On February 14, 2019 Helsinn Group, a Swiss pharmaceutical group focused on building quality cancer care products, and MEI Pharma, Inc. (Nasdaq: MEIP), an oncology company focused on the clinical development of novel therapies for cancer, reported the publication in the medical journal, Blood Advances, published by the American Society of Hematology (ASH) (Free ASH Whitepaper), the results from a Phase II study that evaluated the safety and efficacy of pracinostat, a potent oral pan-histone deacetylase inhibitor (HDACi), in combination with azacitidine, for the treatment of patients suffering from acute myeloid leukemia (AML), who cannot undergo treatment with intensive chemotherapy (IC) (Press release, MEI Pharma, FEB 14, 2019, View Source [SID1234533317]).

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!

AML is an haematological malignancy mostly diagnosed in older patients, with an average diagnosis age of 67 years of age. Although the cure rate for AML patients ≤60 years using intensive chemotherapy (IC) approaches 35% to 40%, it remains poor in older patients, typically not exceeding 15%.

The full article, just published online, Pracinostat plus azacitidine in older patients with newly diagnosed acute myeloid leukemia: results of a phase II study, G. Garcia-Manero et al., shows the results of the Phase II study, assessing pracinostat combined with azacitidine in patients ≥65 years with newly diagnosed AML and ineligible for standard induction chemotherapy. This was a multicentre, open-label, single-arm, two-stage study enrolling 50 patients, evaluating the treatment with oral pracinostat 60 mg/day, 3 days/week, for 3 consecutive weeks plus intravenous azacitidine 75 mg/m2 daily for 7 days in a 28-day cycle, until discontinuation due to progression, intolerable toxicity, intercurrent illness, or per patient request.

Primary endpoints for the Phase II study were the combined rates of complete remission (CR), CR with incomplete count recovery (CRi), and morphologic leukemia-free state (MLFS). Out of the 50 patients, 26 patients (52%) achieved the primary endpoint, with 42% achieving complete remission.

Ninety-four percent and 90% of patients had at least 1 TEAE related to pracinostat and azacitidine, respectively. The most common treatment-related AEs were nausea (56%), fatigue (40%), thrombocytopenia (38%), and neutropenia (30%). Pracinostat plus azacitidine is a well-tolerated and active regimen in the frontline treatment of older patients with AML unfit for intensive therapy.

This investigational study showed that pracinostat in combination with azacitidine is active in the frontline treatment of older patients with AML, unfit for intensive therapy. The CR rate of 42%, the median overall survival (OS) of 19.1 months, a PFS of 12.6 months and 1-year OS rate of 62% have been evidenced in patients unfit for intensive therapy.

These data have shown that pracinostat in combination with azacitidine is a potential treatment option for the frontline treatment of older AML patients unfit for IC. Based on these results, a Phase III, multicenter, double-blind, randomized study of pracinostat with azacitidine vs placebo with azacitidine (NCT03151408) is ongoing to demonstrate an improvement of pracinostat in combination in this difficult-to-treat AML population.

Dr. Guillermo Garcia-Manero, MD Professor, Department of Leukemia, at MD Anderson Cancer Center in Houston, Texas, US, said: "We are thrilled to be in a position to outline the encouraging results of this Phase II study in Blood Advances, as the data is highly encouraging for older patients suffering from acute myeloid leukemia, and who cannot be treated with intensive chemotherapy. We look forward to continuing with our ongoing Phase III study with pacinostat to show improvement of the pracinostat combination vs azacitidine with placebo, in this difficult-to-treat AML patients population."

Sergio Cantoreggi, PhD, Chief Scientific Officer and Helsinn Group Head of R&D, commented: "The publication of this data in Blood Advances, shows the potential of pracinostat in combination with azacitidine as a safe and effective regimen for difficult-to-treat AML patients. There are only few treatment options for older patients suffering from AML and who are unfit for intensive chemotherapy treatment. We are committed to further investigate the effects of this drug combination in an ongoing Phase III study."

Richard Ghalie, M.D., Senior Vice President, Clinical Development at MEI Pharma added: "AML is a rapidly progressing, often fatal disease, with an urgent need for new treatment options. This Phase II study provided the rationale for our ongoing Phase III study and show the potential for pracinostat, in combination with azacytidine, as a treatment option in this AML population. As such, we’re delighted that these data are being published in Blood Advances."

About Pracinostat

Pracinostat is an oral histone deacetylase ("HDAC") inhibitor that is in a pivotal Phase III study in combination with azacitidine for the treatment of adults with newly diagnosed acute myeloid leukemia ("AML") who are unfit for intensive chemotherapy. It is also being evaluated in a Phase II study in patients with high or very high-risk myelodysplastic syndrome ("MDS"). The U.S. Food and Drug Administration has granted Breakthrough Therapy Designation for pracinostat in combination with azacitidine for the treatment of patients with newly diagnosed AML who are ≥75 years of age or unfit for intensive chemotherapy.

In August 2016, Helsinn and MEI Pharma entered into an exclusive license, development and commercialization agreement for pracinostat in AML and other potential indications.

The agreement provides that Helsinn is primarily responsible for development and commercialization for pracinostat in AML and other indications, including MDS.

Pracinostat is an investigational agent and is not approved for commercial use in the U.S. and any country worldwide

On February 14, 2019 Forbius, a clinical-stage company that develops biologics for the treatment of cancer and fibrosis, reported a collaboration agreement with the Icahn School of Medicine at Mount Sinai and the Myeloproliferative Neoplasm Research Consortium (MPN-RC) (Press release, Forbius, FEB 14, 2019, View Source [SID1234533334]). This collaboration will launch an investigator-initiated trial (IIT) evaluating AVID200, a highly potent and isoform-selective TGF-beta inhibitor, as a potential treatment for myelofibrosis (MF). The Phase 1/2 clinical trial will be sponsored by the MPN-RC with NIH grant support and is expected to start during Q1 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 have demonstrated that blocking TGF-beta signaling reverses bone marrow fibrosis and restores hematopoiesis in preclinical models. We believe that selective TGF-beta inhibition by AVID200 could address the underlying cause of bone marrow failure and become the first disease-modifying therapy in MF. Our consortium is eager to commence evaluation of AVID200 in the upcoming clinical study," commented Dr. Ronald Hoffman, founder of the MPN-RC and Director of the Myeloproliferative Disorders Research Program at the Icahn School of Medicine at Mount Sinai.

Forbius is evaluating the immuno-oncology and anti-fibrotic effects of AVID200 in Phase 1 trials, including solid tumors and systemic sclerosis. Additionally, Forbius is expanding the AVID200 clinical development program by supporting IITs through the provision of drug, scientific input, and collaboration on the conduct of translational studies. Additional details pertaining to the prospective IIT in MF will be disclosed in due course.

About the Myeloproliferative Neoplasm Research Consortium (MPN-RC)

The MPN-RC was founded in 2006 and is the only independent, multi-center, international consortium of scientists and clinicians that is dedicated to developing novel therapeutic strategies for MF and other myeloproliferative neoplasms (MPN). The MPN-RC is funded by the NIH to conduct clinical trials based on the most promising preclinical MPN research. The goal of the consortium is to adapt quickly in response to scientific advances and a changing clinical landscape, in order to develop effective therapeutics for MPN patients.

About AVID200

AVID200 is an isoform-selective and highly potent inhibitor of TGF-beta 1 & 3, the two principal pro-fibrotic TGF-beta isoforms. These TGF-beta isoforms are central regulators in the pathogenesis and progression of fibrotic diseases, including MF (Chagraoui et al., 2002). AVID200 was rationally designed to be minimally active against TGF-beta 2, which is a promoter of hematopoiesis and normal cardiac function. This optimal selectivity positions AVID200 to be an effective and well-tolerated therapeutic in MF and other fibrotic diseases.

About Myelofibrosis (MF)

MF is a rare, life-threatening blood cancer characterized by progressive bone marrow fibrosis, which causes ineffective hematopoiesis. Approximately 30,000 people in the US alone are affected by this disease. Currently, there are no approved therapies targeting the underlying bone marrow fibrosis available to MF patients.

On February 14, 2019 Aromics, a biotech company located at the Barcelona Science Park (PCB), reported that it has been awarded with 1,085.659€ from the European Union – through the SME instrument of the Horizon 2020 (H2020-EIC-SMEInst-2018-2020-Phase 2)– for the development of the BERMES project, whose objective is the completion of the regulatory preclinics of NAX035, an innovative therapy for the treatment of malignant mesothelioma, an aggressive and highly refractory tumor directly related to asbestos exposure (Press release, Aromics, FEB 14, 2019, View Source [SID1234554043]).

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!

BERMES, an acronym for "A novel derivative BERberine for Malignant MESothelioma", started on first November 2018 has a duration of two and a half years and a total budget of 1.55 M €. The contribution from the European Union joins the capital of 400,000 euros already raised by the company in 2017 – with the participation of the current owners, corporative partners and also small investors that were incorporated through the crowdfunding biomedicine platform Capital Cells – and the participative loan of 120.000 € allocated by the Catalan Institute of Finance through the corporate entrepreneurship programme IFEM, which is supported by the Agency for Enterprise Competitiveness (ACC1Ó) under the program of grants in the form of a guarantee for the financing of companies participating in corporate entrepreneurship projects by means of co-investment loans (FINPEC).

Malignant mesothelioma is a tumour that emerges in the mesothelium, a thin layer of tissue that surrounds many organs such as the lung, peritoneal cavity, heart or testicles. It is an aggressive malignancy that is highly resistant to current therapies. "Patients with malignant pleural mesothelioma, the most common type, continue to have a poor prognosis, with a survival of less than 10% at five years after diagnosis. Available therapies include surgery combined with chemotherapy and radiotherapy. Most patients, however, are diagnosed in advanced stages of the disease, when chemotherapy is usually the treatment of choice. A chemotherapy with a low rate of response, despite the significant effort made over the last ten years to find a more effective treatment," explains Dr. Carmen Plasencia, the co-founder and CEO of Aromics.

El This is the focus of the BERMES project, which seeks to develop a new cure for this devastating cancer, thus meeting an important medical need.

A public health problem not yet solved

The World Health Organization (WHO) has recognized that all forms of mesothelioma are strongly associated with asbestos exposure. Although recognized as a first-level carcinogen, asbestos is still being used daily in alarming quantities in more than 150 countries according to the International Ban Asbestos Secretariat (IBAS). In fact, the WHO estimates that more than 125 million people are daily at risk of exposure, of which approximately 10% will eventually develop mesothelioma.

"Asbestos still represent a great labour, environmental and public health problem that has not been solved. Even in those countries like EU countries where it is forbidden, this material still remain in many buildings and installations. Factors such as the high costs for the safe removal of elements that contain these mineral, increase the risk of appearance of these tumours," assures Carme Plasencia.

The incidence of this cancer is increasing all over the world, being the countries of the European Union (EU) those that register the highest number of cases despite the use of asbestos was definitively prohibited on 1st January 2005 (Directive 1999/77/EC).

El Notwithstanding, the malignancy has a long latency period (a 44.6 year average from the exposure to the diagnosis) being the incidence peak expected from 2020 onwards. In fact, the European Economic and Social Committee (EESC) estimates that more than 300,000 Europeans will die of mesothelioma by 2030, at that time it is expected that the maximum number of diseases caused by exposure to asbestos will be observed.

A first-in-class drug

The NAX035 compound is one of the most advanced in the Aromics therapy portfolio. It is the first candidate molecule of a new family of antitumour agents (first-in-class) to advance up to the clinical stage.

"It is a pioneering drug, very attractive to the pharmaceutical industry. The Aromics molecule binds to a specific messenger RNA and reduces the levels of a protein that is abnormally expressed in the tumour, and that is causing resistance to current chemotherapy treatments in mesothelioma patients. In this way we aim to address the root cause, stopping the synthesis of this abnormal protein and therefore controlling the disease", says Dr. Plasencia.

The drug has already demonstrated its effectiveness in reducing the tumour size when administered both, orally or intraperitoneally in experimental animal models, showing a good toxicological and safety profile. At the same time, the biotech is working to achieve the orphan designation for NAX035, which would represent an important milestone for the company.

"This project is a clear example of the company’s activity in the area of translational medicine that leads to a better understanding of the progression of the disease and the identification of specific molecular markers relevant to the treatment response, that allow us to develop more efficient therapeutic solutions for the treatment of complex pathologies such as cancer," Dr. Plasencia says.

After completing BERMES project, Aromics’ objective is continuing with the development of the compound up to early clinical stage to prove the efficacy in patients. After the clinical proof of concept, the biotechnology foresees a licencing or co-development agreement on the product with the pharmaceutical industry that will be finally the one leading the development up to the market. Aromics is already in contact with some pharmaceutical companies that have shown interest in the drug.

On February 14, 2019 Tanabe Research Laboratories U.S.A. Inc. (TRL), a subsidiary of Mitsubishi Tanabe Pharmaceutical Corporation, is a California based research, development and clinical stage company specializing in antibody technologies to treat cancer and other diseases with unmet medical needs (Press release, Mitsubishi Tanabe Pharma, FEB 14, 2019, View Source [SID1234533335]). TRL announced today that the U.S. Food and Drug administration (FDA) accepted the company’s first Investigational New Drug (IND) application to initiate a phase I trial for its Antibody Drug Conjugate TR1801-ADC (MT- 8633) in patients with cMet positive solid tumors.

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 excited to be able to move TR1801-ADC into the clinic," said Roland Newman, TRL’s Chief Scientific Officer. "TR1801-ADC is an extremely potent ADC that combines a non-agonizing anti-c-Met antibody developed at TRL, with a pyrrolobenzodiazepine dimer (PBD) toxin, and has demonstrated potent dose dependent anti-tumor activity against Met positive tumors in preclinical models."

The PBDs were developed by TRL’s collaborative partner MedImmune, the global biologics research and development arm of AstraZeneca (LSE: AZN), via its proprietary Spirogen technology and licensed to TRL. PBDs are of an order of magnitude more potent than other warheads currently used with other ADCs, and in the case of TR1801-ADC are linked to the antibody via a site-specific conjugation site.

cMet, also referred to as the hepatic growth factor receptor (HGFR), is a validated target expressed on a variety of tumor types including colorectal, NSCLC, gastric, esophageal, pancreatic, bile duct and many other cancers. "Patients will be selected based on c-Met expression levels using a histological screening system (IHC) to determine their eligibility. Patients that have either cMet gene amplification or are non-gene amplified will both be eligible for the trial as long as they meet the IHC expression cutoff requirement," said Gary Woodnutt, TRL’s VP of Development.

"The acceptance of this IND by the FDA is an important milestone for TRL," said CEO and President Naoki Sakurai, "as it validates our research efforts and represents the first ADC product in a rich future pipeline. This achievement is a result of hard work by our dedicated employees and is the first drug in TRL’s mission of creating therapies with a meaningful clinical benefit for patients."

About TRL:

TRL is an independent subsidiary of MTPC located in San Diego California, whose role is to discover and develop biological drug candidates for therapy. Currently, TRL’s efforts are directed towards antibody-related research to target tumors and other diseases with high unmet needs. TRL has established collaborative relationships with other companies and academic research organizations to develop Antibody Drug Conjugates (ADCs) and to identify therapeutic lead compounds for development. View Source

On February 14. 2019 Evelo Biosciences, Inc. (Nasdaq: EVLO) ("Evelo"), a clinical stage biotechnology company developing monoclonal microbials, a potential new modality of oral biologic medicines, reported financial results and provided a business update for the fourth quarter and full year 2018 (Press release, Evelo Biosciences, FEB 14, 2019, View Source [SID1234533299]).

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!

"Our platform opens up the potential for effective, orally delivered, safe and cost-effective medicines for improved treatments of inflammatory diseases and cancers. In 2018, we made significant progress and advanced our first three product candidates into clinical trials across multiple inflammatory diseases and cancers," said Simba Gill, Ph.D., president and chief executive officer of Evelo. "In 2019, we expect to advance our oncology clinical trials and announce clinical data from our ongoing inflammatory disease clinical trials which may signal the potential for monoclonal microbials as a broadly applicable new modality of medicines."

2018 and Recent Business Highlights:

Inflammation

April 2018 – Evelo initiated a placebo-controlled Phase 1b clinical trial of EDP1066 in healthy volunteers and patients with atopic dermatitis or psoriasis. Following completion of each of the three dose-ascending healthy volunteer cohorts, data was reviewed by the trial’s safety review committee and the trial proceeded as planned into cohorts of patients with atopic dermatitis or psoriasis

November 2018 – Evelo initiated a placebo-controlled Phase 1b clinical trial of EDP1815 in healthy volunteers and patients with atopic dermatitis or psoriasis

Oncology

November 2018 – Entered into clinical collaboration with Merck to evaluate EDP1503 in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy, in multiple cancer indications

December 2018 – Evelo initiated an open-label Phase 1/2 clinical trial of EDP1503 in combination with KEYTRUDA in microsatellite stable colorectal cancer, triple-negative breast cancer, and patients with other tumor types that have relapsed on prior PD-1/L1 inhibitor treatment

January 2019 – The University of Chicago initiated an open-label Phase 2a clinical trial of EDP1503 in combination with KEYTRUDA in naïve melanoma patients and melanoma patients that have relapsed on prior PD-1/L1 inhibitor treatment

Non-Replicating Monoclonal Microbials

Preclinical studies have shown that non-replicating monoclonal microbials, which have been treated to prevent growth and division, maintain activity, opening up the potential to develop non-replicating monoclonal microbial clinical candidates

Monoclonal microbial activity is likely driven by recognition of structural motifs by immune cells in the small intestine and is not dependent on engraftment or colonization

Nominated EDP1867 as a preclinical monoclonal microbial candidate for inflammatory diseases. EDP1867 is the first monoclonal microbial specifically developed as a non-replicating product candidate in Evelo’s pipeline

Anticipated 2019 Clinical Milestones

Initial clinical data from the ongoing Phase 1b clinical trial of EDP1066 in healthy volunteers and patients with psoriasis or atopic dermatitis in the second quarter of 2019

Initiation of an immuno-pharmacology clinical study in healthy volunteers with EDP1066 in 1H 2019, designed to explore additional doses and formulations ahead of potential later stage trials.

Initial clinical data from the ongoing Phase 1b clinical trial of EDP1815 in healthy volunteers and patients with psoriasis or atopic dermatitis in the second half of 2019

Initiation of clinical trials with EDP1066 and EDP1815 in additional inflammatory disease indications in the second half of 2019

Fourth Quarter and Full Year 2018 Financial Results

Cash Position: As of December 31, 2018, cash, cash equivalents and investments were $147.9 million, as compared to cash and cash equivalents of $38.2 million as of December 31, 2017. This increase was due to net proceeds of $81.3 million from the issuance of Series C convertible preferred stock, net proceeds of $75.8 million from Evelo’s initial public offering and $5.0 million of additional drawings from Evelo’s existing debt facility, partially offset by cash used to fund operating activities for the full year 2018. Evelo expects that its cash, cash equivalents and investments will enable it to fund its planned operating expenses and capital expenditure requirements into the second half of 2020.

Research and Development Expenses: R&D expenses were $11.3 million for the three months ended December 31, 2018 and $39.9 million for the full year ended December 31, 2018, compared to $6.1 million for the three months ended December 31, 2017 and $20.0 million for the full year ended December 31, 2017. The increase of $19.9 million for 2018 was due primarily to increases in costs related to Evelo’s inflammation and oncology clinical development programs, and gut-body network platform expenses, as well as increased personnel costs.

General and Administrative Expenses: G&A expenses were $4.7 million for the three months ended December 31, 2018 and $18.2 million for the full year ended December 31, 2018, compared to $2.0 million for the three months ended December 31, 2017 and $7.6 million for the full year ended December 31, 2017. The increase of $10.6 million for 2018 was due primarily to increased general and administrative personnel costs, professional and consulting fees, and facility expenses supporting Evelo’s growing organization and public company infrastructure.

Net Loss Attributable to Common Stockholders: Net loss attributable to common stockholders was $15.4 million for the three months ended December 31, 2018 and $60.9 million for the full year ended December 31, 2018, or $(0.49) and $(2.78) per basic and diluted share, respectively, as compared to a net loss attributable to common stockholders of $9.9 million for the three months ended December 31, 2017 and $34.1 million for the full year ended December 31, 2017,or $(2.57) and $(9.10) per basic and diluted share, respectively.

Conference Call
Evelo will host a conference call and webcast today at 8:30a.m. ET. To access the call please dial (866) 795-3242 (domestic) and (409) 937-8909 (international) and provide the passcode 7986199. A live webcast of the call will be available on the Investors sections of the Evelo website at www.evelobio.com. The archived webcast will be available approximately two hours after the conference call and will be available for 30 days following the call.