On June 27, 2018 Purdue Pharma L.P. reported successful completion of a first-in-human Phase 1 dose escalation study of tinostamustine in patients with relapsed or refractory hematological malignancies for which there are no available therapies (Press release, Purdue Pharma, JUN 27, 2018, View Source [SID1234527497]). The study evaluated the safety and pharmacokinetics, and sought to determine the maximum tolerated dose and inform a Phase 2 dose of tinostamustine. 1

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The multi-acting therapy candidate tinostamustine, previously known as EDO-S101, is a novel and potentially first-in-class alkylating deacetylase inhibitor (AK-DACi) therapy being studied for its potential to improve access to the DNA strands within cancer cells, break them, and counteract the cancer cells’ attempt to repair the DNA damage. It is in development for a range of rare or difficult to treat blood cancers and solid tumors. Based on the results of this Phase I human trial, Purdue will support advancement of tinostamustine into further clinical studies.

"We are pleased with the outcome of this promising early stage oncology program and we believe it has the potential to make meaningful clinical contributions in areas with significant unmet needs," said Craig Landau, MD, president and CEO, Purdue Pharma. "In addition to our established commitments in oncology and neuroscience, we are actively seeking opportunities to collaborate across a number of therapeutic areas as part of our ongoing efforts to diversify our scientific research and bring therapies to market that may improve outcomes for patients."

The reported completion of this study is the first clinical update since Purdue announced in November 2017 significant oncology-related investments to establish a portfolio of drug candidates with the potential to deliver new cancer therapies, in areas of high unmet medical need, to physicians and patients. As part of these investments, Purdue is currently supporting research for four drug candidates across 14 different cancer types. Research on these compounds is being advanced on behalf of Purdue by Mundipharma EDO.

In addition to tinostamustine, Purdue’s clinical stage oncology portfolio includes etoposide toniribate, a novel target-activated topoisomerase inhibitor that delivers the chemotherapy etoposide to tumors in an inactive form where it is ‘switched on’ by enzymes called carboxylesterases. Purdue also has two late pre-clinical stage antibody-drug conjugates, EDO-B776 and EDO-B278, in development. EDO-B776 is being studied for its potential to target the cancer antigen 125 (CA-125) in ovarian cancer. EDO-B278, which targets human tissue factor, is in development for treatment of various solid tumors.

The decision to move tinostamustine into Phase 1 human trials was supported by preclinical studies, which suggest that tinostamustine may deliver both alkylating activity and pan-histone deacetylase (HDAC) inhibition to improve access to the DNA strands within cancer cells, break them, and counteract the cancer cells’ attempt to repair the DNA damage.

Purdue will also continue to selectively seek additional oncology product assets through licensing and acquisition, and the company will maintain a priority interest in candidates with mechanisms complementary to emerging immuno-oncology based treatment paradigms

On June 27, 2018 Pfizer Inc. (NYSE:PFE) reported that the U.S. Food and Drug Administration (FDA) accepted the company’s New Drug Application and granted Priority Review designation for glasdegib, an investigational oral smoothened (SMO) inhibitor, being evaluated for the treatment of adult patients with previously untreated acute myeloid leukemia (AML) in combination with low-dose cytarabine (LDAC), a type of chemotherapy (Press release, Pfizer, JUN 27, 2018, View Source [SID1234527490]).

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"Patients with acute myeloid leukemia who are ineligible for intensive chemotherapy are in critical need of new treatment options to improve their overall survival," said Mace Rothenberg, M.D., chief development officer, Oncology, Pfizer Global Product Development. "In an investigational Phase 2 study, glasdegib in combination with low-dose cytarabine showed a significant improvement in overall survival compared to patients who received low-dose cytarabine alone. Glasdegib is the first smoothened inhibitor to potentially offer such a benefit to patients with acute myeloid leukemia, and we are proud that our application was accepted by the FDA for Priority Review."

The FDA grants Priority Review designation to medicines that may offer significant advances in treatment or may provide a treatment where no adequate therapy exists. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is in December 2018.

The submission is based on results from the Phase 2 BRIGHT 1003 study, a randomized, open-label, multicenter trial investigating glasdegib combined with LDAC (n=88) versus LDAC alone (n=44) in 132 patients with previously untreated AML or high-risk myelodysplastic syndrome (MDS) who were not eligible for intensive chemotherapy. Results demonstrated a significant improvement in the primary endpoint of overall survival (OS). Median OS was 8.8 months for patients treated with glasdegib plus LDAC compared with 4.9 months for patients treated with LDAC only. This difference represented a 49.9 percent reduction in the risk of death for patients treated with glasdegib plus LDAC (HR: 0.501, 95% CI: 0.334, 0.752, one-sided p-value 0.0003). The BRIGHT 1003 results were presented in 2016 at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

The most frequently (≥30% of patients) reported adverse events (AEs) in patients treated with glasdegib plus LDAC compared to LDAC alone were anemia (45% vs 42%), febrile neutropenia (36% vs 27%), nausea (36% vs 12%), decreased appetite (32% vs 12%), fatigue (31% vs 20%) and thrombocytopenia (30% vs 27%). The most frequently (≥15% of patients) reported serious AEs for patients treated with glasdegib plus LDAC compared to LDAC alone were febrile neutropenia (29% vs 20%) and pneumonia (21% vs 17%).

About Glasdegib

Glasdegib is an investigational, oral, once-daily therapy that is thought to inhibit the SMO receptor, thereby disrupting the Hedgehog pathway. Abnormal Hedgehog pathway activation is thought to play a role in the development of multiple types of cancers, including solid tumors and hematologic malignancies. It has not received regulatory approval in any country.

The Phase 3 BRIGHT AML 1019 trial (NCT03416179), which is evaluating the addition of glasdegib to intensive or non-intensive chemotherapy in patients with newly diagnosed AML, began enrolling earlier this year.

About Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and accounts for approximately 80 percent of all cases of acute leukemia.1 An estimated 19,520 people are expected to be diagnosed with AML in the U.S. in 2018.1 Despite recent advancements, only approximately one in four patients with AML survive longer than five years, and additional treatment options are needed to reduce incidence of disease progression and relapse.2,3 This is especially true for patients who are unable to receive intensive chemotherapy and are triaged to other treatments associated with poorer outcomes.

On June 28, 2018 argenx (Euronext & Nasdaq: ARGX), a clinical-stage biotechnology company developing a deep pipeline of differentiated antibody-based therapies for the treatment of severe autoimmune diseases and cancer, reported the achievement of the second of two preclinical milestones towards an investigational new drug (IND) filing for ARGX-115, triggering a further $ 10 million payment from AbbVie (Press release, argenx, JUN 28, 2018, View Source;p=RssLanding&cat=news&id=2356311 [SID1234527488]).

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In April 2016, argenx entered into a development and exclusive license option agreement with AbbVie to develop and commercialize ARGX-115. Under the terms of that agreement, argenx has been responsible for conducting and funding all ARGX-115 research and development activities up to completion of IND-enabling studies.

Over the course of the past two years, argenx has been eligible to receive two preclinical milestones of $ 10 million each. The second milestone was achieved today.

About ARGX-115
ARGX-115 employs argenx’s SIMPLE Antibody(TM) technology and binds specifically to the protein glycoprotein A repetitions predominant (GARP), which plays a key role in the regulation of production and release of active transforming growth factor beta (TGF-beta). ARGX-115 is believed to selectively limit the immunosuppressive activity of activated regulatory T-cells (Tregs), thereby stimulating the immune system to attack cancer cells. While the normal function of Tregs is to suppress certain compartments of the immune system to prevent self-directed immune responses through the release of active TGF-beta, Tregs can also prevent the immune system from recognizing and suppressing pathogenic cells including cancer cells. We believe the selective inhibition of TGF-beta release by Tregs is potentially superior to systemic inhibition of TGF-beta activity or depletion of Tregs and may give rise to therapeutic products with an improved safety profile.

ARGX-115 was discovered under argenx’s Innovative Access Program with the de Duve Institute / Université Catholique de Louvain / WELBIO and exclusively licensed under a research and option agreement in 2013.

On June 27, 2018 Kangpu Biopharmaceuticals, Ltd., a clinical-stage company based in Shanghai, China, reported that a phase I, multi-center, open-label study to evaluate the safety, tolerability, pharmacokinetics and preliminary evidence of antitumor activity of KPG-121 in combination with Enzalutamide in adult subjects with metastatic castration-resistant prostate cancer (mCRPC) has been launched in the United States (Press release, Kangpu Biopharmaceuticals, JUN 27, 2018, View Source [SID1234527486]). The study takes place at 3 medical centers in the US; part of Accelovance’s network of HERO sites dedicated to early phase research in oncology. Specifics of the study can be found on www.clinicaltrials.gov/NCT03569280.

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About KPG-121
KPG-121 is a novel generation of Lenalidomide. Compared with Lenalidomide, KPG-121 has shown enhanced immunomodulatory activities and improved anti-angiogenic properties in the preclinical studies. Results from in vitro assays and in vivo studies of mCRPC animal xenograft models demonstrated that better efficacy was observed for KPG-121 compared to Lenalidomide, when combined with Enzalutamide, Abiraterone Acetate, Apalutamide or Darolutamide. In the combination studies with Enzalutamide, KPG-121 significantly improved anti-tumor efficacy when compared to Enzalutamide alone.

On June 27, 2018 Carisma Therapeutics Inc., formerly CARMA Therapeutics, a privately-held biotechnology company focused on the development of macrophage-based immunotherapeutics, reported the close of a $53 million Series A financing to further expand its technology platform and rapidly drive its programs toward clinical development (Press release, Carisma Therapeutics, JUN 27, 2018, View Source [SID1234527485]). The financing was led by AbbVie Ventures and HealthCap and includes existing seed investors IP Group, Penn Medicine and Grazia Equity. Carisma is also proud to welcome new investors Wellington Partners, TPG Biotech, MRL Ventures Fund and Agent Capital.

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Carisma Therapeutics’ discovery and development efforts are focused on their proprietary CAR-Macrophage platform – the first technology to combine antigen recognition with the effector function of macrophages. The proposed dual mechanism of action includes the ability to directly kill targeted cells and the ability to leverage antigen-presenting cell biology to mount an adaptive immune response. Initial applications for therapeutic candidates will be in the treatment of solid tumors. Other potential applications include the disruption of protein aggregates in multiple disease states. The company anticipates initiating clinical development in 2019.

The Carisma management team is led by Steven Kelly, CEO, who brings nearly 30 years of diverse drug development and commercialization experience at a variety of biotechnology and pharmaceutical companies. The team also includes Dora Mitchell, PhD as Head of Operations and Daniel Cushing, PhD heading development. Carisma is continuing to build its team and currently recruiting a CSO and a CMO.

Founded by Saar Gill, MD, PhD, an assistant professor of Hematology-Oncology in Penn’s Abramson Cancer Center, and Michael Klichinsky, PharmD, a PhD candidate in Systems Pharmacology and Translational Therapeutics, in partnership with the UPstart Program of the Penn Center for Innovation at the University of Pennsylvania, Carisma Therapeutics raised its incubation financing and began operations last summer. The company’s founders will be joined on the Scientific Advisory Board by Drs. Carl H. June, Lisa M. Coussens, Reinhard Andreesen and S. Jane Flint.

"Carisma’s programs combine the unique effector function of macrophages with advances in CAR technology to create a revolutionary approach to adoptive cellular therapy," commented CEO, Steven Kelly. "We are thrilled about the composition of our financing syndicate, which brings varied and deep experience in cell and gene therapy to further support our research and development efforts."

The company’s Board of Directors will be comprised of Margarita Chavez, JD, Managing Director of AbbVie Ventures; Jacob Gunterberg, Partner of HealthCap; Regina Hodits, PhD, Managing Partner of Wellington Partners; Steven Kelly, CEO; Eran Nadav, PhD, Senior Advisor of TPG Biotech; Althea Stillman, PhD, Associate Director at IP Group Inc.; and Bruce Peacock, Chairman.