On December 2, 2016 Acetylon Pharmaceuticals reported that it has entered into an agreement to be acquired by Celgene Corporation (Press release, Acetylon, DEC 2, 2016, View Source [SID1234516903]). Prior to the consummation of the acquisition, Acetylon will spin out a new company, Regenacy Pharmaceuticals, LLC, which will focus on the development of novel drug candidates that selectively regenerate intracellular transport and upregulate gene expression to modify the course of disease. Regenacy will receive exclusive worldwide rights to Acetylon’s Phase 2 selective histone deacetylase 6 (HDAC6) inhibitor, ricolinostat (ACY-1215), for the treatment of certain non-cancer disease indications including neuropathies, as well as Acetylon’s preclinical selective HDAC1,2 inhibitor candidates and patent families for development in all human disease indications including sickle cell disease and beta-thalassemia.

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 acquisition will provide Celgene with, among other things, worldwide rights to Acetylon’s selective HDAC6 inhibitor programs and intellectual property in oncology, neurodegeneration, and autoimmune disease, including its lead drug candidates citarinostat (ACY-241) and ricolinostat (ACY-1215).

Financial terms of the acquisition are not being disclosed. The transaction is subject to customary closing conditions, including the expiration of the applicable waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976. BMO Capital Markets Corp. served as exclusive financial advisor to Acetylon in the transaction.

Key members of the Acetylon executive team will join Regenacy, which will operate out of Acetylon’s former headquarters in Boston’s Seaport District. Regenacy will be owned by Acetylon shareholders (excluding Celgene) and will receive net working capital in Acetylon to fund Regenacy operations.

"Since its founding in 2008, Acetylon has made substantial progress in the development of selective HDAC inhibitors for enhanced therapeutic outcomes," said Walter C. Ogier, President and Chief Executive Officer of Regenacy. "We are excited to continue Acetylon’s legacy through the receipt of rights to many of Acetylon’s most promising compounds and the continued advancement of these clinical and preclinical programs in disease indications outside of Celgene’s areas of strategic focus, where we believe patients may especially benefit from selective HDAC inhibition."

"Acetylon has had a longstanding partnership with Celgene, and their acquisition of our HDAC6 inhibitor programs is a positive event for patients and a favorable outcome for our shareholders and employees," said Marc A. Cohen, Chairman of Acetylon. "Celgene is the optimal partner to realize the fullest potential of Acetylon’s selective HDAC6 inhibitor programs in multiple myeloma and other oncology indications. Their intimate knowledge of citarinostat and extensive experience in oncology make them uniquely qualified to continue development of these exciting programs."

About Selective HDAC Inhibition

Histone deacetylases (HDACs) comprise a family of 18 related enzymes found in most human cells, 11 of which utilize zinc atoms to catalyze the removal of acetyl groups from intracellular proteins. By this function, HDACs can induce structural changes in the DNA-histone complex to result in altered gene expression and protein synthesis. Inappropriate deacetylation can disrupt these processes and contribute to a wide range of diseases, whereas regeneration of acetylation selectively causes apoptosis (cell death) in cancer cells and also induces favorable immunomodulatory effects. Currently available HDAC drugs non-selectively affect the expression of numerous other genes in normal cells as well as disease-causing cells, which can result in side effects such as gastrointestinal dysfunction, lowered blood platelet levels and risk of hemorrhage, and profound fatigue as well as potential for significant cardiac toxicity. Selective inhibition of HDACs is anticipated to reduce or eliminate these often-severe side effects associated with non-selective HDAC inhibition and to enable the development of optimized treatment regimens, including maximally effective combination drug therapies.

On December 2, 2016 PIQUR Therapeutics AG, a Swiss clinical-stage pharmaceutical company, reported that
the U.S. Food & Drug Administration (FDA) has granted orphan drug designation to PIQUR’s lead compound PQR309 for the treatment of primary central nervous system lymphoma (PCNSL) (Press release, PIQUR Therapeutics, DEC 2, 2016, View Source [SID1234527272]).

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!

PCNSL is a very rare and aggressive form of lymphoma involving brain and its linings, eyes or spinal cord. The disease affects less than 1 person in 100,000 in the USA with approximately 7,500 new cases reported annually in the USA, Europe and Japan. Treatment options available for PCNSL are limited, and the prognosis with current therapies is poor.

"We are very pleased to receive FDA orphan drug designation for PQR309 in PCNSL. This is an important regulatory milestone for the company and a significant step towards the clinical advancement of PQR309," said Dr. Ruggero Della Bitta, Chief Medical Officer of PIQUR. "This represents an important step towards addressing a high unmet medical need and bringing a potential treatment to those with this rare and life-threatening disease."

The Orphan Drug Designation Program, administered by the FDA’s Office of Orphan Products Development, is intended to encourage companies to develop therapeutics for diseases that affect fewer than 200,000 people in the USA. The designation provides the company several benefits and incentives, including assistance with clinical study design and drug development, tax credits for qualified clinical trials costs, exemptions from certain FDA application fees, as well as a seven-year period of market exclusivity upon regulatory product approval.

About PQR309
PIQUR’s lead compound, PQR309, is an oral, brain-penetrant, dual inhibitor of the PI3K/mTOR pathway, which is activated in 60 – 80% of human cancers. Unlike most of its competitors, PQR309 crosses the blood-brain barrier, expanding its use to malignant diseases involving the brain. Preclinical and Phase 1 studies have shown PQR309 to have a favorable safety, tolerability and pharmacokinetic profile. In addition, PQR309 has shown both preclinical
activity in various tumor models and clinical activity in Phase 1 and 2 studies.

PQR309 is currently being investigated in five Phase 1 and 2 clinical studies in advanced solid tumors (NCT02483858), relapsed or refractory lymphoma (NCT02249429), relapsed or refractory PCNSL (NCT02669511) and progressive glioblastoma multiforme (NCT02850744). In addition, the PIQHASSO Phase 1/2b study investigates PQR309 in combination with Eisai’s Eribulin in metastatic HER2-negative and triple-negative breast cancer (NCT02723877).

On December 2, 2016 Promedior, Inc., a clinical stage biotechnology company developing novel therapeutics for the treatment of fibrosis, reported that it completed enrollment in two Phase 2 clinical trials to evaluate PRM-151, its lead product candidate (Press release, Promedior, DEC 2, 2016, View Source [SID1234516904]). The idiopathic pulmonary fibrosis (IPF) trial completed the enrollment of 117 patients while the myelofibrosis trial completed enrollment of 84 patients. Promedior plans to present the results of these Phase 2 clinical studies at appropriate medical meetings once they are completed and analyzed.

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!

"We believe attaining these enrollment milestones speaks to both the need for new disease-modifying therapies for IPF and myelofibrosis and the promise that others see in PRM-151, Promedior’s lead product candidate" said Rick Jack, Ph.D., Promedior’s President and COO. "We look forward to completing these trials with the goal to bring PRM-151 forward as a potential new treatment option for patients with IPF and myelofibrosis, and ultimately for other fibrotic diseases."

The IPF clinical trial is a Phase 2 randomized, double-blind, placebo-controlled, pilot study designed to evaluate the efficacy and safety of PRM-151 administered once-a-month to subjects with IPF. The primary endpoint is forced vital capacity (FVC)% predicted change from baseline. For additional details about this clinical trial (NCT02550873), please visit www.clinicaltrials.gov.

The myelofibrosis clinical trial is a randomized, double blind Phase 2 study to determine the efficacy and safety of three different doses of PRM-151 in subjects with Primary Myelofibrosis (PMF), Post-Polycythemia Vera MF (post-PV MF), or Post-Essential Thrombocythemia MF (post-ET MF). Subjects were randomized to one of three dose cohorts: 0.3 mg/kg, 3.0 mg/kg or 10 mg/kg of PRM-151 administered once-a-month. The primary endpoint is bone marrow response rate, defined as the percent of subjects with a reduction in bone marrow fibrosis score by at least one grade according to WHO criteria at any time during the study. For additional details about this clinical trial (NCT01981850), please visit www.clinicaltrials.gov.

About Idiopathic Pulmonary Fibrosis
IPF is a serious, life-limiting lung disease characterized by fibrosis and scarring of lung tissue with a median survival of 3–5 years after diagnosis. Replacement of normal lung tissue by fibrosis results in restriction in the ability to fill the lungs with air and decreased transfer of oxygen from inhaled air into the bloodstream resulting in lower oxygen delivery to the brain and other organs. Patients with IPF most often suffer from progressive shortness of breath, particularly with exertion; chronic, sometimes debilitating, hacking cough; fatigue and weakness, and chest discomfort. Currently available approved drugs slow down but do not halt disease progression and the only curative therapy is lung transplant, an option merely available for a small group of patients. While estimates vary, it is believed that IPF could affect approximately 130,000 patients in the US and approximately 76,000 patients in Europe.

About Myelofibrosis
Myelofibrosis (MF), a type of myeloproliferative neoplasm, is a serious, life-limiting cancer that is characterized by fibrosis of the bone marrow. Replacement of the bone marrow by scar tissue prevents the normal production of blood cells, leading to anemia, fatigue, and increased risk of bleeding and infection. Production of blood cells shifts to the spleen and liver (extramedullary hematopoiesis), which become enlarged, causing severe discomfort, inability to eat, and weakness. Symptomatic myelofibrosis affects approximately 18,000 people per year in the US, with a median age of 61-66.1 The only potentially curative treatment is allogeneic bone marrow transplant, which results in reversal of fibrosis and all symptoms, but is a realistic option for only a small number of patients. Other currently available therapies address the symptoms, but have minimal if any impact on the underlying fibrosis.

About PRM-151
PRM-151, Promedior’s lead product candidate, is a recombinant form of the endogenous human innate immunity protein, pentraxin-2 (PTX-2), which is specifically active at the site of tissue damage. PRM-151 is an agonist that acts as a macrophage polarization factor to prevent and potentially reverse fibrosis. PRM-151 has shown broad anti-fibrotic activity in multiple preclinical models of fibrotic disease, including pulmonary fibrosis, myelofibrosis2, acute and chronic nephropathy, liver fibrosis, and age-related macular degeneration.

Phase 1a and 1b clinical studies in healthy subjects and IPF patients have demonstrated that PRM-151 was well tolerated. Additionally, a Phase 1b study in patients with IPF showed encouraging results in exploratory efficacy end points3. In an earlier Phase 2 trial in myelofibrosis, PRM-151 treatment was well-tolerated and demonstrated decreases in bone marrow fibrosis and stable or improved hematologic parameters4.

On December 2, 2016 Ignyta, Inc. (Nasdaq: RXDX), a biotechnology company focused on precision medicine in oncology, reported data examining the combination of entrectinib and trametinib in overcoming resistance to TRK inhibition during a late-breaking oral plenary presentation (during the Exceptional Response and Expected Resistance Session) at the 2016 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Molecular Targets and Cancer Therapeutics Symposium in Munich, Germany (Press release, Ignyta, DEC 2, 2016, View Source [SID1234516880]). Entrectinib is the company’s orally available, CNS-penetrant tyrosine kinase inhibitor, targeting tumors that harbor TRK, ROS1 or ALK fusions, and is currently in a registration-enabling Phase 2 clinical trial known as STARTRK-2.

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!

"This presentation is a great example of the successful translation of preclinical observations into clinical practice for the benefit of patients," said Alexander Drilon, M.D., of Memorial Sloan Kettering Cancer Center, who presented the data on behalf of the abstract authors at ENA. "The patient experience described in today’s presentation highlights the ability of entrectinib, in combination with a MEK inhibitor, to overcome potential treatment resistance that has been described for TRK inhibitors."

Data presented describe results from a single patient protocol designed to allow co-administration of entrectinib and trametinib, a commercially-approved MEK inhibitor. The patient, diagnosed with mammary analog secretory carcinoma (or MASC) with an NTRK3 fusion—~90-100% of MASC cases have TRK fusions—and previously treated with multiple surgeries, radiation, vinorelbine, carboplatin/paclitaxel, doxorubicin and crizotinib, experienced a rapid and confirmed partial response (89% reduction) with single-agent entrectinib treatment and remained on therapy for nine months. However, during the course of therapy, the patient’s tumor developed a solvent front point mutation, the predicted mechanism of resistance to first generation TRK inhibitors and analogous to a common mechanism of resistance for other TKIs against other fusion targets.

Based on both in vitro and in vivo data developed by Ignyta, indicating that entrectinib plus a MEK inhibitor could overcome such TRK inhibitor resistance, a single patient protocol was created, reviewed by the FDA and implemented to allow for dose escalation of entrectinib in combination with trametinib. While on the combination, all drug-related adverse events (AEs) were grade 1 or 2, and no new AEs specific to the combination were encountered. The patient achieved a 22% reduction in tumor volume and remained on the combination regimen for nearly seven months.

"This single-patient protocol is an excellent example of our vision at Ignyta, leveraging the molecular alterations responsible for cancer’s growth to design rational treatment strategies for patients in their fight against cancer," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "In addition to STARTRK-2, our global Phase 2 basket trial of entrectinib in multiple tumor histologies and STARTRK-NG, our Phase 1/1b trial of entrectinib in pediatric patients with solid tumors, we look forward to further exploration of entrectinib in combination with a MEK inhibitor in a Phase 1/1b clinical trial anticipated to initiate in the second half of 2017."

On December 2, 2016 Stemline Therapeutics, Inc. (Nasdaq:STML) reported that SL-401, a novel targeted therapeutic directed to CD123, will be featured in seven presentations, including three oral presentations, at the 2016 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, being held December 3-6, 2016 at the San Diego Convention Center in San Diego, CA (Press release, Stemline Therapeutics, DEC 2, 2016, View Source [SID1234516890]).

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!

Investigators will deliver an oral presentation on updated clinical data from the SL-401 Phase 2 trial in blastic plasmacytoid dendritic cell neoplasm (BPDCN). Additional presentations include early clinical data from ongoing SL-401 clinical trials in patients with acute myeloid leukemia (AML) in remission with high relapse risk (selected for oral presentation), high-risk myeloproliferative neoplasms (MPN), and relapsed/refractory multiple myeloma. Preclinical data to be presented include an oral presentation of SL-401 activity against cancer stem cells (CSCs) of AML and myelodysplastic syndrome (MDS), as well as SL-401 activity against CSCs of myeloma and SL-401 efficacy in combination with SL-801, a novel XPO1 inhibitor, against myeloma and other malignancies.

Details on the presentations are listed below. Additionally, presentations will be available on the Stemline website, Scientific Presentations tab, after their delivery.

Details on the presentations are as follows:

SL-401 – BPDCN (Clinical) – Oral Presentation
Title: Results from Phase 2 Trial Ongoing Expansion Stage of SL-401 in Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)
Presenter: Naveen Pemmaraju, MD; MD Anderson Cancer Center
Abstract: 342
Session: 613. Acute Myeloid Leukemia: Clinical Studies: Optimizing Current AML Therapy
Date/Time: Sunday, December 4, 2016 10:45 AM PT
Location: Marriott Marquis San Diego Marina, Pacific Ballroom

SL-401 – AML in CR with MRD (Clinical) – Oral Presentation
Title: Results from Ongoing Phase 2 Trial of SL-401 As Consolidation Therapy in Patients with Acute Myeloid Leukemia (AML) in Remission with High Relapse Risk Including Minimal Residual Disease (MRD)
Presenter: Andrew Lane, MD, PhD; Dana-Farber Cancer Institute
Abstract: 215
Session: 613. Acute Myeloid Leukemia: Clinical Studies: Innovations in Induction Therapy
Date/Time: Saturday, December 3, 2016 5:00 PM PT
Location: Marriott Marquis San Diego Marina, San Diego Ballroom AB

SL-401 – Myeloproliferative neoplasms (Clinical)
Title: Results from Ongoing Phase 2 Trial of SL-401 in Patients with Advanced, High-Risk Myeloproliferative Neoplasms Including Chronic Myelomonocytic Leukemia
Presenter: Mrinal Patnaik, MBBS; Mayo Clinic
Abstract: 4245
Session: 634. Myeloproliferative Syndromes: Clinical: Poster III
Date/Time: Monday, December 5, 2016 6:00 PM – 8:00 PM PT
Location: San Diego Convention Center, Hall GH

SL-401 — Multiple myeloma (Clinical)
Title: Results from Ongoing Phase 1/2 Trial of SL-401 in Combination with Pomalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma
Presenter: Myo Htut, MD; City of Hope
Abstract: 5696
Date/Time: Thursday, December 1, 2016 publication release
Location: Published online on ASH (Free ASH Whitepaper) abstract website

SL-401 – AML and MDS cancer stem cells – Oral Presentation
Title: SL-401 Mediates Potent Cytotoxicity Against CD123+ AML and MDS with Excess Blasts and Demonstrates Therapeutic Benefit in PDX Model
Presenter: Rajeswaran Mani, PhD; Ohio State University
Abstract: 580
Session: 604. Molecular Pharmacology and Drug Resistance in Myeloid Diseases: Targeting Leukemia-Initiating Cells
Date/Time: Monday, December 5, 2016 ?7:45 AM PT
Location: San Diego Convention Center, Room 24

SL-401 in combination with SL-801 — Multiple myeloma and other malignancies
Title: SL-401, a Targeted Therapy Directed to the Interleukin-3 Receptor (CD123), and SL-801, a Reversible Inhibitor of Exportin-1 (XPO1), Display Synergistic Anti-Tumor Activity Against Hematologic Malignancies in Vitro
Presenter: Janice Chen, PhD; Stemline
Abstract: 4724
Session: 802. Chemical Biology and Experimental Therapeutics: Poster III
Date/Time: Monday, December 5, 2016 6:00 PM – 8:00 PM PT
Location: San Diego Convention Center, Hall GH

SL-401 – Multiple myeloma
Title: SL-401, a Novel IL-3Rα/CD123—Directed Agent Targets Stem-like Cells in Multiple Myeloma
Presenter: Arghya Ray, PhD; Dana-Farber Cancer Institute
Abstract: 4463
Session: 652. Myeloma: Pathophysiology and Pre-Clinical Studies, excluding Therapy: Poster III
Date/Time: Monday, December 5, 2016 6:00 PM – 8:00 PM PT
Location: San Diego Convention Center, Hall GH