On April 23, 2018 CBT Pharmaceuticals (CBT), a U.S. and China-based innovative biopharmaceutical company committed to becoming a leader in the discovery and development of oncology combination therapies, and CrystalGenomics, Inc., (KOSDAQ:083790), a Korea-based biopharmaceutical company with drug discovery, development and commercialization capabilities, reported a co-development agreement for an investigational combination therapy of CBT-501 and CG200745 across a variety of solid tumors with high unmet medical needs (Press release, CBT Pharmaceuticals, APR 23, 2018, View Source [SID1234525574]).

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Under the terms of the exclusive agreement, CBT and CrystalGenomics will be responsible for the co-development and global commercialization of the combination of CBT-501 and CG200745 in multiple tumor types. A Phase Ib/II study is expected to be initiated by the end of this year.

"This partnership with CrystalGenomics enables CBT to leverage their clinical development expertise while further strengthening our immuno-oncology combination approach to deliver promising best-in-class treatments to patients with cancer," Sanjeev Redkar, Ph.D., President and Chief Executive Officer. "We believe the combination therapy of CBT-501 and CG200745 has the potential to be synergistic for patients across a range of cancers where alternative therapies are needed."

"We are excited to work with the CBT team, who are uniquely qualified to accelerate development of our novel HDAC inhibitor in combination with CBT-501, a differentiated anti-PD1 antibody" said Joong Myung Cho, Ph.D., Chairman and Chief Executive Officer of CrystalGenomics.

Immune checkpoint inhibitors such as the programmed death receptor-1 (PD-1) and ligand (PD-L1) have been considered as major breakthroughs in the treatment of various cancers including melanoma, renal, lung, and bladder cancers. However, despite the robust efficacy observed in these cancers, the majority of patients either do not respond or eventually relapse due to resistance which may be innate or acquired. There has been recent reports suggesting immune enhancing effects of HDAC inhibitors, in addition to their direct anti-tumor properties, making CG200745 a good candidate for combination therapy with CBT-501 for its immunomodulatory effects in addressing the patient population that do not respond to single agent immunotherapy.

About CBT-501

CBT-501 is a novel IgG4 humanized monoclonal antibody against the Programmable Death-1 (PD-1) membrane receptor on immune cells. It has a comparable efficacy profile in in vitro and in vivo studies to the marketed anti-PD-1 antibodies, nivolumab and pembrolizumab, and has a favorable profile with very low antibody-dependent cell-mediated cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) activity. CBT-501 is under evaluation in two Phase I trials designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics in patients with advanced solid tumors, recurrent or refractory to standard of care therapies (NCT03053466, NCT03374007).

About CG200745

CG200745, is a novel pan-HDAC inhibitor currently in Phase II clinical study for pancreatic cancer (NCT02737228) and Phase Ib for myelodysplastic syndrome (NCT02737462) in Korea. CG200745 has the potential to be a best-in-class compound based on preclinical and interim Phase Ib/II clinical data and is projected to have superior pharmacokinetic (PK) profile, pharmacodynamic (PD) response, efficacy, and safety, over other HDAC inhibitors. In its first-in-human study of the toxicity, PK and PD in patients with refractory solid malignancies, stable disease was observed in 57.1% of the subjects treated with CG200745 as monotherapy and excellent safety profile was observed as the maximum tolerated dose (MTD) was never reached (NCT01226407).

On April 23, 2018 Verastem, Inc. (NASDAQ: VSTM), focused on developing and commercializing drugs to improve the survival and quality of life of cancer patients, reported that it will host an Analyst and Investor Day titled, "Duvelisib: Harnessing the Power of Dual PI3K Inhibition," on Wednesday, May 2, 2018 from 10:30 am – 1:00 pm ET in New York City (Press release, Verastem, APR 23, 2018, View Source;p=RssLanding&cat=news&id=2343842 [SID1234525595]).

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The agenda will include an in-depth discussion of the Company’s lead oral oncology candidate, duvelisib, including the unmet need of patients, where phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma inhibitors fit into the treatment paradigm and the opportunity for duvelisib in the growing chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and follicular lymphoma (FL) population and beyond.

The program will also feature key opinion leaders in the hematologic oncology field, including:

Jennifer Brown, MD, PhD
Associate Professor of Medicine, Harvard Medical School Director, and Director, CLL Center of the Division of Hematologic Malignancies, Dana-Farber Cancer Institute
Ian Flinn, MD, PhD
Director, Blood Cancer Research Program at Sarah Cannon Research Institute, and Lead Investigator of the DUO and DYNAMO Studies
Steven Horwitz, MD
Medical Oncologist, Memorial Sloan Kettering Cancer Center and NYC Health + Hospitals/Bellevue
Brian Koffman, MDCM, DCFP, FCFP, DABFP, MSEd
Physician, Medical Director of the Chronic Lymphocytic Leukemia (CLL) Society and CLL Patient
Lori Kunkel, MD
Oncology Drug Development Expert and Biotech Advisor, Member of the Board of Directors at Tocagen Inc., Former Chief Medical Officer, Pharmacyclics
Kindly reach out to Marianne Lambertson at [email protected] for any inquiries.

A live and archived webcast of the event will be available on the "Events and Presentations" page in the "Investors" section of the Company’s website at www.verastem.com. The webcast will be archived for a period of 90 days following the conclusion of the live event.

On April 23, 2018 Alder Biopharmaceuticals, Inc., (NASDAQ:ALDR), a biopharmaceutical company focused on developing novel therapeutic antibodies for the treatment of migraine, reported that Eric Carter, Ph.D., M.D., has been named Interim Chief Medical Officer, effective immediately (Press release, Alder Biopharmaceuticals, 23 23, 2018, View Source [SID1234525596]). His primary responsibilities will include leading the Company through its ongoing Biologics License Application (BLA) submission process for eptinezumab, Alder’s lead investigational product candidate for migraine prevention, and facilitating other clinical and commercial advancement activities. He will report to Paul B. Cleveland, Interim President and Chief Executive Officer. Dr. Carter has served as a consultant to the Company since March 2018.

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Dr. Carter served as Senior Vice President, Chief Medical Officer and Global Head of Clinical & Non-Clinical Development of Allergan Inc. from 2011 to 2015, where he led the organization through 11 domestic and international drug candidate approvals and managed an annual budget of approximately $700 million. With more than 20 years of experience as a physician and as an executive in the pharmaceutical industry, Dr. Carter has overseen the introduction of new drug candidates into clinical development and practice, managed complex processes and global teams and provided support around key commercialization activities for numerous organizations. Dr. Carter currently serves as Chairman of the Scientific Advisory Board of Bioniz Therapeutics, a clinical-stage biopharmaceutical company, and serves on the Board of Directors of Adverum Biotechnologies, a public gene therapy company focused on rare diseases. Dr. Carter received his M.D. from the University of Miami School of Medicine and his Ph.D. in Biochemistry from the University of Cambridge in Cambridge, England.

"Our planned BLA submission for eptinezumab remains our top priority, and we are pleased to welcome Eric to the team as we advance towards commercialization," said Paul B. Cleveland. "Eric has a proven record of success with the clinical development and approval of major drug candidates, and we are confident Alder will benefit from his expertise and leadership during this important time."

"I’m excited to join Alder and lead eptinezumab’s clinical development program in support of the Company’s planned BLA submission," said Dr. Carter. "I look forward to working closely with the Alder team and the physician community as we progress eptinezumab towards approval, with an opportunity to provide a treatment option for millions of migraine sufferers debilitated by their disease."

On April 23, 2018 Eli Lilly and Company (LLY) and Incyte Corporation (INCY) reported that the U.S. Food and Drug Administration’s (FDA) Arthritis Advisory Committee recommended approval of the 2-mg dose of baricitinib, a once-daily oral medication for the treatment of moderately-to-severely active rheumatoid arthritis (RA) for adult patients who have had an inadequate response or intolerance to methotrexate (Press release, Incyte, APR 23, 2018, View Source [SID1234525686]). While the Advisory Committee unanimously supported the efficacy of the 4-mg dose of baricitinib, it did not recommend approval of the 4-mg dose of baricitinib for the proposed indication based on the adequacy of the safety and benefit-risk profiles.

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"We are confident that baricitinib, if approved, can help people in the U.S. manage the challenges of living with RA," said Christi Shaw, president of Lilly Bio-Medicines. "While we are disappointed with the Advisory Committee’s assessment of the data for the 4-mg dose, we are confident in the positive benefit-risk profile of both the 2-mg and the 4-mg doses. We look forward to continuing our work with the FDA on our New Drug Application (NDA) and are hopeful that baricitinib will receive approval in the coming months."

Baricitinib 2-mg and 4-mg doses are approved in more than 40 countries, including the member states of the European Union and Japan.

For both doses, the Advisory Committee voted to support the assessment that baricitinib’s data provide substantial evidence of efficacy. For the 2-mg dose, the Advisory Committee voted in favor of the assessment that baricitinib’s safety data adequately support its approval. For the 4-mg dose, the Advisory Committee voted against the assessment that baricitinib’s safety data was adequate to support its approval based on the proposed indication.

The Advisory Committee’s recommendation was based on baricitinib’s global development program, which included four completed Phase 3 studies. In total, 3,492 patients, who represented a range of treatment experiences, received baricitinib in the global RA development program. The Phase 3 studies evaluated baricitinib’s treatment impact related to RA signs and symptoms, physical function, joint damage progression and other patient-reported outcomes. The Phase 3 program also evaluated recognized risks for RA patients, including serious infection, malignancy, major adverse cardiovascular events (MACE), venous thromboembolism (VTE), and gastrointestinal perforations, along with key laboratory changes. The safety profile of baricitinib is based on 7,860 patient-years of exposure.

"Despite advances in the management of RA over the last 20 years, which include early treatment, optimized use of traditional therapies for rheumatic disease and the advent of newer medications such as biologics, many patients are still struggling to meet treatment targets, and live with debilitating pain, fatigue and other symptoms of RA," said Peter Taylor, MA, PhD, professor, University of Oxford, an expert who attended the Advisory Committee Meeting. "Baricitinib could be a promising option for RA patients in the U.S. who are not achieving adequate disease control with currently available treatments."

The FDA is not required to follow the Advisory Committee’s recommendation, but will consider it during its review of the NDA for baricitinib.

About Baricitinib
Baricitinib is a once-daily oral JAK inhibitor currently in clinical studies for inflammatory and autoimmune diseases. There are four known JAK enzymes: JAK1, JAK2, JAK3 and TYK2. JAK-dependent cytokines have been implicated in the pathogenesis of a number of inflammatory and autoimmune diseases, suggesting that JAK inhibitors may be useful for the treatment of a broad range of inflammatory conditions, including rheumatoid arthritis.

In December 2009, Lilly and Incyte announced an exclusive worldwide license and collaboration agreement for the development and commercialization of baricitinib and certain follow-on compounds for patients with inflammatory and autoimmune diseases. Baricitinib was submitted for regulatory review seeking marketing approval for the treatment of rheumatoid arthritis in the U.S., the European Union and Japan in 2016. Baricitinib was approved in the EU in February 2017 and in Japan in July 2017. In April 2017, the U.S. Food and Drug Administration issued a Complete Response Letter on the New Drug Application for baricitinib. To date, baricitinib has been approved in more than 40 countries and remains under review in several other markets.

On April 21, 2018 Molecular Partners AG (SIX: MOLN), a clinical-stage biopharmaceutical company developing a new class of drugs known as DARPin therapies*, reported that preliminary results from the ongoing Phase 2 study of MP0250 with bortezomib and dexamethasone in patients with relapsed refractory multiple myeloma (RRMM) were presented at the 1st European Myeloma Network Meeting in Turin (Press release, Molecular Partners, APR 21, 2018, View Source [SID1234525567]).

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The presentation in Turin focused on results from the first dose cohort of MP0250 with respect to safety and efficacy. Eight patients were treated with 8 mg/kg of MP0250 and five out of these eight patients showed a documented response: Four patients reached a partial response (PR) and one patient reached a very good partial response (VGPR) at the cut-off date. Four out of the five patients are still on treatment with individual treatment durations of 13, 21, 24 and 33 weeks, respectively. The safety profile was consistent with the known safety profiles of bortezomib and MP0250, respectively. The independent dose escalation committee recommended to continue the clinical study at the higher dose of 12mg/kg and the first patient in the second dose cohort has been dosed recently.

Prof. Dr. Hartmut Goldschmidt (Medical Clinic V, University clinic Heidelberg), the Primary Investigator of the phase 2 study, commented: "We are encouraged by the initial efficacy and good tolerability data of MP0250 in combination with bortezomib and dexamethasone. Despite upcoming new treatment options, multiple myeloma remains an incurable disease and new molecules with innovative mechanism of actions are needed."

"We are pleased by the remarkable activity and the good safety profile that we have seen in the first cohort of this study. We are looking forward to patients being treated with the higher dose of MP0250 (12 mg/kg) and the additional phase 1b/2 study of MP0250 in combination with osimertinib in EGFR-mutated NSCLC," said Dr. Andreas Harstrick, Chief Medical Officer at Molecular Partners.

MP0250 is a proprietary DARPin drug candidate neutralizing VEGF and HGF and thus blocking key escape pathways and resistance. Increases in VEGF and HGF are associated with disease progression in multiple myeloma and have been linked to poor prognosis. They are known to be able to stimulate neovascularization, bone destruction, and myeloma proliferation, migration, and adhesion in the bone marrow. MP0250 shows activity in many preclinical tumor models, including in multiple myeloma models in which it enhances the effects of bortezomib on inhibition of M protein production and bone lysis and reduces invasion of tumor cells. MP0250 has shown a favorable safety profile in a phase 1 clinical study in 45 patients with advanced solid tumors.

In the ongoing phase 2 clinical study[1], the safety and efficacy of MP0250 is examined in combination with bortezomib (Velcade) and dexamethasone in patients with relapsed and refractory multiple myeloma (RRMM) who have failed standard therapies. The study is performed in Germany, Poland and Italy. A total of 40 patients are planned to be treated, 12 patients in the dose-escalation phase (Part 1) to establish a safe dose, and an additional 28 patients in the dose-expansion phase (Part 2) resulting in a total of 34 patients at the target dose.

Additional safety and efficacy data are expected by the end of 2018.

An additional phase 1b/2 study will evaluate MP0250 in combination with osimertinib in patients with EGFR-mutated NSCLC pretreated with osimertinib. The study is conducted in the US and is open for patient enrollment2.

[1] ClinicalTrials.gov identifier NCT03136653
2 ClinicalTrials.gov identifier NCT03418532

Financial Calendar
April 26, 2018 – Q1 2018 Management Statement
August 30, 2018 – Publication of 2018 Half-year Results
November 01, 2018 – Q3 2018 Management Statement
View Source

About the DARPin Difference
DARPin therapeutics are a new class of protein therapeutics opening an extra dimension of multi-specificity and multi-functionality. DARPin candidates are potent, specific, safe and very versatile. They can engage in more than 5 targets at once, offering potential benefits over those offered by conventional monoclonal antibodies or other currently available protein therapeutics. The DARPin technology is a fast and cost-effective drug discovery engine, producing drug candidates with ideal properties for development and very high production yields.
With their good safety profile, low immunogenicity and long half-life in the bloodstream and the eye, DARPin therapies have the potential to advance modern medicine and significantly improve the treatment of serious diseases, including cancer and sight-threatening disorders. Molecular Partners is partnering with Allergan to advance clinical programs in ophthalmology, and is advancing a proprietary pipeline of DARPin drug candidates in oncology. The most advanced global product candidate is abicipar, a molecule currently in Phase 3, in partnership with Allergan.
Several DARPin molecules for various ophthalmic indications are also in development. The most advanced systemic DARPin molecule, MP0250, is in Phase 1 clinical development for the treatment of solid tumors and in Phase 2 development for hematological tumors. In addition, Molecular Partners intends to further evaluate MP0250 for solid tumors in a phase 1b/2 trial for EGFR-mutated NSCLC. MP0274, the second-most advanced DARPin drug candidate in oncology, has broad anti-HER activity; it inhibits HER1, HER2 and HER3-mediated downstream signaling via Her2, leading to induction of apoptosis. MP0274 has moved into Phase 1. Molecular Partners is also advancing a growing preclinical pipeline that features several immuno-oncological development programs. DARPin is a registered trademark owned by Molecular Partners AG.