On August 2, 2017 Bolder BioTechnology, Inc. reported that it has commenced dosing of patients in a Phase 1 clinical trial of its proprietary long-acting granulocyte colony-stimulating factor (G-CSF) analog, BBT-015 (Press release, Bolder BioTechnology, AUG 2, 2017, View Source [SID1234526029]). The trial is designed to study the pharmacokinetics, pharmacodynamics, safety and tolerability of single subcutaneous doses of BBT-015 in healthy human subjects. BBT-015 is being developed as a treatment for chemotherapy-related neutropenia in cancer patients and for Acute Radiation Syndrome.

Joe Cox, Ph.D., Bolder BioTechnology’s President said: "Initiation of this clinical trial represents a major milestone for Bolder BioTechnology and the culmination of many years of effort by our dedicated and talented employees."

"BBT-015 is a novel G-CSF analog that exhibits a longer duration of action and greater potency than other G-CSF products. In preclinical studies, BBT-015 stimulated larger and longer-lasting increases in neutrophils, and faster neutrophil recovery in chemotherapy-treated, neutropenic animals compared to other G-CSF products. BBT-015 also significantly increased survival and accelerated recovery of neutrophils, platelets, and red blood cells in animals exposed to lethal doses of radiation, even when administered 24 hours following radiation exposure."

"BBT-015’s increased potency and longer duration of action may stimulate faster neutrophil recovery in cancer patients and / or allow the drug to be administered less frequently and at lower doses than competing G-CSF products, with associated cost savings for patients."

"G-CSF products are some of the best selling biopharmaceuticals in the world, with annual worldwide sales exceeding $6 billion, primarily from the treatment of neutropenia in cancer patients."

About BBT-015
BBT-015 is a long-acting G-CSF analog produced using site-specific PEGylation technology. G-CSF is a human protein that stimulates production of neutrophils, a type of white blood cell that is important for fighting infections. G-CSF has a short half-life in humans and typically is administered to patients by daily injection. BBT-015 has been selectively modified with the polymer polyethylene glycol at a unique site in the protein, which allows the protein to last longer in patients, reducing the need for frequent administration and increasing the protein’s ability to stimulate long-lasting production of neutrophils.

About Chemotherapy-Related Neutropenia
Neutropenia (severely reduced numbers of neutrophils) is a common side effect of chemotherapy treatment in cancer patients. Neutropenia increases the patient’s risk of developing serious bacterial infection and requiring expensive hospitalization. G-CSF products are commonly administered to cancer patients following chemotherapy to accelerate neutrophil recovery and decrease the length of time that patients are neutropenic.

About Acute Radiation Syndrome
Acute Radiation Syndrome, often referred to as radiation sickness, is a collection of illnesses that occurs following exposure to high doses of ionizing radiation within a short period of time, such as might occur following an accident at a nuclear power plant or detonation of a nuclear weapon. Bone marrow, which is responsible for producing new blood cells, is one of the most radiation-sensitive tissues, and subjects acutely exposed to high doses of radiation typically develop bone marrow aplasia and severe neutropenia and thrombocytopenia (low numbers of platelets) within a few weeks of exposure, Many subjects die from infections due to a lack of neutrophils, or from uncontrolled bleeding due to a lack of platelets.

Abbott has filed a 10-Q – Quarterly report [Sections 13 or 15(d)] with the U.S. Securities and Exchange Commission .

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On August 2, 2017 Polaris Group reported that the first patient has been dosed in its randomized, placebo-controlled, double blind phase 2/3 trial (ATOMIC-meso) in malignant pleural mesothelioma (MPM) patients (Press release, Polaris Pharmaceuticals, AUG 2, 2017, View Source [SID1234526283]). Patients will be randomized to receive ADI‑PEG 20 (pegylated arginine deiminase) or placebo in combination with pemetrexed and cisplatin (PemCis), the standard first-line treatment for MPM (NCT02029690). In addition to this global phase 2/3 study, Polaris Group is currently conducting multiple phase 1 studies, including ADI‑PEG 20 in combination with PemCis in non-small cell lung carcinoma, glioblastoma, and uveal melanoma, in combination with pembrolizumab in advanced solid tumors, and in combination with FOLFOX in hepatocellular carcinoma, gastric cancer, and colorectal cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"ADI‑PEG 20 in combination with chemotherapy agents have demonstrated encouraging efficacy signals for several oncology indications in multiple phase 1 trials. We are working to pursue further investigations so we can bring effective treatments to more patients", said John Bomalaski, M.D., Executive Vice President, Medical Affairs at Polaris Pharmaceuticals, Inc.

About ADI‑PEG 20

ADI‑PEG 20 is a biologic being developed by Polaris Group to treat cancers carrying a major metabolic defect that renders them unable to internally synthesize arginine. Because arginine is essential for protein synthesis and survival of cells, these cancer cells become dependent upon the external supply of arginine to survive and grow. ADI‑PEG 20 is designed to deplete the external supply of arginine, causing arginine-dependent cancer cells to die while leaving the patient’s normal cells unharmed. Multiple cancers have been reported to have a high degree of arginine-dependency and can potentially be treated with ADI‑PEG 20.

On August 2, 2017 Molecular Templates, Inc., (Nasdaq:MTEM) a clinical stage biopharmaceutical company focused on the discovery and development of Engineered Toxin Bodies (ETBs), a new class of targeted biologic therapies that possess unique mechanisms of action in oncology, reported the completion of its previously announced merger with Threshold Pharmaceuticals, Inc. (NASDAQ: THLD, through August 1, 2017), effective as of August 1, 2017 (Press release, Molecular Templates, AUG 2, 2017, View Source [SID1234525558]). Following the completion of the merger, Molecular Templates completed a previously announced $40.0 million equity financing led by venture capital firm Longitude Capital, which invested $20.0 million in the combined company, with an additional $20.0 million from CAM Capital, BVF, Perceptive Advisors and others, including certain affiliates of Molecular Templates. In addition, following the completion of the merger and the Longitude-led financing, the combined company closed a $20.0 million equity investment from Takeda Pharmaceutical Company Ltd. made in connection with Molecular Templates’ entry into a collaboration and license agreement with Takeda. Together with pre-merger cash on Threshold’s balance sheet, and giving effect to the private placements, the combined company has a cash balance of approximately $75.0 million for use in funding its research and development activities.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The holders of shares of Molecular Templates common stock outstanding immediately prior to the merger received 7.7844 shares of Threshold common stock in exchange for each share of Molecular Templates common stock in the merger. The exchange ratio reflects a 1-for-11 reverse stock split effected by Threshold prior to the completion of the merger. Following the completion of the merger and the equity financings, the combined company has approximately 26,880,899 shares of common stock outstanding.

Following the completion of the merger, Threshold changed its name to Molecular Templates, Inc. The combined company will commence trading on August 2, 2017 on The Nasdaq Capital Market under the ticker symbol "MTEM."

"The completion of these transactions is an exciting step in the evolution of Molecular Templates as we enter the public markets," said Eric Poma, Ph.D., President, Chief Executive Officer and Chief Scientific Officer of Molecular Templates. "We are now well-funded and have the resources to further the development of our lead ETB product candidate, MT-3724, with new clinical efficacy and safety data from an MTD expansion study in relapsed/refractory DLBCL patients expected in 2018, and to develop our pipeline of drug candidates based on our next generation ETBs, the first of which is expected to enter the clinic in 2018. We are also committed to exploring Threshold’s evofosfamide (formerly TH-302), which is currently in a Phase 1 clinical trial in combination with ipilimumab in advanced solid tumors."

"I want to express my gratitude to the Threshold stockholders for supporting the merger with Molecular Templates, whose technology and clinical candidates we believe are differentiated with great promise for addressing significant unmet needs in the treatment of patients living with cancer," said Harold ("Barry") E. Selick, Ph.D., Threshold’s former Chief Executive Officer and chairman of the Board of Directors of the combined company. "I am looking forward to supporting the success of the combined organization."

Following the completion of the merger, Threshold moved its corporate headquarters to Austin, Texas. The combined company operates under the leadership of Molecular Templates’ management, including Eric E. Poma, Ph.D., as Chief Executive Officer and Chief Scientific Officer, and Jason Kim, President and Chief Operating Officer. In addition to Dr. Selick continuing as chairman, the Board of Directors of the combined company will include Dr. Poma, Kevin M. Lalande of Santé Ventures, David Hirsch M.D, Ph.D. of Longitude Capital, Scott Morenstein of CAM Capital, David R. Hoffmann of DRH Consulting and Michael Broxson of Takeda Pharmaceuticals.

Threshold’s financial advisor for the transaction is Ladenburg Thalmann & Co. Inc., and Threshold’s legal counsel is Cooley LLP. Molecular Templates’ legal counsel is Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.

About MT-3724
MT-3724 is Molecular Templates’ lead drug candidate. MT-3724 is in a Phase 1 clinical trial in heavily pre-treated non-Hodgkin’s lymphoma patients at the Memorial Sloan-Kettering Cancer Center, the MD Anderson Cancer Center, and the University of Arizona. An expansion arm of the Phase 1 study focused on relapsed and refractory diffuse large lymphoma patients is set to commence enrollment. More information is available at clinicaltrials.gov.

About MT-4019
MT-4019 is Molecular Templates’ preclinical drug candidate targeting CD38. MT-3724 has been awarded a $15.2 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT) to fund development. MT-4019 represents the second generation of Engineered Toxin Bodies (ETBs) that incorporate a proprietarily de-immunized scaffold.

About Evofosfamide
Evofosfamide (formerly TH-302) is an investigational hypoxia-activated prodrug of a bis-alkylating agent that is preferentially activated under severe hypoxic tumor conditions, a feature of many solid tumors. Areas of low oxygen levels (hypoxia) in solid tumors are due to insufficient blood vessel supply. Similarly, the bone marrow of patients with hematological malignancies has also been shown, in some cases, to be severely hypoxic. A Phase 1 clinical trial evaluating evofosfamide in combination with the immune checkpoint antibody, ipilimumab, is currently ongoing at the M.D. Anderson Cancer Center in Houston Texas. At the same time, while the PMDA has just indicated that the current analysis of the MAESTRO data is not sufficient to support the submission of a New Drug Application (NDA) in Japan, Molecular Templates is in ongoing discussions with the PMDA to clarify the scope of an additional study, the results of which may then support the submission of an NDA for evofosfamide in Japan.

On August 2, 2017 AstraZeneca and its haematology research and development centre of excellence, Acerta Pharma, reported that the US Food and Drug Administration (FDA) has accepted and granted priority review for the New Drug Application (NDA) for acalabrutinib, a highly-selective, potent, Bruton tyrosine kinase (BTK) inhibitor (Press release, AstraZeneca, AUG 2, 2017, View Source [SID1234519987]).

The NDA is based on results from the Phase II ACE-LY-004 clinical trial, which evaluated the safety and efficacy of acalabrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL) who have received at least one prior therapy. This follows the FDA’s recent Breakthrough Therapy Designation for acalabrutinib.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer, said: "FDA’s acceptance of the acalabrutinib application and Priority Review illustrates the impact it could have on patients with relapsed or refractory mantle cell lymphoma as we work to bring this potential medicine to those in need as quickly as possible."

Priority Review is granted to applications for medicines that, if approved, would offer a significant improvement in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions.[1] The Prescription Drug User Fee Act (PDUFA) date is during the first quarter of 2018.

Flavia Borellini, PhD, Acerta Pharma Chief Executive Officer, said: "We believe acalabrutinib has the potential to be a very important treatment option for patients with this life-threatening blood cancer. The FDA’s NDA acceptance exemplifies our progress in the acalabrutinib development programme and continues our momentum as we seek to transform care for people with haematologic malignancies."

Results from the ACE-LY-004 clinical trial will be submitted for presentation at a forthcoming medical meeting. The acalabrutinib development programme includes both monotherapy and combination therapy strategies in a broad range of blood cancers and solid tumours. The programme includes the Phase III ACE-LY-308 clinical trial evaluating acalabrutinib as a 1st-line treatment for patients with MCL.[2]

About mantle cell lymphoma (MCL)
Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma (NHL) with poor prognosis.[3],[4],[5],[6] MCL accounts for approximately 3% to 6% of new NHL cases in Western countries each year, with an annual incidence of 0.5 per 100,000 persons and an estimated prevalence of 3.5/100,000.5,[7] The median age at diagnosis is 68 years, with a 3:1 male predominance.5

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

About acalabrutinib
Acalabrutinib is a highly-selective, potent, covalent inhibitor of Bruton tyrosine kinase (BTK) with minimal off-target activity observed in pre-clinical trials.[8],[9],[10] This potential new medicine is in development for the treatment of multiple B-cell and other cancers. The acalabrutinib development programme includes both monotherapy and combination therapy strategies in chronic lymphocytic leukaemia (CLL), MCL, Waldenström macroglobulinemia (WM), follicular lymphoma, diffuse large B-cell lymphoma, and multiple myeloma, as well as monotherapy and combination trials in solid tumours. In total, more than 25 acalabrutinib clinical trials with more than 2,000 patients are underway or have completed. Acalabrutinib was granted Orphan Drug Designation by the FDA for the treatment of patients with MCL in September 2015 and by the European Commission in March 2016 for the treatment of patients with CLL, MCL and WM. Acalabrutinib was granted Breakthrough Therapy Designation by the FDA in August 2017 for the treatment of patients with MCL who have received at least one prior therapy. Acalabrutinib is a potential new medicine not approved for any current use.