On January 17, 2018 CTI BioPharma Corp. (NASDAQ and MTA:CTIC) reported that it expects to receive a $10 million milestone payment in February, 2018 from Teva Pharmaceutical Industries Ltd. related to the achievement of a milestone for U.S. Food and Drug Administration approval of TRISENOX (arsenic trioxide) for first line treatment of acute promyelocytic leukemia (Press release, CTI BioPharma, JAN 17, 2018, View Source;p=RssLanding&cat=news&id=2327170 [SID1234523276]). The milestone will be paid pursuant to an acquisition agreement for TRISENOX previously entered into with Teva under which CTI BioPharma is eligible to receive up to an additional $50 million in payments upon achievement by Teva of specified sales and development milestones related to TRISENOX.

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 January 17, 2018 NanOlogy reproted that it will Present at Drug Development & Delivery Networking Summit (Press release, NanOlogy, JAN 17, 2018, View Source [SID1234523294]).

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!

Event: Drug Development & Delivery Networking Summit
Dates: March 8, 2018
Location: Parsippany, NJ
Event Website: View Source

On January 17, 2018 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development and commercialization of innovative and effective therapeutics for the treatment of cancer, reported initiation of patient dosing in a Phase 1 trial of CA-4948, an orally available small molecule inhibitor of the IRAK4 kinase, for treatment of patients with lymphoma (Press release, Curis, JAN 17, 2018, View Source [SID1234523297]). CA-4948 was discovered at Aurigene and is the second licensed program from the Curis-Aurigene collaboration to enter the clinic.

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 Phase 1 study is designed to evaluate the safety, tolerability, and pharmacokinetic profile of CA-4948; identify any dose-limiting toxicities; and establish the recommended Phase 2 dose for the treatment of patients with lymphomas. The dose escalation stage of the trial will enroll patients with relapsed/refractory non-Hodgkin’s lymphoma, and the expansion stage will focus on specific populations of patients with lymphomas harboring alterations in the MYD88 gene or Toll-like receptor (TLR) signaling pathway.

"We are pleased to announce the advancement of our clinical pipeline with the initiation of the Phase 1 trial for this selective IRAK kinase inhibitor in patients with lymphomas," commented Ali Fattaey, Ph.D., Curis’s president and CEO. "Given the prevalence of activating mutations in the MYD88 gene and the TLR pathway, IRAK4 represents a significant target for the precision treatment of patients with different hematologic malignancies. In addition to its preclinical anti-tumor activity in MYD88-mutated lymphomas, we have observed encouraging effects of CA-4948 in animal models of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) as well as non-oncology inflammatory disease models. We look forward to working with our partner Aurigene to develop CA-4948 and explore clinical opportunities for these conditions in the near future."

"We are excited to have enrolled the first patient in this lymphoma clinical trial and look forward to further investigating CA-4948 as a potential new treatment option for patients with hematologic malignancies," said Mathew Lunning, DO, University of Nebraska Medical Center, an investigator for the study.

"We are delighted with our collaboration that has led to the advancement of the second program into the clinic, an IRAK4 targeting molecule that came out of Aurigene’s discovery efforts over many years," said CSN Murthy, Aurigene’s CEO. "Our investment into Curis exhibits our belief and commitment for this program and beyond as we work with Curis to focus our collective resources to advance exciting drug candidates."

About CA-4948, a Small-Molecule Inhibitor of IRAK4 Kinase

Innate immune responses orchestrated through Toll-like receptors are important mediators of the body’s initial defense against infections, while their dysregulation is associated with certain inflammatory conditions. Toll-like receptor signaling through the adaptor protein MYD88 results in the activation of IRAK4, initiating a signaling cascade that induces cytokine and survival factor expression. MYD88 gene mutations occur in approximately 30 percent of activated B-cell subtype of diffuse large B-cell lymphomas (DLBCL)1,2 and in over 90 percent of cases of the B-cell malignancy Waldenstrom’s macroglobulinemia (WM).3 IRAK4 has been validated as a target in DLBCL and WM disease setting, and its inhibition by CA-4948 has been shown to provide potent in vivo anti-tumor activity in animal models.4,5 IRAK4 inhibitors are also in clinical testing for treatment of patients with rheumatoid arthritis.

1Nature. 2011; 470(7332):115–119
2Immunology and Cell Biology. 2011; 89(6):659–660
3N Engl J Med. 2012; 367(9):826–833
4Cancer Res. 2017; 77(13 Suppl): Abstract 1168
5Blood. 2015;126(23):4004–4004

On January 17, 2018 Circle Pharma, Inc. reported that results from its collaborative work with Pfizer Inc. to develop a potent and orally bioavailable macrocycle modulator of the chemokine receptor, CXCR7, have been published in the Journal of Medicinal Chemistry (Press release, Circle Pharma, JAN 17, 2018, View Source [SID1234523306]).

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 goal of the collaboration was to deploy Circle’s rational design platform for macrocycle therapeutics in order to improve the drug-like characteristics of an existing macrocycle compound, and in particular to develop a cell permeable, orally bioavailable compound with enhanced target affinity. As reported in the publication, the collaboration produced a series of permeable and potent derivative macrocycles, including a compound having >500-fold increase in potency (CXCR7 Ki of ~ 9nM versus 2 uM for the starting compound), good cell permeability and 18% oral bioavailability in rats.

Additionally, permeable CXCR7 binding compounds with novel macrocycle backbone scaffolds were discovered through the efforts of the collaboration. This finding was not described in the publication.

"Cell permeability and orally bioavailability have been long-standing and well recognized challenges in the development of macrocycle therapeutics: nearly all synthetic macrocycle compounds in clinical development are against extracellular targets and are delivered by injection," noted David J. Earp, JD, PhD, Circle’s CEO. "Circle’s rational design approach coupled with efficient, low-cost synthesis uniquely enables us to design cell permeable, bioavailable macrocycles to address therapeutic targets that have been out of reach, including intracellular protein-protein interactions. This is a large target class with significant unmet clinical need."

"This collaboration successfully achieved its very challenging objective of delivering a potent and orally bioavailable macrocycle targeting CXCR7," said Spiros Liras, PhD, Vice President, Medicinal Chemistry, Pfizer.

The open-access scientific paper, entitled "Discovery of Potent and Orally Bioavailable Macrocyclic Peptide–Peptoid Hybrid CXCR7 Modulators," is available at View Source

About Macrocyclic Peptides

Macrocyclic peptides have the potential to allow drug developers to address the large proportion of known therapeutic targets (estimated at up to 80%) that are considered undruggable with conventional small molecule or biologic modalities. In particular, there is great interest in developing macrocycles to modulate protein-protein interactions, which play a role in almost all disease conditions, including cancer, fibrosis, inflammation and infection. However, the development of macrocyclic therapeutics has been limited by the need for a greater understanding of how to develop macrocycles with appropriate pharmacokinetics, cell permeability and oral bioavailability. Circle is applying its ability to design potent macrocycles with intrinsic cell permeability and drug-like characteristics to unlock access to challenging, high value therapeutic targets that have been out of reach by other approaches.

On January 17, 2018 Aeterna Zentaris Inc. (NASDAQ:AEZS) (TSX:AEZS) reported that it has, through a wholly-owned subsidiary, entered into a license and assignment agreement with a wholly-owned subsidiary of Strongbridge Biopharma plc (NASDAQ:SBBP) to carry out development, manufacturing, registration and commercialization of Macrilen (macimorelin) in the United States and Canada (Press release, AEterna Zentaris, JAN 17, 2018, View Source [SID1234523233]).

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 are very excited to partner with Strongbridge on the commercialization of Macrilen (macimorelin) in the U.S. and Canada," said Michael Ward, Chief Executive Officer of Aeterna Zentaris. "We look forward to exploring the various alternatives to monetizing our rights to Macimorelin outside the United States and Canada."

Aeterna Zentaris will receive an upfront cash payment of US$24,000,000 from Strongbridge, and, for as long as Macrilen (macimorelin) is patent-protected, Aeterna Zentaris will be entitled to a 15% royalty on net sales up to US$75,000,000 and an 18% royalty on net sales above US$75,000,000. Following the end of patent protection in United States or Canada for Macrilen (macimorelin), Aeterna Zentaris will be entitled to a 5% royalty on net sales in that country. In addition, Aeterna Zentaris will also receive one-time payments from Strongbridge following the first achievement of the following commercial milestone events:

US$4,000,000 on achieving US$25,000,000 annual net sales,
US$10,000,000 on achieving US$50,000,000 annual net sales,
US$20,000,000 on achieving US$100,000,000 annual net sales,
US$40,000,000 on achieving US$200,000,000 annual net sales, and
US$100,000,000 on achieving US$500,000,000 annual net sales.
Upon approval by the U.S. Food and Drug Administration ("FDA") of a pediatric indication for Macrilen (macimorelin), Aeterna Zentaris will receive a one-time milestone payment of US$5,000,000 from Strongbridge.

Strongbridge will fund 70% of the costs of a worldwide pediatric development program to be run by Aeterna Zentaris with customary oversight from a joint steering committee. The joint steering committee will be comprised of four persons, two of whom will be appointed by each of Strongbridge and Aeterna Zentaris.

The decision to license Macrilen (macimorelin) in the U.S. and Canada was made following a detailed review process undertaken by a committee of independent directors of Aeterna Zentaris. The committee of independent directors of Aeterna Zentaris was advised by Stifel, Nicolaus & Company, Incorporated. Aeterna Zentaris is continuing to explore various alternatives to monetizing its rights to Macimorelin in other countries around the globe, including whether to find other license partners in these jurisdictions or to use its internal resources to commercialize Macimorelin in one or more of these countries.

The Agreement will be filed on SEDAR at www.sedar.com. The foregoing description of the terms of the Agreement does not purport to be complete and is qualified in its entirety by reference to the Agreement.

Macrilen (macimorelin) is an orally-active ghrelin agonist that stimulates the secretion of growth hormone. Macrilen (macimorelin) has been granted orphan drug designation by the FDA for the evaluation of growth hormone deficiency. On December 20, 2017, the FDA granted Aeterna Zentaris marketing approval for Macrilen (macimorelin) to be used in the diagnosis of patients with adult growth hormone deficiency ("AGHD").

AGHD reportedly affects approximately 60,000 adults across the U.S. and Canada. Growth hormone not only plays an important role in growth from childhood to adulthood, but also helps promote a hormonally-balanced health status. AGHD mostly results from damage to the pituitary gland. It is usually characterized by a reduction in bone mineral density, lean body mass, exercise capacity, and overall quality of life as well as an increase of cardiovascular risks.