On January 7, 2019 Agios Pharmaceuticals, Inc. (NASDAQ: AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported its key 2019 initiatives in conjunction with its presentation at the 37th Annual J.P. Morgan Healthcare Conference in San Francisco (Press release, Agios Pharmaceuticals, JAN 7, 2019, View Source [SID1234532570]). The company will webcast its presentation today at 9:30 a.m. PT (12:30 p.m. ET) at investor.agios.com.

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!

"During 2018, just ten years after the founding of Agios, we achieved approval of our second internally discovered oncology medicine, launched a robust registrational program in PK deficiency and successfully opened the company’s seventh IND," said David Schenkein, M.D., chief executive officer at Agios. "Our validated research platform and proven drug development strategy are poised to help drive future growth across our oncology and rare genetic disease portfolios. Our priorities for 2019 include expanding the reach of our IDH inhibitors into the frontline AML and solid tumor settings, completing enrollment in two pivotal studies of mitapivat and exploring the utility of PKR activators in other hemolytic anemias, and furthering clinical development for AG-270 in MTAP deleted tumors and AG-636 in lymphoma."

The company plans to achieve the following milestones in 2019.

Cancer:

Potential FDA approval of the supplemental new drug application (sNDA) for single agent TIBSOVO (ivosidenib) for the treatment of patients with newly diagnosed AML with an IDH1 mutation who are not eligible for standard therapy.

Submit a sNDA to the FDA for TIBSOVO for second line or later IDH1m cholangiocarcinoma by year-end.

Initiate a registration-enabling Phase 3 study of vorasidenib (AG-881) in low-grade glioma with an IDH1 mutation by year-end.

Determine recommended dose of AG-270, a first-in-class methionine adenosyltransferase 2a (MAT2A) inhibitor, in methylthioadenosine phosphorylase (MTAP)-deleted tumors and initiate expansion arms, including a single agent arm in a variety of MTAP deleted cancers and a combination arm in a solid tumor in the first half of 2019.

Initiate a Phase 1 dose-escalation trial of AG-636, an inhibitor of the metabolic enzyme dihydroorotate dehydrogenase (DHODH), in lymphoma in the first half of 2019.

Rare Genetic Diseases:

Complete enrollment in two global pivotal trials for mitapivat in adults with PK deficiency by year-end 2019:

ACTIVATE-T: A single arm trial of approximately 20 regularly transfused patients

ACTIVATE: A 1:1 randomized, placebo-controlled trial of 80 patients who do not receive regular transfusions

Achieve proof-of-concept for mitapivat in thalassemia in the second half of 2019.

The company highlighted select data presentations expected in 2019.

Updated data from the ongoing Phase 1 combination trial of TIBSOVO with azacitidine in patients with newly diagnosed AML with an IDH1 mutation in the first half of 2019.

Data from the perioperative ‘window’ trial with TIBSOVO and AG-881 in IDHm low-grade glioma in the first half of 2019.

Topline data from the Phase 3 ClarIDHy study of TIBSOVO in IDH1m advanced cholangiocarcinoma to be reported in the first half and full data to be presented in the second half of 2019.

Data from the dose-escalation portion of the ongoing Phase 1 study of AG-270 in patients with MTAP-deleted tumors in the second half of 2019.

The company also provided an update on the following 2018 milestones achieved in December:

Submitted an sNDA to the FDA for TIBSOVO for the treatment of patients with newly diagnosed AML with an IDH1 mutation who are not eligible for standard therapy.

Submitted a Marketing Authorization Application to the European Medicines Agency for TIBSOVO for the treatment of adult patients with R/R AML with an IDH1 mutation.

Initiated a Phase 2 proof-of-concept trial of mitapivat in thalassemia.

2018 Year-End Cash and Guidance

Agios ended 2018 with approximately $805 million of cash, cash equivalents and marketable securities. The company expects that its cash, cash equivalents and marketable securities as of December 31, 2018, together with anticipated product and royalty revenue, anticipated interest income, and anticipated expense reimbursements under our collaboration agreements, but excluding any additional program-specific milestone payments, will enable the company to fund its anticipated operating expenses and capital expenditure requirements through at least the end of 2020.

Presentation at 37th Annual J.P. Morgan Healthcare Conference

Agios will webcast its corporate presentation from the 37th Annual J.P. Morgan Healthcare Conference in San Francisco on Monday, January 7, 2019 at 9:30 a.m. PT (12:30 p.m. ET). A live webcast of the presentation can be accessed under "Events & Presentations" in the Investors section of the company’s website at agios.com. A replay of the webcast will be archived on the Agios website for at least two weeks following the presentation

On January 7, 2019 Moleculin Biotech, Inc is presented the corporate presentation (Presentation, Moleculin, JAN 7, 2019, View Source [SID1234532567]).

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 7, 2019 Calithera Biosciences, Inc. (Nasdaq: CALA), a clinical stage biotechnology company focused on discovering and developing novel small molecule drugs directed against tumor metabolism and tumor immunology targets for the treatment of cancer, reported several executive promotions. The company also provided corporate updates, including selected fourth quarter 2018 financial results, financial guidance and corporate milestones for 2019 (Press release, Calithera Biosciences, JAN 7, 2019, View Source [SID1234532564]).

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!

"I am pleased to announce today’s promotions which highlight the talent, skill set and extensive achievements of our executive team," said Susan Molineaux, PhD, President and Chief Executive Officer of Calithera. "It is critical that we have the right leadership in place to reach key clinical milestones as we drive CB-839 towards commercialization with two randomized trials of the glutaminase inhibitor CB-839 for the treatment of patients with advanced renal cell carcinoma. We plan to report data from our Phase 2 ENTRATA trial in 2019, and the global CANTATA trial in 2020. In 2019, we look forward to a number of achievements including the initiation of additional clinical trials of CB-839 in collaboration with Pfizer, and the presentation of data on the arginase inhibitor INCB001158 at a medical meeting in the second half of 2019. Our goal is to have four unique therapeutics in the clinic including CB-280, an oral arginase inhibitor for the treatment of patients with cystic fibrosis, and CB-708, an oral small molecule CD73 inhibitor for the treatment of cancer by the end of 2019."

2019 Milestones

Calithera expects to reach the following milestones in 2019:

CB-839 data from Phase 2 renal cell carcinoma randomized ENTRATA trial 2H19. The ENTRATA trial is a randomized, double-blind trial designed to evaluate the safety and efficacy of CB-839 with everolimus versus everolimus alone in approximately 63 patients with metastatic, clear cell renal cell carcinoma patients who have been treated with at least two prior lines of therapy including a VEGFR-targeting tyrosine kinase inhibitor. The primary endpoint is progression free survival; overall survival will be assessed as a secondary endpoint.

CB-839 enrollment of the Phase 2 renal cell carcinoma CANTATA trial 2H19. The CANTATA trial is a randomized, global, double-blind trial comparing patients treated with CB-839 and cabozantinib to patients treated with cabozantinib alone. The trial will enroll approximately 400 patients with clear cell renal cell carcinoma who have previously received one or two prior lines of therapy. The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for CB-839 in combination with cabozantinib for the treatment of this patient population.

CB-839 combination trial initiations in collaboration with Pfizer 1H19. Calithera and Pfizer have two clinical trial collaborations to evaluate Pfizer’s CDK4/6 inhibitor palbociclib, also known as IBRANCE, and the dual-mechanism poly (ADP-ribose) polymerase (PARP) inhibitor talazoparib also known as TALZENNA, each in combination with the glutaminase inhibitor CB-839.

INCB001158 arginase inhibitor data presentation at a medical meeting 2H19. INCB001158 is a small molecule immuno-oncology therapeutic being evaluated in multiple clinical trials as a single-agent and in combination with immunotherapies and chemotherapy for the treatment of patients with cancer. INCB001158 is being developed as part of a collaboration and license agreement with Incyte.

CB-280 IND acceptance and Phase 1 trial initiation in healthy volunteers 1H19. CB-280 is an arginase inhibitor for the treatment of cystic fibrosis. Arginase is believed to be critical in the pathology of cystic fibrosis. It impairs production of nitric oxide and generates metabolites of arginine that may impair lung function. CB-280 is an orally administered small molecule inhibitor of arginase. An investigational new drug (IND) application for CB-280 is planned for the first half of 2019.

CB-708 IND acceptance and Phase 1 trial initiation 2H19. The immuno-oncology target CD73 is an enzyme that plays a critical role in the process of ATP conversion to adenosine. An IND application for CB-708, an orally administered small molecule inhibitor of CD73, is planned for 2019.

Selected Fourth Quarter 2018 Financial Results and Financial Guidance for 2019

Based upon preliminary estimates, cash, cash equivalents and investments totaled $136.2 million at December 31, 2018. Calithera expects to utilize cash and investments between $75 and $85 million in 2019.

Key Executive Promotions

The promotions for its executive leadership team include Curtis C. Hecht, promoted to Chief Business Officer; Keith Orford M.D., Ph.D., promoted to Chief Medical Officer; and Sam Whiting, M.D., Ph.D., promoted to Senior Vice President of Clinical Development.

Mr. Hecht brings over 25 years of broad pharmaceutical experience including business development, strategic planning and commercialization. He has led business and corporate development efforts since joining Calithera in 2014. Key contributions include the Mars in-licensing agreement for arginase inhibitors, clinical collaborations with Bristol-Myers Squibb, Exelixis and Pfizer and the co-development and commercialization agreement with Incyte for INCB001158. He has built strategic portfolio management and lifecycle team functions, and leads commercial planning. Prior to Calithera, Mr. Hecht was Vice President of Business Development for inVentiv Heath Commercial Solutions. Until 2011, Mr. Hecht was at Roche in commercialization and business development roles of increasing responsibility, including the Global Alliance Director of the Roche-Genentech collaboration. Mr. Hecht has a B.S. in Chemistry from California State University, Sacramento, and an MBA from Carnegie Mellon University.

Dr. Orford has over 11 years of experience in pharmaceutical drug development in oncology and immuno-oncology. Since joining Calithera in 2015, he has overseen clinical development activities, including Clinical Operations and Medical Affairs. He has provided strategic development leadership for the company’s oncology and cystic fibrosis portfolio, including CB-839, a glutaminase inhibitor currently in late stage global clinical trials in renal cell carcinoma as well as multiple other clinical studies across a wide range of tumor types. He also serves as strategic development leader for the clinical collaboration between Calithera and Incyte. Prior to joining Calithera, Dr. Orford was the Clinical Development Lead in the Immuno-Oncology and Combinations Development Performance Unit at GlaxoSmithKline, where he oversaw the clinical activities on multiple early stage clinical trials with targeted agents and novel immune-based therapies. Prior to GlaxoSmithKline, Dr. Orford was at Merck, where he worked on early clinical development programs across oncology and other therapeutic areas. Previously, Dr. Orford was a Research Fellow and Instructor at Massachusetts General Hospital and Harvard Medical School, where he completed clinical training in Internal Medicine, as well as postdoctoral work studying the epigenetic regulation of hematopoietic and embryonic stem cell differentiation. Dr. Orford received his undergraduate, M.D., and Ph.D. degrees from Georgetown University.

Dr. Whiting joined Calithera in May 2016. Dr. Whiting’s deep expertise in clinical oncology gained as an academic medical oncologist and in pharmaceutical drug development have helped fuel the growth of the company’s pipeline. Prior to joining Calithera, Dr. Whiting served as Vice President of Research and Clinical Development at Gradalis. Dr. Whiting previously worked in development of small molecule

targeted and immune-oncology agents at VentiRx Pharmaceuticals and Oncothyreon. Previously, Dr. Whiting served as Assistant Professor of Medical Oncology at the University of Washington, Assistant Member of Clinical Research at the Fred Hutchinson Cancer Research Center, and Clinical Head of Gastrointestinal Oncology at the Seattle Cancer Care Alliance. Dr. Whiting completed fellowship training in medical oncology at the Fred Hutchinson Cancer Research Center. His training in internal medicine was at the ABIM Research Pathway at the University of Washington. Dr. Whiting received his B.S. with Honors in Chemistry from Lewis and Clark College, and his M.D. and Ph.D. as part of the Medical Scientist Training Program at the University of Washington Medical Center.

On January 7, 2019 Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of autoimmune disease, asthma and allergic disease and cancer, reported it will regain rights to develop and commercialize XmAb13676, a CD20 x CD3 bispecific antibody, from Novartis effective June 20, 2019, due to strategic pipeline reprioritization by Novartis (Press release, Xencor, JAN 7, 2019, View Source [SID1234532562]). Xencor granted Novartis co-development and ex-U.S. commercial rights in June 2016 through a collaboration and license agreement to develop and commercialize novel bispecific antibodies, including XmAb13676 and XmAb14045, and to access Xencor’s XmAb bispecific Fc and other Fc technologies. Currently XmAb13676 is being evaluated in an open-label Phase 1, multiple-dose, dose-escalation study to assess its safety, tolerability and preliminary anti-tumor activity in patients with B-cell malignancies, and initial data are expected in 2019.

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 continue to work closely with Novartis across multiple programs in the collaboration, and both companies are eager to advance XmAb14045 in clinical development. Recently we presented encouraging early data from our Phase 1 study in patients with relapsed/refractory AML, observing multiple complete remissions on a weekly dosing schedule, and we continue to optimize dose in that study. Novartis also has internal XmAb preclinical bispecific programs progressing," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "Xencor will continue to develop XmAb13676 as planned, and we believe its tuned potency holds potential for the treatment of patients with B-cell malignancies."

Under the terms of the collaboration agreement, Xencor and Novartis continue to share costs for the worldwide development of XmAb14045 with Xencor maintaining U.S. commercialization rights and Novartis having commercialization rights in the rest of the world, and worldwide development costs for XmAb13676 will be shared until June 2020. Novartis received worldwide rights to Xencor’s bispecific technology to develop and commercialize four additional targets selected by Novartis. Xencor is eligible to receive clinical, regulatory and sales milestone payments for successful programs, as well as tiered, low double-digit royalties for sales of XmAb14045 outside of the U.S. and mid single-digit tiered royalties for worldwide sales of the four proprietary Novartis bispecific molecules.

About XmAb13676

XmAb13676 is a tumor-targeted antibody that contains both a CD20 binding domain and a cytotoxic T-cell binding domain (CD3) in a Phase 1 clinical trial for the treatment of B-cell malignancies. An XmAb bispecific Fc domain serves as the scaffold for these two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on XmAb13676. CD20 is highly expressed on B-cell tumors, including in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). Engagement of CD3 by XmAb13676 activates T cells for highly potent and targeted killing of CD20-expressing tumor cells.

About XmAb14045

XmAb14045 is a tumor-targeted antibody that contains both a CD123 binding domain and a cytotoxic T-cell binding domain (CD3) in a Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and other CD123-expressing hematologic malignancies. An XmAb Bispecific Fc domain serves as the scaffold for these two antigen binding domains and confers long circulating half-life, stability and ease of manufacture on XmAb14045. CD123 is highly expressed on AML cells and leukemic stem cells, and it is associated with poorer prognosis in AML patients. Engagement of CD3 by XmAb14045 activates T cells for highly potent and targeted killing of CD123-expressing tumor cells.

On January 7, 2019 Sanofi (EURONEXT: SAN, NASDAQ: SNY) and Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that they have restructured their global Immuno-oncology Discovery and Development Agreement for new immuno-oncology cancer treatments (Press release, Sanofi, JAN 7, 2019, View Source [SID1234532561]). The 2015 Agreement was scheduled to end in approximately mid-2020, and this revision provides for ongoing collaborative development of two clinical-stage bispecific antibody programs. This provides Sanofi increased flexibility to advance its early-stage immuno-oncology pipeline independently while Regeneron retains all rights to its other immuno-oncology discovery and development programs.

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!

Under the terms of the restructured Agreement:

Sanofi will pay Regeneron $462 million representing the balance of payments due under the original Immuno-oncology Agreement, which covers the Sanofi share of the immuno-oncology discovery program costs for the last quarter of 2018 and up to $120 million in development costs for the two selected clinical-stage bispecific antibodies, plus the termination fee for the other programs under the original immuno-oncology agreement.
Sanofi secures the right to opt-in to the BCMAxCD3 and MUC16xCD3 bispecific programs when proof of concept is achieved or when the allocated funding is expended.
Regeneron will commit up to $70 million to further develop the BCMAxCD3 bispecific antibody for multiple myeloma and up to $50 million to further develop the MUC16xCD3 bispecific for mucin-16 expressing cancers.
Post opt-in, Sanofi will lead development and commercialization of the BCMAxCD3 bispecific and fund 100 percent of development costs, with Regeneron reimbursing up to 50 percent out of its share of collaboration profits. Sanofi and Regeneron will share global profits equally.
Post-opt-in, Regeneron will lead MUC16xCD3 bispecific development and lead commercialization in the U.S. The companies will share development costs and global profits equally. Sanofi will lead commercialization outside the U.S.
The companies’ ongoing collaboration for the development and commercialization of Libtayo (cemiplimab-rwlc), a PD1 antibody, is unaffected by the amended Discovery and Development Agreement.
Regeneron retains full rights to its other immuno-oncology programs.
Under the Immuno-Oncology License and Collaboration Agreement, the companies have developed and received U.S. Food and Drug Administration approval of Libtayo for advanced cutaneous squamous cell carcinoma (CSCC). A regulatory application for Libtayo has also been submitted in the EU. An ongoing joint clinical program is investigating Libtayo in multiple other cancers, and includes potentially pivotal trials in lung, cervical and skin cancers. Libtayo’s safety and efficacy has not been fully evaluated by any regulatory authority for indications beyond advanced CSCC.