On October 15, 2019 Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) ("Takeda") reported that it has entered into an agreement to divest a portfolio of select over-the-counter (OTC) and prescription pharmaceutical assets in a number of Near East, Middle East and Africa (NEMEA) countries within its Growth and Emerging Markets Business Unit to Acino for a total value in excess of $200 million USD (Press release, Takeda, OCT 15, 2019, View Source [SID1234542269]). This is the third transaction in FY19 that furthers Takeda’s strategy to focus on business areas core to its long-term growth and facilitate rapid deleveraging following its acquisition of Shire.

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!

"Takeda remains committed to this region, as we continue our work in accelerating access to our life-changing portfolio of innovative products to meet the needs of patients. We will do this via our commercial activities and Takeda’s Access to Medicines program"

Tweet this
"The divestment of non-core assets sold in NEMEA represents the continued execution of our strategy to optimize our portfolio, invest in the defined core business areas, and accelerate our progress toward reaching our target leverage ratio," said Costa Saroukos, Chief Financial Officer, Takeda.

While these products continue to play important roles in meeting patient needs, they are primarily outside of Takeda’s chosen business areas – Gastroenterology (GI), Rare Diseases, Plasma-Derived Therapies, Oncology and Neuroscience – core to its global long-term growth.

"Takeda remains committed to this region, as we continue our work in accelerating access to our life-changing portfolio of innovative products to meet the needs of patients. We will do this via our commercial activities and Takeda’s Access to Medicines program," said Ricardo Marek, President, Growth and Emerging Markets Business Unit, Takeda. "We are confident that Acino is best positioned to provide uninterrupted access and supply of the divested products to patients."

Takeda intends to use the proceeds from this divestiture to reduce debt and continue to deleverage towards its target of 2.0x net debt/adjusted EBITDA over the next three to five years. Takeda is committed to rapid deleveraging driven by strong cash flow and divestiture proceeds, while also simplifying its portfolio.

Transaction Details

Takeda has agreed to sell a portfolio of approximately 30 select prescription pharmaceutical and OTC products sold in the NEMEA region to Acino, a Swiss pharmaceutical company headquartered in Zurich, with a clear focus on selected markets in the Middle East, Africa, the CIS Region, and Latin America. The following key countries are included in the agreement: Egypt, Saudi Arabia, South Africa, Turkey, Ukraine and United Arab Emirates, as well as other countries.

Under the terms of the agreement, Acino will acquire the rights, title, and interest to the products in the portfolio exclusive to these countries. It is anticipated that primarily sales and marketing professionals supporting the portfolio will transition to Acino at closing of the transaction. The parties will also enter into a multi-year manufacturing and supply agreement, under which Takeda will continue to manufacture the products on behalf of Acino.

The transaction is expected to close in Q4 FY19 (January – March 2020), subject to the satisfaction of customary closing conditions including receipt of applicable antitrust approvals. Until then, these products will continue to be made available by Takeda.

Takeda is being advised by BofA Securities (financial advisor), White & Case (legal advisor), and Deloitte (financial consultant) in this transaction.

On October 15, 2019 Cyteir Therapeutics, a leader in the discovery and development of next-generation synthetic lethal therapies for cancer, reported the close of an additional $40.2 million in the company’s Series B financing, for a total of $75.2 million in this financing (Press release, Cyteir Therapeutics, OCT 15, 2019, View Source [SID1234542288]). The additional funding will be used to expand the clinical investigation of Cyteir’s first-in-class RAD51 inhibitor and lead compound, CYT-0851, and to identify new targets using the company’s novel gain-of-function synthetic lethality screening platform.

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!

Novo Holdings led the round, joined by existing investors Venrock, DROIA Oncology Ventures, Osage University Partners (OUP), Lightstone Ventures and Celgene Corporation. As part of this closing, Karen Hong, Ph.D., of Novo Ventures, which provides consulting services to Novo Holdings, will join the Cyteir Board.

"The continued support for Cyteir from highly knowledgeable investors reflects the growing excitement around our novel application of synthetic lethality," said Markus Renschler, M.D., Cyteir president and CEO. "This financing will support the recently launched first-in-human phase 1/2 study of CYT-0851 while simultaneously allowing us to continue investigating our synthetic lethality platform to find new targets that inhibit DNA damage repair. We believe this approach could lead to valuable new treatment options for cancer patients."

Cyteir’s platform is based on the discovery of a relationship between DNA-damaging enzymes known as cytidine deaminases, and RAD51, a protein that is essential for the repair of DNA breaks. These enzymes are non-damaging in healthy tissues, but gain hyperactive function in a wide range of cancers and cause elevated DNA damage. Cyteir is developing selective small-molecule inhibitors of RAD51 to reduce the ability of cancer cells to self-repair through homologous recombination. This causes the cancer cells to become overwhelmed by accumulated DNA damage and undergo cell death – resulting in the therapeutic effect known as "synthetic lethality."

In preclinical experiments, CYT-0851 demonstrated synergy with PARP inhibitors, consistent with its DNA damage-repair pathway inhibitory activity. These results suggest CYT-0851 has the potential to overcome PARP inhibitor resistance.

Researchers at Sarah Cannon Research Institute in Nashville, Tenn., recently dosed the first patient in a Phase 1/2 study of CYT-0851. This study will enroll up to 200 patients with B-cell malignancies and solid tumors.

"We are pleased to be part of this study, which will help define the potential of an entirely new class of targeted cancer therapy," said Johanna Bendell, M.D., chief development officer at Sarah Cannon Research Institute and the study’s lead investigator. "Pre-clinical evaluations of CYT-0851 have been very encouraging, and we look forward to seeing how this compound impacts patients in this trial."

In March 2019, Cyteir presented pre-clinical data at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) annual meeting that validated the mechanism of action underlying the company’s synthetic lethal platform and confirmed that CYT-0851 is a potent inhibitor of RAD51-mediated homologous recombination with the potential to target multiple cancers that have high levels of cytidine deaminase-related DNA damage. The data indicated that CYT-0851 could potentially be clinically active as a monotherapy against B-cell lymphomas and multiple solid tumors, including pancreatic cancer.

About the CYT-0851 Phase 1/2 Trial

CYT-0851-01 is a phase 1/2 study of CYT-0851 in patients with relapsed, refractory non-Hodgkin lymphoma, chronic lymphocytic leukemia, multiple myeloma, or advanced breast cancer, ovarian cancer, head and neck cancer, soft tissue sarcoma, and pancreatic cancer. The study will be conducted at leading research institutions in the United States. An initial dose-escalation phase will establish the safety and tolerability of CYT-0851 and identify the recommended phase 2 dose. This will be followed by an expansion phase to evaluate response rates among each of six disease cohorts. Cyteir is also developing a companion diagnostic assay to identify patients with tumors that overexpress certain cytidine deaminases that may make them more susceptible to RAD51 inhibition.

About CYT-0851

CYT-0851 is an experimental, oral, selective inhibitor of RAD51, a protein involved in homologous recombination. Cancer cells that overexpress certain DNA-damaging cytidine deaminases rely on RAD51 to repair DNA damage. In preclinical models, inhibition of RAD51 with CYT-0851 induces cell death in cytidine deaminase overexpressing cell lines and reduces proliferation.

On October 15, 2019, Aclaris Therapeutics, Inc. (the "Company") and Rigel Pharmaceuticals, Inc. ("Rigel") reported that it entered into a First Amendment (the "First Amendment") to the License and Collaboration Agreement, originally dated as of August 27, 2015 (the "Original Agreement") (Filing, 8-K, Aclaris Therapeutics, OCT 15, 2019, View Source [SID1234542327]).

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!

Pursuant to the First Amendment, the Company and Rigel agreed to eliminate certain of the development milestones and Rigel released the Company from any obligation to pay a milestone payment for such milestones. The Company also agreed to pay Rigel an amendment fee of $1.5 million to be paid in three equal tranches of $500,000 in January 2020, April 2020 and July 2020. In addition, the parties modified certain other development milestones, and the Company agreed to increase the potential payments payable upon the achievement of such milestones from $10.0 million to $10.5 million in the aggregate. The First Amendment also provides that the Company’s obligation to use commercially reasonable efforts to develop, seek regulatory approval and commercialize at least one product would be deemed satisfied by the Company using commercially reasonable efforts to find a third party to use commercially reasonable efforts to develop, seek regulatory approval and commercialize at least one product.

Except as modified by the First Amendment, all terms and conditions of the Original Agreement remain in full force and effect.

On October 15, 2019 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel immunotherapy treatments for cancer and autoimmune diseases, reported mature positive efficacy data from its TACTI-mel Phase I clinical study combining its lead product candidate, eftilagimod alpha ("efti" or "IMP321") with KEYTRUDA (pembrolizumab) in metastatic melanoma (Press release, Immutep, OCT 15, 2019, View Source [SID1234542252]).

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 data will be presented by Dr. Frédéric Triebel, Chief Scientific Officer and Chief Medical Officer of Immutep at the World Immunotherapy Congress as part of the Festival of Biologics 2019 being held in Basel, Switzerland on 15th October 2019.

Commenting on the positive results, Dr. Triebel said, "The combination therapy with efti shows very encouraging efficacy signals of synergy with KEYTRUDA along with a favourable safety profile so far in this high-risk patient population. Patients are responding well to the combination treatment, their tumours are shrinking and not growing back over a long follow up period. In addition, we have seen the complete disappearance of all target tumour lesions for six patients plus one patient with a metabolic complete response on the PET-scan. The efficacy data is now final with a long follow up, the safety assessment is ongoing."

Overview of Trial

TACTI-mel evaluated the combination of efti with anti-PD-1 therapy KEYTRUDA (pembrolizumab) in 24 patients with unresectable or metastatic melanoma. Patients participating in the trial had a very late stage of disease: 75% classified as M1c (associated with lowest probability of survival), 67% had lung metastasis, 50% had liver metastasis, 50% had elevated LDH (poor prognosis marker) and many had either a suboptimal response or disease progression with pembrolizumab treatment as a monotherapy. All patients received subcutaneous injections of efti every two weeks, with a treatment duration of up to either six or 12 months.

TACTI-mel is a multi-centre, open label clinical trial involving four cohorts of six patients per cohort:

Part A includes the first three cohorts testing different dosages of efti (1mg, 6mg and 30mg) in combination with pembrolizumab, with efti treatment given for six months only and commencing at cycle five of pembrolizumab treatment.

Part B includes the remaining cohort testing a 30mg dosage of efti given for 12 months in combination with pembrolizumab, starting at cycle 1, day 1 of pembrolizumab treatment.

The primary endpoint of the trial is safety and tolerability, with the outcome to determine the recommended dose for a Phase II trial. The trial also evaluated efficacy through Overall Response Rate (ORR), tumour shrinkage and Disease Control Rate (DCR).

Key Findings

Efti has a favourable safety profile in combination with pembrolizumab with no dose-limiting toxicities.

The recommended dosage level for a Phase II trial is 30mg of efti, which is the dosage level currently used in the ongoing TACTI-002 Phase II trial.

Deep (with 12 patients (50 %) having a decrease of ³ 75 % in the target lesions) and durable (9 patients (38 %) being treated for ³ 12 months with pembrolizumab ± efti) responses have been observed.

The key efficacy findings from the trial are:

Part A: Combination treatment began at cycle 5 of pembrolizumab treatment with patients having suboptimal response to pembrolizumab monotherapy and included a dose escalation of efti.

Part B: Combination treatment started from cycle 1 day 1 of pembrolizumab.

Part A+B C1D1 analysis: Performed exploratory analysis starting from cycle 1 day 1 of pembrolizumab, including the 4 cycles pembrolizumab monotherapy ("C1/D1 Analysis") and include pts from part B

The full presentation is available on the Company’s website at View Source

About the TACTI-mel clinical trial

The TACTI-mel (Two ACTive Immunotherapies in melanoma) Phase I clinical trial is a multicentre, open-label study evaluating the combination of eftilagimod alpha ("efti") with pembrolizumab, in unresectable or metastatic melanoma patients that have had either a suboptimal response or had disease progression with pembrolizumab monotherapy (clinicaltrials.gov identifier NCT 02676869).

On October 15, 2019 Checkmate Pharmaceuticals Inc., a clinical stage biopharmaceutical company focused upon activation of innate immunity to treat cancer, reported the appointments of James Wooldridge, MD, as Chief Medical Officer and Steven Hamburger, PhD, as Vice President of Regulatory Affairs (Press release, Checkmate Pharmaceuticals, OCT 15, 2019, View Source [SID1234542271]).

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!

"In the past year, we have made tremendous progress in advancing the development of our lead compound, CMP-001, that is currently in clinical trials in combination with anti-PD-1/L1 antibodies for multiple solid tumor types. I am very pleased to welcome Jim and Steven to the team to continue this momentum," commented Barry Labinger, President and CEO of Checkmate Pharmaceuticals. "Their experience in setting and executing clinical development and regulatory strategies for a variety of cancer therapeutics will be invaluable to us as we advance the development of CMP-001 and build a leading immuno-oncology company."

Dr. Wooldridge has more than 20 years of drug development experience in academia and pharmaceutical and biotechnology companies. He will have responsibility for overall clinical strategy and medical affairs, including regulatory activities and submissions, which will be led by Dr. Hamburger. Prior to joining Checkmate, Dr. Wooldridge served as Chief Medical Officer at Aeglea BioTherapeutics, Inc., where he oversaw development programs in oncology and rare genetic diseases. Previously, he spent 11 years in cancer research at Eli Lilly and Company (Eli Lilly), where he led Oncology US Medical Affairs and more recently served as the Chief Scientific Officer for Immuno-oncology Clinical Development. Prior to Eli Lilly, Dr. Wooldridge conducted clinical and translational research as a faculty member of the University of Missouri in Columbia and the University of Iowa. Dr. Wooldridge is a graduate of William Jewell College, received his MD from Tulane University, and completed his post-graduate training in Internal Medicine and Medical Oncology at the University of Iowa.

Dr. Hamburger was most recently Vice President, Regulatory Affairs & Quality Assurance at Tarveda Therapeutics, Inc. During his career, he has led global regulatory and quality efforts for both emerging biotechnology and large pharmaceutical companies including Baxalta, Castle Creek Pharmaceutical Holdings, Inc., Immunomedics, Inc., Johnson & Johnson, Millennium/Takeda, Savient Pharmaceuticals and Eli Lilly. Dr. Hamburger has played a leadership role in the development and registration of numerous successful drugs, including several in oncology. He holds a PhD in Pharmacology and Toxicology from Indiana University School of Medicine, an MS from Butler University and a BS from the University of Iowa.