated R&D activity Actinium’s patent portfolio has increased to a total of 111 issued and pending patents in the U.S. and internationally, which is up from the 75 reported previously. This intellectual property portfolio, contained within 28 patent families, covers key areas of Actinium’s business. The estate covers ARC generation, composition of matter, formulations, and methods of administration for solid and liquid cancers as well as radionuclide production including the manufacturing of Ac-225 or Actinium-225. Actinium’s recent patent filings pertain to its planned pivotal Actimab-MDS targeted conditioning trial, ARC combination trials of Actimab-A with venetoclax and CLAG-M, as well as its next-generation ARC’s resulting from its AWE technology platform. These follow recent patent filings from Actinium related to its Iomab-ACT next generation lymphodepletion program for CAR-T and adoptive cell therapies that includes four pending patents and one provisional patent application for cancer and non-malignant diseases. These new filings are in addition to Actinium’s broad intellectual property and patent portfolio that cover direct labeling, or conjugation and labeling of a biomolecular targeting agent to a radionuclide warhead, and its development and use as a therapeutic regimen for the treatment of diseases such as cancer. Actinium has patents on the use of the "gold standard" chelator DOTA, an organic compound used to attach, or conjugate, the radionuclide Ac-225 to monoclonal antibodies and any conceivable derivative thereof, as well key patents covering the manufacturing of Ac-225 in a cyclotron. In addition, Actinium extensive know-how and trade secrets in the application of its AWE technology platform to support its existing pipeline and potential collaborations.
Research and development expenses for the year ended December 31, 2018 declined by $0.7 million to $17.0 million compared to $17.7 million for the year ended December 31, 2017. The decrease was primarily attributable to the recognition of payments received from Astellas, with such payments accounted for as a reduction in research and development expenses, as well as lower expenses related to Actimab-A and lower non-cash stock-based compensation expense.
General and administrative expenses declined by $2.5 million to $6.7 million for the year ended December 31, 2018 compared to $9.2 million for the year ended December 31, 2017, primarily due to lower compensation expense, resulting from lower non-cash stock-based compensation expense during 2018 and one-time charges paid to certain former employees in 2017.

Actinium reported a cash and cash equivalent balance of $13.6 million as of December 31, 2018. In its Annual Report of Form 10-K which was filed with the Securities and Exchange Commission on March 15, 2018, the Company’s audited financial statements contained a going concern explanatory paragraph in the audit opinion from Marcum LLP, its independent registered public accounting firm.

Net loss decreased by $2.9 million to $23.7 million for the year ended December 31, 2018 compared to $26.6 million for the year ended December 31, 2017. The decrease was primarily due to lower general and administrative expenses and research and development expenses.

Upcoming Conferences
Actinium’s management will present at the Oppenheimer & Co. 29th Annual Healthcare Conference, being held March 19-20. The details of Actinium’s presentation are as follows:

Presentation Details:
Date: Wednesday, March 20, 2019
Time: 1:35 pm Eastern Time
Room: Consulate
Venue: Westin Grand Central Hotel in New York City

In addition, members of Actinium’s executive, clinical, R&D, commercial and CMC teams will be attending the AACR (Free AACR Whitepaper) or American Association of Cancer Research Annual Meeting being held March 29 – April 3 at the Georgia World Congress Center in Atlanta, Georgia and the TAT or 11th International Symposium on Targeted-Alpha-Therapy being held April 1 – 4 at the Fairmont Chateau Laurier in Ottawa, Canada.

I-Mab Biopharma and MorphoSys Announce Initiation of Pivotal Phase 2 Study of TJ202/MOR202 for Multiple Myeloma

On March 19, 2019 I-Mab Biopharma (I-Mab), a China-based clinical stage biopharmaceutical company exclusively focused on the development of innovative biologics in immuno-oncology and autoimmune diseases, and German biopharma company MorphoSys AG (FSE: MOR; Prime Standard Segment, MDAX & TecDAX;NASDAQ: MOR), reported that the first patient dosing (FPD) has been achieved in a phase 2 multi-center clinical study in Taiwan to evaluate an investigational human CD38 antibody TJ202/MOR202 in patients with relapsed or refractory multiple myeloma (Press release, I-Mab Biopharma, MAR 19, 2019, View Source [SID1234534473]). TJ202/MOR202 is an antibody developed by MorphoSys AG. I-Mab owns the exclusive rights for development and commercialization of TJ202/MOR202 in mainland China, Hong Kong, Macao and Taiwan.

"Advancing TJ202/MOR202 into a late stage phase 2 trial is a significant achievement," said Dr. Joan Shen, M.D., Head of R&D at I-Mab. "We expect that, if approved, TJ202/MOR202 may provide multiple myeloma patients with an important biologics treatment option with its unique benefit that addresses the underlying pathology of the second most common blood cancer worldwide."

The dosing of the first patient triggers a milestone payment of USD 5 million to MorphoSys.

Under I-Mab’s fast-to-market development strategy, the study has been designed as a pivotal trial, which, if successful, could lead to a biologics license application (BLA) in Greater China. The multi-center, single-arm, phase 2 study will be conducted in mainland China and Taiwan to evaluate the efficacy and safety of TJ202/MOR202 in combination with dexamethasone in patients with relapsed or refractory multiple myeloma who have previously received at least two prior lines of treatment. The primary endpoint is to evaluate the objective response rate.

"We are delighted that our partner I-Mab has taken this important step in advancing TJ202/MOR202 into pivotal clinical development in Asia. We see a high medical need for the treatment of patients with multiple myeloma in the Greater China region and look forward to supporting I-Mab in developing this investigational compound for these patients," said Dr. Malte Peters, Chief Development Officer of MorphoSys AG.

With MorphoSys’s support through a licensing agreement in November 2017, I-Mab is currently leading the clinical development of TJ202/MOR202 in Greater China, which includes mainland China, Hong Kong, Macao and Taiwan. In addition to Taiwan, I-Mab has filed an investigational new drug (IND) application to China’s National Medical Products Administration in August 2018.

It should be noted that the recent court decision of the United States (U.S.) District Court of Delaware (1:16-cv-00221-LPS-CJB) has no bearing on the validity and scope of the patents exclusively licensed by I-Mab from MorphoSys AG, whose exclusivity provides protection for I-Mab’s development and commercialization of MOR202 in the Greater China region.

About TJ202/MOR202

TJ202/MOR202 is an investigational human monoclonal antibody derived from MorphoSys’s HuCAL antibody technology. The antibody is directed against CD38 on the surface of multiple myeloma cells, which has been characterized as one of the most strongly and uniformly expressed antigens on the surface of malignant plasma cells. According to its suggested mode of action, the antibody recruits cells of the body’s immune system to kill the tumor through antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). The antibody does not involve complement dependent cytotoxicity, or CDC, an additional immune mechanism involved in tumor cell killing. Scientific researches suggest that an anti-CD38 antibody may have therapeutic potential also in other cancers as well as autoimmune diseases. Based on a licensing agreement between MorphoSys and I-Mab signed in November 2017, I-Mab owns the exclusive rights for development and commercialization of TJ202/MOR202 in mainland China, Taiwan, Hong Kong and Macao.