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TG Therapeutics Announces Orphan Drug Designation for the Combination of TG-1101 and TGR-1202 for the Treatment of Diffuse Large B-cell Lymphoma

On January 24, 2017 TG Therapeutics, Inc. (NASDAQ:TGTX) reported that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation covering the combination of TG-1101 (ublituximab), the Company’s novel, glycoengineered anti-CD20 monoclonal antibody, and TGR-1202 the Company’s oral, next generation PI3K delta inhibitor, for the treatment of patients with diffuse large B-cell lymphoma (DLBCL) (Press release, TG Therapeutics, JAN 24, 2017, View Source [SID1234517546]).

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The combination of TG-1101 and TGR-1202 is currently being evaluated in the UNITY-DLBCL Phase 2b Trial for patients with relapsed or refractory DLBCL as well as the UNITY-CLL Phase 3 Trial for patients with both frontline and previously treated chronic lymphocytic leukemia (CLL).

"We are pleased to receive orphan drug designation for our proprietary combination of TG-1101 and TGR-1202 in diffuse large B-cell lymphoma. This status complements our already strong proprietary protection portfolio which includes composition of matter patents issued for both TG-1101 and TGR-1202, as well as orphan drug designation already granted for the combination in CLL," stated Michael S. Weiss, Executive Chairman and Chief Executive Officer of TG Therapeutics. Mr. Weiss continued, "DLBCL is an area of significant unmet medical need and we are highly encouraged by the early clinical data we have seen in DLBCL patients treated with 1101 plus 1202 and look forward to evaluating this further in our ongoing Phase 2b registration directed trial."

ABOUT ORPHAN DRUG DESIGNATION

Orphan drug designation is granted by the FDA to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S. Orphan drug designation provides certain incentives which may include tax credits towards the cost of clinical trials and prescription drug user fee waivers. If a product that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan product exclusivity.

ABOUT DIFFUSE LARGE B-CELL LYMPHOMA

According to the American Cancer Society, diffuse large B-cell lymphoma (DLBCL) is an aggressive (fast growing) type of non-Hodgkin lymphoma (NHL), a cancer that starts in cells called lymphocytes, which are part of the body’s immune system. Diffuse large B-cell lymphoma is the most common type of NHL in the United States, accounting for about 30% of newly diagnosed cases of NHL. DLBCL occurs in both men and women and can affect any age group, although its prevalence increases with age, with the average age of diagnosis being in the mid-60s.

Cellectar Biosciences Announces Additional US Patent Granted for CLR 131 and CLR 125 in a Broad Range of Solid Tumors

On January 24, 2017 Cellectar Biosciences, Inc. (Nasdaq: CLRB), an oncology-focused clinical stage biotechnology company, reported that the United States Patent and Trademark Office ("USPTO") has granted patent number 9,550,002, which covers method of use for the company’s lead compound, CLR 131, as well as CLR 125, for the treatment of cancer (Press release, Cellectar Biosciences, JAN 24, 2017, View Source [SID1234517543]). The granting of this patent follows the company’s previous announcement of patent allowances for the use of the company’s phospholipid drug conjugate (PDC) delivery platform in these tumor types.

"This patent strengthens our radiotherapeutic intellectual property portfolio and further demonstrates Cellectar’s commitment to optimizing our PDC technology platform," said Jim Caruso, president and CEO of Cellectar. "While we are currently focused on developing CLR 131 for hematologic malignancies such as multiple myeloma, the claims granted provide additional development optionality for Cellectar or a potential partner."

The granted patent covers the use of CLR 131 for the potential treatment of a broad range of malignant solid tumors, which include adrenal, lung, ovarian or cervical, prostate, liver, breast and colon, as well as melanoma or subcutaneous cancers.

About CLR 131
CLR 131 is an investigational compound under development for a range of hematologic malignancies. It is currently being evaluated in a Phase I clinical trial in patients with relapsed or refractory multiple myeloma. The company plans to initiate a Phase II clinical study to assess efficacy in a range of B-cell malignancies in the first quarter of 2017. Based upon pre-clinical and interim Phase I study data, treatment with CLR 131 provides a novel approach to treating hematological diseases and may provide patients with therapeutic benefits, including overall response rate (ORR), an improvement in progression-free survival (PFS) and overall quality of life. CLR 131 utilizes the company’s patented PDC tumor targeting delivery platform to deliver a cytotoxic radioisotope, iodine-131 directly to tumor cells. The FDA has granted Cellectar an orphan drug designation for CLR 131 in the treatment of multiple myeloma.

About CLR 125
CLR 125 is a broad-spectrum, cancer-targeting, radiotherapeutic, which may be uniquely suited to treat micro-metastatic disease. CLR 125 uses the radioisotope iodine-125 conjugated to the company’s proprietary phospholipid drug conjugate (PDC) delivery platform. Similar to CLR 131, the selective uptake and retention of CLR 125 has been observed in malignant tissues during pre-clinical studies. Funded by a recent NCI SBIR award, the company evaluated the feasibility and safety of CLR 125 for the treatment of triple-negative breast cancer (TNBC) in the (neo) adjuvant setting. This program was successfully completed and demonstrated appropriate biodistribution, tolerability, and dose response.

About Phospholipid Drug Conjugates (PDCs)
Cellectar’s product candidates are built upon its patented cancer cell-targeting delivery and retention platform of optimized phospholipid ether-drug conjugates (PDCs). The company deliberately designed its phospholipid ether (PLE) carrier platform to be coupled with a variety of payloads to facilitate both therapeutic and diagnostic applications. The basis for selective tumor targeting of our PDC compounds lies in the differences between the plasma membranes of cancer cells compared to those of normal cells. Cancer cell membranes are highly enriched in lipid rafts, which are glycolipoprotein microdomains of the plasma membrane of cells that contain high concentrations of cholesterol and sphingolipids, and serve to organize cell surface and intracellular signaling molecules. PDCs have been tested in more than 80 different xenograft models of cancer.

Genmab Announces 2016 Net Sales Figures for DARZALEX® (Daratumumab)

On January 24, 2017 Genmab A/S (Nasdaq Copenhagen: GEN) reported that worldwide net sales of DARZALEX (daratumumab) as reported by Johnson & Johnson were USD 572 million in 2016 (Press release, Genmab, JAN 24, 2017, View Source [SID1234517538]). Net sales were USD 471 million in the U.S. and net sales in the rest of the world were USD 101 million. Genmab will receive royalties on the worldwide net sales of DARZALEX under the exclusive worldwide license to Janssen Biotech, Inc. to develop, manufacture and commercialize DARZALEX.

DARZALEX was approved in the U.S. in November 2015 and in Europe in May 2016. Net sales of DARZALEX in the U.S. in 2015 were USD 20 million, resulting in royalty income of DKK 16 million to Genmab.

About DARZALEX (daratumumab)
DARZALEX (daratumumab) injection for intravenous infusion is indicated in the United States 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 and as a monotherapy for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent, or who are double-refractory to a PI and an immunomodulatory agent.1 DARZALEX is the first monoclonal antibody (mAb) to receive U.S. Food and Drug Administration (FDA) approval to treat multiple myeloma. DARZALEX is indicated in Europe for use 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. 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).1,2,3,4,5
Daratumumab is being developed by Janssen Biotech, Inc. under an exclusive worldwide license to develop, manufacture and commercialize daratumumab from Genmab. Five Phase III clinical studies with daratumumab in relapsed and frontline multiple myeloma settings are currently ongoing, and additional studies are ongoing or planned to assess its potential in other malignant and pre-malignant diseases on which CD38 is expressed, such as smoldering myeloma, non-Hodgkin’s lymphoma, NKT-cell lymphoma, amyloidosis, myelodysplastic syndromes and solid tumors. 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.

Domain Therapeutics and Merck enter into a license and collaboration agreement for development of adenosine receptor antagonists in immuno-oncology

On January 23, 2017 Domain Therapeutics reported that a collaboration and licensing agreement with Merck, a leading science and technology company, has been signed for the development of adenosine receptor antagonist drugs specifically designed for oncology and immuno-oncology (Press release, Domain Therapeutics, JAN 23, 2017, View Source [SID1234606730]).

The agreement will involve close collaboration between Merck and Domain Therapeutics to develop and test new agents targeting key adenosine receptors. Merck will support research activities and gain worldwide rights to Domain Therapeutics’ next generation of adenosine receptor inhibitors. Under the terms of the agreement, Domain will be eligible for more than EUR 240 million in milestones, as well as undisclosed royalties.

"With its growing portfolio of immuno-oncology agents, Merck is the ideal partner to develop our adenosine programs," said Pascal Neuville, CEO, Domain Therapeutics. "As a strong collaborator with a leading investigational checkpoint inhibitor, we are confident that through Merck, our programs will progress rapidly."

Adenosine has been identified as a key component in resistance mechanisms for many tumors targeted by immune check-point inhibitors. While blocking certain adenosine receptors has been shown to increase the response to immune checkpoint inhibitors, antagonizing other adenosine receptors has also been shown to slow tumor progression.

"This new generation of adenosine receptor antagonists is an important addition to our immuno-oncology pipeline," said Laszlo Radvanyi, Senior Vice President, Head of Research in Immuno-Oncology at the biopharma business of Merck. "We plan to explore the promise of adenosine receptor antagonists and develop novel compounds to potentially use in new combination immunotherapies for cancer."

Aptose Prioritizes Development of CG’806 First-in Class FLT3/BTK Inhi

On January 23, 2017 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS), a clinical-stage company developing new therapeutics and molecular diagnostics that target the underlying mechanisms of cancer, reported it will prioritize its resources toward the development of CG’806, an oral preclinical compound being developed for patients with FLT3-driven acute myeloid leukemia (AML) and certain BTK-driven B-cell malignancies (Press release, Aptose Biosciences, JAN 23, 2017, View Source [SID1234539165]). Aptose will temporarily delay clinical activities with APTO-253, a phase 1 stage compound for AML, in order to elucidate the cause of recent manufacturing setbacks related to the intravenous formulation of APTO-253, with the intention of restoring the molecule to a state supporting clinical development and partnering.

Although Aptose has two compelling cancer drugs, current resources can support the full development activities of only one at this time. Recent advances with CG’806 have elevated this agent as having the best risk-reward profile to pursue with those resources. Such data established CG’806 as a well-differentiated pan-FLT3 inhibitor that demonstrates tumor eradication in the absence of toxicity in AML xenograft models, and it is on track for development as a therapy for certain AML patients. In addition, CG’806 is a potent non-covalent inhibitor of proliferation among certain BTK-driven B-cell derived cancer cells. The encouraging properties of CG’806, including its potency against well-established targets in diseases of severe medical need, warrant expeditious advancement and prioritization of resources toward this molecule.

"Concurrent evidence of a unique activity profile with CG’806 along with manufacturing delays for APTO-253 have led us to reprioritize our corporate strategy," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "While we remain confident in the viability of APTO-253 as a potential treatment for AML, we believe the greater value proposition to shareholders and patients is to focus our available resources on CG’806."

In November 2015, Aptose’s phase 1b trial of APTO-253 in patients with AML was placed on clinical hold. Since that time, the company has actively evaluated multiple formulation and production methodologies with the goal of developing a superior IV formulation. After successfully manufacturing multiple non-cGMP batches of a new drug product formulation for APTO-253, including a batch that has been stable and soluble for over six months, the company recently encountered an additional manufacturing setback which further delayed the return of APTO-253 to the clinic. While Aptose has made significant advances in understanding the novel c-Myc inhibitory mechanism of APTO-253, additional time will be required to define the cause of the cGMP manufacturing delay and to potentially restore APTO-253 to a state it can be developed clinically and partnered.

Based on information currently available, Aptose expects to report total cash and cash equivalents to be at a similar level as at September 30, 2016. As a result of activities to reprioritize its resources towards the development of CG’806, the cash on hand, which includes additional cash raised through its At-The-Market facility, is expected to provide sufficient resources to fund research and development and operations into Q4, 2017. Information reported above with respect to the financial year ended December 31, 2016 are preliminary and are subject to change and adjustment as the company’s 2016 financial results are finalized. Accordingly, investors are cautioned not to place undue reliance on the foregoing guidance. The company does not intend to continue to provide preliminary results in the future. Aptose expects to report its financial results for the financial year ended December 31, 2016 on or around March 14, 2016.

About CG’806

CG ‘806 is a once daily, oral, first-in-class FLT3/BTK inhibitor. This small molecule demonstrates potent inhibition of mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain), eliminates AML tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with FLT3-driven AML. Likewise, CG’806 demonstrates potent, non-covalent inhibition of the Cys481Ser mutant of the BTK enzyme, suggesting the agent may be developed for CLL and MCL patients that are resistant/refractory/intolerant to covalent BTK inhibitors.

Conference Call and Webcast

Aptose will host a conference call this morning, Monday, January 23, 2017 at 8:30 AM ET. Participants can access the conference call by dialing toll-free (844) 882-7834 (North America toll-free number) or (574) 990-9707 (international dial-in number), using the conference call passcode 58646784. The conference call can also be accessed here and will be available through a link on the Investor Relations section of Aptose’s website at ir.aptose.com. An archived version of the webcast will be available on the company’s website for 30 days.